A fungal perspective on human inborn errors of metabolism: alkaptonuria and beyond

Crucial for the establishment and development of biochemical genetics as a self-standing discipline was Beadle and Tatum's choice of Neurospora crassa as experimental organism some 60 years ago. Although Garrod's insights on biochemical genetics and his astonishingly modern concepts of biochemical individuality and susceptibility to disease had been ignored by their contemporaries, Beadle acknowledged on several occasions how close Garrod had come to the "one-gene-one-enzyme" hypothesis. In an unexpected turn of events, several genes involved in human inborn errors of metabolism, including the gene for Garrod's favorite disease, alkaptonuria, have been characterized by exploitation of the experimental advantages of another mold, Aspergillus nidulans, which shares with N. crassa the experimental advantages that prompted pioneers of biochemical genetics to use them: rapid growth, facile genetic manipulation, and an environment (the composition of the growth medium) that can be manipulated à la carte.     

Last judgment: the visionary biology of J.B.S. Haldane

This paper seeks to reinterpret the life and work of J. B. S. Haldane by focusing on an illuminating but largely ignored essay he published in1927, “The Last Judgment” – the sequel to his better known work, Daedalus (1924). This astonishing essay expresses a vision of the human future over the next 40,000,000 years, one that revises and updates Wellsian futurism with the long range implications of the “new biology” for human destiny. That vision served as a kind of lifelong credo, one that infused and informed his diverse scientific work, political activities, and popular writing, and that gave unity and coherence to his remarkable career. This revised version was published online in July 2006 with corrections to the Cover Date.     

Biosemiotics Within and Without Biological Holism: A Semio-historical Analysis

On the basis of a comparative analysis of the biosemiotic work of Jakob von Uexküll and of various theories on biological holism, this article takes a look at the question: what is the status of a semiotic approach in respect to a holistic one? The period from 1920 to 1940 was the peak-time of holistic theories, despite the fact that agreement on a unified and accepted set of holistic ideas was never reached. A variety of holisms, dependent on the cultural and disciplinary contexts, is sketched here from the works of Jan Smuts, Adolf Meyer-Abich, John Scott Haldane, Kurt Goldstein, Alfred North Whitehead and Wolfgang Köhler. In contrast with his contemporary holists, who used the model of an organism as a unifying explanatory tool for all levels of reality, Jakob von Uexküll confined himself to disciplinary organicism by extending the borders of the definition of “organism” without any intention to surpass the borders of biology itself. The comparison reveals also a significant difference in the perspectives of Uexküll and his contemporary holists, a difference between a view from a subjective centre in contrast with an all-encompassing structural view. Uexküll’s theories are fairly near to J. S. Haldane’s interpretation of an organism as a coordinative centre, but even here their models do not coincide. Although biosemiotics and holistic biology have different theoretical starting points and research-goals, it is possible nonetheless to place them under one and the same doctrinal roof.     

George Beadle: from genes to proteins

George W. Beadle's life spanned much of the period during which genetics changed from an abstract to a molecular science. Beadle himself catalysed the transition from classical to molecular genetics when, together with Edward Tatum, he discovered that each gene is linked to the production of a protein. This article traces his life from a modest farm to the centre of biology and a principal role in the development of the scientific enterprise.     

Comparative metabolic capabilities for Micrococcus luteus NCTC 2665, the "Fleming" strain, and actinobacteria

Putative gene predictions of the Gram positive actinobacteria Micrococcus luteus (NCTC 2665, "Fleming strain") was used to construct a genome scale reconstruction of the metabolic network for this organism. The metabolic network comprises 586 reactions and 551 metabolites, and accounts for 21% of the genes in the genome. The reconstruction was based on the annotated genome and available biochemical information. M. luteus has one of the smallest genomes of actinobacteria with a circular chromosome of 2,501,097 base pairs and a GC content of 73%. The metabolic pathways required for biomass production in silico were determined based on earlier models of actinobacteria. The in silico network is used for metabolic comparison of M. luteus with other actinomycetes, and hence provides useful information for possible future biotechnological exploitation of this organism, e.g., for production of biofuels.     

Mate desertion by male Great Reed Warblers Acrocephalus arundinaceus at the end of the breeding season

Male Great Reed Warblers usually take part in the care of offspring as nest defenders and by feeding young, but at the end of the breeding season they desert their mates with eggs or nestlings. Deserted females continue offspring care. Desertion does not depend on the male's mated status (polygynous or monogamous) nor on his past breeding success. Deserted females compensate for the loss of their partners by increasing the frequency of food-bringing, resulting in a reduction in the amount of time the nestlings are brooded. Although desertion may lead to increased rates of offspring mortality through predation, breeding success of deserted females was high, especially if the male assisted during the early stages. Deserters pay costs by giving up the chance of additional matings and by lowering the reproductive success of existing mates. Male warblers reduce the former cost by choosing the season of desertion and the latter is lowered by the female's high parental ability. A deserter was found to start moulting while his mate was still feeding his nestlings, and an earlier start to the moult may be the primary benefit that he gains. Male Great Reed Warblers usually take part in the care of offspring as nest defenders and by feeding young, but at the end of the breeding season they desert their mates with eggs or nestlings. Deserted females continue offspring care. Desertion does not depend on the male's mated status (polygynous or monogamous) nor on his past breeding success. Deserted females compensate for the loss of their partners by increasing the frequency of food-bringing, resulting in a reduction in the amount of time the nestlings are brooded. Although desertion may lead to increased rates of offspring mortality through predation, breeding success of deserted females was high, especially if the male assisted during the early stages. Deserters pay costs by giving up the chance of additional matings and by lowering the reproductive success of existing mates. Male warblers reduce the former cost by choosing the season of desertion and the latter is lowered by the female's high parental ability. A deserter was found to start moulting while his mate was still feeding his nestlings, and an earlier start to the moult may be the primary benefit that he gains. Male Great Reed Warblers usually take part in the care of offspring as nest defenders and by feeding young, but at the end of the breeding season they desert their mates with eggs or nestlings. Deserted females continue offspring care. Desertion does not depend on the male's mated status (polygynous or monogamous) nor on his past breeding success. Deserted females compensate for the loss of their partners by increasing the frequency of food-bringing, resulting in a reduction in the amount of time the nestlings are brooded. Although desertion may lead to increased rates of offspring mortality through predation, breeding success of deserted females was high, especially if the male assisted during the early stages. Deserters pay costs by giving up the chance of additional matings and by lowering the reproductive success of existing mates. Male warblers reduce the former cost by choosing the season of desertion and the latter is lowered by the female's high parental ability. A deserter was found to start moulting while his mate was still feeding his nestlings, and an earlier start to the moult may be the primary benefit that he gains. Male Great Reed Warblers usually take part in the care of offspring as nest defenders and by feeding young, but at the end of the breeding season they desert their mates with eggs or nestlings. Deserted females continue offspring care. Desertion does not depend on the male's mated status (polygynous or monogamous) nor on his past breeding success. Deserted females compensate for the loss of their partners by increasing the frequency of food-bringing, resulting in a reduction in the amount of time the nestlings are brooded. Although desertion may lead to increased rates of offspring mortality through predation, breeding success of deserted females was high, especially if the male assisted during the early stages. Deserters pay costs by giving up the chance of additional matings and by lowering the reproductive success of existing mates. Male warblers reduce the former cost by choosing the season of desertion and the latter is lowered by the female's high parental ability. A deserter was found to start moulting while his mate was still feeding his nestlings, and an earlier start to the moult may be the primary benefit that he gains. Male Great Reed Warblers usually take part in the care of offspring as nest defenders and by feeding young, but at the end of the breeding season they desert their mates with eggs or nestlings. Deserted females continue offspring care. Desertion does not depend on the male's mated status (polygynous or monogamous) nor on his past breeding success. Deserted females compensate for the loss of their partners by increasing the frequency of food-bringing, resulting in a reduction in the amount of time the nestlings are brooded. Although desertion may lead to increased rates of offspring mortality through predation, breeding success of deserted females was high, especially if the male assisted during the early stages. Deserters pay costs by giving up the chance of additional matings and by lowering the reproductive success of existing mates. Male warblers reduce the former cost by choosing the season of desertion and the latter is lowered by the female's high parental ability. A deserter was found to start moulting while his mate was still feeding his nestlings, and an earlier start to the moult may be the primary benefit that he gains.     

Cognizing "Cognized Models"

In his later work Rappaport acknowledged that his earlier efforts had overemphasized organic and ecological functions in the explanation of cultural phenomena. He then distanced himself from both idealism and reductive materialism and set out to understand the complexities of cultural understandings and ritual. Specifically, he shifted from functionalism to formalism in an effort to understand ritual and its language in relation to cultural norms. Ultimately his analysis was implicitly structural, understanding the part as a constituent of an overarching arrangement and in terms of what Althusser would have called "structural causality." Although his work benefited from this shift from function to structure, Rappaport did not use it to explore the political dimension. However, a holistic ecology such as the one Rappaport essayed must ultimately embrace both political ecology and historical ecology, [cognized models, ritual, political ecology, structural causality-]     

首次自肉毒中毒食品中分离的一株产生E型肉毒毒素的酪酸梭菌

对某卫生防疫站委托本研究室分离病原菌的一份引起肉毒中毒的食品一＂黄豆冬瓜酱＂进行检测和病原菌的分离,从中再次检出了Ｅ型肉毒毒素并分离到一产毒菌种,对该菌种的生物学及生化学特性进行检查,并检测其毒素基因（ＰＣＲ试验）。结果：该分离菌能产生Ｅ型肉毒毒素,ＰＣＲ检测结果也证明其具有Ｅ型肉毒神经毒素基因,但其多项生化特性与Ｅ型肉毒梭菌有明显差异,而与酪酸梭菌完全一致。结果说明该分离菌系产生Ｅ型肉毒毒素的酪酸梭菌,而非Ｅ型肉毒梭菌。由酪酸梭菌引起的食物中毒型肉毒中毒并从中毒食品中分离到该病原菌,这在国际上尚属首次报告。     

The search for purpose in a post-Darwinian universe: George Bernard Shaw, 'creative evolution', and Shavian eugenics: 'The dark side of the force'

The Irish playwright and socialist George Bernard Shaw has been of marginal concern for historians of biology because his vitalist Lamarckism has been viewed as out of step with contemporary science. However, Julian Huxley and J.B.S. Haldane were certainly of the opinion that Shaw was a man of influence in this regard and took pains to counter his views in their own attempts to engage the public in science. Previously, Shaw's colleague and friend H.G. Wells had also agued with Shaw from his own mechanistic neo-Darwinian perspective. The very public debate between Shaw and Wells, which continued to concern Huxley and Haldane, shows that public concern over the moral implications of Darwinism has a long history. Taking into account the opinions of John Maynard Smith on this matter, I suggest that a consideration of Shaw in this context can give us an understanding of the historical popularity of vitalist teleology as well as of the persistent ambivalence to the non-normative character of Darwinism.     

Anecdotal,Historical and Critical Commentaries on Genetics: Wright and Fisher on Inbreeding and Random Drift

Sewall Wright and R. A. Fisher often differed, including on the meaning of inbreeding and random gene frequency drift. Fisher regarded them as quite distinct processes, whereas Wright thought that because his inbreeding coefficient measured both they should be regarded as the same. Since the effective population numbers for inbreeding and random drift are different, this would argue for the Fisher view.SEWALL Wright and R. A. Fisher were central figures in mathematical population genetics; along with J. B. S. Haldane they effectively invented the field and dominated it for many years. On most issues the three were in agreement. In particular, all favored a neo-Darwinian gradualist approach and believed in the importance of a mathematical theory for understanding the evolutionary process. Yet on a few questions Fisher and Wright differed profoundly and argued vehemently. Fisher was contentious and was often involved in controversy, frequently attacking his opponents mercilessly. Wright, in contrast, was very gentle to most people. But there were a few exceptions and Fisher was one. Haldane mostly stayed out of the arguments between them.One question on which the two disagreed was the importance of random gene frequency drift and its role in Wright''s shifting-balance theory of evolution. Wright thought that a structured population with many partially isolated subpopulations, within which there was random drift and among which there was an appropriate amount of migration, offered the greatest chance for evolutionary novelty and could greatly increase the speed of evolution. Fisher thought that a large panmictic population offered the best chance for advantageous genes and gene combinations to spread through the population, unimpeded by random processes. They also disagreed on dominance, Fisher believing that it evolved by selection of dominance modifiers and Wright that it was a consequence of the nature of gene action. These differences were widely argued by population geneticists in the middle third of the twentieth century, and the interested community divided into two camps. Although the issues are not settled, Wright''s shifting-balance theory has less support than it formerly had. As for dominance, there is general quantitative disagreement with Fisher''s explanation of modifiers, but other mechanisms (e.g., selection for more active alleles) have to some extent replaced it. Wright''s theory remains popular and has been generalized and extended (Kacser and Burns 1973).     

The effects of viral load on pseudorabies virus gene expression

Background  

Herpesvirus genes are classified into distinct kinetic groups on the basis of their expression dynamics during lytic growth of the virus in cultured cells at a high, typically 10 plaque-forming units/cell multiplicity of infection (MOI). It has been shown that both the host response and the success of a pathogen are dependent on the quantity of particles infecting an organism. This work is a continuation of an earlier study [1], in which we characterized the overall expression of PRV genes following low-MOI infection. In the present study, we have addressed the question of whether viral gene expressions are dependent on the multiplicity of infection by comparing gene expressions under low and high-MOI conditions.     

Mate desertion by male Great Reed Warblers Acrocephalus arundinaceus at the end of the breeding season

Male Great Reed Warblers usually take part in the care of offspring as nest defenders and by feeding young, but at the end of the breeding season they desert their mates with eggs or nestlings. Deserted females continue offspring care. Desertion does not depend on the male's mated status (polygynous or monogamous) nor on his past breeding success. Deserted females compensate for the loss of their partners by increasing the frequency of food-bringing, resulting in a reduction in the amount of time the nestlings are brooded. Although desertion may lead to increased rates of offspring mortality through predation, breeding success of deserted females was high, especially if the male assisted during the early stages. Deserters pay costs by giving up the chance of additional matings and by lowering the reproductive success of existing mates. Male warblers reduce the former cost by choosing the season of desertion and the latter is lowered by the female's high parental ability. A deserter was found to start moulting while his mate was still feeding his nestlings, and an earlier start to the moult may be the primary benefit that he gains.     

The growth of Geotrichum candidum on whiskey distillery spent wash

Summary A strain of the imperfect fungus Geotrichum candidum was selected for its ability to utilize the low-pH, high biochemical oxygen demand (BOD) waste generated by an Irish malt whiskey distillery. Growth of the organism on this complex medium, in both batch and continuous culture, showed a sequential assimilation of the major components with the most complete carbon assimilation (63.7%) being achieved in batch culture. Optimum temperature for the continuous culture of the organism was found to be 22°C; at this temperature and at a dilution rate of 0.125 h^–1 a productivity of 2.24 g l^–1 h^–1 was obtained. Variations in organism morphology, produced by varying growth rate and nutritional or environmental factors, as well as the potential of the process for the production of single cell protein from carbohydrate-rich waste are discussed.     

A Measurement of Creativity in Western Civilization

It is surprising that anthropologists have neglected the study of creativity (artistic and philosophical) in the higher civilizations and the clustering at times of genius—especially strange that almost no one has followed up Kroeber's analysis of this in his Configurations of Culture Growth. The epicyclical theory made possible the prediction of the curve of creativity during the evolutions of Graeco-Roman and Western civilizations. A five-year empirical, quantitative study of creativity in Western civilization, with resultant name lists attached as on appendix to this paper, resulted in a curve of creativity substantially as predicted; it proved almost identical with Kroeber's conclusions in his Configurations. An earlier study (1958) for Graeco-Roman civilization had had the same results, as Kroeber had acknowledged.     

Analysis of the Salmonella typhimurium proteome through environmental response toward infectious conditions

Salmonella enterica serovar Typhimurium (also known as Salmonella typhimurium) is a facultative intracellular pathogen that causes approximately 8,000 reported cases of acute gastroenteritis and diarrhea each year in the United States. Although many successful physiological, biochemical, and genetic approaches have been taken to determine the key virulence determinants encoded by this organism, the sheer number of uncharacterized reading frames observed within the S. enterica genome suggests that many more virulence factors remain to be discovered. We used a liquid chromatography-mass spectrometry-based "bottom-up" proteomic approach to generate a more complete picture of the gene products that S. typhimurium synthesizes under typical laboratory conditions as well as in culture media that are known to induce expression of virulence genes. When grown to logarithmic phase in rich medium, S. typhimurium is known to express many genes that are required for invasion of epithelial cells. Conversely stationary phase cultures of S. typhimurium express genes that are needed for both systemic infection and growth within infected macrophages. Lastly bacteria grown in an acidic, magnesium-depleted minimal medium (MgM) designed to mimic the phagocytic vacuole have been shown to up-regulate virulence gene expression. Initial comparisons of protein abundances from bacteria grown under each of these conditions indicated that the majority of proteins do not change significantly. However, we observed subsets of proteins whose expression was largely restricted to one of the three culture conditions. For example, cells grown in MgM had a higher abundance of Mg(2+) transport proteins than found in other growth conditions. A second more virulent S. typhimurium strain (14028) was also cultured under these same growth conditions, and the results were directly compared with those obtained for strain LT2. This comparison offered a unique opportunity to contrast protein populations in these closely related bacteria. Among a number of proteins displaying a higher abundance in strain 14028 were the products of the pdu operon, which encodes enzymes required for propanediol utilization. These pdu operon proteins were validated in culture and during macrophage infection. Our work provides further support for earlier observations that suggest pdu gene expression contributes to S. typhimurium pathogenesis.     

A rationale for the therapeutic action of aprotinin.

Aprotinin, a protease inhibitor, has been used in a wide variety of pathophysiological states thought to be associated with an increase in protease activity. Opinion differ with respect to the success of the therapy. This paper proposes a rationale for the therapeutic action of aprotinin based on biochemical and physiological evidence. In the kallikrein-kinin system, in addition to kallikrein, other serine-esterases such as trypsin, plasmin, etc. can generate kinin production. In certain disease states such as pancreatitis there is not only an increase in serine-protease activity but frequently these enzymes reach parts of the organism where they are not found in health. Thus in such circumstances increased production of kinins can result. The consequences of increased kinin generation are discussed in light of work indicating their role in metabolic and circulatory homeostasis. Aprotinin is specifically a serine-esterase inhibitor. It is suggested that perhaps the most important action of this compound is as an inhibitor of the kallikrein-kinin system. On this basis a therapeutic regime in various disease states for the use of aprotinin, which allows for control of kinin generation, is suggested.     

George Gaylord Simpson as mentor and apologist for paleoanthropology

The influence of George Gaylord Simpson (1902–1984) on paleoanthropology provides a well-documented, historical example of how one scientific discipline can impact upon another, bringing the latter quickly “up to speed” without having to retrace ground covered by the former. Paleoanthropologists were bystanders during the formulation of the evolutionary synthesis (1936–1947). After World War II, the younger paleoanthropologists looked to George Gaylord Simpson as one of several mentors regarding the implications of the synthesis for their own discipline. But why Simpson? Having earlier defined the superfamily Hominoidea (1931) as holding the Pongidae and Hominidae and monographed lower primate fossils (e.g., “Studies on the earliest primates,” 1940), Simpson's “Principles of classification and a classification of mammals” (1945) further solidified his reputation as a mammalian systematist. Simpson's Meaning of Evolution (1949) was widely read as an introduction to the synthesis, and his Tempo and Mode in Evolution (1944) made accessible the more complex aspects. Consequently, in the 1950s and 1960s paleoanthropologists invited Simpson to participate in their symposia (e.g., “Some principles of historical biology bearing on human origins,” 1951; “The meaning of taxonomic statements,” 1964), used his books as classroom texts, and cited his publications to support claims for their own work. Later in the 1960s, Simpson moved from mentor to apologist, as the paleoanthropologists were by then familiar with the synthesis and incorporated its theoretical concepts in their interpretations of the many newly discovered hominoid fossils. Simpson now took special care to celebrate these results in his more general, less technical writings, acting as a forceful apologist for the materialistic view of human origins (e.g., “The biological nature of man,” 1966; “The evolutionary concept of man,” 1972). During the 1970s, Simpson's influence waned, and he became just another practitioner at the margin of the discipline. However, anthropologists acknowledged Simpson's earlier impact, for example, when he was invited, yet again, to address them at the 50th anniversary celebration of the American Association of Physical Anthropologists in 1981.     

R.A. Fisher's contributions to genetical statistics

R. A. Fisher (1890-1962) was a professor of genetics, and many of his statistical innovations found expression in the development of methodology in statistical genetics. However, whereas his contributions in mathematical statistics are easily identified, in population genetics he shares his preeminence with Sewall Wright (1889-1988) and J. B. S. Haldane (1892-1965). This paper traces some of Fisher's major contributions to the foundations of statistical genetics, and his interactions with Wright and with Haldane which contributed to the development of the subject. With modern technology, both statistical methodology and genetic data are changing. Nonetheless much of Fisher's work remains relevant, and may even serve as a foundation for future research in the statistical analysis of DNA data. For Fisher's work reflects his view of the role of statistics in scientific inference, expressed in 1949: There is no wide or urgent demand for people who will define methods of proof in set theory in the name of improving mathematical statistics. There is a widespread and urgent demand for mathematicians who understand that branch of mathematics known as theoretical statistics, but who are capable also of recognising situations in the real world to which such mathematics is applicable. In recognising features of the real world to which his models and analyses should be applicable, Fisher laid a lasting foundation for statistical inference in genetic analyses.     

Charles Manning Child (1869-1954): the past, present, and future of metabolic signaling

Charles Manning Child's work focused on metabolic gradients and their influence on organismal development. Early in the 20th century, his work had considerable currency, but by the second half of the century he had become little more than a historical footnote. Yet today Child's ideas are once again topical. While there were issues of cause and effect that Child and his students were never able to address adequately, in hindsight the extent of his eclipse hardly seems warranted. In fact, the demise of Child's theories may have resulted from larger changes in the nature of biology in the early 20th century. Child frequently studied planarians, hydroids, and other animals that are capable of asexual, agametic reproduction, and his theories most clearly apply to such organisms. In contrast, Thomas Hunt Morgan, initially one of Child's competitors in studies of regeneration, later developed the field of transmission genetics based on fruit flies, which can only reproduce via gametes. Child's theories and model systems were largely casualties of the success of Morgan's mechanistic paradigm. Nevertheless, in modern biology metabolic gradients, recast in terms of redox signaling, have become central to understanding both normal and pathological development.