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Nursing assistants (NAs) are critical professionals across the long-term care continuum. Despite the demands of NAs, these frontline personnel experience workplace challenges and turnover at a disproportionate rate compared to other professionals. Much research has explored the experiences of nursing assistants using federal survey data and national datasets. Guided by a socio-ecological model and the job-demands resource model, this study utilized a sequential mixed-methods approach to uncover a more nuanced understanding of NA workplace experience. Results from this combined qualitative ( N = 17) and quantitative ( N = 354) study found that there are several workplace aspects, such as organizational culture and supervisor relationships, that contribute to NA experiences across system levels. Further exploration of direct care tasks directly from nursing assistants is necessary to understand full intentions.

Abstract Biomaterial-associated infections are a major healthcare challenge as they are responsible for high disease burden in critically ill patients. In this study, we have developed drug-eluting antibacterial catheters to prevent catheter-related infections. Niclosamide (NIC), originally an antiparasitic drug, was incorporated into the polymeric matrix of thermoplastic polyurethane (TPU) via solvent casting, and catheters were fabricated using hot-melt extrusion technology. The mechanical and physicochemical properties of TPU polymers loaded with NIC were studied. NIC was released in a sustained manner from the catheters and exhibited in vitro antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis. Moreover, the antibacterial efficacy of NIC-loaded catheters was validated in an in vivo biomaterial-associated infection model using a methicillin-susceptible and methicillin-resistant strain of S. aureus. The released NIC from the produced catheters reduced bacterial colonization of the catheter as well as of the surrounding tissue. In summary, the NIC-releasing hot-melt extruded catheters prevented implant colonization and reduced the bacterial colonization of peri-catheter tissue by methicillin sensitive as well as resistant S. aureus in a biomaterial-associated infection mouse model and has good prospects for preclinical development.

Summary: The relevance of extracellular matrix (ECM) remodeling is reported in white adipose tissue (AT) and obesity-related dysfunctions, but little is known about the importance of ECM remodeling in brown AT (BAT) function. Here, we show that a time course of high-fat diet (HFD) feeding progressively impairs diet-induced thermogenesis concomitantly with the development of fibro-inflammation in BAT. Higher markers of fibro-inflammation are associated with lower cold-induced BAT activity in humans. Similarly, when mice are housed at thermoneutrality, inactivated BAT features fibro-inflammation. We validate the pathophysiological relevance of BAT ECM remodeling in response to temperature challenges and HFD using a model of a primary defect in the collagen turnover mediated by partial ablation of the Pepd prolidase. Pepd-heterozygous mice display exacerbated dysfunction and BAT fibro-inflammation at thermoneutrality and in HFD. Our findings show the relevance of ECM remodeling in BAT activation and provide a mechanism for BAT dysfunction in obesity.

Background: Nursing home (NH) social workers face many challenges in meeting the psychosocial needs of residents while balancing their own well-being needs. Methods: This study employed a cross-sectional survey of NH social workers via social media and professional networks about their coping strategies during COVID-19. Open-ended responses were analyzed qualitatively using the rigorous and accelerated data reduction technique (RADaR). Results: The study included a sample of 63 (N = 63) NH social workers. Four themes defined ways the in which NH social workers coped with stress during COVID-19, including relying on friends and family, mindfulness and spirituality/religion, self-care strategies, and setting boundaries at work. Conclusion: These techniques appear to be effective; however there remains a need for institutional programs and policies to provide the time and space to holistically support coping in NH social workers and to prevent burnout and turnover, particularly during times of crisis.

Background:. Individuals with genetic susceptibility to breast cancer may pursue bilateral prophylactic mastectomy (BPM) and subsequent breast reconstruction. This study aimed to characterize immediate reconstructive trends following BPM. Methods:. The ACS-NSQIP database (2010 -2019) was used to examine differences in demographics and operative outcomes based on breast reconstruction technique following BPM and factors predicting reconstruction type. Results:. Of 1945 patients (mean age, 43.8 ± 11.3 years), implant-based reconstruction (IBR) was most frequently (71.8%) performed following BPM. Patients who underwent IBR (n = 1396) were younger (42.6 years, P < 0.001), more likely to be White (P < 0.05), and more likely to have a BMI less than 25 (P < 0.001). Patients who underwent autologous reconstruction (AR) (n = 186, 45.8 years) were more likely to be Black or African American and have a BMI of 25–30. Patients who underwent mastectomy only (MO) without immediate reconstruction (n = 363) were older (47.6 years), more likely to be Asian, and more likely to have a BMI greater than 35. The MO cohort had the highest frequency of diabetes or smoking history. AR was associated with longer operations, longer lengths of stay, and increased complications. Increasing age and BMI were predictive of AR or MO compared to IBR. Smoking was predictive of MO. Conclusion:. This is the first large-scale study of genetically susceptible patients who underwent BPM demonstrating a significant relationship between patient demographics, operative outcomes, and immediate reconstruction technique. These results provide valuable insight for surgeons and patients during the shared decision-making process.

The mammalian nuclear hormone receptors LRH1 (NR5A2) and SF1 (NR5A1) are close paralogs that can bind the same DNA motif and play crucial roles in gonadal development and function. Lrh1 is essential for follicle development in the ovary and has been proposed to regulate steroidogenesis in the testis. Lrh1 expression in the testis is highly elevated by loss of the sex regulator Dmrt1, which triggers male-to-female transdifferentiation of Sertoli cells. While Sf1 has a well-defined and crucial role in testis development, no function for Lrh1 in the male gonad has been reported. Here we use conditional genetics to examine Lrh1 requirements both in gonadal cell fate reprogramming and in normal development of the three major cell lineages of the mouse testis. We find that loss of Lrh1 suppresses sexual transdifferentiation, confirming that Lrh1 can act as a key driver in reprogramming sexual cell fate. In otherwise wild-type testes, we find that Lrh1 is dispensable in Leydig cells but is required in Sertoli cells for their proliferation, for seminiferous tubule morphogenesis, for maintenance of the blood-testis barrier, for feedback regulation of androgen production, and for support of spermatogenesis. Expression profiling identified misexpressed genes likely underlying most aspects of the Sertoli cell phenotype. In the germ line we found that Lrh1 is required for maintenance of functional spermatogonia, and hence mutants progressively lose spermatogenesis. Reduced expression of the RNA binding factor Nxf2 likely contributes to the SSC defect. Unexpectedly, however, over time the Lrh1 mutant germ line recovered abundant spermatogenesis and fertility. This finding indicates that severe germ line depletion triggers a response allowing mutant spermatogonia to recover the ability to undergo complete spermatogenesis. Our results demonstrate that Lrh1, like Sf1, is an essential regulator of testis development and function but has a very distinct repertoire of functions.

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disorder characterized by recurrent abscesses in the groin and flexural areas. HS is associated with a wide range of comorbidities that complicate the disease course. Although these comorbidities have been well described, it remains unclear how these comorbidities coassociate and whether comorbidity profiles affect disease trajectory. In addition, it is unknown how comorbidity associations are modulated by race and sex. In this comprehensive analysis of 77 million patients in a large US population–based cohort, we examined coassociation patterns among HS comorbidities and identified clinically relevant phenotypic subtypes within HS. We demonstrated that these subtypes not only differed among races, but also influenced clinical outcomes as measured by HS-related emergency department visits and cellulitis. Taken together, our findings provide key insights that elucidate the unique disease trajectories experienced by patients with HS and equip clinicians with a framework for risk stratification and improved targeted care in HS.

In addition to serotonin neurons, the dorsal raphe nucleus (DR) also contains dopamine, glutamate, and GABA neurons. Here, the authors systematically compare the neurochemical identity, cell type specificity, anatomical distribution, and connectivity of DR cells targeted by commonly used Cre lines.

BCL6 corepressor (BCOR) is recurrently mutated in acute myeloid leukaemia and myelodysplastic syndrome. Here, the authors use mouse models to show the mechanism of how inactivation of BCOR in haematopoietic stem cells contributes to the development of leukaemia.

This case study describes implementation of an innovative, online, inter-professional advisory board in the context of transportation equity research. The board was comprised of 14 professionals from social work, transportation planning, and engineering. The board advised the research team on research methods such as sample recruitment strategies and data collection, as well as interpreting the results at the conclusion of the study and forming policy implications. The case study underscores the importance of: 1) ensuring broad, inter-professional membership; 2) utility of online meeting formats for reducing participation barriers and promoting more diverse participation; 3) designing active strategies to promote board members’ interaction and networking during meetings; and 4) continually orientating members to the board’s contribution to the research. Efforts to utilize participatory research methods in transportation equity research may lead to more effective transportation planning and more equitable transportation services.

Background: While improvement in quality of life has long been the ultimate goal in the care of children born with craniofacial anomalies, the intersection between surgical care and psychosocial functioning has not been well understood. A major reason for this discrepancy is the lack of consistent, systematic, validated, and quantitative assessments of psychosocial functioning incorporated as standard of care. Traditional screening within multi-disciplinary teams has relied upon qualitative evaluations by pediatricians, social workers, and psychologists. However, qualitative exams do not allow for the comparison of psychosocial outcomes accurately over time. One of the first steps in establishing psychosocial functioning as a measured health outcome in children with craniofacial anomalies is to chart their typical psychosocial development longitudinally. Our group previously reported that children with craniofacial anomalies are at increased risk for psychosocial dysfunction from ages 8-10 in a cross-sectional analysis. In this work, we evaluate the longitudinal changes over 5 years of the original cohort of children between ages 8-10 as an initial pilot study to develop a psychosocial growth chart for children with craniofacial anomalies. Methods: From 2015 to 2020, children with craniofacial anomalies from the University of California Los Angeles were prospectively evaluated using the Pediatric Patient-Reported Outcomes Measurement Information System to assess anger, anxiety, depression, and peer relationships. Demographics and patient characteristics were also recorded. Changes in psychosocial functioning from ages 8-14 were evaluated using linear regression analyses, and responses at ages 8-10 were compared to responses at ages 11-14 using paired samples t tests. Results: Overall, 29 patients were assessed longitudinally yielding a total of 97 data points (3.34 ± 1.45 per patient), of which 23 patients were surveyed at both ages 8-10 and ages 11-14 yielding 87 data points (3.78 ± 1.24 per patient). Primary diagnosis included cleft lip and/or palate (n = 13), microsomia (n = 6), and others (n = 10). There was a decreasing linear trend from ages 8-14 for anger, anxiety, and depression among all 29 patients. In particular, increasing age was a significant negative predictor of anger (β = -0.25, p = 0.01). Psychosocial functioning improved overall when comparing the responses from ages 8-10 to ages 11-14 among the 23 patients, as characterized by trends of decreased anger, anxiety, and depression and improved peer relationships. In subset analysis, children with cleft lip and/or palate reported significantly higher anxiety symptoms at ages 8-10 (52.1 ± 9.7) than at ages 11-14 (47.1 ± 9.5, p = 0.02). No differences in psychosocial functioning were found when patients were stratified by insurance type, family language, ethnicity, or sex. Conclusions: The current longitudinal study of psychosocial functioning in children with craniofacial anomalies demonstrates age-related changes in concordance with our previous cross-sectional work. The current study serves as the initial pilot study for developing a psychosocial growth chart for children with craniofacial anomalies that may be incorporated as standard of clinical care. Future directions include expansion of longitudinal analyses with potential stratification based on diagnostic subsets and evaluation of children without medical diagnoses for comparison.

This study explored engineers, planners, and social workers interactions around issues of transportation decision-making and transportation equity and identified opportunities for enhanced collaboration and training in anticipation of transformative technologies for environmental justice populations. The study assessed the current level of knowledge among professionals (engineers, planners, and social workers) about the training needs of the other professions under investigation and their own preparation for interprofessional collaboration in order to improve transportation equity for environmental justice populations. The study also identified the benefits and strategies for engineers, planners, and social workers in collaboration on transportation infrastructure and policy decisions. This study used a mixed methods, sequential exploratory design to gather information from engineers, planners, and social workers. The results showed that participants across all three professions saw a need to address the unmet and/or underserved transportation needs of environmental justice populations. Social workers identified advocacy and resource identification among some of the most important transportation-related skills while transportation experts reported data analysis and planning as key skills. The majority of study participants indicated that all three professions can greatly inform transportation planning and that interprofessional collaboration is important for improving and enhancing transportation planning. The participants cited limited interactions and siloed working environments as challenges to effective collaboration across the professions. The authors propose future research recommendations and training/education strategies for enhancing interprofessional collaboration around transportation equity for environmental justice populations.

Roundworm parasite infections are a major cause of human and livestock disease worldwide and a threat to global food security. Disease control currently relies on anthelmintic drugs to which roundworms are becoming increasingly resistant. An alternative approach is control by vaccination and 'hidden antigens', components of the worm gut not encountered by the infected host, have been exploited to produce Barbervax, the first commercial vaccine for a gut dwelling nematode of any host. Here we present the structure of H-gal-GP, a hidden antigen from Haemonchus contortus, the Barber's Pole worm, and a major component of Barbervax. We demonstrate its novel architecture, subunit composition and topology, flexibility and heterogeneity using cryo-electron microscopy, mass spectrometry, and modelling. Importantly, we demonstrate that complexes with the same architecture are present in other Strongylid roundworm parasites including human hookworm. This suggests a common ancestry and the potential for development of a unified hidden antigen vaccine.

Enhancing thermogenesis is a promising therapeutic strategy for promoting metabolic health. Here the authors show that adipocyte-secreted BMP8b contributes to optimizing the thermogenic response by remodeling of the neuro-vascular networks in brown and white adipose tissue.

Antimicrobial peptides are considered promising alternatives to antibiotics. Here the authors developed a computational algorithm that starts with peptides naturally occurring in plants and optimizes this starting material to yield new variants which are highly distinct from the parent peptide.

The Eμ-Myc lymphoma mouse model has been invaluable in the study of this disease. Here, the authors use multiple sequencing strategies to analyse the tumours in these mice and find recurrent inactivating mutations in Bcor, suggesting that this gene has a negative role in Mycsignalling.

Paper-based analytical devices (PADs) and Electrospun Fiber-Based Biosensors (EFBs) have aroused the interest of the academy and industry due to their affordability, sensitivity, ease of use, robustness, being equipment-free, and deliverability to end-users. These features make them suitable to face the need for point-of-care (POC) diagnostics, monitoring, environmental, and quality food control applications. Our work introduces new and experienced researchers in the field to a practical guide for fibrous-based biosensors fabrication with insight into the chemical and physical interaction of fibrous materials with a wide variety of materials for functionalization and biofunctionalization purposes. This research also allows readers to compare classical and novel materials, fabrication techniques, immobilization methods, signal transduction, and readout. Moreover, the examined classical and alternative mathematical models provide a powerful tool for bioanalytical device designing for the multiple steps required in biosensing platforms. Finally, we aimed this research to comprise the current state of PADs and EFBs research and their future direction to offer the reader a full insight on this topic.

Background/Objective: Data suggest that modifiable risk factors such as alcohol and tobacco use may increase the risk of breast cancer (BC) recurrence and reduce survival. Female BC mortality in South Carolina is 40% higher among African Americans (AAs) than European Americans (EAs). Given this substantial racial disparity, using a cross-sectional survey design we examined alcohol and tobacco use in an ethnically diverse statewide study of women with recently diagnosed invasive breast cancer. This included a unique South Carolina AA subpopulation, the Sea Islanders (SI), culturally isolated and with the lowest European American genetic admixture of any AA group.Methods: Participants (42 EAs, 66 non-SI AAs, 29 SIs), diagnosed between August 2011 and December 2012, were identified through the South Carolina Central Cancer Registry and interviewed by telephone within 21 months of diagnosis. Self-reported educational status, alcohol consumption and tobacco use were obtained using elements of the Behavior and Risk Factor Surveillance System questionnaire.Results:Alcohol: EAs were approximately twice as likely to consume alcohol (40%) and to be moderate drinkers (29%) than either AA group (consumers: 24% of non-SI AAs, 21% of SIs; moderate drinkers 15 and 10% respectively). Users tended to be younger, significantly among EAs and non-SI AAs, but not SIs, and to have attained more education. Heavy drinking was rare (≤1%) and binge drinking uncommon (≤10%) with no differences by race/ethnicity. Among both AA subgroups but not EAs, alcohol users were six to nine times more likely to have late stage disease (Regional or Distant), statistically significant but with wide confidence intervals. Tobacco: Current cigarette smoking (daily or occasional) was reported by 14% of EAs, 14% of non-SI AAs and 7% of SIs. Smoking was inversely associated with educational attainment. Use of both alcohol and cigarettes was reported by 3–6% of cases.Conclusions: Prevalences of alcohol and cigarette use were similar to those in the general population, with alcohol consumption more common among EAs. Up to half of cases used alcohol and/or tobacco. Given the risks from alcohol for disease recurrence, and implications of smoking for various health outcomes, these utilization rates are of concern.

ObjectiveThe current study investigated the influence of the coronavirus (COVID-19) pandemic on patients with congenital craniofacial diagnoses.MethodsPatients (n = 66) with craniofacial diagnoses aged between 8 and 17 were prospectively evaluated with longitudinal psychosocial assessments using the anger, anxiety, depressive symptoms, and peer relationships instruments within the pediatric Patient-Reported Outcomes Measurement Information System (PROMIS). The COVID-19 cohort (n = 33) included patients with assessments within 2 years prior to the pandemic (t0) and during the pandemic (t1; March 2020 to March 2021). An age-matched comparison cohort (n = 33) with similar demographics and diagnoses included patients assessed twice over 3 years prior to the pandemic.ResultsAll PROMIS measures were in the average range clinically for both groups across time points. However, the COVID-19 group reported a significant increase in depressive symptoms during the pandemic (t1) compared to pre-pandemic (t0) scores (48.2 ± 10.1 vs 44.3 ± 9.4, P = .04, d = -0.37), while the comparison group did not demonstrate any differences in psychosocial functioning between t0 and t1. For the COVID-19 cohort, only the pandemic timeframe (r = 0.21, P = .03) was significantly associated with increased depressive symptom scores, and no other sociodemographic or medical variables were associated with depressive symptoms.ConclusionsSelf-reported depressive symptoms increased during the COVID-19 pandemic in patients with congenital craniofacial diagnoses. Longitudinal studies are needed to elucidate whether such changes will be persistent or compound known variables associated with psychosocial functioning.

The BCL6 transcriptional repressor is required for the development of germinal center (GC) B cells and diffuse large B cell lymphomas (DLBCLs). Although BCL6 can recruit multiple corepressors, its transcriptional repression mechanism of action in normal and malignant B cells is unknown. We find that in B cells, BCL6 mostly functions through two independent mechanisms that are collectively essential to GC formation and DLBCL, both mediated through its N-terminal BTB domain. These are (1) the formation of a unique ternary BCOR-SMRT complex at promoters, with each corepressor binding to symmetrical sites on BCL6 homodimers linked to specific epigenetic chromatin features, and (2) the “toggling” of active enhancers to a poised but not erased conformation through SMRT-dependent H3K27 deacetylation, which is mediated by HDAC3 and opposed by p300 histone acetyltransferase. Dynamic toggling of enhancers provides a basis for B cells to undergo rapid transcriptional and phenotypic changes in response to signaling or environmental cues.

Male mammals produce sperm for most of postnatal life and therefore require a robust germ line stem cell system, with precise balance between self-renewal and differentiation. Prior work established doublesex- and mab-3-related transcription factor 1 (Dmrt1) as a conserved transcriptional regulator of male sexual differentiation. Here we investigate the role of Dmrt1 in mouse spermatogonial stem cell (SSC) homeostasis. We find that Dmrt1 maintains SSCs during steady state spermatogenesis, where it regulates expression of Plzf, another transcription factor required for SSC maintenance. We also find that Dmrt1 is required for recovery of spermatogenesis after germ cell depletion. Committed progenitor cells expressing Ngn3 normally do not contribute to SSCs marked by the Id4-Gfp transgene, but do so when spermatogonia are chemically depleted using busulfan. Removal of Dmrt1 from Ngn3-positive germ cells blocks the replenishment of Id4-GFP-positive SSCs and recovery of spermatogenesis after busulfan treatment. Our data therefore reveal that Dmrt1 supports SSC maintenance in two ways: allowing SSCs to remain in the stem cell pool under normal conditions; and enabling progenitor cells to help restore the stem cell pool after germ cell depletion.

Patients living with chronic kidney disease (CKD) must balance the medical management of their kidney disease and other chronic conditions with their daily lives, including managing the emotional and psychosocial consequences of living with a chronic disease. Self-management is critical to managing chronic kidney disease, as treatment consists of a complex regimen of medications, dosages, and treatments. This is a particularly important issue for older African American adults who will comprise a significant portion of the older adult population in the coming years. Yet current conceptualizations of self-management behaviors cannot adequately address the needs of this population. Embodiment theory provides a novel perspective that considers how social factors and experiences are embodied within decision-making processes regarding self-management care among older African Americans. This paper will explore how embodiment theory can aid in shifting the conceptualization of self-management from a model of individual choice, to a framework that cannot separate lived experiences of social, political, and racial factors from clinical understandings of self-management behaviors. This shift in the conceptualization of self-management is particularly important to consider for CKD management because the profound illness burdens require significant self-management and care coordination skills.

Abstract This article discusses applications of Second Language Acquisition (SLA) research to the preparation of language coursebooks. The author suggests a number of ways in which SLA research findings can help improve coursebooks and thereby enhance the learning of large numbers of students. Research leads us to consider learners as genuine speakers of the L2, as bilinguals who still have an L1 present in their minds and who do not all go about learning the L2 in the same way. Few coursebooks take into account these and other findings of SLA research, for example: that the acquisition of basic syntax precedes the acquisition of inflectional morphology, that most of the syntax to be learned is really part of the lexicon, or that vocabulary needs to be encountered in a structural and semantic context in order to be effectively acquired. Coursebook authors also need to bear in mind that pronunciation is necessary not only for communication but also for the actual learning of L2 forms, and that some aspects of the L2 writing system need to be explicitly taught. The author provides two sample lessons to illustrate how these research findings might be applied to the writing of a coursebook.

Biomarkers of the age of mosquitoes are required to determine the risk of transmission of various pathogens as each pathogen undergoes a period of extrinsic incubation in the mosquito host. Using the 2-D Difference Gel Electrophoresis (2-D DIGE) procedure, we investigated the abundance of up to 898 proteins from the Yellow Fever and dengue virus vector, Aedes aegypti, during ageing. By applying a mixed-effects model of protein expression, we identified five common patterns of abundance change during ageing and demonstrated an age-related decrease in variance for four of these. This supported a search for specific proteins with abundance changes that remain tightly associated with ageing for use as ageing biomarkers. Using MALDI-TOF/TOF mass spectrometry we identified ten candidate proteins that satisfied strict biomarker discovery criteria (identified in two out of three multivariate analysis procedures and in two cohorts of mosquitoes). We validated the abundances of the four most suitable candidates (Actin depolymerising factor; ADF, Eukaryotic initiation factor 5A; eIF5A, insect cuticle protein Q17LN8, and Anterior fat body protein; AFP) using semi-quantitative Western analysis of individual mosquitoes of six ages. The redox-response protein Manganese superoxide dismutase (SOD2) and electron shuttling protein Electron transfer oxidoreductase (ETO) were subject to post-translational modifications affecting their charge states with potential effects on function. For the four candidates we show remarkably consistent decreases in abundance during ageing, validating initial selections. In particular, the abundance of AFP is an ideal biomarker candidate for whether a female mosquito has lived long enough to be capable of dengue virus transmission. We have demonstrated proteins to be a suitable class of ageing biomarkers in mosquitoes and have identified candidates for epidemiological studies of dengue and the evaluation of new disease reduction projects targeting mosquito longevity.

Bcor (BCL6 corepressor) is a widely expressed gene that is mutated in patients with X-linked Oculofaciocardiodental (OFCD) syndrome. BCOR regulates gene expression in association with a complex of proteins capable of epigenetic modification of chromatin. These include Polycomb group (PcG) proteins, Skp-Cullin-F-box (SCF) ubiquitin ligase components and a Jumonji C (Jmjc) domain containing histone demethylase. To model OFCD in mice and dissect the role of Bcor in development we have characterized two loss of function Bcor alleles. We find that Bcor loss of function results in a strong parent-of-origin effect, most likely indicating a requirement for Bcor in extraembryonic development. Using Bcor loss of function embryonic stem (ES) cells and in vitro differentiation assays, we demonstrate that Bcor plays a role in the regulation of gene expression very early in the differentiation of ES cells into ectoderm, mesoderm and downstream hematopoietic lineages. Normal expression of affected genes (Oct3/4, Nanog, Fgf5, Bmp4, Brachyury and Flk1) is restored upon re-expression of Bcor. Consistent with these ES cell results, chimeric animals generated with the same loss of function Bcor alleles show a low contribution to B and T cells and erythrocytes and have kinked and shortened tails, consistent with reduced Brachyury expression. Together these results suggest that Bcor plays a role in differentiation of multiple tissue lineages during early embryonic development.

Gametogenesis is a sexually dimorphic process requiring profound differences in germ cell differentiation between the sexes. In mammals, the presence of heteromorphic sex chromosomes in males creates additional sex-specific challenges, including incomplete X and Y pairing during meiotic prophase. This triggers formation of a heterochromatin domain, the XY body. The XY body disassembles after prophase, but specialized sex chromatin persists, with further modification, through meiosis. Here, we investigate the function of DMRT7, a mammal-specific protein related to the invertebrate sexual regulators Doublesex and MAB-3. We find that DMRT7 preferentially localizes to the XY body in the pachytene stage of meiotic prophase and is required for male meiosis. In Dmrt7 mutants, meiotic pairing and recombination appear normal, and a transcriptionally silenced XY body with appropriate chromatin marks is formed, but most germ cells undergo apoptosis during pachynema. A minority of mutant cells can progress to diplonema, but many of these escaping cells have abnormal sex chromatin lacking histone H3K9 di- and trimethylation and heterochromatin protein 1beta accumulation, modifications that normally occur between pachynema and diplonema. Based on the localization of DMRT7 to the XY body and the sex chromatin defects observed in Dmrt7 mutants, we conclude that DMRT7 plays a role in the sex chromatin transformation that occurs between pachynema and diplonema. We suggest that DMRT7 may help control the transition from meiotic sex chromosome inactivation to postmeiotic sex chromatin in males. In addition, because it is found in all branches of mammals, but not in other vertebrates, Dmrt7 may shed light on evolution of meiosis and of sex chromatin.

BCOR is a critical regulator of human development. Heterozygous mutations of BCOR in females cause the X-linked developmental disorder Oculofaciocardiodental syndrome (OFCD), and hemizygous mutations of BCOR in males cause gestational lethality. BCOR associates with Polycomb group proteins to form one subfamily of the diverse Polycomb repressive complex 1 (PRC1) complexes, designated PRC1.1. Currently there is limited understanding of differing developmental roles of the various PRC1 complexes. We therefore generated a conditional exon 9-10 knockout Bcor allele and a transgenic conditional Bcor expression allele and used these to define multiple roles of Bcor, and by implication PRC1.1, in mouse development. Females heterozygous for Bcor exhibiting mosaic expression due to the X-linkage of the gene showed reduced postnatal viability and had OFCD-like defects. By contrast, Bcor hemizygosity in the entire male embryo resulted in embryonic lethality by E9.5. We further dissected the roles of Bcor, focusing on some of the tissues affected in OFCD through use of cell type specific Cre alleles. Mutation of Bcor in neural crest cells caused cleft palate, shortening of the mandible and tympanic bone, ectopic salivary glands and abnormal tongue musculature. We found that defects in the mandibular region, rather than in the palate itself, led to palatal clefting. Mutation of Bcor in hindlimb progenitor cells of the lateral mesoderm resulted in 2/3 syndactyly. Mutation of Bcor in Isl1-expressing lineages that contribute to the heart caused defects including persistent truncus arteriosus, ventricular septal defect and fetal lethality. Mutation of Bcor in extraembryonic lineages resulted in placental defects and midgestation lethality. Ubiquitous over expression of transgenic Bcor isoform A during development resulted in embryonic defects and midgestation lethality. The defects we have found in Bcor mutants provide insights into the etiology of the OFCD syndrome and how BCOR-containing PRC1 complexes function in development.

Massive tears of the rotator cuff (RC) are associated with chronic muscle degeneration due to fibrosis, fatty infiltration, and muscle atrophy. The microenvironment of diseased muscle often impairs efficient engraftment and regenerative activity of transplanted myogenic precursors. Accumulating myofibroblasts and fat cells disrupt the muscle stem cell niche and myogenic cell signaling and deposit excess disorganized connective tissue. Therefore, restoration of the damaged stromal niche with non-fibro-adipogenic cells is a prerequisite to successful repair of an injured RC. We generated from human embryonic stem cells (hES) a potentially novel subset of PDGFR-β+CD146+CD34-CD56- pericytes that lack expression of the fibro-adipogenic cell marker PDGFR-α. Accordingly, the PDGFR-β+PDGFR-α- phenotype typified non-fibro-adipogenic, non-myogenic, pericyte-like derivatives that maintained non-fibro-adipogenic properties when transplanted into chronically injured murine RCs. Although administered hES pericytes inhibited developing fibrosis at early and late stages of progressive muscle degeneration, transplanted PDGFR-β+PDGFR-α+ human muscle-derived fibro-adipogenic progenitors contributed to adipogenesis and greater fibrosis. Additionally, transplanted hES pericytes substantially attenuated muscle atrophy at all tested injection time points after injury. Coinciding with this observation, conditioned medium from cultured hES pericytes rescued atrophic myotubes in vitro. These findings imply that non-fibro-adipogenic hES pericytes recapitulate the myogenic stromal niche and may be used to improve cell-based treatments for chronic muscle disorders.

The dorsal raphe (DR) is a heterogeneous nucleus containing dopamine (DA), serotonin (5HT), γ-aminobutyric acid (GABA) and glutamate neurons. Consequently, investigations of DR circuitry require Cre-driver lines that restrict transgene expression to precisely defined cell populations. Here, we present a systematic evaluation of mouse lines targeting neuromodulatory cells in the DR. We find substantial differences in specificity between lines targeting DA neurons, and in penetrance between lines targeting 5HT neurons. Using these tools to map DR circuits, we show that populations of neurochemically distinct DR neurons are arranged in a stereotyped topographical pattern, send divergent projections to amygdala subnuclei, and differ in their presynaptic inputs. Importantly, targeting DR DA neurons using different mouse lines yielded both structural and functional differences in the neural circuits accessed. These results provide a refined model of DR organization and support a comparative, case-by-case evaluation of the suitability of transgenic tools for any experimental application.

Much research exists to support the positive effects of mentorship programs on improving grades and retention rates for MSW students. With the rapid growth in online MSW programs, the need to provide mentorship in electronic formats is also increasing. This retrospective longitudinal study examines the impact of an electronically delivered ("e-mentorship") program on MSW student success factors. Twenty MSW students at risk of program failure, most of whom were geographically dispersed across a South-Central U.S. State, were offered the opportunity to participate in a near-peer mentorship program conducted primarily through electronic means. Students were provided academic resource information and study tips. Those who engaged in e-mentorship worked on action plans aimed at addressing academic barriers. Compared to students who did not contact the mentor for assistance (n = 10), students who actively engaged the mentor (n = 10) showed significant improvement in grades, removal from probationary status, and retention/graduation.

An online qualitative survey explored perceived training, readiness, and needs of recent SW graduates serving older adults. Over half (N = 14) held a master's in social work, with 70% having taken an introductory aging course. Nearly halfcompleted other aging-specific coursework, and 80% did fieldwork with older adults. Participants indicated moderate proficiency in assessing issues like lossestransitions (46.7%), and physical health (53.3%), and advanced expertise in cognitive assessments (60.0%) and caregiver stress management (53.3%). Training deficiencies were noted in disaster readiness, telehealth, and resource coordination. Findings underscore the need for educationfor early-career social workers, ensuring their effective support to older adults. [ABSTRACT FROM AUTHOR]