City divided: Unveiling family ties and genetic structuring of coyotes in Seattle.

Linear barriers pose significant challenges for wildlife gene flow, impacting species persistence, adaptation, and evolution. While numerous studies have examined the effects of linear barriers (e.g., fences and roadways) on partitioning urban and non-urban areas, understanding their influence on gene flow within cities remains limited. Here, we investigated the impact of linear barriers on coyote (Canis latrans) population structure in Seattle, Washington, where major barriers (i.e., interstate highways and bodies of water) divide the city into distinct quadrants. Just under 1000 scats were collected to obtain genetic data between January 2021 and December 2022, allowing us to identify 73 individual coyotes. Notably, private allele analysis underscored limited interbreeding among quadrants. When comparing one quadrant to each other, there were up to 16 private alleles within a single quadrant, representing nearly 22% of the population allelic diversity. Our analysis revealed weak isolation by distance, and despite being a highly mobile species, genetic structuring was apparent between quadrants even with extremely short geographic distance between individual coyotes, implying that Interstate 5 and the Ship Canal act as major barriers. This study uses coyotes as a model species for understanding urban gene flow and its consequences in cities, a crucial component for bolstering conservation of rarer species and developing wildlife friendly cities.

An overwinter protocol for detecting wolverines and other carnivores at camera traps paired with automated scent dispensers.

Camera traps deployed with olfactory attractants are used to survey rare and elusive carnivores. Study areas with deep snowpack and rugged terrain present challenges and risks to field personnel, who traditionally must revisit camera stations regularly to refresh attractants. In such locations, alternative overwinter survey protocols that include a persistent attractant would improve both the safety and efficiency of camera-trap surveys. We present a protocol for installing camera traps and automated scent dispensers on trees at above-average maximum snow depth to eliminate the need for interim service visits and to enable standardized surveys to be conducted throughout the year. Our protocol proved to be effective at attracting and detecting numerous and repeated visits by wolverines, fishers, and other carnivores in two montane regions of the western contiguous United States. The volume, timing, and composition of liquid scent lure released by automated scent dispensers can be varied to target multiple species of interest, and the dispenser can be used in situations where bait rewards may influence the behavior of target species and/or pose human safety concerns.

Gentrification drives patterns of alpha and beta diversity in cities.

While there is increasing recognition that social processes in cities like gentrification have ecological consequences, we lack nuanced understanding of the ways gentrification affects urban biodiversity. We analyzed a large camera trap dataset of mammals (>500 g) to evaluate how gentrification impacts species richness and community composition across 23 US cities. After controlling for the negative effect of impervious cover, gentrified parts of cities had the highest mammal species richness. Change in community composition was associated with gentrification in a few cities, which were mostly located along the West Coast. At the species level, roughly half (11 of 21 mammals) had higher occupancy in gentrified parts of a city, especially when impervious cover was low. Our results indicate that the impacts of gentrification extend to nonhuman animals, which provides further evidence that some aspects of nature in cities, such as wildlife, are chronically inaccessible to marginalized human populations.

Urbanization, climate and species traits shape mammal communities from local to continental scales.

Human-driven environmental changes shape ecological communities from local to global scales. Within cities, landscape-scale patterns and processes and species characteristics generally drive local-scale wildlife diversity. However, cities differ in their structure, species pools, geographies and histories, calling into question the extent to which these drivers of wildlife diversity are predictive at continental scales. In partnership with the Urban Wildlife Information Network, we used occurrence data from 725 sites located across 20 North American cities and a multi-city, multi-species occupancy modelling approach to evaluate the effects of ecoregional characteristics and mammal species traits on the urbanization-diversity relationship. Among 37 native terrestrial mammal species, regional environmental characteristics and species traits influenced within-city effects of urbanization on species occupancy and community composition. Species occupancy and diversity were most negatively related to urbanization in the warmer, less vegetated cities. Additionally, larger-bodied species were most negatively impacted by urbanization across North America. Our results suggest that shifting climate conditions could worsen the effects of urbanization on native wildlife communities, such that conservation strategies should seek to mitigate the combined effects of a warming and urbanizing world.

A Dietary Supplement Containing Fucoidan Preserves Endothelial Glycocalyx through ERK/MAPK Signaling and Protects against Damage Induced by CKD Serum.

(1) Damage to the endothelial glycocalyx (eGC), a protective layer lining the endothelial luminal surface, is associated with chronic kidney disease (CKD), which leads to a worsening of cardiovascular outcomes in these patients. Currently, there are no targeted therapeutic approaches. Whether the dietary supplement EndocalyxTM (ECX) protects against endothelial damage caused by uremic toxins is unknown. (2) We addressed this question by performing atomic force microscopy measurements on living endothelial cells. We examined the effect of ECX on eGC thickness at baseline and with pooled serum from hemodialysis patients. ECX was also successfully administered in vivo in mice, in which eGC was assessed using perfused boundary region measurements by intravital microscopy of cremasteric vessels. (3) Both ECX and fucoidan significantly improved baseline eGC thickness. Our data indicate that these effects are dependent on ERK/MAPK and PI3K signaling. After incubation with eGC damaging serum from dialysis patients, ECX increased eGC height. Intravital microscopy in mice revealed a relevant increase in baseline eGC dimensions after feeding with ECX. (4) We identified a dietary supplement containing glycocalyx substrates and fucoidan as potential mediators of eGC preservation in vitro and in vivo. Our findings suggest that fucoidan may be an essential component responsible for protecting the eGC in acute settings. Moreover, ECX might contribute to both protection and rebuilding of the eGC in the context of CKD.

Prevention of Tracheostomy-Related Pressure Injury: A Systematic Review and Meta-analysis.

BACKGROUND: In the critical care environment, individuals who undergo tracheostomy are highly susceptible to tracheostomy-related pressure injuries. OBJECTIVE: To evaluate the effectiveness of interventions to reduce tracheostomy-related pressure injury in the critical care setting. METHODS: MEDLINE, Embase, CINAHL, and the Cochrane Library were searched for studies of pediatric or adult patients in intensive care units conducted to evaluate interventions to reduce tracheostomy-related pressure injury. Reviewers independently extracted data on study and patient characteristics, incidence of tracheostomy-related pressure injury, characteristics of the interventions, and outcomes. Study quality was assessed using the Cochrane Collaboration's risk-of-bias criteria. RESULTS: Ten studies (2 randomized clinical trials, 5 quasi-experimental, 3 observational) involving 2023 critically ill adult and pediatric patients met eligibility criteria. The incidence of tracheostomy-related pressure injury was 17.0% before intervention and 3.5% after intervention, a 79% decrease. Pressure injury most commonly involved skin in the peristomal area and under tracheostomy ties and flanges. Interventions to mitigate risk of tracheostomy-related pressure injury included modifications to tracheostomy flange securement with foam collars, hydrophilic dressings, and extended-length tracheostomy tubes. Interventions were often investigated as part of care bundles, and there was limited standardization of interventions between studies. Meta-analysis supported the benefit of hydrophilic dressings under tracheostomy flanges for decreasing tracheostomy-related pressure injury. CONCLUSIONS: Use of hydrophilic dressings and foam collars decreases the incidence of tracheostomy-related pressure injury in critically ill patients. Evidence regarding individual interventions is limited by lack of sensitive measurement tools and by use of bundled interventions. Further research is necessary to delineate optimal interventions for preventing tracheostomy-related pressure injury.

Prevention of Endotracheal Tube-Related Pressure Injury: A Systematic Review and Meta-analysis.

BACKGROUND: Hospital-acquired pressure injuries, including those related to airway devices, are a significant source of morbidity in critically ill patients. OBJECTIVE: To determine the incidence of endotracheal tube-related pressure injuries in critically ill patients and to evaluate the effectiveness of interventions designed to prevent injury. METHODS: MEDLINE, Embase, CINAHL, and the Cochrane Library were searched for studies of pediatric or adult patients in intensive care units that evaluated interventions to reduce endotracheal tube-related pressure injury. Reviewers extracted data on study and patient characteristics, incidence of pressure injury, type and duration of intervention, and outcomes. Risk of bias assessment followed the Cochrane Collaboration's criteria. RESULTS: Twelve studies (5 randomized clinical trials, 3 quasi-experimental, 4 observational) representing 9611 adult and 152 pediatric patients met eligibility criteria. The incidence of pressure injury was 4.2% for orotracheal tubes and 21.1% for nasotracheal tubes. Interventions included anchor devices, serial endotracheal tube assessment or repositioning, and barrier dressings for nasotracheal tubes. Meta-analysis revealed that endotracheal tube stabilization was the most effective individual intervention for preventing pressure injury. Nasal alar barrier dressings decreased the incidence of skin or mucosal injury in patients undergoing nasotracheal intubation, and data on effectiveness of serial assessment and repositioning were inconclusive. CONCLUSIONS: Airway device-related pressure injuries are common in critically ill patients, and patients with nasotracheal tubes are particularly susceptible to iatrogenic harm. Fastening devices and barrier dressings decrease the incidence of injury. Evidence regarding interventions is limited by lack of standardized assessments.

PDGFR dimer-specific activation, trafficking and downstream signaling dynamics.

Signaling through the platelet-derived growth factor receptors (PDGFRs) plays a critical role in multiple cellular processes during development. The two PDGFRs, PDGFRα and PDGFRß, dimerize to form homodimers and/or heterodimers. Here, we overcome previous limitations in studying PDGFR dimer-specific dynamics by generating cell lines stably expressing C-terminal fusions of each PDGFR with bimolecular fluorescence complementation (BiFC) fragments corresponding to the N-terminal or C-terminal regions of the Venus fluorescent protein. We find that PDGFRß receptors homodimerize more quickly than PDGFRα receptors in response to PDGF ligand, with increased levels of autophosphorylation. Furthermore, we demonstrate that PDGFRα homodimers are trafficked and degraded more quickly, whereas PDGFRß homodimers are more likely to be recycled back to the cell membrane. We show that PDGFRß homodimer activation results in a greater amplitude of phospho-ERK1/2 and phospho-AKT signaling, as well as increased proliferation and migration. Finally, we demonstrate that inhibition of clathrin-mediated endocytosis leads to changes in cellular trafficking and downstream signaling, particularly for PDGFRα homodimers. Collectively, our findings provide significant insight into how biological specificity is introduced to generate unique responses downstream of PDGFR engagement. This article has an associated First Person interview with the first author of the paper.

Expression of ABC transporters during syncytialization in preeclampsia.

Preeclampsia complicates 2-8% of pregnancies and is associated with prematurity and intrauterine growth restriction. Cholesterol and sterol transport is a key function of the placenta and it is elicited through ATP binding cassette (ABC) transporters. ABCA1 expression changes during trophoblast cell fusion, a process required to form the placental syncytium that enables maternal-fetal nutrient transfer. ABCA1 expression is dysregulated in preeclamptic placentas. But whether ABC transporters expression during trophoblast fusion is disrupted in preeclampsia remains unknown. We investigated if cholesterol and sterol ABC transporters are altered in term and preterm preeclampsia placentas and during human cytotrophoblast syncytialization. Human placental biopsies were collected from healthy term (≥37 weeks; n = 11) and term preeclamptic (≥36 6/7 weeks; n = 8) and pre-term preeclamptic (28-35 weeks; n = 8) pregnancies. Both, protein and mRNA expression for ABCA1, ABCG1, ABCG5, and ABCG8 were evaluated. Primary cytotrophoblasts isolated from a subset of placentas were induced to syncytialize for 96 h and ABCA1, ABCG1 and ABCG8 mRNA expression evaluated at 0 h and 96 h. Protein and gene expression of ABC transporters were not altered in preeclamptic placentas. In the healthy Term group, ABCA1 expression was similar before and after syncytialization. After 96 h of syncytialization, mRNA expression of ABCA1 and ABCG1 increased significantly, while ABCG8 decreased significantly in term-preeclampsia, but not pre-term preeclampsia. While placental expression of ABCA1 and ABCG1 remained unaltered in term preeclampsia, the disruption in their dynamic expression pattern during cytotrophoblast syncytialization suggests that cholesterol transport may contribute to the pathophysiologic role of the placenta in preeclampsia.

Wealth and urbanization shape medium and large terrestrial mammal communities.

Urban biodiversity provides critical ecosystem services and is a key component to environmentally and socially sustainable cities. However, biodiversity varies greatly within and among cities, leading to human communities with changing and unequal experiences with nature. The "luxury effect," a hypothesis that predicts a positive correlation between wealth, typically measured by per capita income, and species richness may be one indication of these inequities. While the luxury effect is well studied for some taxa, it has rarely been investigated for mammals, which provide unique ecosystem services (e.g., biological pest control) and exhibit significant potential for negative human-wildlife interactions (e.g., nuisances or conflicts). We analyzed a large dataset of mammal detections across 20 North American cities to test whether the luxury effect is consistent for medium- to large-sized terrestrial mammals across diverse urban contexts. Overall, support for the luxury effect, as indicated by per capita income, was inconsistent; we found evidence of a luxury effect in approximately half of our study cities. Species richness was, however, highly and negatively correlated with urban intensity in most cities. We thus suggest that economic factors play an important role in shaping urban mammal communities for some cities and species, but that the strongest driver of urban mammal diversity is urban intensity. To better understand the complexity of urban ecosystems, ecologists and social scientists must consider the social and political factors that drive inequitable human experiences with nature in cities.

Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk.

Epidemiological studies indicate that elevated alkaline phosphatase activity is associated with increased cardiovascular disease risk. Other epidemiological data demonstrate that mothers giving multiple childbirths (multipara) are also at increased risk of developing late-onset cardiovascular disease. We hypothesized that these two associations stem from a common cause, the insufficient plasma level of the ectopic mineralization inhibitor inorganic pyrophosphate, which is a substrate of alkaline phosphatase. As alkaline phosphatase activity is elevated in pregnancy, we hypothesized that pyrophosphate concentrations decrease gestationally, potentially leading to increased maternal vascular calcification and cardiovascular disease risk in multipara. We investigated plasma pyrophosphate kinetics pre- and postpartum in sheep and at term in humans and demonstrated its shortage in pregnancy, mirroring alkaline phosphatase activity. Next, we tested whether multiparity is associated with increased vascular calcification in pseudoxanthoma elasticum patients, characterized by low intrinsic plasma pyrophosphate levels. We demonstrated that these patients had increased vascular calcification when they give birth multiple times. We propose that transient shortages of pyrophosphate during repeated pregnancies might contribute to vascular calcification and multiparity-associated cardiovascular disease risk threatening hundreds of millions of healthy women worldwide. Future trials are needed to assess if gestational pyrophosphate supplementation might be a suitable prophylactic treatment to mitigate maternal cardiovascular disease risk in multiparous women.

Pdgfra and Pdgfrb Genetically Interact in the Murine Neural Crest Cell Lineage to Regulate Migration and Proliferation.

Cranial neural crest cells (cNCCs) are migratory, multipotent cells that originate from the forebrain to the hindbrain and eventually give rise to the cartilage and bone of the frontonasal skeleton, among other derivatives. Signaling through the two members of the platelet-derived growth factor receptor (PDGFR) family of receptor tyrosine kinases, alpha and beta, plays critical roles in the cNCC lineage to regulate craniofacial development during murine embryogenesis. Further, the PDGFRs have been shown to genetically interact during murine craniofacial development at mid-to-late gestation. Here, we examined the effect of ablating both Pdgfra and Pdgfrb in the murine NCC lineage on earlier craniofacial development and determined the cellular mechanisms by which the observed phenotypes arose. Our results confirm a genetic interaction between the two receptors in this lineage, as phenotypes observed in an allelic series of mutant embryos often worsened with the addition of conditional alleles. The defects observed here appear to stem from aberrant cNCC migration, as well as decreased proliferation of the facial mesenchyme upon combined decreases in PDGFRα and PDGFRß signaling. Importantly, we found that PDGFRα plays a predominant role in cNCC migration whereas PDGFRß primarily contributes to proliferation of the facial mesenchyme past mid-gestation. Our findings provide insight into the distinct mechanisms by which PDGFRα and PDGFRß signaling regulate cNCC activity and subsequent craniofacial development in the mouse embryo.

Formin-like 1 mediates effector T cell trafficking to inflammatory sites to enable T cell-mediated autoimmunity.

Lymphocyte migration is essential for the function of the adaptive immune system, and regulation of T cell entry into tissues is an effective therapy in autoimmune diseases. Little is known about the specific role of cytoskeletal effectors that mediate mechanical forces and morphological changes essential for migration in complex environments. We developed a new Formin-like-1 (FMNL1) knock-out mouse model and determined that the cytoskeletal effector FMNL1 is selectively required for effector T cell trafficking to inflamed tissues, without affecting naïve T cell entry into secondary lymphoid organs. Here, we identify a FMNL1-dependent mechanism of actin polymerization at the back of the cell that enables migration of the rigid lymphocyte nucleus through restrictive barriers. Furthermore, FMNL1-deficiency impairs the ability of self-reactive effector T cells to induce autoimmune disease. Overall, our data suggest that FMNL1 may be a potential therapeutic target to specifically modulate T cell trafficking to inflammatory sites.

Elimination of "kitome" and "splashome" contamination results in lack of detection of a unique placental microbiome.

BACKGROUND: A placental microbiome, which may be altered in gestational diabetes mellitus (GDM), has been described. However, publications raising doubts about the existence of a placental microbiome that is different than contaminants in DNA extraction kits and reagents ("kitomes") have emerged. The aims of this study were to confirm the existence of a placental microbiome distinct from contaminants and determine if it is altered in GDM mothers. RESULTS: We first enrolled normal weight, obese and GDM mothers (N = 17) at term elective cesarean section delivery in a pilot case control study. Bacterial DNA was extracted from placental parenchyma, maternal and cord blood, maternal vaginal-rectal swabs, and positive and negative controls with the standard Qiagen/MoBio Power Soil kit. Placentas had significantly higher copies of bacterial 16S rRNA genes than negative controls, but the placental microbiome was similar in all three groups and could not be distinguished from contaminants in blank controls. To determine the source and composition of the putative placental bacterial community identified in the pilot study, we expanded the study to 10 subjects per group (N = 30) and increased the number and variety of negative controls (N = 53). We modified our protocol to use an ultraclean DNA extraction kit (Qiagen QIAamp UCP with Pathogen Lysis Tube S), which reduced the "kitome" contamination, but we were still unable to distinguish a placental microbiome from contaminants in negative controls. We noted microbial DNA from the high biomass vaginal-rectal swabs and positive controls in placental and negative control samples and determined that this resulted from close proximity well-to-well cross contamination or "splashome". We eliminated this source of contamination by repeating the sequencing run with a minimum of four wells separating high biomass from low biomass samples. This reduced the reads of bacterial 16S rRNA genes in placental samples to insignificant numbers. CONCLUSIONS: We identified the problem of well-to-well contamination ("splashome") as an additional source of error in microbiome studies of low biomass samples and found a method of eliminating it. Once "kitome" and "splashome" contaminants were eliminated, we were unable to identify a unique placental microbiome.

Modifications of emergency dental clinic protocols to combat COVID-19 transmission.

During the COVID-19 pandemic, incidence rates for dental diseases will continue unabated. However, the intent to prevent the spread of this lethal respiratory disease will likely lead to reduced treatment access due to restrictions on population movements. These changes have the potential to increase dental-related emergency department visits and subsequently contribute to greater viral transmission. Moreover, dentists experience unique challenges with preventing transmission due to frequent aerosol-producing procedures. This paper presents reviews and protocols implemented by directors and residents at the Dental College of Georgia to manage a dental emergency clinic during the COVID-19 pandemic. The methods presented include committee-based prioritization of dental patients, a multilayered screening process, team rotations with social and temporal spacing, and modified treatment room protocols. These efforts aid in the reduction of viral transmission, conservation of personal protective equipment, and expand provider availability. These protocols transcend a university and hospital-based models and are applicable to private and corporate models.

The Limitations of Symptom-based Heart Failure Management.

Heart failure (HF) has emerged as a global epidemic and it affects about 6 million adults in the US. HF medical treatment, as recommended in guidelines, significantly improves survival and quality of life; however, the mortality burden of HF remains high. For decades, treatment has been guided, mainly by symptoms, leading to undertreatment in a range of settings. Current evidence emphasises the unfavourable outcomes of HF even in early stages or in patients who achieve reverse remodeling and remission or recovery under optimised treatment. This should stimulate efforts towards a more objective, rigorous management, covering the entire spectrum of mild, moderate and severe HF.

Pathological mucus and impaired mucus clearance in cystic fibrosis patients result from increased concentration, not altered pH.

Cystic fibrosis (CF) is a recessive genetic disease that is characterised by airway mucus plugging and reduced mucus clearance. There are currently alternative hypotheses that attempt to describe the abnormally viscous and elastic mucus that is a hallmark of CF airways disease, including: 1) loss of CF transmembrane regulator (CFTR)-dependent airway surface volume (water) secretion, producing mucus hyperconcentration-dependent increased viscosity, and 2) impaired bicarbonate secretion by CFTR, producing acidification of airway surfaces and increased mucus viscosity.A series of experiments was conducted to determine the contributions of mucus concentration versus pH to the rheological properties of airway mucus across length scales from the nanoscopic to macroscopic.For length scales greater than the nanoscopic, i.e. those relevant to mucociliary clearance, the effect of mucus concentration dominated over the effect of airway acidification.Mucus hydration and chemical reduction of disulfide bonds that connect mucin monomers are more promising therapeutic approaches than alkalisation.