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Objective Observational studies can impact patient care but must be robust and reproducible. Nonreproducibility is primarily caused by unclear reporting of design choices and analytic procedures. This study aimed to: (1) assess how the study logic described in an observational study could be interpreted by independent researchers and (2) quantify the impact of interpretations' variability on patient characteristics. Materials and Methods Nine teams of highly qualified researchers reproduced a cohort from a study by Albogami et al. The teams were provided the clinical codes and access to the tools to create cohort definitions such that the only variable part was their logic choices. We executed teams' cohort definitions against the database and compared the number of subjects, patient overlap, and patient characteristics. Results On average, the teams' interpretations fully aligned with the master implementation in 4 out of 10 inclusion criteria with at least 4 deviations per team. Cohorts' size varied from one-third of the master cohort size to 10 times the cohort size (2159–63 619 subjects compared to 6196 subjects). Median agreement was 9.4% (interquartile range 15.3–16.2%). The teams' cohorts significantly differed from the master implementation by at least 2 baseline characteristics, and most of the teams differed by at least 5. Conclusions Independent research teams attempting to reproduce the study based on its free-text description alone produce different implementations that vary in the population size and composition. Sharing analytical code supported by a common data model and open-source tools allows reproducing a study unambiguously thereby preserving initial design choices. [ABSTRACT FROM AUTHOR]

Gray seals were historically distributed along the northeastern coast of the United States, but bounties and lack of protection reduced numbers and they were rarely observed for most of the 20th century. Once protections were enacted, the population started to rebound. Here, we describe the recolonization and recovery of gray seals in the United States, focusing on the re-establishment of pupping sites. We fit individual generalized linear models to various time series (1988–2019) to estimate rates of increase in observed pup counts at four of the more data-rich sites. Annual rate of increase at individual sites ranged from −0.2% (95% CI : −2.3–1.9%) to 26.3% (95% CI : 21.6–31.4%). The increase in sites and number of pups born in the United States is driven by population growth and immigration from Canadian colonies and is part of a larger recovery of the Northwest Atlantic population. Wildlife protection, a healthy source population, habitat availability, and species traits that allow for dispersal and high productivity were all important factors in this recovery. [ABSTRACT FROM AUTHOR]

Motivation Genome scale metabolic models (GSMMs) are increasingly important for systems biology and metabolic engineering research as they are capable of simulating complex steady-state behaviour. Constraints based models of this form can include thousands of reactions and metabolites, with many crucial pathways that only become activated in specific simulation settings. However, despite their widespread use, power and the availability of tools to aid with the construction and analysis of large scale models, little methodology is suggested for their continued management. For example, when genome annotations are updated or new understanding regarding behaviour is discovered, models often need to be altered to reflect this. This is quickly becoming an issue for industrial systems and synthetic biotechnology applications, which require good quality reusable models integral to the design, build, test and learn cycle. Results As part of an ongoing effort to improve genome scale metabolic analysis, we have developed a test-driven development methodology for the continuous integration of validation data from different sources. Contributing to the open source technology based around COBRApy, we have developed the gsmodutils modelling framework placing an emphasis on test-driven design of models through defined test cases. Crucially, different conditions are configurable allowing users to examine how different designs or curation impact a wide range of system behaviours, minimizing error between model versions. Availability and implementation The software framework described within this paper is open source and freely available from http://github.com/SBRCNottingham/gsmodutils. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Burying beetles (Nicrophorus vespilloides) bear distinctive and variable orange-black patterning on their elytra and produce an anal exudate from their abdomen when threatened. During breeding, the anal exudates contribute to the antimicrobial defense of the breeding resource. We investigated whether the anal exudates also provide a responsive chemical defense, which is advertised to potential avian predators by the beetle's orange and black elytral markings. We found that that the orange-black elytral markings of the burying beetle are highly conspicuous for avian predators against range of backgrounds, by using computer simulations. Using bioassays with wood ants, we also showed that the burying beetle's anal exudates are aversive to potential predators. From these results, and other evidence in the literature, we conclude that the evidence for aposematism in the burying beetle is as strong as the evidence for many other classically aposematic species, such as defended Hymenopterans, ladybirds, or poisonous frogs. Nevertheless, we also report unexpectedly high levels of individual variation in coloration and chemical defenses, as well as sex differences. We suggest that this variation might be partly due to conflicting selection pressures, particularly on the dual function of the exudates, and partly to nutritional differences in the developmental environment. The ecology of the burying beetles (Nicrophorus spp.) differs markedly from better-studied aposematic insects. This genus thus offers new potential for understanding the evolution of aposematism in general. [ABSTRACT FROM AUTHOR]

Animal genitalia are diverse and a growing body of evidence suggests that they evolve rapidly under post-copulatory sexual selection. This process is predicted to be more intense in polyandrous species, although there have been very few comparative studies of the relationship between the complexity of genital structures in males and measures of the degree of polyandry. In some bushcricket families, males possess sclerotized copulatory structures known as titillators, which are inserted into the female's genital chamber and moved rhythmically. Like other genital structures, bushcricket titillators are widely used as important taxonomic characters and show considerable variation across species in structure, shape, and the extent to which they are spined. Here, we examine relationships between the presence/absence of titillators, titillator complexity, and both mating frequency and the degree of polyandry in bushcrickets, using phylogenetic comparative analyses. Using published sources combined with original observations, data were obtained for the mean level of polyandry, the duration of the male and female sexual refractory periods, and the level of complexity of titillators. To analyze data, we fitted phylogenetic generalized least squares models. No significant relationships were found between titillator presence or complexity and either the level of polyandry, duration of the male's sexual refractory period, or the ratio of the female and male sexual refractory periods. The duration of the female's refractory period, however, was positively associated with titillator presence and negatively associated with titillator complexity. The data therefore partially support the hypothesis that postcopulatory sexual selection drives genital evolution in this taxon. [ABSTRACT FROM AUTHOR]

As the sampling frequency and resolution of Earth observation imagery increase, there are growing opportunities for novel applications in population monitoring. New methods are required to apply established analytical approaches to data collected from new observation platforms (e.g., satellites and unmanned aerial vehicles). Here, we present a method that estimates regional seasonal abundances for an understudied and growing population of gray seals (Halichoerus grypus) in southeastern Massachusetts, using opportunistic observations in Google Earth imagery. Abundance estimates are derived from digital aerial survey counts by adapting established correction-based analyses with telemetry behavioral observation to quantify survey biases. The result is a first regional understanding of gray seal abundance in the northeast US through opportunistic Earth observation imagery and repurposed animal telemetry data. As species observation data from Earth observation imagery become more ubiquitous, such methods provide a robust, adaptable, and cost-effective solution to monitoring animal colonies and understanding species abundances. [ABSTRACT FROM AUTHOR]

Which sex should care for offspring is a fundamental question in evolution. Invertebrates, and insects in particular, show some of the most diverse kinds of parental care of all animals, but to date there has been no broad comparative study of the evolution of parental care in this group. Here, we test existing hypotheses of insect parental care evolution using a literature-compiled phylogeny of over 2000 species. To address substantial uncertainty in the insect phylogeny, we use a brute force approach based on multiple random resolutions of uncertain nodes. The main transitions were between no care (the probable ancestral state) and female care. Male care evolved exclusively from no care, supporting models where mating opportunity costs for caring males are reduced-for example, by caring for multiple broods-but rejecting the 'enhanced fecundity' hypothesis that male care is favored because it allows females to avoid care costs. Biparental care largely arose by males joining caring females, and was more labile in Holometabola than in Hemimetabola. Insect care evolution most closely resembled amphibian care in general trajectory. Integrating these findings with the wealth of life history and ecological data in insects will allow testing of a rich vein of existing hypotheses. [ABSTRACT FROM AUTHOR]

Desiccation is a particular risk for small animals in arid environments. In response, many organisms “construct niches,” favorable microenvironments where they spend part or all of their life cycle. Some maintain such environments for their offspring via parental care. Insect eggs are often protected from desiccation by parentally derived gels, casings, or cocoons, but active parental protection of offspring from desiccation has never been demonstrated. Most free-living thrips (Thysanoptera) alleviate water loss via thigmotaxis (crevice seeking). In arid Australia, Acacia thrips (Phlaeothripidae) construct many kinds of niche. Some thrips induce galls; others, like Dunatothrips aneurae, live and breed within “domiciles” made from loosely glued phyllodes. The function of domiciles is unknown; like other constructed niches, they may 1) create favorable microenvironments, 2) facilitate feeding, 3) protect from enemies, or a combination. To test the first 2 alternatives experimentally, field-collected domiciles were destroyed or left intact. Seven-day survival of feeding and nonfeeding larval stages was monitored at high (70–80%) or low (8–10%, approximately ambient) humidity. Regardless of humidity, most individuals survived in intact domiciles, whereas for destroyed domiciles, survival depended on humidity, suggesting parents construct and maintain domiciles to prevent offspring desiccating. Feeding and nonfeeding larvae had similar survival patterns, suggesting the domicile’s role is not nutritional. Outside domiciles, survival at “high” humidity was intermediate, suggesting very high humidity requirements, or energetic costs of wandering outside domiciles. D. aneurae commonly cofound domiciles; cofoundresses may benefit both from shared nestbuilding costs, and from “deferred byproduct mutualism,” that is, backup parental care in case of mortality.Tiny Acacia thrips build communal “domiciles” in arid Australia. Here I show that domiciles prevent desiccation, ensuring offspring survival—a novel kind of parental care in insects. We suspect many insect parents perform this function for offspring, but it has never been demonstrated experimentally. If larvae require parental care, this suggests one reason thrips are sometimes communal: if a female dies, her nestmates can ensure her offspring survive. [ABSTRACT FROM PUBLISHER]

The function of nuptial gifts has generated longstanding debate. Nuptial gifts consumed during ejaculate transfer may allow males to transfer more ejaculate than is optimal for females. However, gifts may simultaneously represent male investment in offspring. Evolutionary loss of nuptial gifts can help elucidate pressures driving their evolution. In most katydids (Orthoptera: Tettigoniidae), males transfer a spermatophore comprising two parts: the ejaculate-containing ampulla and the spermatophylax-a gelatinous gift that females eat during ejaculate transfer. Many species, however, have reduced or no spermatophylaces and many have prolonged copulation. Across 44 katydid species, we tested whether spermatophylaces and prolonged copulation following spermatophore transfer are alternative adaptations to protect the ejaculate. We also tested whether prolonged copulation was associated with (i) male cercal adaptations, helping prevent female disengagement, and (ii) female resistance behavior. As predicted, prolonged copulation following (but not before) spermatophore transfer was associated with reduced nuptial gifts, differences in the functional morphology of male cerci, and behavioral resistance by females during copulation. Furthermore, longer copulation following spermatophore transfer was associated with larger ejaculates, across species with reduced nuptial gifts. Our results demonstrate that nuptial gifts and the use of grasping cerci to prolong ejaculate transfer are functionally equivalent. [ABSTRACT FROM AUTHOR]

Seed germination is a critical stage in the plant life cycle and the first step toward successful plant establishment. Therefore, understanding germination is of important ecological and agronomical relevance. Previous research revealed that different seed compartments (testa, endosperm, and embryo) control germination, but little is known about the underlying spatial and temporal transcriptome changes that lead to seed germination. We analyzed genome-wide expression in germinating Arabidopsis (Arabidopsis thaliana) seeds with both temporal and spatial detail and provide Web-accessible visualizations of the data reported (vseed.nottingham.ac.uk). We show the potential of this highresolution data set for the construction of meaningful coexpression networks, which provide insight into the genetic control of germination. The data set reveals two transcriptional phases during germination that are separated by testa rupture. The first phase is marked by large transcriptome changes as the seed switches from a dry, quiescent state to a hydrated and active state. At the end of this first transcriptional phase, the number of differentially expressed genes between consecutive time points drops. This increases again at testa rupture, the start of the second transcriptional phase. Transcriptome data indicate a role for mechano-induced signaling at this stage and subsequently highlight the fates of the endosperm and radicle: senescence and growth, respectively. Finally, using a phylotranscriptomic approach, we show that expression levels of evolutionarily young genes drop during the first transcriptional phase and increase during the second phase. Evolutionarily old genes show an opposite pattern, suggesting a more conserved transcriptome prior to the completion of germination. [ABSTRACT FROM AUTHOR]

Thrips of the genus Dunatothrips ( Thysanoptera: Phlaeothripidae) construct domiciles by tying phyllodes of Australian Acacia trees together with silk-like glue. Females often co-found domiciles (pleometrosis), an apparently cooperative behaviour that potentially provides insights into social evolution. However, little is known about their basic natural history, limiting the scope for testable predictions. Here, we address this crucial prerequisite step by investigating some key outstanding questions in the most common species, D. aneurae, on its host, Acacia aneura. We detail distribution in space and time, mating, dispersal, domicile building and defence. Dunatothrips aneurae was distributed in loosely reproductively synchronized patches, and tended to prefer east-facing, terminal phyllodes on thin-phyllode A. aneura varieties. Mature domiciles contained middens, concentrated areas of waste, suggesting active maintenance of domiciles and the potential for the division of labour. We observed inbreeding and outbreeding. Dunatothrips aneurae males engaged in short, truncated matings with sisters before dispersing locally, mating with females in nearby immature domiciles; longer distance dispersal, although it must happen, is still undocumented. Males and females mated multiply. Lone females required male presence to initiate domiciles, constructed them without male help and lost wings on nesting by abscission. Silk production occurred well before egg laying. Aggression or defence appeared to be entirely absent. Taken together, these observations suggest that research into co-founding behaviour should focus on: (1) local crowding; (2) lack of aggression; and (3) potential division of labour with respect to egg production, silk production and domicile maintenance. These results should provide a springboard for questions on the potential evolution of cooperation in this species. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, 109, 802-816. [ABSTRACT FROM AUTHOR]

Major histocompatibility complex (MHC) genes play a critical role in vertebrate immune response and because the MHC is linked to a significant number of auto-immune and other diseases it is of great medical interest. Here we describe the clone-based sequencing and subsequent annotation of the MHC region of the gorilla genome. Because the MHC is subject to extensive variation, both structural and sequence-wise, it is not readily amenable to study in whole genome shotgun sequence such as the recently published gorilla genome. The variation of the MHC also makes it of evolutionary interest and therefore we analyse the sequence in the context of human and chimpanzee. In our comparisons with human and reannotated chimpanzee MHC sequence we find that gorilla has a trimodular RCCX cluster, versus the reference human bimodular cluster, and additional copies of Class I (pseudo)genes between Gogo-K and Gogo-A (the orthologues of HLA-K and -A). We also find that Gogo-H (and Patr-H) is coding versus the HLA-H pseudogene and, conversely, there is a Gogo- DQB2 pseudogene versus the HLA-DQB2 coding gene. Our analysis, which is freely available through the VEGA genome browser, provides the research community with a comprehensive dataset for comparative and evolutionary research of the MHC. [ABSTRACT FROM AUTHOR]

Model organisms are becoming increasingly important for the study of complex diseases such as type 1 diabetes (T1D). The non-obese diabetic (NOD) mouse is an experimental model for T1D having been bred to develop the disease spontaneously in a process that is similar to humans. Genetic analysis of the NOD mouse has identified around 50 disease loci, which have the nomenclature Idd for insulin-dependent diabetes, distributed across at least 11 different chromosomes. In total, 21 Idd regions across 6 chromosomes, that are major contributors to T1D susceptibility or resistance, were selected for finished sequencing and annotation at the Wellcome Trust Sanger Institute. Here we describe the generation of 40.4 mega base-pairs of finished sequence from 289 bacterial artificial chromosomes for the NOD mouse. Manual annotation has identified 738 genes in the diabetes sensitive NOD mouse and 765 genes in homologous regions of the diabetes resistant C57BL/6J reference mouse across 19 candidate Idd regions. This has allowed us to call variation consequences between homologous exonic sequences for all annotated regions in the two mouse strains. We demonstrate the importance of this resource further by illustrating the technical difficulties that regions of inter-strain structural variation between the NOD mouse and the C57BL/6J reference mouse can cause for current next generation sequencing and assembly techniques. Furthermore, we have established that the variation rate in the Idd regions is 2.3 times higher than the mean found for the whole genome assembly for the NOD/ShiLtJ genome, which we suggest reflects the fact that positive selection for functional variation in immune genes is beneficial in regard to host defence. In summary, we provide an important resource, which aids the analysis of potential causative genes involved in T1D susceptibility. [ABSTRACT FROM AUTHOR]

Akainothrips francisi sp. nov. is shown to be an inquiline (i.e. it invades, and breeds within, domiciles of another species). Currently, its only known host is Dunatothrips aneurae, a subsocial thrips that creates silken domiciles by securing together phyllodes of mulga ( Acacia aneura) in the arid zone of Australia. We found Ak. francisi prolifically breeding inside live D. aneurae host domiciles, both immature and mature. Akainothrips francisi did not kill its host and we saw no evidence of antagonistic host-inquiline interactions. This is thus the second demonstrably inquiline species of Acacia thrips, although other possible inquilines have been suggested including two Akainothrips. We found that Ak. francisi occurred with positive density dependence, and was associated with moderately reduced host reproduction. This latter association was especially evident in larger host domiciles, suggesting that Ak. francisi either inhibits further host reproduction after invasion or exploits poor quality hosts more successfully. Sex ratios were slightly female biased. Akainothrips francisi males were exceptionally variable in size, colour, and foreleg size compared to females, with morphs co-occurring within domiciles, suggesting sexual selection and the possibility of different male reproductive strategies. The discovery of Ak. francisi highlights particular morphological affinities among known or suspected inquiline Acacia thrips within Akainothrips and other genera, allowing us to hypothesize a common origin of this lifestyle from within Akainothrips. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, ••, ••-••. [ABSTRACT FROM AUTHOR]

The article reviews the documentary film "Stonewall Uprising: A Film Documentary," directed and produced by Kate Davis and David Heilbroner.

Rats and dogs chronically treated with high doses of sulbactam are known to sequester protein-bound glycogen in their hepatocytes. As a result, previous UK studies of sulbactam/ampicillin excluded patients suffering from diabetes mellitus. This study examined the effects of sulbactam/ampicillin compared to flucloxacillin/ampicillin on diabetic control, the ability to mobilize glycogen and the pancreatic beta cell response to glucagon, in diabetic patients suffering from soft tissue infection. There was no significant effect between treatment groups on any of these parameters. Sulbactam/ampicillin is unlikely to have an adverse effect on diabetic control in clinical practice when used short term in the doses employed in this study. [ABSTRACT FROM AUTHOR]

The selectins are cell adhesion molecules whose carbohydrate-binding domain (C-type lectin) is thought to be involved in leukocyte adhesion to activated vascular endothelium in the inflammatory process. A series of peptides, based on a conserved region (YYWIGIRK-NH) of the lectin domain of E-, L- and P-selectins, were analysed for their ability to block selectin-mediated cell adhesion , and neutrophil infiltration into sites of inflammation . The peptides inhibited the adhesion of myeloid cells to recombinant forms of E- and P-selectin. The adhesion of myeloid cells to human endothelial cells, stimulated to express E-selectin, was also inhibited by the peptides. Finally, the peptides blocked the adhesion of lymphocytes, expressing L-selectin, to high endothelial venules in lymph nodes which contain the ligand for L-selectin. A clear structure-activity relationship was established when peptides of different amino acid chain lengths were tested in these assays. Peptides lacking tyrosine residues (e.g. WIGIR-NH) at their amino terminus were poor inhibitors of selectin-mediated cell adhesion . The peptides that were found to be inhibitors of cell adhesion were also found to inhibit (up to 70%) neutrophil infiltration into sites of inflammation in a thioglycollate-induced peritonitis mouse model system. They also significantly reduced (>50%) the migration of neutrophils into cytokine-treated skin. These results strongly suggest that compounds based on these tyrosine-containing, selectin-derived peptides could be used as anti-inflammatory therapeutic agents. [ABSTRACT FROM PUBLISHER]

The article reviews the film "J. Edgar," directed by Clint Eastwood, and starring Leonardo DiCaprio.

Manual annotation of genomic data is extremely valuable to produce an accurate reference gene set but is expensive compared with automatic methods and so has been limited to model organisms. Annotation tools that have been developed at the Wellcome Trust Sanger Institute (WTSI, http://www.sanger.ac.uk/.) are being used to fill that gap, as they can be used remotely and so open up viable community annotation collaborations. We introduce the ‘Blessed’ annotator and ‘Gatekeeper’ approach to Community Annotation using the Otterlace/ZMap genome annotation tool. We also describe the strategies adopted for annotation consistency, quality control and viewing of the annotation.Database URL: http://vega.sanger.ac.uk/index.html [ABSTRACT FROM AUTHOR]