Conservation Genetics of a Declining Bumble Bee in Western North America; The Influence of Geography, Dispersal Limitation, and Anthopogenic Activity

Conservation biology addresses the problem of species loss by identifying species in need of protection. Conservation biology has subfields to address different aspects of biodiversity loss, including genetics and sociology. I used genetic approaches to assess the conservation status of western bumble bees, a bumble bee species of conservation concern. The western bumble bee is a bumble bee species that ranges from Alaska to New Mexico and as far east as Wyoming and Colorado. This species is disappearing in some places. It may soon be listed as endangered in the United States and is already listed as endangered in parts of its Canadian distribution. To complicate the problem further, the western bumble bee might really be two cryptic species. Recent genetic analyses indicate that there might be a northern species (Mckay’s bumble bee) and a southern species (the western bumble bee). I used DNA from specimens collected across the range and ran genetic analyses to estimate the relationships between western bumble bees and Mckay’s bumble bees. This study provided enough evidence to conclude that they are, in fact, two species. Next, I compared patterns of genetic diversity in the two species to environmental variables to determine how the environment influences how the bees to move across the landscape. I compared patterns of genetic diversity in bees that were collected between 1960 through 2020. Western bumble bees showed patterns of slightly decreasing genetic diversity through time from 1960 to 2019, but Mckay’s bumble bee did not. For both species, nighttime temperatures during the spring and proximity to a native fungal parasite were important predictors of differences in genetic diversity among samples. The distance from parasites is probably important because specimens that are near infections are more likely to be infected themselves. Although we found decreases in genetic diversity for western bumble bees, there is still enough genetic diversity in present-day populations for the species to recover if the effects of the drivers of the declines are managed. Finally, I surveyed 974 conservationists from diverse backgrounds to measure their understanding, trust, and motivation to action from conservation genetic studies. This is important because molecular methods provide important insight into the conservation status of at-risk species, but they are not used very often when land managers make conservation decisions. The results indicate that lack of understanding, but not trust, may be a barrier to increased use of molecular methods in conservation actions

Influence of Wildfire Disturbance and Post-Fire Seeding on Vegetation and Insects in Sagebrush Habitats

Disturbance events alter community composition and structure because of differences in resistance and resilience of individual taxa, changes in habitat resulting in colonization by new taxa and alteration of biotic interaction patterns. Recent changes in disturbance types, frequencies and intensities caused by anthropogenic activities may further alter community composition and structure if these disturbances exceed the tolerances or adaptations of some taxa. In sagebrush steppe habitats of the western United States, wildfire is the current dominant disturbance type, burning millions of hectares annually. Further, up to 90% of sagebrush-steppe ecosystems are affected by anthropogenic influences such as invasive species. Post-fire seeding treatments are widely used to reduce soil erosion, control the establishment of invasive plant species, and restore habitat for wildlife. We investigated insect community responses to wildfire and post-fire seeding in sagebrush-steppe habitats in southwestern Idaho by comparing insect communities among three condition classes (hereafter treatments): burned-and-seeded (BS), burned-and-unseeded (BX), and unburned (UX), which served as a control. We also quantified indirect effects of treatments on insects by assessing vegetation composition and structure (height) differences among these treatments. We found post-fire seeding changed the vegetation composition at BS plots compared to the BX plots by increasing the amount of seeded bunchgrasses and forbs, but these seeding efforts did not achieve the vegetation composition of UX plots because sagebrush was not successfully re-established. We found evidence to suggest that differences in vegetation among treatments affected the composition of insect assemblages. The strongest difference was between UX and burned (BS and BX) plots, but we found some evidence that insect communities were influenced by vegetation differences between BS and BX plots when UX plots were removed from the analysis. Correlations between insect families and vegetation variables provide useful information for evaluating potential effects of shrubland fires on insects and how best to support their post-fire recovery. This information could be useful to assess the potential for recovery of insect assemblages to various disturbance types, which could in turn inform the development of ecological models to potentially predict the threshold of tolerance for functional groups of insects to disturbances

Variation in practice patterns among specialties in the acute management of atrial fibrillation

Abstract Background Atrial fibrillation (AF) is commonly managed by a variety of specialists. Current guidelines differ in their recommendations leading to uncertainty regarding important clinical decisions. We sought to document practice pattern variation among cardiologists, emergency physicians (EP) and hospitalists at a single academic, tertiary-care center. Methods A survey was created containing seven clinical scenarios of patients presenting with AF. We analyzed respondent choices regarding rate vs rhythm control, thromboembolic treatment and hospitalization strategies. Finally, we contrasted our findings with a comparable Australasian survey to provide an international reference. Results There was a 78% response rate (124 of 158), 37% hospitalists, 31.5% cardiologists, and 31.5% EP. Most respondents chose rate over rhythm control (92.2%; 95% CI, 89.1% - 94.5%) and thromboembolic treatment (67.8%; 95% CI, 63.8% - 71.7%). Compared to both hospitalists and EPs, cardiologists were more likely to choose thromboembolic treatment for new and paroxysmal AF (adjusted OR 2.38; 95% CI, 1.05 - 5.41). They were less likely to favor hospital admission across all types of AF (adjusted OR 0.36; 95% CI, 0.17 - 0.79) but thought cardiology consultation was more important (adjusted OR 1.88, 95% CI, 0.97 - 3.64). Australasian physicians were more aggressive with rhythm control for paroxysmal AF with low CHADS2 score compared to US physicians. Conclusions Significant variation exists among specialties in the management of acute AF, likely reflecting a lack of high quality research to direct the provider. Future studies may help to standardize practice leading to decreased rates of hospitalization and overall cost.http://deepblue.lib.umich.edu/bitstream/2027.42/110777/1/12872_2015_Article_9.pd

Western Bumble Bee: Declines in the Continental United States and Range-Wide Information Gaps

In recent decades, many bumble bee species have declined due to changes in habitat, climate, and pressures from pathogens, pesticides, and introduced species. The western bumble bee (Bombus occidentalis), once common throughout western North America, is a species of concern and will be considered for listing by the U.S. Fish and Wildlife Service (USFWS) under the Endangered Species Act (ESA). We attempt to improve alignment of data collection and research with USFWS needs to consider redundancy, resiliency, and representation in the upcoming species status assessment. We reviewed existing data and literature on B. occidentalis, highlighting information gaps and priority topics for research. Priorities include increased knowledge of trends, basic information on several life‐history stages, and improved understanding of the relative and interacting effects of stressors on population trends, especially the effects of pathogens, pesticides, climate change, and habitat loss. An understanding of how and where geographic range extent has changed for the two subspecies of B. occidentalis is also needed. We outline data that could be easily collected in other research projects that would increase their utility for understanding range‐wide trends of bumble bees. We modeled the overall trend in occupancy from 1998 to 2018 of Bombus occidentalis within the continental United States using existing data. The probability of local occupancy declined by 93% over 21 yr from 0.81 (95% CRI = 0.43, 0.98) in 1998 to 0.06 (95% CRI = 0.02, 0.16) in 2018. The decline in occupancy varied spatially by landcover and other environmental factors. Detection rates vary in both space and time, but peak detection across the continental United States occurs in mid‐July. We found considerable spatial gaps in recent sampling, with limited sampling in many regions, including most of Alaska, northwestern Canada, and the southwestern United States. We therefore propose a sampling design to address these gaps to best inform the ESA species status assessment through improved assessment of how the spatial distribution of stressors influences occupancy changes. Finally, we request involvement via data sharing, participation in occupancy sampling with repeated visits to distributed survey sites, and complementary research to address priorities outlined in this paper

Characterization of a Clp Protease Gene Regulator and the Reaeration Response in Mycobacterium tuberculosis

Mycobacterium tuberculosis (MTB) enters a non-replicating state when exposed to low oxygen tension, a condition the bacillus encounters in granulomas during infection. Determining how mycobacteria enter and maintain this state is a major focus of research. However, from a public health standpoint the importance of latent TB is its ability to reactivate. The mechanism by which mycobacteria return to a replicating state upon re-exposure to favorable conditions is not understood. In this study, we utilized reaeration from a defined hypoxia model to characterize the adaptive response of MTB following a return to favorable growth conditions. Global transcriptional analysis identified the ∼100 gene Reaeration Response, induced relative to both log-phase and hypoxic MTB. This response includes chaperones and proteases, as well as the transcription factor Rv2745c, which we characterize as a Clp protease gene regulator (ClgR) orthologue. During reaeration, genes repressed during hypoxia are also upregulated in a wave of transcription that includes genes crucial to transcription, translation and oxidative phosphorylation and culminates in bacterial replication. In sum, this study defines a new transcriptional response of MTB with potential relevance to disease, and implicates ClgR as a regulator involved in resumption of replication following hypoxia

RNA delivery by extracellular vesicles in mammalian cells and its applications.

The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery