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Mosquitoes transmit pathogens that pose a threat to millions of people globally. Unfortunately, widespread insecticide resistance makes it difficult to control these public health pests. General mechanisms of resistance, such as target site mutations or increased metabolic activity, are well established. However, many questions regarding the dynamics of these adaptations in the context of developmental and environmental conditions require additional exploration. One aspect of resistance that deserves further study is the role of heat shock proteins (HSPs) in insecticide tolerance. Studies show that mosquitoes experiencing heat stress before insecticide exposure demonstrate decreased mortality. This is similar to the observed reciprocal reduction in mortality in mosquitoes exposed to insecticide prior to heat stress. The environmental shifts associated with climate change will result in mosquitoes occupying environments with higher ambient temperatures, which could enhance existing insecticide resistance phenotypes. This physiological relationship adds a new dimension to the problem of insecticide resistance and further complicates the challenges that vector control and public health personnel face. This article reviews studies illustrating the relationship between insecticide resistance and HSPs or hsp genes as well as the intersection of thermotolerance and insecticide resistance. Further study of HSPs and insecticide resistance could lead to a deeper understanding of how environmental factors modulate the physiology of these important disease vectors to prepare for changing climatic conditions and the development of novel strategies to prevent vector-borne disease transmission.

This paper seeks to address the wider questions of populism and its seeming contemporary rise within the specific context of the Philippines, regarding education. Starting from the assumption that neither politics nor education sits above cultures or spaces autonomously acting upon them but instead emerges with/because/against particularities; after a brief overview of populism, I explore the conceptual characteristics in context. This is informed from my own experiences of living and researching in the Philippines, including experience of the Mindanao conflict but also the failure of liberalism in the Philippines more generally, the failure of western education to 'develop' the nation and the reactions that led to the populists rise of Duterte. The paper offers an understanding of the complexities of populism and offers some hope to how education can meet the challenge through a specific example of critical participatory community education.

Established populations of Aedes aegypti, a mosquito vector of multiple major arthropod-borne viruses, were first found in three California (CA) cities in 2013. From 2013 to April 2021, Ae. aegypti thwarted almost all control efforts to stop its spread and expanded its range to 308 cities, including Exeter, in 22 counties in CA. Population genomic analyses have suggested that multiple genetically distinct Ae. aegypti populations were introduced into CA. However Ae. aegypti collected for the first time in 2014 in Exeter, appeared to be different from three major genetic clusters found elsewhere in CA. Due to intense control efforts by the Delta Vector Control District (DVCD), Ae. aegypti was thought to have been eliminated from Exeter in 2015. Unfortunately, it was recollected in 2018. It was not clear if the reemergence of Ae. aegypti in Exeter was derived from the bottlenecked remnants of the original 2014 Exeter population or from an independent invasion from a different population derived from surrounding areas. The goal of this work was to determine which of these scenarios occurred (recovery after bottleneck or reintroduction after elimination) and if elimination and reintroduction occurred to identify the origin of the invading population using a population genomic approach. Our results support the reintroduction after elimination hypothesis. The source of reintroduction, however, was unexpectedly from the southern CA cluster rather than from other two geographically closer central CA genetic clusters. We also conducted a knockdown resistance mutation profile, which showed Exeter 2014 had the lowest level of resistant alleles compared to the other populations, could have contributed towards DVCD’s ability to locally eliminate Ae. aegypti in 2014.

BackgroundSame-day HIV testing and antiretroviral therapy (ART) initiation is being widely implemented. However, the optimal timing of ART among patients with tuberculosis (TB) symptoms is unknown. We hypothesized that same-day treatment (TB treatment for those diagnosed with TB; ART for those not diagnosed with TB) would be superior to standard care in this population.Methods and findingsWe conducted an open-label trial among adults with TB symptoms at initial HIV diagnosis at GHESKIO in Haiti; participants were recruited and randomized on the same day. Participants were randomized in a 1:1 ratio to same-day treatment (same-day TB testing with same-day TB treatment if TB diagnosed; same-day ART if TB not diagnosed) versus standard care (initiating TB treatment within 7 days and delaying ART to day 7 if TB not diagnosed). In both groups, ART was initiated 2 weeks after TB treatment. The primary outcome was retention in care with 48-week HIV-1 RNA

Abstract Introduction Emergency departments (ED) are incorporating Peer Support Specialists (PSSs) to help with patient care for substance use disorders (SUDs). Despite rapid growth in this area, little is published regarding workflow, expectations of the peer role, and core components of the PSS intervention. This study describes these elements in a national sample of ED-based peer support intervention programs. Methods A survey was conducted to assess PSS site characteristics as part of site selection process for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) evaluating PSS effectiveness, Surveys were distributed to clinical sites affiliated with the 16 CTN nodes. Surveys were completed by a representative(s) of the site and collected data on the PSS role in the ED including details regarding funding and certification, services rendered, role in medications for opioid use disorder (MOUD) and naloxone distribution, and factors impacting implementation and maintenance of ED PSS programs. Quantitative data was summarized with descriptive statistics. Free-text fields were analyzed using qualitative content analysis. Results A total of 11 surveys were completed, collected from 9 different states. ED PSS funding was from grants (55%), hospital funds (46%), peer recovery organizations (27%) or other (18%). Funding was anticipated to continue for a mean of 16 months (range 12 to 36 months). The majority of programs provided “general recovery support (81%) Screening, Brief Intervention, and Referral to Treatment (SBIRT) services (55%), and assisted with naloxone distribution to ED patients (64%). A minority assisted with ED-initiated buprenorphine (EDIB) programs (27%). Most (91%) provided services to patients after they were discharged from the ED. Barriers to implementation included lack of outpatient referral sources, barriers to initiating MOUD, stigma at the clinician and system level, and lack of ongoing PSS availability due to short-term grant funding. Conclusions The majority of ED-based PSSs were funded through time-limited grants, and short-term grant funding was identified as a barrier for ED PSS programs. There was consistency among sites in the involvement of PSSs in facilitation of transitions of SUD care, coordination of follow-up after ED discharge, and PSS involvement in naloxone distribution.

Insecticide resistance is a multifaceted response and an issue across taxa. Aedes aegypti, the mosquito that vectors Zika, dengue, chikungunya, and yellow fever, demonstrates high levels of pyrethroid resistance across the globe, presenting a challenge to public health officials. To examine the transcriptomic shifts across time after exposure to permethrin, a 3'Tag-Seq analysis was employed on samples 6, 10, and 24 h after exposure along with controls. Differential expression analysis revealed significant shifts in detoxifying enzymes and various energy-producing metabolic processes. These findings indicate significant alterations in gene expression associated with key energy mobilization pathways within the system. These changes encompass a coordinated response involving lipolysis, beta-oxidation, and the citric acid cycle, required for the production of energetic molecules such as ATP, NADH, NADPH, and FADH. These findings highlight a complex interplay of metabolic processes that may have broader implications for understanding insect physiology and response to environmental stimuli. Among the upregulated detoxifying enzymes are cytochrome P450s, glutathione s-transferases and peroxidases, and ATP-binding cassette transporters. Additionally, eight heat shock genes or genes with heat shock domains exhibit the highest fold change across time. Twenty-four hours after exposure, samples indicate a global downregulation of these processes, though principal component analysis suggests lasting signatures of the response. Understanding the recovery response to insecticide exposure provides information on possible new genetic and synergist targets to explore.

Global amphibian declines are compounded by deadly disease outbreaks caused by the chytrid fungus, Batrachochytrium dendrobatidis (Bd). Much has been learned about the roles of amphibian skin-produced antimicrobial components and microbiomes in controlling Bd, yet almost nothing is known about the roles of skin-resident immune cells in anti-Bd defenses. Mammalian mast cells reside within and serve as key immune sentinels in barrier tissues like skin. Accordingly, we investigated the roles of Xenopus laevis frog mast cells during Bd infections. Our findings indicate that enrichment of X. laevis skin mast cells confers anti-Bd protection and ameliorates the inflammation-associated skin damage caused by Bd infection. This includes a significant reduction in infiltration of Bd-infected skin by neutrophils, promoting mucin content within cutaneous mucus glands, and preventing Bd-mediated changes to skin microbiomes. Mammalian mast cells are known for their production of the pleiotropic interleukin-4 (IL4) cytokine and our findings suggest that the X. laevis IL4 plays a key role in manifesting the effects seen following cutaneous mast cell enrichment. Together, this work underscores the importance of amphibian skin-resident immune cells in anti-Bd defenses and illuminates a novel avenue for investigating amphibian host–chytrid pathogen interactions.

Summary: Combinatorial signaling by proinflammatory cytokines synergizes to exacerbate toxicity to cells and tissue injury during acute infections. To explore synergism at the gene-regulatory level, we investigated the dynamics of transcription and chromatin signaling in response to dual cytokines by integrating nascent RNA imaging mass spectrometry, RNA sequencing, amplification-independent mRNA quantification, assay for transposase-accessible chromatin using sequencing (ATAC-seq), and transcription factor profiling. Costimulation with interferon-gamma (IFNγ) and tumor necrosis factor alpha (TNFα) synergistically induced a small subset of genes, including the chemokines CXCL9, -10, and -11. Gene induction coincided with increased chromatin accessibility at non-coding regions enriched for p65 and STAT1 binding sites. To discover coactivator dependencies, we conducted a targeted chemogenomic screen of transcriptional inhibitors followed by modeling of inhibitor dose-response curves. These results identified high efficacy of either p300/CREB-binding protein (CBP) or bromodomain and extra-terminal (BET) bromodomain inhibitors to disrupt induction of synergy genes. Combination p300/CBP and BET bromodomain inhibition at half-maximal inhibitory concentrations (subIC50) synergistically abrogated IFNγ/TNFα-induced chemokine gene and protein levels.

Obesity is a significant public health concern that is closely associated with various comorbidities such as heart disease, stroke, type II diabetes (T2D), and certain cancers. Due to the central role of adipose tissue in many disease etiologies and the pervasive nature in the body, engineered adipose tissue models are essential for drug discovery and studying disease progression. This study validates a fat-on-a-chip (FOAC) model derived from primary mature adipocytes. Our FOAC model uses a Micronit perfusion device and introduces a novel approach for collecting continuous data by using two non-invasive readout techniques, resazurin and glucose uptake. The Micronit platform proved to be a reproducible model that can effectively maintain adipocyte viability, metabolic activity, and basic functionality, and is capable of mimicking physiologically relevant responses such as adipocyte hypertrophy and insulin-mediated glucose uptake. Importantly, we demonstrate that adipocyte size is highly dependent on extracellular matrix properties, as adipocytes derived from different patients with variable starting lipid areas equilibrate to the same size in the hyaluronic acid hydrogel. This model can be used to study T2D and monitor adipocyte responses to insulin for longitudinally tracking therapeutic efficacy of novel drugs or drug combinations.

Following anterior cruciate ligament reconstruction (ACLR), patients exhibit abnormal walking mechanics and quadriceps dysfunction. Quadriceps dysfunction has been largely attributed to muscle atrophy and weakness. While important, these factors do not capture intrinsic properties of muscle that govern its ability to generate force and withstand load. While fascicle abnormalities after ACLR have been documented in early stages of recovery (<12 mo), long-term effects of ACLR on fascicle mechanics remain unexplored. We evaluated quadriceps fascicle mechanics during walking 3 years post-ACLR and examined the relationship with knee mechanics. Participants included 24 individuals with ACLR and 24 Controls. Linear mixed models compared the ACLR, Contralateral, and Controls limbs for (1) quadriceps strength, (2) fascicle architecture and mechanics, and (3) knee mechanics. No difference in strength or overall fascicle length excursions was found between limbs. The ACLR limb exhibited longer fascicles at heel strike and peak knee extension moment (P <.001–.004), and smaller fascicle angles at heel strike, peak knee extension moment, and overall suppressed fascicle angle excursions (P <.001–.049) relative to the Contralateral and/or Control limb. This indicates an abnormality in fascicle architecture and mechanics following ACLR and suggests abnormalities in contractile function that cannot be explained by muscle weakness and may contribute to long-term gait irregularities. [ABSTRACT FROM AUTHOR]

Objective: The present study examined if identification with mainstream American culture (acculturation) and heritage culture (enculturation) are differentially associated with blackouts and other drinking consequences among male and female college students of color. Participants: Participants were college students (N = 150) who self-identified as a racial/ethnic minority and endorsed blackouts in the past year. Methods: Regression models were used to examine gender-by-acculturation/enculturation interaction effects on alcohol-induced blackout and other alcohol-related consequences. Results: While acculturation was not significantly associated with either drinking outcome, enculturation showed a significant relationship with blackout frequency. Gender moderated this relationship; greater enculturation was associated with increased blackout frequency among male but not female students. Conclusions: The present findings suggest the importance of considering the interplay between enculturation and gender in understanding alcohol use among college students of color. Men who endorse high levels of enculturation may be at an increased risk of experiencing negative drinking-related consequences.

Heterogeneity in endothelial cell (EC) sub-phenotypes is becoming increasingly appreciated in atherosclerosis progression. Still, studies quantifying EC heterogeneity across whole transcriptomes and epigenomes in both in vitro and in vivo models are lacking. Multiomic profiling concurrently measuring transcriptomes and accessible chromatin in the same single cells was performed on six distinct primary cultures of human aortic ECs (HAECs) exposed to activating environments characteristic of the atherosclerotic microenvironment in vitro. Meta-analysis of single-cell transcriptomes across 17 human ex vivo arterial specimens was performed and two computational approaches quantitatively evaluated the similarity in molecular profiles between heterogeneous in vitro and ex vivo cell profiles. HAEC cultures were reproducibly populated by four major clusters with distinct pathway enrichment profiles and modest heterogeneous responses: EC1-angiogenic, EC2-proliferative, EC3-activated/mesenchymal-like, and EC4-mesenchymal. Quantitative comparisons between in vitro and ex vivo transcriptomes confirmed EC1 and EC2 as most canonically EC-like, and EC4 as most mesenchymal with minimal effects elicited by siERG and IL1B. Lastly, accessible chromatin regions unique to EC2 and EC4 were most enriched for coronary artery disease (CAD)-associated single-nucleotide polymorphisms from Genome Wide Association Studies (GWAS), suggesting that these cell phenotypes harbor CAD-modulating mechanisms. Primary EC cultures contain markedly heterogeneous cell subtypes defined by their molecular profiles. Surprisingly, the perturbations used here only modestly shifted cells between subpopulations, suggesting relatively stable molecular phenotypes in culture. Identifying consistently heterogeneous EC subpopulations between in vitro and ex vivo models should pave the way for improving in vitro systems while enabling the mechanisms governing heterogeneous cell state decisions.

While there are various studies investigating the effect of freezing on palatability characteristics, thawing has not received the same level of interest. Therefore, the objective of this study was to investigate the effects of various thawing methods on beef palatability. Paired beef strip loins (n = 15 pairs) were obtained from a commercial processing facility for palatability evaluation, and 6 additional strip loins were collected for thawing characteristic data. The paired loins were sectioned into 6 sections of 4 steaks each, and each section assigned a thawing method. Thaw methods included thawing in the refrigerator, cold water, microwave, hot water, on the counter, and cooking from frozen. Steaks were aged a total of 21 d prior to freezing. Consumer sensory panelists (N = 120) found no differences (P > 0.05) among all thawing methods for each palatability characteristic. Within trained sensory panels (n = 8 panelists/session), thawing in the refrigerator and cold water were rated higher (P < 0.05) for overall tenderness than thawing in the microwave and cooking from frozen. Cooking steaks from frozen was rated higher (P < 0.05) for beef flavor intensity than all other thawing methods by trained sensory panelists. Steaks thawed in the microwave had the highest (P < 0.05) percentage of cook loss, followed by cooking from frozen, with all other methods being similar (P > 0.05). Similarly, steaks thawed in the microwave and in hot water had a higher (P < 0.05) thawing loss percentage than steaks thawed on the counter, in cold water, or in the refrigerator. These results indicate thawing method had minimal differences on overall beef palatability and objective quality measures. Therefore, consumers and foodservice establishments should use their preferred thaw method based on convenience, taking food safety and time into consideration.

Although studies evaluating freezing are prevalent, most have used varied postmortem aging times to facilitate study design. The lack of a comprehensive study evaluating equally aged fresh and frozen steaks prevents a true under-standing of the impact of freezing. Therefore, the objective of this study was to determine the eating quality and consumer perception differences between fresh and frozen beef steaks of 3 equal aging periods. Beef carcasses were selected from a processing plant on 2 kill dates 1 wk apart to allow for a 1-wk freezing period, fabricated, and aged for 21, 28, or 35 d. On the same day, all samples of equal aging periods were fed to consumer and trained sensory panelists, sheared for shear force, and powdered for lab assays. For consumer panels, the first 4 steaks were given with no additional information, whereas the last 4 steaks were served with the labels “previously frozen” or “fresh, never frozen.” The consumer panelists rated the frozen samples as more tender (P0.05). Even when given additional information, the perception of quality was not impacted (P>0.05). Similarly, the trained panelists rated the frozen samples higher (P

Introduction: Anterior cruciate ligament (ACL) injury is frequently accompanied by quadriceps muscle atrophy, a process closely linked to mitochondrial health and mitochondria-specific autophagy. However, the temporal progression of key quadricep atrophy-mediating events following ACL injury remains poorly understood. To advance our understanding, we conducted a longitudinal study to elucidate key parameters in quadriceps autophagy and mitophagy.Methods: Long-Evans rats were euthanized at 7, 14, 28, and 56 days after non-invasive ACL injury that was induced via tibial compression overload; controls were not injured. Vastus lateralis muscle was extracted, and subsequent immunoblotting analysis was conducted using primary antibodies targeting key proteins involved in autophagy and mitophagy cellular processes.Results: Our findings demonstrated dynamic changes in autophagy and mitophagy markers in the quadriceps muscle during the recovery period after ACL injury. The early response to the injury was characterized by the induction of autophagy at 14 days (Beclin1), indicating an initial cellular response to the injury. Subsequently, at 14 days we observed increase in the elongation of autophagosomes (Atg4B), suggesting a potential remodeling process. The autophagosome flux was also augmented between 14- and 28 days (LC3-II/LC3-I ratio and p62). Notably, at 56 days, markers associated with the elimination of damaged mitochondria were elevated (PINK1, Parkin, and VDAC1), indicating a possible ongoing cellular repair and restoration process.Conclusion: These data highlight the complexity of muscle recovery after ACL injury and underscore the overlooked but crucial role of autophagy and mitophagy in promoting the recovery process.

Abstract Aqueous suspensions of swelling clays display a nematic sol-gel transition at very low solid concentrations. The underlying microstructure of the gel has remained a point of contention since the time of Irving Langmuir and has been a major obstacle to fully realizing the potential of clays for practical applications. Here, we comprehensively probe the microstructure of a smectite clay suspension using ultra-small angle neutron/X-ray scattering and find that the nematic gel is structurally ordered and contains entities that are at least an order of magnitude larger than the individual particles. Complementary cryo-electron microscopy shows the presence of domains having particle-particle ordering responsible for nematic texture and regions of particle-particle aggregation responsible for gel-like behavior. We find that the smectic clay gels have a hybrid microstructure with co-existing repulsive nematic domains and attractive disordered domains.

Abstract Insecticide resistance is a multifaceted response and an issue across taxa. Aedes aegypti, the mosquito that vectors Zika, dengue, chikungunya, and yellow fever, demonstrates high levels of pyrethroid resistance across the globe, presenting a challenge to public health officials. To examine the transcriptomic shifts across time after exposure to permethrin, a 3’Tag-Seq analysis was employed on samples 6, 10, and 24 h after exposure along with controls. Differential expression analysis revealed significant shifts in detoxifying enzymes and various energy-producing metabolic processes. These findings indicate significant alterations in gene expression associated with key energy mobilization pathways within the system. These changes encompass a coordinated response involving lipolysis, beta-oxidation, and the citric acid cycle, required for the production of energetic molecules such as ATP, NADH, NADPH, and FADH. These findings highlight a complex interplay of metabolic processes that may have broader implications for understanding insect physiology and response to environmental stimuli. Among the upregulated detoxifying enzymes are cytochrome P450s, glutathione s-transferases and peroxidases, and ATP-binding cassette transporters. Additionally, eight heat shock genes or genes with heat shock domains exhibit the highest fold change across time. Twenty-four hours after exposure, samples indicate a global downregulation of these processes, though principal component analysis suggests lasting signatures of the response. Understanding the recovery response to insecticide exposure provides information on possible new genetic and synergist targets to explore.

Abstract Shotgun proteomics is essential for protein identification and quantification in biomedical research, but protein isoform characterization is challenging due to the extensive number of peptides shared across proteins, hindering our understanding of protein isoform regulation and their roles in normal and disease biology. We systematically assess the challenge and opportunities of shotgun proteomics-based protein isoform characterization using in silico and experimental data, and then present SEPepQuant, a graph theory-based approach to maximize isoform characterization. Using published data from one induced pluripotent stem cell study and two human hepatocellular carcinoma studies, we demonstrate the ability of SEPepQuant in addressing the key limitations of existing methods, providing more comprehensive isoform-level characterization, identifying hundreds of isoform-level regulation events, and facilitating streamlined cross-study comparisons. Our analysis provides solid evidence to support a widespread role of protein isoform regulation in normal and disease processes, and SEPepQuant has broad applications to biological and translational research.

Regulation of gene expression requires the combinatorial binding of sequence-specific transcription factors (TFs) at promoters and enhancers. Prior studies showed that alterations in the spacing between TF binding sites can influence promoter and enhancer activity. However, the relative importance of TF spacing alterations resulting from naturally occurring insertions and deletions (InDels) has not been systematically analyzed. To address this question, we first characterized the genome-wide spacing relationships of 73 TFs in human K562 cells as determined by ChIP-seq (chromatin immunoprecipitation sequencing). We found a dominant pattern of a relaxed range of spacing between collaborative factors, including 45 TFs exclusively exhibiting relaxed spacing with their binding partners. Next, we exploited millions of InDels provided by genetically diverse mouse strains and human individuals to investigate the effects of altered spacing on TF binding and local histone acetylation. These analyses suggested that spacing alterations resulting from naturally occurring InDels are generally tolerated in comparison to genetic variants directly affecting TF binding sites. To experimentally validate this prediction, we introduced synthetic spacing alterations between PU.1 and C/EBPβ binding sites at six endogenous genomic loci in a macrophage cell line. Remarkably, collaborative binding of PU.1 and C/EBPβ at these locations tolerated changes in spacing ranging from 5 bp increase to >30 bp decrease. Collectively, these findings have implications for understanding mechanisms underlying enhancer selection and for the interpretation of non-coding genetic variation.

This study examines the phenotypic differences between wild-derived F2 Central Valley mosquitoes and the insecticide-susceptible Rockefeller (Rock) lab strain of Ae. aegypti. Given the rarity of wild pyrethroid-susceptible populations, the focus of this work is to develop an understanding of the resistance physiology in this invasive mosquito population and explore the potential of metabolites as diagnostic biomarkers for metabolic resistance. This study utilizes metabolomic, gene expression, and lifespan data for a comparison between strains. The findings indicate that wild-derived mosquitoes with greater metabolic resistance have a lifespan sensitivity to restricted larval nutrition. In terms of metabolism and gene expression, Central Valley mosquitoes show increased activity in oxidoreductase, glutathione metabolism, and the pentose phosphate pathway. Conversely, Rock mosquitoes display signs of metabolic inefficiency and mitochondrial dysregulation, likely tolerated due to the consistency and nutritional abundance of a controlled lab environment. The study also examines Ae. aegypti P450 and GSTE profiles in relation to other insecticide-resistant groups. While metabolomic data can differentiate our study groups, the challenges in biomarker development arise from few detected markers meeting high fold change thresholds.

Fewer than 25% of global health leadership positions worldwide are held by women, adversely impacting women's health and widening gendered health disparities. The Female Global Scholars (FGS) Program, established in 2018 at Weill Cornell Medicine, is a two-year hybrid training and peer-mentorship program that promotes the retention and advancement of early-career female investigators conducting health research in low- and middle-income countries (LMICs). The purpose of this study is to determine the impact of the FGS Program on individual career advancement, academic productivity, and research self-efficacy. This mixed-methods study followed an explanatory sequential design. Participants completed an electronic survey collecting information on demographics, academic milestones, and research skill competency. Survey data were descriptively analyzed using R (Version 1.4.1106). In-depth interviews explored perceptions of the impact of the FGS Program on career development. The authors independently reviewed and thematically analyzed de-identified transcripts using NVivo (Version 13). In June 2022, twelve participants completed the survey. The median age was 40 years; 90% carried an MD, PhD, or other post-graduate degree. Since joining the FGS Program, respondents achieved a combined total of eight awarded grants, five academic promotions, 12 oral scientific presentations and 35 first-author peer-reviewed publications. Thematic analysis identified four overarching themes: gaining confidence through mimicry; improved self-efficacy to address gendered challenges; real-world application of scientific and career development skills; and building multi-disciplinary communities in a protected female-only space. We demonstrate that this low-cost training and mentorship program successfully addresses critical barriers that impede women's advancement in global health research. Our data may inform the adaptation of this initiative across other academic institutions.

African swine fever (ASF) causes significant morbidity and mortality in both domestic and wild suids (Sus scrofa), and disease outbreaks convey profound economic costs to impacted industries due to death loss, the cost of culling exposed/infected animals as the primary disease control measure, and trade restrictions. The co-occurrence of domestic and wild suids significantly complicates ASF management given the potential for wild populations to serve as persistent sources for spillover. We describe the unique threat of African swine fever virus (ASFV) introduction to the United States from epidemiological and ecological perspectives with a specific focus on disease management at the wild-domestic swine interface. The introduction of ASF into domestic herds would require a response focused on containment, culling, and contact tracing. However, detection of ASF among invasive wild pigs would require a far more complex and intensive response given the challenges of detection, containment, and ultimately elimination among wild populations. We describe the state of the science available to inform preparations for an ASF response among invasive wild pigs, describe knowledge gaps and the associated studies needed to fill those gaps, and call for an integrated approach for preparedness that incorporates the best available science and acknowledges sociological attributes and the policy context needed for an integrated disease response.

BackgroundSince their detection in 2013, Aedes aegypti has become a widespread urban pest in California. The availability of cryptic larval breeding sites in residential areas and resistance to insecticides pose significant challenges to control efforts. Resistance to pyrethroids is largely attributed to mutations in the voltage gated sodium channels (VGSC), the pyrethroid site of action. However, past studies have indicated that VGSC mutations may not be entirely predictive of the observed resistance phenotype.MethodsTo investigate the frequencies of VGSC mutations and the relationship with pyrethroid insecticide resistance in California, we sampled Ae. aegypti from four locations in the Central Valley, and the Greater Los Angeles area. Mosquitoes from each location were subjected to an individual pyrethrum bottle bioassay to determine knockdown times. A subset of assayed mosquitoes from each location was then analyzed to determine the composition of 5 single nucleotide polymorphism (SNP) loci within the VGSC gene.ResultsThe distribution of knockdown times for each of the five Californian populations sampled was non-parametric with potentially bimodal distributions. One group succumbs to insecticidal effects around 35-45 min and the second group lasts up to and beyond the termination of the assay (120+ min). We detected 5 polymorphic VGSC SNPs within the sampled California populations. One is potentially new and alternatively spliced (I915K), and four are documented and associated with resistance: F1534C, V1016I, V410L and S723T. The Central Valley populations (Clovis, Dinuba, Sanger and Kingsburg) are fairly homogenous with only 5% of the mosquitoes showing heterozygosity at any given position. In the Greater LA mosquitoes, 55% had at least one susceptible allele at any of the five SNP loci. The known resistance allele F1534C was detected in almost all sampled mosquitoes (99.4%). We also observe significant heterogeneity in the knockdown phenotypes of individuals with the identical VGSC haplotypes suggesting the presence of additional undefined resistance mechanisms.ConclusionsResistance associated VGSC SNPs are prevalent, particularly in the Central Valley. Interestingly, among mosquitoes carrying all 4 resistance associated SNPs, we observe significant heterogeneity in bottle bioassay profiles suggesting that other mechanisms are important to the individual resistance of Ae. aegypti in California.

AimsWhile most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation.Methods and resultsWe carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro.ConclusionsA large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.

Abstract Purpose The purpose of this study is to compare the early results of patient-reported outcomes between two generations of a total knee system. Methods Between June 2018 and April 2020, 121 first-generation, cemented TKAs (89 patients) and 123 s-generation, cemented TKAs (98 patients) were performed by a single surgeon. Demographic and surgical data were collected from all patients. Starting at the 6-month follow-up, patient-reported outcome measures Knee Injury and Osteoarthritis Outcome Score, Joint Reconstruction (KOOS-JR) and Knee Society (KS) clinical and radiographic scores were prospectively recorded. This study represents a retrospective review of these prospectively collected data. Results There were no statistically significant differences between the two groups in terms of demographic variables such as age, body mass index, gender and race. KOOS-JR and Knee Society (KS) scores improved significantly (p

The unplanned shift to online instruction due to the COVID-19 pandemic challenged many instructors teaching large-enrollment courses to design learning environments that actively engaged all students. We looked at how one instructor used her instructional team--a group of student assistants with diverse, structured responsibilities--to adapt her large-enrollment (>500 students) introductory chemistry course to a live-remote format, as well as the impact the team's involvement had on students' reported experiences of online learning. We found that the instructional team's involvement was instrumental in adapting the course to the live-remote online format. The integration of the instructional team had a significant positive impact on students' experiences in the course, including their perceptions of social and cognitive engagement and teacher presence. Students in the section with the integrated instructional team also outperformed students in other sections of the same course on standardized course exams and final course grade. These results suggest that a structured instructional team composed of students can be a mechanism for promoting positive student experiences and learning in large-enrollment, remote STEM courses.

Tsetse flies (genus Glossina), the sole vectors of African trypanosomiasis, are distinct from most other insects, due to dramatic morphological and physiological adaptations required to support their unique biology. These adaptations are driven by demands associated with obligate hematophagy and viviparous reproduction. Obligate viviparity entails intrauterine larval development and the provision of maternal nutrients for the developing larvae. The reduced reproductive capacity/rate associated with this biology results in increased inter- and intra-sexual competition. Here, we use phase contrast microcomputed tomography (pcMicroCT) to analyze morphological adaptations associated with viviparous biology. These include (1) modifications facilitating abdominal distention required during blood feeding and pregnancy, (2) abdominal and uterine musculature adaptations for gestation and parturition of developed larvae, (3) reduced ovarian structure and capacity, (4) structural features of the male-derived spermatophore optimizing semen/sperm delivery and inhibition of insemination by competing males and (5) structural features of the milk gland facilitating nutrient incorporation and transfer into the uterus. Three-dimensional analysis of these features provides unprecedented opportunities for examination and discovery of internal morphological features not possible with traditional microscopy techniques and provides new opportunities for comparative morphological analyses over time and between species.

Gut-associated phages are hypothesized to alter the abundance and activity of their bacterial hosts, contributing to human health and disease. Although temperate phages constitute a significant fraction of the gut virome, the effects of lysogenic infection are underexplored. We report that the temperate phage, Bacteroides phage BV01, broadly alters its host's transcriptome, the prominent human gut symbiont Bacteroides vulgatus. This alteration occurs through phage-induced repression of a tryptophan-rich sensory protein (TspO) and represses bile acid deconjugation. Because microbially modified bile acids are important signals for the mammalian host, this is a mechanism by which a phage may influence mammalian phenotypes. Furthermore, BV01 and its relatives in the proposed phage family Salyersviridae are ubiquitous in human gut metagenomes, infecting a broad range of Bacteroides hosts. These results demonstrate the complexity of phage-bacteria-mammal relationships and emphasize a need to better understand the role of temperate phages in the gut microbiome.

Background: Since their detection in 2013, Aedes aegypti has become a widespread urban pest in California. The availability of cryptic larval breeding sites in residential areas and resistance to insecticides pose significant challenges to control efforts. Resistance to pyrethroids is largely attributed to mutations in the voltage gated sodium channels (VGSC), the pyrethroid site of action. However, past studies have indicated that VGSC mutations may not be entirely predictive of the observed resistance phenotype. Methods: To investigate the frequencies of VGSC mutations and the relationship with pyrethroid insecticide resistance in California, we sampled Ae. aegypti from four locations in the Central Valley, and the Greater Los Angeles area. Mosquitoes from each location were subjected to an individual pyrethrum bottle bioassay to determine knockdown times. A subset of assayed mosquitoes from each location was then analyzed to determine the composition of 8 single nucleotide polymorphism (SNP) loci within the VGSC gene. Results: The distribution of knockdown times for each of the five Californian populations sampled was non-parametric with bimodal distributions. One group succumbs to insecticidal effects around 35-45 minutes and the second group lasts up to and beyond the termination of the assay (120+ minutes). We detected 5 SNPs polymorphic within California populations. One is potentially new and alternatively spliced (I915K), and four are known and associated with resistance: F1534C, V1016I, V410L and S723T. The Central Valley populations (Clovis, Dinuba, Sanger and Kingsburg) are fairly homogenous with only 5% of the mosquitoes showing heterozygosity at any given position. In the Greater LA mosquitoes 55% had at least one susceptible allele at any of the five SNPs. The known resistance allele F1534C was detected in almost all sampled mosquitoes (99.4%). We observe significant heterogeneity in individuals with the same genotypes, confirming that the resistance SNPs alone cannot. Conclusions: Resistance associated VGSC SNPs are prevalent, particularly in the Central Valley. Interestingly, among mosquitoes with all 4 resistance associated SNPs, we observe heterogeneity in bottle bioassay profiles suggesting that other mechanisms are important to the individual resistance of Ae. aegypti in California.