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These findings suggest that diet may be an important driver of gut microbial community structure in the birds from each lake, and the obvious differentiation in their gut microbial structures may indicate that the bacteria are highly sensitive to food sources at both lakes. © 2020 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.BACKGROUND Targeting fibroblast growth factor receptor 1 (FGFR1) is a potential treatment for squamous cell lung cancer (SQCLC). So far, treatment decision in clinical studies is based on gene amplification. However, only a minority of patients have shown durable response. Furthermore, former studies have revealed contrasting results regarding the impact of FGFR1 amplification and expression on patient's prognosis. AIMS Here, we analyzed prevalence and correlation of FGFR1 gene amplification and protein expression in human lung cancer and their impact on overall survival. MATERIALS & METHODS FGFR1 gene amplification and protein expression were analyzed by fluorescence in situ hybridization and immunohistochemistry (IHC) in 208 SQCLC and 45 small cell lung cancers (SCLC). Furthermore, FGFR1 protein expression was analyzed in 121 pulmonary adenocarcinomas (ACs). Amplification and expression were correlated to each other, clinicopathological characteristics, and overall survival. RESULTS FGFR1 was amplified in 23% of SQCLC and 8% of SCLC. Amplification was correlated to males (P = .027) but not to overall survival. Specificity of immunostaining was verified by cellular CRISPR/Cas9 FGFR1 knockout. FGFR1 was strongly expressed in 9% of SQCLC, 35% of AC, and 4% of SCLC. Expression was correlated to females (P = .0187) and to the absence of lymph node metastasis in SQCLC (P = .018) with no significant correlation to overall survival. Interestingly, no significant correlation between amplification and expression was detected. DISCUSSION FGFR1 gene amplification does not seem to correlate to protein expression. CONCLUSION We believe that patient selection for FGFR1 inhibitors in clinical studies should be reconsidered. Neither FGFR1 amplification nor expression influences patient's prognosis. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.Noble gases, especially xenon (Xe), have been shown to have antiapoptotic effects in treating hypoxia ischemia related injuries. Currently, in vivo gas delivery is systemic and performed through inhalation, leading to reduced efficacy at the injury site. This report provides a first demonstration of the encapsulation of pure Xe, Ar, or He in phospholipid-coated sub-10 µm microbubbles, without the necessity of stabilizing perfluorocarbon additives. Optimization of shell compositions and preparation techniques show that dipalmitoylphosphatidylcholine (DSPC) with DSPE-PEG5000 can produce stable microbubbles upon shaking, while DBPC blended with either DSPE-PEG2000 or DSPE-PEG5000 produces a high yield of microbubbles via a sonication/centrifugation method. Xe and Ar concentrations released into the microbubble suspension headspace are measured using GC-MS, while Xe released directly in solution is detected by the fluorescence quenching of a Xe-sensitive cryptophane molecule. Bubble production is found to be amenable to scale-up while maintaining their size distribution and stability. Excellent ultrasound contrast is observed in a phantom for several minutes under physiological conditions, while an intravenous administration of a bolus of pure Xe microbubbles provides significant contrast in a mouse in pre- and post-lung settings (heart and kidney, respectively), paving the way for image-guided, localized gas delivery for theranostic applications. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Obstructive sleep apnea (OSA) may contribute to kidney injury by activation of the renin-angiotensin system (RAS), which is reduced by continuous positive airway pressure (CPAP) therapy. A biomarker in the urine that reflects renal RAS activity could identify patients at risk of kidney injury and monitor their response to CPAP therapy. Nine patients with OSA and six matched control subjects without OSA were recruited. Renal RAS activity was measured by the renovasoconstrictor response to Angiotensin II challenge, a validated marker of RAS activity, and urine samples were collected in all subjects at baseline and repeated in those with OSA following treatment with CPAP. A broad range (1,310) of urine analytes was measured including 26 associated with the RAS signaling pathway. The OSA group was a similar age and weight as the control group (48.7 ± 10.4 vs. 47.7 ± 9.3 yrs; BMI 36.9 ± 7.2 vs. 34.7 ± 2.5 kg/m2 ) and had severe sleep apnea (ODI 51.1 ± 26.8 vs. 4.3 ± 2/hour) and nocturnal hypoxemia (mean SaO2 87 ± 5.2 vs. 92.6 ± 1.1%). CPAP corrected OSA associated with a return of the renovasocontrictor response to Angiotensin II to control levels. Partial least squares (PLS) logistic regression analysis showed significant separation between pre- and post-CPAP levels (p less then .002) when all analytes were used, and a strong trend when only RAS-associated analytes were used (p = .05). These findings support the concept that urine analytes may be used to identify OSA patients who are susceptible to kidney injury from OSA before renal function deteriorates and to monitor the impact of CPAP therapy on renal RAS activity. © 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.The photosynthetic α-proteobacterium Rhodobacter capsulatus reduces and thereby fixes atmospheric dinitrogen (N2 ) by a molybdenum (Mo)-nitrogenase and an iron-only (Fe)-nitrogenase. Differential expression of the structural genes of Mo-nitrogenase (nifHDK) and Fe-nitrogenase (anfHDGK) is strictly controlled and activated by NifA and AnfA, respectively. In contrast to NifA-binding sites, AnfA-binding sites are poorly defined. Here, we identified two highly similar AnfA-binding sites in the R. capsulatus anfH promoter by studying the effects of promoter mutations on in vivo anfH expression and in vitro promoter binding by AnfA. Comparison of the experimentally determined R. capsulatus AnfA-binding sites and presumed AnfA-binding sites from other α-proteobacteria revealed a consensus sequence of dyad symmetry, TAC-N6 -GTA, suggesting that AnfA proteins bind their target promoters as dimers. Chromosomal replacement of the anfH promoter by the nifH promoter restored anfHDGK expression and Fe-nitrogenase activity in an R. capsulatus strain lacking AnfA suggesting that AnfA is required for AnfHDGK production, but dispensable for biosynthesis of the iron-only cofactor and electron delivery to Fe-nitrogenase, pathways activated by NifA. 4-HNE compound library chemical These observations strengthen our model, in which the Fe-nitrogenase system in R. capsulatus is largely integrated into the Mo-nitrogenase system. © 2020 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.The human immunodeficiency virus (HIV) pandemic heavily affects sub-Saharan Africa. It is associated with persistently active Epstein-Barr virus (EBV) infection. To determine if this translates into increased frequency of EBV-associated gastric cancer (EBVaGC), we evaluated molecular profiles of gastric cancer (GC) in Zambia. Patients with GC or premalignant gastric lesions were enrolled in Lusaka, Zambia. We used patients without any of these lesions as a control group. Chromogenic in situ hybridization (CISH) on tumor tissue was used to identify EBVaGC. To identify the microsatellite unstable subtype, immunofluorescence staining for MutL homolog 1 (MLH1) was used. Exposure to EBV and HIV was assessed serologically. We enrolled 369 patients (median age 52 years [IQR 41-65]; 198 (54%) female). Of these, 72 (20%) had GC and 35 (9%) had gastric premalignant lesions (PL). link2 CISH identified EBVaGC in 5/44 (11%) of those with adequate tissue, while MLH1 loss was identified in 29/45 (64%). Both GC and PL were associated with the highest titers of antibodies to Early antigen-diffuse (OR 2.5, 95% CI 1.0-6.1, P = .048 and OR 3.9, 95% CI 1.1-12.9, P = .03, respectively) at high concentrations. Human immunodeficiency virus infection was associated with a range of antibodies to EBV, but not with any cancer subtype. Despite the association of HIV with persistent EBV, the proportion of EBVaGC in Zambia is similar to populations with a low prevalence of HIV infection. The proportion of microsatellite unstable tumors may be higher than other populations. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.During embryonic development, excitatory projection neurons migrate in the cerebral cortex giving rise to organised layers. Periventricular heterotopia (PH) is a group of aetiologically heterogeneous disorders in which a subpopulation of newborn projection neurons fails to initiate their radial migration to the cortex, ultimately resulting in bands or nodules of grey matter lining the lateral ventricles. Although a number of genes have been implicated in its cause, currently they only satisfactorily explain the pathogenesis of the condition for 50% of patients. Novel gene discovery is complicated by the extreme genetic heterogeneity recently described to underlie its cause. Here, we study the neurodevelopmental role of endothelin-converting enzyme-2 (ECE2) for which two biallelic variants have been identified in two separate patients with PH. Our results show that manipulation of ECE2 levels in human cerebral organoids and in the developing mouse cortex leads to ectopic localisation of neural progenitors and neurons. We uncover the role of ECE2 in neurogenesis, and mechanistically, we identify its involvement in the generation and secretion of extracellular matrix proteins in addition to cytoskeleton and adhesion. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.BACKGROUND Anemia is common in liver cirrhosis. This generally infers a fall in total hemoglobin mass (tHb-mass). However, hemoglobin concentration ([Hb]) may fall due to an expansion in plasma volume (PV). The "optimized carbon monoxide rebreathing method" (oCOR) measures tHb-mass directly and PV (indirectly using hematocrit). It relies upon carboxyhemoglobin (COHb) distribution throughout the entire circulation. In healthy subjects, such distribution is complete within 6-8 min. Given the altered circulatory dynamics in cirrhosis, we sought in this pilot study, to assess whether this was true in cirrhosis. link3 The primary aim was to ascertain if the standard timings for the oCOR were applicable to patients with chronic liver disease and cirrhosis. The secondary aim was to explore the applicability of standard CO dosing methodologies to this patient population. METHODS Sixteen patients with chronic liver parenchymal disease were studied. However, tHb-mass was determined using the standard oCOR technique before elfine and validate appropriate dosing regimens. © 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.INTRODUCTION Incidence of high altitude-related sickness is increasing due to more number of people visiting the areas of high altitude which may result in life-threatening conditions including acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), high altitude cerebral edema (HACE), and High-altitude pulmonary hypertension (HAPH). We hypothesized that an advanced yoga regimen may be beneficial in dealing with the physiology of acclimatization. METHODS Anthropometric, Biochemical, and Psychological assessments were carried out in 48 participants before and after the advance meditation program (AMP) in the experimental group. Individuals with an age range of 20-65 years with no comorbidities were included in the study. Participants were exposed to AMP for 4 days. All assessments were carried out at the baseline and after the course. Prakriti was constituted for all participants using a standard questionnaire. The study was carried out after obtaining the written informed consent as per the guidelines outlined by the Institute Ethics Committee.
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