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.     

A Mathematical Biologist’s Guide to Absolute and Convective Instability

Mathematical models have been highly successful at reproducing the complex spatiotemporal phenomena seen in many biological systems. However, the ability to numerically simulate such phenomena currently far outstrips detailed mathematical understanding. This paper reviews the theory of absolute and convective instability, which has the potential to redress this inbalance in some cases. In spatiotemporal systems, unstable steady states subdivide into two categories. Those that are absolutely unstable are not relevant in applications except as generators of spatial or spatiotemporal patterns, but convectively unstable steady states can occur as persistent features of solutions. The authors explain the concepts of absolute and convective instability, and also the related concepts of remnant and transient instability. They give examples of their use in explaining qualitative transitions in solution behaviour. They then describe how to distinguish different types of instability, focussing on the relatively new approach of the absolute spectrum. They also discuss the use of the theory for making quantitative predictions on how spatiotemporal solutions change with model parameters. The discussion is illustrated throughout by numerical simulations of a model for river-based predator–prey systems.     

Survivin’s Dual Role: An Export’s View

Survivin is proposed to function as a mitotic regulator and an apoptosis inhibitor duringdevelopment and pathogenesis. As such, survivin has aroused keen interest in disparateareas of basic and translational research. Survivin acts as a subunit of the chromosomalpassenger complex (CPC), composed of the mitotic kinase Aurora-B, Borealin 5 and INCENP,and is essential for proper chromosome segregation and cytokinesis. Our recent findingsindicate that the nuclear export receptor Crm1 is critically involved in tethering the CPC to thecentromere by interacting with a leucine-rich nuclear export signal (NES), evolutionaryconserved in all mammalian survivin proteins. In addition, the survivin/Crm1 interaction10 seems to be required for the cytoprotective activity of survivin, because export deficientsurvivin fails to protect tumor cells against cancer therapy-induced apoptosis. These findingsappear of clinical relevance since preferential nuclear localization of survivin turned out to bea favorable prognostic factor in cancer patients. Besides emphasizing the functionalsignificance of the Crm1/survivin interface, we suggest to exploit the pharmacogenetic15 interference with survivin’s export as a novel strategy to antagonize survivin’s activity.     

A Statistical Perspective on Prevention Trials: A View from the Women’s Health Initiative

Chronic disease prevention trials test strategies to reduce the risk of a specific health event in generally healthy people. These strategies are often thought to affect other health conditions and their use in the population requires a very favorable safety profile. A prevention trial assessing such a strategy is most valuable when designed to capture the overall public health impact and hence provide more comprehensive, reliable information for policy and practice. This broad agenda, and particularly the assessment of multiple outcomes, creates statistical challenges in the design, monitoring, and reporting of such a trial. In this article these issues are described in the context of the Women’s Health Initiative, a large randomized prevention trial testing three interventions in post-menopausal women: hormone therapy, a low-fat diet and calcium and vitamin D supplementation. Each intervention was hypothesized to influence multiple chronic disease rates including cardiovascular disease, stroke, cancers, and fractures. Here the design, monitoring, and reporting of the WHI trials is reviewed in the context of multiple outcomes and the approach to a global assessment of these interventions is described.     

A Megafauna’s Microfauna: Gastrointestinal Parasites of New Zealand’s Extinct Moa (Aves: Dinornithiformes)

We perform the first multidisciplinary study of parasites from an extinct megafaunal clade using coprolites from the New Zealand moa (Aves: Dinornithiformes). Ancient DNA and microscopic analyses of 84 coprolites deposited by four moa species (South Island giant moa, Dinornis robustus; little bush moa, Anomalopteryx didiformis; heavy-footed moa, Pachyornis elephantopus; and upland moa, Megalapteryx didinus) reveal an array of gastrointestinal parasites including coccidians (Cryptosporidium and members of the suborder Eimeriorina), nematodes (Heterakoidea, Trichostrongylidae, Trichinellidae) and a trematode (Echinostomida). Parasite eggs were most prevalent and diverse in coprolites from lowland sites, where multiple sympatric moa species occurred and host density was therefore probably higher. Morphological and phylogenetic evidence supports a possible vicariant Gondwanan origin for some of the moa parasites. The discovery of apparently host-specific parasite taxa suggests paleoparasitological studies of megafauna coprolites may provide useful case-studies of coextinction.     

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.

A Bird’s Eye View of Discard Reforms: Bird-Borne Cameras Reveal Seabird/Fishery Interactions

Commercial capture fisheries produce huge quantities of offal, as well as undersized and unwanted catch in the form of discards. Declines in global catches and legislation to ban discarding will significantly reduce discards, but this subsidy supports a large scavenger community. Understanding the potential impact of declining discards for scavengers should feature in an eco-system based approach to fisheries management, but requires greater knowledge of scavenger/fishery interactions. Here we use bird-borne cameras, in tandem with GPS loggers, to provide a unique view of seabird/fishery interactions. 20,643 digital images (one min⁻¹) from ten bird-borne cameras deployed on central place northern gannets Morus bassanus revealed that all birds photographed fishing vessels. These were large (>15 m) boats, with no small-scale vessels. Virtually all vessels were trawlers, and gannets were almost always accompanied by other scavenging birds. All individuals exhibited an Area-Restricted Search (ARS) during foraging, but only 42% of ARS were associated with fishing vessels, indicating much ‘natural’ foraging. The proportion of ARS behaviours associated with fishing boats were higher for males (81%) than females (30%), although the reasons for this are currently unclear. Our study illustrates that fisheries form a very important component of the prey-landscape for foraging gannets and that a discard ban, such as that proposed under reforms of the EU Common Fisheries Policy, may have a significant impact on gannet behaviour, particularly males. However, a continued reliance on ‘natural’ foraging suggests the ability to switch away from scavenging, but only if there is sufficient food to meet their needs in the absence of a discard subsidy.     

Wild Bird’s-eye View of Influenza Virus A(H1N1) Phylogenetic Evolution

Wild bird fecal samples collected and characterized by the USDA as part of a national surveillance effort were sequenced to study the genetic relatedness of avian, swine, and human H1 and N1 subtypes. Our results find that the 2009 H1N1 human outbreak is closely related to swine virus, but falls into different clades in the H1 and N1 trees. Further, there is evidence of multiple viral genetic exchanges between birds and swine. Ongoing research across host species contributes to an understanding of the circulation of influenza viruses.