Siegelcullen8027

2020. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email journals.permissions@oup.com.AIMS The G protein-coupled estrogen receptor 1 (GPER) may modulate some effects of aldosterone. Additionally, G-1 (a GPER agonist) can lower blood pressure (BP) and promote T cell-mediated anti-inflammatory responses. This study aimed to test the effects of G-1 and G-15 (a GPER antagonist) on aldosterone-induced hypertension in mice, and to examine the cellular mechanisms involved. METHODS AND RESULTS C57Bl/6 (wild-type, WT), RAG1-deficient and GPER-deficient mice were infused with vehicle, aldosterone (0.72 mg/kg/d S.C. plus 0.9% NaCl for drinking) ± G-1 (0.03 mg/kg/d S.C.) and/or G-15 (0.3 mg/kg/d S.C.) for 14 d. G-1 attenuated aldosterone-induced hypertension in male WT but not male GPER-deficient mice. G-15 alone did not alter hypertension but it prevented the anti-hypertensive effect of G-1. NSC 119875 supplier In intact female WT mice, aldosterone-induced hypertension was markedly delayed and suppressed compared with responses in males, with BP remaining unchanged until after d 7. By contrast, co-administration of aldostern. Targeting the GPER may have therapeutic potential to treat hypertension. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email journals.permissions@oup.com.MOTIVATION High-throughput sequencing discovers many naturally occurring disulfide-rich peptides or cystine-rich peptides (CRPs) with diversified bioactivities. However, their structure information, which is very important to peptide drug discovery, is still very limited. RESULTS We have developed a CRP-specific structure prediction method called CRiSP, based on a customized template database with cystine-specific sequence alignment and three machine-learning predictors. The modeling accuracy is significantly better than several popular general-purpose structure modeling methods, and our CRiSP can provide useful model quality estimations. AVAILABILITY The CRiSP server is freely available on the website at http//wulab.com.cn/CRISP. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. © The Author(s) (2020). Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.A growing body of evidence indicates that cardiac regeneration after myocardial infarction can be achieved by stimulating the endogenous capacity of cardiomyocytes to replicate. This process is controlled, both positively and negatively, by a large set of non-coding RNAs. Some of the microRNAs (miRNAs) that can stimulate cardiomyocyte proliferation are expressed in embryonic stem cells and are required to maintain pluripotency (e.g. the miR-302∼367 cluster). Others also govern the proliferation of different cell types, including cancer cells (e.g. the miR-17∼92 cluster). Additional miRNAs were discovered through systematic screenings (e.g. miR-199a-3p and miR-590-3p). Several miRNAs instead suppress cardiomyocyte proliferation and are involved in the withdrawal of cardiomyocytes from the cell cycle after birth (e.g. the let-7 and miR-15 families). Similar regulatory roles on cardiomyocytes proliferation are also exerted by a few long non-coding RNAs. This body of information has obvious therapeutic implicatiols.permissions@oup.com.Fatty acids (FA) play a major role in relation to mucosal immune responses, epithelial barrier functions, oxidative stress and inflammatory reactions. The dietary FA composition and the molecular structures (chain length and number of double bonds) influence digestion, absorption and metabolism, and the bioactivity of the FA. Piglets post-weaning having an immature intestine and not fully formed immune functions are very vulnerable to invading microorganisms. Manipulation of the milk FA composition via sow nutrition, or inclusion of dietary fat sources in the feed for newly weaned pigs, may be used as a strategic tool to enhance pig performance and their gut health and function pre- and post-weaning. Medium-chain fatty acids (MCFA) are absorbed directly into the portal blood and may contribute with immediate energy for the enterocytes. In addition, the MCFA, similarly to the short-chain fatty acids (SCFA), possess antibacterial effects and may thereby prevent overgrowth of pathogenic bacteria in the gastroint oxidative stress. Oxidative stress accompanies infectious diseases, and the development of lipid peroxides and other reactive oxygen products may be harmful to the epithelial barrier function. link2 Fatty acid peroxides from the feed may also be absorbed with other lipid-solubles and thereby harm the intestinal function. Hence, antioxidative protection is important for the enteric cells. In conclusion, manipulation of the dietary FA composition can influence the gut health and function in pigs and may support a normal immune system and modulate resistance to infectious diseases during especially stressful phases of a pig's life such as post-weaning. © The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND The influenza A(H3N2) vaccine was updated from clade 3C.3a in 2015-16 to a clade 3C.2a strain for both 2016-17 and 2017-18. Circulating 3C.2a viruses showed considerable diversity in the hemagglutinin glycoprotein and the egg-adapted vaccine strain also bore mutations, notably T160K loss-of-glycosylation. METHODS Vaccine effectiveness (VE) in 2016-17 and 2017-18 was assessed by test-negative-design, explored by A(H3N2) phylogenetic sub-cluster and prior season's vaccination history. RESULTS In 2016-17, A(H3N2) VE was 36%(95%CI=18-50%) comparable with (43%;95%CI=24-58%) or without (33%;95%CI=-16-64%) prior vaccination in 2015-16. In 2017-18,VE was 14%(95%CI=-8-31%)lower with (9%;95%CI=-18-30%) versus without (45%;95%CI=-7-71%) prior vaccination in 2016-17. CONCLUSIONS Exploring VE by phylogenetic sub-cluster and prior vaccination history reveals informative heterogeneity, but requires enhanced sample-size. Pivotal mutations conferring loss-of-glycosylation, and repeat vaccination with unchanged antigen, may be associated with reduced VE. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.BACKGROUND We compared the cost-effectiveness of 10 weeks of outreach rehabilitation (intervention) versus usual care (control) for ambulatory nursing home residents after hip fracture. METHODS Enrollment occurred February 2011 through June 2015 in a Canadian metropolitan region. 77 participants were allocated in a 21 ratio to receive a 10-week rehabilitation program (intervention) or usual care (control) (46 intervention; 31 control). Using a payer perspective, we performed main and sensitivity analyses. Health outcome was measured by quality-adjusted life years(QALYs), using the EQ5D, completed at study entry, 3-, 6-, and 12-months. We obtained patient-specific data for outpatient visits, physician claims, and inpatient re-admissions; the trial provided rehabilitation utilization/cost data. We estimated incremental cost and incremental effectiveness. RESULTS Groups were similar at study entry; the mean age was 87.9±6.6 years, 54(71%) were female and 58(75%) had severe cognitive impairment. EQ5D QALYs scoresermissions, please e-mail journals.permissions@oup.com.BACKGROUND Electroconvulsive therapy (ECT) is a highly effective and fast-acting treatment for depression used in the clinic. link3 Its mechanism of therapeutic action remains uncertain. Previous studies have focused on documenting neuroplasticity in the early phase following electroconvulsive seizures (ECS), an animal model of ECT. Here, we investigate whether changes in synaptic plasticity and non-neuronal plasticity (vascular and mitochondria) are sustained 3 months after repeated ECS trial. METHODS ECS or sham treatment was given daily for one day or 10 days to a genetic animal model of depression the Flinders Sensitive and Resistant Line (FSL/FRL) rats. Stereological principles were employed to quantify numbers of synapses and mitochondria, and length of microvessels in the hippocampus 24 hours after a single ECS, 3 months after 10 ECS treatments (one a day for 10 days) and sham-treatment. Brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) protein levels were quantified with immunohistochemistry. Results A single ECS treatment significantly increased the volume of hippocampal CA1-stratum radiatum (SR), the total length of microvessels, mitochondria number and synapse number. The observed changes were sustained as shown in the multiple ECS treatment group analyzed 3 months after the last of 10 ECS treatments. CONCLUSION A single ECS caused rapid effects of synaptic plasticity and non-neuronal plasticity, while repeated ECS induced long-lasting changes in the efficacy of synaptic plasticity and non-neuronal plasticity at least up to 3 months after ECS. © The Author(s) 2020. Published by Oxford University Press on behalf of CINP.BACKGROUND Disturbed self-regulation, taste reward, as well as somatosensory and visuospatial processes were thought to drive binge eating and purging behaviors that characterize bulimia nervosa (BN). Although studies have implicated a central role of the striatum in these dysfunctions, there have been no direct investigations on striatal functional connectivity (FC) in BN from a network perspective. METHOD We calculated the FC of striatal subregions based on the resting-state fMRI data of 51 BN patients and 53 healthy women. RESULTS Compared with the healthy women, BN patients showed increased positive FC in bilateral striatal nuclei and thalamus for nearly all of the striatal subregions, and increased negative FC in bilateral primary sensorimotor cortex and occipital areas for both ventral striatum and putamen subregions. Only for the putamen subregions, we observed reduced negative FC in the prefrontal (bilateral superior and middle frontal gyri) and parietal (right inferior parietal lobe and precuneus) areas. Several striatal connectivities with occipital and primary sensorimotor cortex significantly correlated with the severity of bulimia. CONCLUSION The findings indicate BN-related alterations in striatal FC with the dorsolateral prefrontal cortex supporting self-regulation, the subcortical striatum and thalamus involved in taste reward, as well as the visual occipital and sensorymotor regions mediating body image, which contribute to our understanding of neural circuitry of BN and encourage future therapeutic developments for BN by modulating striatal pathway. © The Author(s) 2020. Published by Oxford University Press on behalf of CINP.BACKGROUND AND AIMS Intestinal failure (IF) is a feared complication of Crohn's disease (CD). Although cumulative loss of small bowel due to bowel resections is thought to be the dominant cause, the causes and outcomes have not been reported. METHODS Consecutive adult patients referred to a national intestinal failure unit 2000-2018 with a diagnosis of CD and subsequently treated with parenteral nutrition during at least 12 months were included in this longitudinal cohort study. Data were extracted from a prospective institutional clinical database and patient records. RESULTS 121 patients were included. 62 (51%) of patients developed IF as a consequence of abdominal sepsis complicating abdominal surgery, while small bowel resection, primary disease activity and proximal stoma were less common causes (31, 12 and 6%, respectively). 32 had perianastomotic sepsis, and 15 of those had documented risk factors for anastomotic dehiscence. On Kaplan-Meier analysis, 40% of all patients regained nutritional autonomy within 10 years and none did subsequently.