Miracle-dz/UniFAR-FTUs huggingface dataset:
How Boundaries Form: Linked Nonautonomous Feedback Loops Regulate Pattern Formation in Yeast Colonies

How do boundaries between cells of different types form? Such boundaries are critical for metazoan development, but even in microorganisms, boundaries between cells of different types form in communities such as colonies. Under conditions in which budding yeast form colonies and then undergo meiosis/sporulation, the resulting colonies are organized such that a sharply defined layer of meiotic cells overlays a layer of unsporulated cells termed “feeder cells. ” This differentiation pattern requires activation of both the Rlm1/cell-wall integrity pathway and the Rim101/alkaline-response pathway. In the current study, we analyzed the connection between these two signaling pathways in regulating colony development by determining expression patterns and cell-autonomy relationships. We present evidence that two parallel cell-nonautonomous positive-feedback loops are active in colony patterning, an Rlm1-Slt2 loop active in feeder cells and an Rim101-Ime1 loop active in meiotic cells. The Rlm1-Slt2 loop is expressed first and subsequently activates the Rim101-Ime1 loop through a cell-nonautonomous mechanism. Once activated, each feedback loop activates the cell fate specific to its colony region. At the same time, cell-autonomous mechanisms inhibit ectopic fates within these regions. In addition, once the second loop is active, it represses the first loop through a cell-nonautonomous mechanism. Linked cell-nonautonomous positive-feedback loops, by amplifying small differences in microenvironments, may be a general mechanism for pattern formation in yeast and other organisms.
Rapid Growth and Metabolism of Uropathogenic Escherichia coli in Relation to Urine Composition

Uropathogenic Escherichia coli (UPEC) strains cause a majority of urinary tract infections (UTIs). Since UPEC strains can become antibiotic resistant, adjunct or alternate therapies are urgently needed. UPEC strains grow extremely rapidly in patients with UTIs. Thus, this review focuses on the relation between urine composition and UPEC growth and metabolism. SUMMARY Uropathogenic Escherichia coli (UPEC) strains cause a majority of urinary tract infections (UTIs). Since UPEC strains can become antibiotic resistant, adjunct or alternate therapies are urgently needed. UPEC strains grow extremely rapidly in patients with UTIs. Thus, this review focuses on the relation between urine composition and UPEC growth and metabolism. Compilation of urinary components from two major data sources suggests the presence of sufficient amino acids and carbohydrates as energy sources and abundant phosphorus, sulfur, and nitrogen sources. In a mouse UTI model, mutants lacking enzymes of the tricarboxylic acid cycle, gluconeogenesis, and the nonoxidative branch of the pentose cycle are less competitive than the corresponding parental strains, which is consistent with amino acids as major energy sources. Other evidence suggests that carbohydrates are required energy sources. UPEC strains in urine ex vivo and in vivo express transporters for peptides, amino acids, carbohydrates, and iron and genes associated with nitrogen limitation, amino acid synthesis, nucleotide synthesis, and nucleotide salvage. Mouse models confirm the requirement for many, but not all, of these genes. Laboratory evolution studies suggest that rapid nutrient uptake without metabolic rewiring is sufficient to account for rapid growth. Proteins and pathways required for rapid growth should be considered potential targets for alternate or adjunct therapies.
Associations between nocturnal sleep duration, midday nap duration and body composition among adults in Southwest China

Objective We aim to explore the relationship between nocturnal sleep duration (NSD) and midday nap duration (MND) with body composition among Southwest Chinese adults. Methods Data on sleep duration of 3145 adults in Southwest China (59.4% women) were obtained between 2014 and 2015 through questionnaires. Height, weight, and waist circumference (WC) were measured to calculate body composition (body mass index (BMI), percentage of body fat (%BF), and fat mass index (FMI)). Linear regression models were used to assess gender-specific associations between NSD and body composition. The relationship between MND with the odds of overweight and central obesity has been evaluated by logistic regression models. Results NSD has the inverse relation with males’ BMI, WC, %BF and FMI after adjusting for all covariates (all P <0.0007), exclusive of females’ (all P >0.4). After adjustment for potential confounders, compared to the subjects in the no midday nap group, the subjects who napped 0.1–1 hour were independently associated with a less prevalence of overweight in both women (OR: 0.72, 95%CI: 0.55–0.95) and men (OR: 0.71, 95%CI: 0.52–0.98). MND was not associated with central obesity. Conclusions Among Southwest Chinese adults, lower NSD might be related to higher BMI, WC, %BF and FMI among men. Additionally, MND is associated with overweight in adults.
A Head-to-Head Comparison of Four Artemisinin-Based Combinations for Treating Uncomplicated Malaria in African Children: A Randomized Trial

Artemisinin-based combination therapies (ACTs) are the mainstay for the management of uncomplicated malaria cases. However, up-to-date data able to assist sub-Saharan African countries formulating appropriate antimalarial drug policies are scarce.Between 9 July 2007 and 19 June 2009, a randomized, non-inferiority (10% difference threshold in efficacy at day 28) clinical trial was carried out at 12 sites in seven sub-Saharan African countries. Each site compared three of four ACTs, namely amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL), or chlorproguanil-dapsone-artesunate (CD+A). Overall, 4,116 children 6-59 mo old with uncomplicated Plasmodium falciparum malaria were treated (1,226 with AL, 1,002 with ASAQ, 413 with CD+A, and 1,475 with DHAPQ), actively followed up until day 28, and then passively followed up for the next 6 mo. At day 28, for the PCR-adjusted efficacy, non-inferiority was established for three pair-wise comparisons: DHAPQ (97.3%) versus AL (95.5%) (odds ratio [OR]: 0.59, 95% CI: 0.37-0.94); DHAPQ (97.6%) versus ASAQ (96.8%) (OR: 0.74, 95% CI: 0.41-1.34), and ASAQ (97.1%) versus AL (94.4%) (OR: 0.50, 95% CI: 0.28-0.92). For the PCR-unadjusted efficacy, AL was significantly less efficacious than DHAPQ (72.7% versus 89.5%) (OR: 0.27, 95% CI: 0.21-0.34) and ASAQ (66.2% versus 80.4%) (OR: 0.40, 95% CI: 0.30-0.53), while DHAPQ (92.2%) had higher efficacy than ASAQ (80.8%) but non-inferiority could not be excluded (OR: 0.35, 95% CI: 0.26-0.48). CD+A was significantly less efficacious than the other three treatments. Day 63 results were similar to those observed at day 28.This large head-to-head comparison of most currently available ACTs in sub-Saharan Africa showed that AL, ASAQ, and DHAPQ had excellent efficacy, up to day 63 post-treatment. The risk of recurrent infections was significantly lower for DHAPQ, followed by ASAQ and then AL, supporting the recent recommendation of considering DHAPQ as a valid option for the treatment of uncomplicated P. falciparum malaria.ClinicalTrials. gov NCT00393679; Pan African Clinical Trials Registry PACTR2009010000911750
Pediatric enteral nutrition therapy for burn victims: when should it be initiated?

Objective To review the scientific evidence regarding the initiation of enteral nutrition in the pediatric burn population. Methods This study was a systematic review and meta-analysis of randomized clinical trials comparing early enteral nutrition and late enteral nutrition in individuals aged 1 month to 18 years with burns. The MEDLINE/PubMed, Embase and Cochrane Library databases were searched using the terms "burns", "fires", "child nutrition disorders", "nutritional support" and related terms. Results Three articles that included a total of 781 patients were identified. There was no significant difference in the mortality rate between the early and late groups (OR = 0.72, 95%CI = 0.46 - 1.15, p = 0.17). Patients who received early enteral nutrition had a 3.69-day reduction in the length of hospital stay (mean difference = -3.69, 95%CI = -4.11 - -3.27, p < 0.00001). There was a higher incidence of diarrhea and vomiting and decreased intestinal permeability in the early group. This group also presented higher a serum insulin concentration and insulin/glucagon ratio as well as lower caloric deficit and weight loss when compared to the control group. Conclusion Analysis of the different intragroup variables suggests the importance of starting nutritional support early. Considering the number of pediatric burn patients, there is a need for robust studies with greater scientific impact.
Quantitative and Qualitative Factors Associated with Social Isolation Among Graduate and Professional Health Science Students

Objective. To determine the prevalence of social isolation and associated factors in graduate and professional health science students. Methods. Quantitative and qualitative data were gathered via an online survey from graduate and professional students in the colleges of dentistry, medicine, nursing, pharmacy, and public health at a Midwestern university. Questions assessed students’ demographics, weekly activity hours, support systems, and financial concerns, and included the 20-item UCLA Loneliness Scale. Logistic regression was performed using the binary outcome of feeling socially isolated (yes/no) and examined program-related respondent comments using thematic analysis. Results. There were 427 survey respondents with 398 completing the full survey. Students answering the social isolation question (n=386) were included in the regression analysis. Nearly one-fifth (19.4%) of respondents indicated social isolation, with the highest percentage among nursing respondents (40.7%). Lacking a strong support, being a non-native English speaker, having caregiving responsibilities, and experiencing “lonely” items described in the UCLA Loneliness Scale were positively associated with social isolation. The ability to discuss feelings with friends in their professional program and experiencing “non-lonely” items were negatively associated with social isolation. Ninety-six comments revealed nine risk factor themes in four categories: individual (feeling different from peers, personality, employment), interpersonal (competition/exclusionary atmosphere, faculty relationship), organization (too busy with coursework, isolating program) and community (relocation reduces social support). Student-involvement in organizations (activities encouraging socialization) and community (support from outside the group) were protective factors. Conclusion. Understanding associated factors and designing strategies to reduce student social isolation may enhance the quality and well-being of future health professionals and scientists.
Gnrh1-induced responses are indirect in female medaka Fsh cells

Reproductive function in vertebrates is stimulated by gonadotropin-releasing hormone (GnRH) that controls the synthesis and release of the two pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH, which regulates different stages of gonadal development, are produced by two different cell types in the fish pituitary, in contrast to mammals and birds, thus allowing the investigation of their differential regulation. In the present work, we show by fluorescent in situ hybridization that Lh cells in adult female medaka express Gnrh receptors, whereas Fsh cells do not. This is confirmed by patch clamp recordings and cytosolic Ca2+ measurements on dispersed pituitary cells, where Lh cells, but not Fsh cells, respond to Gnrh1 by increased action potential frequencies and cytosolic Ca2+ levels. In contrast, both Fsh and Lh cells are able to respond electrically and by elevating the cytosolic Ca2+ levels to Gnrh1 in brain-pituitary tissue slices. Using Ca2+ uncaging in combination with patch clamp recordings and cytosolic Ca2+ measurements, we show that Fsh and Lh cells form homo- and heterotypic networks in the pituitary. Taken together, these results show that the effects of Gnrh1 on Fsh release in adult female medaka is indirect, likely mediated via Lh cells.
Posttraumatic Stress Disorder and Risk for Stroke in Young and Middle-Aged Adults: A 13-Year Cohort Study.

Background and Purpose- In older populations, transient ischemic attack (TIA) and ischemic stroke have been linked to psychological factors, including posttraumatic stress disorder (PTSD). Whether PTSD also increases risk for early incident stroke in young adults is unknown. Methods- We prospectively assessed the incidence of TIA and ischemic stroke in a cohort of 987 855 young and middle-aged Veterans (mean age of 30.29±9.19 years; 87.8% men, 64.4% white) who first accessed care through the Veterans Health Administration from October 2001 to November 2014 and were free of TIA and ischemic stroke at baseline. For each outcome, time-varying multivariate Cox models were constructed to examine the effect of PTSD on incident stroke. We also assessed for effect modification by sex. Additional sensitivity analyses controlled for healthcare utilization. Results- Over a 13-year period, TIA and ischemic stroke were diagnosed in 766 and 1877 patients, respectively. PTSD was diagnosed in 28.6% of the sample during follow-up. In unadjusted analyses, PTSD was significantly associated with new-onset TIA (hazard ratio [HR], 2.02; 95% CI, 1.62-2.52) and ischemic stroke (HR, 1.62; 95% CI, 1.47-1.79). In fully adjusted models, the association between PTSD and incident TIA (HR, 1.61; 95% CI, 1.27-2.04) and ischemic stroke (HR, 1.36; 95% CI, 1.22-1.52) remained significant. The effect of PTSD on ischemic stroke risk was stronger in men than in women (HR, 0.63; 95% CI, 0.47-0.86; P=0.003), but no effect of sex was found for TIA. Conclusions- PTSD is associated with a significant increase in risk of early incident TIA and ischemic stroke independent of established stroke risk factors, coexisting psychiatric disorders, and healthcare utilization. Sex moderated the relationship for adults with ischemic stroke but not TIA. These findings suggest that psychological factors, including PTSD, may be important targets for future age-specific prevention strategies for young adults.
Tracing the origin of the placental trophoblast cells in mouse embryo development†

Abstract The placenta, which originates from the trophectoderm (TE), is the first organ to form during mammalian embryogenesis. Recent studies based on bioinformatics analysis have revealed that heterogeneous gene expression initiates cell-fate decisions and directs two distinct cell fates by modulating the balance of pluripotency and differentiation as early as the four-cell stage. However, direct developmental evidence to support this is still lacking. To address at which stage the cell fate of the TE and inner cell mass (ICM) is determined, in this study, we administered a microinjection of Cre mRNA into a single blastomere of the mTmG mouse at different cleavage stages before implantation to examine the distributions of the descendants of the single-labeled cell in the mouse fetus and the placenta at E12.5. We found that the descendants of the labeled cells at the two-cell stage contributed to both the placenta and the fetus. Notably, the derivatives of the labeled cells at the four-cell stage fell into three categories: (1) distributed in both embryonic and extraembryonic lineages, (2) distributed only in mouse placental trophoblast layers, or (3) distributed only in the lineage derived from the ICM. In addition, these results fell in line with single-cell studies focusing on gene expression patterns that characterize particular lineages within the blastocyst. In conclusion, this study shows that the four-cell blastomeres differ in their individual developmental properties insofar as they contribute to either or both the ICM and trophoblast fate. Summary sentence The four-cell blastomeres differ in their individual developmental properties insofar as they contribute to either or both the embryonic and extraembryonic lineage.
Modulation of T Regulatory and Dendritic Cell Phenotypes Following Ingestion of Bifidobacterium longum, AHCC® and Azithromycin in Healthy Individuals

The probiotic Bifidus BB536 (BB536), which contains Bifidobacterium longum, has been shown to have enhanced probiotic effects when given together with a standardized extract of cultured Lentinula edodes mycelia (AHCC®, Amino Up Co. Ltd., Sapporo, Japan). BB536 and AHCC® may modulate T cell and dendritic cell (DC) phenotypes, and cytokine profiles to favour anti-inflammatory responses following antibiotic ingestion. We tested the hypothesis that orally administered BB536 and/or AHCC®, results in modulation of immune effector cells with polarisation towards anti-inflammatory responses following antibiotic usage. Forty healthy male volunteers divided into 4 equal groups were randomised to receive either placebo, BB536, AHCC® or a combination for 12 days in a double-blind manner. After 7 days volunteers also received 250 mg azithromycin for 5 days. Cytokine profiles from purified CD3+ T cells stimulated with PDB-ionomycin were assessed. CD4+ CD25+ forkhead box P3 (Foxp3) expression and peripheral blood DC subsets were assessed prior to treatment and subsequently at 7 and 13 days. There was no difference in cytokine secretion from stimulated CD3+ T cells between treatment groups. Compared with baseline, Foxp3 expression (0.45 ± 0.1 vs. 1.3 ± 0.4; p = 0.002) and interferon-gamma/interleukin-4 (IFN-γ/IL-4) ratios were increased post-treatment in volunteers receiving BB536 (p = 0.031), although differences between groups were not significant. For volunteers receiving combination BB536 and AHCC®, there was an increase in myeloid dendritic cells (mDC) compared with plasmacytoid DC (pDC) counts (80% vs. 61%; p = 0.006) at post treatment time points. mDC2 phenotypes were more prevalent, compared with baseline, following combination treatment (0.16% vs. 0.05%; p = 0.002). Oral intake of AHCC® and BB536 may modulate T regulatory and DC phenotypes to favour anti-inflammatory responses following antibiotic usage.
Economic Implications of Rasburicase Treatment in Adult Patients with Tumour Lysis Syndrome

Background:Rasburicase is a recombinant urate-oxidase enzyme used to reduce high levels of plasma uric acid (PUA) resulting from tumour lysis syndrome (TLS). Rasburicase reduces PUA levels within 4 hours of administration, thereby minimizing the risk of serious complications from TLS. Treatment pattern analyses indicate rasburicase is often used in combination with allopurinol; however, no studies have evaluated the clinical and economic consequences of this pattern of care. The purpose of this study was to compare hospitalization costs, overall length of stay (LOS), and critical-care LOS in patients receiving rasburicase with or without allopurinol. Methods:Hospital claims data from the Premier Perspective Database were used to conduct this retrospective analysis. Patients in the Premier hospital database who were administered rasburicase or combination therapy (rasburicase + allopurinol) within 2 days of hospital admission were eligible for study inclusion. Patients were excluded if they were <18 years of age or received haemodialysis (or any other renal replacement therapy support) on admission. Rasburicase patients were propensity-score-matched to combination therapy patients based on gender, race, hospital type (urban/rural, teaching), provider type, payer type, admission source, use of electrolyte modification therapy, critical-care admission and presence of a cancer diagnosis. Differences in healthcare costs, overall LOS and critical-care LOS were assessed using g-distributed generalized linear models with a log-link function. Results: The study population comprised 66 patients receiving rasburicase monotherapy matched to 66 patients receiving combination therapy. Mean age was 62.9 years, and 29% were female. Patients initiated on combination therapy had a shorter mean duration of rasburicase administration than patients initiated on monotherapy (2.1 vs 2.7 days) [p = 0.0059]. Additionally, rasburicase monotherapy incurred an average total cost of $US35 843 per hospitalization, compared with $US46 672 for those receiving combination ORIGINAL RESEARCH ARTICLE Appl Health Econ Health Policy 2012; 10 (6): 431-44
Metarhizium robertsii ammonium permeases (MepC and Mep2) contribute to rhizoplane colonization and modulates the transfer of insect derived nitrogen to plants

The endophytic insect pathogenic fungi (EIPF) Metarhizium promotes plant growth through symbiotic association and the transfer of insect-derived nitrogen. However, little is known about the genes involved in this association and the transfer of nitrogen. In this study, we assessed the involvement of six Metarhizium robertsii genes in endophytic, rhizoplane and rhizospheric colonization with barley roots. Two ammonium permeases (MepC and Mep2) and a urease, were selected since homologous genes in arbuscular mycorrhizal fungi were reported to play a pivotal role in nitrogen mobilization during plant root colonization. Three other genes were selected on the basis on RNA-Seq data that showed high expression levels on bean roots, and these encoded a hydrophobin (Hyd3), a subtilisin-like serine protease (Pr1A) and a hypothetical protein. The root colonization assays revealed that the deletion of urease, hydrophobin, subtilisin-like serine protease and hypothetical protein genes had no impact on endophytic, rhizoplane and rhizospheric colonization at 10 or 20 days. However, the deletion of MepC resulted in significantly increased rhizoplane colonization at 10 days whereas ΔMep2 showed increased rhizoplane colonization at 20 days. In addition, the nitrogen transporter mutants also showed significantly higher 15N incorporation of insect derived nitrogen in barley leaves in the presence of nutrients. Insect pathogenesis assay revealed that disruption of MepC, Mep2, urease did not reduce virulence toward insects. The enhanced rhizoplane colonization of ΔMep2 and ΔMepC and insect derived nitrogen transfer to plant hosts suggests the role of MepC and Mep2 in Metarhizium-plant symbiosis.