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Scientists routinely use images to display data. Readers often examine figures first; therefore, it is important that figures are accessible to a broad audience. Many resources discuss fraudulent image manipulation and technical specifications for image acquisition; however, data on the legibility and interpretability of images are scarce. We systematically examined these factors in non-blot images published in the top 15 journals in 3 fields; plant sciences, cell biology, and physiology (n = 580 papers). Common problems included missing scale bars, misplaced or poorly marked insets, images or labels that were not accessible to colorblind readers, and insufficient explanations of colors, labels, annotations, or the species and tissue or object depicted in the image. Papers that met all good practice criteria examined for all image-based figures were uncommon (physiology 16%, cell biology 12%, plant sciences 2%). We present detailed descriptions and visual examples to help scientists avoid common pitfalls when publishing images. Our recommendations address image magnification, scale information, insets, annotation, and color and may encourage discussion about quality standards for bioimage publishing.

There is increasing scrutiny around how science is communicated to the public. For instance, a Twitter account @justsaysinmice (with 70.4K followers in January 2021) was created to call attention to news headlines that omit that mice, not humans, are the ones for whom the study findings apply. This is the case of many headlines reporting on Alzheimer disease (AD) research. AD is characterized by a degeneration of the human brain, loss of cognition, and behavioral changes, for which no treatment is available. Around 200 rodent models have been developed to study AD, even though AD is an exclusively human condition that does not occur naturally in other species and appears impervious to reproduction in artificial animal models, an information not always disclosed. It is not known what prompts writers of news stories to either omit or acknowledge, in the story’s headlines, that the study was done in mice and not in humans. Here, we raised the hypothesis that how science is reported by scientists plays a role on the news reporting. To test this hypothesis, we investigated whether an association exists between articles’ titles and news’ headlines regarding the omission, or not, of mice. To this end, we analyzed a sample of 623 open-access scientific papers indexed in PubMed in 2018 and 2019 that used mice either as models or as the biological source for experimental studies in AD research. We found a significant association (p < 0.01) between articles’ titles and news stories’ headlines, revealing that when authors omit the species in the paper’s title, writers of news stories tend to follow suit. We also found that papers not mentioning mice in their titles are more newsworthy and significantly more tweeted than papers that do. Our study shows that science reporting may affect media reporting and asks for changes in the way we report about findings obtained with animal models used to study human diseases., This study reveals that when scientists omit from the papers’ title that research findings were obtained using mice, as opposed to humans, the media tend to replicate the trend by omitting the use of mice from the news stories headlines that report on these papers, thereby perpetuating the misleading omission.

In the scientific literature, spin refers to reporting practices that distort the interpretation of results and mislead readers so that results are viewed in a more favourable light. The presence of spin in biomedical research can negatively impact the development of further studies, clinical practice, and health policies. This systematic review aims to explore the nature and prevalence of spin in the biomedical literature. We searched MEDLINE, PreMEDLINE, Embase, Scopus, and hand searched reference lists for all reports that included the measurement of spin in the biomedical literature for at least 1 outcome. Two independent coders extracted data on the characteristics of reports and their included studies and all spin-related outcomes. Results were grouped inductively into themes by spin-related outcome and are presented as a narrative synthesis. We used meta-analyses to analyse the association of spin with industry sponsorship of research. We included 35 reports, which investigated spin in clinical trials, observational studies, diagnostic accuracy studies, systematic reviews, and meta-analyses. The nature of spin varied according to study design. The highest (but also greatest) variability in the prevalence of spin was present in trials. Some of the common practices used to spin results included detracting from statistically nonsignificant results and inappropriately using causal language. Source of funding was hypothesised by a few authors to be a factor associated with spin; however, results were inconclusive, possibly due to the heterogeneity of the included papers. Further research is needed to assess the impact of spin on readers’ decision-making. Editors and peer reviewers should be familiar with the prevalence and manifestations of spin in their area of research in order to ensure accurate interpretation and dissemination of research., Author summary In the scientific literature, spin refers to reporting practices that distort the interpretation of results and mislead readers so that results are viewed in a more favourable light. The presence of spin in biomedical research can negatively impact the development of further studies, clinical practice, and health policies. We conducted a systematic review to explore the nature and prevalence of spin in the biomedical literature. We included 35 reports, which investigated spin in clinical trials, observational studies, diagnostic accuracy studies, systematic reviews, and meta-analyses. The nature of spin varied according to study design. The highest (but also greatest) variability in the prevalence of spin was present in trials. Some of the common practices used to spin results included detracting from statistically nonsignificant results and inappropriately using causal language. Source of funding was hypothesised by a few authors to be a factor associated with spin; however, results were inconclusive, possibly due to the heterogeneity of the included papers. Further research is needed to assess the impact of spin on readers’ decision-making. Editors and peer reviewers should be familiar with the prevalence and manifestations of spin in their area of research in order to ensure accurate interpretation and dissemination of research.

Humans are altering biological systems at unprecedented rates, and these alterations often have longer-term evolutionary impacts. Most obvious is the spread of resistance to pesticides and antibiotics. There are a wide variety of management strategies available to slow this evolution, and there are many reasons for using them. In this paper, we focus on the economic aspects of evolution management and ask: When is it economically beneficial for an individual decision-maker to invest in evolution management? We derive a simple dimensionless inequality showing that it is cost-effective to manage evolution when the percentage increase in the effective life span of the biological resource that management generates is larger than the percentage increase in annual profit that could be obtained by not managing evolution. We show how this inequality can be used to determine optimal investment choices for single decision-makers, to determine Nash equilibrium investment choices for multiple interacting decision-makers, and to examine how these equilibrium choices respond to regulatory interventions aimed at stimulating investment in evolution management. Our results are illustrated with examples involving Bacillus thuringiensis (Bt) crops and antibiotic use in fish farming., Humans are altering biological systems at unprecedented rates and these alterations often have longer-term evolutionary impacts, such as the spread of resistance to pesticides and antibiotics. In this study, a simple mathematical criterion is derived determining when it is economically beneficial to invest in strategies for controlling and managing evolutionary change.

The transition from mitosis into the first gap phase of the cell cycle in budding yeast is controlled by the Mitotic Exit Network (MEN). The network interprets spatiotemporal cues about the progression of mitosis and ensures that release of Cdc14 phosphatase occurs only after completion of key mitotic events. The MEN has been studied intensively; however, a unified understanding of how localisation and protein activity function together as a system is lacking. In this paper, we present a compartmental, logical model of the MEN that is capable of representing spatial aspects of regulation in parallel to control of enzymatic activity. We show that our model is capable of correctly predicting the phenotype of the majority of mutants we tested, including mutants that cause proteins to mislocalise. We use a continuous time implementation of the model to demonstrate that Cdc14 Early Anaphase Release (FEAR) ensures robust timing of anaphase, and we verify our findings in living cells. Furthermore, we show that our model can represent measured cell–cell variation in Spindle Position Checkpoint (SPoC) mutants. This work suggests a general approach to incorporate spatial effects into logical models. We anticipate that the model itself will be an important resource to experimental researchers, providing a rigorous platform to test hypotheses about regulation of mitotic exit., This study presents a logical compartmental model of the yeast mitotic exit network (MEN) that represents spatial aspects of regulation. The model correctly predicts the majority of published MEN phenotypes and reveals both the role of the Cdc14 early anaphase release and a link between mitosis length and checkpoint competence.

With exciting new NASA plans for a sustainable return to the moon, astronauts will once again leave Earth’s protective magnetosphere only to endure higher levels of radiation from galactic cosmic radiation (GCR) and the possibility of a large solar particle event (SPE). Gateway, lunar landers, and surface habitats will be designed to protect crew against SPEs with vehicle optimization, storm shelter concepts, and/or active dosimetry; however, the ever penetrating GCR will continue to pose the most significant health risks especially as lunar missions increase in duration and as NASA sets its aspirations on Mars. The primary risks of concern include carcinogenesis, central nervous system (CNS) effects resulting in potential in-mission cognitive or behavioral impairment and/or late neurological disorders, degenerative tissue effects including circulatory and heart disease, as well as potential immune system decrements impacting multiple aspects of crew health. Characterization and mitigation of these risks requires a significant reduction in the large biological uncertainties of chronic (low-dose rate) heavy-ion exposures and the validation of countermeasures in a relevant space environment. Historically, most research on understanding space radiation-induced health risks has been performed using acute exposures of monoenergetic single-ion beams. However, the space radiation environment consists of a wide variety of ion species over a broad energy range. Using the fast beam switching and controls systems technology recently developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory, a new era in radiobiological research is possible. NASA has developed the “GCR Simulator” to generate a spectrum of ion beams that approximates the primary and secondary GCR field experienced at human organ locations within a deep-space vehicle. The majority of the dose is delivered from protons (approximately 65%–75%) and helium ions (approximately 10%–20%) with heavier ions (Z ≥ 3) contributing the remainder. The GCR simulator exposes state-of-the art cellular and animal model systems to 33 sequential beams including 4 proton energies plus degrader, 4 helium energies plus degrader, and the 5 heavy ions of C, O, Si, Ti, and Fe. A polyethylene degrader system is used with the 100 MeV/n H and He beams to provide a nearly continuous distribution of low-energy particles. A 500 mGy exposure, delivering doses from each of the 33 beams, requires approximately 75 minutes. To more closely simulate the low-dose rates found in space, sequential field exposures can be divided into daily fractions over 2 to 6 weeks, with individual beam fractions as low as 0.1 to 0.2 mGy. In the large beam configuration (60 × 60 cm2), 54 special housing cages can accommodate 2 to 3 mice each for an approximately 75 min duration or 15 individually housed rats. On June 15, 2018, the NSRL made a significant achievement by completing the first operational run using the new GCR simulator. This paper discusses NASA’s innovative technology solution for a ground-based GCR simulator at the NSRL to accelerate our understanding and mitigation of health risks faced by astronauts. Ultimately, the GCR simulator will require validation across multiple radiogenic risks, endpoints, doses, and dose rates., This study describes how NASA’s new earth-based galactic cosmic ray simulator is being used to accelerate our understanding of the effects of space radiation exposure on astronauts and to validate countermeasures for exploration missions. For the first time, research teams can study mixed field ion and dose rate effects in a simulated space environment.

Schistosomes infect over 200 million people. The prodigious egg output of these parasites is the sole driver of pathology due to infection, yet our understanding of sexual reproduction by schistosomes is limited because normal egg production is not sustained for more than a few days in vitro. Here, we describe culture conditions that support schistosome sexual development and sustained egg production in vitro. Female schistosomes rely on continuous pairing with male worms to fuel the maturation of their reproductive organs. Exploiting these new culture conditions, we explore the process of male-stimulated female maturation and demonstrate that physical contact with a male worm, and not insemination, is sufficient to induce female development and the production of viable parthenogenetic haploid embryos. We further report the characterization of a nuclear receptor (NR), which we call Vitellogenic Factor 1 (VF1), that is essential for female sexual development following pairing with a male worm. Taken together, these results provide a platform to study the fascinating sexual biology of these parasites on a molecular level, illuminating new strategies to control schistosome egg production., Schistosomes infect over 200 million people worldwide. This paper describes culture conditions that support sexual development and sustained egg production of the human parasitic flatworm Schistosoma mansoni in vitro, providing new insights into its reproductive biology.

Access to analytical code is essential for transparent and reproducible research. We review the state of code availability in ecology using a random sample of 346 nonmolecular articles published between 2015 and 2019 under mandatory or encouraged code-sharing policies. Our results call for urgent action to increase code availability: only 27% of eligible articles were accompanied by code. In contrast, data were available for 79% of eligible articles, highlighting that code availability is an important limiting factor for computational reproducibility in ecology. Although the percentage of ecological journals with mandatory or encouraged code-sharing policies has increased considerably, from 15% in 2015 to 75% in 2020, our results show that code-sharing policies are not adhered to by most authors. We hope these results will encourage journals, institutions, funding agencies, and researchers to address this alarming situation., Publication of the analytical code underlying a scientific study is increasingly expected or even mandated by journals, allowing others to reproduce the results. However, a survey of more than 300 recently published ecology papers finds the majority have no code publicly available, handicapping efforts to improve scientific transparency.

When acting in a complex visual environment, it is essential to be able to flexibly allocate attention to parts of the visual scene that may contain goal-relevant information. The paper by Jia et al. provides novel evidence that our brains sequentially sample different objects in a visual scene. The results were obtained using "temporal response functions," in which unique electroencephalographic (EEG) signals corresponding to the processing of 2 continuously presented objects were isolated in an object-specific way. These response functions were dominated by 10-Hz alpha-band activity. Crucially, the different objects were sequentially sampled at a rate of about 2 Hz. These findings provide important neurophysiological insights into how our visual system operates in complex environments.

Insects determine their body segments in two different ways. Short-germband insects, such as the flour beetle Tribolium castaneum, use a molecular clock to establish segments sequentially. In contrast, long-germband insects, such as the vinegar fly Drosophila melanogaster, determine all segments simultaneously through a hierarchical cascade of gene regulation. Gap genes constitute the first layer of the Drosophila segmentation gene hierarchy, downstream of maternal gradients such as that of Caudal (Cad). We use data-driven mathematical modelling and phase space analysis to show that shifting gap domains in the posterior half of the Drosophila embryo are an emergent property of a robust damped oscillator mechanism, suggesting that the regulatory dynamics underlying long- and short-germband segmentation are much more similar than previously thought. In Tribolium, Cad has been proposed to modulate the frequency of the segmentation oscillator. Surprisingly, our simulations and experiments show that the shift rate of posterior gap domains is independent of maternal Cad levels in Drosophila. Our results suggest a novel evolutionary scenario for the short- to long-germband transition and help explain why this transition occurred convergently multiple times during the radiation of the holometabolan insects., Author summary Different insect species exhibit one of two distinct modes of determining their body segments (known as segmentation) during development: they either use a molecular oscillator to position segments sequentially, or they generate segments simultaneously through a hierarchical gene-regulatory cascade. The sequential mode is ancestral, while the simultaneous mode has been derived from it independently several times during evolution. In this paper, we present evidence suggesting that simultaneous segmentation also involves an oscillator in the posterior end of the embryo of the vinegar fly, Drosophila melanogaster. This surprising result indicates that both modes of segment determination are much more similar than previously thought. Such similarity provides an important step towards our understanding of the frequent evolutionary transitions observed between sequential and simultaneous segmentation.

Individuals chronically infected with HIV-1 harbor complex viral populations within their bloodstreams. Recently, it has come to light that when these people infect others, the new infection is typically established by only one or a small number of virions from within this complex viral swarm. An important goal is to characterize the biological properties of HIV-1 virions that seed and exist early in new human infections because these are potentially the only viruses against which a prophylactic HIV-1 vaccine would need to elicit protection. This includes understanding how the Envelope (Env) protein of these virions interacts with the T-cell receptor CD4, which supports attachment and entry of HIV-1 into target cells. We examined early HIV-1 isolates for their ability to infect cells via the CD4 receptor of 15 different primate species. Primates were the original source of HIV-1 and now serve as valuable animal models for studying HIV-1. We find that most primary isolates of HIV-1 from the blood, including early isolates, are highly selective and enter cells through some primate CD4 receptor orthologs but not others. This phenotype is remarkably consistent, regardless of route of transmission, viral subtype, or time of isolation post infection. We show that the weak CD4 binding affinity of blood-derived HIV-1 isolates is what makes them sensitive to the small sequence differences in CD4 from one primate species to the next. To substantiate this, we engineered an early HIV-1 Env to have high, medium, or low binding affinity to CD4, and we show that it loses the ability to enter cells via the CD4 receptor of many primate species as the binding affinity gets weaker. Based on the phenotype of selective use of primate CD4, we find that weak CD4 binding appears to be a nearly universal property of HIV-1 circulating in the bloodstream. Therefore, weak binding to CD4 must be a selected and important property in the biology of HIV-1 in the body. We identify six primate species that encode CD4 receptors that fully support the entry of early HIV-1 isolates despite their low binding affinity for CD4. These findings will help inform long-standing efforts to model HIV-1 transmission and early disease in primates., The current animal model for HIV, the macaque, encodes a CD4 receptor that is non-permissive for HIV entry. This paper reveals that six primate species encode CD4 receptors compatible with HIV infection, potentially making them powerful tools for the study of HIV biology. Furthermore, weak CD4 binding is a nearly constant, and apparently selected, property of HIV circulating in the human bloodstream.

Hepatitis A virus (HAV), an enigmatic and ancient pathogen, is a major causative agent of acute viral hepatitis worldwide. Although there are effective vaccines, antivirals against HAV infection are still required, especially during fulminant hepatitis outbreaks. A more in-depth understanding of the antigenic characteristics of HAV and the mechanisms of neutralization could aid in the development of rationally designed antiviral drugs targeting HAV. In this paper, 4 new antibodies—F4, F6, F7, and F9—are reported that potently neutralize HAV at 50% neutralizing concentration values (neut50) ranging from 0.1 nM to 0.85 nM. High-resolution cryo-electron microscopy (cryo-EM) structures of HAV bound to F4, F6, F7, and F9, together with results of our previous studies on R10 fragment of antigen binding (Fab)-HAV complex, shed light on the locations and nature of the epitopes recognized by the 5 neutralizing monoclonal antibodies (NAbs). All the epitopes locate within the same patch and are highly conserved. The key structure-activity correlates based on the antigenic sites have been established. Based on the structural data of the single conserved antigenic site and key structure-activity correlates, one promising drug candidate named golvatinib was identified by in silico docking studies. Cell-based antiviral assays confirmed that golvatinib is capable of blocking HAV infection effectively with a 50% inhibitory concentration (IC50) of approximately 1 μM. These results suggest that the single conserved antigenic site from complete HAV capsid is a good antiviral target and that golvatinib could function as a lead compound for anti-HAV drug development., Structures of hepatitis A virus in complex with five neutralizing antibodies reveal a single conserved antigenic site and pinpoint key structure-activity correlates, allowing in silico screening to identify a potent candidate inhibitor drug, golvatinib., Author summary Hepatitis A virus (HAV) is a unique, hepatotropic human picornavirus that infects approximately 1.5 million people annually and continues to cause mortality despite a successful vaccine. There are no licensed therapeutic drugs to date. Better knowledge of HAV antigenic features and neutralizing mechanisms will facilitate the development of HAV-targeting antiviral drugs. In this study, we report 4 potent HAV-specific neutralizing monoclonal antibodies (NAbs), together with our previous reported R10, that efficiently inhibit HAV infection by blocking attachment to the host cell. All 5 epitopes are located within the same patch and are highly conserved across 6 genotypes of human HAV, which suggests a single antigenic site for HAV, highlighting a prime target for structure-based drug design. Analysis of complexes with the 5 NAbs with varying neutralizing activities pinpointed key structure-activity correlates. By using a robust in silico docking method, one promising inhibitor named golvatinib was successfully identified from the DrugBank Database. In vitro assays confirmed its ability to block viral infection and revealed its neutralizing mechanism. Our approach could be useful in the design of effective drugs for picornavirus infections.

Data, including information generated from them by processing and analysis, are an asset with measurable value. The assets that biological research funding produces are the data generated, the information derived from these data, and, ultimately, the discoveries and knowledge these lead to. From the time when Henry Oldenburg published the first scientific journal in 1665 (Proceedings of the Royal Society) to the founding of the United States National Library of Medicine in 1879 to the present, there has been a sustained drive to improve how researchers can record and discover what is known. Researchers' experimental work builds upon years and (collectively) billions of dollars' worth of earlier work. Today, researchers are generating data at ever-faster rates because of advances in instrumentation and technology, coupled with decreases in production costs. Unfortunately, the ability of researchers to manage and disseminate their results has not kept pace, so their work cannot achieve its maximal impact. Strides have recently been made, but more awareness is needed of the essential role that biological data resources, including biocuration, play in maintaining and linking this ever-growing flood of data and information. The aim of this paper is to describe the nature of data as an asset, the role biocurators play in increasing its value, and consistent, practical means to measure effectiveness that can guide planning and justify costs in biological research information resources' development and management.

Eukaryotic protein kinases regulate most cellular functions by phosphorylating targeted protein substrates through a highly conserved catalytic core. In the active state, the catalytic core oscillates between open, intermediate, and closed conformations. Currently, the intramolecular interactions that regulate the active state mechanics are not well understood. Here, using cAMP-dependent protein kinase as a representative model coupled with biochemical, biophysical, and computational techniques, we define a set of highly conserved electrostatic and hydrophobic interactions working harmoniously to regulate these mechanics. These include the previously identified salt bridge between a lysine from the β3-strand and a glutamate from the αC-helix as well as an electrostatic interaction between the phosphorylated activation loop and αC-helix and an ensemble of hydrophobic residues of the Regulatory spine and Shell. Moreover, for over three decades it was thought that the highly conserved β3-lysine was essential for phosphoryl transfer, but our findings show that the β3-lysine is not required for phosphoryl transfer but is essential for the active state mechanics., Author Summary Eukaryotic protein kinases (EPKs) regulate over a third of the human proteome by transferring the γ-phosphate from adenosine triphosphate (ATP) to a protein substrate in a process known as protein phosphorylation. Biochemical and biophysical studies have shown that EPKs undergo multiconformational rearrangements in which the catalytic core is oscillating between open, intermediate, and closed conformations when active. Presently, the intramolecular interactions that regulate this dynamic process are not well understood. In this paper, we show how a set of conserved electrostatic and hydrophobic interactions harmoniously regulate the active state mechanics. The electrostatic interactions involve the highly conserved salt bridge between the lysine from subdomain-II and glutamate from subdomain-III as well as an interaction between the activation loop and αC-helix. The hydrophobic interactions include the nonlinear motifs known as the Regulatory spine and Shell that traverse both lobes of the catalytic core. Furthermore, our findings show that the highly conserved “catalytic lysine” is not directly required for phosphoryl transfer but rather serves as a hub that aligns and positions the dynamic core elements required for catalysis.

Positive-strand RNA viruses build extensive membranous replication compartments to support replication and protect the virus from antiviral responses by the host. These viruses require host factors and various lipids to form viral replication complexes (VRCs). The VRCs built by Tomato bushy stunt virus (TBSV) are enriched with phosphatidylethanolamine (PE) through a previously unknown pathway. To unravel the mechanism of PE enrichment within the TBSV replication compartment, in this paper, the authors demonstrate that TBSV co-opts the guanosine triphosphate (GTP)-bound active form of the endosomal Rab5 small GTPase via direct interaction with the viral replication protein. Deletion of Rab5 orthologs in a yeast model host or expression of dominant negative mutants of plant Rab5 greatly decreases TBSV replication and prevents the redistribution of PE to the sites of viral replication. We also show that enrichment of PE in the viral replication compartment is assisted by actin filaments. Interestingly, the closely related Carnation Italian ringspot virus, which replicates on the boundary membrane of mitochondria, uses a similar strategy to the peroxisomal TBSV to hijack the Rab5-positive endosomes into the viral replication compartments. Altogether, usurping the GTP-Rab5–positive endosomes allows TBSV to build a PE-enriched viral replication compartment, which is needed to support peak-level replication. Thus, the Rab family of small GTPases includes critical host factors assisting VRC assembly and genesis of the viral replication compartment., Author Summary Plants, animals, and humans are threatened by positive-stranded RNA viruses, which are one of the major groups of intracellular pathogens. To support robust virus replication, these viruses subvert intracellular membranes and co-opt host proteins into virus-induced replication compartments. Tomato bushy stunt virus (TBSV) is a model virus used in yeast to dissect the roles of lipids and proteins in virus replication. In this work, the authors show that one of the two TBSV replication proteins interacts with the guanosine triphosphate (GTP)-bound Rab5 small GTPase, which allows the virus to take advantage of phosphatidylethanolamine (PE)-rich endosomes to build viral replication compartments consisting of peroxisomes. Peak level of TBSV replication depends on the co-opted abundant PE-rich Rab5-positive membranes in plants, too.

The One Health initiative is a global effort fostering interdisciplinary collaborations to address challenges in human, animal, and environmental health. While One Health has received considerable press, its benefits remain unclear because its effects have not been quantitatively described. We systematically surveyed the published literature and used social network analysis to measure interdisciplinarity in One Health studies constructing dynamic pathogen transmission models. The number of publications fulfilling our search criteria increased by 14.6% per year, which is faster than growth rates for life sciences as a whole and for most biology subdisciplines. Surveyed publications clustered into three communities: one used by ecologists, one used by veterinarians, and a third diverse-authorship community used by population biologists, mathematicians, epidemiologists, and experts in human health. Overlap between these communities increased through time in terms of author number, diversity of co-author affiliations, and diversity of citations. However, communities continue to differ in the systems studied, questions asked, and methods employed. While the infectious disease research community has made significant progress toward integrating its participating disciplines, some segregation—especially along the veterinary/ecological research interface—remains., "One Health" is a global initiative fostering interdisciplinary collaborations to address health challenges. Although an empirical analysis of published disease models shows a rapid growth in cross-disciplinary "One Health" collaborations, the continued segregation of medical, veterinary, and ecological communities poses an ongoing challenge., Author Summary A cohesive reaction to emerging threats requires the efficient dissemination of knowledge and methodologies across multiple disciplinary boundaries. A “One Health” approach has been advocated to facilitate cross-disciplinary communication and research in responding to challenges in human, animal, and environmental health. We empirically describe collaboration networks surrounding one aspect of this One Health initiative: infectious disease transmission models. A systematic literature review and social network analysis showed that dynamic disease modelling grew faster than most biological and natural science disciplines over the last 25 y, yet the field remains somewhat compartmentalized. Many researchers contribute to a broad, cross-disciplinary group of journals, but publications from veterinarians and ecologists remain segregated into relatively discrete communities. While the veterinary and ecological communities regularly reference the broad, cross-disciplinary group, they only rarely cite each other; furthermore, the highest-tiered medical journals contributed very few papers to our search. Therefore, our results are somewhat mixed: while One Health may have precipitated a great deal of research interest in infectious disease, it has not fully overcome the barriers that segregate its contributing disciplines.

Autophagy is the mechanism by which cellular material is delivered to lysosomes and degraded. This process has become a major focus of biological and biomedical research with thousands of papers published each year and rapidly growing appreciation that autophagy affects many normal and pathological processes. However, as we learn more about this evolutionarily ancient process, we are discovering that autophagy's effects may work for both the good and the bad of an organism. Here, I discuss some of these context-dependent findings and how, as we make sense of them, we can try to apply our knowledge for practical purposes.

Once there were ten identical monkeys. Their father made them draw lots and gave the winner a long bamboo pole. Each day the monkey with the pole whacks coconuts out of a tree, his brothers catch them and shell them, and they all feed off the proceeds. The monkey carrying the pole finds it quite hard and is normally very tired by the end of the day; over the years, he wonders whether it's worth the hassle. But one day there's an almighty flood. The monkey with the pole is lagging behind as usual and watches his nine brothers drown in the distance. When the flood abates, he walks on, finds a mate, and eventually passes the pole on to one of his ten identical children. Bacterial populations grow rapidly and asexually, generating millions of genetically identical progeny. Traditionally, it has been assumed that if these bugs are placed in a uniform environment, then they'll behave identically—nature and nurture are invariant, so there is neither motivation nor mechanism for diversity. Increasingly, however, we're appreciating that there are many intrinsic advantages to diversity, and nature can readily exploit this by using stochastic mechanisms to program populations of organisms to vary despite genetic and environmental uniformity. As with the monkeys, however, there are several ways in which it can pay to be different. One obvious way in which diversity of phenotype can yield dividends is by allowing specialization: “division of labor.” The unpleasant human pathogen Salmonella Typhimurium is one bug that's already known to do this; a small proportion of a genetically identical horde of invading bacteria express high levels of virulence factors called ttss-1, while the majority produce only low levels. The ttss-1 genes encode Type III Secretory System 1, a large and complex molecular “hypodermic needle” that allows the high-expressing “T+” bugs to inject the host cells full of effector proteins. These proteins in turn manipulate the host cells in a range of ways that favor proliferation by the T+ bacteria's more numerous low ttss-1-expressing “T−” brethren, thereby promoting virulence. A paper just published in PLOS Biology by Markus Arnoldini, Martin Ackermann, and colleagues adds a biologically intriguing and potentially clinically important twist to this touching tale of cooperation in Salmonella. They start from the observation that the T+ subpopulation seems to grow more slowly, and the authors check this in detail using an elegant high-throughput single-cell method based on time-lapse movies of a microfluidic system and bacteria containing a fluorescent reporter of ttss-1 expression (Figure 1). Slow growth is often associated with tolerance of antibiotics, however, so the authors ask the direct question of whether the T+ cells are better able to survive the ravages of a dose of ciprofloxacin. They were, and the authors then confirm that survival depends on the ability to turn on ttss-1 and does not involve the emergence of drug resistance by mutation. The T+ bugs were also more tolerant to kanamycin, a structurally and functionally unrelated antibiotic, and even survived high, clinically relevant doses of both drugs. Figure 1 Bugs in tubes. A 13-hour time-lapse montage of images from the microfluidics device used for this study. The bottom of each tube is closed so that as bugs divide they move up the tube and are shed at the top. The blue bar in the middle indicates normal ... The assumption was that the costly expression of abundant protein (in this case, ttss-1) caused slow growth, and slow growth caused tolerance. The authors tested this mechanistic chain by artificially slowing the growth of bugs that couldn't express ttss-1 and by gratuitously expressing high levels of an arbitrary protein, LacZ. Both experiments made bugs more tolerant to antibiotics. Like the monkey's pole, ttss-1 expression is therefore the agent both of a continuing cooperative behavior (virulence) and a burdensome bet hedge that pays off (tolerance) when disaster strikes. A potentially alarming consequence of this is that treating an infection with antibiotics might inadvertently select for virulence by preferentially culling nonvirulent (T−) cells. To examine whether this is possible, the authors set up a competition between normal Salmonella (which can switch stochastically between T+ and T− states) and a genetically avirulent one which is always T−. In the absence of antibiotic, the unburdened avirulent bugs win, but if antibiotic is present, the hedged bet pays off, and the switchers take over. The study therefore shows that two fundamental drivers of cellular heterogeneity—division-of-labor and bet hedging—can be intricately intertwined by the sharing of a common agent. The authors wonder whether this entanglement means that bet hedging might serve to prevent cheater mutants (those which can't switch to a T+ phenotype but freeload off those that can) from subverting the division-of-labor system. Crucially, when the heterogeneous traits involved are drug tolerance and virulence, then unfortunate clinical consequences may arise from the peculiar confluence of two facts—that expression of virulence proteins is expensive enough to slow cellular growth and that slow cellular growth helps bacteria to weather the presence of antibiotics. Clearly we need a better understanding of this unforeseen potential downside of antibiotic treatment; we don't want to select for killers when we aim to cure. Arnoldini M, Vizcarra IA, Pena-Miller R, Stocker N, Diard M, et al. (2014) Bistable Expression of Virulence Genes in Salmonella Leads to the Formation of an Antibiotic-Tolerant Subpopulation. doi:10.1371/journal.pbio.1001928

Reproductive competition often continues long after copulation ends. This article reviews the field and introduces a new paper showing that nematode sperm can directly harm the female germ line., Intense reproductive competition often continues long after animals finish mating. In many species, sperm from one male compete with those from others to find and fertilize oocytes. Since this competition occurs inside the female reproductive tract, she often influences the outcome through physical or chemical factors, leading to cryptic female choice. Finally, traits that help males compete with each other are sometimes harmful to females, and female countermeasures may thwart the interests of males, which can lead to an arms race between the sexes known as sexually antagonistic coevolution. New studies from Caenorhabditis nematodes suggest that males compete with each other by producing sperm that migrate aggressively and that these sperm may be more likely to win access to oocytes. However, one byproduct of this competition appears to be an increased probability that these sperm will go astray, invading the ovary, prematurely activating oocytes, and sometimes crossing basement membranes and leaving the gonad altogether. These harmful effects are sometimes observed in crosses between animals of the same species but are most easily detected in interspecies crosses, leading to dramatically lowered fitness, presumably because the competitiveness of the sperm and the associated female countermeasures are not precisely matched. This mismatch is most obvious in crosses involving individuals from androdioecious species (which have both hermaphrodites and males), as predicted by the lower levels of sperm competition these species experience. These results suggest a striking example of sexually antagonistic coevolution and dramatically expand the value of nematodes as a laboratory system for studying postcopulatory interactions.