Sin Nombre Virus and the Emergence of Other Hantaviruses: A Review of the Biology, Ecology, and Disease of a Zoonotic Pathogen.

Sin Nombre virus (SNV) is an emerging virus that was first discovered in the Four Corners region of the United States in 1993. The virus causes a disease known as Hantavirus Pulmonary Syndrome (HPS), sometimes called Hantavirus Cardiopulmonary Syndrome (HCPS), a life-threatening illness named for the predominance of infection of pulmonary endothelial cells. SNV is one of several rodent-borne hantaviruses found in the western hemisphere with the capability of causing this disease. The primary reservoir of SNV is the deer mouse (Peromyscus maniculatus), and the virus is transmitted primarily through aerosolized rodent excreta and secreta. Here, we review the history of SNV emergence and its virus biology and relationship to other New World hantaviruses, disease, treatment, and prevention options.

Forty years of monitoring increasing sea turtle relative abundance in the Gulf of Mexico.

Longitudinal data sets for population abundance are essential for studies of imperiled organisms with long life spans or migratory movements, such as marine turtles. Population status trends are crucial for conservation managers to assess recovery effectiveness. A direct assessment of population growth is the enumeration of nesting numbers and quantifying nesting attempts (successful nests/unsuccessful attempts) and emergence success (number of hatchlings leaving the nest) because of the substantial annual variations due to nest placement, predation, and storm activity. We documented over 133,000 sea turtle crawls for 50.9 km of Florida Gulf of Mexico coastline from 1982 to 2021 for a large loggerhead turtle nesting aggregation and a recovering remnant population of green sea turtles. Over time both species have emerged to nest significantly earlier in the year and green sea turtle nesting seasons have extended. Nest counts and hatchling production for both species have significantly increased, but the rate of emergence success of hatchlings leaving nests has not changed for loggerheads and has declined for green sea turtles. Sea level rise and coastal developments undoubtedly influence coastal habitats in the long-term, impacting nest site selection and potential recruitment from the loss of emerged hatchlings. However, the present indications for steady Gulf of Mexico recovery of loggerhead and green sea turtles counter findings of the Florida Atlantic coasts. This study indicates that effective conservation practices can be detected within time scales of 1-2 turtle generations.

Role of Differences in Respiratory Syncytial Virus F and G Glycoproteins on Susceptibility to Inactivation by Antimicrobial Peptides LL-37 and Human Beta-Defensins.

Antimicrobial peptides are proteins that have been found to be an important factor in the natural immune response to a variety of pathogens. Respiratory syncytial virus (RSV) is a respiratory pathogen with the capability to cause serious upper and lower respiratory infections in infants and children and is a major viral cause of infant mortality. There is currently no functional vaccine for the virus, as recent efforts have been hindered by the virus's low immunogenicity, its ability to effectively mutate, and underlying instabilities of potential vaccines. Previous studies have shown that antimicrobial peptides may affect viral replication and spread of RSV. Our study evaluates the susceptibility of chimeric strains of RSV that express different fusion (F) and attachment (G) proteins to susceptibilities to inactivation by LL-37 and human beta-defensins (hBDs) hBD-1, hBD-3, and hBD-4. We show that LL-37 and hBD-3 result in dose-dependent, strain-independent inactivation of RSV, whereas treatment with either hBD-1 or hBD-4 appears more variable between strains. This suggests a potential role of the viral structural proteins in mitigating the inhibitory effects of the peptides. This study provides the first evidence of the sensitivity of RSV to several hBDs and indicates a role of LL-37 and beta-defensins in both limiting establishment of natural RSV infections and in the therapeutic treatment of severe RSV disease.

Examining the lineage autonomous role of ß3-integrin in muscle regeneration.

Skeletal muscles can regenerate over the lifetime from resident muscle stem cells (MuSCs). Interactions between MuSCs and extracellular matrix (ECM) proteins are essential for muscle regeneration. The best-known receptors for ECM proteins are integrins, a family composed of twenty-some heterodimeric combinations of an α- and a ß-subunit. ß1-integrin (encoded by Itgb1) is required for quiescence, proliferation, migration, and fusion of Pax7+ MuSCs in the mouse model. ß3-integrin (encoded by Itgb3) has been reported to be critical for the myogenic differentiation of C2C12 myoblasts, and Itgb3 germline mutant mice were shown to regenerate few if any myofibers after injury. To investigate the autonomous role of Itgb3 in the myogenic lineage in vivo, we conditionally inactivated a floxed Itgb3 allele (Itgb3F ) by constitutive Pax7-Cre and tamoxifen-inducible Pax7-CreERT2 drivers. Unexpectedly, we found no defects in muscle regeneration in both conditional knockout models. In vitro studies using Itgb3 mutant myoblasts or RNAi knockdown of Itgb3 in myoblasts also did not reveal a role for myogenic differentiation. As ß1- and ß3-integrins share ECM ligands and downstream signaling effectors, we further examined Itgb3's role in a Itgb1 haploid background. Still, we found no evidence for an autonomous role of Itgb3 in muscle regeneration in vivo. Thus, while Itgb3 is critical for the differentiation of C2C12 cells, the regenerative defects reported for the Itgb3 germline mutant are not due to its role in the MuSC. We conclude that if ß3-integrin does have a role in Pax7+ MuSCs, it is compensated by ß1- and/or another ß-integrin(s).

Does transcatheter aortic valve alignment matter?

Objective: This study investigates the effect of transcatheter aortic valve (TAV) angular alignment on the postprocedure haemodynamics. TAV implantation has emerged as an effective alternative to surgery when treating valve dysfunction. However, the benefit of avoiding surgery is paid back by the inability to remove the native diseased leaflets and accurately position the device in relation to the aortic root, and the literature has shown the root anatomy and substitute position can play an essential role on valve function. Methods: A commercial TAV was placed in a silicone mock aortic root in vitro, including mock native leaflets, and either aligned commissure-to-commissure or in maximum misalignment. Haemodynamic performance data at various stroke volumes were measured, and Particle Image Velocimetry analysis was performed at a typical stroke volume for rest conditions. The two configurations were also studied without mock native leaflets, for comparison with previous in vitro studies. Results: Haemodynamic performance data were similar for all configurations. However, imaging analysis indicated that valve misalignment resulted in the central jet flow not extending to the root wall in the native commissures' vicinity, replaced by a low shear flow, and a reduction of upper sinus flow of 40%, increasing flow stagnation in the sinus. Conclusions: TAV misalignment did not result in a significant change in valve hydrodynamic performance, but determined some change in the fluid flow patterns, which may promote pathological scenarios, such as increased thrombogenicity of blood flow within the sinuses of Valsalva, and plaque formation around the lumen of the sinotubular junction.

Cell volume changes contribute to epithelial morphogenesis in zebrafish Kupffer's vesicle.

How epithelial cell behaviors are coordinately regulated to sculpt tissue architecture is a fundamental question in biology. Kupffer's vesicle (KV), a transient organ with a fluid-filled lumen, provides a simple system to investigate the interplay between intrinsic cellular mechanisms and external forces during epithelial morphogenesis. Using 3-dimensional (3D) analyses of single cells we identify asymmetric cell volume changes along the anteroposterior axis of KV that coincide with asymmetric cell shape changes. Blocking ion flux prevents these cell volume changes and cell shape changes. Vertex simulations suggest cell shape changes do not depend on lumen expansion. Consistent with this prediction, asymmetric changes in KV cell volume and shape occur normally when KV lumen growth fails due to leaky cell adhesions. These results indicate ion flux mediates cell volume changes that contribute to asymmetric cell shape changes in KV, and that these changes in epithelial morphology are separable from lumen-generated forces.

Mosaic Labeling and 3-Dimensional Morphological Analysis of Single Cells in the Zebrafish Left-right Organizer.

A transient epithelial structure called the left-right organizer (LRO) establishes left-right asymmetry in vertebrate embryos. Developmental defects that alter LRO formation result in left-right patterning errors that often lead to congenital heart malformations. However, little is known about mechanisms that regulate individual cell behaviors during LRO formation. To address this, we developed a Cre-loxP based method to mosaically label precursor cells, called dorsal forerunner cells, that give rise to the zebrafish LRO known as Kupffer's vesicle. This methodology allows lineage tracing, 3-dimensional (3D) reconstruction and morphometric analysis of single LRO cells in living embryos. The ability to visualize and quantify individual LRO cell dynamics provides an opportunity to advance our understanding of LRO development, and in a broader sense, investigate the interplay between intrinsic biochemical mechanisms and extrinsic mechanical forces that drive morphogenesis of epithelial tissues.

Employers' perception of the costs and the benefits of hiring individuals with autism spectrum disorder in open employment in Australia.

Research has examined the benefits and costs of employing adults with autism spectrum disorder (ASD) from the perspective of the employee, taxpayer and society, but few studies have considered the employer perspective. This study examines the benefits and costs of employing adults with ASD, from the perspective of employers. Fifty-nine employers employing adults with ASD in open employment were asked to complete an online survey comparing employees with and without ASD on the basis of job similarity. The findings suggest that employing an adult with ASD provides benefits to employers and their organisations without incurring additional costs.

Paxillin genes and actomyosin contractility regulate myotome morphogenesis in zebrafish.

Paxillin (Pxn) is a key adapter protein and signaling regulator at sites of cell-extracellular matrix (ECM) adhesion. Here, we investigated the role of Pxn during vertebrate development using the zebrafish embryo as a model system. We have characterized two Pxn genes, pxna and pxnb, in zebrafish that are maternally supplied and expressed in multiple tissues. Gene editing and antisense gene knockdown approaches were used to uncover Pxn functions during zebrafish development. While mutation of either pxna or pxnb alone did not cause gross embryonic phenotypes, double mutants lacking maternally supplied pxna or pxnb displayed defects in cardiovascular, axial, and skeletal muscle development. Transient knockdown of Pxn proteins resulted in similar defects. Irregular myotome shape and ECM composition were observed, suggesting an "inside-out" signaling role for Paxillin genes in the development of myotendinous junctions. Inhibiting non-muscle Myosin-II during somitogenesis altered the subcellular localization of Pxn protein and phenocopied pxn gene loss-of-function. This indicates that Paxillin genes are effectors of actomyosin contractility-driven morphogenesis of trunk musculature in zebrafish. Together, these results reveal new functions for Pxn during muscle development and provide novel genetic models to elucidate Pxn functions.

Evolution and Expression of Paxillin Genes in Teleost Fish.

BACKGROUND: Paxillin family proteins regulate intracellular signaling downstream of extracellular matrix adhesion. Tissue expression patterns and cellular functions of Paxillin proteins during embryo development remain poorly understood. Additionally, the evolution of this gene family has not been thoroughly investigated. RESULTS: This report characterizes the evolution and expression of a novel Paxillin gene, called Paxillin-b, in Teleosts. Alignments indicate that Teleost Paxillin-a and Paxillin-b proteins are highly homologous to each other and to human Paxillin. Phylogenetic and synteny analyses suggest that these genes originated from the duplication of an ancestral Paxillin gene that was in a common ancestor of Teleosts and Tetrapods. Analysis of the spatiotemporal expression profiles of Paxillin-a and Paxillin-b using zebrafish revealed both overlapping and distinct domains for Paxillin-a and Paxillin-b during embryo development. Localization of zebrafish Paxillin orthologs expressed in mammalian cells demonstrated that both proteins localize to focal adhesions, similar to mammalian Paxillin. This suggests these proteins regulate adhesion-dependent processes in their endogenous tissues. CONCLUSION: Paxillin-a and Paxillin-b were generated by duplication in Teleosts. These genes likely play similar roles as Paxillin genes in other organisms. This work provides a framework for functional investigation of Paxillin family members during development using the zebrafish as an in vivo model system.

The Costs and Benefits of Employing an Adult with Autism Spectrum Disorder: A Systematic Review.

BACKGROUND: Despite an ambition from adults with Autism Spectrum Disorder (ASD) to be employed, there are limited opportunities for competitive employment for this group. Employment is not only an entitlement enjoyed by others in society, but employing adults with ASD also has economic benefits by decreasing lost productivity and resource costs for this group. Few studies have explored the cost-benefit ratio for employing adults with ASD and even fewer have taken the viewpoint of the employer, particularly applying this situation to ASD. Until such study occurs, employers may continue to be reluctant to employ adults from this group. OBJECTIVE: This review aimed to examine the costs, benefits and the cost-benefit ratio of employing adults with ASD, from a societal perspective and from the perspective of employers. METHODS: Eight databases were searched for scientific studies within defined inclusion criteria. These databases included CINAHL Plus, Cochrane Library, Emerald, Ovid Medline, ProQuest, PsycINFO, Scopus and Web of Science. RESULTS AND CONCLUSION: Enhancing the opportunities for adults with ASD to join the workforce is beneficial from a societal perspective, not only from an inclusiveness viewpoint, but also from a strict economic standpoint. Providing supported employment services for adults with ASD does not only cut the cost compared with providing standard care, it also results in better outcomes for adults with ASD. Despite the fact that ASD was the most expensive group to provide vocational rehabilitation services for, adults with ASD have a strong chance of becoming employed once appropriate measures are in place. Hence, rehabilitation services could be considered as a worthwhile investment. The current systematic review uncovered the fact that very few studies have examined the benefits, the costs and the cost-benefit ratio of employing an adult with ASD from the perspective of employers indicating a need for this topic to be further explored.