Human–Black Bear Conflicts: A Review of Common Management Practices

The objective of this monograph is to provide wildlife professionals, who respond to human–bear conflicts, with an appraisal of the most common techniques used for mitigating conflicts as well as the benefits and challenges of each technique in a single document. Most human–black bear conflict occurs when people make anthropogenic foods like garbage, dog food, domestic poultry, or fruit trees available to bears. Bears change their behavior to take advantage of these resources and may damage property or cause public safety concerns in the process. Managers and the public need to understand the available tools to stop human–bear conflict and reduce effects on bear populations.https://digitalcommons.usu.edu/hwi_monographs/1002/thumbnail.jp

Variation in diet of desert bighorn sheep (Ovis canadensis nelsoni): Tradeoffs associated with parturition

Selection of forage and habitats is driven by nutritional needs of individuals. Some species may sacrifice nutritional quality of forage for the mother in favor of safety of offspring (risk-averse strategy), immediately following parturition. We studied diet quality and forage selection by bighorn sheep before and following parturition to determine how nutritional demands associated with rearing offspring influenced forage acquisition. We used desert bighorn sheep, Ovis canadensis nelsoni, to investigate that potential tradeoff. We captured and radio-collared female bighorn sheep from 2016 to 2018. We used vaginal implant transmitters (VIT)s in pregnant females to identify parturition and to capture and radio-collar neonates to monitor survival of young. We collected fecal samples throughout the breeding season and throughout the year to understand diet quality and composition throughout those temporal periods. We determined diet quality and composition for pre-parturient females, females provisioning offspring, females that lost offspring, and non-pregnant individuals using fecal nitrogen and DNA metabarcoding analyses. Additionally, we compared the diet quality and composition of offspring and adult females during the spring, as well as summer and winter months. Our results indicated differences in diet quality between individuals provisioning offspring and those whose offspring had died. Females that were provisioning dependent young had lower quality diets than those that lost their offspring. Diet composition among those groups was also markedly different; females that had lost an offspring had a more diverse diet than did females with dependent young. Diet quality differed among seasons, wherein offspring and adult females had higher quality diets during the spring months, with decreasing quality as the year progressed. Diet diversity was similar across seasons, although spring months tended to be most diverse. Our results support tradeoffs associated with risk-averse strategies made by adult females associated with parturition. Nutritional quality of forage was linked to provisioning status, indicating that females were trading diet quality for safety of offspring, but those females whose offspring had died selected high quality forages. Those results help explain habitat selection observed in mountain ungulates around parturition and provide further insight into the evolutionary processes and adaptive significance exhibited by those specialized artiodactyls

Viral Bcl-2-Mediated Evasion of Autophagy Aids Chronic Infection of γHerpesvirus 68

γ-herpesviruses (γHVs) have developed an interaction with their hosts wherein they establish a life-long persistent infection and are associated with the onset of various malignancies. One critical virulence factor involved in the persistency of murine γ-herpesvirus 68 (γHV68) is the viral homolog of the Bcl-2 protein (vBcl-2), which has been implicated to counteract both host apoptotic responses and autophagy pathway. However, the relative significance of the two activities of vBcl-2 in viral persistent infection has yet to be elucidated. Here, by characterizing a series of loss-of-function mutants of vBcl-2, we have distinguished the vBcl-2-mediated antagonism of autophagy from the vBcl-2-mediated inhibition of apoptosis in vitro and in vivo. A mutant γHV68 virus lacking the anti-autophagic activity of vBcl-2 demonstrates an impaired ability to maintain chronic infections in mice, whereas a mutant virus lacking the anti-apoptotic activity of vBcl-2 establishes chronic infections as efficiently as the wild-type virus but displays a compromised ability for ex vivo reactivation. Thus, the vBcl-2-mediated antagonism of host autophagy constitutes a novel mechanism by which γHVs confer persistent infections, further underscoring the importance of autophagy as a critical host determinant in the in vivo latency of γ-herpesviruses

Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability.

To identify genetic causes of intellectual disability (ID), we screened a cohort of 986 individuals with moderate to severe ID for variants in 565 known or candidate ID-associated genes using targeted next-generation sequencing. Likely pathogenic rare variants were found in ∼11% of the cases (113 variants in 107/986 individuals: ∼8% of the individuals had a likely pathogenic loss-of-function [LoF] variant, whereas ∼3% had a known pathogenic missense variant). Variants in SETD5, ATRX, CUL4B, MECP2, and ARID1B were the most common causes of ID. This study assessed the value of sequencing a cohort of probands to provide a molecular diagnosis of ID, without the availability of DNA from both parents for de novo sequence analysis. This modeling is clinically relevant as 28% of all UK families with dependent children are single parent households. In conclusion, to diagnose patients with ID in the absence of parental DNA, we recommend investigation of all LoF variants in known genes that cause ID and assessment of a limited list of proven pathogenic missense variants in these genes. This will provide 11% additional diagnostic yield beyond the 10%-15% yield from array CGH alone.Action Medical Research (SP4640); the Birth Defect Foundation (RG45448); the Cambridge National Institute for Health Research Biomedical Research Centre (RG64219); the NIHR Rare Diseases BioResource (RBAG163); Wellcome Trust award WT091310; The Cell lines and DNA bank of Rett Syndrome, X-linked mental retardation and other genetic diseases (member of the Telethon Network of Genetic Biobanks (project no. GTB12001); the Genetic Origins of Congenital Heart Disease Study (GO-CHD)- funded by British Heart Foundation (BHF)This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/humu.2290

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Finding Diagnostically Useful Patterns in Quantitative Phenotypic Data.

Trio-based whole-exome sequence (WES) data have established confident genetic diagnoses in ∼40% of previously undiagnosed individuals recruited to the Deciphering Developmental Disorders (DDD) study. Here we aim to use the breadth of phenotypic information recorded in DDD to augment diagnosis and disease variant discovery in probands. Median Euclidean distances (mEuD) were employed as a simple measure of similarity of quantitative phenotypic data within sets of ≥10 individuals with plausibly causative de novo mutations (DNM) in 28 different developmental disorder genes. 13/28 (46.4%) showed significant similarity for growth or developmental milestone metrics, 10/28 (35.7%) showed similarity in HPO term usage, and 12/28 (43%) showed no phenotypic similarity. Pairwise comparisons of individuals with high-impact inherited variants to the 32 individuals with causative DNM in ANKRD11 using only growth z-scores highlighted 5 likely causative inherited variants and two unrecognized DNM resulting in an 18% diagnostic uplift for this gene. Using an independent approach, naive Bayes classification of growth and developmental data produced reasonably discriminative models for the 24 DNM genes with sufficiently complete data. An unsupervised naive Bayes classification of 6,993 probands with WES data and sufficient phenotypic information defined 23 in silico syndromes (ISSs) and was used to test a "phenotype first" approach to the discovery of causative genotypes using WES variants strictly filtered on allele frequency, mutation consequence, and evidence of constraint in humans. This highlighted heterozygous de novo nonsynonymous variants in SPTBN2 as causative in three DDD probands

POLR3B is associated with a developmental and epileptic encephalopathy with myoclonic‐atonic seizures and ataxia

Objective: POLR3B encodes the second largest subunit of RNA polymerase III, which is essential for transcription of small non-coding RNAs. Biallelic pathogenic variants in POLR3B are associated with an inherited hypomyelinating leukodystrophy. Recently, de novo heterozygous variants in POLR3B were reported in six individuals with ataxia, spasticity, and demyelinating peripheral neuropathy. Three of these individuals had epileptic seizures. The aim of this article is to precisely define the epilepsy phenotype associated with de novo heterozygous POLR3B variants. Methods: We used online gene-matching tools to identify 13 patients with de novo POLR3B variants. We systematically collected genotype and phenotype data from clinicians using two standardized proformas. Results: All 13 patients had novel POLR3B variants. Twelve of 13 variants were classified as pathogenic or likely pathogenic as per American College of Medical Genetics (ACMG) criteria. Patients presented with generalized myoclonic, myoclonic-atonic, atypical absence, or tonic-clonic seizures between the ages of six months and 4 years. Epilepsy was classified as epilepsy with myoclonic-atonic seizures (EMAtS) in seven patients and “probable EMAtS” in two more. Seizures were treatment resistant in all cases. Three patients became seizure-free. All patients had some degree of developmental delay or intellectual disability. In most cases developmental delay was apparent before the onset of seizures. Three of 13 cases were reported to have developmental stagnation or regression in association with seizure onset. Treatments for epilepsy that were reported by clinicians to be effective were: sodium valproate, which was effective in five of nine patients (5/9) who tried it; rufinamide (2/3); and ketogenic diet (2/3). Additional features were ataxia/incoordination (8/13); microcephaly (7/13); peripheral neuropathy (4/13), and spasticity/hypertonia (6/13). Significance: POLR3B is a novel genetic developmental and epileptic encephalopathy (DEE) in which EMAtS is the predominant epilepsy phenotype. Ataxia, neuropathy, and hypertonia may be variously observed in these patients

The effects of “pulling levers” focused deterrence strategies on crime

A number of American police departments have been experimenting with new problem-oriented policing frameworks to prevent gang and group-involved violence generally known as the “pulling levers” focused deterrence strategies. Focused deterrence strategies honor core deterrence ideas, such as increasing risks faced by offenders, while finding new and creative ways of deploying traditional and non-traditional law enforcement tools to do so, such as directly communicating incentives and disincentives to targeted offenders. Pioneered in Boston to halt serious gang violence, the focused deterrence framework has been applied in many American cities through federally sponsored violence prevention programs. In its simplest form, the approach consists of selecting a particular crime problem, such as gang homicide; convening an interagency working group of law enforcement, social-service, and community-based practitioners; conducting research to identify key offenders, groups, and behavior patterns; framing a response to offenders and groups of offenders that uses a varied menu of sanctions (“pulling levers”) to stop them from continuing their violent behavior; focusing social services and community resources on targeted offenders and groups to match law enforcement prevention efforts; and directly and repeatedly communicating with offenders to make them understand why they are receiving this special attention. These new strategic approaches have been applied to a range of crime problems, such as overt drug markets and individual repeat offenders, and have shown promising results in the reduction of crime. Objectives: To synthesize the extant evaluation literature and assess the effects of pulling levers focused deterrence strategies on crime. Conclusions: We conclude that pulling levers focused deterrence strategies seem to be effective in reducing crime. However, we urge caution in interpreting these results because of the lack of more rigorous randomized controlled trials in the existing body of scientific evidence on this approach

The clinical and genetic spectrum of inherited glycosylphosphatidylinositol deficiency disorders

Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural history data. In this multinational retrospective observational study, we systematically analyse the molecular spectrum, phenotypic characteristics, and natural history of 83 individuals from 75 unique families with IGDs, including 70 newly reported individuals: the largest single cohort to date. Core clinical features were developmental delay or intellectual disability (DD/ID, 90%), seizures (83%), hypotonia (72%), and motor symptoms (64%). Prognostic and biologically significant neuroimaging features included cerebral atrophy (75%), cerebellar atrophy (60%), callosal anomalies (57%), and symmetric restricted diffusion of the central tegmental tracts (60%). Sixty-one individuals had multisystem involvement including gastrointestinal (66%), cardiac (19%), and renal (14%) anomalies. Though dysmorphic features were appreciated in 82%, no single dysmorphic feature had a prevalence >30%, indicating substantial phenotypic heterogeneity. Follow-up data were available for all individuals, 15 of whom were deceased at the time of writing. Median age at seizure onset was 6 months. Individuals with variants in synthesis stage genes of the GPI-AP exhibited a significantly shorter time to seizure onset than individuals with variants in transamidase and remodelling stage genes of the GPI-AP (P=0.046). Forty individuals had intractable epilepsy. The majority of individuals experienced delayed or absent speech (95%); motor delay with non-ambulance (64%); and severe-to-profound DD/ID (59%). Individuals with a developmental epileptic encephalopathy (51%) were at greater risk of intractable epilepsy (P=0.003), non-ambulance (P=0.035), ongoing enteral feeds (P<0.001), and cortical visual impairment (P=0.007). Serial neuroimaging showed progressive cerebral volume loss in 87.5% and progressive cerebellar atrophy in 70.8%, indicating a neurodegenerative process. Genetic analyses identified 93 unique variants (106 total), including 22 novel variants. Exploratory analyses of genotype-phenotype correlations using unsupervised hierarchical clustering identified novel genotypic predictors of clinical phenotype and long-term outcome with meaningful implications for management. In summary, we expand both the mild and severe phenotypic extremities of the IGDs; provide insights into their neurological basis; and, vitally, enable meaningful genetic counselling for affected individuals and their families