TOWARDS AN ORTHOGRAPHY OF BIRD SONG.

The classical conception of the progress of science is that of amassing observations, classifying them, proceeding from classification to general principle, and thence to theory. But this conception of science can be more properly applied to natural history than to the physical sciences. The advance of the physical sciences depends so much on the apparatus of measurement that very often a happy accident, which releases to a dozen laboratories a new technique, will affect not only the field of future exploration but even the current scientific theory in that field.     

Animal tool-use

The sight of an animal making and using a tool captivates scientists and laymen alike, perhaps because it forces us to question some of our ideas about human uniqueness. Does the animal know how the tool works? Did it anticipate the need for the tool and make it in advance? To some, this fascination with tools seems arbitrary and anthropocentric; after all, animals engage in many other complex activities, like nest building, and we know that complex behaviour need not be cognitively demanding. But tool-using behaviour can also provide a powerful window into the minds of living animals, and help us to learn what capacities we share with them - and what might have changed to allow for the incontrovertibly unique levels of technology shown by modern humans.     

Diploidy, evolution and sex

A new gene for a new purpose may be created by mutation of a pre-existing gene. But if that original gene is still required for its original purpose, and is to be retained side by side with the new, a spare copy is needed initially as raw material for the innovation. Thus in haploids the original gene must be duplicated before it is modified. But in diploids a spare copy of every gene is always available, and a mutant allele serving a new purpose can be easily established and maintained by heterosis in parallel with the old allele. Subsequent gene duplication will lead, via crossing-over, to insertion of the new gene in tandem with the old, as a permanent addition to the genome. Calculations show that diploids can thus enlarge their genomes with new genes for new purposes much more readily than haploids; in particular, they can more easily evolve the complex gene control systems characteristic of differentiated multicellular organisms. Sexual reproduction preserves diploidy, and so can be seen as the basis of these richer possibilities for evolutionary innovation.     

How to do it. Participate in an international conference.

Attending an international conference should be instructive and fun. But it can also be alarming and lonely. Although participating in scientific conferences is now almost essential to medical career development, no medical school describes how to make the most of the opportunity as part of its curriculum. Here are some hints on how to get yourself organised so that the experience can be both scientifically productive and enjoyable. In essence, you should travel, see places, meet people, make friends, and identify one or two ideas that you can apply in your own work or research.     

The formal darwinism project in outline

The formal darwinism project aims to provide a mathematical framework within which important fundamental ideas in large parts of biology can be articulated, including Darwin's central argument in The Origin (that mechanical processes of inheritance and reproduction can give rise to the appearance of design), modern extensions of evolutionary theory including ESS theory and inclusive fitness, and Dawkins' synthesis of them into a single structure. A new kind of argument is required to link equations of motion on the one hand to optimisation programs on the other, and a major point is that the biologist's concept of fitness maximisation is not represented by concepts from dynamical systems such as Lyapunov functions and gradient functions. The progress of the project so far is reviewed, though with only a brief glance at the rather complicated mathematics itself, and the centrality of fitness maximisation ideas to many areas of biology is emphasised.     

The reality of the higher taxonomic categories

A higher category is the result of a population's breaking-throuh into a new adaptive zone (attaining a new grade), and the subsequent adaptive radiation tiere. The taxonomic level of the new group is determined by the amount (quantitative and ualitative) of radiation that occurs; and tgis amount in turn is determined by the number of open sub-zones in the new zone and by the genetic plasticity of the new population. The more the new adaptive zone differs from the old one, the less likely a new population can survive in it. Should such survival occur, however, adaptations of the new population to the new zone will appear quickly. The new population will rapidly become quite different from the old one, minimizing the likelihood of finding intermediate forms, i. e., “missing links.” In addition, the intermediate population – the early entrants into the new zone – will be less well adapted to it than their descendents, and will become extinct. The combination of rapid extinction and an ephemeral transitional population explains the apparent gaps between higher-category taxa. These ideas do not help in solving such dilemmas of taxonomists as equivalence of taxa in different groups, and the taxonomic level at which to place a given group of species. But a higher taxonomic category itself is the result of a very real biological phenomenon, and that fact must influence systematicists.     

Environmental and Health Implications of Nanotechnology—Have Innovators Learned the Lessons from Past Experiences?

Nanotechnology (NT) is expected to bring about novel technological designs and materials resulting in a wide spectrum of applications. Experience gained from past innovations shows that new technologies are often accompanied by undesired side-effects. If such side-effects are neglected or underestimated, they may result in damage. In this article we examine whether innovators, the pioneers of technological advance in nanotechnology, are aware of the lessons that can be learned from adverse effects that have occurred in connection with several past innovations. Based on the results of a survey taken among innovators we discuss what consequences the innovators draw for the present innovation process and which priorities they set when dealing with environmental and health risks of nanotechnology. Results suggest that innovators may be not very sensitive to early scientific warnings regarding risks of nanotechnology. The innovators are confident that risks are assessable and manageable on a “business as usual” basis. They consider lacking public acceptance as a potential hurdle for innovation and many innovators are afraid of a backlash. Nevertheless, they seldom engage in risk communication or stakeholder dialogue. Picking up recommendations voiced by the innovators interviewed, we sketch some possible approaches as to how innovators could tackle the potential risks of nanotechnology in a proactive manner.     

On the horizon: a blood test for prions

A recent paper by Castilla et al. reported the detection of prions in the blood of scrapie-infected hamsters using a biochemical amplification method that is conceptually analogous to the polymerase chain reaction. This technological advance raises the possibility that prion diseases in humans and livestock could soon be diagnosed using blood samples if several technical limitations can be overcome.     

代谢物组学及其在微生物研究中的应用

代谢物组学(metabolomics)是继基因组学(genomics)、蛋白质组学(proteomics)后发展起来的一门新学科。对代谢物组学的含义,研究方法及流程,特别是其在微生物中的应用进行了介绍,包括使用代谢物组学中的NMR技术研究微生物在降解环境污染物中的作用;使用代谢物组学技术研究微生物代谢通量,从而在分析代谢通量的基础上通过代谢工程改变代谢通量,提高目的产物的得率;确定所获得基因库中沉默基因的功能;运用代谢物组学分析方法阐明生物体系对于环境变化的响应,从而协助我们确定最佳的取样时间及最佳分析组织,设计实验。随后简要对代谢物组学发展动态进行了展望。     

The Medawar Lecture 1998 is science dangerous?

The idea that science is dangerous is deeply embedded in our culture, particularly in literature, yet science provides the best way of understanding the world. Science is not the same as technology. In contrast to technology, reliable scientific knowledge is value-free and has no moral or ethical value. Scientists are not responsible for the technological applications of science; the very nature of science is that it is not possible to predict what will be discovered or how these discoveries could be applied. The obligation of scientists is to make public both any social implications of their work and its technological applications. A rare case of immoral science was eugenics. The image of Frankenstein has been turned by the media into genetic pornography, but neither cloning nor stem cells or gene therapy raise new ethical issues. There are no areas of research that are so socially sensitive that research into them should be proscribed. We have to rely on the many institutions of a democratic society: parliament, a free and vigorous press, affected groups and the scientists themselves. That is why programmes for the public understanding of science are so important. Alas, we still do not know how best to do this.     

Teaching critical thinking in a developmental biology course at an American liberal arts college

We all expect our students to learn facts and concepts, but more importantly, we want them to learn how to evaluate new information from an educated and skeptical perspective; that is, we want them to become critical thinkers. For many of us who are scientists and teachers, critical thought is either intuitive or we learned it so long ago that it is not at all obvious how to pass on the skills to our students. Explicitly discussing the logic that underlies the experimental basis of developmental biology is an easy and very successful way to teach critical thinking skills. Here, I describe some simple changes to a lecture course that turn the practice of critical thinking into the centerpiece of the learning process. My starting point is the "Evidence and Antibodies" sidelight in Gilbert's Developmental Biology (2000), which I use as an introduction to the ideas of correlation, necessity and sufficiency, and to the kinds of experiments required to gather each type of evidence: observation ("show it"), loss of function ("block it") and gain of function ("move it"). Thereafter, every experiment can be understood quickly by the class and discussed intelligently with a common vocabulary. Both verbal and written reinforcement of these ideas dramatically improve the students' ability to evaluate new information. In particular, they are able to evaluate claims about cause and effect; they become experts at distinguishing between correlation and causation. Because the intellectual techniques are so powerful and the logic so satisfying, the students come to view the critical assessment of knowledge as a fun puzzle and the rigorous thinking behind formulating a question as an exciting challenge.     

变长度Motif识别中的Gibbs抽样算法(英文)

Motif识别是计算生物学中的重要问题.处理缺失数据的方法被大家广泛应用于生物序列中的Motif识别,例如EM算法,Gibbs抽样等等.现在识别Motif的方法都是首先假定Motif的长度是给的,但是,事实上Motif的长度是未知的,在这篇文章中,我们用Gibbs抽样算法在寻找Motif的位置的同时确定Motif的长度.     

外源性物质提高精子受精能力研究进展

受精是一个复杂的生物学过程,精子必须具备良好的运动功能,同时需经获能和顶体反应才能实现受精。通过添加外源性物质,来改善精子体外存活时间,提高精子的运动能力,尤其是冷冻保存精子解冻后的受精能力,被认为是借助实验手段在体外改善精子功能,从而提高受精率的一个有效途径。可添加的外源性生物活性物质种类很多,通常有咖啡因、氨基多糖类物质、己酮可可碱、生殖激素类物质、细胞因子、维生素、抗氧化剂、牛黄酸和一些酶类物质等。本文对精子常用的外源性添加物质的研究进展进行了总结,在此基础提出了寻找新的外源添加物质的思路和途径。     

Hypotheses and humility: Ideas do not have to be right to be useful

Hypotheses need not be completely right to be useful. A hypothesis that explains an important aspect of the world, but not all of the world, can stimulate new ideas and new experiments which take science forward. Phlogiston is a typical case study. While not universally accepted at the time, and subsequently proved to be wrong, the hypothesis that there was a ‘fire-giving’ substance in inflammable materials prompted the development of quantitative chemistry, and the subsequent discovery of oxygen. Hypotheses today do not have to explain all aspects of the world perfectly. But they should be honest about those aspects they do not explain, and demonstrate some humility in their limitations. It is very unlikely that a single idea explains everything in a biological system. Theorists should recognise this: if they do not, their readers will, and will discount their ideas because of their lack of awareness of their context. Humility may get you a hearing.     

Evolution, hypotheses, and the question of whether humans are still evolving

A central requirement of this journal is that ideas should be testable. Can evolutionary ideas be tested? Ones about the past evolutionary history can be, but only if the hypothesis extends beyond describing what has happened into its present day implications. Evolutionary mechanisms can clearly be tested if they apply to fast-growing species, or provide specific tests of outcomes that would not otherwise be expected. But the future path of evolution, and especially of human evolution, is a more fraught area. There are still strong selective pressures on humans even in the affluent, urban West, deriving from pre-reproductive mortality, family size and age, and reproductive success. I skim the evidence that all three factors have substantial genetic components, and hence are likely to be the subject of future human evolution, and challenge readers to consider what testable hypotheses about human evolution these forces suggest.     

Skeletal biology and behavior in ancient humans

For many years, it has been known that archaic hominids had more robust long bones than do living populations, a fact that has been linked to their more physically strenuous lives. But many questions remain. How much stronger, for example, were Neanderthals than living humans? And what does this difference in strength tell us about the behavior of our ancestors? Recent research has shown that some of our earlier assumptions about robusticity and behavior in earlier humans are either simplistic or untrue. For example, it is now clear that although earlier humans were, on the average, stronger than living peoples, this is not invariably the case. Some modern human groups have even stronger humeri than those of Neanderthals. The fact that changes in robusticity do not always neatly coincide with subsistence or technological change suggests that interpretations derived in large measure from stone-tool technology and other artifactual evidence may be misleading. This new information on physical strength in earlier humans necessitates a reassessment of traditional ideas about earlier human behavior.     

Heterologous gene expression in bacterial systems under reduced oxygen tensions. Small-scale optimization precedes industrial fermentation

The expression of heterologous fusion proteins from the anaerobically inducible Escherichia coli nitrite reductase nirB promoter has been described using a number of different industrial regimes, but which have proved impractical for scaling down to suit primary research purposes. This paper describes the novel application of microbiological gas sachets generating anaerobic and microaerophilic environments to evaluate the inducible expression under the influence of nirB of heterologous proteins by attenuated vaccine strains of Salmonella typhimurium. The conditions of reduced oxygen tension model those found in lymphoid organs colonized by Salmonella in vivo and so can be used to optimize the vaccine dose prior to administration. Modeling in vivo promoter inducibility to monitor the stability of a plasmid within attenuated vaccine strains of bacteria offers an attractive alternative to antibiotic resistance, which is not permitted for clinical use in humans. This technological advance may be utilized to optimize heterologous gene expression in any microaerophilic bacterial system as a pilot, prior to production-scale applications.     

A chronology of plankton dynamics in silico: how computer models have been used to study marine ecosystems

Research on plankton ecology in the oceans has traditionally been conducted via two scientific approaches: in situ (in the field) and in vitro (in the laboratory). There is, however, a third approach: exploring plankton dynamics in silico, or using computer models as tools to study marine ecosystems. Models have been used for this purpose for over 60 years, and the innovations and implementations of historical studies provide a context for how future model applications can continue to advance our understanding. To that end, this paper presents a chronology of the in silico approach to plankton dynamics, beginning with modeling pioneers who worked in the days before computers. During the first 30 years of automated computation, plankton modeling focused on formulations for biological processes and investigations of community structure. The changing technological context and conceptual paradigms of the late-1970s and 1980s resulted in simulations becoming more widespread research tools for biological oceanographers. This period saw rising use of models as hypothesis-testing tools, and means of exploring the effects of circulation on spatial distributions of organisms. Continued computer advances and increased availability of data in the 1990s allowed old approaches to be applied to old and new problems, and led to developments of new approaches. Much of the modeling in the new millennium so far has incorporated these sophistications, and many cutting-edge applications have come from a new generation of plankton scientists who were trained by modeling gurus of previous eras. The future directions for modeling plankton dynamics are rooted in the historical studies.     

The future of the past in the present: biodiversity informatics and geological time

The biological and palaeontological communities have approached the problem of informatics separately, creating a divide between communities that is both technological and sociological in nature. In this paper we describe one new advance towards solving this problem - expanding the Scratchpads platform to deal with geological time. In creating this system we have attempted to make our work open to existing communities by providing a webservice of geological time data via the GBIF Vocabularies site. We have also ensured that our system can adapt to changes in the definition of geological time intervals and is capable of querying datasets independently of the format of geological age data used.     

AlphaFold – A Personal Perspective on the Impact of Machine Learning

I outline how over my career as a protein scientist Machine Learning has impacted my area of science and one of my pastimes, chess, where there are some interesting parallels. In 1968, modelling of three-dimensional structures was initiated based on a known structure as a template, the problem of the pathway of protein folding was posed and bets were taken in the emerging field of Machine Learning on whether computers could outplay humans at chess. Half a century later, Machine Learning has progressed from using computational power combined with human knowledge in solving problems to playing chess without human knowledge being used, where it has produced novel strategies. Protein structures are being solved by Machine Learning based on human-derived knowledge but without templates. There is much promise that programs like AlphaFold based on Machine Learning will be powerful tools for designing entirely novel protein folds and new activities. But, will they produce novel ideas on protein folding pathways and provide new insights into the principles that govern folds?