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ABSTRACT Promoting diversity in the scientific workforce is crucial for harnessing the potential of available talent and ensuring equitable access to Science, Technology, Engineering, Mathematics, and Medicine (STEM-M) careers. We have developed an innovative program called Postbaccalaureate Research Opportunity to Promote Equity in Learning (PROPEL) that provides scientific and career development training for postbaccalaureate scholars from historically excluded backgrounds in STEM-M fields with an interest in pursuing a PhD or MD/PhD degree. Our program is distinct from other postbaccalaureate programs in that scholars are hired by individual labs rather than funded centrally by the program. This funding mechanism removes the idea that central funding is necessary to encourage faculty to train diverse scholars and allows the program to scale dynamically according to the needs of the scientific community. The PROPEL program started in 2020 with six scholars and has since grown to an enrollment of over 100, making it the largest postbaccalaureate program for biomedical research in the country. Here, we describe the program structure and curriculum, our strategy for recruitment, the enrollment trends, the program demographics, metrics of scholar engagement, and outcomes for scholars who completed the program in 2023. Our experience demonstrates the strong demand from both scholars and faculty for programming of this type and describes the feasibility of implementation.

Our understanding of the transitions of human embryonic stem cells (hESCs) between distinct stages of pluripotency relies predominantly on regulation by transcriptional and epigenetic programs with limited insight on the role of established morphological changes. We report remodeling of the actin cytoskeleton of hESCs as they transition from primed to naïve pluripotency which includes assembly of a ring of contractile actin filaments encapsulating colonies of naïve hESCs. Activity of the Arp2/3 complex is required for formation of the actin ring, to establish uniform cell mechanics within naïve colonies, to promote nuclear translocation of the Hippo pathway effectors YAP and TAZ, and for effective transition to naïve pluripotency. RNA-sequencing analysis confirms that Arp2/3 complex activity regulates Hippo signaling in hESCs, and impaired naïve pluripotency with inhibited Arp2/3 complex activity is rescued by expressing a constitutively active, nuclear-localized YAP-S127A. Moreover, expression of YAP-S127A partially restores the actin filament fence with Arp2/3 complex inhibition, suggesting that actin filament remodeling is both upstream and downstream of YAP activity. These new findings on the cell biology of hESCs reveal a mechanism for cytoskeletal dynamics coordinating cell mechanics to regulate gene expression and facilitate transitions between pluripotency states.

During the 2022 multinational outbreak of monkeypox virus (MPXV) infection, the antiviral drug tecovirimat (TPOXX; SIGA Technologies, Inc., https://www.siga.com) was deployed in the United States on a large scale for the first time. The MPXV F13L gene homologue encodes the target of tecovirimat, and single amino acid changes in F13 are known to cause resistance to tecovirimat. Genomic sequencing identified 11 mutations previously reported to cause resistance, along with 13 novel mutations. Resistant phenotype was determined using a viral cytopathic effect assay. We tested 124 isolates from 68 patients; 96 isolates from 46 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of tecovirimat treatment, whereas most isolates identified by routine surveillance of patients not treated with tecovirimat remained sensitive. The frequency of resistant viruses remains relatively low (

The fruit fly, Drosophila melanogaster, is an experimentally tractable model system that has recently emerged as a powerful “new approach methodology” (NAM) for chemical safety testing. As oogenesis is well conserved at the molecular and cellular level, measurements of Drosophila fecundity can be useful for identifying chemicals that affect reproductive health across species. However, standard Drosophila fecundity assays have been difficult to perform in a high-throughput manner because experimental factors such as the physiological state of the flies and environmental cues must be carefully controlled to achieve consistent results. In addition, exposing flies to a large number of different experimental conditions (such as chemical additives in the diet) and manually counting the number of eggs laid to determine the impact on fecundity is time-consuming. We have overcome these challenges by combining a new multiwell fly culture strategy with a novel 3D-printed fly transfer device to rapidly and accurately transfer flies from one plate to another, the RoboCam, a low-cost, custom-built robotic camera to capture images of the wells automatically, and an image segmentation pipeline to automatically identify and quantify eggs. We show that this method is compatible with robust and consistent egg laying throughout the assay period and demonstrate that the automated pipeline for quantifying fecundity is very accurate (r2 = 0.98 for the correlation between the automated egg counts and the ground truth). In addition, we show that this method can be used to efficiently detect the effects on fecundity induced by dietary exposure to chemicals. Taken together, this strategy substantially increases the efficiency and reproducibility of high-throughput egg-laying assays that require exposing flies to multiple different media conditions.

Abstract Achieving high solar-to-hydrogen (STH) efficiency concomitant with long-term durability using low-cost, scalable photo-absorbers is a long-standing challenge. Here we report the design and fabrication of a conductive adhesive-barrier (CAB) that translates >99% of photoelectric power to chemical reactions. The CAB enables halide perovskite-based photoelectrochemical cells with two different architectures that exhibit record STH efficiencies. The first, a co-planar photocathode-photoanode architecture, achieved an STH efficiency of 13.4% and 16.3 h to t60, solely limited by the hygroscopic hole transport layer in the n-i-p device. The second was formed using a monolithic stacked silicon-perovskite tandem, with a peak STH efficiency of 20.8% and 102 h of continuous operation before t60 under AM 1.5G illumination. These advances will lead to efficient, durable, and low-cost solar-driven water-splitting technology with multifunctional barriers.

The morphologically variable genus Archidendron is the second largest mimosoid legume genus from the Indomalayan-Australasian region, yet it has not been well represented in phylogenetic studies. Phylogenies that have included multiple representatives of Archidendron suggest it may not be monophyletic, and the same applies to Archidendropsis, another understudied genus of the Archidendron clade. The most comprehensive phylogeny of Archidendron and Archidendropsis to date is presented, based on four nuclear markers (ITS, ETS, SHMT and RBPCO). Exemplars from all genera of the wider Archidendron clade are sampled, including representatives of all series within Archidendron and the two subgenera of Archidendropsis. Our results confirm that Archidendron and Archidendropsis are not monophyletic. Within Archidendron, only one series (ser. Ptenopae) is resolved as monophyletic and species of Archidendron are divided into two primarily geographic lineages. One clade is distributed in western Malesia and mainland Asia and includes most representatives of series Clypeariae, while the other is mostly restricted to eastern Malesia and Australia and includes representatives of the seven other series plus two samples of series Clypeariae. No taxonomic changes are made for Archidendron due to the high level of topological uncertainty and the lack of discrete macromorphological characters separating these two lineages. Each of the two subgenera of Archidendropsis is monophyletic but they are not closely related. A new genus endemic to Queensland (Australia), Heliodendron Gill.K. Br. & Bayly, gen. nov., is described for the former Archidendropsis subg. Basaltica, and combinations for its three species are proposed: Heliodendron basalticum (F. Muell.) Gill.K. Br. & Bayly, comb. nov., Heliodendron thozetianum (F. Muell.) Gill.K. Br. & Bayly, comb. nov., and Heliodendron xanthoxylon (C.T. White & W.D. Francis) Gill.K. Br. & Bayly, comb. nov.

Background: Despite the high cost of low birth weight and the persistent challenge of racial inequities affecting the Arab American community, there has been limited research to identify and examine risk factors for these inequities with validated data on Arab American ethnicity and recent population stressors. Objectives: This study examined whether the 2016 presidential election is associated with low birth weight among non-Hispanic White, Arab American, Hispanic, and non-Hispanic Black women. Design: This population-based study of singleton births in Michigan (2008–2017) used an algorithm to identify mothers who were of Arab descent. Methods: We used logistic regression to estimate odds ratios and 95% confidence intervals for the association between race/ethnicity and the odds of low birth weight. We examined whether these associations differed before and after the 2016 presidential election and according to maternal education. Results: There were 1,019,738 births, including 66,272 (6.5%) classified as low birth weight. The odds of having a low-birth-weight infant were higher among all minority women compared to non-Hispanic White women. The association was similar before and after the 2016 presidential election and stronger among women with higher levels of education. Conclusion: This is the first study to estimate low birth weight among Arab American women in the context of political events. There are opportunities for future studies to discuss this issue in depth.

Abstract Human rabies remains a globally significant public health problem. Replacement of polyclonal anti-rabies immunoglobulin (RIG), a passive component of rabies post-exposure prophylaxis (PEP), with a monoclonal antibody (MAb), would eliminate the cost and availability constraints associated with RIG. Our team has developed and licensed a human monoclonal antibody RAB1 (Rabishield©), as the replacement for RIG where canine rabies is enzootic. However, for the highly diverse rabies viruses of North America, a cocktail containing two or more MAbs targeting different antigenic sites of the rabies glycoprotein should be included to ensure neutralization of all variants of the virus. In this study, two MAb cocktails, R172 (RAB1-RAB2) and R173 (RAB1-CR57), were identified and evaluated against a broad range of rabies variants from North America. R173 was found to be the most potent cocktail, as it neutralized all the tested North American RABV isolates and demonstrated broad coverage of isolates from both terrestrial and bat species. R173 could be a promising candidate as an alternative or replacement for RIG PEP in North America.

With regards to the relationship between mental and physical health conditions, some studies predict increased headache frequency as a result of exposure to stressful situations. Thus, the purpose of our study was to investigate whether headache characteristics among a sample of university students (N = 234) correlated with fear of COVID-19, stress and quality of life vis-à-vis the pandemic. We found statistically significant positive correlations between headache frequency and both general stress and quality of life. Further, results from a multiple regression analysis suggested that fear of COVID-19 did not account for incremental variance in headache intensity. Explanations for our key findings, limitations of our study, and future directions for post pandemic studies on headache experience are outlined.

Photoelectrochemical (PEC) water splitting, which utilizes sunlight and water to produce hydrogen fuel, is potentially one of the most sustainable routes to clean energy. One challenge to success is that, to date, similar materials and devices measured in different labs or by different operators lead to quantitatively different results, due to the lack of accepted standard operating procedures and established protocols for PEC efficiency testing. With the aim of disseminating good practices within the PEC community, we provide a vetted protocol that describes how to prepare integrated components and accurately measure their solar-to-hydrogen (STH) efficiency (ηSTH). This protocol provides details on electrode fabrication, ηSTH test device assembly, light source calibration, hydrogen evolution measurement, and initial material qualification by photocurrent measurements under monochromatic and broadband illumination. Common pitfalls in translating experimental results from any lab to an accurate STH efficiency under an AM1.5G reference spectrum are discussed. A III–V tandem photocathode is used to exemplify the process, though with small modifications, the protocol can be applied to photoanodes as well. Dissemination of PEC best practices will help those approaching the field and provide guidance for comparing the results obtained at different lab sites by different groups.

Abstract Waste isolation is a key strategy for mitigating risk from municipal solid waste (MSW) and hazardous waste streams. Conventional covers at MSW facilities are designed for a 30‐yr post‐closure period where compacted soils and geosynthetics are used to minimize percolation into buried waste. Recently, evapotranspiration (ET) covers have shown beneficial use for MSW management. Evapotranspiration covers encourage infiltration, storage, and transpiration of precipitation to minimize percolation. Such covers may also have beneficial use for long‐term waste issues, such as at Uranium Mill Tailings Radiation Control Act (UMTRCA) sites. These sites were covered by a clay radon barrier to create tortuous flow paths that allow radioactive decay and attenuation of short‐lived, radon‐222 gas. For long‐term waste isolation, an ET‐radon cover may provide greater resilience by exploiting natural processes instead of resisting them. This update presents a review of the current state‐of‐the‐science regarding ET covers and considerations for long‐term applications.

Photoelectrochemical (PEC) water splitting, one of the most promising technologies for clean hydrogen generation, has drawn considerable attention over the past few decades. Achieving simultaneous highly efficient and stable unassisted PEC water splitting has been the “holy grail” in clean and renewable fuel generation. State-of-the-art photoelectrodes have shown relatively high efficiencies (∼10–20%). Still, their stability is limited due to photoelectrode chemical instability, electrolyte resistance, mass transfer issues, and an often unoptimized experimental setup. In this work, we present a framework and a set of protocols for conducting long-term stability experiments and further provide details on several critical factors such as light source calibration, choosing the right counter electrode, the configuration of the PEC cell, and photoelectrode sample preparation.

Abstract Aim To infer relationships between populations of the semi‐arid, mallee eucalypt, Eucalyptus behriana, to build hypotheses regarding evolution of major disjunctions in the species' distribution and to expand understanding of the biogeographical history of southeastern Australia. Location Southeastern Australia. Taxon Eucalyptus behriana (Myrtaceae, Angiospermae). Methods We developed a large dataset of anonymous genomic loci for 97 samples from 11 populations of E. behriana using double digest restriction site‐associated DNA sequencing (ddRAD‐seq), to determine genetic relationships between the populations. These relationships, along with species distribution models, were used to construct hypotheses regarding environmental processes that have driven fragmentation of the species’ distribution. Results Greatest genetic divergence was between populations on either side of the Lower Murray Basin. Populations west of the Basin showed greater genetic divergence between one another than the eastern populations. The most genetically distinct population in the east (Long Forest) was separated from others by the Great Dividing Range. A close relationship was found between the outlying northernmost population (near West Wyalong) and those in the Victorian Goldfields despite a large disjunction between them. Conclusions Patterns of genetic variation are consistent with a history of vicariant differentiation of disjunct populations. We infer that an early disjunction to develop in the species distribution was that across the Lower Murray Basin, an important biogeographical barrier separating many dry sclerophyll plant taxa in southeastern Australia. Additionally, our results suggest that the western populations fragmented earlier than the eastern ones. Fragmentation, both west and east of the Murray Basin, is likely tied to climatic changes associated with glacial‐interglacial cycles although it remains possible that major geological events including uplift of the Mount Lofty Ranges and basalt flows in the Newer Volcanics Province also played a role.

Cell types in the adult Drosophila ovary vary during homeostasis and differing environmental conditions. Here, the authors use single-cell RNA-sequencing to identify 26 ovarian cell populations and show cellular plasticity in which escort cells can convert to follicle stem cells upon starvation.

Metastatic spread of testicular cancer has been well documented, with 95% of cases involving para-aortic retroperitoneal lymph nodes. Mesenteric lymphatic basins do not lie within the canonical drainage pathway of the testes and represent a rare site of metastasis. Various mechanisms of spread to the mesentery have been described, including direct extension and haematogenous dissemination. We present a case of a previously-well 43-year-old man who presented with right scrotal discomfort and intermittent lower back pain, who was found to have mesenteric metastases from a non-seminomatous germ cell tumour of the testis. Managing lymphadenopathy that lies outside of standard resection templates remains a complex surgical challenge. Here we present the first case in the English medical literature with co-existing supradiaphragmatic axillary and mediastinal nodal disease.

Using questionnaires and serologic testing, we evaluated bat and lyssavirus exposure among persons in an area of Nigeria that celebrates a bat festival. Bats from festival caves underwent serologic testing for phylogroup II lyssaviruses (Lagos bat virus, Shimoni bat virus, Mokola virus). The enrolled households consisted of 2,112 persons, among whom 213 (10%) were reported to have ever had bat contact (having touched a bat, having been bitten by a bat, or having been scratched by a bat) and 52 (2%) to have ever been bitten by a bat. Of 203 participants with bat contact, 3 (1%) had received rabies vaccination. No participant had neutralizing antibodies to phylogroup II lyssaviruses, but >50% of bats had neutralizing antibodies to these lyssaviruses. Even though we found no evidence of phylogroup II lyssavirus exposure among humans, persons interacting with bats in the area could benefit from practicing bat-related health precautions.

While prior research shows that pharmaceutical innovation generates measurable benefits for society, over the last 70 years, the innovative activities of pharmaceutical firms have dramatically declined. In this study, we develop and test the hypothesis that to innovate, pharmaceutical firms must have access to capital through well-developed financial markets. Using a broad cross-country sample from 1989 to 2016, we document that financial market development is associated with greater levels of pharmaceutical innovation. To draw stronger causal inferences, and to overcome potential endogeneity issues, we use both instrumental variable and difference-in-difference analysis. Our results suggest that access to capital markets plays a vital role in pharmaceutical innovation.

Acacia (Leguminosae, Caesalpinioideae, mimosoid clade) is the largest and most widespread genus of plants in the Australian flora, occupying and dominating a diverse range of environments, with an equally diverse range of forms. For a genus of its size and importance, Acacia currently has surprisingly few genomic resources. Acacia pycnantha, the golden wattle, is a woody shrub or tree occurring in south-eastern Australia and is the country’s floral emblem. To assemble a genome for A. pycnantha, we generated long-read sequences using Oxford Nanopore Technology, 10x Genomics Chromium linked reads, and short-read Illumina sequences, and produced an assembly spanning 814 Mb, with a scaffold N50 of 2.8 Mb, and 98.3% of complete Embryophyta BUSCOs. Genome annotation predicted 47,624 protein-coding genes, with 62.3% of the genome predicted to comprise transposable elements. Evolutionary analyses indicated a shared genome duplication event in the Caesalpinioideae, and conflict in the relationships between Cercis (subfamily Cercidoideae) and subfamilies Caesalpinioideae and Papilionoideae (pea-flowered legumes). Comparative genomics identified a suite of expanded and contracted gene families in A. pycnantha, and these were annotated with both GO terms and KEGG functional categories. One expanded gene family of particular interest is involved in flowering time and may be associated with the characteristic synchronous flowering of Acacia. This genome assembly and annotation will be a valuable resource for all studies involving Acacia, including the evolution, conservation, breeding, invasiveness, and physiology of the genus, and for comparative studies of legumes.

Introduction. Bladder neck abscesses are rare urologic pathologies with very few cases published in modern literature. This report explores a case of a bladder neck mass incidentally found on computed tomography (CT) imaging in a patient with an iliopsoas abscess. Case Presentation. We present a case of a 60-year-old woman who was recently treated for sepsis secondary to an iliopsoas abscess in July of 2022. A CT scan revealed an indeterminate structure in the posterior inferior left paramedian bladder wall. During a cystoscopy with transurethral resection of the mass, an abscess was uncovered and evacuated. A postoperative Foley catheter was left in place, and the patient recovered without any complications. Conclusion. At the time of publication, the patient feels well and denies pain or lower urinary tract symptoms. Although bladder abscesses are exceptionally rare, incidental findings during cystoscopy may warrant further investigation in patients with comorbid abscesses.

A 50-year-old male underwent small volume TURP for median lobe prostatic hypertrophy. Post-procedure, a 3-way urethral catheter was placed. He subsequently developed flank pain, anuria and creatinine rise. CT demonstrated bilateral obstructive uropathy.In the absence of obstructing lesions, it was suspected that the catheter balloon may have caused obstruction of bilateral ureteric orifices. Balloon deflation (from 30 to 10 mL) and catheter repositioning resulted in rapid resolution of pain and resumption of urine output.Urologists should consider the catheter balloon as a cause of obstructive uropathy, especially after procedures where normal trigonal anatomy is disrupted.

Recent developments in Transformer language models now allow users to predict the probability of different sentences and to predict missing words more accurately than before. This new information and perspective can be used to form judgments on novel textual emendations and to further quantify existing historical editorial judgments. We examine the importance of analyzing an author’s corpus, and the impact of the Good-Turing theory of frequency estimation when predicting missing words. We will also outline some of the limits of what Transformer language models can do, and how to practically evaluate them.

Organelle genomes are typically represented as single, static, circular molecules. However, there is evidence that the chloroplast genome exists in two structural haplotypes and that the mitochondrial genome can display multiple circular, linear or branching forms. We sequenced and assembled chloroplast and mitochondrial genomes of the Golden Wattle, Acacia pycnantha, using long reads, iterative baiting to extract organelle-only reads, and several assembly algorithms to explore genomic structure. Using a de novo assembly approach agnostic to previous hypotheses about structure, we found that different assemblies revealed contrasting arrangements of genomic segments; a hypothesis supported by mapped reads spanning alternate paths.

Photoelectrochemical water splitting presents an integrated means storing sunlight into fuels, yet high optical losses and corrosion limit device performance. Here, authors boost absorption and durability in gallium-indium phosphide photocathodes via a sulfurized and nanostructured protection layer.

Our understanding of the transitions of human embryonic stem cells (hESCs) between distinct stages of pluripotency relies predominantly on regulation by transcriptional and epigenetic programs with limited insight on the role of established morphological changes. We report remodeling of the actin cytoskeleton of hESCs as they transition from primed to naïve pluripotency which includes assembly of a ring of contractile actin filaments encapsulating colonies of naïve hESCs. Activity of the Arp2/3 complex is required for formation of the actin ring, to establish uniform cell mechanics within naïve colonies, to promote nuclear translocation of the Hippo pathway effectors YAP and TAZ, and for effective transition to naïve pluripotency. RNA-sequencing analysis confirms that Arp2/3 complex activity regulates Hippo signaling in hESCs, and impaired naïve pluripotency with inhibited Arp2/3 complex activity is rescued by expressing a constitutively active, nuclear-localized YAP-S127A. Moreover, expression of YAP-S127A partially restores the actin filament fence with Arp2/3 complex inhibition, suggesting that actin filament remodeling is both upstream and downstream of YAP activity. These new findings on the cell biology of hESCs reveal a mechanism for cytoskeletal dynamics coordinating cell mechanics to regulate gene expression and facilitate transitions between pluripotency states.

Abstract Soil moisture is a critical land surface variable, affecting a wide variety of climatological, agricultural, and hydrological processes. Determining the current soil moisture status is possible via a variety of methods, including in situ monitoring, remote sensing, and numerical modeling. Although all of these approaches are rapidly evolving, there is no cohesive strategy or framework to integrate these diverse information sources to develop and disseminate coordinated national soil moisture products that will improve our ability to understand climate variability. The National Coordinated Soil Moisture Monitoring Network initiative has developed a national strategy for network coordination with NOAA's National Integrated Drought Information System. The strategy is currently in review within NOAA, and work is underway to implement the initial milestones of the strategy. This update reviews the goals and steps being taken to establish this national‐scale coordination for soil moisture monitoring in the United States.

PREMISE Universal target enrichment kits maximize utility across wide evolutionary breadth while minimizing the number of baits required to create a cost‐efficient kit. The Angiosperms353 kit has been successfully used to capture loci throughout the angiosperms, but the default target reference file includes sequence information from only 6–18 taxa per locus. Consequently, reads sequenced from on‐target DNA molecules may fail to map to references, resulting in fewer on‐target reads for assembly, and reducing locus recovery. METHODS We expanded the Angiosperms353 target file, incorporating sequences from 566 transcriptomes to produce a ‘mega353’ target file, with each locus represented by 17–373 taxa. This mega353 file is a drop‐in replacement for the original Angiosperms353 file in HybPiper analyses. We provide tools to subsample the file based on user‐selected taxon groups, and to incorporate other transcriptome or protein‐coding gene data sets. RESULTS Compared to the default Angiosperms353 file, the mega353 file increased the percentage of on‐target reads by an average of 32%, increased locus recovery at 75% length by 49%, and increased the total length of the concatenated loci by 29%. DISCUSSION Increasing the phylogenetic density of the target reference file results in improved recovery of target capture loci. The mega353 file and associated scripts are available at: https://github.com/chrisjackson‐pellicle/NewTargets.

The Meanings of Adolescent Masculinity Scale (MAMS) and the Adolescent Masculinity Ideology in Relationships Scale (AMIRS) were designed by American researchers to assess masculinity in adolescent boys. Given that masculinities differ cross-culturally, though, these scales may not be viable for use with non-American populations. In the current study, 221 Irish adolescents completed the MAMS and the AMIRS. Using confirmatory factor analyses (CFAs), the MAMS’s and the AMIRS’s factor structures were tested. Results indicated poor goodness-of-fit in both cases. Attempts to improve the models were unsuccessful. Accordingly, neither the MAMS nor the AMIRS appear to be structurally valid within an Irish context. We recommend that researchers consider cultural variations when designing, validating, and utilizing indicators of masculinity.

Among 15–24 year olds in Ireland, completed suicide was responsible for 4.1 times more male deaths than female deaths in 2014 (World Health Organization [WHO], 2017). Few international research studies have investigated the relationship between masculinity [as assessed by a measure of gender role conflict (GRC)] and suicide ideation, and none have done so with Irish adolescents. Therefore, the purpose of the current study was to investigate the relationships between a new measure of GRC developed specifically for use with Irish adolescents (I-GRCS-A; O’Beaglaoich et al., 2016), and depression, self-esteem, and negative/protective suicide ideation. A sample of 176 adolescent boys (M = 16.9, SD = 0.94) from a non-clinical population participated in the study. Regression analyses and tests of mediation revealed that depression significantly mediated the relationship between GRC and negative suicide ideation, whilst self-esteem and depression significantly mediated the relationship between GRC and positive suicide ideation. Implications and limitations of the current study are outlined and directions for future research are discussed.

Abstract A trans-agency workshop on the blood–brain interface (BBI), sponsored by the National Heart, Lung and Blood Institute, the National Cancer Institute and the Combat Casualty Care Research Program at the Department of Defense, was conducted in Bethesda MD on June 7–8, 2016. The workshop was structured into four sessions: (1) blood sciences; (2) exosome therapeutics; (3) next generation in vitro blood–brain barrier (BBB) models; and (4) BBB delivery and targeting. The first day of the workshop focused on the physiology of the blood and neuro-vascular unit, blood or biofluid-based molecular markers, extracellular vesicles associated with brain injury, and how these entities can be employed to better evaluate injury states and/or deliver therapeutics. The second day of the workshop focused on technical advances in in vitro models, BBB manipulations and nanoparticle-based drug carrier designs, with the goal of improving drug delivery to the central nervous system. The presentations and discussions underscored the role of the BBI in brain injury, as well as the role of the BBB as both a limiting factor and a potential conduit for drug delivery to the brain. At the conclusion of the meeting, the participants discussed challenges and opportunities confronting BBI translational researchers. In particular, the participants recommended using BBI translational research to stimulate advances in diagnostics, as well as targeted delivery approaches for detection and therapy of both brain injury and disease.

Reverse cholesterol transport (RCT) is thought to be an atheroprotective function of HDL, and macrophage-specific RCT in mice is inversely associated with atherosclerosis. We developed a novel method using 3H-cholesterol nanoparticles to selectively trace macrophage-specific RCT in vivo in humans. Use of 3H-cholesterol nanoparticles was initially tested in mice to assess the distribution of tracer and response to interventions known to increase RCT. Thirty healthy subjects received 3H-cholesterol nanoparticles intravenously, followed by blood and stool sample collection. Tracer counts were assessed in plasma, nonHDL, HDL, and fecal fractions. Data were analyzed by using multicompartmental modeling. Administration of 3H-cholesterol nanoparticles preferentially labeled macrophages of the reticuloendothelial system in mice, and counts were increased in mice treated with a liver X receptor agonist or reconstituted HDL, as compared with controls. In humans, tracer disappeared from plasma rapidly after injection of nanoparticles, followed by reappearance in HDL and nonHDL fractions. Counts present as free cholesterol increased rapidly and linearly in the first 240 min after nadir; counts in cholesteryl ester increased steadily over time. Estimates of fractional transfer rates of key RCT steps were obtained. These results support the use of 3H-cholesterol nanoparticles as a feasible approach for the measurement of macrophage RCT in vivo in humans.

The follicle stem cells (FSCs) in the Drosophila ovary are an important experimental model for the study of epithelial stem cell biology. Although decades of research support the conclusion that there are two FSCs per ovariole, a recent study used a novel clonal marking system to conclude that there are 15–16 FSCs per ovariole. We performed clonal analysis using both this novel clonal marking system and standard clonal marking systems, and identified several problems that may have contributed to the overestimate of FSC number. In addition, we developed new methods for accurately measuring clone size, and found that FSC clones produce, on average, half of the follicle cells in each ovariole. Our findings provide strong independent support for the conclusion that there are typically two active FSCs per ovariole, though they are consistent with up to four FSCs per germarium.

The spatiotemporal variability of soil water content (SWC) at the remote sensing scale requires dense monitoring for calibration and validation. Here, we present an overview of the Texas Soil Observation Network (TxSON), an intensively monitored area in the semiarid rangelands of the central Texas Hill Country. TxSON is a dense network consisting of 40 in situ locations nested at 36, 9, and 3 km within the Equal-Area Scalable Earth Grid and serves as a Core Calibration and Validation Site for NASA’s Soil Moisture Active Passive mission. The 4-yr dataset consists of hourly SWC measured at 5, 10, 20, and 50 cm. The SWC data are upscaled using arithmetic, Voronoi, and inverse distance weighting for 36-, (2) 9-, and (5) 3-km grid cells. We present the site selection, environmental characteristics, network design, quality assurance (QA), upscaling algorithms, and data structure. Ancillary data include bulk density, particle size, and carbon content for each site and depth. We also provide automated QA for each location and scripts to use our binary flagging in upscaling methods. To summarize, the 36-km grid cell has a mean bulk density of 1.34 ± 0.18 g cm and a loam textural class. The in situ SWC has a root mean square error of 0.029 m m against gravimetric data from 14 field campaigns. TxSON continues to add new locations with additional dense networks planned in other ecotones of the Edwards Plateau. The time series data along with scripts to import, plot, and upscaled SWC are available at .

Today’s smartphones allow for a wide range of “big data” measurement, for example, ecological momentary assessment (EMA), whereby behaviours are repeatedly assessed within a person’s natural environment. With this type of data, we can better understand – and predict – risk for behavioral and health issues and opportunities for (self-monitoring) interventions. In this mixed-methods feasibility study, through convenience sampling we collected data from 32 participants (aged 16–24) over a period of three months. To gain more insight into the app experiences of youth with mental health problems, we interviewed a subsample of 10 adolescents who received psycthological treatment. The results from this feasibility study indicate that emojis) can be used to identify positive and negative feelings, and individual pattern analyses of emojis may be useful for clinical purposes. While adolescents receiving mental health care are positive about future applications, these findings also highlight some caveats, such as possible drawback of inaccurate representation and incorrect predictions of emotional states. Therefore, at this stage, the app should always be combined with professional counseling. Results from this small pilot study warrant replication with studies of substantially larger sample size.

Mild traumatic brain injury (mTBI), also known as concussion, is a serious public health challenge. Although most patients recover, a substantial minority suffers chronic disability. The mechanisms underlying mTBI-related detrimental effects remain poorly understood. Although animal models contribute valuable preclinical information and improve our understanding of the underlying mechanisms following mTBI, only few studies have used diffusion tensor imaging (DTI) to study the evolution of axonal injury following mTBI in rodents. It is known that DTI shows changes after human concussion and the role of delineating imaging findings in animals is therefore to facilitate understanding of related mechanisms. In this work, we used a rodent model of mTBI to investigate longitudinal indices of axonal injury. We present the results of 45 animals that received magnetic resonance imaging (MRI) at multiple time points over a 2-week period following concussive or sham injury yielding 109 serial observations. Overall, the evolution of DTI metrics following concussive or sham injury differed by group. Diffusion tensor imaging changes within the white matter were most noticeable 1 week following injury and returned to baseline values after 2 weeks. More specifically, we observed increased fractional anisotropy in combination with decreased radial diffusivity and mean diffusivity, in the absence of changes in axial diffusivity, within the white matter of the genu corpus callosum at 1 week post-injury. Our study shows that DTI can detect microstructural white matter changes in the absence of gross abnormalities as indicated by visual screening of anatomical MRI and hematoxylin and eosin (H&E)-stained sections in a clinically relevant animal model of mTBI. Whereas additional histopathologic characterization is required to better understand the neurobiological correlates of DTI measures, our findings highlight the evolving nature of the brain’s response to injury following concussion.

Early life experiences program brain structure and function and contribute to behavioral endophenotypes in adulthood. Epigenetic control of gene expression by those experiences affect discrete brain regions involved in mood, cognitive function and regulation of hypothalamic-pituitary-adrenal (HPA) axis. In rodents, acute restraint stress increases the expression of the repressive histone H3 lysine 9 tri-methylation (H3K9me3) in hippocampal fields, including the CA3 pyramidal neurons. These CA3 neurons are crucially involved in cognitive function and mood regulation as well as activation of glucocorticoid (CORT) secretion. CA3 neurons also exhibit structural and functional changes after early-life stress (ELS) as well as after chronic stress in adulthood. Using a protocol of chronic ELS induced by limited bedding and nesting material followed by acute-swim stress (AS) in adulthood, we show that mice with a history of ELS display a blunted CORT response to AS, despite exhibiting activation of immediate early genes after stress similar to that found in control mice. We find that ELS induced persistently increased expression of the repressive H3K9me3 histone mark in the CA3 subfield at baseline that was subsequently decreased following AS. In contrast, AS induced a transient increase of this mark in control mice. Using translating ribosome affinity purification (TRAP) method to isolate CA3 translating mRNAs, we found that expression of genes of the epigenetic gene family, GABA/glutamate family, and glucocorticoid receptors binding genes were decreased transiently in control mice by AS and showed a persistent reduction in ELS mice. In most cases, AS in ELS mice did not induce gene expression changes. A stringent filtering of genes affected by AS in control and ELS mice revealed a noteworthy decrease in gene expression change in ELS mice compared to control. Only 18 genes were selectively regulated by AS in ELS mice and encompassed pathways such as circadian rhythm, inflammatory response, opioid receptors, and more genes included in the glucocorticoid receptor binding family. Thus, ELS programs a restricted translational response to stress in stress-sensitive CA3 neurons leading to persistent changes in gene expression, some of which mimic the transient effects of AS in control mice, while leaving in operation the immediate early gene response to AS.

Traumatic brain injury (TBI) is highly prevalent and there is currently no adequate treatment. Understanding the underlying mechanisms governing TBI and recovery remains an elusive goal. The heterogeneous nature of injury and individual’s response to injury have made understanding risk and susceptibility to TBI of great importance. Epidemiologic studies have provided evidence of sex-dependent differences following TBI. However, preclinical models of injury have largely focused on adult male animals. Here, we review 50 studies that have investigated TBI in both sexes using animal models. Results from these studies are highly variable and model dependent, but largely show females to have a protective advantage in behavioral outcomes and pathology following TBI. Further research of both sexes using newer models that better recapitulate mild and repetitive TBI is needed to characterize the nature of sex-dependent injury and recovery, and ultimately identifies targets for enhanced recovery.