Female teat size is a reliable indicator of annual breeding success in European badgers: Genetic validation

Assessing which females have bred successfully is a central requirement in many ecological field studies, providing an estimate of the effective female population size. Researchers have applied teat measurements previously to assess whether females, in a variety of mammalian species, have bred; however, this technique has not been validated genetically. Furthermore, several analytical techniques are available to classify individuals, but their misclassification rates have not been compared. We used 22 microsatellite loci to assign maternity, with 95% confidence, within a high-density population of European badgers Meles meles, as plural and subterranean breeding means that maternity cannot be inferred from behavioural observations. The teat lengths and diameters of 136 females, measured May–July 1994–2005, from social groups in which all offspring were assigned a mother, were reliable indicators of recent breeding success. A Generalised Linear Mixed Model (GLMM) classified both breeding and non-breeding females with lower error rates than discriminant analyses and crude teat-size criteria. The GLMM model logit probability = −20 + 1.8 month + 1.6 mean teat length + 1.0 mean teat diameter can be applied quickly in the field to assess the probability with which a female badger should be assigned maternity. This is a low-cost measure which, after validation, could be used in other badger or mammalian populations to assess the breeding success of females. This may be a particularly useful welfare tool for veterinary practitioners, especially during badger culls

Alarmins in frozen shoulder: a molecular association between inflammation and pain

Background: The pathophysiological mechanisms behind proliferation of fibroblasts and deposition of dense collagen matrix in idiopathic frozen shoulder remain unclear. Alarmins (also known as danger signals) are endogenous molecules that are released into the extracellular milieu after infection or tissue injury and that signal cell and tissue damage. Purpose: To investigate whether the presence of alarmins is higher in patients with idiopathic frozen shoulder than in control subjects. Study Design: Controlled laboratory study. Methods: Shoulder capsule samples were collected from 10 patients with idiopathic frozen shoulder and 10 patients with unstable shoulders (control). The samples were stained with hematoxylin and eosin (H&E) and analyzed by immunohistochemistry using antibodies against alarmin molecules including high-mobility group protein B1 (HMGB1), interleukin 33, S100A8, S100A9, and the peripheral nerve marker PGP9.5. Immunoreactivities were rated in a blinded fashion from “none” to “strong.” Immunohistochemical distribution within the capsule was noted. Before surgery, patient-ranked pain frequency, severity, stiffness, and the range of passive shoulder motion were recorded and statistically analyzed. Results: Compared with control patients, patients with frozen shoulder had greater frequency and severity of self-reported pain (P = .02) and more restricted range of motion in all planes (P < .05). H&E-stained capsular tissue from frozen shoulder showed fibroblastic hypercellularity and increased subsynovial vascularity. Immunoreactivity of alarmins was significantly stronger in frozen shoulder capsules compared with control capsules (P < .05). Furthermore, the expression of the alarmin molecule HMGB1 significantly correlated (r > 0.9, P < .05) with the severity of patient-reported pain. Conclusion: This study demonstrates a potential role for key molecular danger signals in frozen shoulder and suggests an association between the expression of danger molecules and the pain experienced by patients

Estimating the Population Benefits of Blood Pressure Lowering: A Wide-Angled Mendelian Randomization Study in UK Biobank.

Background The causal relevance of elevated blood pressure for several cardiovascular diseases (CVDs) is uncertain, as is the population impact of blood pressure lowering. This study systematically assesses evidence of causality for various CVDs in a 2-sample Mendelian randomization framework, and estimates the potential reduction in the prevalence of these diseases attributable to long-term population shifts in the distribution of systolic blood pressure (SBP). Methods and Results We investigated associations of genetically predicted SBP as predicted by 256 genetic variants with 21 CVDs in UK Biobank, a population-based cohort of UK residents. The sample consisted of 376 703 participants of European ancestry, aged 40 to 69 years at recruitment. Genetically predicted SBP was positively associated with 14 of the outcomes (P<0.002), including dilated cardiomyopathy, endocarditis, peripheral vascular disease, and rheumatic heart disease. Using genetic variation to estimate the long-term impact of blood pressure lowering on disease in a middle-aged to early late-aged UK-based population, population reductions in SBP were predicted to result in an overall 16.9% (95% CI, 12.2%-21.3%) decrease in morbidity for a 5-mm Hg decrease from a population mean of 137.7 mm Hg, 30.8% (95% CI, 22.8%-38.0%) decrease for a 10-mm Hg decrease, and 56.2% (95% CI, 43.7%-65.9%) decrease for a 22.7-mm Hg decrease in SBP (22.7 mm Hg represents a shift from the current mean SBP to 115 mm Hg). Conclusions Risk of many CVDs is influenced by long-term differences in SBP. The burden of a broad range of CVDs could be substantially reduced by long-term population-wide reductions in the distribution of blood pressure

Comparable foraging effort and habitat use between two geographically proximate tropical seabird colonies

Effective seabird conservation requires understanding their marine spatial ecology. Tracking can reveal details of their foraging ecology and habitat use, as well as the suitability of marine protected areas for at-sea conservation, but results are often regionally specific. Here we characterised the foraging behaviour of tropical breeding brown boobies Sula leucogaster in the Chagos Archipelago, Western Indian Ocean, and tested habitat requirements. GPS tracking of thirteen individuals from two colonies, located 142 km apart on the same atoll (Great Chagos Bank), showed similar foraging effort and habitat preferences despite differences in season and breeding stage. Brown boobies from both tracked populations foraged close to the colony along the atoll shelf edge, avoiding deep oceanic areas and shallow waters of the Great Chagos Bank atoll, but within the Chagos Archipelago Marine Protected Area. Sea-level height anomaly and sea surface temperature were important foraging predictors at both sites, although birds experienced distinct environmental conditions between colonies. These results suggest that while brown boobies have colony-specific at-sea foraging areas, similarities in habitat drivers of distribution and foraging behaviour can inform predictions of distributions at other colonies within the archipelago, with important benefits for at-sea conservation efforts

From route to dive: multi-scale habitat selection in a foraging tropical seabird

Comprehending how environmental variability shapes foraging behaviour across habitats is key to unlocking insights into consumer ecology. Seabirds breeding at high latitudes are exemplars of how marine consumers can adapt their behaviours to make use of predictable foraging opportunities, but prey tends to be less predictable in tropical oceanic ecosystems and may require alternative foraging behaviours. Here we used GPS and time-depth recorder loggers to investigate the foraging behaviour of central placed adult red-footed boobies (Sula sula rubripes), a tropical seabird that forages in oceanic waters via diving, or by capturing aerial prey such as flying fish in flight. Dive bout dynamics revealed that red-footed boobies appeared to exploit denser, but more sparsely distributed prey patches when diving further from the colony. Furthermore, although we found no evidence of environmentally driven habitat selection along their foraging routes, red-footed boobies preferentially dived in areas with higher sea surface temperatures and chlorophyll-a concentrations compared to conditions along their foraging tracks. This multi-scale variation implies that habitat selection differs between foraging routes compared to dive locations. Finally, red-footed booby dives were deepest during the middle of the day when light penetration was greatest. Ultimately, we highlight the importance of gaining insights into consumer foraging across different ecosystems, thereby broadening understanding of how animals might respond to changing environmental conditions

Risk exposure trade-offs in the ontogeny of sexual segregation in Antarctic fur seal pups

Sexual segregation has important ecological implications, but its initial development in early life stages is poorly understood. We investigated the roles of size dimorphism, social behavior, and predation risk on the ontogeny of sexual segregation in Antarctic fur seal, Arctocephalus gazella, pups at South Georgia. Beaches and water provide opportunities for pup social interaction and learning (through play and swimming) but increased risk of injury and death (from other seals, predatory birds, and harsh weather), whereas tussock grass provides shelter from these risks but less developmental opportunities. One hundred pups were sexed and weighed, 50 on the beach and 50 in tussock grass, in January, February, and March annually from 1989 to 2018. Additionally, 19 male and 16 female pups were GPS-tracked during lactation from December 2012. Analysis of pup counts and habitat use of GPS-tracked pups suggested that females had a slightly higher association with tussock grass habitats and males with beach habitats. GPS-tracked pups traveled progressively further at sea as they developed, and males traveled further than females toward the end of lactation. These sex differences may reflect contrasting drivers of pup behavior: males being more risk prone to gain social skills and lean muscle mass and females being more risk averse to improve chances of survival, ultimately driven by their different reproductive roles. We conclude that sex differences in habitat use can develop in a highly polygynous species prior to the onset of major sexual size dimorphism, which hints that these sex differences will increasingly diverge in later life

Distance tuneable integral membrane protein containing floating bilayers via in situ directed self-assembly

Model membranes allow for structural and biophysical studies on membrane biochemistry at the molecular level, albeit on systems of reduced complexity which can limit biological accuracy. Floating supported bilayers offer a means of producing planar lipid membrane models not adhered to a surface, which allows for improved accuracy compared to other model membranes. Here we communicate the incorporation of an integral membrane protein complex, the multidomain β-barrel assembly machinery (Bam), into our recently developed in situ self-assembled floating supported bilayers. Using neutron reflectometry and quartz crystal microbalance measurements we show this sample system can be fabricated using a two-step self-assembly process. We then demonstrate the complexity of the model membrane and tuneability of the membrane-to-surface distance using changes in the salt concentration of the bulk solution. Results demonstrate an easily fabricated, biologically accurate and tuneable membrane assay system which can be utilized for studies on integral membrane proteins within their native lipid matrix

Distance tuneable integral membrane protein containing floating bilayers via in situ directed self-assembly

Model membranes allow for structural and biophysical studies on membrane biochemistry at the molecular level, albeit on systems of reduced complexity which can limit biological accuracy. Floating supported bilayers offer a means of producing planar lipid membrane models not adhered to a surface, which allows for improved accuracy compared to other model membranes. Here we communicate the incorporation of an integral membrane protein complex, the multidomain β-barrel assembly machinery (Bam), into our recently developed in situ self-assembled floating supported bilayers. Using neutron reflectometry and quartz crystal microbalance measurements we show this sample system can be fabricated using a two-step self-assembly process. We then demonstrate the complexity of the model membrane and tuneability of the membrane-to-surface distance using changes in the salt concentration of the bulk solution. Results demonstrate an easily fabricated, biologically accurate and tuneable membrane assay system which can be utilized for studies on integral membrane proteins within their native lipid matrix

Helminth induced monocytosis conveys protection from respiratory syncytial virus infection in mice

Background: Respiratory syncytial virus (RSV) infection in infants is a major cause of viral bronchiolitis and hospitalisation. We have previously shown in a murine model that ongoing infection with the gut helminth Heligmosomoides polygyrus protects against RSV infection through type I interferon (IFN-I) dependent reduction of viral load. Yet, the cellular basis for this protection has remained elusive. Given that recruitment of mononuclear phagocytes to the lung is critical for early RSV infection control, we assessed their role in this coinfection model. Methods: Mice were infected by oral gavage with H. polygyrus. Myeloid immune cell populations were assessed by flow cytometry in lung, blood and bone marrow throughout infection and after secondary infection with RSV. Monocyte numbers were depleted by anti-CCR2 antibody or increased by intravenous transfer of enriched monocytes. Results: H. polygyrus infection induces bone marrow monopoiesis, increasing circulatory monocytes and lung mononuclear phagocytes in a IFN-I signalling dependent manner. This expansion causes enhanced lung mononuclear phagocyte counts early in RSV infection that may contribute to the reduction of RSV load. Depletion or supplementation of circulatory monocytes prior to RSV infection confirms that these are both necessary and sufficient for helminth induced antiviral protection. Conclusions: H. polygyrus infection induces systemic monocytosis contributing to elevated mononuclear phagocyte numbers in the lung. These cells are central to an anti-viral effect that reduces the peak viral load in RSV infection. Treatments to promote or modulate these cells may provide novel paths to control RSV infection in high risk individuals.</p

Spatial mapping of hematopoietic clones in human bone marrow

UNLABELLED: Clonal hematopoiesis (CH) is the expansion of somatically mutated cells in the hematopoietic compartment of individuals without hematopoietic dysfunction. Large CH clones (i.e., \u3e2% variant allele fraction) predispose to hematologic malignancy, but CH is detected at lower levels in nearly all middle-aged individuals. Prior work has extensively characterized CH in peripheral blood, but the spatial distribution of hematopoietic clones in human bone marrow is largely undescribed. To understand CH at this level, we developed a method for spatially aware somatic mutation profiling and characterized the bone marrow of a patient with polycythemia vera. We identified the complex clonal distribution of somatic mutations in the hematopoietic compartment, the restriction of somatic mutations to specific subpopulations of hematopoietic cells, and spatial constraints of these clones in the bone marrow. This proof of principle paves the way to answering fundamental questions regarding CH spatial organization and factors driving CH expansion and malignant transformation in the bone marrow. SIGNIFICANCE: CH occurs commonly in humans and can predispose to hematologic malignancy. Although well characterized in blood, it is poorly understood how clones are spatially distributed in the bone marrow. To answer this, we developed methods for spatially aware somatic mutation profiling to describe clonal heterogeneity in human bone marrow. See related commentary by Austin and Aifantis, p. 139