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The tricolored blackbird, Agelaius tricolor, is a gregarious species that forms enormous breeding and foraging colonies in wetland and agricultural habitats, primarily in California, USA. Once extremely abundant, species numbers have declined dramatically in the past century, largely due to losses of breeding and foraging habitats. Tricolored blackbirds are currently listed as Endangered by the IUCN, and Threatened under the California Endangered Species Act. Increased genetic information is needed to detail the evolutionary consequences of a species-wide bottleneck and inform conservation management. Here, we present a contiguous tricolored blackbird reference genome, assembled with PacBio HiFi long reads and Dovetail Omni-C data to generate a scaffold-level assembly containing multiple chromosome-length scaffolds. This genome adds a valuable resource for important evolutionary and conservation research on tricolored blackbirds and related species.

Habitat-specific thermal responses are well documented in various organisms and likely determine the vulnerability of populations to climate change. However, the underlying roles of genetics and plasticity that shape such habitat-specific patterns are rarely investigated together. Here we examined the thermal plasticity of the butterfly Bicyclus dorothea originating from rainforest and ecotone habitats in Cameroon under common garden conditions. We also sampled wild-caught butterflies from forest and ecotone sites and used RADseq to explore genome-wide population differentiation. We found differences in the level of phenotypic plasticity across habitats. Specifically, ecotone populations exhibited greater sensitivity in wing eyespot features with variable development temperatures relative to rainforest populations. Known adaptive roles of wing eyespots in Bicyclus species suggest that this morphological plasticity is likely under divergent selection across environmental gradients. However, we found no distinct population structure of genome-wide variation between habitats, suggesting high level of ongoing gene flow between habitats is homogenizing most parts of the genome.

Human genetic studies have linked rare coding variants in microglial genes, such as TREM2, and more recently PLCG2 to Alzheimer’s disease (AD) pathology. The P522R variant in PLCG2 has been shown to confer protection for AD and to result in a subtle increase in enzymatic activity. PLCγ2 is a key component of intracellular signal transduction networks and induces Ca2+ signals downstream of many myeloid cell surface receptors, including TREM2. To explore the relationship between PLCγ2 and TREM2 and the role of PLCγ2 in regulating immune cell function, we generated human induced pluripotent stem cell (iPSC)- derived macrophages from isogenic lines with homozygous PLCG2 knockout (Ko). Stimulating TREM2 signalling using a polyclonal antibody revealed a complete lack of calcium flux and IP1 accumulation in PLCγ2 Ko cells, demonstrating a non-redundant role of PLCγ2 in calcium release downstream of TREM2. Loss of PLCγ2 led to broad changes in expression of several macrophage surface markers and phenotype, including reduced phagocytic activity and survival, while LPS-induced secretion of the inflammatory cytokines TNFα and IL-6 was unaffected. We identified additional deficits in PLCγ2- deficient cells that compromised cellular adhesion and migration. Thus, PLCγ2 is key in enabling divergent cellular functions and might be a promising target to increase beneficial microglial functions.

Background and Objective:We evaluated the metabolomic profile in CSF, serum and urine of participants with idiopathic intracranial hypertension (IIH) compared to controls and measured changes in metabolism associated with clinical markers of disease activity and treatment.Methods:A case-control study compared women aged 18-55 years with active IIH (Friedman diagnostic criteria), to a sex, age and body mass index matched control group. IIH participants were identified from neurology and ophthalmology clinics from National Health Service hospitals and underwent a prospective intervention to induce disease remission through weight loss with re-evaluation at 12 months. Clinical assessments included lumbar puncture, headache, papilledema and visual measurements. Spectra of CSF, serum and urine metabolites were acquired utilizing proton nuclear magnetic resonance spectroscopy.Results:Urea was lower in IIH (CSF; controls median ±IQR 0.196 ±0.008, IIH 0.058 ±0.059, pDiscussion:We observed metabolic disturbances that are evident in CSF, serum and urine of IIH participants, suggesting global metabolic dysregulation. Altered ketone body metabolites normalized following therapeutic weight loss. CSF:serum urea ratio was altered which may influence ICP dynamics and headache. Elevated CSF acetate, known to stimulate trigeminal sensitization, was associated with headache morbidity. These alterations of metabolic pathways specific to IIH provide biological insight and warrants mechanistic evaluation.

Identifying areas of high evolutionary potential is a judicious strategy for developing conservation priorities in the face of environmental change. For wide-ranging species occupying heterogeneous environments, the evolutionary forces that shape distinct populations can vary spatially. Here, we investigate patterns of genomic variation and genotype-environment associations in the hermit thrush (Catharus guttatus), a North American songbird, at broad (across the breeding range) and narrow spatial scales (at a hybrid zone). We begin by building a genoscape or map of genetic variation across the breeding range and find five distinct genetic clusters within the species, with the greatest variation occurring in the western portion of the range. Genotype-environment association analyses indicate higher allelic turnover in the west than in the east, with measures of temperature surfacing as key predictors of putative adaptive genomic variation rangewide. Sincebroad patterns detected across a species' range represent the aggregate of many locally adapted populations, we investigate whether our broadscale analysis is consistent with a finer scale analysis. We find that top rangewide temperature-associated loci vary in their clinal patterns (e.g., steep clines vs. fixed allele frequencies) across a hybrid zone in British Columbia, suggesting that the environmental predictors and the associated candidate loci identified in the rangewide analysis are of variable importance in this particular region. However, two candidate loci exhibit strong concordance with the temperature gradient in British Columbia, suggesting a potential role for temperature-related barriers to gene flow and/or temperature-driven ecological selection in maintaining putative local adaptation. This study demonstrates how patterns identified at the broad (macrogeographic) scale can be validated by investigating genotype-environment correlations at the local (microgeographic) scale. Furthermore, our results highlight the importance of considering the spatial distribution of putative adaptive variation when assessing population-level sensitivity to climate change and other stressors.

Preserving biodiversity under rapidly changing climate conditions is challenging. One approach for estimating impacts and their magnitude is to model current relationships between genomic and environmental data and then to forecast those relationships under future climate scenarios. In this way, understanding future genomic and environmental relationships can help guide management decisions, such as where to establish new protected areas where populations might be buffered from high temperatures or major changes in rainfall. However, climate warming is only one of many anthropogenic threats one must consider in rapidly developing parts of the world. In Central Africa, deforestation, mining, and infrastructure development are accelerating population declines of rainforest species. Here we investigate multiple anthropogenic threats in a Central African rainforest songbird, the little greenbul (Andropadus virens). We examine current climate and genomic variation in order to explore the association between genome and environment under future climate conditions. Specifically, we estimate Genomic Vulnerability, defined as the mismatch between current and predicted future genomic variation based on genotype–environment relationships modeled across contemporary populations. We do so while considering other anthropogenic impacts. We find that coastal and central Cameroon populations will require the greatest shifts in adaptive genomic variation, because both climate and land use in these areas are predicted to change dramatically. In contrast, in the more northern forest–savanna ecotones, genomic shifts required to keep pace with climate will be more moderate, and other anthropogenic impacts are expected to be comparatively low in magnitude. While an analysis of diverse taxa will be necessary for making comprehensive conservation decisions, the species‐specific results presented illustrate how evolutionary genomics and other anthropogenic threats may be mapped and used to inform mitigation efforts. To this end, we present an integrated conceptual model demonstrating how the approach for a single species can be expanded to many taxonomically diverse species.

Understanding how risk factors affect populations across their annual cycle is a major challenge for conserving migratory birds. For example, disease outbreaks may happen on the breeding grounds, the wintering grounds, or during migration and are expected to accelerate under climate change. The ability to identify the geographic origins of impacted individuals, especially outside of breeding areas, might make it possible to predict demographic trends and inform conservation decision‐making. However, such an effort is made more challenging by the degraded state of carcasses and resulting low quality of DNA available. Here, we describe a rapid and low‐cost approach for identifying the origins of birds sampled across their annual cycle that is robust even when DNA quality is poor. We illustrate the approach in the common loon (Gavia immer), an iconic migratory aquatic bird that is under increasing threat on both its breeding and wintering areas. Using 300 samples collected from across the breeding range, we develop a panel of 158 single‐nucleotide polymorphisms (SNP) loci with divergent allele frequencies across six genetic subpopulations. We use this SNP panel to identify the breeding grounds for 142 live nonbreeding individuals and carcasses. For example, genetic assignment of loons sampled during botulism outbreaks in parts of the Great Lakes provides evidence for the significant role the lakes play as migratory stopover areas for loons that breed across wide swaths of Canada, and highlights the vulnerability of a large segment of the breeding population to botulism outbreaks that are occurring in the Great Lakes with increasing frequency. Our results illustrate that the use of SNP panels to identify breeding origins of carcasses collected during the nonbreeding season can improve our understanding of the population‐specific impacts of mortality from disease and anthropogenic stressors, ultimately allowing more effective management.

Background TREM2 is a microglial cell surface receptor, with risk mutations linked to Alzheimer’s disease (AD), including R47H. TREM2 signalling via SYK aids phagocytosis, chemotaxis, survival, and changes to microglial activation state. In AD mouse models, knockout (KO) of TREM2 impairs microglial clustering around amyloid and prevents microglial activation. The R47H mutation is proposed to reduce TREM2 ligand binding. We investigated cell phenotypes of the R47H mutant and TREM2 KO in a model of human microglia, and compared their transcriptional signatures, to determine the mechanism by which R47H TREM2 disrupts function. Methods We generated human microglia-like iPSC-macrophages (pMac) from isogenic induced pluripotent stem cell (iPSC) lines, with homozygous R47H mutation or TREM2 knockout (KO). We firstly validated the effect of the R47H mutant on TREM2 surface and subcellular localization in pMac. To assess microglial phenotypic function, we measured phagocytosis of dead neurons, cell morphology, directed migration, survival, and LPS-induced inflammation. We performed bulk RNA-seq, comparing significant differentially expressed genes (DEGs; p Results R47H modified surface expression and shedding of TREM2, but did not impair TREM2-mediated signalling, or gross phenotypes that were dysregulated in the TREM2 KO (phagocytosis, motility, survival). However, altered gene expression in the R47H TREM2 pMac overlapped by 90% with the TREM2 KO and was characterised by dysregulation of genes involved with immunity, proliferation, activation, chemotaxis, and adhesion. Downregulated mediators of ECM adhesion included the vitronectin receptor αVβ3, and consequently, R47H TREM2 pMac adhered weakly to vitronectin compared with WT pMac. To counteract these transcriptional defects, we investigated TGFβ1, as a candidate upstream regulator. TGFβ1 failed to rescue vitronectin adhesion of pMac, although it improved αVβ3 expression. Conclusions The R47H mutation is not sufficient to cause gross phenotypic defects of human pMac under standard culture conditions. However, overlapping transcriptional defects with TREM2 KO supports the hypothesised partial loss-of-function effects of the R47H mutation. Furthermore, transcriptomics can guide us to more subtle phenotypic defects in the R47H cells, such as reduced cell adhesion, and can be used to predict targets for therapeutic intervention.

Habitat loss and alteration has driven many species into decline, often to the point of requiring protection and intervention to avert extinction. Genomic data provide the opportunity to inform conservation and recovery efforts with details about vital evolutionary processes with a resolution far beyond that of traditional genetic approaches. The tricolored blackbird (Agelaius tricolor) has suffered severe losses during the previous century largely due to anthropogenic impacts on their habitat. Using a dataset composed of a whole genome paired with reduced representation libraries (RAD-Seq) from samples collected across the species' range, we find evidence for panmixia using multiple methods, including PCA (no geographic clustering), admixture analyses (ADMIXTURE and TESS conclude K=1), and comparisons of genetic differentiation (average FST=0.029). Demographic modeling approaches recovered an ancient decline that had a strong impact on genetic diversity but did not detect any effect from the known recent decline. We also did not detect any evidence for selection, and hence adaptive variation, at any site, either geographic or genomic. These results indicate that species continues to have high vagility across its range despite population decline and habitat loss and should be managed as a single unit.

Space-based tracking technology using low-cost miniature tags is now delivering data on fine-scale animal movement at near-global scale. Linked with remotely sensed environmental data, this offers a biological lens on habitat integrity and connectivity for conservation and human health; a global network of animal sentinels of environmental change. Publisher PDF

Hypothermic and normothermic machine perfusion in kidney transplantation are purported to exert a beneficial effect on post-transplant outcomes compared to the traditionally used method of static cold storage. Kidney perfusion techniques provide a window for organ reconditioning and quality assessment. However, how best to deliver these preservation methods or improve organ quality has not yet been conclusively defined. This review summarises the promising advances in machine perfusion science in recent years, which have the potential to further improve early graft function and prolong graft survival.

Humid tropical forests play a dominant role in the functioning of Earth but are under increasing threat from changes in land use and climate. How forest vulnerability varies across space and time and what level of stress forests can tolerate before facing a tipping point are poorly understood. Here, we develop a tropical forest vulnerability index (TFVI) to detect and evaluate the vulnerability of global tropical forests to threats across space and time. We show that climate change together with land-use change have slowed the recovery rate of forest carbon cycling. Temporal autocorrelation, as an indicator of this slow recovery, increases substantially for above-ground biomass, gross primary production, and evapotranspiration when climate stress reaches a critical level. Forests in the Americas exhibit extensive vulnerability to these stressors, while in Africa, forests show relative resilience to climate, and in Asia reveal more vulnerability to land use and fragmentation. TFVI can systematically track the response of tropical forests to multiple stressors and provide early-warning signals for regions undergoing critical transitions.

Birds exhibit a remarkable array of seasonal migrations. Despite much research describing migratory behaviour, the underlying forces driving how a species' breeding and wintering populations redistribute each year, that is, migratory connectivity, remain largely unknown. Here, we test the hypothesis that birds migrate in a way that minimises energy expenditure while considering intraspecific competition for energy acquisition, by developing a modelling framework that simulates an optimal redistribution of individuals between breeding and wintering areas. Using 25 species across the Americas, we find that the model accurately predicts empirical migration patterns, and thus offers a general explanation for migratory connectivity based on first ecological and energetic principles. Our model provides a strong basis for exploring additional processes underlying the ecology and evolution of migration, but also a framework for predicting how migration impacts local adaptation across seasons and how environmental change may affect population dynamics in migratory species.

Thermal adaptation to habitat variability can determine species vulnerability to environmental change. For example, physiological tolerance to naturally low thermal variation in tropical forests species may alter their vulnerability to climate change impacts, compared with open habitat species. However, the extent to which habitat-specific differences in tolerance derive from within-generation versus across-generation ecological or evolutionary processes are not well characterized. Here we studied thermal tolerance limits of a Central African butterfly (Bicyclus dorothea) across two habitats in Cameroon: a thermally stable tropical forest and the more variable ecotone between rainforest and savanna. Second generation individuals originating from the ecotone, reared under conditions common to both populations, exhibited higher upper thermal limits (CTmax) than individuals originating from forest (∼3°C greater). Lower thermal limits (CTmin) were also slightly lower for the ecotone populations (∼1°C). Our results are suggestive of local adaptation driving habitat-specific differences in thermal tolerance (especially CTmax) that hold across generations. Such habitat-specific thermal limits may be widespread for tropical ectotherms and could affect species vulnerability to environmental change. However, microclimate and within-generation developmental processes (e.g. plasticity) will mediate these differences, and determining the fitness consequences of thermal variation for ecotone and rainforest species will require continued study of both within-generation and across-generation eco-evolutionary processes. This article has an associated First Person interview with the first author of the paper., Summary: The thermal tolerance of Bicyclus dorothea is habitat-specific with higher CTmax in ecotone populations compared to their forest counterparts, while CTmin was relatively similar across habitats.

Identifying population genetic structure is useful for inferring evolutionary process and comparing the resulting structure with subspecies boundaries can aid in species management. The American Kestrel (Falco sparverius) is a widespread and highly diverse species with 17 total subspecies, only 2 of which are found north of U.S./Mexico border (F. s. paulus is restricted to southeastern United States, while F. s. sparverius breeds across the remainder of the U.S. and Canadian distribution). In many parts of their U.S. and Canadian range, American Kestrels have been declining, but it has been difficult to interpret demographic trends without a clearer understanding of gene flow among populations. Here we sequence the first American Kestrel genome and scan the genome of 197 individuals from 12 sampling locations across the United States and Canada in order to identify population structure. To validate signatures of population structure and fill in sampling gaps across the U.S. and Canadian range, we screened 192 outlier loci in an additional 376 samples from 34 sampling locations. Overall, our analyses support the existence of 5 genetically distinct populations of American Kestrels—eastern, western, Texas, Florida, and Alaska. Interestingly, we found that while our genome-wide genetic data support the existence of previously described subspecies boundaries in the United States and Canada, genetic differences across the sampled range correlate more with putative migratory phenotypes (resident, long-distance, and short-distance migrants) rather than a priori described subspecies boundaries per se. Based on our results, we suggest the resulting 5 genetically distinct populations serve as the foundation for American Kestrel conservation and management in the face of future threats.

1. ForestsarebeingconvertedtoagriculturethroughouttheAfrotropics,drivingde- clines in sensitive rainforest taxa such as understorey birds. The ongoing expansion of cocoa agriculture, a common small-scale farming commodity, has contributed to the loss of 80% rainforest cover in some African countries. African cocoa farms may provide habitat for biodiversity, yet little is known about their suitability for vertebrate fauna, or the effect of farm management on animal communities. 2. Here, we report the first in-depth investigation into avian diversity and commu- nity composition in African cocoa, by assembling a dataset of 9,566 individual birds caught across 83 sites over 30 years in Southern Cameroon. We compared bird diversity in mature forest and cocoa using measures of alpha, beta and gamma diversity, and we investigated the effect of cocoa farm shade and forest cover on bird communities. 3. Gammadiversitywashigherincocoathanforest,thoughalphadiversitywassimi- lar, indicating a higher dissimilarity (beta diversity) between cocoa farms. Cocoa farms differed from forest in community composition, with a distinctive decrease in relative abundance of insectivores, forest specialists and ant-followers and an increase in frugivores. 4. Within cocoa farms, we found that farms with high shade cover in forested land- scapes resulted in higher relative abundance and richness of sensitive forest spe- cies; shady farms contained up to five times the proportion of forest specialists than sunny farms. 5. Synthesis and applications. Sunny African cocoa farms were less able to support sensitive bird guilds compared with shaded farms in forested landscapes. Ourfindings support the notion that certain ecological and dietary guilds, such as ant-followers and forest specialists are disproportionately affected by land-use change. In light of the current push to increase cocoa production in sub-Saharan Africa, our results provide policymakers opportunities for more wildlife-friendly cocoa schemes that maximize avian diversity.

We analyze a readout scheme for Majorana qubits based on dispersive coupling to a resonator. We consider two variants of Majorana qubits: the Majorana transmon and the Majorana box qubit. In both cases, the qubit-resonator interaction can produce sizeable dispersive shifts in the MHz range for reasonable system parameters, allowing for submicrosecond readout with high fidelity. For Majorana transmons, the light-matter interaction used for readout manifestly conserves Majorana parity, which leads to a notion of quantum nondemolition (QND) readout that is stronger than for conventional charge qubits. In contrast, Majorana box qubits only recover an approximately QND readout mechanism in the dispersive limit where the resonator detuning is large. We also compare dispersive readout to longitudinal readout for the Majorana box qubit. We show that the latter gives faster and higher fidelity readout for reasonable parameters, while having the additional advantage of being manifestly QND, and so may prove to be a better readout mechanism for these systems.

Global loss of biodiversity has placed new urgency on the need to understand factors regulating species response to rapid environmental change. While specialists are often less resilient to rapid environmental change than generalists, species-level analyses may obscure the extent of specialization when locally adapted populations vary in climate tolerances. Until recently, quantification of the degree of climate specialization in migratory birds below the species level was hindered by a lack of genomic and tracking information, but recent technological advances have helped to overcome these barriers. Here we take a genome-wide genetic approach to mapping population-specific migratory routes and quantifying niche breadth within genetically distinct populations of a migratory bird, the willow flycatcher (Empidonax traillii), which exhibits variation in the severity of population declines across its breeding range. While our sample size is restricted to the number of genetically distinct populations within the species, our results support the idea that locally adapted populations of the willow flycatcher with narrow climatic niches across seasons are already federally listed as endangered or in steep decline, while populations with broader climatic niches have remained stable in recent decades. Overall, this work highlights the value of quantifying niche breadth within genetically distinct groups across time and space when attempting to understand the factors that facilitate or constrain the response of locally adapted populations to rapid environmental change.

Cardiac 18F-FDG PET has been used in clinics to assess myocardial glucose metabolism. Its ability for imaging myocardial glucose transport, however, has rarely been exploited in clinics. Using the dynamic FDG-PET scans of ten patients with coronary artery disease, we investigate in this paper appropriate dynamic scan and kinetic modeling protocols for efficient quantification of myocardial glucose transport. Three kinetic models and the effect of scan duration were evaluated by using statistical fit quality, assessing the impact on kinetic quantification, and analyzing the practical identifiability. The results show that the kinetic model selection depends on the scan duration. The reversible two-tissue model was needed for a one-hour dynamic scan. The irreversible two-tissue model was optimal for a scan duration of around 10-15 minutes. If the scan duration was shortened to 2-3 minutes, a one-tissue model was the most appropriate. For global quantification of myocardial glucose transport, we demonstrated that an early dynamic scan with a duration of 10-15 minutes and irreversible kinetic modeling was comparable to the full one-hour scan with reversible kinetic modeling. Myocardial glucose transport quantification provides an additional physiological parameter on top of the existing assessment of glucose metabolism and has the potential to enable single tracer multiparametric imaging in the myocardium., 10 pages, 8 figures

One of the most iconic wild equids, the plains zebra occupies a broad region of sub-Saharan Africa and exhibits a wide range of phenotypic diversity in stripe patterns that have been used to classify multiple subspecies. After decades of relative stability, albeit with a loss of at least one recognized subspecies, the total population of plains zebras has undergone an approximate 25% decline since 2002. Individuals with abnormal stripe patterns have been recognized in recent years but the extent to which their appearance is related to demography and/or genetics is unclear. Investigating population genetic health and genetic structure are essential for developing effective strategies for plains zebra conservation. We collected DNA from 140 plains zebra, including seven with abnormal stripe patterns, from nine locations across the range of plains zebra, and analyzed data from restriction site-associated and whole genome sequencing (RAD-seq, WGS) libraries to better understand the relationships between population structure, genetic diversity, inbreeding, and abnormal phenotypes. We found that genetic structure did not coincide with described subspecific variation, but did distinguish geographic regions in which anthropogenic habitat fragmentation is associated with reduced gene flow and increased evidence of inbreeding, especially in certain parts of East Africa. Further, zebras with abnormal striping exhibited increased levels of inbreeding relative to normally striped individuals from the same populations. Our results point to a genetic cause of stripe pattern abnormalities, and dramatic evidence of the consequences of habitat fragmentation.

Adaptation across climate gradients can provide the raw material needed for evolutionary response to climate change. In migratory species, studies of local climate adaptation are made challenging by seasonal movement, where it is unclear to what extent individuals track their local climate niches across the annual cycle. In the migratory songbird yellow warbler ( Setophaga petechia ), we test the hypothesis that individuals track similar climates between their breeding and wintering ranges. Further, we examine whether adaptation to local climate might lead to morphological differences among populations and different demographic responses to temporal climate variability. We find a correlation between wintering and breeding precipitation but not temperature regimes at the level of the individual bird. Specifically, birds from the driest wintering regions migrate to the driest breeding regions. Additionally, we find an association between bill size and breeding season precipitation which, given documented climate-associated genomic variation, suggests adaptation to local precipitation gradients might exist on the breeding grounds. Finally, we show geographic variation in the effect of precipitation on demography, with higher precipitation associated with population increases in some regions and declines in others. Taken together, our results suggest that variation in climate optima exists across the breeding range of yellow warblers and provide a potential mechanism for parallel selection across the annual cycle.

BACKGROUND: TREM2 is a microglial cell surface receptor, with risk mutations linked to Alzheimer’s disease (AD), including R47H. Binding of ligands to TREM2 triggers Syk-dependent signalling through the DAP12 co-receptor, leading to phagocytosis, survival, and changes to microglial activation state. In biochemical assays, R47H impairs TREM2 binding to phosphatidylserine, a lipid “eat-me” signal exposed by apoptotic neurons. The effect of R47H TREM2 upon phagocytosis of apoptotic neurons by human microglia has not yet been reported. METHODS: We generated human microglia-like iPSC-macrophages (pMac) from isogenic induced pluripotent stem cell (iPSC) lines with homozygous R47H mutation or TREM2 knockout (KO). To assess microglial phenotypic function in the mutants, we measured: (1) pro-inflammatory cytokine responses by ELISA; (2) survival after growth factor-withdrawal; (3) phagocytosis by novel high-content imaging assays, using two neuron-derived cargoes that expose phosphatidylserine (fixed SH-SY5Ys and synaptosomes). Downstream signalling resulting from TREM2 activation was additionally assessed by assaying Syk phosphorylation and calcium flux. RESULTS: We demonstrated that TREM2 KO strongly diminished both pMac survival and neural phagocytosis, while having little impact on inflammatory cytokine response. R47H TREM2 modified surface expression and shedding of TREM2, but did not impair TREM2-mediated signalling, survival, or phagocytosis. CONCLUSIONS: Under healthy conditions in culture, the R47H mutation is not sufficient to cause defects in phagocytosis or survival of human pMac, unlike more severe T66M or W50C TREM2 loss-of-function mutations. We hypothesise that R47H TREM2 affects other microglia phenotypes yet to be explored, and/or that pathogenic manifestation requires other stressors relating to neurodegenerative disease.

Pyrenestes finches are unique among birds in showing a non-sex-determined polymorphism in bill size and are considered a textbook example of disruptive selection. Morphs breed randomly with respect to bill size, and differ in diet and feeding performance relative to seed hardness. Previous breeding experiments are consistent with the polymorphism being controlled by a single genetic factor. Here, we use genome-wide pooled sequencing to explore the underlying genetic basis of bill morphology and identify a single candidate region. Targeted resequencing reveals extensive linkage disequilibrium across a 300 Kb region containing the insulin-like growth factor 1 (IGF1) gene, with a single 5-million-year-old haplotype associating with phenotypic dominance of the large-billed morph. We find no genetic similarities controlling bill size in the well-studied Darwin’s finches (Geospiza). Our results show how a single genetic factor may control bill size and provide a foundation for future studies to examine this phenomenon within and among avian species., Pyrenestes finches have a bill size polymorphism thought to be maintained by disruptive selection. Here, the authors identify a single candidate region, including insulin-like growth factor 1, differentiating small and large bill size morphs and a wider region differentiating the mega-billed morph.

Through the rise of global commodity chains, consumer demand in China and the USA has given rise to the extraction of natural resources in the Congo Basin. The Chinese market for high-valued animal products such as elephant ivory and pangolin scales has encouraged poaching, exploitation and trafficking of these goods in Africa. Chinese demand for other African commodities, however, remains less well known. Using data across a 15-year period (2001–2015), we analysed the relationship between Chinese timber imports and tree-cover loss in the Congo Basin. Tree-cover loss was measured via remote sensing and the value of imports was obtained from official trade statistics. Results indicate that the total accumulated export of wood from Congo Basin countries to China doubled between 2001 and 2015, with 50% of exports originating from Cameroon and the Republic of Congo. We found a positive relationship between measures of Chinese logging and the loss of tree cover in the Congo Basin. Further investigation of the timber products market showed that US demand for Chinese-made furniture was positively correlated with Chinese timber imports from the Congo Basin. These findings suggest that US demand for furniture encourages Chinese economic actors to harvest timber from Congo Basin forests. Our results help to illuminate the complex environmental and economic drivers surrounding trade and deforestation and can help inform consumers about more sustainable ways to purchase wood products from one of the world's preeminent biodiversity hotspots.

Yellow warblers already in decline As the climate changes, species' ability to adapt to changing conditions may relate directly to their future persistence. Determining whether and when this will happen is challenging, however, because it is difficult to tease apart the causes of decline or maintenance. Bay et al. looked at the relationship between genomic variation and the environment in North American populations of the yellow warbler (see the Perspective by Fitzpatrick and Edelsparre). Genes linked to exploratory and migratory behavior were important for successful climate adaptation. Furthermore, populations identified as “genetically vulnerable” because of limited climate-associated genomic variation were already declining. Science , this issue p. 83 ; see also p. 29

We developed nuclear single nucleotide polymorphism (SNP) markers for the Painted Bunting (Passerina ciris) using next-generation sequencing genotyping on the Illumina HiSeq4000 platform. Following the best-RAD approach, we sequenced 96 individuals from five breeding populations occurring in the United States. We assessed the discerning power of 105,000 SNPs and confirmed the quality of these markers in population differentiation studies. We detected outlier SNPs within or near protein coding genes, including sequences coding for olfactory receptors which may relate to migratory navigation. Finally, we provide a novel list of 33 primer pairs flanking SNPs to link individuals to regional populations and improve our understanding of the evolution of this migratory songbird.

Understanding the environmental contributors to population structure is of paramount importance for conservation in urbanized environments. We used spatially explicit models to determine genetic population structure under current and future environmental conditions across a highly fragmented, human-dominated environment in Southern California to assess the effects of natural ecological variation and urbanization. We focused on 7 common species with diverse habitat requirements, home-range sizes, and dispersal abilities. We quantified the relative roles of potential barriers, including natural environmental characteristics and an anthropogenic barrier created by a major highway, in shaping genetic variation. The ability to predict genetic variation in our models differed among species: 11-81% of intraspecific genetic variation was explained by environmental variables. Although an anthropogenically induced barrier (a major highway) severely restricted gene flow and movement at broad scales for some species, genetic variation seemed to be primarily driven by natural environmental heterogeneity at a local level. Our results show how assessing environmentally associated variation for multiple species under current and future climate conditions can help identify priority regions for maximizing population persistence under environmental change in urbanized regions.

The little greenbul, a common rainforest passerine from sub-Saharan Africa, has been the subject of long-term evolutionary studies to understand the mechanisms leading to rainforest speciation. Previous research found morphological and behavioural divergence across rainforest-savannah transition zones (ecotones), and a pattern of divergence with gene flow suggesting divergent natural selection has contributed to adaptive divergence and ecotones could be important areas for rainforests speciation. Recent advances in genomics and environmental modelling make it possible to examine patterns of genetic divergence in a more comprehensive fashion. To assess the extent to which natural selection may drive patterns of differentiation, here we investigate patterns of genomic differentiation among populations across environmental gradients and regions. We find compelling evidence that individuals form discrete genetic clusters corresponding to distinctive environmental characteristics and habitat types. Pairwise FST between populations in different habitats is significantly higher than within habitats, and this differentiation is greater than what is expected from geographic distance alone. Moreover, we identified 140 SNPs that showed extreme differentiation among populations through a genomewide selection scan. These outliers were significantly enriched in exonic and coding regions, suggesting their functional importance. Environmental association analysis of SNP variation indicates that several environmental variables, including temperature and elevation, play important roles in driving the pattern of genomic diversification. Results lend important new genomic evidence for environmental gradients being important in population differentiation.

We evaluated a soft tissue oxygen saturation (Sto2) measurement at triage for predicting admission to the hospital in adults presenting to the emergency department (ED) in addition to data routinely gathered at triage.This was a prospective, observational, single center study of adults presenting to the ED for evaluation. Research assistants obtained thenar eminence Sto2 measurements on subjects in ED triage. ED providers not involved in the study then made all management and disposition decisions. We prospectively collected data on each subject's final ED disposition (admission versus discharge). We identified the optimal Sto2 cutoff value for predicting admission. We then used logistic regression modeling to describe the added predictive value of Sto2 beyond routinely collected triage data including Emergency Severity Index level, age, and vital signs.We analyzed 2588 adult (17years) subjects with 743 subjects (28.7%) admitted to the hospital. Sto276% was the optimal diagnostic cutoff for predicting admission. Of subjects with Sto276%, 158 of 384 (41.1%) underwent admission versus 585 of 2204 (26.5%) subjects with Sto2≥76. After controlling for age, vital signs, and ESI level in the logistic regression analysis, Sto276% had an odds ratio of 1.54 (95% confidence interval (CI), 1.19 to 1.98) for predicting admission.Sto2 may provide additional prognostic data to routine triage assessment regarding the disposition for undifferentiated adult patients presenting to the ED.

The Baird’s tapir ( Tapirus bairdii ) is the largest terrestrial mammal dwelling in the neotropics and the only native representative of the order Perissodactyla. This species is under a great threat due to the impacts of hunting and habitat loss. Therefore, implementation of conservation strategies, in situ and ex situ, is urgent. However, to improve effectiveness of these strategies knowledge of the species level of genetic variability is needed. We collected samples (hair, feces and blood) from T. bairdii individuals kept in captivity in 4 zoos in Mexico and the field (feces) to extract DNA. We analyzed tapir levels of genetic variability focusing on a 511 bp region of the mtDNA D-loop and a set of 6 microsatellite loci. We found a relatively low allelic richness Rs = 3.94 but a relatively high frequency of private alleles (6 out of 24) and a variability of mother lines higher than reported in other studies (7 haplotypes with 15 polymorphic sites, Hd = 0.846 and Pi = 0.0128). Our results suggest that there might be a relatively high genetic diversity in tapir population inhabiting southern Mexico.

1.Identifying migratory connections across the annual cycle is important for studies of migrant ecology, evolution, and conservation. While recent studies have demonstrated the utility of high-resolution SNP-based genetic markers for identifying population-specific migratory patterns, the accuracy of this approach relative to other intrinsic tagging techniques has not yet been assessed. 2.Here, using a straightforward application of Bayes’ Rule, we develop a method for combining inferences from high-resolution genetic markers, stable isotopes, and habitat suitability models, to spatially infer the breeding origin of migrants captured anywhere along their migratory pathway. Using leave-one-out cross validation, we compare the accuracy of this combined approach with the accuracy attained using each source of data independently. 3.Our results indicate that when each method is considered in isolation, the accuracy of genetic assignments far exceeded that of assignments based on stable isotopes or habitat suitability models. However, our joint assignment method consistently resulted in small, but informative increases in accuracy and did help to correct misassignments based on genetic data alone. We demonstrate the utility of the combined method by identifying previously undetectable patterns in the timing of migration in a North American migratory songbird, the Wilson's warbler. 4.Overall, our results support the idea that while genetic data provides the most accurate method for tracking animals using intrinsic markers, when each method is considered independently, there is value in combining all three methods. The resulting methods are provided as part of a new computationally-efficient R-package, GAIAH, allowing broad application of our statistical framework to other migratory animal systems. This article is protected by copyright. All rights reserved.