The imperative for inclusion: A gender analysis of genetics

It has now been more than thirty years since Joan Wallach Scott (1986) argued that gender is a legitimate and necessary category of historical analysis that applies to all fields, including genetics. In the intervening years, a substantial body of work has appeared that adds women to the historiography of genetics. While this is a necessary component for including gender as a category of analysis in genetics, it is not sufficient. Gender analysis involves the broader goal of integrating gender into the interrogation of how social factors within research practices and institutional organization influence scientific work and knowledge production in genetics. This article argues for the imperative for inclusion—including both women and gender analysis—which, taken together, not only provide a more equitable and informative picture of the discipline's development, but also yield a historiography that more faithfully reflects the activity of doing science.     

Microbiome,probiotics and neurodegenerative diseases: deciphering the gut brain axis

The gut microbiota is essential to health and has recently become a target for live bacterial cell biotherapies for various chronic diseases including metabolic syndrome, diabetes, obesity and neurodegenerative disease. Probiotic biotherapies are known to create a healthy gut environment by balancing bacterial populations and promoting their favorable metabolic action. The microbiota and its respective metabolites communicate to the host through a series of biochemical and functional links thereby affecting host homeostasis and health. In particular, the gastrointestinal tract communicates with the central nervous system through the gut–brain axis to support neuronal development and maintenance while gut dysbiosis manifests in neurological disease. There are three basic mechanisms that mediate the communication between the gut and the brain: direct neuronal communication, endocrine signaling mediators and the immune system. Together, these systems create a highly integrated molecular communication network that link systemic imbalances with the development of neurodegeneration including insulin regulation, fat metabolism, oxidative markers and immune signaling. Age is a common factor in the development of neurodegenerative disease and probiotics prevent many harmful effects of aging such as decreased neurotransmitter levels, chronic inflammation, oxidative stress and apoptosis—all factors that are proven aggravators of neurodegenerative disease. Indeed patients with Parkinson’s and Alzheimer’s diseases have a high rate of gastrointestinal comorbidities and it has be proposed by some the management of the gut microbiota may prevent or alleviate the symptoms of these chronic diseases.     

From ‘Beastly Philosophy’ to Medical Genetics: Eugenics in Russia and the Soviet Union

This essay offers an overview of the three distinct periods in the development of Russian eugenics: Imperial (1900–1917), Bolshevik (1917–1929), and Stalinist (1930–1939). Began during the Imperial era as a particular discourse on the issues of human heredity, diversity, and evolution, in the early years of the Bolshevik rule eugenics was quickly institutionalized as a scientific discipline—complete with societies, research establishments, and periodicals—that aspired an extensive grassroots following, generated lively public debates, and exerted considerable influence on a range of medical, public health, and social policies. In the late 1920s, in the wake of Joseph Stalin's ‘Great Break’, eugenics came under intense critique as a ‘bourgeois’ science and its proponents quickly reconstituted their enterprise as ‘medical genetics’. Yet, after a brief period of rapid growth during the early 1930s, medical genetics was dismantled as a ‘fascist science’ towards the end of the decade. Based on published and original research, this essay examines the factors that account for such an unusual—as compared to the development of eugenics in other locales during the same period—historical trajectory of Russian eugenics.     

Bacterial aging: from mechanistic basis to evolutionary perspective

Aging—defined as the progressive impairment of an organism’s functional capacity, resulting from deleterious changes in cells, organs, and biological systems—is one of the most fundamental features of Eukaryotes, from humans to the unicellular budding yeast Saccharomyces cerevisiae. It has recently been reported that this may also be the case for certain (if not all) types of bacteria. In this paper, the current view on the mechanistic background and evolutionary significance of bacterial kind of aging is presented, with particular emphasis on the role of asymmetric cell division, the characteristics of stationary growth phase, and the role of oxidative protein damage.     

灰色及其改进模型在人口预测中的应用

在灰色GM（1,1）模型和优化的等维递补GM（1,1）模型的基础上,构建了灰色＋BP神经网络组合模型。对2001～2005年我国人口的变化分析后,建立人口总量模型进行预测,利用原始教据建立的灰色＋BP神经网络组合模型预测我国2008年以后五年的人口总量为13．39亿、13．49亿、13．60亿、13．7亿、13．79亿,有逐年上升的趋势。经综合误差分析和后验差检验均为“优秀”,说明该模型具有一定的应用价值。     

Experimental design and reporting standards for metabolomics studies of mammalian cell lines

Metabolomics is an analytical technique that investigates the small biochemical molecules present within a biological sample isolated from a plant, animal, or cultured cells. It can be an extremely powerful tool in elucidating the specific metabolic changes within a biological system in response to an environmental challenge such as disease, infection, drugs, or toxins. A historically difficult step in the metabolomics pipeline is in data interpretation to a meaningful biological context, for such high-variability biological samples and in untargeted metabolomics studies that are hypothesis-generating by design. One way to achieve stronger biological context of metabolomic data is via the use of cultured cell models, particularly for mammalian biological systems. The benefits of in vitro metabolomics include a much greater control of external variables and no ethical concerns. The current concerns are with inconsistencies in experimental procedures and level of reporting standards between different studies. This review discusses some of these discrepancies between recent studies, such as metabolite extraction and data normalisation. The aim of this review is to highlight the importance of a standardised experimental approach to any cultured cell metabolomics study and suggests an example procedure fully inclusive of information that should be disclosed in regard to the cell type/s used and their culture conditions. Metabolomics of cultured cells has the potential to uncover previously unknown information about cell biology, functions and response mechanisms, and so the accurate biological interpretation of the data produced and its ability to be compared to other studies should be considered vitally important.     

Current cases in which epitope mimicry is considered a component cause of autoimmune disease: Guillain-Barré syndrome

Some patients develop Guillain-Barré syndrome (GBS) after the administration of bovine gangliosides. Patients with GBS subsequent to Campylobacter jejuni enteritis frequently have IgG antibody to GM1 ganglioside. Miller Fisher syndrome (MFS), a variant of GBS, is associated with IgG antibody to GQ1b ganglioside. Molecular mimicry between GM1 and lipopolysaccharide of C. jejuni isolated from patients with GBS, and between GQ1b and C. jejuni lipopolysaccharides from patients with MFS have been demonstrated. The molecular mimicry between infectious agents and gangliosides may function in the production of anti-ganglioside antibodies. This sugar mimicry is one possible cause of the Guillain-Barré and Miller Fisher syndromes; however, unidentified host factors may contribute to the development of these syndromes.     

Reprogramming the metabolome rescues retinal degeneration

Metabolomics studies in the context of ophthalmology have largely focused on identifying metabolite concentrations that characterize specific retinal diseases. Studies involving mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy have shown that individuals suffering from retinal diseases exhibit metabolic profiles that markedly differ from those of control individuals, supporting the notion that metabolites may serve as easily identifiable biomarkers for specific conditions. An emerging branch of metabolomics resulting from biomarker studies, however, involves the study of retinal metabolic dysfunction as causes of degeneration. Recent publications have identified a number of metabolic processes—including but not limited to glucose and oxygen metabolism—that, when perturbed, play a role in the degeneration of photoreceptor cells. As a result, such studies have led to further research elucidating methods for prolonging photoreceptor survival in an effort to halt degeneration in its early stages. This review will explore the ways in which metabolomics has deepened our understanding of the causes of retinal degeneration and discuss how metabolomics can be used to prevent retinal degeneration from progressing to its later disease stages.     

Disciplining cattle reproduction: Veterinary reproductive science,bull infertility,and the mid-twentieth century transformation of Swedish dairy cattle breeding

From the 1940s, reproductive physiology and livestock genetics transformed dairy cattle breeding and became, in conjunction with the new reproductive technology of artificial insemination, important drivers of agricultural modernization in most countries with significant dairying. While this is well known, we know less about the longer-term interplay between specifically veterinary interests in reproduction and the institutional development of cattle breeding. In the present paper, I therefore examine the veterinary disciplining of cattle reproduction—its constitution as a veterinary scientific discipline and the extension of veterinary control over it—in mid-twentieth century Sweden. I show how veterinary scientists derived legitimacy for their fledgling discipline by engaging with the problems of practical breeding, and that in doing so they also exercised influence over breeding’s development. By making bulls’ reproductive disturbances visible and framing them as hereditary, they undermined the conservative interests of commercial breeders. The development of veterinary reproductive science thereby played an important role in reshaping the culture, economy, and regulations of cattle breeding in Sweden as it shifted from a prewar regime dominated by elite breeders to a postwar regime that, ostensibly, served all dairy farmers in the country.     

Apoptosis and aging: increased resistance to apoptosis enhances the aging process

Apoptosis is a vital component in the evolutionarily conserved host defense system. Apoptosis is the guardian of tissue integrity by removing unfit and injured cells without evoking inflammation. However, apoptosis seems to be a double-edged sword since during low-level chronic stress, such as in aging, increased resistance to apoptosis can lead to the survival of functionally deficient, post-mitotic cells with damaged housekeeping functions. Senescent cells are remarkably resistant to apoptosis, and several studies indicate that host defense mechanisms can enhance anti-apoptotic signaling, which subsequently induces a senescent, pro-inflammatory phenotype during the aging process. At the molecular level, age-related resistance to apoptosis involves (1) functional deficiency in p53 network, (2) increased activity in the NF-κB-IAP/JNK axis, and (3) changes in molecular chaperones, microRNAs, and epigenetic regulation. We will discuss the molecular basis of age-related resistance to apoptosis and emphasize that increased resistance could enhance the aging process.     

What's nu? A re-examination of Maxwell's ‘ratio-of-units’ argument,from the mechanical theory of the electromagnetic field to ‘On the elementary relations between electrical measurements’

This re-examination of the earliest version of Maxwell's most important argument for the electromagnetic theory of light—the equality between the speed of wave propagation in the electromagnetic ether and the ratio of electrostatic to electromagnetic measures of electrical quantity—establishes unforeseen connections between Maxwell's theoretical electrical metrology and his mechanical theory of the electromagnetic field. Electrical metrology was not neutral with respect to field-theoretic versus action-at-a-distance conceptions of electro-magnetic interaction. Mutual accommodation between these conceptions was reached by Maxwell on the British Association for the Advancement of Science (BAAS) Committee on Electrical Standards by exploiting the measurement of the medium parameters—electric inductive capacity and magnetic permeability—on an arbitrary scale. While he always worked within this constraint in developing the ‘ratio-of-units’ argument mathematically, I maintain that Maxwell came to conceive of the ratio ‘as a velocity’ by treating the medium parameters as physical quantities that could be measured absolutely, which was only possible via the correspondences between electrical and mechanical quantities established in the mechanical theory. I thereby correct two closely-related misconceptions of the ratio-of-units argument—the counterintuitive but widespread notion that the ratio is naturally a speed, and the supposition that Maxwell either inferred or proved this from its dimensional formula.     

Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes

Positive (adaptive) selection has recently been implied in human superoxide dismutase 1 (SOD1), a highly abundant antioxidant protein with energy signaling and antiaging functions, one of very few examples of direct selection on a human protein product (exon); the molecular drivers of this selection are unknown. We mapped 30 extant SOD1 sequences to the recently established mammalian species tree and inferred ancestors, key substitutions, and signatures of selection during the protein’s evolution. We detected elevated substitution rates leading to great apes (Hominidae) at ~1 per 2 million years, significantly higher than in other primates and rodents, although these paradoxically generally evolve much faster. The high evolutionary rate was partly due to relaxation of some selection pressures and partly to distinct positive selection of SOD1 in great apes. We then show that higher stability and net charge and changes at the dimer interface were selectively introduced upon separation from old world monkeys and lesser apes (gibbons). Consequently, human, chimpanzee and gorilla SOD1s have a net charge of ?6 at physiological pH, whereas the closely related gibbons and macaques have ?3. These features consistently point towards selection against the malicious aggregation effects of elevated SOD1 levels in long-living great apes. The findings mirror the impact of human SOD1 mutations that reduce net charge and/or stability and cause ALS, a motor neuron disease characterized by oxidative stress and SOD1 aggregates and triggered by aging. Our study thus marks an example of direct selection for a particular chemical phenotype (high net charge and stability) in a single human protein with possible implications for the evolution of aging.     

Von Neumann’s impossibility proof: Mathematics in the service of rhetorics

According to what has become a standard history of quantum mechanics, in 1932 von Neumann persuaded the physics community that hidden variables are impossible as a matter of principle, after which leading proponents of the Copenhagen interpretation put the situation to good use by arguing that the completeness of quantum mechanics was undeniable. This state of affairs lasted, so the story continues, until Bell in 1966 exposed von Neumann’s proof as obviously wrong. The realization that von Neumann’s proof was fallacious then rehabilitated hidden variables and made serious foundational research possible again. It is often added in recent accounts that von Neumann’s error had been spotted almost immediately by Grete Hermann, but that her discovery was of no effect due to the dominant Copenhagen Zeitgeist.We shall attempt to tell a story that is more historically accurate and less ideologically charged. Most importantly, von Neumann never claimed to have shown the impossibility of hidden variables tout court, but argued that hidden-variable theories must possess a structure that deviates fundamentally from that of quantum mechanics. Both Hermann and Bell appear to have missed this point; moreover, both raised unjustified technical objections to the proof. Von Neumann’s argument was basically that hidden-variables schemes must violate the “quantum principle” that physical quantities are to be represented by operators in a Hilbert space. As a consequence, hidden-variables schemes, though possible in principle, necessarily exhibit a certain kind of contextuality.As we shall illustrate, early reactions to Bohm’s theory are in agreement with this account. Leading physicists pointed out that Bohm’s theory has the strange feature that pre-existing particle properties do not generally reveal themselves in measurements, in accordance with von Neumann’s result. They did not conclude that the “impossible was done” and that von Neumann had been shown wrong.     

The Replication of Hertz's Cathode Ray Experiments

I reappraise in detail Hertz's cathode ray experiments. I show that, contrary to Buchwald's (1995) evaluation, the core experiment establishing the electrostatic properties of the rays was successfully replicated by Perrin (probably) and Thomson (certainly). Buchwald's discussion of ‘current purification’ is shown to be a red herring. My investigation of the origin of Buchwald's misinterpretation of this episode reveals that he was led astray by a focus on what Hertz ‘could do’—his experimental resources. I argue that one should focus instead on what Hertz wanted to achieve—his experimental goals. Focusing on these goals, I find that his explicit and implicit requirements for a successful investigation of the rays’ properties are met by Perrin and Thomson. Thus, even by Hertz's standards, they did indeed replicate his experiment.     

The Philosopher's conception of Mathesis Universalis from Descartes to Leibniz

In Descartes, the concept of a ‘universal science’ differs from that of a ‘mathesis universalis’, in that the latter is simply a general theory of quantities and proportions. Mathesis universalis is closely linked with mathematical analysis; the theorem to be proved is taken as given, and the analyst seeks to discover that from which the theorem follows. Though the analytic method is followed in the Meditations, Descartes is not concerned with a mathematisation of method; mathematics merely provides him with examples. Leibniz, on the other hand, stressed the importance of a calculus as a way of representing and adding to what is known, and tried to construct a ‘universal calculus’ as part of his proposed universal symbolism, his ‘characteristica universalis’. The characteristica universalis was never completed—it proved impossible, for example, to list its basic terms, the ‘alphabet of human thoughts’—but parts of it did come to fruition, in the shape of Leibniz's infinitesimal calculus and his various logical calculi. By his construction of these calculi, Leibniz proved that it is possible to operate with concepts in a purely formal way.     

Mechanisms of cellular invasion by intracellular parasites

Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world’s population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite–host cell interactions, forming the basis of the parasite’s cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.     

Kuhn on incommensurability and theory choice

The incommensurability of two theories seems to problematize theory comparisons, which allow for the selection of the better of the two theories. If so, it becomes puzzling how the quality of theories can improve with time, i.e. how science can progress across changes in incommensurable theories. I argue that in papers published in the 1990s, Kuhn provided a novel way to resolve this apparent tension between incommensurability and scientific progress. He put forward an account of their compatibility which worked not by downplaying the negative consequences of incommensurability but instead by allowing them to reach their natural end: a process of specialisation. This development in Kuhn’s thought has yet to be properly recorded but it is also interesting in its own right. It shows how a robust version of incommensurability—one which really does have severe negative consequences for scientists’ capacity to perform comparative evaluations of incommensurable theories—need make no puzzle of the progress of science.     

Early research on the biological effects of microwave radiation: 1940–1960

Two overriding considerations shaped the development of early research on the biological effects of microwave radiation—possible medical application (diathermy) and uncertainty about the hazards of exposure to radar. Reports in the late 1940s and early 1950s of hazards resulting from microwave exposure led to the near abandonment of medical research related to microwave diathermy at the same time that military and industrial concern over hazards grew, culminating in the massive research effort known as ‘the Tri-Service program’ (1957–1960). Both the early focus on medical application and the later search for hazards played important roles in dictating how this field of research developed as a science.     

Can patents prohibit research? On the social epistemology of patenting and licensing in science

A topic of growing importance within philosophy of science is the epistemic implications of the organization of research. This paper identifies a promising approach to social epistemology—nonideal systems design—and uses it to examine one important aspect of the organization of research, namely the system of patenting and licensing and its role in structuring the production and dissemination of knowledge. The primary justification of patenting in science and technology is consequentialist in nature. Patenting should incentivize research and thereby promote the development of knowledge, which in turn facilitates social progress. Some have disputed this argument, maintaining that patenting actually inhibits knowledge production. In this paper, I make a stronger argument; in some areas of research in the US—in particular, research on GM seeds—patents and patent licenses can be, and are in fact being, used to prohibit some research. I discuss three potential solutions to this problem: voluntary agreements, eliminating patents, and a research exemption. I argue against eliminating patents, and I show that while voluntary agreements and a research exemption could be helpful, they do not sufficiently address the problems of access that are discussed here. More extensive changes in the organization of research are necessary.