Replication origin plasticity, Taylor-made: inhibition vs recruitment of origins under conditions of replication stress

Among his many contributions to the field of chromosome structure and dynamics, J. Herbert Taylor showed that eukaryotic cells have many more potential replication origins than they use, which they can recruit when replication forks are slowed to complete S-phase in a timely fashion. Thirty years later, his findings raise an important but largely overlooked paradox. Although new data have confirmed his results, a larger body of data has revealed that slowing replication forks activates an S-phase checkpoint cascade that inhibits initiation from unfired origins until the stress is relieved. In this paper, in celebration of Taylor’s work published in Chromosoma 30 years ago, I draw attention to this paradox and offer some plausible models to explain how replication stress can both inhibit and recruit new origins. I hope that this essay will stimulate further experimentation into the basis of Taylor’s original findings.     

Brocchi,Darwin, and Transmutation: Phylogenetics and Paleontology at the Dawn of Evolutionary Biology

Giambattista Brocchi’s (1814) monograph (see Dominici, Evo Edu Outreach, this issue, 2010) on the Tertiary fossils of the Subappenines in Italy—and their relation to the living molluscan fauna—contains a theoretical, transmutational perspective (“Brocchian transmutation”). Unlike Lamarck (1809), Brocchi saw species as discrete and fundamentally stable entities. Explicitly analogizing the births and deaths of species with those of individual organisms (“Brocchi’s analogy”), Brocchi proposed that species have inherent longevities, eventually dying of old age unless driven to extinction by external forces. As for individuals, births and deaths of species are understood to have natural causes; sequences of births and deaths of species produce genealogical lineages of descent, and faunas become increasingly modernized through time. Brocchi calculated that over 50% of his fossil species are still alive in the modern fauna. Brocchi’s work was reviewed by Horner (1816) in Edinburgh. Brocchi’s influence as a transmutational thinker is clear in Jameson’s (1827) “geological illustrations” in his fifth edition of his translation of Cuvier’s Theory of the Earth (read by his student Charles Darwin) and in the anonymous essays of 1826 and 1827 published in the Edinburgh New Philosophical Journal—which also carried a notice of Brocchi’s death in 1827. The notion that new species replace older, extinct ones—in what today would be called an explicitly phylogenetic context—permeates these essays. Herschel’s (1830) discussion of temporal replacement of species and the modernization of faunas closely mirrors these prior discussions. His book, dedicated to the search for natural causes of natural phenomena, was read by Charles Darwin while a student at Cambridge. Darwin’s work on HMS Beagle was in large measure an exploration of replacement patterns of “allied forms” of endemic species in time and in space. His earliest discussions of transmutation, in his essay February 1835, as well as the Red Notebook and the early pages of Notebook B (the latter two written in 1837 back in England), contain Brocchi’s analogy, including the idea of inherent species longevities. Darwin’s first theory of the origin of species was explicitly saltational, invoking geographic isolation as the main cause of the abrupt appearance of new species. We conclude that Darwin was testing the predicted patterns of both Brocchian and Lamarckian transmutation as early as 1832 at the outset of his work on the Beagle.     

Associational resistance for mule’s ears with sagebrush neighbors

Many examples of associational resistance have been reported, in which a plant’s neighbors reduce the rate of damage by herbivores that it experiences. Despite 30 years of interest and hundreds of examples of associational resistance, we still know very little about how plants avoid their herbivores. This lack of mechanistic understanding prevents us from predicting when or where associational resistance will be important or might affect species’ distributions. I demonstrate here that the plant neighborhoods that surrounded focal mule’s ears (Wyethia mollis) individuals affected the damage they received. In particular, distance between a focal mule’s ears individual and its nearest sagebrush neighbor (Artemisia tridentata) was a good predictor of how much leaf area the mule’s ears would lose to herbivores over 2 years. Mule’s ears close to sagebrush suffered less loss than those with more distant nearest sagebrush neighbors. Mule’s ears with near sagebrush neighbors suffered half the leaf loss as mule’s ears with sagebrush experimentally removed. This associational resistance was probably not caused by sagebrush attracting or increasing populations of predators of generalist herbivores. Sagebrush is known to emit chemicals that are feeding deterrents to generalist grasshoppers and these deterrents were probably involved here. Volatile chemicals emitted by damaged sagebrush have been found to induce resistance in neighboring plants of several species. However, I found no evidence for such eavesdropping here as mule’s ears gained associational resistance from sagebrush neighbors whether or not those sagebrush neighbors had been experimentally damaged. Understanding the mechanisms responsible for associational resistance is critical to predicting where and when it will be important.     

Inflammation,Aging, and Cancer: Tumoricidal Versus Tumorigenesis of Immunity

Acute inflammation is a highly regulated defense mechanism of immune system possessing two well-balanced and biologically opposing arms termed apoptosis (‘Yin’) and wound healing (‘Yang’) processes. Unresolved or chronic inflammation (oxidative stress) is perhaps the loss of balance between ‘Yin’ and ‘Yang’ that would induce co-expression of exaggerated or ‘mismatched’ apoptotic and wound healing factors in the microenvironment of tissues (‘immune meltdown’). Unresolved inflammation could initiate the genesis of many age-associated chronic illnesses such as autoimmune and neurodegenerative diseases or tumors/cancers. In this perspective ‘birds’ eye’ view of major interrelated co-morbidity risk factors that participate in biological shifts of growth-arresting (‘tumoricidal’) or growth-promoting (‘tumorigenic’) properties of immune cells and the genesis of chronic inflammatory diseases and cancer will be discussed. Persistent inflammation is perhaps a common denominator in the genesis of nearly all age-associated health problems or cancer. Future challenging opportunities for diagnosis, prevention, and/or therapy of chronic illnesses will require an integrated understanding and identification of developmental phases of inflammation-induced immune dysfunction and age-associated hormonal and physiological readjustments of organ systems. Designing suitable cohort studies to establish the oxido-redox status of adults may prove to be an effective strategy in assessing individual’s health toward developing personal medicine for healthy aging.     

August Weismann Embraces the Protozoa

This paper examines the contents and institutional context of August Weismann’s long essay on Amphimixis (1891). Therein he presented detailed discussions of his on-going studies of reduction division and parthenogenesis, but more to the point, he included an elaborate examination of émile Maupas’s two major publications in protozoology. To understand the relevance of this part to the other two, the author briefly reviews highpoints in earlier nineteenth century protozoology and concludes that only in the mid-1870s and 1880s did protozoa add an important dimension to heredity theory. Otto Bütschli and then Maupas provided Weismann with a deeper understanding of how conjugation and fertilization were related but not identical processes. This allowed him to integrate the two into a fuller understanding of evolution by natural selection.     

Experimenting with Transmutation: Darwin, the Beagle, and Evolution

Detailed analysis of Darwin’s scientific notes and other writings from the Beagle voyage reveals a focus on endemism and replacement of allied taxa in time and in space that began early in the journey. Though it is impossible to determine exactly when Darwin became a transmutationist, the evidence suggests that he was conversant with the transmutational ideas of Lamarck and others and testing (“experimenting” with) them—before he received a copy of Lyell’s Principles of Geology, vol. 2, in November 1832, in which Lyell describes and disputes Lamarck’s theory. To the two rhea species of Patagonia and the four mockingbird species of the Galapagos, we can now add the living Patagonian cavy (rodent) species, and its extinct putatively related species that Darwin collected at Monte Hermoso (Bahia Blanca) in the Fall of 1832, as a replacement pattern absolutely critical to the development of Darwin’s transmutational thinking. Darwin developed his first transmutational theory by adopting “Brocchi’s analogy” (Rudwick 2008)—i.e. that births and deaths of species are analogous to the births and deaths of individuals. Births and deaths of species, as of individuals, are thus explicable in terms of natural causes. Darwin explored these themes and the replacement of the extinct cavy by the modern species explicitly in his February 1835 essay (Darwin 1835a).

Ontogeny, anatomy, and the problem of homology: Carl Gegenbaur and the American tradition of cell lineage studies

Summary In this paper we analyze Carl Gegenbaur’s conception of the relationship between embryology (“Ontogenie”) and comparative anatomy and his related ideas about homology. We argue that Gegenbaur’s conviction of the primacy of comparative anatomy and his careful consideration of caenogenesis led him to a more balanced view about the relationship between ontogeny and phylogeny than his good friend Ernst Haeckel. We also argue that Gegenbaur’s ideas about the centrality of comparative anatomy and his definitions of homology actually laid the conceptual foundations for Hans Spemann’s (1915) later analysis of homology. We also analyze Gegenbaur’s reception in the United States and how the discussions between E.B. Wilson and Edwin Conklin about the role of the “embryological criterion of homology” and the latter’s argument for an even earlier concept of cellular homology reflect the recurring theme of preformism in ontogeny, a theme that finds its modern equivalent in various genetic definitions of homology, only recently challenged by the emerging synthesis of evolutionary developmental biology. Finally, we conclude that Gegenbaur’s own careful methodological principles can serve as an important model for proponents of present day “evo-devo”, especially with respect to the integration of ontogeny with phylogeny embedded in comparative anatomy.     

A proposal for re-defining the way the aetiology of schizophrenia and bipolar human psychiatric diseases is investigated

“The two big problems — the nature of development and the nature of the mind — are being subdued. I don’t know whether there will be beautiful, general theories to come out of this — something really nice like Watson and Crick’s double helix — or whether there will be an accumulation of more and more details. I’ll confess to a secret hope for the former” (Crow 2000).     

The niche of the potto,Perodicticus potto

Some new field observations on West African pottos are presented and compared with previously published information on substrate use and diet. This evidence suggests that the predominant means by which pottos find food is by carefully searching branches in the forest canopy with their noses and that gums and slow-moving invertebrates found on branch surfaces are major components of their diet. When fruits are scarce, gums may be the potto’s chief source of energy. It is argued that the potto’s deliberate locomotion and some of its anatomical peculiarities are related primarily to this diet and foraging behavior, rather than to concealment from predators or the capture of birds, two factors previously suggested to have been important in the evolution of the potto’s locomotor technique. The potto’s niche is compared to that of other lorisid primates and is found to resemble closely that of Galago crassicaudatusin several respects.     

Flow simulation along a seal: the impact of an external device

An increasing number of marine mammal studies on physiology, behaviour and ecology rely on data, which have been collected from back-mounted devices, such as bio-logging tags and satellite transmitters. However, external devices may influence an animal’s hydrodynamics, behaviour and energy expenditure and, therefore, can impede the individual animal. To investigate the influence of external devices on seals, the water flow along a grey seal was simulated using computational fluid dynamics calculations. The simulations revealed several changes in forces and moments and thus balance, due to this device. The investigated satellite transmitter creates an average 12% increase of the drag coefficient. Additionally, there are significant relative transmitter-induced increases in pitching moment (32%) and lift (240%). The simulations also showed that the transmitter generates areas of decreased wall shear stress on the seal’s back. The results of this study demonstrate that external devices can change the hydrodynamics of the seal, which is expected to alter the seal’s physiology and behaviour and its use of the ecosystem. Long-term attachment may have adverse effects on the animal’s welfare. It is important to take these effects into consideration when studying tagged seals; otherwise, the value of the data obtained will be poor. Therefore, interpretations and extrapolations regarding ‘natural behaviour’ of animals in their ‘natural environment’ should only be made with great caution.     

Kinship,Family, and Gender Effects in the Ultimatum Game

Kinship and reciprocity are two main predictors of altruism. The ultimatum game has been used to study altruism in many small-scale societies. We used the ultimatum game to examine effects of individuals’ family and kin relations on altruistic behavior in a kin-based horticultural community in rural Dominica. Results show sex-specific effects of kin on ultimatum game play. Average coefficient of relatedness to the village was negatively associated with women’s ultimatum game proposals and had little effect on men’s proposals. Number of brothers in the village was positively associated with men’s ultimatum game proposals and negatively associated with women’s proposals. Similarly, presence of father in the village was associated with higher proposals by men and lower proposals by women. We interpret the effect of brothers on men’s proposals as a consequence of local competition among brothers. We speculate that daughter-biased parental care in this community creates a sense of entitlement among women with brothers, which may explain the inverse relation between number of brothers and women’s ultimatum game proposals. The pattern of results may be consistent with how matrifocality affects cultural models of fairness differently along gender and family lines.     

The Study of Golgi Apparatus in Alzheimer’s Disease

Alzheimer’s disease is an irreversible, progressive neurodegenerative disorder leading invariably to death, usually within 7–10 years after diagnosis and is the leading cause of dementia in the elderly. Not only is Alzheimer’s disease a tragic disease in which people suffer from neurodegeneration in the years to come, it also becomes an incredible burden on the public health system. However, there is currently no effective treatment to halt the progression or prevent the onset of Alzheimer’s disease. This is partly due to the fact that the complex pathophysiology of Alzheimer’s disease is not yet completely understood. Recently, Golgi apparatus is found to play an important role in Alzheimer’s disease. In this review, we discuss the changes of Golgi apparatus during clinical progression and pathological development of Alzheimer’s disease. First, changes of Golgi apparatus size in Alzheimer’s disease are summarized. We then address the role of Golgi apparatus in the neuropathology of Alzheimer’s disease. Finally, the role of Golgi apparatus in the pathogenesis of Alzheimer’s disease is discussed. Understanding the contribution of Golgi apparatus dysfunction to Alzheimer’s disease and its pathophysiological basis will significantly impact our ability to develop more effective therapies for Alzheimer’s disease.     

Molecular biology in the Soviet Russia (An essay)

Stages of the evolvement and development of the major directions of molecular biology in the 1950–1980’s and its prehistory bracketing the 1920–1940’s are considered against the backgrounds of the history of the Soviet science. Short outlines of the lives and activities of the leading scientists who shaped the directions of and provided for success in studying supramolecular cell structures and molecular mechanisms of processes on a cellular level. This essay, which is far from exhaustive in describing the problems that the Soviet scientists have been dealing with, does not cover the studies of the last decade, nor does it evaluate the contributions of the living molecular biologists.     

From Punch to Profile

In this essay an aspect of my research is highlighted that has its roots in the mid seventies with the implementation of the ‘Palkovits punch’ procedure. This methodology was introduced when radiochemical and radio-immunoassay methods became sufficiently sensitive to measure key molecules for chemical neurotransmission and metabolism in minute amounts of brain tissue. For application of today’s laser guided microdissection this knowledge of functional neuro-anatomy is indispensable.Special Issue Dedicated to Miklós Palkovits.     

Resistance to tetracycline, macrolide-lincosamide-streptogramin, trimethoprim, and sulfonamide drug classes

The discovery and use of antimicrobial agents in the last 50 yr has been one of medicine’s greatest achievements. These agents have reduced morbidity and mortality of humans and animals and have directly contributed to human’s increased life span. However, bacteria are becoming increasingly resistant to these agents by mutations, which alter existing bacterial proteins, and/or acquisition of new genes, which provide new proteins. The latter are often associated with mobile elements that can be exchanged quickly across bacterial populations and may carry multiple antibiotic genes fo resistance. In some case, virulence factors are also found on these same mobile elements. There is mounting evidence that antimicrobial use in agriculture, both plant and animal, and for environmental purposes does influence the antimicrobial resistant development in bacteria important in humans and in reverse. In this article, we will examine the genes which confer resistance to tetracycline, macrolide-lincosamide-streptogramin (MLS), trimethoprim, and sulfonamide.     

Capitalist Contexts for Darwinian Theory: Land, Finance, Industry and Empire

When socio-economic contexts are sought for Darwin’s science, it is customary to turn to the Industrial Revolution. However, important issues about the long run of England’s capitalisms can only be recognised by taking a wider view than Industrial Revolution historiographies tend to engage. The role of land and finance capitalisms in the development of the empire is one such issue. If we historians of Darwin’s science allow ourselves a distinction between land and finance capitalisms on the one hand and industrial capitalism on the other; and if we ask with which side of this divide were Darwin and his theory of branching descent by natural selection aligned, then reflection on leading features of that theory, including its Malthusian elements, suggests that the answer is often and largely, though not exclusively: on the land side. The case of Wallace, socialist opponent of land capitalism, may not be as anomalous for this suggestion as one might at first think. Social and economic historians have reached no settled consensuses on the long-run of England’s capitalisms. We historians of Darwin’s science would do well to import some of these unsettled states of discussion into our own work over the years to come.     

Deep cerebellar neurons mirror the spinal cord’s gain to implement an inverse controller

Smooth and coordinated motion requires precisely timed muscle activation patterns, which due to biophysical limitations, must be predictive and executed in a feed-forward manner. In a previous study, we tested Kawato’s original proposition, that the cerebellum implements an inverse controller, by mapping a multizonal microcomplex’s (MZMC) biophysics to a joint’s inverse transfer function and showing that inferior olivary neuron may use their intrinsic oscillations to mirror a joint’s oscillatory dynamics. Here, to continue to validate our mapping, we propose that climbing fiber input into the deep cerebellar nucleus (DCN) triggers rebounds, primed by Purkinje cell inhibition, implementing gain on IO’s signal to mirror the spinal cord reflex’s gain thereby achieving inverse control. We used biophysical modeling to show that Purkinje cell inhibition and climbing fiber excitation interact in a multiplicative fashion to set DCN’s rebound strength; where the former primes the cell for rebound by deinactivating its T-type Ca2⁺ channels and the latter triggers the channels by rapidly depolarizing the cell. We combined this result with our control theory mapping to predict how experimentally injecting current into DCN will affect overall motor output performance, and found that injecting current will proportionally scale the output and unmask the joint’s natural response as observed by motor output ringing at the joint’s natural frequency. Experimental verification of this prediction will lend support to a MZMC as a joint’s inverse controller and the role we assigned underlying biophysical principles that enable it.     

Wikipedia as an encyclopaedia of life

In a 2003 essay E. O. Wilson outlined his vision for an “encyclopaedia of life” comprising “an electronic page for each species of organism on Earth”, each page containing “the scientific name of the species, a pictorial or genomic presentation of the primary type specimen on which its name is based, and a summary of its diagnostic traits.” Although biodiversity informatics has generated numerous online resources, including some directly inspired by Wilson’s essay (e.g., iSpecies and EOL), we are still some way from the goal of having available online all relevant information about a species, such as its taxonomy, evolutionary history, genomics, morphology, ecology, and behaviour. While the biodiversity community has been developing a plethora of databases, some with overlapping goals and duplicated content, Wikipedia has been slowly growing to the point where it now has over 100,000 pages on biological taxa. My goal in this essay is to explore the idea that, largely independent of the aims of biodiversity informatics and well-funded international efforts, Wikipedia has emerged as potentially the best platform for fulfilling E. O. Wilson’s vision.     

History of the word photosynthesis and evolution of its definition

In 1893, Charles Barnes (1858–1910) proposed that the biological process for ‘synthesis of complex carbon compounds out of carbonic acid, in the presence of chlorophyll, under the influence of light’ should be designated as either ‘photosyntax’ or ‘photosynthesis.’ He preferred the word ‘photosyntax,’ but ‘photosynthesis’ came into common usage as the term of choice. Later discovery of anoxygenic photosynthetic bacteria and photophosphorylation necessitated redefinition of the term. This essay examines the history of changes in the meaning of photosynthesis. This revised version was published online in June 2006 with corrections to the Cover Date.     

Cell Cultures from Marine Invertebrates: New Insights for Capturing Endless Stemness

Despite several decades of extensive research efforts, there is yet no single permanent cell line available from marine invertebrates as these cells stop dividing in vitro within 24–72 h after their isolation, starting cellular quiescence. This ubiquitous quiescent state should be modified in a way that at least some of the quiescent cells will become pluripotent, so they will have the ability to divide and become immortal. Following the above need, this essay introduces the rationale that the discipline of marine invertebrates’ cell culture should gain from applying of two research routes, relevant to mammalian systems but less explored in the marine arena. The first is the use of adult stem cells (ASC) from marine organisms. Many marine invertebrate taxa maintain large pools of ASC in adulthood. Ample evidence attests that these cells from sponges, cnidarians, flatworms, crustaceans, mollusks, echinoderms, and ascidians play important roles in maintenance, regeneration, and asexual cloning, actively proliferating in vivo, resembling the vertebrates’ cancer stem cells features. The second route is to target resting somatic cell constituents, manipulating them in the same way as has recently been performed on mammalian induced pluripotent stem (iPS) cells. While “iPS cells” are the outcome of an experimental manipulation, ASC are natural and rather frequent in a number of marine invertebrates. Above two cell categories reveal that there are more than a few types of seeds (cells) waiting to be sowed in the right soil (in vitro environmental conditions) for acquiring stemness and immortality. This rationale carries the potential to revolutionize the discipline of marine invertebrate cell cultures. When cultured “correctly,” ASC and “iPS cells” from marine invertebrates may stay in their primitive stage and proliferate without differentiating into cells lineages, harnessing the stem cell’s inherent abilities of self-replication versus differentiated progenies, toward the development of immortal cell lines.