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

Higher occurrence of nausea and vomiting after total hip arthroplasty using general versus spinal anesthesia: an observational study.

BACKGROUND: Under the assumption that postoperative nausea and vomiting (PONV) may occur after total hip arthroplasty (THA) regardless of the anesthetic technique used, it is not clear whether general (GA) or spinal (SA) anesthesia has higher causal effect on this occurrence. Conflicting results have been reported. METHODS: In this observational study, we selected all elective THA interventions performed in adults between 1999 and 2008 in a Swiss orthopedic clinic under general or spinal anesthesia. To assess the effect of anesthesia type on the occurrence of PONV, we used the propensity score and matching methods, which allowed us to emulate the design and results of an RCT. RESULTS: Among 3922 procedures, 1984 (51 %) patients underwent GA, of which 4.1 % experienced PONV, and 1938 underwent SA, of which 3.5 % experienced PONV. We found that the average treatment effect on the treated, i.e. the effect of anesthesia type for a sample of individuals that actually received spinal anesthesia compared to individuals who received GA, was ATET = 2.00 % [95 % CI, 0.78-3.19 %], which translated into an OR = 1.97 [95 % CI 1.35; 2.87]. CONCLUSION: This suggests that the type of anesthesia is not neutral regarding PONV, general anesthesia being more strongly associated with PONV than spinal anesthesia in orthopedic surgery

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

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

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

Transcriptomic Characterization of Temperature Stress Responses in Larval Zebrafish

Temperature influences nearly all biochemical, physiological and life history activities of fish, but the molecular mechanisms underlying the temperature acclimation remains largely unknown. Previous studies have identified many temperature-regulated genes in adult tissues; however, the transcriptional responses of fish larvae to temperature stress are not well understood. In this study, we characterized the transcriptional responses in larval zebrafish exposed to cold or heat stress using microarray analysis. In comparison with genes expressed in the control at 28°C, a total of 2680 genes were found to be affected in 96 hpf larvae exposed to cold (16°C) or heat (34°C) for 2 and 48h and most of these genes were expressed in a temperature-specific and temporally regulated manner. Bioinformatic analysis identified multiple temperature-regulated biological processes and pathways. Biological processes overrepresented among the earliest genes induced by temperature stress include regulation of transcription, nucleosome assembly, chromatin organization and protein folding. However, processes such as RNA processing, cellular metal ion homeostasis and protein transport and were enriched in genes up-regulated under cold exposure for 48 h. Pathways such as mTOR signalling, p53 signalling and circadian rhythm were enriched among cold-induced genes, while adipocytokine signalling, protein export and arginine and praline metabolism were enriched among heat-induced genes. Although most of these biological processes and pathways were specifically regulated by cold or heat, common responses to both cold and heat stresses were also found. Thus, these findings provide new interesting clues for elucidation of mechanisms underlying the temperature acclimation in fish

Self-Management education for adults with poorly controlled epILEpsy (SMILE (UK)): a randomised controlled trial protocol

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.National Institute for Health Research Health Technology Assessment Programme; reference 09/165/01

Automated control and optimisation of laser driven ion acceleration

The interaction of relativistically intense lasers with opaque targets represents a highly non-linear, multi-dimensional parameter space. This limits the utility of sequential 1D scanning of experimental parameters for the optimisation of secondary radiation, although to-date this has been the accepted methodology due to low data acquisition rates. High repetition-rate (HRR) lasers augmented by machine learning present a valuable opportunity for efficient source optimisation. Here, an automated, HRR-compatible system produced high fidelity parameter scans, revealing the influence of laser intensity on target pre-heating and proton generation. A closed-loop Bayesian optimisation of maximum proton energy, through control of the laser wavefront and target position, produced proton beams with equivalent maximum energy to manually-optimized laser pulses but using only 60% of the laser energy. This demonstration of automated optimisation of laser-driven proton beams is a crucial step towards deeper physical insight and the construction of future radiation sources