Fine-scale genetic structure reflects sex-specific dispersal strategies in a population of sociable weavers (Philetairus socius).

Dispersal is a critical driver of gene flow, with important consequences for population genetic structure, social interactions and other biological processes. Limited dispersal may result in kin-structured populations in which kin selection may operate, but it may also increase the risk of kin competition and inbreeding. Here, we use a combination of long-term field data and molecular genetics to examine dispersal patterns and their consequences for the population genetics of a highly social bird, the sociable weaver (Philetairus socius), which exhibits cooperation at various levels of sociality from nuclear family groups to its unique communal nests. Using 20 years of data, involving capture of 6508 birds and 3151 recaptures at 48 colonies, we found that both sexes exhibit philopatry and that any dispersal occurs over relatively short distances. Dispersal is female-biased, with females dispersing earlier, further, and to less closely related destination colonies than males. Genotyping data from 30 colonies showed that this pattern of dispersal is reflected by fine-scale genetic structure for both sexes, revealed by isolation by distance in terms of genetic relatedness and significant genetic variance among colonies. Both relationships were stronger among males than females. Crucially, significant relatedness extended beyond the level of the colony for both sexes. Such fine-scale population genetic structure may have played an important role in the evolution of cooperative behaviour in this species, but it may also result in a significant inbreeding risk, against which female-biased dispersal alone is unlikely to be an effective strategy.The authors' research received funding from the Natural Environment Research Council (NERC, UK; NE/G018588/1 and NE/K015257/1) to BJH, the DST-NRF Centre of Excellence at the Percy FitzPatrick Institute of African Ornithology and the Portuguese Science and Technology Foundation (FCT PTDC/BIA-BEC/103818/2008) to RC, the CNRS and region Languedoc Roussillon to CD, St John’s College, Cambridge, and the University of Cape Town to CNS, and the European MC-IRSES (FP7-PEOPLE-2012-IRSES; ‘Cooperation’ 318994) to RC, CD, REvD and BJH.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/mec.1330

Resource:A Cellular Developmental Taxonomy of the Bone Marrow Mesenchymal Stem Cell Population in Mice

Mesenchymal stem cells (MSCs) play pivotal roles in tissue (re)generation. In the murine bone marrow, they are thought to reside within the Sca-1(+) CD51(+) bone marrow stromal cell population. Here, using scRNAseq, we aimed to delineate the cellularheterogeneity of this MSC-enriched population throughout development. At the fetal stage, the MSC population is relatively homogeneous with subsets predicted to contain stem/progenitor cells, based on transcriptional modeling and marker expression. These subsets decline in relative size throughout life, with postnatal emergence of specialized clusters, including hematopoietic stem/progenitor cell (HSPC) niches. In fetal development, these stromal HSPC niches are lacking, but subsets of endothelial cells express HSPC factors, suggesting that they may provide initial niches for emerging hematopoiesis. This cellular taxonomy of the MSC population upon development is anticipated to provide a resource aiding the prospective identification of cellular subsets and molecular mechanisms driving bone marrow (re)generation

Myeloid cells promote interferon signaling-associated deterioration of the hematopoietic system

Innate and adaptive immune cells participate in the homeostatic regulation of hematopoietic stem cells (HSCs). Here, we interrogate the contribution of myeloid cells, the most abundant cell type in the mammalian bone marrow, in a clinically relevant mouse model of neutropenia. Long-term genetic depletion of neutrophils and eosinophils results in activation of multipotent progenitors but preservation of HSCs. Depletion of myeloid cells abrogates HSC expansion, loss of serial repopulation and lymphoid reconstitution capacity and remodeling of HSC niches, features previously associated with hematopoietic aging. This is associated with mitigation of interferon signaling in both HSCs and their niches via reduction of NK cell number and activation. These data implicate myeloid cells in the functional decline of hematopoiesis, associated with activation of interferon signaling via a putative neutrophil-NK cell axis. Innate immunity may thus come at the cost of system deterioration through enhanced chronic inflammatory signaling to stem cells and their niches

A Single-Cell Taxonomy Predicts Inflammatory Niche Remodeling to Drive Tissue Failure and Outcome in Human AML

Cancer initiation is orchestrated by an interplay between tumor-initiating cells and their stromal/immune environment. Here, by adapted single-cell RNA sequencing, we decipher the predicted signaling between tissue-resident hematopoietic stem/progenitor cells (HSPC) and their neoplastic counterparts with their native niches in the human bone marrow. LEPR + stromal cells are identified as central regulators of hematopoiesis through predicted interactions with all cells in the marrow. Inflammatory niche remodeling and the resulting deprivation of critical HSPC regulatory factors are predicted to repress high-output hematopoietic stem cell subsets in NPM1-mutated acute myeloid leukemia (AML), with relative resistance of clonal cells. Stromal gene signatures reflective of niche remodeling are associated with reduced relapse rates and favorable outcomes after chemotherapy across all genetic risk categories. Elucidation of the intercellular signaling defining human AML, thus, predicts that inflammatory remodeling of stem cell niches drives tissue repression and clonal selection but may pose a vulnerability for relapse-initiating cells in the context of chemotherapeutic treatment.</p

The nitrogen, carbon and greenhouse gas budget of a grazed, cut and fertilised temperate grassland

Intensively managed grazed grasslands in temperate climates are globally important environments for the exchange of the greenhouse gases (GHGs) carbon dioxide (CO2), nitrous oxide (N2O) and methane (CH4). We assessed the N and C budget of a mostly grazed and occasionally cut and fertilised grassland in SE Scotland by measuring or modelling all relevant imports and exports to the field as well as changes in soil C and N stocks over time. The N budget was dominated by import from inorganic and organic fertilisers (21.9 g N m−2 a−1) and losses from leaching (5.3 g N m−2 a−1), N2 emissions (2.9 g N m−2 a−1), and NOx and NH3 volatilisation (3.9 g N m−2 a−1), while N2O emission was only 0.6 g N m−2 a−1. The efficiency of N use by animal products (meat and wool) averaged 9.9 % of total N input over only-grazed years (2004–2010). On average over 9 years (2002–2010), the balance of N fluxes suggested that 6.0 ± 5.9 g N m−2 a−1 (mean ± confidence interval at p > 0.95) were stored in the soil. The largest component of the C budget was the net ecosystem exchange of CO2 (NEE), at an average uptake rate of 218 ± 155 g C m−2 a−1 over the 9 years. This sink strength was offset by carbon export from the field mainly as grass offtake for silage (48.9 g C m−2 a−1) and leaching (16.4 g C m−2 a−1). The other export terms, CH4 emissions from the soil, manure applications and enteric fermentation, were negligible and only contributed to 0.02–4.2 % of the total C losses. Only a small fraction of C was incorporated into the body of the grazing animals. Inclusion of these C losses in the budget resulted in a C sink strength of 163 ± 140 g C m−2 a−1. By contrast, soil stock measurements taken in May 2004 and May 2011 indicated that the grassland sequestered N in the 0–60 cm soil layer at 4.51 ± 2.64 g N m−2 a−1 and lost C at a rate of 29.08 ± 38.19 g C m−2 a−1. Potential reasons for the discrepancy between these estimates are probably an underestimation of C losses, especially from leaching fluxes as well as from animal respiration. The average greenhouse gas (GHG) balance of the grassland was −366 ± 601 g CO2 eq. m−2 yr−1 and was strongly affected by CH4 and N2O emissions. The GHG sink strength of the NEE was reduced by 54 % by CH4 and N2O emissions. Estimated enteric fermentation from ruminating sheep proved to be an important CH4 source, exceeding the contribution of N2O to the GHG budget in some years

Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants (the SToP-BPD study): Statistical analysis plan

Background: Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth with short-term and long-term adverse consequences. Although the glucocorticoid dexamethasone has been proven to be beneficial for the prevention of BPD, there are concerns about an increased risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. The aim of the Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants (SToP-BPD) trial is to assess the efficacy and safety of postnatal hydrocortisone administration for the reduction of death or BPD in ventilator-dependent preterm infants. Methods/design: The SToP-BPD study is a multicentre, double-blind, placebo-controlled hydrocortisone trial in preterm infants at risk for BPD. After parental informed consent is obtained, ventilator-dependent infants are randomly allocated to hydrocortisone or placebo treatment during a 22-day period. The primary outcome measure is the composite outcome of death or BPD at 36 weeks postmenstrual age. Secondary outcomes are short-term effects on pulmonary condition and long-term neurodevelopmental sequelae assessed at 2 years corrected age. Complications of treatment, other serious adverse events and suspected unexpected serious adverse reactions are reported as safety outcomes. This pre-specified statistical analysis plan was written and submitted without knowledge of the unblinded data

Institutionalizing Provider-Initiated HIV Testing and Counselling for Children: An Observational Case Study from Zambia

Background: Provider-initiated testing and counselling (PITC) is a priority strategy for increasing access for HIV-exposed children to prevention measures, and infected children to treatment and care interventions. This article examines efforts to scale-up paediatric PITC at a second-level hospital located in Zambia’s Southern Province, and serving a catchment area of 1.2 million people. Methods and Principal Findings: Our retrospective case study examined best practices and enabling factors for rapid institutionalization of PITC in Livingstone General Hospital. Methods included clinical observations, key informant interviews with programme management, and a desk review of hospital management information systems (HMIS) uptake data following the introduction of PITC. After PITC roll-out, the hospital experienced considerably higher testing uptake. In a 36-month period following PITC institutionalization, of total inpatient children eligible for PITC (n = 5074), 98.5 % of children were counselled, and 98.2 % were tested. Of children tested (n = 4983), 15.5 % were determined HIVinfected; 77.6 % of these results were determined by DNA polymerase chain reaction (PCR) testing in children under the age of 18 months. Of children identified as HIV-infected in the hospital’s inpatient and outpatient departments (n = 1342), 99.3 % were enrolled in HIV care, including initiation on co-trimoxazole prophylaxis. A number of good operational practices and enabling factors in the Livingstone General Hospital experience can inform rapid PIT

Endothelium-derived stromal cells contribute to hematopoietic bone marrow niche formation

Bone marrow stromal cells (BMSCs) play pivotal roles in tissue maintenance and regeneration. Their origins, however, remain incompletely understood. Here we identify rare LNGFR+ cells in human fetal and regenerative bone marrow that co-express endothelial and stromal markers. This endothelial subpopulation displays transcriptional reprogramming consistent with endothelial-to-mesenchymal transition (EndoMT) and can generate multipotent stromal cells that reconstitute the bone marrow (BM) niche upon transplantation. Single-cell transcriptomics and lineage tracing in mice confirm robust and sustained contributions of EndoMT to bone precursor and hematopoietic niche pools. Interleukin-33 (IL-33) is overexpressed in subsets of EndoMT cells and drives this conversion process through ST2 receptor signaling. These data reveal generation of tissue-forming BMSCs from mouse and human endothelial cells and may be instructive for approaches to human tissue regeneration

European Respiratory Society International Congress, Paris, 2018:highlights from the Clinical Assembly

This article contains highlights and a selection of the scientific advances from the European Respiratory Society’s Clinical Assembly (Assembly 1 and its five respective groups) that were presented at the 2018 European Respiratory Society International Congress in Paris, France. The most relevant topics from each of the groups will be discussed, covering a wide range of areas including clinical problems, rehabilitation and chronic care, thoracic imaging, interventional pulmonology, and general practice and primary care. The newest research, actual data and highlight sessions will be discussed