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1.
Samuel Caddick 《EMBO reports》2008,9(12):1174-1176
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2.
Wolinsky H 《EMBO reports》2010,11(11):830-833
Sympatric speciation—the rise of new species in the absence of geographical barriers—remains a puzzle for evolutionary biologists. Though the evidence for sympatric speciation itself is mounting, an underlying genetic explanation remains elusive.For centuries, the greatest puzzle in biology was how to account for the sheer variety of life. In his 1859 landmark book, On the Origin of Species, Charles Darwin (1809–1882) finally supplied an answer: his grand theory of evolution explained how the process of natural selection, acting on the substrate of genetic mutations, could gradually produce new organisms that are better adapted to their environment. It is easy to see how adaptation to a given environment can differentiate organisms that are geographically separated; different environmental conditions exert different selective pressures on organisms and, over time, the selection of mutations creates different species—a process that is known as allopatric speciation.It is more difficult to explain how new and different species can arise within the same environment. Although Darwin never used the term sympatric speciation for this process, he did describe the formation of new species in the absence of geographical separation. “I can bring a considerable catalogue of facts,” he argued, “showing that within the same area, varieties of the same animal can long remain distinct, from haunting different stations, from breeding at slightly different seasons, or from varieties of the same kind preferring to pair together” (Darwin, 1859).It is more difficult to explain how new and different species can arise within the same environmentIn the 1920s and 1930s, however, allopatric speciation and the role of geographical isolation became the focus of speciation research. Among those leading the charge was Ernst Mayr (1904–2005), a young evolutionary biologist, who would go on to influence generations of biologists with his later work in the field. William Baker, head of palm research at the Royal Botanic Gardens, Kew in Richmond, UK, described Mayr as “one of the key figures to crush sympatric speciation.” Frank Sulloway, a Darwin Scholar at the Institute of Personality and Social Research at the University of California, Berkeley, USA, similarly asserted that Mayr''s scepticism about sympatry was central to his career.The debate about sympatric and allopatric speciation has livened up since Mayr''s death…Since Mayr''s death in 2005, however, several publications have challenged the notion that sympatric speciation is a rare exception to the rule of allopatry. These papers describe examples of both plants and animals that have undergone speciation in the same location, with no apparent geographical barriers to explain their separation. In these instances, a single ancestral population has diverged to the extent that the two new species cannot produce viable offspring, despite the fact that their ranges overlap. The debate about sympatric and allopatric speciation has livened up since Mayr''s death, as Mayr''s influence over the field has waned and as new tools and technologies in molecular biology have become available.Sulloway, who studied with Mayr at Harvard University, in the late 1960s and early 1970s, notes that Mayr''s background in natural history and years of fieldwork in New Guinea and the Solomon Islands contributed to his perception that the bulk of the data supported allopatry. “Ernst''s early career was in many ways built around that argument. It wasn''t the only important idea he had, but he was one of the strong proponents of it. When an intellectual stance exists where most people seem to have gotten it wrong, there is a tendency to sort of lay down the law,” Sulloway said.Sulloway also explained that Mayr “felt that botanists had basically led Darwin astray because there is so much evidence of polyploidy in plants and Darwin turned in large part to the study of botany and geographical distribution in drawing evidence in The Origin.” Indeed, polyploidization is common in plants and can lead to ‘instantaneous'' speciation without geographical barriers.In February 2006, the journal Nature simultaneously published two papers that described sympatric speciation in animals and plants, reopening the debate. Axel Meyer, a zoologist and evolutionary biologist at the University of Konstanz, Germany, demonstrated with his colleagues that sympatric speciation has occurred in cichlid fish in Lake Apoyo, Nicaragua (Barluenga et al, 2006). The researchers claimed that the ancestral fish only seeded the crater lake once; from this, new species have evolved that are distinct and reproductively isolated. Meyer''s paper was broadly supported, even by critics of sympatric speciation, perhaps because Mayr himself endorsed sympatric speciation among the cichlids in his 2001 book What Evolution Is. “[Mayr] told me that in the case of our crater lake cichlids, the onus of showing that it''s not sympatric speciation lies with the people who strongly believe in only allopatric speciation,” Meyer said.…several scientists involved in the debate think that molecular biology could help to eventually resolve the issueThe other paper in Nature—by Vincent Savolainen, a molecular systematist at Imperial College, London, UK, and colleagues—described the sympatric speciation of Howea palms on Lord Howe Island (Fig 1), a minute Pacific island paradise (Savolainen et al, 2006a). Savolainen''s research had originally focused on plant diversity in the gesneriad family—the best known example of which is the African violet—while he was in Brazil for the Geneva Botanical Garden, Switzerland. However, he realized that he would never be able prove the occurrence of sympatry within a continent. “It might happen on a continent,” he explained, “but people will always argue that maybe they were separated and got together after. […] I had to go to an isolated piece of the world and that''s why I started to look at islands.”Open in a separate windowFigure 1Lord Howe Island. Photo: Ian Hutton.He eventually heard about Lord Howe Island, which is situated just off the east coast of Australia, has an area of 56 km2 and is known for its abundance of endemic palms (Sidebar A). The palms, Savolainen said, were an ideal focus for sympatric research: “Palms are not the most diverse group of plants in the world, so we could make a phylogeny of all the related species of palms in the Indian Ocean, southeast Asia and so on.”…the next challenges will be to determine which genes are responsible for speciation, and whether sympatric speciation is common

Sidebar A | Research in paradise

Alexander Papadopulos is no Tarzan of the Apes, but he has spent a couple months over the past two years aloft in palm trees hugging rugged mountainsides on Lord Howe Island, a Pacific island paradise and UNESCO World Heritage site.Papadopulos—who is finishing his doctorate at Imperial College London, UK—said the views are breathtaking, but the work is hard and a bit treacherous as he moves from branch to branch. “At times, it can be quite hairy. Often you''re looking over a 600-, 700-metre drop without a huge amount to hold onto,” he said. “There''s such dense vegetation on most of the steep parts of the island. You''re actually climbing between trees. There are times when you''re completely unsupported.”Papadopulos typically spends around 10 hours a day in the field, carrying a backpack and utility belt with a digital camera, a trowel to collect soil samples, a first-aid kit, a field notebook, food and water, specimen bags, tags to label specimens, a GPS device and more. After several days in the field, he spends a day working in a well-equipped field lab and sleeping in the quarters that were built by the Lord Howe governing board to accommodate the scientists who visit the island on various projects. Papadopulos is studying Lord Howe''s flora, which includes more than 200 plant species, about half of which are indigenous.Vincent Savolainen said it takes a lot of planning to get materials to Lord Howe: the two-hour flight from Sydney is on a small plane, with only about a dozen passengers on board and limited space for equipment. Extra gear—from gardening equipment to silica gel and wood for boxes in which to dry wet specimens—arrives via other flights or by boat, to serve the needs of the various scientists on the team, including botanists, evolutionary biologists and ecologists.Savolainen praised the well-stocked researcher station for visiting scientists. It is run by the island board and situated near the palm nursery. It includes one room for the lab and another with bunks. “There is electricity and even email,” he said. Papadoupulos said only in the past year has the internet service been adequate to accommodate video calls back home.Ian Hutton, a Lord Howe-based naturalist and author, who has lived on the island since 1980, said the island authorities set limits on not only the number of residents—350—but also the number of visitors at one time—400—as well as banning cats, to protect birds such as the flightless wood hen. He praised the Imperial/Kew group: “They''re world leaders in their field. And they''re what I call ‘Gentlemen Botanists''. They''re very nice people, they engage the locals here. Sometimes researchers might come here, and they''re just interested in what they''re doing and they don''t want to share what they''re doing. Not so with these people. Savolainen said his research helps the locals: “The genetics that we do on the island are not only useful to understand big questions about evolution, but we also always provide feedback to help in its conservation efforts.”Yet, in Savolainen''s opinion, Mayr''s influential views made it difficult to obtain research funding. “Mayr was a powerful figure and he dismissed sympatric speciation in textbooks. People were not too keen to put money on this,” Savolainen explained. Eventually, the Leverhulme Trust (London, UK) gave Savolainen and Baker £70,000 between 2003–2005 to get the research moving. “It was enough to do the basic genetics and to send a research assistant for six months to the island to do a lot of natural history work,” Savolainen said. Once the initial results had been processed, the project received a further £337,000 from the British Natural Environment Research Council in 2008, and €2.5 million from the European Research Council in 2009.From the data collected on Lord Howe Island, Savolainen and his team constructed a dated phylogenetic tree showing that the two endemic species of the palm Howea (Arecaceae; Fig 2) are sister taxa. From their tree, the researchers were able to establish that the two species—one with a thatch of leaves and one with curly leaves—diverged long after the island was formed 6.9 million years ago. Even where they are found in close proximity, the two species cannot interbreed as they flower at different times.Open in a separate windowFigure 2The two species of Howea palm. (A) Howea fosteriana (Kentia palm). (B) Howea belmoreana. Photos: William Baker, Royal Botanical Gardens, Kew, Richmond, UK.According to the researchers, the palm speciation probably occurred owing to the different soil types in which the plants grow. Baker explained that there are two soil types on Lord Howe—the older volcanic soil and the younger calcareous soils. The Kentia palm grows in both, whereas the curly variety is restricted to the volcanic soil. These soil types are closely intercalated—fingers and lenses of calcareous soils intrude into the volcanic soils in lowland Lord Howe Island. “You can step over a geological boundary and the palms in the forest can change completely, but they remain extremely close to each other,” Baker said. “What''s more, the palms are wind-pollinated, producing vast amounts of pollen that blows all over the place during the flowering season—people even get pollen allergies there because there is so much of the stuff.” According to Savolainen, that the two species have different flowering times is a “way of having isolation so that they don''t reproduce with each other […] this is a mechanism that evolved to allow other species to diverge in situ on a few square kilometres.”According to Baker, the absence of a causative link has not been demonstrated between the different soils and the altered flowering times, “but we have suggested that at the time of speciation, perhaps when calcareous soils first appeared, an environmental effect may have altered the flowering time of palms colonising the new soil, potentially causing non-random mating and kicking off speciation. This is just a hypothesis—we need to do a lot more fieldwork to get to the bottom of this,” he said. What is clear is that this is not allopatric speciation, as “the micro-scale differentiation in geology and soil type cannot create geographical isolation”, said Baker.…although molecular data will add to the debate, it will not settle it aloneThe results of the palm research caused something of a splash in evolutionary biology, although the study was not without its critics. Tod Stuessy, Chair of the Department of Systematic and Evolutionary Botany at the University of Vienna, Austria, has dealt with similar issues of divergence on Chile''s Juan Fernández Islands—also known as the Robinson Crusoe Islands—in the South Pacific. From his research, he points out that on old islands, large ecological areas that once separated species—and caused allopatric speciation—could have since disappeared, diluting the argument for sympatry. “There are a lot of cases [in the Juan Fernández Islands] where you have closely related species occurring in the same place on an island, even in the same valley. We never considered that they had sympatric origins because we were always impressed by how much the island had been modified through time,” Stuessy said. “What [the Lord Howe researchers] really didn''t consider was that Lord Howe Island could have changed a lot over time since the origins of the species in question.” It has also been argued that one of the palm species on Lord Howe Island might have evolved allopatrically on a now-sunken island in the same oceanic region.In their response to a letter from Stuessy, Savolainen and colleagues argued that erosion on the island has been mainly coastal and equal from all sides. “Consequently, Quaternary calcarenite deposits, which created divergent ecological selection pressures conducive to Howea species divergence, have formed evenly around the island; these are so closely intercalated with volcanic rocks that allopatric speciation due to ecogeographic isolation, as Stuessy proposes, is unrealistic” (Savolainen et al, 2006b). Their rebuttal has found support in the field. Evolutionary biologist Loren Rieseberg at the University of British Columbia in Vancouver, Canada, said: “Basically, you have two sister species found on a very small island in the middle of the ocean. It''s hard to see how one could argue anything other than they evolved there. To me, it would be hard to come up with a better case.”Whatever the reality, several scientists involved in the debate think that molecular biology could help to eventually resolve the issue. Savolainen said that the next challenges will be to determine which genes are responsible for speciation, and whether sympatric speciation is common. New sequencing techniques should enable the team to obtain a complete genomic sequence for the palms. Savolainen said that next-generation sequencing is “a total revolution.” By using sequencing, he explained that the team, “want to basically dissect exactly what genes are involved and what has happened […] Is it very special on Lord Howe and for this palm, or is [sympatric speciation] a more general phenomenon? This is a big question now. I think now we''ve found places like Lord Howe and [have] tools like the next-gen sequencing, we can actually get the answer.”Determining whether sympatric speciation occurs in animal species will prove equally challenging, according to Meyer. His own lab, among others, is already looking for ‘speciation genes'', but this remains a tricky challenge. “Genetic models […] argue that two traits (one for ecological specialisation and another for mate choice, based on those ecological differences) need to become tightly linked on one chromosome (so that they don''t get separated, often by segregation or crossing over). The problem is that the genetic basis for most ecologically relevant traits are not known, so it would be very hard to look for them,” Meyer explained. “But, that is about to change […] because of next-generation sequencing and genomics more generally.”Many researchers who knew Mayr personally think he would have enjoyed the challenge to his viewsOthers are more cautious. “In some situations, such as on isolated oceanic islands, or in crater lakes, molecular phylogenetic information can provide strong evidence of sympatric speciation. It also is possible, in theory, to use molecular data to estimate the timing of gene flow, which could help settle the debate,” Rieseberg said. However, he cautioned that although molecular data will add to the debate, it will not settle it alone. “We will still need information from historical biogeography, natural history, phylogeny, and theory, etc. to move things forward.”Many researchers who knew Mayr personally think he would have enjoyed the challenge to his views. “I can only imagine that it would''ve been great fun to engage directly with him [on sympatry on Lord Howe],” Baker said. “It''s a shame that he wasn''t alive to comment on [our paper].” In fact, Mayr was not really as opposed to sympatric speciation as some think. “If one is of the opinion that Mayr opposed all forms of sympatric speciation, well then this looks like a big swing back the other way,” Sulloway commented. “But if one reads Mayr carefully, one sees that he was actually interested in potential exceptions and, as best he could, chronicled which ones he thought were the best candidates.”Mayr''s opinions aside, many biologists today have stronger feelings against sympatric speciation than he did himself in his later years, Meyer added. “I think that Ernst was more open to the idea of sympatric speciation later in his life. He got ‘softer'' on this during the last two of his ten decades of life that I knew him. I was close to him personally and I think that he was much less dogmatic than he is often made out to be […] So, I don''t think that he is spinning in his grave.” Mayr once told Sulloway that he liked to take strong stances, precisely so that other researchers would be motivated to try to prove him wrong. “If they eventually succeeded in doing so, Mayr felt that science was all the better for it.”? Open in a separate windowAlex Papadopulos and Ian Hutton doing fieldwork on a very precarious ridge on top of Mt. Gower. Photo: William Baker, Royal Botanical Gardens, Kew, Richmond, UK.  相似文献   

3.
Greener M 《EMBO reports》2008,9(11):1067-1069
A consensus definition of life remains elusiveIn July this year, the Phoenix Lander robot—launched by NASA in 2007 as part of the Phoenix mission to Mars—provided the first irrefutable proof that water exists on the Red Planet. “We''ve seen evidence for this water ice before in observations by the Mars Odyssey orbiter and in disappearing chunks observed by Phoenix […], but this is the first time Martian water has been touched and tasted,” commented lead scientist William Boynton from the University of Arizona, USA (NASA, 2008). The robot''s discovery of water in a scooped-up soil sample increases the probability that there is, or was, life on Mars.Meanwhile, the Darwin project, under development by the European Space Agency (ESA; Paris, France; www.esa.int/science/darwin), envisages a flotilla of four or five free-flying spacecraft to search for the chemical signatures of life in 25 to 50 planetary systems. Yet, in the vastness of space, to paraphrase the British astrophysicist Arthur Eddington (1822–1944), life might be not only stranger than we imagine, but also stranger than we can imagine. The limits of our current definitions of life raise the possibility that we would not be able to recognize an extra-terrestrial organism.Back on Earth, molecular biologists—whether deliberately or not—are empirically tackling the question of what is life. Researchers at the J Craig Venter Institute (Rockville, MD, USA), for example, have synthesized an artificial bacterial genome (Gibson et al, 2008). Others have worked on ‘minimal cells'' with the aim of synthesizing a ‘bioreactor'' that contains the minimum of components necessary to be self-sustaining, reproduce and evolve. Some biologists regard these features as the hallmarks of life (Luisi, 2007). However, to decide who is first in the ‘race to create life'' requires a consensus definition of life itself. “A definition of the precise boundary between complex chemistry and life will be critical in deciding which group has succeeded in what might be regarded by the public as the world''s first theology practical,” commented Jamie Davies, Professor of Experimental Anatomy at the University of Edinburgh, UK.For most biologists, defining life is a fascinating, fundamental, but largely academic question. It is, however, crucial for exobiologists looking for extra-terrestrial life on Mars, Jupiter''s moon Europa, Saturn''s moon Titan and on planets outside our solar system.In their search for life, exobiologists base their working hypothesis on the only example to hand: life on Earth. “At the moment, we can only assume that life elsewhere is based on the same principles as on Earth,” said Malcolm Fridlund, Secretary for the Exo-Planet Roadmap Advisory Team at the ESA''s European Space Research and Technology Centre (Noordwijk, The Netherlands). “We should, however, always remember that the universe is a peculiar place and try to interpret unexpected results in terms of new physics and chemistry.”The ESA''s Darwin mission will, therefore, search for life-related gases such as carbon dioxide, water, methane and ozone in the atmospheres of other planets. On Earth, the emergence of life altered the balance of atmospheric gases: living organisms produced all of the Earth'' oxygen, which now accounts for one-fifth of the atmosphere. “If all life on Earth was extinguished, the oxygen in our atmosphere would disappear in less than 4 million years, which is a very short time as planets go—the Earth is 4.5 billion years old,” Fridlund said. He added that organisms present in the early phases of life on Earth produced methane, which alters atmospheric composition compared with a planet devoid of life.Although the Darwin project will use a pragmatic and specific definition of life, biologists, philosophers and science-fiction authors have devised numerous other definitions—none of which are entirely satisfactory. Some are based on basic physiological characteristics: a living organism must feed, grow, metabolize, respond to stimuli and reproduce. Others invoke metabolic definitions that define a living organism as having a distinct boundary—such as a membrane—which facilitates interaction with the environment and transfers the raw materials needed to maintain its structure (Wharton, 2002). The minimal cell project, for example, defines cellular life as “the capability to display a concert of three main properties: self-maintenance (metabolism), reproduction and evolution. When these three properties are simultaneously present, we will have a full fledged cellular life” (Luisi, 2007). These concepts regard life as an emergent phenomenon arising from the interaction of non-living chemical components.Cryptobiosis—hidden life, also known as anabiosis—and bacterial endospores challenge the physiological and metabolic elements of these definitions (Wharton, 2002). When the environment changes, certain organisms are able to undergo cryptobiosis—a state in which their metabolic activity either ceases reversibly or is barely discernible. Cryptobiosis allows the larvae of the African fly Polypedilum vanderplanki to survive desiccation for up to 17 years and temperatures ranging from −270 °C (liquid helium) to 106 °C (Watanabe et al, 2002). It also allows the cysts of the brine shrimp Artemia to survive desiccation, ultraviolet radiation, extremes of temperature (Wharton, 2002) and even toyshops, which sell the cysts as ‘sea monkeys''. Organisms in a cryptobiotic state show characteristics that vary markedly from what we normally consider to be life, although they are certainly not dead. “[C]ryptobiosis is a unique state of biological organization”, commented James Clegg, from the Bodega Marine Laboratory at the University of California (Davies, CA, USA), in an article in 2001 (Clegg, 2001). Bacterial endospores, which are the “hardiest known form of life on Earth” (Nicholson et al, 2000), are able to withstand almost any environment—perhaps even interplanetary space. Microbiologists isolated endospores of strict thermophiles from cold lake sediments and revived spores from samples some 100,000 years old (Nicholson et al, 2000).…life might be not only stranger than we imagine, but also stranger than we can imagineAnother problem with the definitions of life is that these can expand beyond biology. The minimal cell project, for example, in common with most modern definitions of life, encompass the ability to undergo Darwinian evolution (Wharton, 2002). “To be considered alive, the organism needs to be able to undergo extensive genetic modification through natural selection,” said Professor Paul Freemont from Imperial College London, UK, whose research interests encompass synthetic biology. But the virtual ‘organisms'' in computer simulations such as the Game of Life (www.bitstorm.org/gameoflife) and Tierra (http://life.ou.edu/tierra) also exhibit life-like characteristics, including growth, death and evolution—similar to robots and other artifical systems that attempt to mimic life (Guruprasad & Sekar, 2006). “At the moment, we have some problems differentiating these approaches from something biologists consider [to be] alive,” Fridlund commented.…to decide who is first in the ‘race to create life'' requires a consensus definition of lifeBoth the genetic code and all computer-programming languages are means of communicating large quantities of codified information, which adds another element to a comprehensive definition of life. Guenther Witzany, an Austrian philosopher, has developed a “theory of communicative nature” that, he claims, differentiates biotic and abiotic life. “Life is distinguished from non-living matter by language and communication,” Witzany said. According to his theory, RNA and DNA use a ‘molecular syntax'' to make sense of the genetic code in a manner similar to language. This paragraph, for example, could contain the same words in a random order; it would be meaningless without syntactic and semantic rules. “The RNA/DNA language follows syntactic, semantic and pragmatic rules which are absent in [a] random-like mixture of nucleic acids,” Witzany explained.Yet, successful communication requires both a speaker using the rules and a listener who is aware of and can understand the syntax and semantics. For example, cells, tissues, organs and organisms communicate with each other to coordinate and organize their activities; in other words, they exchange signals that contain meaning. Noradrenaline binding to a β-adrenergic receptor in the bronchi communicates a signal that says ‘dilate''. “If communication processes are deformed, destroyed or otherwise incorrectly mediated, both coordination and organisation of cellular life is damaged or disturbed, which can lead to disease,” Witzany added. “Cellular life also interprets abiotic environmental circumstances—such as the availability of nutrients, temperature and so on—to generate appropriate behaviour.”Nonetheless, even definitions of life that include all the elements mentioned so far might still be incomplete. “One can make a very complex definition that covers life on the Earth, but what if we find life elsewhere and it is different? My opinion, shared by many, is that we don''t have a clue of how life arose on Earth, even if there are some hypotheses,” Fridlund said. “This underlies many of our problems defining life. Since we do not have a good minimum definition of life, it is hard or impossible to find out how life arose without observing the process. Nevertheless, I''m an optimist who believes the universe is understandable with some hard work and I think we will understand these issues one day.”Both synthetic biology and research on organisms that live in extreme conditions allow biologists to explore biological boundaries, which might help them to reach a consensual minimum definition of life, and understand how it arose and evolved. Life is certainly able to flourish in some remarkably hostile environments. Thermus aquaticus, for example, is metabolically optimal in the springs of Yellowstone National Park at temperatures between 75 °C and 80 °C. Another extremophile, Deinococcus radiodurans, has evolved a highly efficient biphasic system to repair radiation-induced DNA breaks (Misra et al, 2006) and, as Fridlund noted, “is remarkably resistant to gamma radiation and even lives in the cooling ponds of nuclear reactors.”In turn, synthetic biology allows for a detailed examination of the elements that define life, including the minimum set of genes required to create a living organism. Researchers at the J Craig Venter Institute, for example, have synthesized a 582,970-base-pair Mycoplasma genitalium genome containing all the genes of the wild-type bacteria, except one that they disrupted to block pathogenicity and allow for selection. ‘Watermarks'' at intergenic sites that tolerate transposon insertions identify the synthetic genome, which would otherwise be indistinguishable from the wild type (Gibson et al, 2008).Yet, as Pier Luigi Luisi from the University of Roma in Italy remarked, even M. genitalium is relatively complex. “The question is whether such complexity is necessary for cellular life, or whether, instead, cellular life could, in principle, also be possible with a much lower number of molecular components”, he said. After all, life probably did not start with cells that already contained thousands of genes (Luisi, 2007).…researchers will continue their attempts to create life in the test tube—it is, after all, one of the greatest scientific challengesTo investigate further the minimum number of genes required for life, researchers are using minimal cell models: synthetic genomes that can be included in liposomes, which themselves show some life-like characteristics. Certain lipid vesicles are able to grow, divide and grow again, and can include polymerase enzymes to synthesize RNA from external substrates as well as functional translation apparatuses, including ribosomes (Deamer, 2005).However, the requirement that an organism be subject to natural selection to be considered alive could prove to be a major hurdle for current attempts to create life. As Freemont commented: “Synthetic biologists could include the components that go into a cell and create an organism [that is] indistinguishable from one that evolved naturally and that can replicate […] We are beginning to get to grips with what makes the cell work. Including an element that undergoes natural selection is proving more intractable.”John Dupré, Professor of Philosophy of Science and Director of the Economic and Social Research Council (ESRC) Centre for Genomics in Society at the University of Exeter, UK, commented that synthetic biologists still approach the construction of a minimal organism with certain preconceptions. “All synthetic biology research assumes certain things about life and what it is, and any claims to have ‘confirmed'' certain intuitions—such as life is not a vital principle—aren''t really adding empirical evidence for those intuitions. Anyone with the opposite intuition may simply refuse to admit that the objects in question are living,” he said. “To the extent that synthetic biology is able to draw a clear line between life and non-life, this is only possible in relation to defining concepts brought to the research. For example, synthetic biologists may be able to determine the number of genes required for minimal function. Nevertheless, ‘what counts as life'' is unaffected by minimal genomics.”Partly because of these preconceptions, Dan Nicholson, a former molecular biologist now working at the ESRC Centre, commented that synthetic biology adds little to the understanding of life already gained from molecular biology and biochemistry. Nevertheless, he said, synthetic biology might allow us to go boldly into the realms of biological possibility where evolution has not gone before.An engineered synthetic organism could, for example, express novel amino acids, proteins, nucleic acids or vesicular forms. A synthetic organism could use pyranosyl-RNA, which produces a stronger and more selective pairing system than the natural existent furanosyl-RNA (Bolli et al, 1997). Furthermore, the synthesis of proteins that do not exist in nature—so-called never-born proteins—could help scientists to understand why evolutionary pressures only selected certain structures.As Luisi remarked, the ratio between the number of theoretically possible proteins containing 100 amino acids and the real number present in nature is close to the ratio between the space of the universe and the space of a single hydrogen atom, or the ratio between all the sand in the Sahara Desert and a single grain. Exploring never-born proteins could, therefore, allow synthetic biologists to determine whether particular physical, structural, catalytic, thermodynamic and other properties maximized the evolutionary fitness of natural proteins, or whether the current protein repertoire is predominately the result of chance (Luisi, 2007).In the final analysis, as with all science, deep understanding is more important than labelling with words.“Synthetic biology also could conceivably help overcome the ‘n = 1 problem''—namely, that we base biological theorising on terrestrial life only,” Nicholson said. “In this way, synthetic biology could contribute to the development of a more general, broader understanding of what life is and how it might be defined.”No matter the uncertainties, researchers will continue their attempts to create life in the test tube—it is, after all, one of the greatest scientific challenges. Whether or not they succeed will depend partly on the definition of life that they use, though in any case, the research should yield numerous insights that are beneficial to biologists generally. “The process of creating a living system from chemical components will undoubtedly offer many rich insights into biology,” Davies concluded. “However, the definition will, I fear, reflect politics more than biology. Any definition will, therefore, be subject to a lot of inter-lab political pressure. Definitions are also important for bioethical legislation and, as a result, reflect larger politics more than biology. In the final analysis, as with all science, deep understanding is more important than labelling with words.”  相似文献   

4.
Wolinsky H 《EMBO reports》2011,12(2):107-109
Considering a patient''s ethnic background can make some diagnoses easier. Yet, ‘racial profiling'' is a highly controversial concept and might soon be replaced by the advent of individualized medicine.In 2005, the US Food and Drug Administration (FDA; Bethesda, MD, USA) approved BiDil—a combination of vasodilators to treat heart failure—and hailed it as the first drug to specifically treat an ethnic group. “Approval of a drug to treat severe heart failure in self-identified black population is a striking example of how a treatment can benefit some patients even if it does not help all patients,” announced Robert Temple, the FDA''s Director of Medical Policy. “The information presented to the FDA clearly showed that blacks suffering from heart failure will now have an additional safe and effective option for treating their condition” (Temple & Stockbridge, 2007). Even the National Medical Association—the African-American version of the American Medical Association—advocated the drug, which was developed by NitroMed, Inc. (Lexington, MA, USA). A new era in medicine based on racial profiling seemed to be in the offing.By January 2008, however, the ‘breakthrough'' had gone bust. NitroMed shut down its promotional campaign for BiDil—a combination of the vasodilators isosorbide dinitrate, which affects arteries and veins, and hydralazine hydrochloride, which predominantly affects arteries. In 2009, it sold its BiDil interests and was itself acquired by another pharmaceutical company.In the meantime, critics had largely discredited the efforts of NitroMed, thereby striking a blow against the drug if not the concept of racial profiling or race-based medicine. Jonathan Kahn, a historian and law professor at Hamline University (St Paul, MN, USA), described the BiDil strategy as “a leap to genetics.” He demonstrated that NitroMed, motivated to extend its US patent scheduled to expire in 2007, purported to discover an advantage for a subpopulation of self-identified black people (Kahn, 2009). He noted that NitroMed conducted a race-specific trial to gain FDA approval, but, as there were no comparisons with other populations, it never had conclusive data to show that BiDil worked in black people differently from anyone else.“If you want to understand heart failure, you look at heart failure, and if you want to understand racial disparities in conditions such as heart failure or hypertension, there is much to look at that has nothing to do with genetics,” Kahn said, adding “that jumping to race as a genetic construct is premature at best and reckless generally in practice.” The USA, he explained, has a century-old tradition of marketing to racial and ethnic groups. “BiDil brought to the fore the notion that you can have ethnic markets not only in things like cigarettes and food, but also in pharmaceuticals,” Kahn commented.“BiDil brought to the fore the notion that you can have ethnic markets not only in things like cigarettes and food, but also in pharmaceuticals”However, despite BiDil''s failure, the search for race-based therapies and diagnostics is not over. “What I have found is an increasing, almost exponential, rise in the use of racial and ethnic categories in biotechnology-related patents,” Kahn said. “A lot of these products are still in the pipeline. They''re still patent applications, they''re not out on the market yet so it''s hard to know how they''ll play out.”The growing knowledge of the human genome is also providing new opportunities to market medical products aimed at specific ethnic groups. The first bumpy steps were taken with screening for genetic risk factors for breast cancers. Myriad Genetics (Salt Lake City, UT, USA) holds broad patents in the USA for breast-cancer screening tests that are based on mutations of the BRCA1 and BRCA2 genes, but it faced challenges in Europe, where critics raised concerns about the high costs of screening.The growing knowledge of the human genome is also providing new opportunities to market medical products aimed at specific ethnic groupsThe European Patent Office initially granted Myriad patents for the BRCA1 and BRCA2-based tests in 2001, after years of debate. But it revoked the patent on BRCA1 in 2005, which was again reversed in 2009. In 2005 Myriad decided to narrow the scope of BRCA2 testing on the basis of ethnicity. The company won a patent to predict breast-cancer risk in Ashkenazi Jewish women on the basis of BRCA2 mutations, which occur in one in 100 of these women. Physicians offering the test are supposed to ask their patients whether they are in this ethnic group, and then pay a fee to Myriad.Kahn said Myriad took this approach to package the test differently in order to protect its financial interests. However, he commented, the idea of ethnic profiling by asking women whether they identify themselves as Ashkenazi Jewish and then paying extra for an ‘ethnic'' medical test did not work in Europe. “It''s ridiculous,” Kahn commented.After the preliminary sequence of the human genome was published a decade ago, experts noted that humans were almost the same genetically, implying that race was irrelevant. In fact, the validity of race as a concept in science—let alone the use of the word—has been hotly debated. “Race, inasmuch as the concept ought to be used at all, is a social concept, not a biological one. And using it as though it were a biological one is as a much an ethical problem as a scientific problem,” commented Samia Hurst, a physician and bioethicist at Geneva University Medical School in Switzerland.Switzerland.Open in a separate window© Monalyn Gracia/CorbisCiting a popular slogan: “There is no gene for race,” she noted, “there doesn''t seem to be a single cluster of genes that fits with identification within an ethnic group, let alone with disease risks as well. We''re also in an increasingly mixed world where many people—and I count myself among them—just don''t know what to check on the box. If you start counting up your grandparents and end up with four different ethnic groups, what are you going to do? So there are an increasing number of people who just don''t fit into those categories at all.”Still, some dismiss criticism of racial profiling as political correctness that could potentially prevent patients from receiving proper care. Sally Satel, a psychiatrist in Washington, DC, USA, does not shy away from describing herself as a racially profiling physician and argues that it is good medicine. A commentator and resident scholar at the nonpartisan conservative think tank, the American Enterprise Institute (Washington, DC, USA), Satel wrote the book PC, M.D.: How Political Correctness is Corrupting Medicine. “In practicing medicine, I am not color blind. I take note of my patient''s race. So do many of my colleagues,” she wrote in a New York Times article entitled “I am a racially profiling doctor” (Satel, 2002).…some dismiss criticism of racial profiling as political correctness that could potentially prevent patients from receiving proper careSatel noted in an interview that it is an undeniable fact that black people tend to have more renal disease, Native Americans have more diabetes and white people have more cystic fibrosis. She said these differences can help doctors to decide which drugs to prescribe at which dose and could potentially lead researchers to discover new therapies on the basis of race.Satel added that the mention of race and medicine makes many people nervous. “You can dispel that worry by taking pains to specify biological lineage. Simply put, members of a group have more genes in common than members of the population at large. Some day geneticists hope to be able to conduct genomic profiles of each individual, making group identity irrelevant, but until then, race-based therapeutics has its virtues,” she said. “Denying the relationship between race and medicine flies in the face of clinical reality, and pretending that we are all at equal risk for health problems carries its own dangers.”However, Hurst contended that this approach may be good epidemiology, rather than racial profiling. Physicians therefore need to be cautious about using skin colour, genomic data and epidemiological data in decision making. “If African Americans are at a higher risk for hypertension, are you not going to check for hypertension in white people? You need to check in everyone in any case,” she commented.Hurst said European physicians, similarly to their American colleagues, deal with race and racial profiling, albeit in a different way. “The way in which we struggle with it is strongly determined by the history behind what could be called the biases that we have. If you have been a colonial power, if the past is slavery or if the past or present is immigration, it does change some things,” she said. “On the other hand, you always have the difficulty of doing fair and good medicine in a social situation that has a kind of ‘them and us'' structure. Because you''re not supposed to do medicine in a ‘them and us'' structure, you''re supposed to treat everyone according to their medical needs and not according to whether they''re part of ‘your tribe'' or ‘another tribe''.”Indeed, social factors largely determine one''s health, rather than ethnic or genetic factors. August A. White III, an African-American orthopaedic surgeon at Harvard Medical School (Boston, MA, USA) and author of the book Seeing Patients: Unconscious Bias In Health Care, noted that race is linked to disparities in health care in the USA. A similar point can be made in Europe where, for example, Romani people face discrimination in several countries.White said that although genetic research shows that race is not a scientific concept, the way people are labelled in society and how they are treated needs to be taken into account. “It''d be wonderful at some point if we can pop one''s key genetic information into a computer and get a printout of which medications are best of them and which doses are best for them,” he commented. “In the meantime though, I advocate careful operational attempts to treat everyone as human beings and to value everyone''s life, not devalue old people, or devalue women, or devalue different religious faiths, etc.”Notwithstanding the scientific denunciation, a major obstacle for the concept of racial profiling has been the fact that the word ‘race'' itself is politically loaded, as a result of, among other things, the baggage of eugenics and Nazi racism and the legacies of slavery and colonialism. Richard Tutton, a sociologist at Lancaster University in the UK, said that British scientists he interviewed for a Wellcome Trust project a few years ago prefer the term ethnicity to race. “Race is used in a legal sense in relation to inequality, but certainly otherwise, ethnicity is the preferred term, which obviously is different to the US” he said. “I remember having conversations with German academics and obviously in Germany you couldn''t use the R-word.”Jan Helge Solbakk, a physician, theologian and medical ethicist at the University of Oslo in Norway, said the use of the term race in Europe is a non-starter because it makes it impossible for the public and policy-makers to communicate. “I think in Europe it would be politically impossible to launch a project targeting racial differences on the genetic level. The challenge is to find not just a more politically correct concept, but a genetically more accurate concept and to pursue such research questions,” he said. According to Kahn, researchers therefore tend to refer to ethnicity rather than race: “They''re talking about European, Asian and African, but they''re referring to it as ethnicity instead of race because they think somehow that''s more palatable.”Regardless, race-based medicine might just be a stepping stone towards more refined and accurate methods, with the advent of personalized medicine based on genomics, according to Leroy Hood, whose work has helped to develop tools to analyse the human genome. The focus of his company—the Institute for Systems Biology (Seattle, WA, USA)—is to identify genetic variants that can inform and help patients to pioneer individualized health care.“Race as a concept is disappearing with interbreeding,” Hood said. “Race distinction is going to slowly fade away. We can use it now because we have signposts for race, which are colour, fairness, kinkiness of hair, but compared to a conglomeration of things that define a race, those are very few features. The race-defining features are going to be segregating away from one another more and more as the population becomes racially heterogeneous, so I think it''s going to become a moot point.”Hood instead advocates “4P” health care—“Predictive, Personalized, Preventive and Participatory.” “My overall feeling about the race-based correlations is that it is far more important to think about the individual and their individual unique spectra of health and wellness,” he explained. “I think we are not going to deal in the future with racial or ethnic populations, rather medicine of the future is going to be focused entirely on the individual.”Yet, Arthur Caplan, Director of the Center for Bioethics at the University of Pennsylvania (Philadelphia, PA, USA), is skeptical about the prospects for both race-based and personalized medicine. “Race-based medicine will play a minor role over the next few years in health care because race is a minor factor in health,” he said. “It''s not like we have a group of people who keel over dead at 40 who are in the same ethnic group.”Caplan also argued that establishing personalized genomic medicine in a decade is a pipe dream. “The reason I say that is it''s not just the science,” he explained. “You have to redo the whole health-care system to make that possible. You have to find manufacturers who can figure out how to profit from personalized medicine who are both in Europe and the United States. You have to have doctors that know how to prescribe them. It''s a big, big revamping. That''s not going to happen in 10 years.”Hood, however, is more optimistic and plans to advance the concept with pilot projects; he believes that Europe might be the better testing ground. “I think the European systems are much more efficient for pioneering personalized medicine than the United States because the US health-care system is utterly chaotic. We have every combination of every kind of health care and health delivery. We have no common shared vision,” he said. “In the end we may well go to Europe to persuade a country to really undertake this. The possibility of facilitating a revolution in health care is greater in Europe than in the United States.”  相似文献   

5.

Background

In the current era of strong worldwide market couplings the global financial village became highly prone to systemic collapses, events that can rapidly sweep throughout the entire village.

Methodology/Principal Findings

We present a new methodology to assess and quantify inter-market relations. The approach is based on the correlations between the market index, the index volatility, the market Index Cohesive Force and the meta-correlations (correlations between the intra-correlations.) We investigated the relations between six important world markets—U.S., U.K., Germany, Japan, China and India—from January 2000 until December 2010. We found that while the developed “western” markets (U.S., U.K., Germany) are highly correlated, the interdependencies between these markets and the developing “eastern” markets (India and China) are volatile and with noticeable maxima at times of global world events. The Japanese market switches “identity”—it switches between periods of high meta-correlations with the “western” markets and periods when it behaves more similarly to the “eastern” markets.

Conclusions/Significance

The methodological framework presented here provides a way to quantify the evolvement of interdependencies in the global market, evaluate a world financial network and quantify changes in the world inter market relations. Such changes can be used as precursors to the agitation of the global financial village. Hence, the new approach can help to develop a sensitive “financial seismograph” to detect early signs of global financial crises so they can be treated before they develop into worldwide events.  相似文献   

6.
Rinaldi A 《EMBO reports》2012,13(1):24-27
Does the spin of an electron allow birds to see the Earth''s magnetic field? Andrea Rinaldi investigates the influence of quantum events in the biological world.The subatomic world is nothing like the world that biologists study. Physicists have struggled for almost a century to understand the wave–particle duality of matter and energy, but many questions remain unanswered. That biological systems ultimately obey the rules of quantum mechanics might be self-evident, but the idea that those rules are the very basis of certain biological functions has needed 80 years of thought, research and development for evidence to begin to emerge (Sidebar A).

Sidebar A | Putting things in their place

Although Erwin Schrödinger (1887–1961) is often credited as the ‘father'' of quantum biology, owing to the publication of his famous 1944 book, What is Life?, the full picture is more complex. While other researchers were already moving towards these concepts in the 1920s, the German theoretical physicist Pascual Jordan (1902–1980) was actually one of the first to attempt to reconcile biological phenomena with the quantum revolution that Jordan himself, working with Max Born and Werner Heisenberg, largely ignited. “Pascual Jordan was one of many scientists at the time who were exploring biophysics in innovative ways. In some cases, his ideas have proven to be speculative or even fantastical. In others, however, his ideas have proven to be really ahead of their time,” explained Richard Beyler, a science historian at Portland State University, USA, who analysed Jordan''s contribution to the rise of quantum biology (Beyler, 1996). “I think this applies to Jordan''s work in quantum biology as well.”Beyler also remarked that some of the well-known figures of molecular biology''s past—Max Delbrück is a notable example—entered into their studies at least in part as a response or rejoinder to Jordan''s work. “Schrödinger''s book can also be read, on some level, as an indirect response to Jordan,” Beyler said.Jordan was certainly a complex personality and his case is rendered more complicated by the fact that he explicitly hitched his already speculative scientific theories to various right-wing political philosophies. “During the Nazi regime, for example, he promoted the notion that quantum biology served as evidence for the naturalness of dictatorship and the prospective death of liberal democracy,” Beyler commented. “After 1945, Jordan became a staunch Cold Warrior and saw in quantum biology a challenge to philosophical and political materialism. Needless to say, not all of his scientific colleagues appreciated these propagandistic endeavors.”Pascual Jordan [pictured above] and the dawn of quantum biology. From 1932, Jordan started to outline the new field''s background in a series of essays that were published in journals such as Naturwissenschaften. An exposition of quantum biology is also encountered in his book Die Physik und das Geheimnis des organischen Lebens, published in 1941. Photo courtesy of Luca Turin.Until very recently, it was not even possible to investigate whether quantum phenomena such as coherence and entanglement could play a significant role in the function of living organisms. As such, researchers were largely limited to computer simulations and theoretical experiments to explain their observations (see A quantum leap in biology, www.emboreports.org). Recently, however, quantum biologists have been making inroads into developing methodology to measure the degree of quantum entanglement in light-harvesting systems. Their breakthrough has turned once ephemeral theories into solid evidence, and has sparked the beginning of an entirely new discipline.How widespread is the direct relevance of quantum effects in nature is hard to say and many scientists suspect that there are only a few cases in which quantum mechanics have a crucial role. However, interest in the field is growing and researchers are looking for more examples of quantum-dependent biological systems. In a way, quantum biology can be viewed as a natural evolution of biophysics, moving from the classical to the quantum, from the atomic to the subatomic. Yet the discipline might prove to be an even more intimate and further-reaching marriage that could provide a deeper understanding of things such as protein energetics and dynamics, and all biological processes where electrons flow.Recently […] quantum biologists have been making inroads into developing methodology to measure the degree of quantum entanglement in light-harvesting systemsAmong the biological systems in which quantum effects are believed to have a crucial role is magnetoreception, although the nature of the receptors and the underlying biophysical mechanisms remain unknown. The possibility that organisms use a ferromagnetic material (magnetite) in some cases has received some confirmation, but support is growing for the explanation lying in a chemical detection mechanism with quantum mechanical properties. This explanation posits a chemical compass based on the light-triggered production of a radical pair—a pair of molecules each with an unpaired electron—the spins of which are entangled. If the products of the radical pair system are spin-dependent, then a magnetic field—like the geomagnetic one—that affects the direction of spin will alter the reaction products. The idea is that these reaction products affect the sensitivity of light sensors in the eye, thus allowing organisms to ‘see'' magnetic fields.The research comes from a team led by Thorsten Ritz at the University of California Irvine, USA, and other groups, who have suggested that the radical pair reaction takes place in the molecule cryptochrome. Cryptochromes are flavoprotein photoreceptors first identified in the model plant Arabidopsis thaliana, in which they play key roles in growth and development. More recently, cryptochromes have been found to have a role in the circadian clock of fruit flies (Ritz et al, 2010) and are known to be present in migratory birds. Intriguingly, magnetic fields have been shown to have an effect on both Arabidopsis seedlings, which respond as though they have been exposed to higher levels of blue light, and Drosophila, in which the period length of the clock is lengthened, mimicking the effect of increased blue light signal intensity on cryptochromes (Ahmad et al, 2007; Yoshii et al, 2009).“The study of quantum effects in biological systems is a rapidly broadening field of research in which intriguing phenomena are yet to be uncovered and understood”Direct evidence that cryptochrome is the avian magnetic compass is currently lacking, but the molecule does have some features that make its candidacy possible. In a recent review (Ritz et al, 2010), Ritz and colleagues discussed the mechanism by which cryptochrome might form radical pairs. They argued that “Cryptochromes are bound to a light-absorbing flavin cofactor (FAD) which can exist in three interconvertable [sic] redox forms: (FAD, FADH, FADH),” and that the redox state of FAD is light-dependent. As such, both the oxidation and reduction of the flavin have radical species as intermediates. “Therefore both forward and reverse reactions may involve the formation of radical pairs” (Ritz et al, 2010). Although speculative, the idea is that a magnetic field could alter the spin of the free electrons in the radical pairs resulting in altered photoreceptor responses that could be perceived by the organism. “Given the relatively short time from the first suggestion of cryptochrome as a magnetoreceptor in 2000, the amount of studies from different fields supporting the photo-magnetoreceptor and cryptochrome hypotheses […] is promising,” the authors concluded. “It suggests that we may be only one step away from a true smoking gun revealing the long-sought after molecular nature of receptors underlying the 6th sense and thus the solution of a great outstanding riddle of sensory biology.”Research into quantum effects in biology took off in 2007 with groundbreaking experiments from Graham Fleming''s group at the University of California, Berkeley, USA. Fleming''s team were able to develop tools that allowed them to excite the photosynthetic apparatus of the green sulphur bacterium Chlorobium tepidum with short laser pulses to demonstrate that wave-like energy transfer takes place through quantum coherence (Engel et al, 2007). Shortly after, Martin Plenio''s group at Ulm University in Germany and Alán Aspuru-Guzik''s team at Harvard University in the USA simultaneously provided evidence that it is a subtle interplay between quantum coherence and environmental noise that optimizes the performance of biological systems such as the photosynthetic machinery, adding further interest to the field (Plenio & Huelga, 2008; Rebentrost et al, 2009). “The recent Quantum Effects in Biological Systems (QuEBS) 2011 meeting in Ulm saw an increasing number of biological systems added to the group of biological processes in which quantum effects are suspected to play a crucial role,” commented Plenio, one of the workshop organizers; he mentioned the examples of avian magnetoreception and the role of phonon-assisted tunnelling to explain the function of the sense of smell (see below). “The study of quantum effects in biological systems is a rapidly broadening field of research in which intriguing phenomena are yet to be uncovered and understood,” he concluded.“The area of quantum effects in biology is very exciting because it is pushing the limits of quantum physics to a new scale,” Yasser Omar from the Technical University of Lisbon, Portugal commented. ”[W]e are finding that quantum coherence plays a significant role in the function of systems that we previously thought would be too large, too hot—working at physiological temperatures—and too complex to depend on quantum effects.”Another growing focus of quantum biologists is the sense of smell and odorant recognition. Mainstream researchers have always favoured a ‘lock-and-key'' mechanism to explain how organisms detect and distinguish different smells. In this case, the identification of odorant molecules relies on their specific shape to activate receptors on the surface of sensory neurons in the nasal epithelium. However, a small group of ‘heretics'' think that the smell of a molecule is actually determined by intramolecular vibrations, rather than by its shape. This, they say, explains why the shape theory has so far failed to explain why different molecules can have similar odours, while similar molecules can have dissimilar odours. It also goes some way to explaining how humans can manage with fewer than 400 smell receptors.…determining whether quantum effects have a role in odorant recognition has involved assessing the physical violations of such a mechanism […] and finding that, given certain biological parameters, there are noneA recent study in Proceedings of the National Academy of Sciences USA has now provided new grist for the mill for ‘vibrationists''. Researchers from the Biomedical Sciences Research Center “Alexander Fleming”, Vari, Greece—where the experiments were performed—and the Massachusetts Institute of Technology (MIT), USA, collaborated to replace hydrogen with deuterium in odorants such as acetophenone and 1-octanol, and asked whether Drosophila flies could distinguish the two isotopes, which are identically shaped but vibrate differently (Franco et al, 2011). Not only were the flies able to discriminate between the isotopic odorants, but when trained to discriminate against the normal or deuterated isotopes of a compound, they could also selectively avoid the corresponding isotope of a different odorant. The findings are inconsistent with a shape-only model for smell, the authors concluded, and suggest that flies can ‘smell molecular vibrations''.“The ability to detect heavy isotopes in a molecule by smell is a good test of shape and vibration theories: shape says it should be impossible, vibration says it should be doable,” explained Luca Turin from MIT, one of the study''s authors. Turin is a major proponent of the vibration theory and suggests that the transduction of molecular vibrations into receptor activation could be mediated by inelastic electron tunnelling (Fig 1; see also The scent of life, www.emboreports.org). “The results so far had been inconclusive and complicated by possible contamination of the test odorants with impurities,” Turin said. “Our work deals with impurities in a novel way, by asking flies whether the presence of deuterium isotope confers a common smell character to odorants, much in the way that the presence of -SH in a molecule makes it smell ‘sulphuraceous'', regardless of impurities. The flies'' answer seems to be ‘yes''.”Open in a separate windowFigure 1Diagram of a vibration-sensing receptor using an inelastic electron tunnelling mechanism. An odorant—here benzaldehyde—is depicted bound to a protein receptor that includes an electron donor site at the top left to which an electron—blue sphere—is bound. The electron can tunnel to an acceptor site at the bottom right while losing energy (vertical arrow) by exciting one or more vibrational modes of the benzaldehyde. When the electron reaches the acceptor, the signal is transduced via a G-protein mechanism, and the olfactory stimulus is triggered. Credit: Luca Turin.One of the study''s Greek co-authors, Efthimios Skoulakis, suggested that flies are better suited than humans at doing this experiment for a couple of reasons. “[The flies] seem to have better acuity than humans and they cannot anticipate the task they will be required to complete (as humans would), thus reducing bias in the outcome,” he said. “Drosophila does not need to detect deuterium per se to survive and be reproductively successful, so it is likely that detection of the vibrational difference between such a compound and its normal counterpart reflects a general property of olfactory systems.”The question of whether quantum mechanics really plays a non-trivial role in biology is still hotly debated by physicists and biologists alikeJennifer Brookes, a physicist at University College London, UK, explained that recent advances in determining whether quantum effects have a role in odorant recognition has involved assessing the physical violations of such a mechanism in the first instance, and finding that, given certain biological parameters, there are none. “The point being that if nature uses something like the quantized vibrations of molecules to ‘measure'' a smell then the idea is not—mathematically, physically and biologically—as eccentric as it at first seems,” she said. Moreover, there is the possibility that quantum mechanics could play a much broader role in biology than simply underpinning the sense of smell. “Odorants are not the only small molecules that interact unpredictably with large proteins; steroid hormones, anaesthetics and neurotransmitters, to name a few, are examples of ligands that interact specifically with special receptors to produce important biological processes,” Brookes wrote in a recent essay (Brookes, 2010).The question of whether quantum mechanics really plays a non-trivial role in biology is still hotly debated by physicists and biologists alike. “[A] non-trivial quantum effect in biology is one that would convince a biologist that they needed to take an advanced quantum mechanics course and learn about Hilbert space and operators etc., so that they could understand the effect,” argued theoretical quantum physicists Howard Wiseman and Jens Eisert in their contribution to the book Quantum Aspects of Life (Wiseman & Eisert, 2008). In their rational challenge to the general enthusiasm for a quantum revolution in biology, Wiseman and Eisert point out that a number of “exotic” and “implausible” quantum effects—including a quantum life principle, quantum computing in the brain, quantum computing in genetics, and quantum consciousness—have been suggested and warn researchers to be cautious of “ideas that are more appealing at first sight than they are realistic” (Wiseman & Eisert, 2008).“One could easily expect many more new exciting ideas and discoveries to emerge from the intersection of two major areas such as quantum physics and biology”Keeping this warning in mind, the view of life from a quantum perspective can still provide a deeper insight into the mechanisms that allow living organisms to thrive without succumbing to the increasing entropy of their environment. But does quantum biology have practical applications? “The investigation of the role of quantum physics in biology is fascinating because it could help explain why evolution has favoured some biological designs, as well as inspire us to develop more efficient artificial devices,” Omar said. The most often quoted examples of such devices are solar collectors that would use efficient energy transport mechanisms inspired by the quantum proficiency of natural light-harvesting systems, and quantum computing. But there is much more ahead. In 2010, the Pentagon''s cutting-edge research branch, DARPA (Defense Advanced Research Projects Agency, USA), launched a solicitation for innovative proposals in the area of quantum effects in a biological environment. “Proposed research should establish beyond any doubt that manifestly quantum effects occur in biology, and demonstrate through simulation proof-of-concept experiments that devices that exploit these effects could be developed into biomimetic sensors,” states the synopsis (DARPA, 2010). This programme will thus look explicitly at photosynthesis, magnetic field sensing and odour detection to lay the foundations for novel sensor technologies for military applications.Clearly a number of civil needs could also be fulfilled by quantum-based biosensors. Take, for example, the much sought-after ‘electronic nose'' that could replace the use of dogs to find drugs or explosives, or could assess food quality and safety. Such a device could even be used to detect cancer, as suggested by a recent publication from a Swedish team of researchers who reported that ovarian carcinomas emit a different array of volatile signals to normal tissue (Horvath et al, 2010). “Our goal is to be able to screen blood samples from apparently healthy women and so detect ovarian cancer at an early stage when it can still be cured,” said the study''s leading author György Horvath in a press release (University of Gothenburg, 2010).Despite its already long incubation time, quantum biology is still in its infancy but with an intriguing adolescence ahead. “A new wave of scientists are finding that quantum physics has the appropriate language and methods to solve many problems in biology, observing phenomena from a different point of view and developing new concepts. The next important steps are experimental verification/falsification,” Brookes said. “One could easily expect many more new exciting ideas and discoveries to emerge from the intersection of two major areas such as quantum physics and biology,” Omar concluded.  相似文献   

7.
Nodal Morphogens     
Nodal signals belong to the TGF-β superfamily and are essential for the induction of mesoderm and endoderm and the determination of the left–right axis. Nodal signals can act as morphogens—they have concentration-dependent effects and can act at a distance from their source of production. Nodal and its feedback inhibitor Lefty form an activator/inhibitor pair that behaves similarly to postulated reaction–diffusion models of tissue patterning. Nodal morphogen activity is also regulated by microRNAs, convertases, TGF-β signals, coreceptors, and trafficking factors. This article describes how Nodal morphogens pattern embryonic fields and discusses how Nodal morphogen signaling is modulated.In his 1901 book “Regeneration,” Thomas Hunt Morgan speculated that “if we suppose the materials or structures that are characteristic of the vegetative half are gradually distributed from the vegetative to the animal half in decreasing amounts, then any piece of the egg will contain more of these things at one pole than the other” and “gastrulation depends on the relative amounts of the materials in the different parts of the blastula” (Morgan 1901). Although Morgan’s speculations referred to the sea urchin embryo, they foretold our current understanding of morphogen gradients in frog and fish development. Morgan’s “materials,” “structures,” and “things” are the Nodal signals that create a vegetal-to-animal activity gradient to regulate germ layer formation and patterning. This article discusses how Nodal signaling provides positional information to fields of cells. I first portray the components of the signaling pathway and describe the role of Nodal signals in mesendoderm induction and left–right axis specification. I then discuss how Nodal morphogen gradients are thought to be generated, modulated, and interpreted.  相似文献   

8.
The psycho gene     
Philip Hunter 《EMBO reports》2010,11(9):667-669
While the idea of a ‘criminal gene'' is nonsense, there is growing evidence that some psychopathic behaviour might indeed be grounded in genesThe notion that genes play an important role in many diseases has been widely accepted, but many find it much harder to acknowledge a similar link with particular behaviour or even predisposition to crime. Partly for this reason, the study of behavioural genetics remains a controversial topic, with disagreement not just over the science itself, but even more so about the therapeutic, societal and legal implications.Too much might have been made too soon of early findings that made correlations between alleles of certain genes and tendencies to antisocial or criminal behaviour. Indeed, most researchers in the field were appalled by the decision of an Italian appeal court in 2009 to cut the sentence of a convicted murderer by one year on the grounds that he had a version of the MAOA gene, which has been linked to aggression and violence (Feresin, 2009). There is equal dismay over some US courts that went the other way and accepted genetic factors as evidence for the prosecution, leading to higher sentences on the basis that people with particular alleles cannot be cured and will remain a risk to society for longer.“Taking genetic factors into account when sentencing is plain stupid, unless we are talking about something like Down''s syndrome or some other syndrome that drastically reduces intelligence and executive functioning,” insisted Anthony Walsh from the Criminal Justice Department at Boise State University in Idaho, USA. “This is the kind of “genetic determinism” that liberals have worried themselves silly over. They just have to take one or two neuroscience and genetic classes to dispense with their ‘my genes/neurons'' made me do it. Nothing relieves one of the obligation to behave civilized.”Nonetheless, the case against specific alleles has been accumulating, notably for the low-expression variant of MAOA, known as MAOA-L, which has been linked in various studies with increased risk of violent and aggressive behaviour. The gene MAOA encodes monoamine oxidase A, an enzyme that degrades amine neurotransmitters, such as dopamine, noradrenalin and serotonin. A rare genetic disorder caused by an MAOA mutation leads to MAOA deficiency and in turn an excess of monoamine transmitters, causing excessive impulsive behaviour including hypersexuality, sleep disorder and extreme mood swings as well as a tendency to violence, which is known as Brunner syndrome.…the study of behavioural genetics remains a controversial topic, with disagreement not just over the science itself, but even more so about the therapeutic, societal and legal implicationsBut while Brunner''s syndrome is rare, having only been identified in five males of one extended family, the MAOA-L variant is extremely common and occurs in about 40% of the population. Clearly, most of these people are peaceable and have never committed a crime, and yet a study involving researchers from Austria, Italy and the USA—headed by Andreas Meyer-Lindenberg, Director of the Central Institute of Mental Health in Mannheim, Germany—has discovered that at least males with this variant had neurobiological structural factors that would predispose them to violence (Meyer et al, 2006).Using structural MRI scanning, the study identified that people with MAOA-L were more likely to have a smaller limbic system—the hippocampus, amygdala, anterior thalamic nuclei and limbic cortex—which participates in emotion, behaviour and long-term memory. The team then applied functional MRI, which measures changes in blood flow, and discovered that the MAOA-L group also showed hyperresponsiveness of the amygdala during tasks such as copying facial expressions. The amygdala is associated with emotional processing and the MAOA-L group was less able to inhibit strong emotional impulses.But some trigger is still needed to tip MAOA-L people towards violence. An earlier study suggested that this trigger could be persistent maltreatment during childhood (Caspi et al, 2002). At first sight, this suggests that nearly half the human population are predisposed to violence given these triggers, but the situation is not quite that bad—it is merely nearly half of men. Women are protected in two ways: the MAOA gene is linked to the X chromosome so that women with the MAOA-L variety on one chromosome usually have a normal allele on the other; and there is circumstantial evidence that women are also protected by other genes from being disposed to violence.In any case, caution is needed to interpret the findings of Mayer-Lindenberg''s group about the MAOA-L allele, according to Ahmad Hariri, Investigator at the Institute for Genome Sciences & Policy at Duke University (Durham, NC, USA). “This is a significant basic science finding linking genes to brain to behaviour,” he said. “But it is not a significant clinical finding in and of itself. Only in as much as this very, very, very subtle bias in the brain tips the balance toward an aggressive response to provocation is this finding even remotely clinically relevant.” In fact, as Meyer-Lindenberg himself has commented, the MAOA-L allele is just one of several genes—most of which are still not identified—that increase risk of violent or antisocial behaviour.But the whole story takes a rather different turn in the case of psychopathy, which is now widely regarded as a congenital state characterized by lack of empathy or moral compass and defined at least partly by genes, in contrast to other forms of sociopathy or antisocial personality disorder (APD), in which environmental factors make a major contribution (Fontaine & Viding, 2008).“Taking genetic factors into account when sentencing is plain stupid…”“…it is useful to think of psychopathy as mainly the product of genes and sociopathy as more subject to environmental influences”“Psychopathy does seem to be heritable, and appears to have its basis at least in part in “biological” factors linked to basic emotional systems, so that the mature psychopath never develops a complete set of pro-social emotions like empathy, guilt, and the ability to truly care about and for others,” said Richard Wiebe, who specializes in the link between psychology and criminology at Fitchburg State College in Fitchburg, MA, USA. Wiebe added though that the heritability of underlying genetic factors had yet to be conclusively established. “In other words, we know that the dependent variable, that is psychopathy, is heritable, but not enough about its causes to say that they are heritable. Nevertheless it is useful to think of psychopathy as mainly the product of genes and sociopathy as more subject to environmental influences.”Environmental factors do play a part in the behaviour of psychopaths, but in a different way than in other people who develop antisocial tendencies. The condition is more common than was once thought and affects about 0.6% of the population, according to a recent study conducted in the UK (Coid et al, 2009). Obviously, psychopathy does not always lead to crime or extreme violent behaviour; indeed its occurrence in the population used to be significantly underestimated because it was diagnosed only in people who had already shown extreme behaviour when many psychopaths do not.As there is no genetic or clinical test as yet, psychopathy is still diagnosed in terms of behaviour, but taking account of various factors in combination. Robert Hare, who led the UK study and is now at the Department of Psychology of the University of British Columbia in Vancouver, Canada, has designed a test known as the ‘Psychopathy Checklist—Revised'' of about 20 symptoms that he uses to diagnose psychopathy. These include pathological lying, superficial charm, lack of empathy and guilt, proneness to boredom and sexual promiscuity.Although it is not part of the Hare checklist, psychopaths can also be detected by their lack of a “startle reflex”, which means failure of their nervous system to respond to images or events that frighten or shock other people, such as pictures of a decapitated corpse. These tests work just as well for psychopaths who have never indulged in violence and apparently lead normal lives. They can also be used to identify psychopathy in children, who exhibit the same symptoms, in particular pathological lying, lack of empathy, tendency to violence, and lack of startle reflex—in fact, several studies have found evidence of inherited psychopathy in quite young children (Viding et al, 2005).It also appears that psychopathy is more common in men than women. This supports the theory that psychopathy might be an adaptive personality trait that gives men a reproductive advantage through greater tendency and ability to form numerous relationships and so have more children. This is unproven, but it is certainly true that male psychopaths tend to form large numbers of short-term relationships and can have an almost seductive charm.However, the trait would lose its advantage if it became too common in the population. A particular trait tends only to be advantageous in certain environmental conditions as was pointed out in the context of psychopathy by Essi Viding, Co-Director of the Developmental Risk and Resilience Unit at the Department of Psychology at University College London, UK. “I think that the simple game of evolution is to ensure survival of the species under different environmental conditions,” she said. “In some conditions it may be adaptive to be anxious and cooperative, in other conditions it may be good to exploit and be antisocial. This of course is effectively contrasting alleles that have very different effects. Hence, the same allele may serve an individual very well (and in a socially acceptable manner) in one situation, but not in another.”…psychopathy might be an adaptive personality trait that gives men a reproductive advantage through greater tendency and ability to form numerous relationships and so have more childrenThis leads back to the observation that psychopathy seems to be more common in men than women, which could have two possible explanations. First, it might be true at the genetic and neurological level, in particular if some of the relevant genes are linked to the X chromosome. Yet, this is speculative as few genes have been identified that contribute specifically to psychopathy, with most of the evidence for its heritability being statistical. There is the case of the X-linked MAOA gene, but that has only been associated with general antisocial tendencies.…irrespective of where future research leads, genes should not influence sentencing decisions one way or the other because they can never be deemed responsible for behaviourThere is in any case an alternative explanation for the apparent gender difference in psychopathic prevalence. Alice Jones, specialist in childhood and adolescent psychopathy and antisocial behaviour at Goldsmiths College, University of London, UK, suggests that the condition could be much more common among women than studies suggest. It might be that women will, in many cases, fail to register on the Hare Psychopathy Checklist—Revised because the more extreme traits are cushioned by other female factors. “There is some evidence to support this idea,” said Jones, citing work by Randy Salekin at the University of Alabama, in the USA (Salekin et al, 1997) who found that just as many women as men pass the Hare test in terms of their lack of empathy, but not on the more violent and impulsive criteria. “So, while the interpersonal aspects of psychopathy seem to be present and similar in males and females, the behavioural aspects of psychopathy are very much male-heavy,” said Jones.This comes back to the question of treatment and sentencing. Viding argues that irrespective of where future research leads, genes should not influence sentencing decisions one way or the other because they can never be deemed responsible for behaviour. “Any gene alone will be neither necessary, nor sufficient to predispose someone to high levels of psychopathic traits and as such, the responsibility for choosing to offend still resides with an individual,” she said. “Most ‘risk genes'' are common in the population and yet do not cause the majority of the individuals carrying them to offend.”But the situation is different when it comes to treatment—the appropriate therapy will depend on underlying personality tendencies. Psychopaths tend not to respond well to punishment because they cannot associate it with acts they do not consider in any way morally wrong, according to Jones. But they are more likely to respond to reward. “One example of this is currently underway at a school in Buckinghamshire (UK) for primary aged children with Emotional and Behavioural Difficulties,” said Jones. “There have been very encouraging reports from teachers so far. The intervention is largely reward based, and the pupils gain rewards by working toward reaching their behavioural targets each week. Pupils can ‘cash-in'' their rewards daily, or they can save them up for a more substantial reward later in the week.”Whether this will help these children to lead constructive adult lives remains to be seen. It does provide further evidence though that while it might not be possible to cure psychopaths, it may be possible to direct their selfish tendencies away from crime and violence towards more positive and creative activities.  相似文献   

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Philip Hunter 《EMBO reports》2010,11(8):583-586
Current research aims to produce traditional biofuels from algae, but their potential to generate sustainable energy might be even greater and more ‘natural''At the time of writing, oil continues to pour into the Gulf of Mexico. It is one of the worst environmental disasters in human history and a shocking reminder of the costs of our addiction to fossil fuels. However, the alternative sources of sustainable energy, such as wind, waves and sunshine, cannot alone replace fossil fuels in the short or even medium term. As nuclear fusion is bogged down by almost intractable engineering challenges, and nuclear fission produces toxic and radioactive waste, research has focused increasingly on converting solar energy into electricity or fuels through photosynthesis—either through the use of artificial compounds that mimic the process, or bioengineered organisms that do it ‘naturally''.…research has focused increasingly on converting solar energy into electricity or fuels through photosynthesis…In the ‘natural'' camp, microalgae—single-celled algae—have emerged as the most promising candidates, mainly because of their potential for converting solar energy more efficiently and with less negative environmental impact than the alternatives, especially biofuel crops such as corn and soy, for example. Cyanobacteria, which are photosynthesizing prokaryotes, rather than single-celled eukaryotes, also hold promise in this regard. However, as Ben Graziano, technology commercialization manager at the Carbon Trust, an independent non-profit company set up by the UK government to develop low-carbon energy technologies, pointed out: “We may look at cyanobacteria in the future […] but they produce different co-products and we need to look at those when producing a commercial case for biofuel production.”Perhaps surprisingly, the principal foundations of algae biofuel research were laid in the USA during the presidency of George W. Bush, particularly at the US National Renewable Energy Laboratory (NREL; Golden, CO), the largest federal agency dedicated to research on alternative energy. The interest in algae was triggered by the growing conviction that microalgae could greatly reduce the amount of land or water surface needed to produce sustainable energy, according to Mike Seibert, research fellow at NREL. “Corn grain ethanol—a current biofuel—has a solar energy conversion efficiency of about 0.05%, and thus has a huge land footprint,” he explained. “Replacing all the gasoline used in the USA with corn grain ethanol would take a corn field 1,000 miles (1,600 km) a side. Algae on the other hand have [a] theoretical conversion efficiency of 10% and in practice, 2%, and so could replace all US gasoline in an area 110 miles (176 km) a side.”Given this promise, Europe is racing to catch up with the USA. A lobbying group, the European Algae Biomass Association (EABA), has been established with support from the European Commission to promote research and generate funding, thus demonstrating confidence that the commercial production of algae biofuels can be achieved, perhaps within as little as a decade. In the UK, the Carbon Trust has established a programme to achieve commercial-scale production of biofuels from algae by 2020. “I think by then it will have achieved parity with current biofuels, reaching US$1 per litre production costs, about 10 times cheaper than is possible with algae today,” Graziano said.But the large-scale potential of algae biofuels remains unproven and requires more fundamental research, cautioned Pierre-Antoine Vernon, project manager of the European Biodiesel Board (EBB), a non-profit organization in Brussels, Belgium, set up in 1997 by biofuel producers to promote the development and use of biofuel in the European Union (EU). “It should be kept in mind that this is not yet a mature technology, as indicated by the diversity of algae strains, processing techniques and end products, which are typical for a nascent industry sector trying to identify the right technological path to the objective pursued,” he said.The interest in algae was triggered by the growing conviction that microalgae could greatly reduce the amount of land or water surface needed to produce sustainable energy…There are also regulatory and commercial factors that might inhibit large-scale deployment of algae farms for biofuel production. “You should not underestimate the regulatory barriers to the introduction of new technologies,” Vernon said. “The EBB is currently facing strong opposition from the oil and car industries in the context of the technical standardisation for biodiesel and diesel.”Such opposition is rooted partly in the vested interests of the oil industry, but also in a natural desire to raise the bar when it comes to monitoring the safety and environmental suitability of biofuels, which must be seen to be squeaky clean and as carbon neutral as possible. “Biofuels use is under scrutiny wherever they are used, even while they represent a mere 5% of fuels used in the EU,” Vernon said. “By contrast, the remaining 95% of fossil fuels are still free from sustainability reporting, and even massive oil spills with incomparably higher consequences on biodiversity and the environment are not likely to prompt the introduction of sustainability criteria.”There are also regulatory and commercial factors that might inhibit large-scale deployment of algae farms for biofuel productionThis last point is now being put to the test by the BP spillage in the Gulf of Mexico; US President Barack Obama, in his Oval Office speech in June, called for a new focus on alternative sources of energy. Yet even this is a double-edged sword for the biofuel industry, according to Mike Griffin, an expert on the impact of oil spills from Carnegie Mellon University (Pittsburgh, PA, USA). “For the next five years you will see more money in oil spill effects work,” he said. “More money flows after each major spill until the politicians forget. This could mean less money for everything else since, with our economic situation, the pie is shrinking.”Nevertheless, the future of algae biofuel research seems secure, even if the extent of funding depends on larger economic factors. Apart from energy conversion efficiency, algae could score from other by-products that would improve the economics of production. As Vernon noted, the economics of algae is similar to that of current biofuels in the sense that you need to find applications for the main product—the oil used to make biofuels—and the by-products, mainly protein and carbohydrates. “For soybean, which was cultivated to produce soybean meal to feed cattle long before biofuels existed, an application was already there. For algae, the challenge is to find a species whose ‘algae meal'' can be used before considering biofuels production.” Promisingly, it looks as if the “algae meal” too could be used to feed animals (Becker, 2007).In addition to protein and the oils that are used for biofuels, algae also produce carbohydrates, which could be used to produce biogas: methane and carbon dioxide. “You can recycle the CO2 back into the system, and burn the methane to produce electricity, yielding water and more CO2, which again would go back into the algae pond,” Graziano explained.Furthermore, the conversion of lipids into biofuels can, as Vernon pointed out, be accomplished by using methods established for biodiesel production from plants. “That is one way to harness the potential of algae, as one possible feedstock for biodiesel production, by making them produce lipids that can in turn be trans-esterified into biodiesel,” he said. “Trans-esterification is a rather simple chemical reaction, for which tried-and-tested production technology emitting little greenhouse gas is available.”There is also the more remote possibility of generating electricity directly from algae. Researchers from Stanford University in the USA and Yonsei University in Seoul, South Korea, inserted gold nanoelectrodes into individual cells, drawing one picoampere (10−12 A) of current from each (Ryu et al, 2010). At this level it would take about a trillion photosynthesizing cells more than an hour to generate the amount of energy stored in a single AA battery. Yet, as the study''s lead author Won Hyoung Ryu from Yonsei University pointed out, electricity could be generated more efficiently by cutting out the intermediate step of producing biofuels, or even by creating hydrogen, for example, as a direct output—the hydrogen would still need to be burned first. “The extraction of photosynthetic electrons requires fewer energy conversion steps compared with hydrogen-based electricity production that requires at least three steps such as solar to hydrogen, hydrogen to heat, and finally heat to electricity,” Ryu said. “Every conversion step involves a certain degree of energy loss.”But, as Ryu conceded, there are fundamental challenges to overcome: “First, we need to find a way to access the thylakoid membranes of millions of cells in parallel to obtain practically meaningful energy. Second, we still use external energy—overvoltage—to extract the photosynthetic electrons.” At present, energy to has to be put in before it can be extracted—an issue that certainly needs to be resolved if microalgae biofuels are ever to be used as constituents of self-charging batteries, for example. Doing so would also involve other challenges such as dealing with dead cells and waste products, which would have to be recycled within the battery.Apart from energy conversion efficiency, algae could score from other by-products that would improve the economics of productionIn the shorter term, microalgae will therefore be used to produce ‘traditional'' biofuels, given the proven advantages of algae over land plants. According to Anastasios Melis, whose laboratory at the University of California, Berkeley, USA, specializes in microalgae, cyanobacteria and plant photosynthesis: “Proven commercial scale productivities of microalgae and cyanobacteria are much better than those of plants because of the ‘carpeting effect'' […] Also, microalgae and cyanobacteria do not invest photosynthate into roots, which is biomass that cannot be harvested or exploited. There may also be secondary reasons for the efficiency advantage, such as the fact that larger plants are often limited by the supply of carbon dioxide, since their stomata tend to close under bright sunlight to protect the tissues against photo damage.”Yet, microalgae also show reduced photosynthetic efficiency under bright sunlight. The reason is that most algal species have adapted to the low light levels below the surface of the ocean by developing large chlorophyll-based antennae for harvesting as much of the limited light available as possible. A lot of energy is then wasted under stronger sunlight because the cell is incapable of converting it all, with the rest mostly dissipated as heat. This wasteful process also mops up the incoming radiation and prevents it reaching cells at greater depths, thus further limiting the scope for the high-cell populations that are necessary to increase energy conversion.Melis and colleagues have tackled this problem by engineering strains with shorter light-harvesting antennae by using DNA insertion mutagenesis in a model species, Chlamydomonas reinhardtii (Melis, 2007). This technique has a long history of use in gene discovery, but the sophistication required to develop algal cells that convert energy more efficiently is new. The fundamental idea is to create random mutations and identify those that generate the desired phenotype, in this case shorter light-harvesting antennae. Melis also inserted an exogenous DNA tag alongside the new base pairs, thus enabling him to locate the genomic DNA flanking the mutation. The gene affected by that mutation can then be identified as one associated with the development of light-harvesting antennae, if these are truncated in the resulting cell.But, as with all mutations, there is a high probability that these will cause other less desirable phenotypic changes in addition to the shortened antennae. Indeed, it has turned out that such phenotypic changes often include reduced photosynthetic efficiency, thus defeating the object of the exercise. In response, Melis developed screening processes to identify those strains with truncated antennae but with fully functioning photosynthesis. This entails visually inspecting candidate colonies, as those with low densities of chlorophyll and therefore short harvesting antennae are yellowish in colour rather than green. The selected strains are then cultured and tested for energy yields during photosynthesis to identify the most efficient energy converters.Melis has already demonstrated that cells with truncated antennae are illuminated much more uniformly in dense cultures and achieve the desired effect of creating a thick carpet of algae that efficiently harvest light. “Accordingly, the truncated light-harvesting chlorophyll antenna size property may find application in the commercial exploitation of microalgae and plants for the generation of biomass, biofuel, chemical feedstock, as well as nutraceutical and pharmaceutical products,” he said.Improving the ability of algae to harvest light is an important step towards improving the efficiency of photosynthesis, especially in the densely populated volumes of water in algae biofuel farms (Fig 1). There is also the hope of going further to bioengineer microalgae to produce biofuels or electricity directly, to cut out the need to convert lipids into biofuels such as biodiesel or hydrogen. This is a harder challenge because it involves engineering a truly fundamental change in the second stage of photosynthesis—the Calvin cycle—to redirect the energy liberated by splitting water away from the normal production of glucose and towards the desired biofuel or electricity.Open in a separate windowFigure 1Schematic drawing of an algae farm for the production of biofuels.Fortunately, evolution has provided a good starting point with the hydrogenase enzyme protecting against damage when the Calvin cycle is unable to mop up all the electrons produced by the light-harvesting process. This can happen just after sunrise when light harvesting kicks in but the Calvin cycle has not yet ‘woken up'' from its night''s rest. Under these circumstances, hydrogenase guides the electrons directly to the protons produced by splitting water to form hydrogen. The enzyme is eventually inhibited by oxygen liberated from the Calvin cycle as it gets going to allow normal photosynthesis to resume for the day.There is also the hope of going further to bioengineer microalgae to produce biofuels or electricity directly…Research has therefore focused on holding back this oxygen feedback mechanism to increase production of hydrogen. The first breakthrough came in 2000 when Melis and Seibert reported that reducing sulphate levels in algal cultures would cut the rate of photosynthesis (Melis et al, 2000). The result was a 90% reduction in oxygen production, sufficient to allow the hydrogenase enzyme to continue diverting electrons towards protons to yield hydrogen for a longer period.Although it was a considerable step forward, it did not solve the problem because the C. reinhardtii cells soon died when deprived of sulphate. Melis, Seibert and others have since worked on various methods to achieve the same effect at a molecular level without depriving the cells of sulphate ions, by diverting electrons away from the Calvin cycle while maintaining overall levels of photosynthesis. This involves getting a number of things right and will probably require tuning several genes at the whole genome level to achieve the desired objectives.The recent announcement by Craig Venter that he has created a synthetic bacterium by transplanting the genome from another species of bacteria (Gibson et al, 2010) has therefore added a new twist to the story. Venter''s technology could enable scientists to make changes to algae at the level of the whole genome, custom-building a suite of enzymatic tools to redirect the energy produced by photosynthesis. Venter''s team took bacteria from the genus Mycoplasma mycoides and re-engineered its genome from digitized sequence information. The resulting genome was then transplanted into bacterial cells of another genus, Mycoplasma capricolum, which then acquired all the phenotypic properties of M. mycoides and was capable of self-replication.Venter''s development might prove a significant step on the road towards algae-derived biofuels, according to Ryu. “I think it is a smart move and look forward to hearing what would come out in the near future,” he said. “Regardless of whether it works or fails, we will always learn something. For our approach, genomic manipulation can help greatly.” A key target, Ryu explained, will be the ferredoxin proteins that act as biological capacitors in photosynthesis by accepting electrons from the chlorophyll antennae and carrying them to the Calvin cycle. “In genetically-modified algae, ferredoxin stops delivering the photosynthetic electrons to the Calvin cycle […] Then we have a better chance of stealing the electrons,” Ryu said.Such exciting prospects stoke further optimism that science could at last provide a significant and sustainable source of energy that could be delivered in a variety of forms that might include transportation fuels, hydrogen, large-scale electricity production and possibly self-charging organic batteries.  相似文献   

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Suran M 《EMBO reports》2011,12(1):27-30
Few environmental disasters are as indicting of humanity as major oil spills. Yet Nature has sometimes shown a remarkable ability to clean up the oil on its own.In late April 2010, the BP-owned semi-submersible oilrig known as Deepwater Horizon exploded just off the coast of Louisiana. Over the following 84 days, the well from which it had been pumping spewed 4.4 million barrels of crude oil into the Gulf of Mexico, according to the latest independent report (Crone & Tolstoy, 2010). In August, the US Government released an even grimmer estimate: according to the federal Flow Rate Technical Group, up to 4.9 million barrels were excreted during the course of the disaster. Whatever the actual figure, images from NASA show that around 184.8 million gallons of oil have darkened the waters just 80 km from the Louisiana coast, where the Mississippi Delta harbours marshlands and an abundance of biodiversity (NASA Jet Propulsion Laboratory, 2010; Fig 1).…the Deepwater incident is not the first time that a massive oil spill has devastated marine and terrestrial ecosystems, nor is it likely to be the lastOpen in a separate windowFigure 1Images of the Deepwater Horizon oil slick in the Gulf of Mexico. These images were recorded by NASA''s Terra spacecraft in May 2010. The image dimensions are 346 × 258 kilometres and North is toward the top. In the upper panel, the oil appears bright turquoise owing to the combination of images that were used from the Multi-angle Imaging SpectroRadiometer (MISR) aboard the craft. The Mississippi Delta, which harbors marshlands and an abundance of biodiversity, is visible in the top left of the image. The white arrow points to a plume of smoke and the red cross-hairs indicate the former location of the drilling rig. The lower two panels are enlargements of the smoke plume, which is probably the result of controlled burning of collected oil on the surface.© NASA/GSFC/LaRC/JPL, MISR TeamThe resulting environmental and economic situation in the Gulf is undoubtedly dreadful—the shrimp-fishing industry has been badly hit, for example. Yet the Deepwater incident is not the first time that a massive oil spill has devastated marine and terrestrial ecosystems, nor is it likely to be the last. In fact, the US National Oceanic and Atmospheric Association (NOAA) deals with approximately 300 oil spills per year and the Deepwater catastrophe—despite its extent and the enormous amount of oil released—might not be as terrible for the environment as was originally feared. Jacqueline Michel, a geochemist who has worked on almost every major oil spill since the 1970s and who is a member of NOAA''s scientific support team for the Gulf spill, commented that “the marshes and grass are showing some of the highest progresses of [oil] degradation because of the wetness.” This rapid degradation is partly due to an increased number of oil-consuming microbes in the water, whose population growth in response to the spill is cleaning things up at a relatively fast pace (Hazen et al, 2010).It therefore seems that, however bad the damage, Nature''s capacity to repair itself might prevent the unmitigated disaster that many feared on first sight of the Deepwater spill. As the late social satirist George Carlin (1937–2008) once put it: “The planet will shake us off like a bad case of fleas, a surface nuisance[.] The planet will be here for a long, long—LONG—time after we''re gone, and it will heal itself, it will cleanse itself, because that''s what it does, it''s a self-correcting system.”Michel believes that there are times when it is best to leave nature alone. In such cases the oil will degrade naturally by processes as simple as exposure to sunlight—which can break it down—or exposure to the air—which evaporates many of its components. “There have been spills where there was no response because we knew we were going to cause more harm,” Michel said. “Although we''re going to remove heavier layers of surface oil [in this case], the decision has been made to leave oil on the beach because we believe it will degrade in a timescale of months […] through natural processing.”To predict the rate of general environmental recovery, Michel said one should examine the area''s fauna, the progress of which can be very variable. Species have different recovery rates and although it takes only weeks or months for tiny organisms such as plankton to bounce back to their normal population density, it can take years for larger species such as the endangered sea turtle to recover.…however bad the damage, Nature''s capacity to repair itself might prevent the unmitigated disaster that many feared on first sight…Kimberly Gray, professor of environmental chemistry and toxicology at Northwestern University (Evanston, IL, USA), is most concerned about the oil damaging the bottom of the food chain. “Small hits at the bottom are amplified as you move up,” she explained. “The most chronic effects will be at the base of the food chain […] we may see lingering effects with the shrimp population, which in time may crash. With Deepwater, it''s sort of like the straw that broke the shrimp''s back.”Wetlands in particular are a crucial component of the natural recovery of ecosystems, as they provide flora that are crucial to the diets of many organisms. They also provide nesting grounds and protective areas where fish and other animals find refuge from predation. “Wetlands and marsh systems are Nature''s kidneys and they''ve been damaged,” Gray said. The problem is exacerbated because the Louisiana wetlands are already stressed in the aftermath of Hurricane Katrina, which devastated the Gulf coast in August 2005, and because of constant human activity and environmental damage. As Gray commented, “Nature has a very powerful capacity to repair itself, but what''s happening in the modern day is assault after assault.”Ron Thom, a marine ecologist at Pacific Northwest National Laboratory—a US government-funded research facility (Richland, WA, USA)—has done important research on coastal ecosystems. He believes that such habitats are able to decontaminate themselves to a limited degree because of evolution. “[Coastal-related ecosystems are] pretty resilient because they''ve been around a long time and know how to survive,” he said.As a result, wetlands can decontaminate themselves of pollutants such as oil, nitrate and phosphate. However, encountering large amounts of pollutants in a short period of time can overwhelm the healing process, or even stop it altogether. “We did some experiments here in the early 90s looking at the ability for salt marshes to break down oil,” Thom said. “When we put too much oil on the surface of the marsh it killed everything.” He explained that the oil also destroyed the sediment–soil column, where plant roots are located. Eventually, the roots disintegrated and the entire soil core fell apart. According to Thom, the Louisiana marshes were weakened by sediment and nutrient starvation, which suggests that the Deepwater spill destroyed below-ground material in some locations. “You can alter a place through a disturbance so drastic that it never recovers to what it used to be because things have changed so much,” he said.“Nature has a very powerful capacity to repair itself, but what''s happening in the modern day is assault after assault”Michael Blum, a coastal marsh ecologist at Tulane University in New Orleans, said that it is hard to determine the long-term effects of the oil because little is known about the relevant ecotoxicology—the effect of toxic agents on ecosystems. He has conducted extensive research on how coastal marsh plants respond to stress: some marshes might be highly susceptible to oil whereas others could have evolved to deal with natural oil seepage to metabolize hydrocarbons. In the former, marshes might perish after drastic exposure to oil leading to major shifts in plant communities. In the latter case, the process of coping with oil could involve the uptake of pollutants in the oil—known as polycyclic aromatic hydrocarbons (PAHs)—and their reintroduction into the environment. “If plants are growing in the polluted sediments and tapping into those contaminated sources, they can pull that material out of the soil and put it back into the water column or back into the leaf tissue that is a food source for other organisms,” Blum explained.In addition to understanding the responses of various flora, scientists also need to know how the presence of oil in an ecosystem affects the fauna. One model that is used to predict the effects of oil on vertebrates is the killifish; a group of minnows that thrive in the waters of Virginia''s Elizabeth River, where they are continuously exposed to PAHs deposited in the water by a creosote factory (Meyer & Di Giulio, 2003). “The killifish have evolved tolerance to the exposure of PAHs over chronic, long-term conditions,” Blum said. “This suggests that something similar may occur elsewhere, including in Gulf Coast marshes exposed to oil.”Although Michel is optimistic about the potential for environmental recovery, she pointed out that no two spills are the same. “There are lot of things we don''t know, we never had a spill that had surface release for so long at this water depth,” she said. Nevertheless, to better predict the long-term effects, scientists have turned to data from similar incidents.In 1989, the petroleum tanker Exxon Valdez struck Bligh Reef off the coast of Prince William Sound in Alaska and poured a minimum of 11 million gallons of oil into the water—enough to fill 125 Olympic-sized swimming pools. Senior scientist at NOAA, Stanley Rice of Juno, Alaska, studies the long-term effects of the spill and the resulting oil-related issues in Prince William Sound. Rice has worked with the spill since day 3 and, 20 years later, he is seeing major progress. “I never want to give the impression that we had this devastating oil spill in 1989 and it''s still devastating,” he said. “We have pockets of a few species where lingering oil hurts their survival, but in terms of looking at the Sound in its entirety […] it''s done a lot of recovery in 20 years.”…little is known about the relevant ecotoxicology—the effect of toxic agents on ecosystemsDespite the progress, Rice is still concerned about one group of otters. The cold temperature of the water in the Sound—rarely above 5 °C—slows the disintegration of the oil and, every so often, the otters come in contact with a lingering pocket. When they are searching for food, for example, the otters often dig into pits containing oil and become contaminated, which damages their ability to maintain body temperature. As a result, they cannot catch as much food and starve because they need to consume the equivalent of 25% of their body weight every day (Rice, 2009).“Common colds or worse, pneumonia, are extremely debilitating to an animal that has to work literally 365 days a year, almost 8 to 12 hours a day,” Rice explained. “If they don''t eat enough to sustain themselves, they die of hyperthermia.” Nevertheless, in just the last two years, Rice has finally seen the otter population rebound.Unlike the otters, one pod of orca whales has not been so lucky. Since it no longer has any reproductive females, the pod will eventually become extinct. However, as it dies out, orca prey such as seals and otters will have a better chance of reproducing. “There are always some winners and losers in these types of events,” Rice said. “Nature is never static.”The only ‘loser'' that Rice is concerned about at the moment is the herring, as many of their populations have remained damaged for the past 20 years. “Herring are critical to the ecosystem,” he said. “[They are] a base diet for many species […] Prince William Sound isn''t fully recovered until the herring recover.”North America is not alone in dealing with oil-spill disasters—Europe has had plenty of experience too. One of the worst spills occurred when the oil tanker Prestige leaked around 20 million gallons of oil into the waters of the Galacian coast in Northern Spain in 2002. This also affected the coastline of France and is considered Spain''s worst ecological disaster.“The impacts of the Prestige were indeed severe in comparison with other spills around the world,” said attorney Xabier Ezeizabarrena, who represented the Fishermen Guilds of Gipuzkoa in a lawsuit relating to the spill. “Some incidents aren''t even reported, but in the European Union the ratio is at least one oil spill every six months.”For disasters involving oil, oceanographic data to monitor and predict the movement of the spill is essentialIn Ezeizabarrena''s estimation, Spanish officials did not respond appropriately to the leak. The government was denounced for towing the shipwreck further out into the Atlantic Ocean—where it eventually sank—rather than to a port. “There was a huge lack of measures and tools from the Spanish government in particular,” Ezeizabarrena said. “[However], there was a huge response from civil society […] to work together [on restoration efforts].”Ionan Marigómez, professor of cellular biology at the University of the Basque Country, Spain, was the principal investigator on a federal coastal-surveillance programme named Orbankosta. He recorded the effects of the oil on the Basque coast and was a member of the Basque government''s technical advisory commission for the response to the Prestige spill. He was also chair of the government''s scientific committee. “Unfortunately, most of us scientists were not prepared to answer questions related to the biological impact of restoration strategies,” Marigómez said. “We lacked data to support our advice since continued monitoring is not conducted in the area […] and most of us had developed our scientific activity with too much focus on each one''s particular area when the problem needed a holistic view.”…the world consumes approximately 31 billion barrels of oil per year; more than 700 times the amount that leaked during the Deepwater spillFor disasters involving oil, oceanographic data to monitor and predict the movement of the spill is essential. Clean-up efforts were initially encouraged in Spain, but data provided by coastal-inspection programmes such as Orbankosta informed the decision to not clean up the Basque shoreline, allowing the remaining oil debris to disintegrate naturally. In fact, the cleaning activity that took place in Galicia only extended the oil pollution to the supralittoral zone—the area of the beach splashed by the high tide, rather than submerged by it—as well as to local soil deposits. On the Basque coast, restoration efforts were limited to regions where people were at risk, such as rocky areas near beaches and marinas.Eight years later, Galicia still suffers from the after-effects of the Prestige disaster. Thick subsurface layers of grey sand are found on beaches, sometimes under sand that seems to be uncontaminated. In Corme-Laxe Bay and Cies Island in Galicia, PAH levels have decreased. Studies have confirmed, however, that organisms exposed to the area''s sediments had accumulated PAHs in their bodies. Marigómez, for example, studied the long-term effects of the spill on mussels. Depending on their location, PAH levels decreased in the sampled mussel tissue between one and two years after the spill. However, later research showed that certain sites suffered later increases in the level of PAHs, due to the remobilization of oil residues (Cajaraville et al, 2006). Indeed, many populations of macroinvertebrate species—which are the keystones of coastal ecosystems—became extinct at the most-affected locations, although neighbouring populations recolonized these areas. The evidence suggests that only time will tell what will happen to the Galicia ecosystem. The same goes for oil-polluted environments around the world.The concern whether nature can recover from oil spills might seem extreme, considering that oil is a natural product derived from the earth. But too much of anything can be harmful and oil would remain locked underground without human efforts to extract it. “As from Paracelsus'' aphorism, the dose makes the poison,” Marigómez said.According to the US Energy Information Administration, the world consumes approximately 31 billion barrels of oil per year; more than 700 times the amount that leaked during the Deepwater spill. Humanity continues, in the words of some US politicians, to “drill, baby, drill!” On 12 October 2010, less than a year after the Gulf Coast disaster, US President Barack Obama declared that he was lifting the ban on deepwater drilling. It appears that George Carlin got it right again when he satirized a famous American anthem: “America, America, man sheds his waste on thee, and hides the pines with billboard signs from sea to oily sea!”  相似文献   

13.
The French government has ambitious goals to make France a leading nation for synthetic biology research, but it still needs to put its money where its mouth is and provide the field with dedicated funding and other support.Synthetic biology is one of the most rapidly growing fields in the biological sciences and is attracting an increasing amount of public and private funding. France has also seen a slow but steady development of this field: the establishment of a national network of synthetic biologists in 2005, the first participation of a French team at the International Genetically Engineered Machine competition in 2007, the creation of a Master''s curriculum, an institute dedicated to synthetic and systems biology at the University of Évry-Val-d''Essonne-CNRS-Genopole in 2009–2010, and an increasing number of conferences and debates. However, scientists have driven the field with little dedicated financial support from the government.Yet the French government has a strong self-perception of its strengths and has set ambitious goals for synthetic biology. The public are told about a “new generation of products, industries and markets” that will derive from synthetic biology, and that research in the field will result in “a substantial jump for biotechnology” and an “industrial revolution”[1,2]. Indeed, France wants to compete with the USA, the UK, Germany and the rest of Europe and aims “for a world position of second or third”[1]. However, in contrast with the activities of its competitors, the French government has no specific scheme for funding or otherwise supporting synthetic biology[3]. Although we read that “France disposes of strong competences” and “all the assets needed”[2], one wonders how France will achieve its ambitious goals without dedicated budgets or detailed roadmaps to set up such institutions.In fact, France has been a straggler: whereas the UK and the USA have published several reports on synthetic biology since 2007, and have set up dedicated governing networks and research institutions, the governance of synthetic biology in France has only recently become an official matter. The National Research and Innovation Strategy (SNRI) only defined synthetic biology as a “priority” challenge in 2009 and created a working group in 2010 to assess the field''s developments, potentialities and challenges; the report was published in 2011[1].At the same time, the French Parliamentary Office for the Evaluation of Scientific and Technological Choices (OPECST) began a review of the field “to establish a worldwide state of the art and the position of our country in terms of training, research and technology transfer”. Its 2012 report entitled The Challenges of Synthetic Biology[2] assessed the main ethical, legal, economic and social challenges of the field. It made several recommendations for a “controlled” and “transparent” development of synthetic biology. This is not a surprise given that the development of genetically modified organisms and nuclear power in France has been heavily criticized for lack of transparency, and that the government prefers to avoid similar future controversies. Indeed, the French government seems more cautious today: making efforts to assess potential dangers and public opinion before actually supporting the science itself.Both reports stress the necessity of a “real” and “transparent” dialogue between science and society and call for “serene […] peaceful and constructive” public discussion. The proposed strategy has three aims: to establish an observatory, to create a permanent forum for discussion and to broaden the debate to include citizens[4]. An Observatory for Synthetic Biology was set up in January 2012 to collect information, mobilize actors, follow debates, analyse the various positions and organize a public forum. Let us hope that this observatory—unlike so many other structures—will have a tangible and durable influence on policy-making, public opinion and scientific practice.Many structural and organizational challenges persist, as neither the National Agency for Research nor the National Centre for Scientific Research have defined the field as a funding priority and public–private partnerships are rare in France. Moreover, strict boundaries between academic disciplines impede interdisciplinary work, and synthetic biology is often included in larger research programmes rather than supported as a research field in itself. Although both the SNRI and the OPECST reports make recommendations for future developments—including setting up funding policies and platforms—it is not clear whether these will materialize, or when, where and what size of investments will be made.France has ambitious goals for synthetic biology, but it remains to be seen whether the government is willing to put ‘meat to the bones'' in terms of financial and institutional support. If not, these goals might come to be seen as unrealistic and downgraded or they will be replaced with another vision that sees synthetic biology as something that only needs discussion and deliberation but no further investment. One thing is already certain: the future development of synthetic biology in France is a political issue.  相似文献   

14.
Philip Hunter 《EMBO reports》2010,11(3):166-169
Psychologists, anthropologists and biologists are uncovering the bigger picture behind the development of empathy and altruismMany philosophers and anthropologists might argue that among the attributes that make humans unique, it is our ability to reason morally that sets us apart from all other animals—perhaps in addition to our capacity for spirituality. From Ancient Greece and the Roman Republic, to sixth century China and the European Enlightenment; philosophers throughout the ages have pondered why humans can feel empathy or behave altruistically—and, indeed, why they even contemplate it. Only later, in the twentieth century, did the biological sciences join the quest for understanding by seeking genetic, neurological and evolutionary explanations of self-awareness and morality.The answer has so far been elusive, as biologists have neither been able to find the ‘moral'' gene—if such a thing exists—nor to identify a specific cluster of neurons or region of the brain that takes care of ethical decision making. Yet, some parts of the picture are emerging and they reveal a relationship between the complex emotional processes that enable empathy and altruism and the advanced cognitive abilities, such as mirror self-recognition (MSR), that emerged with the evolution of the more complex structural and functional components of the brain. In addition, these studies show that many more animal species than we had appreciated, including birds, display more or less primitive versions of these traits.These findings have led to a proliferation of research into ‘human-like'' social behaviour in animals. “Empathy research is really taking off, not only on adult humans in neuroscience or on children, but also animals,” commented Dutch primatologist Frans de Waal, now at Emory University in Atlanta, GA, USA, who analyses the behaviour of chimpanzees to gain insight into their emotional and cognitive abilities. “We have collected thousands of observations of so-called consolation behaviour in chimpanzees. As soon as one among them is distressed, for example losing a fight, falling from a tree, or encountering a snake, others will come over to provide reassurance. They embrace the distressed chimp or try to calm him or her with a kiss and grooming. This behaviour is typical of chimps and other apes, and is used in research on children as the main behavioural marker of ‘sympathetic concern'',” he explained.Clues about the cognitive functions and neurological features underlying ‘sympathetic concern'' can be elucidated by correlating the results from studies of children with those of higher animals that appear capable of feeling empathy and possibly altruism. “In children, MSR emerges between 18–24 months of age and its onset is concurrent with the emergence of empathic behaviour and other indices of the theory of mind,” commented Diana Reiss, a specialist in the evolution of intelligence at Hunter College of the City University of New York, USA. Reiss also pointed out that all species that exhibit MSR have large, complex brains relative to their body weight, with evidence of a developmental link between MSR and empathy, as in human children.Researchers are now working to identify the neurological basis for this link, why it evolved and how it develops with the growing individual. MSR, widely regarded as an important requirement for empathic or altruistic behaviour, has now been identified in several species beyond the great apes and humans. Although MSR is not itself interesting from the perspective of cognitive evolution—it confers no direct selective advantage—as de Waal pointed out, the importance of the mirror test resides in what it tells us about the ability of animals to analyse their relationship with their environment, especially with respect to their social partners. “The mirror test is interesting not because it shows that an animal has the capacity for self-recognition but because of the cognitive abilities that are associated with MSR,” he explained.…biologists have neither been able to find the ‘moral'' gene—if such a thing exists—nor to identify a specific cluster of neurons or region of the brain that takes care of ethical decision makingGordon Gallup originally demonstrated MSR in animals in 1970 (Gallup, 1970). He developed a test in which a visible coloured mark is made on a part of the animal''s body that it cannot see without using a mirror. The test determines whether the animal can use the reflection to locate the mark and then touch or rub it, thus revealing that it can tell the reflection is of itself and not of another individual. Since Gallup''s early experiments, MSR has been seen in a number of animals, most notably dolphins (Reiss & Marino, 2001), the Asian elephant (Plotnik et al, 2006) and, a first for birds, the magpie (Prior et al, 2008).Although MSR has now been demonstrated in several species, it is clearly confined to a small group with highly evolved social interactions. Most species in this group are also set apart from the rest of the animal kingdom because they have spindle neurons, which are believed to be a vital component of large brains capable of empathic social behaviour. These neurons tend to be larger and have a streamlined bipolar structure that is well-adapted for the rapid and coordinated transmission of signals. Also known as von Economo neurons (VEN), they occur in areas of the cortex that process a large number of input signals from other brain regions, in particular the fronto-insular cortex and anterior cingulate cortex. Functionally, the VEN architecture seems to be optimized for the parallel receipt and processing of a large amount of diverse information.“Recent research has reported that spindle neurons are found to occur only in the brains of a few species—humans, the great apes, whales, dolphins and elephants—leading to the speculation that they are a possible obligatory neuronal adaptation in very large brains, permitting fast information processing and transfer along highly specific projections and that evolved in relation to emerging social behaviours,” commented Reiss, who was the first to demonstrate MSR in dolphins along with her colleague Lori Marino, also at Emory University. “It has been further suggested that these specialized brain cells may be involved in processing emotions and underlie empathic behaviour.”Although MSR has now been demonstrated in several species, it is clearly confined to a small group with highly evolved social interactionsFurthermore, the absence of spindle neurons in all other primates suggests that these evolved independently among the great apes and other species that are capable of MSR. This finding leads to the question of whether the brains of higher social animals that have spindle neurons have further common structural or functional features that also evolved in parallel. A recent study suggests that this has happened, at least in the case of elephants and humans, both of which have similar extensive regions of neocortex, which is the neurological structure responsible for sensory perception, motor commands and higher level thought processes (Goodman et al, 2009). The study examined several mammalian species to record the number of nucleotide substitutions in genes that have a crucial role in the brain; the results showed that the most substitutions occur in humans and elephants. This suggests that elephant and human brains have both encountered strong selection for this particular group of genes, which the other animals included in the study clearly had not.However, any suggestion that specific neurological structures are essential, at least for MSR, has been challenged by the discovery of MSR in magpies, which do not even have a neocortex. Although the detailed structures are different, the forebrains of magpies, along with some other members of the crow family, are large and have high neuron densities that are more comparable with humans than other bird species. Although spindle neurons have not yet been observed in magpies, their existence in birds has not been ruled out. In any case, it might be that magpies evolved more complex brain functions without the help of spindle neurons to speed up communication.Nonetheless, there seems to be a clear correlation between the emergence of MSR and empathic behaviour. Magpies, for example, have been subject to extensive research precisely because their ecological conditions have driven the evolution of social intelligence (Prior et al, 2008). They steal and store food, but they also form stable partnerships based to some extent on trust, which requires discrimination between other individuals and judgments about their intentions.…the enhanced cognitive and social interactive abilities of dolphins and great apes have allowed these species to develop rudimentary levels of morality and altruismIn the case of dolphins, the selective pressures they face are associated with their social groups—known as pods—which are able to cooperate with neighbouring groups in times of danger or when there is an opportunity to hunt for food on a larger scale. Dolphins are carnivores and have developed highly skilled cooperative techniques for hunting prey, similar to a pack of wolves hunting, but in three dimensions. Dolphins also devote a large amount of time to training their offspring to hunt and survive, and they are the only non-human mammals that exhibit strong evidence of vocal mimicry and physical imitation (Reiss et al, 1997).Although they live in superficially different ecosystems, dolphins and the great apes have been subject to fundamentally similar selective pressures, according to Marino, who co-authored the seminal study of vocal mimicry in dolphins. “Despite the seemingly disparate environmental pressures that would shape cetacean—the mammalian group including dolphins, whales and porpoises—and primate cognitive evolution, these drivers were actually extremely similar,” she said. “Both evolved complex levels of social interaction, and, in that respect, dolphins and primates evolved in, conceptually, very similar environments.”According to Marino, dolphin brain enlargement occurred only when they began to develop the use of echolocation to coordinate hunting and other activities. But other animals have developed echolocation without enlarging their brains. In the case of cetaceans and especially dolphins, Marino believes the key evolutionary driver was the incorporation of this technique into a complex system of social interaction. She argues that the enhanced cognitive and social interactive abilities of dolphins and great apes have allowed these species to develop rudimentary levels of morality and altruism.“Ongoing findings from studies of both primate and cetacean behaviour provide support for the conclusion that social complexity involves the evolution of morality,” Marino explained. “This is true in a number of ways. From an ultimate evolutionarily point of view, complex group living requires ways to regulate interactions among individuals in order to keep the group intact. Frans de Waal has provided abundant evidence for this argument in primates and I would contend the same is true of cetaceans. On a proximate level, much of the morality we see in primate and cetacean groups is underwritten by empathy, which is enabled by the kind of awareness of self and other that dolphins and primates—particularly great apes and humans—demonstrate.”Such behaviour might have evolved partly because altruism enhanced individual survival chances—providing that the cost was not too great. But, according to Antonio Damasio, Director of the Brain and Creativity Institute at the University of Southern California in Los Angeles, CA, USA, the key driver might have been that altruism enabled individuals to make ‘wiser'' decisions. Humans might be unique in the degree to which we apply ethics and morality to rational decision-making, but the presence of empathy in animals provides important clues about the neurological underpinnings of these abilities. In particular, research with animals might help to settle the long-standing argument about whether morality and altruism can be regarded as independent of the brain''s hardware, or whether morality is hard-wired into the brain and is a product of our neurological evolution.…humans commonly appear to balance rational and emotional factors when making judgements, creating the impression that there are distinct neural systems competing with each otherSome studies seem to suggest that the latter is true. For example, an experiment at the University of Zurich, Switzerland, in which subjects were asked to divide up a sum of money on a supposedly fair basis, found that the disruption of cognition altered the moral behaviour of the participants. In the so-called Ultimatum Game, one of the two participants—who does not know how much money is available—is required to make an offer to the other, who does know the size of the pot. If the second player does not accept, neither player receives anything, so in a sense it can be seen as a test of indignation versus greed. If the pot is big, the second player might decide to swallow his or her pride and accept it. The first player, however, might decide to make a generous offer in order to be sure it would be accepted. During the game, the Swiss researchers applied low-frequency transcranial magnetic stimulation to disrupt either the right or left dorsolateral prefrontal cortex of their test subjects. Disruption of the right side made them more susceptible to ‘immoral'' decisions as they were more willing to make offers that they judged to be unfair to their partners. Yet, they retained their ability to determine fairness. The researchers concluded that the right side of the prefrontal cortex has an implicit role in determining how to apply moral or ethical standards to information made available by cognitive processes (Sanfey et al, 2003).This suggests that morality is hard-wired and does not exist independently of the brain''s complex biochemistry, at least according to Damasio. “Emotions and feelings, as we know them, are related to our ‘wet'' biology, to our flesh,” he said. “Formally you can construct them in robotic artefacts but there is no reason to believe [that] they would be the same.”In this regard, Michael Koenigs, from the Department of Psychiatry at the University of Wisconsin–Madison, USA, pointed out that humans commonly appear to balance rational and emotional factors when making judgements, creating the impression that there are distinct neural systems competing with each other. “From a psychological standpoint, in the midst of a sticky moral dilemma it can certainly feel like your mind is being pulled in two different directions,” he said. “And in terms of the brain, it is very clear that certain areas are more concerned with emotion and affect, while other areas are more associated with ‘cold'' cognitive processes. Both systems play a role in determining morality, but at the neural level the relationship between the systems is more of an integration than a competition.”Until recently there was very little direct observation of these neurological processes at work. However, recent research based on functional magnetic resonance imaging has revealed that ‘true'' and ‘false'' statements activate different regions of the prefrontal cortex. The researchers found that people tend to use separate processes to resolve the distinctions between true and false statements, unless the answer is blindingly obvious (Marques et al, 2009). They concluded that people accept statements as true initially and confirm this merely by a call to memory. However, if the initial check suggests that the statement might be false, further reasoning is required to confirm the rejection. “The idea supported by this paper and others is that when the statement to verify is true—and by default we assume [that] it is—the task is to find if we have or recognize that information in our memory,” explained Frederico Marques, one of the authors of the study from the University of Lisbon, Portugal. “When we do not find that information, or if we have doubts, we further process the information, more like problem solving.”Animals that are capable of MSR also possess primitive abilities to assess truth or falsehood. Magpies, for example, have to decide whether a particular individual can be trusted to not steal food. Of course, more research is needed to provide further insight into the neurological processes involved in such assessments and to illuminate the evolutionary history of such a skill. What is established, however, is that the roots of complex social behaviour and the capacity for abstract thought—as well as ethical judgment, perhaps—can be found predominantly in the more advanced warm-blooded and social vertebrates. The capacity for morality is perhaps not, after all, uniquely human.  相似文献   

15.

Background

The basis for correctly assessing the burden of parasitic infections and the effects of interventions relies on a somewhat shaky foundation as long as we do not know how reliable the reported laboratory findings are. Thus virtual microscopy, successfully introduced as a histopathology tool, has been adapted for medical parasitology.

Methodology/Principal Findings

Specimens containing parasites in tissues, stools, and blood have been digitized and made accessible as a “webmicroscope for parasitology” (WMP) on the Internet (http://www.webmicroscope.net/parasitology).These digitized specimens can be viewed (“navigated” both in the x-axis and the y-axis) at the desired magnification by an unrestricted number of individuals simultaneously. For virtual microscopy of specimens containing stool parasites, it was necessary to develop the technique further in order to enable navigation in the z plane (i.e., “focusing”). Specimens were therefore scanned and photographed in two or more focal planes. The resulting digitized specimens consist of stacks of laterally “stiched” individual images covering the entire area of the sample photographed at high magnification. The digitized image information (∼10 GB uncompressed data per specimen) is accessible at data transfer speeds from 2 to 10 Mb/s via a network of five image servers located in different parts of Europe. Image streaming and rapid data transfer to an ordinary personal computer makes web-based virtual microscopy similar to conventional microscopy.

Conclusion/Significance

The potential of this novel technique in the field of medical parasitology to share identical parasitological specimens means that we can provide a “gold standard”, which can overcome several problems encountered in quality control of diagnostic parasitology. Thus, the WMP may have an impact on the reliability of data, which constitute the basis for our understanding of the vast problem of neglected tropical diseases. The WMP can be used also in the absence of a fast Internet communication. An ordinary PC, or even a laptop, may function as a local image server, e.g., in health centers in tropical endemic areas.  相似文献   

16.
Following the publication of the Origin of Species in 1859, many naturalists adopted the idea that living organisms were the historical outcome of gradual transformation of lifeless matter. These views soon merged with the developments of biochemistry and cell biology and led to proposals in which the origin of protoplasm was equated with the origin of life. The heterotrophic origin of life proposed by Oparin and Haldane in the 1920s was part of this tradition, which Oparin enriched by transforming the discussion of the emergence of the first cells into a workable multidisciplinary research program.On the other hand, the scientific trend toward understanding biological phenomena at the molecular level led authors like Troland, Muller, and others to propose that single molecules or viruses represented primordial living systems. The contrast between these opposing views on the origin of life represents not only contrasting views of the nature of life itself, but also major ideological discussions that reached a surprising intensity in the years following Stanley Miller’s seminal result which showed the ease with which organic compounds of biochemical significance could be synthesized under putative primitive conditions. In fact, during the years following the Miller experiment, attempts to understand the origin of life were strongly influenced by research on DNA replication and protein biosynthesis, and, in socio-political terms, by the atmosphere created by Cold War tensions.The catalytic versatility of RNA molecules clearly merits a critical reappraisal of Muller’s viewpoint. However, the discovery of ribozymes does not imply that autocatalytic nucleic acid molecules ready to be used as primordial genes were floating in the primitive oceans, or that the RNA world emerged completely assembled from simple precursors present in the prebiotic soup. The evidence supporting the presence of a wide range of organic molecules on the primitive Earth, including membrane-forming compounds, suggests that the evolution of membrane-bounded molecular systems preceded cellular life on our planet, and that life is the evolutionary outcome of a process, not of a single, fortuitous event.It is generally assumed that early philosophers and naturalists appealed to spontaneous generation to explain the origin of life, but in fact, the possibility of life emerging directly from nonliving matter was seen at first as a nonsexual reproductive mechanism. This changed with the transformist views developed by Erasmus Darwin, Georges Louis Leclerc de Buffon, and, most importantly, by Jean-Baptiste de Lamarck, all of whom invoked spontaneous generation as the mechanism that led to the emergence of life, and not just its reproduction. “Nature, by means of of heat, light, electricity and moisture”, wrote Lamarck in 1809, “forms direct or spontaneous generation at that extremity of each kingdom of living bodies, where the simplest of these bodies are found”.Like his predecessors, Charles Darwin surmised that plants and animals arose naturally from some primordial nonliving matter. As early as 1837 he wrote in his Second Notebook that “the intimate relation of Life with laws of chemical combination, & the universality of latter render spontaneous generation not improbable.” However, Darwin included few statements about the origin of life in his books. He avoided the issue in the Origin of Species, in which he only wrote “… I should infer from analogy that probably all organic beings which have ever lived on this Earth have descended from some one primordial form, into which life was first breathed” (Peretó et al. 2009).Darwin added few remarks on the origin of life his book, and his reluctance surprised many of his friends and followers. In his monograph on the radiolaria, Haeckel wrote “The chief defect of the Darwinian theory is that it throws no light on the origin of the primitive organism—probably a simple cell—from which all the others have descended. When Darwin assumes a special creative act for this first species, he is not consistent, and, I think, not quite sincere …” (Haeckel 1862).Twelve years after the first publication of the Origin of Species, Darwin wrote the now famous letter to his friend Hooker in which the idea of a “warm little pond” was included. Mailed on February 1st, 1871, it stated that “It is often said that all the conditions for the first production of a living organism are now present, which could ever have been present. But if (and Oh! what a big if!) we could conceive in some warm little pond with all sorts of ammonia and phosphoric salts—light, heat, electricity &c. present, that a proteine compound was chemically formed, ready to undergo still more complex changes, at the present day such matter wd be instantly devoured, or absorbed, which would not have been the case before living creatures were formed.” Although Darwin refrained from any further public statements on how life may have appeared, his views established the framework that would lead to a number of attempts to explain the origin of life by introducing principles of historical explanation (Peretó et al. 2009). Here I will describe this history, and how it is guiding current research into the question of life’s origins.  相似文献   

17.
18.
Hunter P 《EMBO reports》2011,12(3):205-207
A more complete catalogue of the Earth''s fauna and flora and a more holistic view of man-made environmental problems could help to slow the rate of biodiversity loss.In the wake of the admission from the United Nations (UN) that, to date, efforts have failed to even slow down the rate of extinction across almost all plant and animal taxa (CBD, 2010), the fight to reverse the human-induced loss of biodiversity is entering a new chapter. The failure to achieve the targets set in 2002 for reducing decline has led to a revised strategy from the Campaign for Biodiversity (CBD). This new approach recognizes that species conservation cannot be treated in isolation from other issues facing humans, including climate change, water scarcity, poverty, agricultural development and global conflict. It also acknowledges that declining biodiversity cannot be tackled properly without a more accurate inventory of the species in existence today. Thus, a large part of the strategy to combat species decline focuses on building an exhaustive catalogue of life.The Global Strategy for Plant Conservation includes such a plan. The intention is to compile an online flora of known plants by 2020, which should enable comprehensive conservation efforts to gather steam. Peter Wyse Jackson, president of the Missouri Botanical Garden in the USA, said that around 25% of the estimated 400,000 plant species in the world, are thought to be threatened. He said that around 850 botanical gardens have, between them, collected around 100,000 species, but only a quarter of these are from the threatened group. “World Flora online will then be an essential baseline to determine the status of individual plant species and threats to them,” Jackson explained. “By 2020 it is proposed that at least 75% of known threatened plants should be conserved both in the wild and in existing collections.”…an online flora of known plants […] should enable comprehensive conservation efforts to gather steamMissouri Botanical Gardens will have an important role in the project and Jackson commented that the first step of the plan has already been achieved: the establishment of an online checklist of flora that is needed to build a comprehensive database of the plant species in the world.Yet, some other plans to halt species decline have drawn criticism. “In my opinion, whilst such international targets are useful to motivate individuals, states and wider society to do conservation, they are not necessarily realistic because they are often ‘pulled out of the hat'' with very little science behind them,” commented Shonil Bhagwat, senior research fellow at the School of Geography and the Environment at Oxford University.The revised CBD plan specifies measures for reversing the decline in biodiversity. One target is to enlarge protected areas for wildlife, within which activities such as logging are prohibited. Ecological corridors could then connect these areas to allow migration and create a network of ‘safe'' places for wildlife.Such a corridor is being created between two parts of the Brazilian Atlantic rainforest—the Pau Brasil National Park and the Monte Pascoal National Park—both of which are already protected. “Well-managed protected areas keep away biodiversity threats, such as deforestation, invasive species, hunting and poaching,” explained Arnd Alexander Rose, marketing manager for Brazil at The Nature Conservancy, a conservation organization that operates on all continents. “We think that the connectivity between the national parks is essential for the long-term permanence of local species, especially fauna,” Rose said.Worldwide, only around 6% of coastlines are within protected areas, but around 12% of the total land area is protected—a figure that is perhaps higher than many would expect, reflecting the large size of many national parks and other designated wildlife zones. Nevertheless, the coverage of different habitats varies greatly: “Only 5% of the world''s temperate needle-leaf forests and woodlands, 4.4% of temperate grasslands and 2.2% of lake systems are protected” (CBD, 2010). The aim of the CBD is to increase the total area of protected land to 17% by 2020, and also to expand the protected coastal zones, as well as extending the area of protected oceans to 10%.Things at sea, however, are different; both in terms of biodiversity and protection. The biggest threat to many marine species is not direct human activity—poaching or habitat encroachment, for example—but the impact of increased ocean acidity due to rising atmospheric carbon dioxide levels. Halting or reversing this increase will therefore contribute to the marine conservation effort and biodiversity in the long term.However, the first task is to establish the extent of marine biodiversity, particularly in terms of invertebrate animals, which are not well catalogued. Ian Poiner is CEO of the Australian Institute of Marine Science and chair of the steering committee for the first Census of Marine Life (Census of Marine Life, 2010), which has revealed the enormity of our remaining uncertainty. “So far 250,000 species [of invertebrates] have been formally described, but at least another 750,000 remain to be discovered, and I think it could be as many as 10 million,” Poiner said. As evidence for this uncertainty he points to the continuing high rate of discovery of new species around coral reefs, where each organism also tends to come with a new parasite. The situation is compounded by the problem of how to define diversity among prokaryotes.“…250,000 species [of invertebrates] have been formally described, but at least another 750,000 remain to be discovered…”Even if the number of non-vertebrate marine species remaining to be discovered turns out to be at the low end of estimates, Poiner points out that the abundance and diversity of life in the oceans will still be far greater than was expected before the census. For fish—a group that has been more extensively analysed than invertebrates—Poiner notes that there are several thousand species yet to be discovered, in addition to the 25,000 or more known species.The levels of diversity are perhaps most surprising for microorganisms. It was expected that these organisms would be present in astronomically large numbers—they are thought to account for 50–90% of the biomass in the oceans, as measured by total amount of carbon—but the high degree of genetic divergence found within even relatively small areas was unexpected. “We found there are about 38,000 kinds of bacteria in a litre of sea water,” Poiner said. “We also found that rarity is common, especially for microbes. If you take two separate litre samples of sea water just 10 or 20 kilometres apart, only a small percentage of the 38,000 bacteria types in each one are of the same kind. The challenge now is to find out why most are so rare.”This mystery is confounded by another result of the census: there is a much greater degree of connectedness than had been expected. Many fish, and even smaller invertebrate species, travel huge distances and navigate with great accuracy, rather like migratory birds. “Pacific white sharks will travel long distances and come back to within 50 metres from where they started,” Poiner said, by way of example.The behaviour of the sharks was discovered by using new tags, measuring just a few centimetres across, that can be attached to the heads of any large creatures to track their location and measure temperature, conductivity—and thereby salinity—and depth. For smaller creatures, such as baby salmon, a different technology is used that involves the attachment of passive acoustic sensors to their bodies. These trigger a signal when the fish swim through arrays of acoustic receivers that are installed in shallower waters at locations throughout the oceans.Although tagging and acoustic monitoring are providing new information about the movements and interactions of many species throughout the oceans, the huge task remains of identifying and cataloguing those species. For this, the quickly maturing technique of DNA barcoding has been useful and provides a relatively inexpensive and convenient way of assessing whether a specimen belongs to a new species or not. The method uses a short DNA sequence in the mitochondrial gene for cytochrome c oxidase subunit 1 (CO1)—around 600 base pairs in most species—which differs little within species but significantly between them (Kress & Erickson, 2008).The Marine Census programme involves several barcoding centres that have determined barcodes for more than 2,000 of the 7,000 known species of holozooplankton, for example (Census of Marine Zooplankton: http://www.cmarz.org). Holozooplankton are small, completely planktonic invertebrates—which spend their lives floating or swimming in open water—and are a particularly sensitive marker of environmental changes such as ocean warming or acidification.DNA barcoding can also be applied to prokaryotes, although it requires alternative sequences owing to the lack of mitochondria. In addition, horizontal gene transfer and uncertainty about how to define prokaryotic species complicate the task of cataloguing them. Nevertheless, by targeting a suitable core subset of a few genes, bacteria and archaea can be identified quite accurately, and barcoding can increase our knowledge and understanding of their behaviour and evolution.Such techniques could be applied to the identification of marine prokaryotic species, but Poiner argues that they need further refinement and will probably need to be combined with analytical methods that help estimate the total diversity, given that it is impossible to identify every single species at present. Indeed, the task of assessing the diversity of even land-based microorganisms is difficult, but such cataloguing is a prerequisite for accurate assessment of their response to environmental change.“There is a general rule that the smaller things are the less we know about them,” commented Stephen Blackmore, Regius Keeper of the Royal Botanical Gardens in Edinburgh, UK, a leading centre for conservation research. “I think it is very difficult or too early to say how biodiversity at the microscopic level is being impacted. Some of the newer approaches using DNA diversity to see, for example, what microorganisms are present in soil, will be important.”In the immediate future, advanced DNA analysis techniques have a more urgent application: the identification of genetic diversity within eukaryotic species. This is important because it determines the ability of populations to cope with rapid change: a species with greater genetic diversity is more likely to have individuals with phenotypes capable of surviving changes in habitat, temperature or nutrient availability. Genetic evidence will help to determine the secret of success for many invasive species of plants and animals, as they have already adapted to human influence.“A major emerging theme is to look at the genetic diversity present in wild plant populations and to try to correlate this with identifying the populations that are best suited for coping with climate change,” Blackmore said. “But it''s a very new field and so far not much is being funded. Meanwhile, the immediate prospect is that plants will continue slipping away more or less un-noticed. Even where the landscape appears green there is generally a steady erosion of plant biodiversity going, on driven by the shrinking of natural habitats, the encroachment of invasive species, climate change and land management practices.”Yet Blackmore is optimistic that knowledge of how to preserve biodiversity is increasing, even for less adaptable species. “We know how to, for example, grow food crops in ways that are more beneficial to biodiversity, but the desire for the cheapest food means that uptake is too limited. We know how to do most of the things needed to protect biodiversity. Unfortunately they are not being done.”There is hope, though, that increased understanding of biodiversity as a single, interconnected problem—rather than a series of unrelated hot spots and particular species—will lead to more coherent strategies for arresting global decline. The fate of flowering plants, for example, is intimately tied to their pollinators and seed dispersers. Most land animals in turn depend directly or indirectly on plants. “Since plants are the base of the food chain in all terrestrial environments, the threats to animals are increasing even more rapidly than those to the plants they depend upon,” Blackmore noted. “It is still the case, however, that most conservation action is framed in terms of charismatic animals—such as tigers, whales, polar bears and pandas—rather than on the continuation of the kinds of place they require to live in.”Due to human nature, this ‘cute'' framing of the problem is perhaps inevitable. However, if it creates a groundswell of public concern leading to voluntary involvement and donation towards biodiversity conservation, then all species might benefit in the end. After all, animals and plants do not respect arbitrary human boundaries, so an ecological corridor and protected habitat created for tigers will also benefit other, less ‘cuddly'' species.  相似文献   

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Femtobiology freeze-frames crucial split seconds of chemical reactions to investigate how enzymes function. The potential prize from this knowledge could be new avenues for drug development or ways to produce clean energy.Along with replication and mutability, living beings are set apart from the mineral background they inhabit by their metabolism—their ability to catalyse chemical reactions. Since Linus Pauling first proposed that these reactions are made possible by enzymes that recognize and bind tightly to their substrates at a crucial transition point [1], it has become increasingly clear that understanding these reactions requires details of the precise molecular alignments that take place at the level of femtoseconds (10−15s).This transition state is the ‘point of no return'' for colliding molecules in a chemical reaction. Beyond it, the reactants inevitably go on to form new products; before it, the reaction does not take place. It lasts for tens to hundreds of femtoseconds, when the molecules are at a state of maximum energy from which they will fall either towards completing the reaction, or with equal likelihood, away from it. The role of the enzyme is to enable the molecules to negotiate this energy summit and to reach the point of completing the reaction.Many processes, including protein folding and the splitting of water during photosynthesis, pass through more than one transition state. Unravelling them all is a challenging task, but the potential prizes are great and might include the ability to harness reactions to produce carbon-neutral energy, for example, by mimicking or exploiting photosynthesis. There are also great therapeutic possibilities, as cell replication in cancer or metabolic processes in pathogens could be halted by intervening at transition states to block key reactions.This therapeutic avenue was first explored in 1986 by Richard Wolfenden, now at the University of North Carolina at Chapel Hill, USA, who calculated that conformational changes in the active site of an enzyme at the transition state should enable it to bind to the reactants with huge strength to overcome the energy barrier [2]. This, in turn, suggested that suitably designed analogues, mimicking the reactants at the transition state, could intervene by binding to the enzyme during that brief window, thus rendering the enzyme ineffective.However, the technologies needed to gather information about transition states have only become available during the past decade. The principle technology in use is X-ray absorption spectroscopy (XAS), which is combined with an ultra-fast laser in an arrangement known as a ‘pump probe''. This setup determines the geometrical shape of the approaching molecular orbitals and the distribution of electrostatic charge around them. The XAS provides information about charge distribution, whilst the pump probe yields details of the geometrical structure during the crucial femtoseconds of the transition state.The pump probe splits a short laser pulse into two separate pulses by a timescale corresponding to the period of the relevant molecular vibrations. The first pulse—the pump—excites the sample, whereas the second pulse—the probe—measures the changes caused by the first. This information can be used to determine the structural details of the transition state, thus enabling the hunt for suitable analogues. Vern Schramm''s laboratory at the Albert Einstein College of Medicine of Yeshiva University, in New York, USA, is doing exactly this. “Our approach gives geometry and electrostatic information for the transition state,” Schramm explained. “We can use computational approaches to compare these to large numbers of related molecules to see which best mimic the transition state.” Schramm''s team has already applied this to develop a drug that targets Plasmodium falciparum—the protozoan parasite that causes malaria. The drug blocks the crucial purine pathway with a transition-state analogue [3]. Plasmodium is a purine auxotroph, meaning that it cannot manufacture the molecule directly. Instead, the parasite makes purines indirectly, through an enzyme called purine nucleoside phosphorylase that synthesizes a purine precursor called hypoxanthine. Schramm''s transition analogue, BCX4945, binds to the active site of the enzyme at the transition state and so blocks its action, starving the parasite of purine.…the potential prizes are great and might include the ability to harness reactions to produce carbon-neutral energy, for example, by mimicking or exploiting photosynthesisIn trials, BCX4945 cleared P. falciparum infection in night monkeys of the Aotus genus—a model close to that of human malarial infection. But there was some re-emergence of the parasite at reduced levels after a few days, similar to the pattern observed with conventional anti-malarial drugs. The drug has been licensed to BioCryst Pharmaceuticals, which is providing it to third parties, under license, for clinical trials. “One such party is now evaluating the drug for a go/no-go decision to go forward into a small-controlled human trial,” commented Schramm. We expect that party to make that decision by mid-2013.”Meanwhile, Schramm has planned laboratory studies to determine the exact mechanism of drug action, off-target effects and the efficiency of different drug combinations in night monkeys, as well as the rate of resistance formation in the parasite to BCX4945. However, he is having trouble finding funding for the research, as the eventual treatment would require more than three doses per day, making it difficult to deploy in regions that suffer from malaria and have poor health infrastructure. Nevertheless, Schramm is convinced that the drug has great potential because of its low toxicity and different mode of action, which starves the parasite. It has certainly demonstrated that transition-state analogues can work.In the meantime, Schramm''s group is targeting human immunodeficiency virus (HIV), which has also resisted attempts to develop satisfactory therapies that are both effective and have acceptably low side effects. The aim is to inhibit the HIV-1 protease that cleaves newly synthesized polypeptides to enable the virus particles to become infectious and invade new cells. HIV protease inhibitors have been used for years, but resistant strains of HIV have emerged. Schramm believes that a transition-state analogue might overcome this problem of resistance. “We recently solved the transition-state structures of HIV protease native and drug-resistant enzymes,” he said. “Surprisingly, the transition states are identical. Thus, the resistance does not come from altered transition-state structure. The result shows that if a transition-state analogue can be found for the reaction, it should efficiently inhibit both the native and resistant enzymes.”Although such an approach holds great promise, there are significant challenges for developing drugs that mimic transition states. One is that solving the structure of the transition state itself is not sufficient, as the analogues might still not be suitable for use in humans. Kinases, for example, perform a wide variety of signalling and other functions by transferring phosphate groups. “In kinases, we understand the transition states, but biologically compatible mimics of the transition state have not been achieved,” Schramm said.Even when biologically compatible, effective mimics are available, they might still prove inappropriate owing to unanticipated effects on other pathways. Schramm also pointed out that an inhibitor can be too powerful, irrespective of its mode of action. “Some human targets are essential and it will be harmful to cause complete inhibition for long periods. An example is the target of statins, HMGCoA reductase, which is the pacemaker enzyme for cholesterol, but also for all other steroid hormones,” he explained. This biochemical knowledge of the target is crucial for using transition-state analogues, Schramm noted. “When the target is unique to a pathogen, for example, their use is ideal. But when the target is a host enzyme, for example in cancer, animal experiments are essential to show that the analogue has the desired effect with limited toxicity.”Femtobiology is not only focused on identifying transition-state analogues for drug development; researchers are also digging into photosynthesis, given its potential for yielding carbon-neutral fuels and electric power. Photosynthesis involves two photoreactions that harvest light to energize electrons through a plethora of associated enzymes and co-factors. The crucial first step is carried out by photosystem 2 (PS2), which uses light energy to split two water molecules into oxygen and four electrons. The electrons are transferred to the Calvin cycle in which they convert carbon dioxide into carbohydrates.…the technologies needed to gather information about transition states have only become available during the past decadeThe water-splitting part of PS2 is the crucial component for solar energy conversion because it is the engine of the whole system and the key to its high efficiency [4]. “Understanding the water-splitting reaction and identifying the various reaction steps and intermediates is of key importance and will be very important for the development of new and efficient artificial systems,” explained Villy Sundstrom, whose team at Lund University in Sweden works on solar energy conversion research.The water splitting occurs in a cluster of four manganese ions and one calcium ion in a five-state cycle. To analyse the process accurately requires elucidating the precise structure of each stage, each of which lasts for only a short period. An important step forward was made in 2011, with the production of a model of the complex in the ground S1-state by X-ray crystallography at a resolution of 1.9 Å [5]. This still left the great challenge of determining the structure of the transient S2-, S3- and S4-states, but provided essential information that stimulated further work on the structure of the S2-state [6]. The study of the S2-state, by Khandavalli Lakshmi and colleagues at The Baruch ‘60 Center for Biochemical Solar Energy Research in Troy, New York, USA, involved the use of PS2 isolated from three species—two cyanobacteria and spinach. The researchers trapped the oxygen-evolving complex (OEC) in the S2-intermediate-state by low temperature illumination.Lakshmi''s team used a technique called two-dimensional hyperfine sublevel correlation spectroscopy to detect weak magnetic interactions between the manganese cluster of the S2-state and the surrounding protons. “The major breakthrough of the 1.9 Å X-ray crystal structure [of the S1-state] is that it identifies all of the amino acid ligands of the Mn4Ca-oxo cluster and four water molecules that are directly coordinated to the metal ions,” Lakshmi said. This helped the team with their detective work in locating all the structural units within 5 Å of the Mn4Ca-oxo cluster that might be involved. “This leads to several likely candidates that include amino acid ligands that are directly co-ordinated to the cluster, amino acid side chains that are not co-ordinated to the cluster, two water molecules that are co-ordinated to the manganese ion, two water molecules that are co-ordinated to the Ca2+ ion and nine water molecules that form a hydrogen bond network in the vicinity of the Mn4Ca-oxo cluster in the crystal structure,” Lakshmi explained.…biochemical knowledge of the target is crucial for using transition-state analogues…One of the interesting findings was that the S2-states of the three organisms studied were almost indistinguishable. “In an unexpected but welcome surprise, we observe that the hyperfine spectra of the S2-state of the OEC of PSII from Thermosynechococcus vulcanus, the PsbB variant of Synechocystis PCC 6803 and spinach are identical,” Lakshmi said. “This suggests that the OEC of PSII is highly conserved in the three species”.There is still some way to go to unravel all S-states of PS2, Lakshmi conceded. “There are several open questions on the fate of the water molecules in the S-states that warrant immediate attention,” she said. These include the precise location and binding of the substrate water molecules, the oxidation state of the manganese ions that ligate the substrate water molecules and precise geometry of the Mn4Ca-oxo cluster.In parallel with the structural and functional analysis of the S-states of PS2, research has been ongoing into artificial systems that use catalysts other than the Mn4Ca-oxo for water splitting. Such systems had only achieved levels of efficiency usually two orders of magnitude lower than PS2 itself, in terms of the rate of oxygen production. But a major advance uses a ruthenium catalyst to achieve water oxidation rates similar to PS2 [7]. There is just one important caveat: the catalyst does not use light to drive the oxidation, it uses an acidic solution of ammonium cerium nitrate, a compound of the rare earth metal cerium. However, the team believes that the high rates of oxidation achieved with the ruthenium catalyst could lead to water oxidation technology based on more abundant elements, such as the first-row metals rather than rare earth ones. In the future, they hope that the knowledge gained about these artificial catalysts and how they work will pave the way to the light-driven generation of molecular hydrogen by water splitting.Whilst the ultimate aims of directly harnessing photosynthesis for human benefit, and the creation of an artificial system that rivals the water-splitting efficiency of PS2 would be huge steps forward with profound implications for energy production, the end is a long way off. In the meantime, the growing interest in split-second moments at the catalytic centres of many enzymes continues to enhance our knowledge of the metabolism and lays the groundwork for progress in drug development, energy production and other areas.  相似文献   

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