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The combination of autonomous recording units (ARUs) and machine learning enables scalable biodiversity monitoring. These data are often analysed using occupancy models, yet methods for integrating machine learning outputs with these models are rarely compared. Using the Yucatán black howler monkey as a case study, we evaluated four approaches for integrating ARU data and machine learning outputs into occupancy models: (i) standard occupancy models with verified data, and false-positive occupancy models using (ii) presence-absence data, (iii) counts of detections, and (iv) continuous classifier scores. We assessed estimator accuracy and the effects of decision threshold, temporal subsampling, and verification strategies. We found that classifier-guided listening with a standard occupancy model provided an accurate estimate with minimal verification effort. The false-positive models yielded similarly accurate estimates under specific conditions, but were sensitive to subjective choices including decision threshold. The inability to determine stable parameter choices a priori, coupled with the increased computational complexity of several models (i.e. the detection-count and continuous-score models), limits the practical application of false-positive models. In the case of a high-performance classifier and a readily detectable species, classifier-guided listening paired with a standard occupancy model provides a practical and efficient approach for accurately estimating occupancy.

Ocelots (Leopardus pardalis) are listed as least concern on the International Union for Conservation of Nature (IUCN) Red list of Threatened Species, yet we lack knowledge on basic demographic parameters across much of the ocelot’s geographic range, including population density. We used camera-trapping methodology and spatially explicit capture-recapture (SECR) models with sex-specific detection function parameters to estimate ocelot densities across 7 field sites over 1 to 12 years (from data collected during 2002–2015) in Belize, Central America. Ocelot densities in the broadleaf rainforest sites ranged between 7.2 and 22.7 ocelots/100 km², whereas density in the pine (Pinus spp.) forest site was 0.9 ocelots/100 km². Applying an inverse-variance weighted average over all years for each broadleaf site increased precision and resulted in average density ranging from 8.5 to 13.0 ocelots/100 km². Males often had larger movement parameter estimates and higher detection probabilities at their activity centers than females. In most years, the sex ratio was not significantly different from 50:50, but the pooled sex ratio estimated using an inverse weighted average over all years indicated a female bias in 1 site, and a male bias in another. We did not detect any population trends as density estimates remained relatively constant over time; however, the power to detect such trends was generally low. Our SECR density estimates were lower but more precise than previous estimates and indicated population stability for ocelots in Belize.

It is not possible to systematically screen the environment for rabies virus (RABV) using current approaches. We sought to determine under what conditions RABV is detectable from feces and other accessible samples from infected wildlife to broaden the number of biological samples that could be used to test for RABV. We employed a recently-developed quantitative RT-PCR assay called the “LN34 panlyssavirus real-time RT-PCR assay”, which is highly sensitive and specific for all variants of RABV. We harvested and tested brain tissue, fecal, and/or mouth swab samples from 25 confirmed RABV positive bats of six species. To determine if rabies RNA lasts in feces sufficiently long post-defecation to use it as a surveillance tool, we tested fecal samples from 10 bats at the time of sample collection and after 24 hours of exposure to ambient conditions, with an additional test on six bats out to 72 hours. To assess whether we could pool fecal pellets and still detect a positive, we generated dilutions of known positives at 1:1, 1:10, 1:50, and 1:200. For six individuals for which matched brain, mouth swab, and fecal samples were tested, results were positive for 100%, 67%, and 67%, respectively. For the first time test to 24 hours, 63% of feces that were positive at time 0 were still positive after 24 hours, and 50% of samples at 72 hours were positive across all three replicates. Pooling tests revealed that fecal positives were detected at 1:10 dilution, but not at 1:50 or 1:200. Our preliminary results suggest that fecal samples hold promise for a rapid and non-invasive environmental screening system.

The efficiency of base editing is substantially increased by optimizing expression and nuclear localization of the editing enzymes. CRISPR base editing enables the creation of targeted single-base conversions without generating double-stranded breaks. However, the efficiency of current base editors is very low in many cell types. We reengineered the sequences of BE3, BE4Gam, and xBE3 by codon optimization and incorporation of additional nuclear-localization sequences. Our collection of optimized constitutive and inducible base-editing vector systems dramatically improves the efficiency by which single-nucleotide variants can be created. The reengineered base editors enable target modification in a wide range of mouse and human cell lines, and intestinal organoids. We also show that the optimized base editors mediate efficient in vivo somatic editing in the liver in adult mice.

Genetic Alzheimer's disease (AD) risk factors associate with reduced defensive amyloid β plaque-associated microglia (AβAM), but the contribution of modifiable AD risk factors to microglial dysfunction is unknown. In AD mouse models, we observe concomitant activation of the hypoxia-inducible factor 1 (HIF1) pathway and transcription of mitochondrial-related genes in AβAM, and elongation of mitochondria, a cellular response to maintain aerobic respiration under low nutrient and oxygen conditions. Overactivation of HIF1 induces microglial quiescence in cellulo, with lower mitochondrial respiration and proliferation. In vivo, overstabilization of HIF1, either genetically or by exposure to systemic hypoxia, reduces AβAM clustering and proliferation and increases Aβ neuropathology. In the human AD hippocampus, upregulation of HIF1α and HIF1 target genes correlates with reduced Aβ plaque microglial coverage and an increase of Aβ plaque-associated neuropathology. Thus, hypoxia (a modifiable AD risk factor) hijacks microglial mitochondrial metabolism and converges with genetic susceptibility to cause AD microglial dysfunction.

Sepsis arises from diverse and incompletely understood dysregulated host response processes following infection that leads to life-threatening organ dysfunction. Here we showed that neutrophils and emergency granulopoiesis drove a maladaptive response during sepsis. We generated a whole-blood single-cell multiomic atlas (272,993 cells, n  = 39 individuals) of the sepsis immune response that identified populations of immunosuppressive mature and immature neutrophils. In co-culture, CD66b + sepsis neutrophils inhibited proliferation and activation of CD4 + T cells. Single-cell multiomic mapping of circulating hematopoietic stem and progenitor cells (HSPCs) (29,366 cells, n  = 27) indicated altered granulopoiesis in patients with sepsis. These features were enriched in a patient subset with poor outcome and a specific sepsis response signature that displayed higher frequencies of IL1R2 + immature neutrophils, epigenetic and transcriptomic signatures of emergency granulopoiesis in HSPCs and STAT3-mediated gene regulation across different infectious etiologies and syndromes. Our findings offer potential therapeutic targets and opportunities for stratified medicine in severe infection. Knight and colleagues report altered granulopoiesis and increased frequency of immature neutrophil subsets with immunosuppressive properties in a subset of patients with sepsis with poor outcome.

Environmental (e)DNA has rapidly become a powerful biomonitoring tool, particularly in aquatic ecosystems. This approach has not been as widely adopted in terrestrial communities where the methods of vertebrate eDNA collection have varied from the use of secondary collectors such as blood feeding parasites and spider webs, to washing surfaces of leaves and soil sampling. Recent studies have demonstrated the potential of direct collection of eDNA from air sampling, but none have tested how effective airborne eDNA sampling might be in a biodiverse environment. We used three prototype samplers to actively sample a mixed neotropical bat community in a partially controlled environment. We assess whether airborne eDNA can accurately characterize a high diversity community with skewed abundances and to determine if filter design impacts DNA collection and taxonomic recovery. Our study provides evidence for the accuracy of airborne eDNA as a detection tool and highlights its potential for monitoring high density, diverse assemblages such as bat roosts. Analysis of air samples recovered >91% of the species present and some limited relationship between species abundance and read count. Our data suggests this method can accurately depict a diverse mixed‐mammal community, particularly when the location is contained (e.g., a roost, den or burrow) but also highlights the potential for secondary transfer of eDNA material on clothing and equipment. Our results also demonstrate that simple, inexpensive, battery‐operated homemade air samplers can collect an abundance of eDNA from the air, opening the opportunity for sampling in remote environments. We use novel prototype filters to collect eDNA from the air in a highly diverse and ecologically complex mammal community under controlled conditions. We recovered more than 90% of the known taxa including rare species. Our data demonstrates that airborne DNA can efficiently document an ecologically complex community, particularly in a confined space like a roost or cave.

Leptonycteris nivalis (the Mexican long-nosed bat) is an endangered nectar-feeding bat species that follows “nectar corridors” as it migrates from Mexico to the southwestern United States. Locating these nectar corridors is key to their conservation and may be possible using environmental DNA (eDNA) from these bats. Hence, we developed and tested DNA metabarcoding and qPCR eDNA assays to determine whether L. nivalis could be detected by sampling the agave flowers on which it feeds. We sampled plants with known bat visitations in the Sierra Madre Oriental in Laguna de Sanchez (LS), Nuevo León, Mexico, and in the Chisos Mountains in Big Bend National Park, TX, USA (CB). A total of 13 samples included both swabs of agave umbels and cuttings of individual flowers. DNA metabarcoding was performed as a PCR multiplex that targeted bats (SFF-COI), arthropods (ANML-COI), and plants (ITS2 and rbcL). We targeted arthropods and plants in parallel with bats because future metabarcoding studies may wish to examine all the pollinators and plants within the nectar corridor. We developed and tested the sensitivity and specificity of two qPCR assays. We found that both DNA metabarcoding and qPCR were highly successful at detecting L. nivalis (11 of 13 for DNA metabarcoding and 12 of 13 for qPCR). Swabs and flower cuttings and both qPCR assays detected the species over four replicates. We suggest that L. nivalis leaves substantial DNA behind as it forages for nectar. We also suggest that future studies examine the time since sampling to determine its effect on detection success. The DNA metabarcoding multiplex will be useful for parallel questions regarding pollination ecology, while, with further testing, the qPCR assays will be effective for large-scale sampling for the detection of migration corridors and foraging areas. This work may be relevant to other nectar-feeding bat species, which can likely be detected with similar methodologies.

The objective of this paper is to provide an overview of the strengths, limitations and lessons learned from estimating the burden from musculoskeletal (MSK) conditions in the Global Burden of Disease 2010 Study (GBD 2010 Study). It should be read in conjunction with the other GBD 2010 Study papers published in this journal. The strengths of the GBD 2010 Study include: the involvement of a MSK expert group; development of new and more valid case definitions, functional health states, and disability weights to better reflect the MSK conditions; the extensive series of systematic reviews undertaken to obtain data to derive the burden estimates; and the use of a new, more advanced version of the disease-modelling software (DisMod-MR). Limitations include: many regions of the world did not have data; the extent of heterogeneity between included studies; and burden does not include broader aspects of life, such as participation and well-being. A number of lessons were learned. Ongoing involvement of experts is critical to ensure the success of future efforts to quantify and monitor this burden. A paradigm shift is urgently needed among global agencies in order to alleviate the rapidly increasing global burden from MSK conditions. Prevention and control of MSK disability are required, along with health system changes. Further research is needed to improve understanding of the predictors and clinical course across different settings, and the ways in which MSK conditions can be better managed and prevented.

Objective Small mammals such as the Julia Creek dunnart ( Sminthopsis douglasi ) may be difficult to detect using traditional trapping methods. Here, we conducted a pilot study to determine whether eDNA collected from soil and/or air could detect the presence of terrestrial vertebrates, including S. douglasi , in a semi-arid, open grassland environment. Results Airborne eDNA analysis returned vertebrate DNA from five sample sites ( n  = 7), whereas soil eDNA analysis returned vertebrate DNA from a single site ( n  = 7). The Julia Creek dunnart was not detected in any of the experimental samples. However, several airborne eDNA samples did return strong matches to three terrestrial vertebrates, the long-haired rat ( Rattus villosissimus ), red kangaroo ( Osphranter rufus ) and brown quail ( Synoicus ypsilophorus ), all native species known to occur commonly in the study area. Overall, our preliminary findings suggest that the effectiveness of airborne and soil-derived eDNA in detecting terrestrial vertebrates was constrained by high human signal and low sampling intensity. For future studies, we recommend a number of field and lab-based refinements to increase the likelihood of detecting more taxa, particularly those that occur at low density. Clinical trial number Not applicable