SNAPSHOT USA 2019 : a coordinated national camera trap survey of the United States

This article is protected by copyright. All rights reserved.With the accelerating pace of global change, it is imperative that we obtain rapid inventories of the status and distribution of wildlife for ecological inferences and conservation planning. To address this challenge, we launched the SNAPSHOT USA project, a collaborative survey of terrestrial wildlife populations using camera traps across the United States. For our first annual survey, we compiled data across all 50 states during a 14-week period (17 August - 24 November of 2019). We sampled wildlife at 1509 camera trap sites from 110 camera trap arrays covering 12 different ecoregions across four development zones. This effort resulted in 166,036 unique detections of 83 species of mammals and 17 species of birds. All images were processed through the Smithsonian's eMammal camera trap data repository and included an expert review phase to ensure taxonomic accuracy of data, resulting in each picture being reviewed at least twice. The results represent a timely and standardized camera trap survey of the USA. All of the 2019 survey data are made available herein. We are currently repeating surveys in fall 2020, opening up the opportunity to other institutions and cooperators to expand coverage of all the urban-wild gradients and ecophysiographic regions of the country. Future data will be available as the database is updated at eMammal.si.edu/snapshot-usa, as well as future data paper submissions. These data will be useful for local and macroecological research including the examination of community assembly, effects of environmental and anthropogenic landscape variables, effects of fragmentation and extinction debt dynamics, as well as species-specific population dynamics and conservation action plans. There are no copyright restrictions; please cite this paper when using the data for publication.Publisher PDFPeer reviewe

Identification of candidate Parkinson disease genes by integrating genome-wide association study, expression, and epigenetic data sets

Importance Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD. Objective To investigate what genes and genomic processes underlie the risk of sporadic PD. Design and Setting This genetic association study used the bioinformatic tools Coloc and transcriptome-wide association study (TWAS) to integrate PD case-control GWAS data published in 2017 with expression data (from Braineac, the Genotype-Tissue Expression [GTEx], and CommonMind) and methylation data (derived from UK Parkinson brain samples) to uncover putative gene expression and splicing mechanisms associated with PD GWAS signals. Candidate genes were further characterized using cell-type specificity, weighted gene coexpression networks, and weighted protein-protein interaction networks. Main Outcomes and Measures It was hypothesized a priori that some genes underlying PD loci would alter PD risk through changes to expression, splicing, or methylation. Candidate genes are presented whose change in expression, splicing, or methylation are associated with risk of PD as well as the functional pathways and cell types in which these genes have an important role. Results Gene-level analysis of expression revealed 5 genes (WDR6 [OMIM 606031], CD38 [OMIM 107270], GPNMB [OMIM 604368], RAB29 [OMIM 603949], and TMEM163 [OMIM 618978]) that replicated using both Coloc and TWAS analyses in both the GTEx and Braineac expression data sets. A further 6 genes (ZRANB3 [OMIM 615655], PCGF3 [OMIM 617543], NEK1 [OMIM 604588], NUPL2 [NCBI 11097], GALC [OMIM 606890], and CTSB [OMIM 116810]) showed evidence of disease-associated splicing effects. Cell-type specificity analysis revealed that gene expression was overall more prevalent in glial cell types compared with neurons. The weighted gene coexpression performed on the GTEx data set showed that NUPL2 is a key gene in 3 modules implicated in catabolic processes associated with protein ubiquitination and in the ubiquitin-dependent protein catabolic process in the nucleus accumbens, caudate, and putamen. TMEM163 and ZRANB3 were both important in modules in the frontal cortex and caudate, respectively, indicating regulation of signaling and cell communication. Protein interactor analysis and simulations using random networks demonstrated that the candidate genes interact significantly more with known mendelian PD and parkinsonism proteins than would be expected by chance. Conclusions and Relevance Together, these results suggest that several candidate genes and pathways are associated with the findings observed in PD GWAS studies

Oscillatory wall strain reduction precedes arterial intimal hyperplasia in a murine model

Cardiovascular diseases (CVD) remain the most common cause of death in the United States. Additionally, peripheral artery disease affects thousands of people each year. A major underlying cause of these diseases is the occlusion of the coronary or peripheral arteries due to arteriosclerosis. To overcome this, a number of vascular interventions have been developed including angioplasty, stenting, endarterectomies and bypass grafts. Although all of these methods are capable of restoring blood flow to the distal organ after occlusion, they are all plagued by unacceptably high restenosis rates. While the biological reactions that occur as a result of each of these methods differ, the initiating factor of both the primary atherosclerosis and subsequent failure of vascular interventions appears to be intimal hyperplasia (IH). Intimal hyperplasia is most simply defined as the expansion of multiple layers of cells internally to the internal elastic lamina of the blood vessel. This excessive cellular growth leads to arterial stenosis, plaque formation and inflammatory reactions. Despite extensive research the underlying factors that cause IH remain unclear. A quantity of research to date has implicated endothelial cell mechanosensation as the mechanism by which IH is initiated with evidence positively correlating wall shear stress with IH. Others, however, have demonstrated that changes in the stresses applied to the wall in vitro can modulate IH independent of hemodynamic shear stress. Thus, relations between wall tensile stress and IH in vivo may shed light on the underlying mechanisms of IH. Since noninvasive measurement of wall tensile stress in vivo is difficult, it is most feasible to measure oscillatory wall strain which is intimately related to wall tensile stress through the mechanical properties of the arterial wall. In this dissertation, we hypothesize that reductions in oscillatory wall strain precede the formation of intimal hyperplasia in a murine model. To test our hypothesis, we first developed a novel, high spatial and temporal resolution method to measure oscillatory wall strains in the murine common carotid artery. We validated this method both in vitro using an arterial phantom and in vivo using a murine model of abdominal aortic aneurysms. To assess relationships between strain and IH, we applied our strain measurement technique to a recently developed mouse model of IH. In this model, a suture is used to create a focal stenosis and reduce flow through the common carotid artery by 85%; resulting in proximal IH formation. Using this approach, we identified a relationship between oscillatory strain reductions and IH. Subsequent analysis demonstrated that early reductions in mechanical strain just 4 days after focal stenosis creation correlate with IH formation nearly 1 month later. Since IH is not expected to form by day 4 in this model, we went on to assess changes in gross vascular morphology at day 4. We discovered that, although strains are significantly reduced by day 4, no significant IH can be observed, suggesting that changes in wall structure are resulting in strain reductions. At day 4 post-op, we observed cellular proliferation and leukocyte recruitment to the wall without intimal hyperplasia. These studies suggest that early reductions in mechanical strain may be an important predictor of IH formation. Clinically, this relation could be important for the development of novel techniques for predicting IH formation before it becomes hemodynamically significant.</p

Structure-Based Design of an Iminoheterocyclic β‑Site Amyloid Precursor Protein Cleaving Enzyme (BACE) Inhibitor that Lowers Central Aβ in Nonhuman Primates

We describe successful efforts to optimize the in vivo profile and address off-target liabilities of a series of BACE1 inhibitors represented by <b>6</b> that embodies the recently validated fused pyrrolidine iminopyrimidinone scaffold. Employing structure-based design, truncation of the cyanophenyl group of <b>6</b> that binds in the S3 pocket of BACE1 followed by modification of the thienyl group in S1 was pursued. Optimization of the pyrimidine substituent that binds in the S2′–S2″ pocket of BACE1 remediated time-dependent CYP3A4 inhibition of earlier analogues in this series and imparted high BACE1 affinity. These efforts resulted in the discovery of difluorophenyl analogue <b>9</b> (MBi-4), which robustly lowered CSF and cortex Aβ₄₀ in both rats and cynomolgus monkeys following a single oral dose. Compound <b>9</b> represents a unique molecular shape among BACE inhibitors reported to potently lower central Aβ in nonrodent preclinical species