Toward telomere-to-telomere cat genomes for precision medicine and conservation biology.

Genomic data from species of the cat family Felidae promise to stimulate veterinary and human medical advances, and clarify the coherence of genome organization. We describe how interspecies hybrids have been instrumental in the genetic analysis of cats, from the first genetic maps to propelling cat genomes toward the T2T standard set by the human genome project. Genotype-to-phenotype mapping in cat models has revealed dozens of health-related genetic variants, the molecular basis for mammalian pigmentation and patterning, and species-specific adaptations. Improved genomic surveillance of natural and captive populations across the cat family tree will increase our understanding of the genetic architecture of traits, population dynamics, and guide a future of genome-enabled biodiversity conservation.

Tree House Explorer: A Novel Genome Browser for Phylogenomics.

Tree House Explorer (THEx) is a genome browser that integrates phylogenomic data and genomic annotations into a single interactive platform for combined analysis. THEx allows users to visualize genome-wide variation in evolutionary histories and genetic divergence on a chromosome-by-chromosome basis, with continuous sliding window comparisons to gene annotations (GFF/GTF), recombination rates, and other user-specified, highly customizable feature annotations. THEx provides a new platform for interactive phylogenomic data visualization to analyze and interpret the diverse evolutionary histories woven throughout genomes. Hosted on Conda, THEx integrates seamlessly into new or pre-existing workflows.

Ultracontinuous Single Haplotype Genome Assemblies for the Domestic Cat (Felis catus) and Asian Leopard Cat (Prionailurus bengalensis).

In addition to including one of the most popular companion animals, species from the cat family Felidae serve as a powerful system for genetic analysis of inherited and infectious disease, as well as for the study of phenotypic evolution and speciation. Previous diploid-based genome assemblies for the domestic cat have served as the primary reference for genomic studies within the cat family. However, these versions suffered from poor resolution of complex and highly repetitive regions, with substantial amounts of unplaced sequence that is polymorphic or copy number variable. We sequenced the genome of a female F1 Bengal hybrid cat, the offspring of a domestic cat (Felis catus) x Asian leopard cat (Prionailurus bengalensis) cross, with PacBio long sequence reads and used Illumina sequence reads from the parents to phase >99.9% of the reads into the 2 species' haplotypes. De novo assembly of the phased reads produced highly continuous haploid genome assemblies for the domestic cat and Asian leopard cat, with contig N50 statistics exceeding 83 Mb for both genomes. Whole-genome alignments reveal the Felis and Prionailurus genomes are colinear, and the cytogenetic differences between the homologous F1 and E4 chromosomes represent a case of centromere repositioning in the absence of a chromosomal inversion. Both assemblies offer significant improvements over the previous domestic cat reference genome, with a 100% increase in contiguity and the capture of the vast majority of chromosome arms in 1 or 2 large contigs. We further demonstrated that comparably accurate F1 haplotype phasing can be achieved with members of the same species when one or both parents of the trio are not available. These novel genome resources will empower studies of feline precision medicine, adaptation, and speciation.

Caregivers' Perceptions and Responses to a New Norm: The Missing Link in Addressing Adolescent Sexting Behaviors in the U.S.

Youth sharing of self- or peer-produced sexual content via electronic communications, dubbed by the media as "sexting" (i.e., sexting behaviors), has generated concern among a wide variety of adult stakeholders in the U.S. Experts recognize the need to integrate perspectives and knowledge about adolescents' sexting behaviors from individuals who interact with adolescents (e.g., their caregivers) to inform the development of prevention policy and practice. The present study fills this gap by interviewing 10 separate groups of caregivers in three different states, with the sole focus on adolescent sexting behaviors. Results indicated seven themes: (1) characteristics of adolescent sexting behaviors, (2) influences on sexting behaviors, (3) communication about sexting behaviors, (4) gender and sexting behaviors, (5) sociohistorical conditions and sexting behaviors, (6) consequences of sexting behaviors, and (7) ways to address sexting behaviors; multiple themes emerged within each of the seven parent codes. Findings inform the need to integrate adolescent sexting behaviors into comprehensive sexual education curricula and to develop educational content on adolescent sexting behaviors for adolescents and caregivers in online and printable handout formats. Clearly defining sexting and norms around sexting are of particular importance in such educational materials.

Child Sexual Abuse in Organizational Settings: A Research Framework to Advance Policy and Practice.

Recent decades have produced growing public attention to the problem of child sexual abuse (CSA) occurring within civic institutions, school settings, youth sports, religious institutions, and other youth-serving organizations. Often amid considerable media and public scrutiny, such institutions have been called upon to improve their responses to sexual abuse incidents, address underlying organizational conditions that may foster such incidents, and develop viable systems of early intervention and prevention. These system challenges, in turn, have produced growing demand for high-quality research that can refine our understanding of the correlates and dynamics of sexual abuse within institutional settings and can help identify the parameters of effective strategies and responses. This article introduces a special issue of Sexual Abuse featuring emerging scholarship focused on CSA within organizational settings and sets forth a framework for further advancing the base of knowledge in this vital area of policy and practice.

Campus Sexual Assault: Forging an Action-Focused Research Agenda.

In recent years, the problem of campus-based sexual assault has emerged as a prominent matter of concern for institutions of higher education. Amid expanded media attention and a shifting policy landscape, many institutions have grappled with programmatic and legal challenges related to systems of investigation and adjudication of sexual assault cases. Meanwhile, many have worked to develop and deploy proactive preventive measures including those involving bystander engagement, peer-driven interventions, sexual assault awareness campaigns, self-defense programs, and the innovative use of social media and other technology. In this context, there is a growing need for high-quality empirical research that can shed light on the extent and nature of campus sexual assault; evaluate existing institutional systems and processes; and promote the development, testing, and evaluation of novel approaches that respond to unmet needs and challenges. As an introduction to a special journal issue devoted to this nascent but rapidly emerging field of inquiry, this article offers context and perspective on the vital role that research can play in the development and advancement of effective policies and strategies to prevent and effectively respond to campus-based sexual assault.

What's in a Name? Evaluating the Effects of the "Sex Offender" Label on Public Opinions and Beliefs.

Particularly over the past two decades, the terms sex offender and juvenile sex offender (JSO) have attained increasingly common usage in media and public policy discourse. Although often applied as factual descriptors, the labels may evoke strong subconscious associations with a population commonly presumed to be compulsive, at high risk of re-offense, and resistant to rehabilitation. Such associations, in turn, may exert considerable impact on expressions of support for certain policies as well as public beliefs and opinions about adults and youth who have perpetrated sexual offenses. The current study systematically evaluated the impact of the "sex offender" and "JSO" labels through series of items administered to a nationally stratified and matched sample from across the United States. The study employed an experimental design, in which one group of participants (n = 498) ranked their levels of agreement with a series of statements utilizing these labels, and a control group (n = 502) responded to a matched set of statements substituting the labels with more neutral descriptive language. Findings support the hypothesis that use of the "sex offender" label strengthens public support for policies directed at those who have perpetrated sexual crimes, including public Internet disclosure, residency restrictions, and social networking bans. The "JSO" label is demonstrated to produce particularly robust effects, enhancing support for policies that subject youth to public Internet notification and affecting beliefs about youths' propensity to re-offend as adults. Implications for public policy, media communication, and research are explored and discussed.

Collateral Consequences of Juvenile Sex Offender Registration and Notification: Results From a Survey of Treatment Providers.

Among many in the research, policy, and practice communities, the application of sex offender registration and notification (SORN) to juveniles who sexually offend (JSO) has raised ongoing concerns regarding the potential collateral impacts on youths' social, mental health, and academic adjustment. To date, however, no published research has systematically examined these types of collateral consequences of juvenile SORN. Based on a survey of a national sample of treatment providers in the United States, this study investigates the perceived impact of registration and notification on JSO across five key domains: mental health, harassment and unfair treatment, school problems, living instability, and risk of reoffending. Results indicate that treatment providers overwhelmingly perceive negative consequences associated with registration with an incremental effect of notification indicating even greater concern across all five domains. Providers' demographics, treatment modalities, and client profile did not influence their perceptions of the collateral consequences suggesting that provider concern about the potential harm of SORN applied to juveniles is robust. Policy implications are discussed.

"Brothers Under the Bridge": Factors Influencing the Transience of Registered Sex Offenders in Florida.

The transience of registered sex offenders (RSOs) is a major impediment to reentry success, particularly because it has been linked to increased absconding and recidivism, and thus decreased community safety. Unfortunately, there is limited existing research on what factors most influence this transience. The purpose of this study was to identify and explore the relative influence of factors predicting transience for RSOs. Using data gathered from the Florida sex offender registry and multiple supplemental state and federal data sources, the analysis revealed a number of county- and individual-level characteristics that are associated with the likelihood of RSO transience. At the county level, these include residence restriction coverage, housing affordability, and population density. At the individual level, these include age, minority status, victim type (minor vs. adult), risk level, supervision status, and prior failure to register convictions. Implications for policy and practice are discussed.

Catch me if you can: an analysis of fugitive sex offenders.

The presumed dangers presented by sex offenders who have absconded from authorities have played a prominent role in public discourse surrounding state and federal sex offender management policy. The current study is the first to empirically investigate the characteristics of absconded sex offenders and explore how this group compares to other groups of sex offenders. Utilizing data from the Florida sex offender registry (N = 23,557), this exploratory study compares the characteristics and risk factors of absconders with those of compliant and noncompliant (nonabsconding) registrants as well as with those with convictions for failure to register (FTR). Absconders, as a group, were less likely than compliant registrants to be listed as predators, and less likely than both compliants and noncompliants to have a minor victim or to be a repeat sex offender. Absconders were also least likely to have a prior FTR conviction, but those with a previous FTR conviction were more likely to abscond from registration than probation. The findings fail to support the hypothesis that fugitive sex offenders are more sexually dangerous (especially to children), and suggest a multitude of explanations for absconding.

Karyotypic stasis and swarming influenced the evolution of viral tolerance in a species-rich bat radiation.

The emergence of COVID-19 and severe acute respiratory syndrome (SARS) has prioritized understanding bats' viral tolerance. Myotis bats are exceptionally species rich and have evolved viral tolerance. They also exhibit swarming, a cryptic behavior where large, multi-species assemblages gather for mating, which has been hypothesized to promote interspecific hybridization. To resolve the coevolution of genome architecture and their unusual antiviral tolerance, we undertook a phylogenomic analysis of 60 Old World Myotis genomes. We demonstrate an extensive history of introgressive hybridization that has replaced the species phylogeny across 17%-93% of the genome except for pericentromeric regions of macrochromosomes. Introgression tracts were enriched on microchromosome regions containing key antiviral pathway genes overexpressed during viral challenge experiments. Together, these results suggest that the unusual Myotis karyotype may have evolved to selectively position immune-related genes in high recombining genomic regions prone to introgression of divergent alleles, including a diversity of interleukin loci responsible for the release of pro-inflammatory cytokines.

A genomic timescale for placental mammal evolution.

The precise pattern and timing of speciation events that gave rise to all living placental mammals remain controversial. We provide a comprehensive phylogenetic analysis of genetic variation across an alignment of 241 placental mammal genome assemblies, addressing prior concerns regarding limited genomic sampling across species. We compared neutral genome-wide phylogenomic signals using concatenation and coalescent-based approaches, interrogated phylogenetic variation across chromosomes, and analyzed extensive catalogs of structural variants. Interordinal relationships exhibit relatively low rates of phylogenomic conflict across diverse datasets and analytical methods. Conversely, X-chromosome versus autosome conflicts characterize multiple independent clades that radiated during the Cenozoic. Genomic time trees reveal an accumulation of cladogenic events before and immediately after the Cretaceous-Paleogene (K-Pg) boundary, implying important roles for Cretaceous continental vicariance and the K-Pg extinction in the placental radiation.

Single-haplotype comparative genomics provides insights into lineage-specific structural variation during cat evolution.

The role of structurally dynamic genomic regions in speciation is poorly understood due to challenges inherent in diploid genome assembly. Here we reconstructed the evolutionary dynamics of structural variation in five cat species by phasing the genomes of three interspecies F1 hybrids to generate near-gapless single-haplotype assemblies. We discerned that cat genomes have a paucity of segmental duplications relative to great apes, explaining their remarkable karyotypic stability. X chromosomes were hotspots of structural variation, including enrichment with inversions in a large recombination desert with characteristics of a supergene. The X-linked macrosatellite DXZ4 evolves more rapidly than 99.5% of the genome clarifying its role in felid hybrid incompatibility. Resolved sensory gene repertoires revealed functional copy number changes associated with ecomorphological adaptations, sociality and domestication. This study highlights the value of gapless genomes to reveal structural mechanisms underpinning karyotypic evolution, reproductive isolation and ecological niche adaptation.

Reappraisal of gap analysis for effusive crises at Piton de la Fournaise.

Effective and rapid effusive crisis response is necessary to mitigate the risks associated with lava flows that could threaten or inundate inhabited or visited areas. At Piton de la Fournaise (La Réunion, France), well-established protocols between Observatoire Volcanologique du Piton de la Fournaise - Institut de Physique du Globe de Paris (OVPF-IPGP) and civil protection, and between scientists of a multinational array of institutes, allow effective tracking of eruptive crises and hazard management embracing all stakeholders. To assess the outstanding needs for such responses Tsang and Lindsay (J Appl Volcanol 9:9, 2020) applied a gap analysis to assess research gaps in terms of preparedness, response and recovery at 11 effusive centers, including Piton de la Fournaise. For Piton de la Fournaise, their gap analysis implied widespread gaps in the state of knowledge. However, their work relied on incomplete and erroneous data and methods, resulting in a gap analysis that significantly underrepresented this state of knowledge. We thus here re-build a correct database for Piton de la Fournaise, properly define the scope of an appropriate gap analysis, and provide a robust gap analysis, finding that there are, actually, very few gaps for Piton de la Fournaise. This is a result of the existence of a great quantity of published work in the peer-reviewed literature, as well as frequent reports documenting event impact in the local press and observatory reports. At Piton de la Fournaise, this latter (observatory-based) resource is largely due to the efforts of OVPF-IPGP who have a wealth of experience having responded to 81 eruptions since its creation in 1979 through the end of September 2021. Although welcome and necessary, especially if it is made by a group of scientists outside the local management of the volcanic risk (i.e., a neutral group), such gap analysis need to be sure to fully consider all available peer-reviewed literature, as well as newspaper reports, observatory releases and non-peer-reviewed eruption reports, so as to be complete and correct. Fundamentally, such an analysis needs to consider the information collected and produced by the volcano observatory charged with handling surveillance operations and reporting duties to civil protection for the volcano under analysis. As a very minimum, to ensure that a necessarily comprehensive and complete treatment of the scientific literature has been completed, we recommend that a third party expert, who is a recognized specialist in terms of research at the site considered, reviews and checks the material used for the gap analysis before final release of recommendations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13617-021-00111-w.

Magma fragmentation and particle size distributions in low intensity mafic explosions: the July/August 2015 Piton de la Fournaise eruption.

Understanding magma fragmentation mechanisms in explosive eruptions is a key requirement for volcanic hazard assessment, eruption management and risk mitigation. This paper focuses on a type case small explosivity eruption (July-August 2015 eruption of Piton de la Fournaise). These eruptions, despite being often overlooked, are exceedingly frequent on local-to-global scales and constitute a significant hazard in vent-proximal areas, which are often populated by guides, tourists and, indeed, volcanologists due to their accessibility. The explosions presented here are ideal cases for the study of the dynamics of magma fragmentation and how it relates to the size distribution of scoria generated at the vent. We documented these events visually and thermally, and characterised the products through sample-return. This allowed us to describe small-scale gas bursts sending ejecta up to 30 m during intermittent lava fountains. Surface tension instabilities and inertial forces played a major role in fragmentation processes and generated particles with coarse-skewed distributions and median diameters ranging from - 8 to - 10 ϕ. However, with time distributions of particles in the most energetic fountains shifted towards more symmetrical shapes as median grains sizes became finer. Analyses of sequences of images demonstrate that the evolution of particle size distributions with time is due to instability of magma droplets and (in-flight) fragmentation.

Protective and reversal actions of a novel peptidomimetic against a pivotal toxin implicated in Alzheimer's disease.

Despite the many attempts to understand the aetiology of Alzheimer's disease, the basic mechanisms accounting for the progressive cycle of neuronal loss are still unknown. Previous work has suggested that the pivotal molecule mediating neurodegeneration could be an independently acting peptide cleaved from acetylcholinesterase. This previously unidentified agent acts as a signalling molecule in selectively vulnerable groups of cells where erstwhile developmental mechanisms are activated inappropriately to have a toxic effect in the context of the mature brain. We have previously shown that the toxic actions of this peptide, whose level is doubled in the Alzheimer brain, can be blocked by a cyclised variant (NBP14). However, the size and properties of NBP14 would render it unlikely as a feasible therapeutic candidate. Here therefore we test a synthetic peptidomimetic (NB-0193), modelled on the binding of NBP14 to the target alpha-7 nicotinic receptor, and benchmarked against it to screen for reversal effects using real-time optical imaging in rat brain slices. The blocking action of NB-0193 was confirmed by testing its effect against peptide-induced calcium influx in cell cultures, where it showed a dose-dependent profile over a trophic-toxic range. Moreover, NB-0193 presented promising pharmacokinetic characteristics and could therefore prompt a new therapeutic approach against Alzheimer's disease.

One-, two- and three-phase viscosity treatments for basaltic lava flows.

Lava flows comprise three-phase mixtures of melt, crystals, and bubbles. While existing one-phase treatments allow melt phase viscosity to be assessed on the basis of composition, water content, and/or temperature, two-phase treatments constrain the effects of crystallinity or vesicularity on mixture viscosity. However, three-phase treatments, allowing for the effects of coexisting crystallinity and vesicularity, are not well understood. We investigate existing one- and two-phase treatments using lava flow case studies from Mauna Loa (Hawaii) and Mount Etna (Italy) and compare these with a three-phase treatment that has not been applied previously to basaltic mixtures. At Etna, melt viscosities of 425 ± 30 Pa s are expected for well-degassed (0.1 w. % H(2)O), and 135 ± 10 Pa s for less well-degassed (0.4 wt % H(2)O), melt at 1080°C. Application of a three-phase model yields mixture viscosities (45% crystals, 25-35% vesicles) in the range 5600-12,500 Pa s. This compares with a measured value for Etnean lava of 9400 ± 1500 Pa s. At Mauna Loa, the three-phase treatment provides a fit with the full range of field measured viscosities, giving three-phase mixture viscosities, upon eruption, of 110-140 Pa s (5% crystals, no bubble effect due to sheared vesicles) to 850-1400 Pa s (25-30% crystals, 40-60% spherical vesicles). The ability of the three-phase treatment to characterize the full range of melt-crystal-bubble mixture viscosities in both settings indicates the potential of this method in characterizing basaltic lava mixture viscosity.

Collateral Consequences and Effectiveness of Sex Offender Registration and Notification: Law Enforcement Perspectives.

A growing body of research has examined the collateral effects of sex offender registration and notification (SORN), particularly those related to offenders' social and economic reintegration into society. Although studies have examined public, offender, treatment provider, and other criminal justice perspectives on SORN's collateral impacts, few have elicited the views of law enforcement (LE) professionals who have contact with registered offenders. This study presents results from a mixed method study examining LE perspectives on collateral consequences and effectiveness of SORN. Results indicate that, although overall LE concern regarding collateral impacts is limited, those who are most engaged in SORN-related duties are significantly more likely to indicate such concern, and also more likely to believe that SORN was an effective public safety tool. Importantly, respondents in states with larger registries expressed greater concern over collateral consequences, and less belief in SORN's public safety efficacy. Implications for policy and practice are discussed.

Dose-dependent effect and pharmacokinetics of fexinidazole and its metabolites in a mouse model of human African trypanosomiasis.

Human African trypanosomiasis (HAT) is a neglected tropical disease, with a population of 70 million at risk. Current treatment options are limited. In the search for new therapeutics, the repurposing of the broad-spectrum antiprotozoal drug fexinidazole has completed Phase III trials with the anticipation that it will be the first oral treatment for HAT. This study used the recently validated bioluminescence imaging model to assess the dose and rate of kill effect of fexinidazole in infected mice, and the dose-dependent effect of fexinidazole on trypanosome infection. Pharmacokinetics of fexinidazole in plasma and central nervous system (CNS) compartments were similar in both infected and uninfected mice. Drug distribution within the CNS was further examined by microdialysis, showing similar levels in the cortex and hippocampus. However, high variability in drug distribution and exposure was found between mice.

Sexual offender recidivism risk: what we know and what we need to know.

If all sexual offenders are dangerous, why bother assessing their risk to reoffend? Follow-up studies, however, typically find sexual recidivism rates of 10%-15% after five years, 20% after 10 years, and 30%-40% after 20 years. The observed rates underestimate the actual rates because not all offences are detected; however, the available research does not support the popular notion that sexual offenders inevitably reoffend. Some sexual offenders are more dangerous than others. Much is known about the static, historical factors associated with increased recidivism risk (e.g., prior offences, age, and relationship to victims). Less is known about the offender characteristics that need to change in order to reduce that risk. There has been considerable research in recent years demonstrating that structured risk assessments are more accurate than unstructured clinical assessments. Nevertheless, the limitations of actuarial risk assessments are sufficient that experts have yet to reach consensus on the best methods for combining risk factors into an overall evaluation.