The patient’s hay-fever diary: three years of results from Germany

The patient’s hay-fever diary (PHD) is a newly developed, internet-based tool for self-documentation of pollen-induced symptoms (eyes, nose and airways), general well-being and medication use. In Germany, more than 1,600 users made over 60,500 reports in 3 years (2009–2011). An analysis of these reports reveal that the nose symptom “sneezing” is the most commonly reported (3/10 of reports), followed by eye symptom “itching” and nose “blocked”. In addition, medication use follows a similar pattern every year, with tablets being the most commonly used medication type (up to 60 % of the reports made in the years 2009 and 2011). Temporal variations in overall symptoms and organ-specific symptom scores are found to be associated with atmospheric concentrations of birch and grass pollen. Data from the PHD can be analysed with the aid of various mathematical methods and may provide information about symptoms and their severity for pollen-allergic sufferers. They may also be valuable for clinical studies in immunotherapy with pollen extracts.     

The ‘division of labour’ model of eye evolution

The ‘division of labour’ model of eye evolution is elaborated here. We propose that the evolution of complex, multicellular animal eyes started from a single, multi-functional cell type that existed in metazoan ancestors. This ancient cell type had at least three functions: light detection via a photoreceptive organelle, light shading by means of pigment granules and steering through locomotor cilia. Located around the circumference of swimming ciliated zooplankton larvae, these ancient cells were able to mediate phototaxis in the absence of a nervous system. This precursor then diversified, by cell-type functional segregation, into sister cell types that specialized in different subfunctions, evolving into separate photoreceptor cells, shading pigment cells (SPCs) or ciliated locomotor cells. Photoreceptor sensory cells and ciliated locomotor cells remained interconnected by newly evolving axons, giving rise to an early axonal circuit. In some evolutionary lines, residual functions prevailed in the specialized cell types that mirror the ancient multi-functionality, for instance, SPCs expressing an opsin as well as possessing rhabdomer-like microvilli, vestigial cilia and an axon. Functional segregation of cell types in eye evolution also explains the emergence of more elaborate photosensory–motor axonal circuits, with interneurons relaying the visual information.     

The Yank of Dobzhansky’s Bequest

Dobzhansky studied mechanisms of balancing selection using systems of inversions in Drosophila and he soon found that changes in inversion frequencies along generations in experimental populations conformed to the expectation for a simple model of heterosis. However, other more complex modes of selection, like rare male advantage, were later found to affect the maintenance of inversion polymorphisms. Here we show that a more realistic (and complex) model than heterosis—integrating all known fitness component estimates obtained in independent experiments for the ST/CH system of inversions in Drosophila pseudoobscura—not only conforms to but actually also predicts the inversion frequencies. This concludes this line of work and points to other selection mechanisms than heterosis that were also considered by Dobzhansky—frequency- and sex-dependent selection—as potential mechanisms of balancing selection responsible for the maintenance of the inversion polymorphisms in Drosophila.     

The Rediscovery of Buffon’s Tarsier

The tarsier described by Buffon and Daubenton (1765) is the source of all scientific names given to tarsiers, with the sole exception of Simia syrichta Linnaeus 1758, until the early the 19th century, and most even up to the 1820s. It is therefore extremely important to try to determine precisely what this individual might have been. We here summarize what is known of the specimen and its history, and of other specimens with which it has potentially been confused. We argue that, though there is some room for doubt, in all probability this important species still exists.     

The Impact of Lamarck’s Theory of Evolution Before Darwin’s Theory

This paper analyzes the impact that Lamarckian evolutionary theory had in the scientific community during the period between the advent of Zoological Philosophy and the publication Origin of Species. During these 50 years Lamarck’s model was a well known theory and it was discussed by the scientific community as a hypothesis to explain the changing nature of the fossil record throughout the history of Earth. Lamarck’s transmutation theory established the foundation of an evolutionary model introducing a new way to research in nature. Darwin’s selectionist theory was proposed in 1859 to explain the origin of species within this epistemological process. In this context, Charles Lyell’s Principles of Geology and Auguste Comte’s Cours de Philosophie Positive appear as two major works for the dissemination of Lamarck’s evolutionary ideology after the death of the French naturalist in 1829.     

The N’s and O’s of Drosophila glycoprotein glycobiology

The past 25 years have seen significant advances in understanding the diversity and functions of glycoprotein glycans in Drosophila melanogaster. Genetic screens have captured mutations that reveal important biological activities modulated by glycans, including protein folding and trafficking, as well as cell signaling, tissue morphogenesis, fertility, and viability. Many of these glycan functions have parallels in vertebrate development and disease, providing increasing opportunities to dissect pathologic mechanisms using Drosophila genetics. Advances in the sensitivity of structural analytic techniques have allowed the glycan profiles of wild-type and mutant tissues to be assessed, revealing novel glycan structures that may be functionally analogous to vertebrate glycans. This review describes a selected set of recent advances in understanding the functions of N-linked and O-linked (non-glycosaminoglycan) glycoprotein glycans in Drosophila with emphasis on their relatedness to vertebrate organisms.     

The Patient’s View: Issues of Theory and Practice

Almost all the knowledge now produced about psychiatry includes what is called “the patient’s or client’s perspective.” This paper analyzes how this notion has been framed in the discourses on mental health over the last two decades, particularly in mental health research and in anthropology. The very concept of the “patient’s perspective” is a social and historical construct. Despite its remarkable prevalence, the notion remains vague. Mental health research pictures it as a stable attribute of the individual. Anthropologists integrate the contextual nature of the patient view; but they still largely envision the psychiatric patient as a rational actor producing narratives based on common sense. However, in psychiatric practice, the client’s perspective is not something the patient individually produces; it is rather shaped by and in a context. To explore this process, my research investigated interactions between staff and patients in a French community mental health center, and showed that the client’s perspective is the result of a collective process. Further analysis demonstrates that eliciting or producing the patient’s view is sometimes considered a therapeutic goal in itself, since being granted the status of a rational and narrative actor gives access to the most valued model of care, one that is based on partnership. Being an outcome that is negotiated between patients and care providers, the “patient’s view” then becomes a new resource in mental health settings.

The Central Theme of Parkinson’s Disease: α-Synuclein

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, defined by the presence of resting tremor, muscular rigidity, bradykinesia, and postural instability. PD is characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta of the midbrain. The neuropathological hallmark of the disease is the presence of intracytoplasmic inclusions, called Lewy bodies (LBs) and Lewy neurites (LNs), containing α-synuclein, a small protein which is widely expressed in the brain. The α-synuclein gene, SNCA, is located on chromosome 4q22.1; SNCA-linked PD shows an autosomal dominant inheritance pattern with a relatively early onset age, and it usually progresses rapidly. Three missense mutations, A53T, A30P, and E46K, in addition to gene multiplications of the SNCA have been described so far. Although it is clear that LBs and LNs contain mainly the α-synuclein protein, the mechanism(s) which leads α-synuclein to accumulate needs to be elucidated. The primary question in the molecular pathology of PD is how wild-type α-synuclein aggregates in PD, and which interacting partner(s) plays role(s) in the aggregation process. It is known that dopamine synthesis is a stressfull event, and α-synuclein expression somehow affects the dopamine synthesis. The aberrant interactions of α-synuclein with the proteins in the dopamine synthesis pathway may cause disturbances in cellular mechanisms. The normal physiological folding state of α-synuclein is also important for the understanding of pathological aggregates. Recent studies on the α-synuclein protein and genome-wide association studies of the α-synuclein gene show that PD has a strong genetic component, and both familial and idiopathic PD have a common denominator, α-synuclein, at the molecular level. It is clear that the disease process in Parkinson’s disease, as in other neurodegenerative disorders, is very complicated; there can be several different molecular pathways which are responsible for diverse and possibly also unrelated functions inside the neuron, playing roles in PD pathogenesis.     

The small world of shakespeare’s plays

Drama, at least according to the Aristotelian view, is effective inasmuch as it successfully mirrors real aspects of human behavior. This leads to the hypothesis that successful dramas will portray fictional social networks that have the same properties as those typical of human beings across ages and cultures. We outline a methodology for investigating this hypothesis and use it to examine ten of Shakespeare’s plays. The cliques and groups portrayed in the plays correspond closely to those which have been observed in spontaneous human interaction, including in hunter-gatherer societies, and the networks of the plays exhibit “small world” properties of the type which have been observed in many human-made and natural systems.     

The P’s and Q’s of cellular PrP-Aβ interactions

Prion disease research has opened up the “black-box” of neurodegeneration, defining a key role for protein misfolding wherein a predominantly alpha-helical precursor protein, PrP^C, is converted to a disease-associated, β-sheet enriched isoform called PrP^Sc. In Alzheimer disease (AD) the Aβ peptide derived from the β-amyloid precuror protein APP folds in β-sheet amyloid. Early thoughts along the lines of overlap may have been on target,¹ but were eclipsed by a simultaneous (but now anachronistic) controversy over the role of PrP^Sc in prion diseases.^2,3 Nonetheless, as prion diseases such as Creutzfeldt-Jakob Disease (CJD) are themselves rare and can include an overt infectious mode of transmission, and as familial prion diseases and familial AD involve different genes, an observer might reasonably have concluded that prion research could occasionally catalyze ideas in AD, but could never provide concrete overlaps at the mechanistic level. Surprisingly, albeit a decade or three down the road, several prion/AD commonalities can be found within the contemporary literature. One important prion/AD overlap concerns seeded spread of Aβ aggregates by intracerebral inoculation much like prions,⁴ and, with a neuron-to-neuron ‘spreading’ also reported for pathologic forms of other misfolded proteins, Tau^5,6 and α-synuclein in the case of Parkinson Disease.^7,8 The concept of seeded spread has been discussed extensively elsewhere, sometimes under the rubric of “prionoids”⁹, and lies outside the scope of this particular review where we will focus upon PrP^C. From this point the story can now be subdivided into four strands of investigation: (1) pathologic effects of Aβ can be mediated by binding to PrP^C,¹⁰ (2) the positioning of endoproteolytic processing events of APP by pathologic (β-cleavage + γ-cleavage) and non-pathologic (α-cleavage + γ-cleavage) secretase pathways is paralleled by seemingly analogous α- and β-like cleavage of PrP^C (Fig. 1) (3) similar lipid raft environments for PrP^C and APP processing machinery,^11-13 and perhaps in consequence, overlaps in repertoire of the PrP^C and APP protein interactors (“interactomes”),^14,15 and (4) rare kindreds with mixed AD and prion pathologies.¹⁶ Here we discuss confounds, consensus and conflict associated with parameters that apply to these experimental settings.     

The photobiology of Hydra’s periodic activity

Hydra’s response to a light pulse is a phase shift of the state of bioelectric activity correlated with the periodic shortening-elongation behaviour. The direction and absolute value of a phase shift depend on intensity, direction, application phase (along the periodic activity state), and wavelength of the light pulse. Repetitive pulses entrain the behavioural cycle. The period of the behavioural cycle depends on intensity and wavelength of steady background illumination; however, the light effect is not exerted isotropically along all the phases of the behavioural cycle. Inferences are drawn on light influence on the behaviour pacemaking mechanism. By using polyclonal antibodies against squid rhodopsin, an opsin-like protein has been identified in the ectodermal layer, presumably in sensory cells.     

The difficult legacy of Turing’s wager

Neuron modeling may be said to have originated with the Hodgkin and Huxley action potential model in 1952 and Rall’s models of integrative activity of dendrites in 1964. Over the ensuing decades, these approaches have led to a massive development of increasingly accurate and complex data-based models of neurons and neuronal circuits. ModelDB was founded in 1996 to support this new field and enhance the scientific credibility and utility of computational neuroscience models by providing a convenient venue for sharing them. It has grown to include over 1100 published models covering more than 130 research topics. It is actively curated and developed to help researchers discover and understand models of interest. ModelDB also provides mechanisms to assist running models both locally and remotely, and has a graphical tool that enables users to explore the anatomical and biophysical properties that are represented in a model. Each of its capabilities is undergoing continued refinement and improvement in response to user experience. Large research groups (Allen Brain Institute, EU Human Brain Project, etc.) are emerging that collect data across multiple scales and integrate that data into many complex models, presenting new challenges of scale. We end by predicting a future for neuroscience increasingly fueled by new technology and high performance computation, and increasingly in need of comprehensive user-friendly databases such as ModelDB to provide the means to integrate the data for deeper insights into brain function in health and disease.     

The AlphaFold Database of Protein Structures: A Biologist’s Guide

AlphaFold, the deep learning algorithm developed by DeepMind, recently released the three-dimensional models of the whole human proteome to the scientific community. Here we discuss the advantages, limitations and the still unsolved challenges of the AlphaFold models from the perspective of a biologist, who may not be an expert in structural biology.     

The ‘tyranny of reproduction’: Could ectogenesis further women’s liberation?

This paper imagines what the liberatory possibilities of (full) ectogenesis are, insofar as it separates woman from female reproductive function. Even before use with human infants, ectogenesis productively disrupts the biological paradigm underlying current gender categories and divisions of labour. I begin by presenting a theory of women’s oppression drawn from the radical feminisms of the 1960s, which sees oppression as deeply rooted in biology. On this view, oppressive social meanings are overlaid upon biology and body, as artefacts of culture and history. I then argue that ectogenesis should be pursued to replace two modes of assisted gestation that can be seen as outgrowths of oppressive assumptions about women's function, ectogenesis should be pursued to replace two modes of assisted gestation. These are gestational surrogacy and uterine transplant, which arise partly from gendered, pronatalist, and geneticist norms. These practices are supported by assumptions about women’s identity and value. Pursuing technologies such as ectogenesis, which weaken the presumed link between biology and gender, is beneficial to (trans-inclusionary radical) feminist aims, as part of a broad project of challenging dominant power relations resting on and maintaining gender categories. By allowing the conceptual separation of female reproductive function from ‘woman’, ectogenesis raises questions about how we determine who counts in this gender identity, and also how we value those who claim the identity ‘woman’. I conclude that ectogenesis has the potential to challenge traditional patriarchal family structures, and thence all other male-dominated structures (of work, education, cultural production), allowing a reimagining of the family and society in more radical ways than we have yet achieved.     

Watching the ‘Eugenic Experiment’ Unfold: The Mixed Views of British Eugenicists Toward Nazi Germany in the Early 1930s

Historians of the eugenics movement have long been ambivalent in their examination of the links between British hereditary researchers and Nazi Germany. While there is now a clear consensus that American eugenics provided significant material and ideological support for the Germans, the evidence remains less clear in the British case where comparatively few figures openly supported the Nazi regime and the left-wing critique of eugenics remained particularly strong. After the Second World War British eugenicists had to push back against the accusation that their science was intrinsically dictatorial or totalitarian and, as a result, many of their early perceptions of the Nazis were ignored or rationalised away. Further, historians in recent years have focused more directly on the social reformist elements of eugenics, discussing the links between hereditary science and the birth control and feminist movements in addition to others. While undoubtedly making valuable contributions to the scholarly understanding of the eugenic milieu in the interwar years, these studies have neglected to recontextualize the sentiments of British eugenicists who did indeed view the Nazi government positively in the early years of the 1930s. This article argues that there was a significant, though not numerically sizable, faction in the British eugenics movement, though mostly outside the Eugenics Society itself, in the early 1930s that viewed the Nazi Germany as an admirable state for its implementation of eugenic principles. One of these figures was later interned by his own government for being too closely aligned with the German regime, though he argued that this affinity was driven by the quest for scientific truth rather than politics. Eugenics in Britain thus contained a greater diversity of views toward Germany than scholars have previously assumed, warranting more research into the individuals and organizations harbouring these views.