Population structure and pathogen interaction of Escherichia coli in freshwater: Implications of land-use for water quality and public health in Aotearoa New Zealand.

Freshwater samples (n = 199) were obtained from 41 sites with contrasting land-uses (avian, low impact, dairy, urban, sheep and beef, and mixed sheep, beef and dairy) and the E. coli phylotype of 3980 isolates (20 per water sample enrichment) was determined. Eight phylotypes were identified with B1 (48.04%), B2 (14.87%) and A (14.79%) the most abundant. Escherichia marmotae (n = 22), and Escherichia ruysiae (n = 1), were rare (0.68%) suggesting that these environmental strains are unlikely to confound water quality assessments. Phylotypes A and B1 were overrepresented in dairy and urban sites (p < 0.0001), whilst B2 were overrepresented in low impact sites (p < 0.0001). Pathogens ((Salmonella, Campylobacter, Cryptosporidium or Giardia) and the presence of diarrhoeagenic E. coli-associated genes (stx and eae) were detected in 89.9% (179/199) samples, including 80.5% (33/41) of samples with putative non-recent faecal inputs. Quantitative PCR to detect microbial source tracking targets from human, ruminant and avian contamination were concordant with land-use type and E. coli phylotype abundance. This study demonstrated that a potential recreational health risk remains where pathogens occurred in water samples with low E. coli concentration, potential non-recent faecal sources, low impact sites and where human, ruminant and avian faecal sources were absent.

A metagenomics-based approach to decipher the resistome and mobilome of two seahorse species, Hippocampus barbouri and Hippocampus comes.

This study aimed to explore the abundance and diversity of antibiotic resistance genes (ARGs) in seahorses (Hippocampus barbouri and Hippocampus comes) and their surrounding environment. The combination of shotgun metagenomics and bioinformatics demonstrated a higher abundance of ARGs in seahorse-associated microbiomes, particularly in skin and gut samples, compared to water and sediment. Interestingly, genes conferring multidrug resistance (e.g., acrB, acrF, cpxA, msbA, and oqxB) were highly prevalent in all samples, especially in skin and gut samples. High levels of genes conferring resistance to fluoroquinolones (e.g., mfd and emrB), ß-lactam (e.g., blaCMY-71, blaOXA-55, and penA), aminocoumarin (e.g., mdtB and mdtC), and peptide antibiotics (arnA, pmrE, and rosA) were also observed in skin and gut samples. An enrichment of mobile genetic elements (MGEs) was also observed in the analyzed samples, highlighting their potential role in facilitating the acquisition and spread of ARGs. In fact, the abundance of mobilization (MOB) relaxases (e.g., MOBF, MOBP, MOBT, and MOBV) in gut and skin samples suggests a high potential for conjugation events. The occurrence of ARGs and MGEs in seahorses and the surrounding environment raises concerns about their transmission to humans, either through direct contact or the consumption of contaminated seafood. To the best of our knowledge, this study represents the first comprehensive analysis of ARGs in seahorse-associated microbiomes, and its results emphasize the need for monitoring and controlling the spread of ARGs in environmental settings.

OOPS: Object-Oriented Polarization Software for analysis of fluorescence polarization microscopy images.

Most essential cellular functions are performed by proteins assembled into larger complexes. Fluorescence Polarization Microscopy (FPM) is a powerful technique that goes beyond traditional imaging methods by allowing researchers to measure not only the localization of proteins within cells, but also their orientation or alignment within complexes or cellular structures. FPM can be easily integrated into standard widefield microscopes with the addition of a polarization modulator. However, the extensive image processing and analysis required to interpret the data have limited its widespread adoption. To overcome these challenges and enhance accessibility, we introduce OOPS (Object-Oriented Polarization Software), a MATLAB package for object-based analysis of FPM data. By combining flexible image segmentation and novel object-based analyses with a high-throughput FPM processing pipeline, OOPS empowers researchers to simultaneously study molecular order and orientation in individual biological structures; conduct population assessments based on morphological features, intensity statistics, and FPM measurements; and create publication-quality visualizations, all within a user-friendly graphical interface. Here, we demonstrate the power and versatility of our approach by applying OOPS to punctate and filamentous structures.

Asymptomatic and slowly progressive anti-MDA5 ILD: A report of three cases deviating from a notoriously rapidly progressive ILD.

Background: Anti-melanoma differentiation-associated gene 5-positive (anti-MDA5) dermatomyositis (DM) is a rare autoimmune disease associated with rapidly-progressive interstitial lung disease (RP-ILD.) The reported morbidity and 6-month mortality remains high from 33 to 66 % with RP-ILD most often developing within three months of diagnosis. Most cases require aggressive immunosuppression with combination therapy. Asymptomatic or slowly progressive cases of anti-MDA5 ILD are not well described in the literature. We report three cases of Latino patients with asymptomatic or slowly progressive anti-MDA5 ILD.Case descriptions. Case 1: A 54-year-old woman from Honduras with known diagnosis of anti-MDA5 dermatomyositis presented for ILD. She denied respiratory symptoms. Computed tomography (CT) chest showed multifocal patchy areas of scattered groundglass opacities throughout all lobes of the lungs, predominately in a subpleural distribution within the lower lobes. Pulmonary function testing (PFTs) showed mild-to-moderate restriction. She was treated with mycophenolate mofetil monotherapy for her skin manifestations. At 18 months follow-up, she denied respiratory symptoms, and PFTs were normal. Case 2: An 80-year-old man from Cuba was seen in pulmonary clinic to establish care. He was diagnosed with pulmonary fibrosis 11 years earlier with positive anti-MDA5. He denied respiratory symptoms. PFTs showed moderate obstruction and mild to moderate restriction. CT chest showed reduced lung volumes and findings compatible with usual interstitial pneumonia. He was started on nintedanib. Fifteen months following the initial visit, his PFTs remained stable. Follow-up CT chest showed stable pulmonary fibrosis. At all subsequent visits, he reported mild to moderate, slowly progressive dyspnea on exertion and was maintained on nintedanib. Thirteen years after his initial ILD diagnosis, he was diagnosed with pancreatic adenocarcinoma. Case 3: A 70-year-old woman from Peru presented to pulmonary clinic with cough for two months. She also reported pain in several metacarpophalangeal joints. She denied dyspnea. Rheumatologic serologies revealed positive anti-MDA5. PFTs were normal. Her cough was treated with cough suppressants and resolved. At a subsequent visit 8 months after presentation, she denied respiratory symptoms, and her joint pain remained mild. Given her lack of respiratory symptoms and normal PFTs, she was not initiated on ILD-specific treatment. Conclusions: While anti-MDA5 ILD is certainly associated with RP-ILD, clinicians should maintain awareness that there may be cases of asymptomatic or slowly progressive ILD as well.

Fluorescence-Based Proteoliposome Methods to Monitor Redox-Active Transition Metal Transmembrane Translocation by Metal Transporters.

Transmembrane transition metal transporter proteins are central gatekeepers in selectively controlling vectorial metal cargo uptake and extrusion across cellular membranes in all living organisms, thus playing key roles in essential and toxic metal homeostasis. Biochemical characterization of transporter-mediated translocation events and transport kinetics of redox-active metals, such as iron and copper, is challenged by the complexity in generating reconstituted systems in which vectorial metal transport can be studied in real time. We present fluorescence-based proteoliposome methods to monitor redox-active metal transmembrane translocation upon reconstitution of purified metal transporters in artificial lipid bilayers. By encapsulating turn-on/-off iron or copper-dependent sensors in the proteoliposome lumen and conducting real-time transport assays using small unilamellar vesicles (SUVs), in which selected purified Fe(II) and Cu(I) transmembrane importer and exporter proteins have been reconstituted, we provide a platform to monitor metal translocation events across lipid bilayers in real time. The strategy is modular and expandable toward the study of different transporter families featuring diverse metal substrate selectivity and promiscuity.

Disruption of neural periodicity predicts clinical response after deep brain stimulation for obsessive-compulsive disorder.

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy ( NCT05915741 ). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high degree of predictability. In patients with persistent symptoms (non-responders), predictability of the neural data remained consistently high. On the other hand, in patients who improved symptomatically (responders), predictability of the neural data was significantly diminished. This neural feature accurately classified clinical status even in patients with limited duration recordings, indicating generalizability that could facilitate therapeutic decision-making.

Mapping Africa's EV revolution.

Six years ago, my colleagues and I published an article in the World Economic Forum asking if Africa was ready for the electric vehicle (EV) revolution. At that time, the African EV sector was nascent, and we concluded that more data and research were needed to draw firmer conclusions, emphasizing the absence of Africa-specific data in major EV publications and calling for dedicated analysis tailored to the continent's needs.

Prolactin mitigates chronic stress-induced maladaptive behaviors and physiology in ovariectomized female rats.

Stress is a major risk factor for several neuropsychiatric disorders in women, including postpartum depression. During the postpartum period, diminished ovarian hormone secretion increases susceptibility to developing depressive symptoms. Pleiotropic peptide hormones, like prolactin, are markedly released during lactation and suppress hypothalamic-pituitary-adrenal axis responses in women and acute stress-induced behavioral responses in female rodents. However, the effects of prolactin on chronic stress-induced maladaptive behaviors remain unclear. Here, we used chronic variable stress to induce maladaptive physiology in ovariectomized female rats and concurrently administered prolactin to assess its effects on several depression-relevant behavioral, endocrine, and neural characteristics. We found that chronic stress increased sucrose anhedonia and passive coping in saline-treated, but not prolactin-treated rats. Prolactin treatment did not alter stress-induced thigmotaxis, corticosterone (CORT) concentrations, hippocampal cell activation or survival. However, prolactin treatment reduced basal CORT concentrations and increased dopaminergic cells in the ventral tegmental area. Further, prolactin-treated rats had reduced microglial activation in the ventral hippocampus following chronic stress exposure. Together, these data suggest prolactin mitigates chronic stress-induced maladaptive behaviors and physiology in hypogonadal females. Moreover, these findings imply neuroendocrine-immune mechanisms by which peptide hormones confer stress resilience during periods of low ovarian hormone secretion.

Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment.

BACKGROUND: The SARS-CoV-2 virus activates maternal and placental immune responses. Such activation in the setting of other infections during pregnancy is known to impact fetal brain development. The effects of maternal immune activation on neurodevelopment are mediated at least in part by fetal brain microglia. However, microglia are inaccessible for direct analysis, and there are no validated non-invasive surrogate models to evaluate in utero microglial priming and function. We have previously demonstrated shared transcriptional programs between microglia and Hofbauer cells (HBCs, or fetal placental macrophages) in mouse models. METHODS AND RESULTS: We assessed the impact of maternal SARS-CoV-2 on HBCs isolated from 24 term placentas (N = 10 SARS-CoV-2 positive cases, 14 negative controls). Using single-cell RNA-sequencing, we demonstrated that HBC subpopulations exhibit distinct cellular programs, with specific subpopulations differentially impacted by SARS-CoV-2. Assessment of differentially expressed genes implied impaired phagocytosis, a key function of both HBCs and microglia, in some subclusters. Leveraging previously validated models of microglial synaptic pruning, we showed that HBCs isolated from placentas of SARS-CoV-2 positive pregnancies can be transdifferentiated into microglia-like cells (HBC-iMGs), with impaired synaptic pruning behavior compared to HBC models from negative controls. CONCLUSION: These findings suggest that HBCs isolated at birth can be used to create personalized cellular models of offspring microglial programming.

Understanding the Phase Behavior of a Multistimuli-Responsive Elastin-like Polymer: Insights from Dynamic Light Scattering Analysis.

Elastin-like polymers are a class of stimuli-responsive protein polymers that hold immense promise in applications such as drug delivery, hydrogels, and biosensors. Yet, understanding the intricate interplay of factors influencing their stimuli-responsive behavior remains a challenging frontier. Using temperature-controlled dynamic light scattering and zeta potential measurements, we investigate the interactions between buffer, pH, salt, water, and protein using an elastin-like polymer containing ionizable lysine residues. We observed the elevation of transition temperature in the presence of the common buffering agent HEPES at low concentrations, suggesting a "salting-in" effect of HEPES as a cosolute through weak association with the protein. Our findings motivate a more comprehensive investigation of the influence of buffer and other cosolute molecules on elastin-like polymer behavior.

Shotgun Metagenomics Reveals Taxonomic and Functional Patterns of the Microbiome Associated with Barbour's Seahorse (Hippocampus barbouri).

This study aimed to investigate the taxonomic and functional patterns of the microbiome associated with Barbour's seahorse (Hippocampus barbouri) using a combination of shotgun metagenomics and bioinformatics. The analyses revealed that Pseudomonadota and Bacillota were the dominant phyla in the seahorse skin microbiome, whereas Pseudomonadota and, to a lesser extent, Bacillota and Bacteroidota were the dominant phyla in the seahorse gut microbiome. Several metabolic pathway categories were found to be enriched in the skin microbiome, including amino acid metabolism, carbohydrate metabolism, cofactor and vitamin metabolism, energy metabolism, nucleotide metabolism, as well as membrane transport, signal transduction, and cellular community-prokaryotes. In contrast, the gut microbiome exhibited enrichment in metabolic pathways associated with the metabolism of terpenoids and polyketides, biosynthesis of other secondary metabolites, xenobiotics biodegradation and metabolism, and quorum sensing. Additionally, although the relative abundance of bacteriocins in the skin and gut was slightly similar, notable differences were observed at the class level. Specifically, class I bacteriocins were found to be more abundant in the skin microbiome, whereas class III bacteriocins were more abundant in the gut microbiome. To the best of our knowledge, this study represents the first comprehensive examination of the taxonomic and functional patterns of the skin and gut microbiome in Barbour's seahorse. These findings can greatly contribute to a deeper understanding of the seahorse-associated microbiome, which can play a pivotal role in predicting and controlling bacterial infections, thereby contributing to the success of aquaculture and health-promoting initiatives.

Genetic regulators of a resource polyphenism interact to couple predatory morphology and behaviour.

Phenotypic plasticity often requires the coordinated response of multiple traits observed individually as morphological, physiological or behavioural. The integration, and hence functionality, of this response may be influenced by whether and how these component traits share a genetic basis. In the case of polyphenism, or discrete plasticity, at least part of the environmental response is categorical, offering a simple readout for determining whether and to what degree individual components of a plastic response can be decoupled. Here, we use the nematode Pristionchus pacificus, which has a resource polyphenism allowing it to be a facultative predator of other nematodes, to understand the genetic integration of polyphenism. The behavioural and morphological consequences of perturbations to the polyphenism's genetic regulatory network show that both predatory activity and ability are strongly influenced by morphology, different axes of morphological variation are associated with different aspects of predatory behaviour, and rearing environment can decouple predatory morphology from behaviour. Further, we found that interactions between some polyphenism-modifying genes synergistically affect predatory behaviour. Our results show that the component traits of an integrated polyphenic response can be decoupled and, in principle, selected upon individually, and they suggest that multiple routes to functionally comparable phenotypes are possible.

Telemedicine and Resource Utilization in Pulmonary Clinic.

BACKGROUND: Telemedicine use increased with the Covid-19 pandemic. The impact of telemedicine on resource use in pulmonary clinics is unknown. METHODS: This retrospective cohort study identified adults with pulmonary clinic visits at the University of Miami Hospital and Clinics (January 2018-December 2021). The primary exposure was telemedicine versus in-person visits. Standard statistics were used to describe the cohort and compare patients stratified by visit type. Multivariable logistic regression models evaluated the association of telemedicine with resource use (primarily, computed tomography [CT] orders placed within 7 days of visit). RESULTS: 21,744 clinic visits were included: 5,480 (25.2%) telemedicine and 16,264 (74.8%) in-person. In both, the majority were < 65-years-old, female, and identified as Hispanic white. Patients seen with telemedicine had increased odds of having CT scans ordered within 7 days (adjusted odds ratio [aOR] 1.34, [95% confidence interval 1.04-1.74]); and decreased odds of chest x-rays (aOR 0.37 [0.23-0.57]). Telemedicine increased odds of contact of any kind with our healthcare system within 30-days (aOR 1.56 [1.29-1.88]) and 90-days (aOR 1.39 [1.17-1.64]). Specifically, telemedicine visits had decreased odds of emergency department visits and hospitalizations (30 days: aOR 0.54 [0.38-0.76]; 90 days: aOR 0.68 [0.52-0.89]), but increased odds of phone calls and electronic health record inbox messages (30 days: aOR 3.44 [2.73-4.35]; 90 days: aOR 3.58 [2.95-4.35]). CONCLUSIONS: Telemedicine was associated with an increased odds of chest CT order with a concomitant decreased odds of chest x-ray order. Increased contact with the healthcare system with telemedicine may represent a larger time burden for outpatient clinicians.

Understanding the Role of Extension Professionals in Public Health and One Health in Kansas.

This study aims to understand the roles of selected extension professionals (EPs) in the field of public health and One Health and the challenges involved in performing these duties to their communities in the state of Kansas. To evaluate the role of EPs in public health and One Health, researchers interviewed nine (9) EPs following a set of structured questions. Emerging themes were extrapolated from the responses of the EPs. Researchers assigned codes for qualitative analysis and assigned themes related to public health, One Health, and effective delivery of services. Researchers identified the following themes related to the role of EPs in public health (youth development, physical activity, personal health care, proper nutrition, access to transportation), One Health (food safety and food security, environmental health, disease control and prevention) and effective delivery of services (community engagement, collaboration, challenges in implementation). The study provided an overview of the diverse roles that EPs play in public health and One Health, keys on how to engage the community effectively, and challenges in extending services to the community.

Serum Proteomics Distinguish Subtypes of NMO Spectrum Disorder and MOG Antibody-Associated Disease and Highlight Effects of B-Cell Depletion.

BACKGROUND AND OBJECTIVES: AQP4 antibody-positive NMOSD (AQP4-NMOSD), MOG antibody-associated disease (MOGAD), and seronegative NMOSD (SN-NMOSD) are neuroautoimmune conditions that have overlapping clinical manifestations. Yet, important differences exist in these diseases, particularly in B-cell depletion (BCD) efficacy. Yet, the biology driving these differences remains unclear. Our study aims to clarify biological pathways distinguishing these diseases beyond autoantibodies and investigate variable BCD effects through proteomic comparisons. METHODS: In a retrospective study, 1,463 serum proteins were measured in 53 AQP4-NMOSD, 25 MOGAD, 18 SN-NMOSD, and 49 healthy individuals. To identify disease subtype-associated signatures, we examined serum proteins in patients without anti-CD20 B-cell depletion (NoBCD). We then assessed the effect of BCD treatment within each subtype by comparing proteins between BCD-treated and NoBCD-treated patients. RESULTS: In NoBCD-treated patients, serum profiles distinguished the 3 diseases. AQP4-NMOSD showed elevated type I interferon-induced chemokines (CXCL9 and CXCL10) and TFH chemokine (CXCL13). MOGAD exhibited increased cytotoxic T-cell proteases (granzyme B and granzyme H), while SN-NMOSD displayed elevated Wnt inhibitory factor 1, a marker for nerve injury. Across all subtypes, BCD-treated patients showed reduction of B-cell-associated proteins. In AQP4-NMOSD, BCD led to a decrease in several inflammatory pathways, including IL-17 signaling, cytokine storm, and macrophage activation. By contrast, BCD elevated these pathways in patients with MOGAD. BCD had no effect on these pathways in SN-NMOSD. DISCUSSION: Proteomic profiles show unique biological pathways that distinguish AQP4-NMOSD, MOGAD, or SN-NMOSD. Furthermore, BCD uniquely affects inflammatory pathways in each disease type, providing an explanation for the disparate therapeutic response in AQP4-NMOSD and MOGAD.

The UK clinical eye research strategy: refreshing research priorities for clinical eye research in the UK.

OBJECTIVES: To validate and update the 2013 James Lind Alliance (JLA) Sight Loss and Vision Priority Setting Partnership (PSP)'s research priorities for Ophthalmology, as part of the UK Clinical Eye Research Strategy. METHODS: Twelve ophthalmology research themes were identified from the JLA report. They were allocated to five Clinical Study Groups of diverse stakeholders who reviewed the top 10 research priorities for each theme. Using an online survey (April 2021-February 2023), respondents were invited to complete one or more of nine subspecialty surveys. Respondents indicated which of the research questions they considered important and subsequently ranked them. RESULTS: In total, 2240 people responded to the survey (mean age, 59.3 years), from across the UK. 68.1% were female. 68.2% were patients, 22.3% healthcare professionals or vision researchers, 7.1% carers, and 2.1% were charity support workers. Highest ranked questions by subspecialty: Cataract (prevention), Cornea (improving microbial keratitis treatment), Optometric (impact of integration of ophthalmic primary and secondary care via community optometric care pathways), Refractive (factors influencing development and/or progression of refractive error), Childhood onset (improving early detection of visual disorders), Glaucoma (effective and improved treatments), Neuro-ophthalmology (improvements in prevention, diagnosis and treatment of neurodegeneration affecting vision), Retina (improving prevention, diagnosis and treatment of dry age-related macular degeneration), Uveitis (effective treatments for ocular and orbital inflammatory diseases). CONCLUSIONS: A decade after the initial PSP, the results refocus the most important research questions for each subspecialty, and prime targeted research proposals within Ophthalmology, a chronically underfunded specialty given the substantial burden of disability caused by eye disease.

Gut microbiota composition links to variation in functional domains across psychiatric disorders.

OBJECTIVE: Changes in microbial composition are observed in various psychiatric disorders, but their specificity to certain symptoms or processes remains unclear. This study explores the associations between the gut microbiota composition and the Research Domain Criteria (RDoC) domains of functioning, representing symptom domains, specifically focusing on stress-related and neurodevelopmental disorders in patients with and without psychiatric comorbidity. METHODS: The gut microbiota was analyzed in 369 participants, comprising 272 individuals diagnosed with a mood disorder, anxiety disorder, attention deficit/hyperactivity disorder, autism spectrum disorder, and/or substance use disorder, as well as 97 psychiatrically unaffected individuals. The RDoC domains were estimated using principal component analysis (PCA) with oblique rotation on a range of psychiatric, psychological, and personality measures. Associations between the gut microbiota and the functional domains were assessed using multiple linear regression and permanova, adjusted for age, sex, diet, smoking, medication use and comorbidity status. RESULTS: Four functional domains, aligning with RDoC's negative valence, social processes, cognitive systems, and arousal/regulatory systems domains, were identified. Significant associations were found between these domains and eight microbial genera, including associations of negative valence with the abundance of the genera Sellimonas, CHKCI001, Clostridium sensu stricto 1, Oscillibacter, and Flavonifractor; social processes with Sellimonas; cognitive systems with Sporobacter and Hungatella; and arousal/regulatory systems with Ruminococcus torques (all pFDR < 0.05). CONCLUSION: Our findings demonstrate associations between the gut microbiota and the domains of functioning across patients and unaffected individuals, potentially mediated by immune-related processes. These results open avenues for microbiota-focused personalized interventions, considering psychiatric comorbidity. However, further research is warranted to establish causality and elucidate mechanistic pathways.

Allele frequency dynamics under sex-biased demography and sex-specific inheritance in a pedigreed jay population.

Sex-biased demography, including sex-biased survival or migration, can alter allele frequency changes across the genome. In particular, we can expect different patterns of genetic variation on autosomes and sex chromosomes due to sex-specific differences in life histories, as well as differences in effective population size, transmission modes, and the strength and mode of selection. Here, we demonstrate the role that sex differences in life history played in shaping short-term evolutionary dynamics across the genome. We used a 25-year pedigree and genomic dataset from a long-studied population of Florida Scrub-Jays (Aphelocoma coerulescens) to directly characterize the relative roles of sex-biased demography and inheritance in shaping genome-wide allele frequency trajectories. We used gene dropping simulations to estimate individual genetic contributions to future generations and to model drift and immigration on the known pedigree. We quantified differential expected genetic contributions of males and females over time, showing the impact of sex-biased dispersal in a monogamous system. Due to female-biased dispersal, more autosomal variation is introduced by female immigrants. However, due to male-biased transmission, more Z variation is introduced by male immigrants. Finally, we partitioned the proportion of variance in allele frequency change through time due to male and female contributions. Overall, most allele frequency change is due to variance in survival and births. Males and females make similar contributions to autosomal allele frequency change, but males make higher contributions to allele frequency change on the Z chromosome. Our work shows the importance of understanding sex-specific demographic processes in characterizing genome-wide allele frequency change in wild populations.

Barriers to neurosurgery for medical students: a national study focused on the intersectionality of gender and race.

OBJECTIVE: Despite 51.2% of medical school graduates being female, only 29.8% of neurosurgery residency applicants are female. Furthermore, only 12.6% of neurosurgery applicants identify as underrepresented in medicine (URM). Evaluating the entry barriers for female and URM students is crucial in promoting the equity and diversity of the neurosurgical workforce. The objective of this study was to evaluate barriers to neurosurgery for medical students while considering the interaction between gender and race. METHODS: A Qualtrics survey was distributed widely to US medical students, assessing 14 factors of hesitancy toward neurosurgery. Likert scale responses, representing statement agreeability, converted to numeric values on a 7-point scale were analyzed by Mann-Whitney U-test and ANOVA comparisons with Bonferroni correction. RESULTS: Of 540 respondents, 68.7% were female and 22.6% were URM. There were 22.6% male non-URM, 7.4% male URM, 53.5% female non-URM, and 15.2% female URM respondents. The predominant reasons for hesitancy toward neurosurgery included work/life integration, length of training, competitiveness of residency position, and perceived malignancy of the field. Females were more hesitant toward neurosurgery due to maternity/paternity needs (p = 0.005), the absence of seeing people like them in the field (p < 0.001), and opportunities to pursue health equity work (p < 0.001). Females were more likely to have difficulties finding a mentor in neurosurgery who represented their identities (p = 0.017). URM students were more hesitant toward neurosurgery due to not seeing people like them in the field (p < 0.001). Subanalysis revealed that when students were stratified by both gender and URM status, there were more reasons for hesitancy toward neurosurgery that had significant differences between groups (male URM, male non-URM, female URM, and female non-URM students), suggesting the importance of intersectionality in this analysis. CONCLUSIONS: The authors highlight the implications of gender and racial diversity in the neurosurgical workforce on medical student interest and recruitment. Their findings suggest the importance of actively working to address these barriers, including 1) maternity/paternity policy reevaluation, standardization, and dissemination; and 2) actively providing resources for the creation of mentorship relationships for both women and URM students in an effort to create a workforce that aligns with the changing demographics of medical graduates to continue to improve diversity in neurosurgery.

Dsg2 ectodomain organization increases throughout desmosome assembly.

Desmosomes are intercellular junctions that regulate mechanical integrity in epithelia and cardiac muscle. Dynamic desmosome remodeling is essential for wound healing and development, yet the mechanisms governing junction assembly remain elusive. While we and others have shown that cadherin ectodomains are highly organized, how this ordered architecture emerges during assembly is unknown. Using fluorescence polarization microscopy, we show that desmoglein 2 (Dsg2) ectodomain order gradually increases during 8 h of assembly, coinciding with increasing adhesive strength. In a scratch wound assay, we observed a similar increase in order in desmosomes assembling at the leading edge of migratory cells. Together, our findings indicate that cadherin organization is a hallmark of desmosome maturity and may play a role in conferring adhesive strength.