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We examined academic advisors' clinically significant symptoms of major depressive disorder (MDD) and generalized anxiety disorder (GAD), including whether there are statistically significant relationships between advisors' demographic characteristics, work-related variables, institutional variables, burnout, resilience, and risk of clinically significant MDD/GAD symptoms. We analyzed survey data of academic advisors collected from February to March 2023 (n = 777) and found that 16.9% of advisors met the criteria for MDD while 29.6% met the criteria for GAD, rates higher than national averages. While there were some demographic differences, advisors who experienced higher rates of burnout had increased odds of experiencing MDD and GAD symptoms. In addition, advisors' resilience was associated with decreased odds of experiencing MDD and GAD symptoms.

This study examined whether there are statistically significant relationships between academic advisors' demographic characteristics, advising-related variables, institutional variables, organizational context variables, and burnout during the COVID-19 pandemic. We used a national sample of academic advisors' survey data collected from February to March 2023 (n = 821). The results suggest 40.8% of academic advisors feel burned out from their work at least once a week to every day. The demographic characteristics and institutional variables did not explain a significant amount of variance in advisors' burnout; however, advising caseload and organizational context variables (i.e., workload, reward, community, and values) were consistently and significantly (p < 0.05) associated with advisors' emotional exhaustion, depersonalization, and lack of personal accomplishment.

The RNA dependent RNA polymerase (RdRp) in SARS-CoV-2 is a highly conserved enzyme responsible for viral genome replication/transcription. To understand how the viral RdRp achieves fidelity control during such processes, here we computationally investigate the natural non-cognate vs. cognate nucleotide addition and selectivity during viral RdRp elongation. We focus on the nucleotide substrate initial binding (RdRp active site open) to the prechemical insertion (active site closed) of the RdRp. The current studies were first carried out using microsecond ensemble equilibrium all-atom molecular dynamics (MD) simulations. Due to the slow conformational changes (from open to closed) during nucleotide insertion and selection, enhanced or umbrella sampling methods have been further employed to calculate the free energy profiles of the nucleotide insertion. Our studies find notable stability of noncognate dATP and GTP upon initial binding in the active-site open state. The results indicate that while natural cognate ATP and Remdesivir drug analogue (RDV-TP) are biased toward stabilization in the closed state to facilitate insertion, the natural non-cognate dATP and GTP can be well trapped in off-path initial binding configurations and prevented from insertion so that to be further rejected. The current work thus presents the intrinsic nucleotide selectivity of SARS-CoV-2 RdRp for natural substrate fidelity control, which should be considered in antiviral drug design.

Abstract Bacteroides species are abundant, prevalent, and stable members of the human gut microbiota, making them a promising chassis for developing long-term interventions for chronic diseases. Engineering Bacteroides as in situ bio-factories, however, requires efficient protein secretion tools, which are currently lacking. Here, we systematically investigate methods to enable heterologous protein secretion in Bacteroides. We identify a collection of secretion carriers that can export functional proteins across multiple Bacteroides species at high titers. To understand the mechanistic drivers of Bacteroides secretion, we characterize signal peptide sequence features, post-secretion extracellular fate, and the size limit of protein cargo. To increase titers and enable flexible control of protein secretion, we develop a strong, self-contained, inducible expression circuit. Finally, we validate the functionality of our secretion carriers in vivo in a mouse model. This toolkit promises to enable expanded development of long-term living therapeutic interventions for chronic gastrointestinal disease.

Abstract Considerable research shows that crime is concentrated at a few proprietary places: addresses and facilities. Emerging research suggests that proprietary places may radiate crime: activities at a place increase the risk of crime in the area around it. Weaknesses in the research create uncertainty about radiation, so we need more rigorous research. To conduct this research, we need a theory of crime radiation that operates at two spatial levels: the proprietary place and the area. This paper describes such a theory. Our theory states that crime radiation stems from the interaction between place management decisions at the place and offenders searching for opportunities in the area. Place managers create crime opportunities inside and outside their places. Offenders exploit place managers’ creations by deliberately searching for opportunities or by chancing upon the opportunities. The ways place managers and offenders interact gives rise to three types of crime radiation: hot dot, veiled dot, and cold dot. Finally, we propose questions crime scientists should answer to better understand crime radiation.

Cancer research training programs build our future biomedical workforce. Training is often centered for students residing close to research institutions, making access more challenging for rural students. A cancer research training program was developed for high school students residing in five geographical regions across Oregon. Training was tiered in duration and intensity across the three years, including a one-week Introduction program and subsequent 10-week summer research training programs (Immersion and Intensive). A total of 60 students participated in in-person and/or virtual training, with Immersion students receiving mentored shadowing experiences in clinical care, public health, and outreach in their home communities. Laboratory rotations at a research-intensive institution enabled students to sample research environments before selecting an area of interest for Intensive training the following summer. Aligning with Self-Determination Theory, the Knight Scholars Program aims to build competence, relatedness, and autonomy of its trainees in biomedical sciences. The program exposed students to a wide range of interprofessional careers and collaborative teams, enabling scholars to envision themselves in various paths. Results show strong gains in interest and research self-efficacy for both Introduction and Immersion scholars, with findings highlighting the importance of representation within mentoring and training efforts.

This publication was created to help Florida Extension specialists and their mentors in understanding their roles and responsibilities and the way their expertise fits within the Florida Cooperative Exten­sion Service (FCES). Written by Matt Benge, Karlibeth Leitheiser, Saqib Mukhtar, Karla P. Shelnutt, LaToya O’Neal, Maia McGuire, Shannon J. Horrillo, and Peyton N. Beattie, and published by the UF/IFAS Department of Agricultural Education and Communication, September 2024.

BackgroundEpisodic high-altitude exposure leads to optic disc edema and retinopathy. It is uncertain whether high-altitude exposure is a risk factor for nonarteritic anterior ischemic optic neuropathy (NAION).MethodsWe performed a single-center, retrospective, cross-sectional case study of 5 patients with high-altitude-associated NAION (HA-NAION) from April 2014 to April 2019. Main study parameters included known vascular risk factors for NAION, evolution of visual acuity, visual field, optic disc, and macula measurements.ResultsWe studied 5 eyes of 5 patients with HA-NAION that occurred at 7,000-9,000 ft above sea level, 28 patients with classic NAION that developed at sea level (normal altitude NAION or NA-NAION), and 40 controls. All 5 patients with HA-NAION had clinically confirmed NAION by a neuro-ophthalmologist within 3-21 days of onset and comprehensive follow-up evaluations (average follow-up of 23 months). Other than high-altitude exposure, 4 of 5 patients had undiagnosed obstructive sleep apnea (OSA, apnea-hypopnea index 5.4-22.2) and 1 had systemic vascular risk factors. All patients had disc-at-risk in the contralateral eye. The best-corrected distance visual acuity was 20/20 to 20/70 (median logMAR 0) at presentation and 20/70 to counting finger (median logMAR 0) at ≥6 months. Automated static perimetry revealed average mean deviation of -18.6 dB at presentation and -22.1 dB at ≥6 months. The average retinal nerve fiber layer was 244 µm (80-348 µm) at onset and 59 µm (55-80 µm) at ≥6 months. The average ganglion cell complex thickness was 50 µm (43-54 µm) at onset and 52 µm (50-55 µm) at ≥6 months. The patients with OSA were started on home continuous positive airway pressure treatment. Visual outcomes were similar in patients with HA-NAION and NA-NAION. - After addressing all NAION risk factors, no new events occurred in the HA-NAION group within 2-8 years with or without repeat high-altitude exposure.ConclusionsNAION can occur under high-altitude conditions. HA-NAION is associated with relatively younger age at onset, disc-at-risk, and OSA. These patients exhibit a relatively progressive course of vision loss after initial onset and severe thinning of optic nerves on optical coherence tomography. Treatment for OSA is recommended, especially with repeated high-altitude exposure.

Abstract Acquired resistance remains a major challenge for therapies targeting oncogene activated pathways. KRAS is the most frequently mutated oncogene in human cancers, yet strategies targeting its downstream signaling kinases have failed to produce durable treatment responses. Here, we developed multiple models of acquired resistance to dual-mechanism ERK/MAPK inhibitors across KRAS-mutant pancreatic, colorectal, and lung cancers, and then probed the long-term events enabling survival against this class of drugs. These studies revealed that resistance emerges secondary to large-scale transcriptional adaptations that are diverse and cell line-specific. Transcriptional reprogramming extends beyond the well-established early response, and instead represents a dynamic, evolved process that is refined to attain a stably resistant phenotype. Mechanistic and translational studies reveal that resistance to dual-mechanism ERK/MAPK inhibition is broadly susceptible to manipulation of the epigenetic machinery, and that Mediator kinase, in particular, can be co-targeted at a bottleneck point to prevent diverse, cell line-specific resistance programs.

Abstract VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20–150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood–brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p

This paper describes the creation of a theme-based first quarter, of a two quarter sequence, general chemistry laboratory course following an argument driven inquiry format and employing specifications grading. The course contains four, two-week projects investigating the chemistry of a popular sports drink. The sugar content, dye concentration, buffering capacity, and the kinetics of dye decomposition are investigated for various flavors of Gatorade. Specifications grading is used to foster teamwork and to provide an opportunity for revision and resubmission of student work. A modified LCAS survey measured student perception of course content.

Introduction: Many survivors of preterm birth (37 weeks gestation) and very preterm participants (≤32 weeks gestation). Ex vivo RNA was collected from brushings with sufficient cell numbers and in vitro RNA was extracted from cultured cells, with bulk RNA sequencing performed on both the sample types. Differential gene expression was assessed using the limma-trend pipeline and pathway enrichment identified using Reactome and GO analysis. To corroborate gene expression data, cytokine concentrations were measured in cell culture supernatant.Results: Transcriptomic analysis to compare term and preterm cells revealed 2,321 genes differentially expressed in ex vivo samples and 865 genes differentially expressed in cultured basal cell samples. Over one third of differentially expressed genes were related to host immunity, with interferon signalling pathways dominating the pathway enrichment analysis and IRF1 identified as a hub gene. Corroboration of disrupted interferon release showed that concentrations of IFN-α2 were below measurable limits in term samples but elevated in preterm samples [19.4 (76.7) pg/ml/µg protein, p = 0.03]. IFN-γ production was significantly higher in preterm samples [3.3 (1.5) vs. 9.4 (17.7) pg/ml/µg protein; p = 0.01] as was IFN-β [7.8 (2.5) vs. 13.6 (19.5) pg/ml/µg protein, p = 0.01].Conclusion: Host immunity may be compromised in the preterm nasal airway epithelium in early life. Altered immune responses may lead to cycles of repeated infections, causing persistent inflammation and tissue damage which can have significant impacts on long-term respiratory function.

Abstract Patterns of genetic variation reflect interactions among microevolutionary forces that vary in strength with changing demography. Here, patterns of variation within and among samples of the mouthbrooding gafftopsail catfish (Bagre marinus, Family Ariidae) captured in the U.S. Atlantic and throughout the Gulf of Mexico were analyzed using genomics to generate neutral and non‐neutral SNP data sets. Because genomic resources are lacking for ariids, linkage disequilibrium network analysis was used to examine patterns of putatively adaptive variation. Finally, historical demographic parameters were estimated from site frequency spectra. The results show four differentiated groups, corresponding to the (1) U.S. Atlantic, and the (2) northeastern, (3) northwestern, and (4) southern Gulf of Mexico. The non‐neutral data presented two contrasting signals of structure, one due to increases in diversity moving west to east and north to south, and another to increased heterozygosity in the Atlantic. Demographic analysis suggested that recently reduced long‐term effective population size in the Atlantic is likely an important driver of patterns of genetic variation and is consistent with a known reduction in population size potentially due to an epizootic. Overall, patterns of genetic variation resemble that of other fishes that use the same estuarine habitats as nurseries, regardless of the presence/absence of a larval phase, supporting the idea that adult/juvenile behavior and habitat are important predictors of contemporary patterns of genetic structure.

Abstract Diarrhea caused by Shigella has been associated with high morbidity and mortality in young children worldwide. There are no licensed vaccines, and those clinically advanced have restricted coverage as they elicit serotype-specific immunity while disease is caused by multiple circulating serotypes. Our group had previously reported a close association between serum antibodies to the Shigella virulence factor VirG (or IcsA) and clinical protection in infected individuals. VirG is highly conserved among Shigella strains and appealing as a broad-spectrum vaccine candidate. In this study, we investigated the immunogenicity and protective capacity of VirG as a subunit vaccine in mice. The surface-exposed alpha (α) domain of VirG (VirGα) was produced as a recombinant protein. This region has almost identical immune reactivity to full-length VirG. Administered intramuscularly with alum, VirGα elicited robust immune responses and high protective efficacy against S. flexneri 2a and S. sonnei. Almost complete protection was afforded by VirGα given intranasally with the E. coli double mutant heat-labile toxin (dmLT). VirGα-specific antibodies recognized VirG expressed on live Shigella, and blocked Shigella adhesion and invasion to human colonic cells. These results show for the first time that VirGα is a promising cross-protective vaccine candidate to prevent Shigella infection.

This paper describes the creation of a theme-based first quarter, of a two quarter sequence, general chemistry laboratory course following an argument driven inquiry format and employing specifications grading. The course contains four, two-week projects investigating the chemistry of a popular sports drink. The sugar content, dye concentration, buffering capacity, and the kinetics of dye decomposition are investigated for various flavors of Gatorade. Specifications grading is used to foster teamwork and to provide an opportunity for revision and resubmission of student work. A modified LCAS survey measured student perception of course content.

Remote delivery approaches to laboratory courses in the response to the COVID-19 pandemic have included a spectrum spanning passive options such as providing students with prerecorded videos of experiments to replacing in-person laboratory experiences with immersive virtual reality environments. While interactive activities that require students to make choices about experimental design or procedure, mimicking levels of inquiry present in in-person laboratory experiments, are preferred, creating custom activities of this type often require expensive equipment, a media production team, and knowledge of multiple programming languages. The open source, nonlinear storytelling platform, Twine, provides a free alternative that allows instructors to create custom interactive choose-your-own-adventure activities based on their existing laboratory curriculum and inclusive of text, images, and video clips. We used Twine to create a choose-your-own-adventure laboratory activity as the final experiment in a remote delivery format organic chemistry laboratory course that allowed students to obtain customized data based on their experimental choices. We expanded this work to create an entire course of Twine choose-your-own-adventure laboratory activities for a third term organic chemistry laboratory course.