Compositional Diversity of the Vestan Regolith Derived from Howardite Compositions and Dawn VIR Spectra

Howardite, eucrite and diogenite meteorites likely come from asteroid 4 Vesta [1]. Howardites - physical mixtures of eucrites and diogenites - are of two subtypes: regolithic howardites were gardened in the true regolith; fragmental howardites are simple polymict breccias [2]. The Dawn spacecraft imaged the howarditic surface of Vesta with the visible and infrared mapping spectrometer (VIR) resulting in qualitative maps of the distributions of distinct diogenite-rich and eucrite-rich terranes [3, 4]. We are developing a robust basis for quantitative mapping of the distribution of lithologic types using spectra acquired on splits of well-characterized howardites [5, 6]. Spectra were measured on sample powders sieved to <75 m in the laboratories of the Istituto di Astrofisica e Planetologia Spaziali and Brown University. Data reduction was done using the methods developed to process Dawn VIR spectra [4]. The band parameters for the ~1 and ~2 m pyroxene absorption features (hereafter BI and BII) can be directly compared to Dawn VIR results. Regolithic howardites have shallower BI and BII absorptions compared to fragmental howardites with similar compositions. However, there are statistically significant correlations between Al or Ca contents and BI or BII center wavelengths regardless of howardite subtype. Diogenites are poor in Al and Ca while eucrites are rich in these elements. The laboratory spectra can thus be directly correlated with the percentage of eucrite material contained in the howardites. We are using these correlations to quantitatively map Al and Ca distributions, and thus the percentage of eucritic material, in the current regolith of Vesta

Alcohol and other drug use at school leavers’ celebrations

Background - A significant proportion of adolescents who attend celebratory events often engage in substantial alcohol and other drug use. We examined patterns, influences and impacts of drug consumption at an end of schooling life celebration. Methods - Seventeen- to 18-year-old Australians who intended to attend (n = 541) and who attended the celebration (n = 405), respectively, completed pre- and post-event surveys. Results - Males consumed 18.44 and females 13.24 Australian standard drinks on an average day during the school leavers' event. Compared with their last social event, there was greater alcohol (P < 0.0005) and ecstasy use (P < 0.046 for Day 1 and P < 0.008 on Day 3). However, the number of drinks consumed per hour appeared to be similar across contexts. Most (87%) experienced at least one negative outcome attributed to alcohol and other drug use. Safety strategies were frequently used and appeared to be protective against some of the most common harms (hangover, vomiting, black out and unprotected sex). Conclusions - The use of alcohol and other drugs at this celebratory event appears to be reflective of the greater than usual number of drinking hours that are available to participants. The use of safety strategies can be successful in mitigating some of the most common drug-related harms

Zebrafish hoxd4a Acts Upstream of meis1.1 to Direct Vasculogenesis, Angiogenesis and Hematopoiesis

10.1371/journal.pone.0058857PLoS ONE83

CHOP Mediates Endoplasmic Reticulum Stress-Induced Apoptosis in Gimap5-Deficient T Cells

Gimap5 (GTPase of the immunity-associated protein 5) has been linked to the regulation of T cell survival, and polymorphisms in the human GIMAP5 gene associate with autoimmune disorders. The BioBreeding diabetes-prone (BBDP) rat has a mutation in the Gimap5 gene that leads to spontaneous apoptosis of peripheral T cells by an unknown mechanism. Because Gimap5 localizes to the endoplasmic reticulum (ER), we hypothesized that absence of functional Gimap5 protein initiates T cell death through disruptions in ER homeostasis. We observed increases in ER stress-associated chaperones in T cells but not thymocytes or B cells from Gimap5−/− BBDP rats. We then discovered that ER stress-induced apoptotic signaling through C/EBP-homologous protein (CHOP) occurs in Gimap5−/− T cells. Knockdown of CHOP by siRNA protected Gimap5−/− T cells from ER stress-induced apoptosis, thereby identifying a role for this cellular pathway in the T cell lymphopenia of the BBDP rat. These findings indicate a direct relationship between Gimap5 and the maintenance of ER homeostasis in the survival of T cells

A Novel Role for the Centrosomal Protein, Pericentrin, in Regulation of Insulin Secretory Vesicle Docking in Mouse Pancreatic β-cells

The centrosome is important for microtubule organization and cell cycle progression in animal cells. Recently, mutations in the centrosomal protein, pericentrin, have been linked to human microcephalic osteodysplastic primordial dwarfism (MOPD II), a rare genetic disease characterized by severe growth retardation and early onset of type 2 diabetes among other clinical manifestations. While the link between centrosomal and cell cycle defects may account for growth deficiencies, the mechanism linking pericentrin mutations with dysregulated glucose homeostasis and pre-pubertal onset of diabetes is unknown. In this report we observed abundant expression of pericentrin in quiescent pancreatic β-cells of normal animals which led us to hypothesize that pericentrin may have a critical function in β-cells distinct from its known role in regulating cell cycle progression. In addition to the typical centrosome localization, pericentrin was also enriched with secretory vesicles in the cytoplasm. Pericentrin overexpression in β-cells resulted in aggregation of insulin-containing secretory vesicles with cytoplasmic, but not centrosomal, pericentriolar material and an increase in total levels of intracellular insulin. RNAi- mediated silencing of pericentrin in secretory β-cells caused dysregulated secretory vesicle hypersecretion of insulin into the media. Together, these data suggest that pericentrin may regulate the intracellular distribution and secretion of insulin. Mice transplanted with pericentrin-depleted islets exhibited abnormal fasting hypoglycemia and inability to regulate blood glucose normally during a glucose challenge, which is consistent with our in vitro data. This previously unrecognized function for a centrosomal protein to mediate vesicle docking in secretory endocrine cells emphasizes the adaptability of these scaffolding proteins to regulate diverse cellular processes and identifies a novel target for modulating regulated protein secretion in disorders such as diabetes

Prolonged COVID-19 symptom duration in people with systemic autoimmune rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey

OBJECTIVE: We investigated prolonged COVID-19 symptom duration, defined as lasting 28 days or longer, among people with systemic autoimmune rheumatic diseases (SARDs). METHODS: We analysed data from the COVID-19 Global Rheumatology Alliance Vaccine Survey (2 April 2021-15 October 2021) to identify people with SARDs reporting test-confirmed COVID-19. Participants reported COVID-19 severity and symptom duration, sociodemographics and clinical characteristics. We reported the proportion experiencing prolonged symptom duration and investigated associations with baseline characteristics using logistic regression. RESULTS: We identified 441 respondents with SARDs and COVID-19 (mean age 48.2 years, 83.7% female, 39.5% rheumatoid arthritis). The median COVID-19 symptom duration was 15 days (IQR 7, 25). Overall, 107 (24.2%) respondents had prolonged symptom duration (≥28 days); 42/429 (9.8%) reported symptoms lasting ≥90 days. Factors associated with higher odds of prolonged symptom duration included: hospitalisation for COVID-19 vs not hospitalised and mild acute symptoms (age-adjusted OR (aOR) 6.49, 95% CI 3.03 to 14.1), comorbidity count (aOR 1.11 per comorbidity, 95% CI 1.02 to 1.21) and osteoarthritis (aOR 2.11, 95% CI 1.01 to 4.27). COVID-19 onset in 2021 vs June 2020 or earlier was associated with lower odds of prolonged symptom duration (aOR 0.42, 95% CI 0.21 to 0.81). CONCLUSION: Most people with SARDs had complete symptom resolution by day 15 after COVID-19 onset. However, about 1 in 4 experienced COVID-19 symptom duration 28 days or longer; 1 in 10 experienced symptoms 90 days or longer. Future studies are needed to investigate the possible relationships between immunomodulating medications, SARD type/flare, vaccine doses and novel viral variants with prolonged COVID-19 symptoms and other postacute sequelae of COVID-19 among people with SARDs

DEAD-Box Protein Ddx46 Is Required for the Development of the Digestive Organs and Brain in Zebrafish

Spatially and temporally controlled gene expression, including transcription, several mRNA processing steps, and the export of mature mRNA to the cytoplasm, is essential for developmental processes. It is well known that RNA helicases of the DExD/H-box protein family are involved in these gene expression processes, including transcription, pre-mRNA splicing, and rRNA biogenesis. Although one DExD/H-box protein, Prp5, a homologue of vertebrate Ddx46, has been shown to play important roles in pre-mRNA splicing in yeast, the in vivo function of Ddx46 remains to be fully elucidated in metazoans. In this study, we isolated zebrafish morendo (mor), a mutant that shows developmental defects in the digestive organs and brain, and found that it encodes Ddx46. The Ddx46 transcript is maternally supplied, and as development proceeds in zebrafish larvae, its ubiquitous expression gradually becomes restricted to those organs. The results of whole-mount in situ hybridization showed that the expression of various molecular markers in these organs is considerably reduced in the Ddx46 mutant. Furthermore, splicing status analysis with RT-PCR revealed unspliced forms of mRNAs in the digestive organ and brain tissues of the Ddx46 mutant, suggesting that Ddx46 may be required for pre-mRNA splicing during zebrafish development. Therefore, our results suggest a model in which zebrafish Ddx46 is required for the development of the digestive organs and brain, possibly through the control of pre-mRNA splicing

Impact of HIV-related stigma on treatment adherence: systematic review and meta-synthesis

Introduction: Adherence to HIV antiretroviral therapy (ART) is a critical determinant of HIV-1 RNA viral suppression and health outcomes. It is generally accepted that HIV-related stigma is correlated with factors that may undermine ART adherence, but its relationship with ART adherence itself is not well established. We therefore undertook this review to systematically assess the relationship between HIV-related stigma and ART adherence. Methods: We searched nine electronic databases for published and unpublished literature, with no language restrictions. First we screened the titles and abstracts for studies that potentially contained data on ART adherence. Then we reviewed the full text of these studies to identify articles that reported data on the relationship between ART adherence and either HIV-related stigma or serostatus disclosure. We used the method of meta-synthesis to summarize the findings from the qualitative studies. Results: Our search protocol yielded 14,854 initial records. After eliminating duplicates and screening the titles and abstracts, we retrieved the full text of 960 journal articles, dissertations and unpublished conference abstracts for review. We included 75 studies conducted among 26,715 HIV-positive persons living in 32 countries worldwide, with less representation of work from Eastern Europe and Central Asia. Among the 34 qualitative studies, our meta-synthesis identified five distinct third-order labels through an inductive process that we categorized as themes and organized in a conceptual model spanning intrapersonal, interpersonal and structural levels. HIV-related stigma undermined ART adherence by compromising general psychological processes, such as adaptive coping and social support. We also identified psychological processes specific to HIV-positive persons driven by predominant stigmatizing attitudes and which undermined adherence, such as internalized stigma and concealment. Adaptive coping and social support were critical determinants of participants’ ability to overcome the structural and economic barriers associated with poverty in order to successfully adhere to ART. Among the 41 quantitative studies, 24 of 33 cross-sectional studies (71%) reported a positive finding between HIV stigma and ART non-adherence, while 6 of 7 longitudinal studies (86%) reported a null finding (Pearson's χ 2=7.7; p=0.005). Conclusions: We found that HIV-related stigma compromised participants’ abilities to successfully adhere to ART. Interventions to reduce stigma should target multiple levels of influence (intrapersonal, interpersonal and structural) in order to have maximum effectiveness on improving ART adherence