The gastrointestinal tract maintains energy and glucose homeostasis, in part through nutrient-sensing and subsequent signaling to the brain and other tissues. In this review, we highlight the role of ...small intestinal nutrient-sensing in metabolic homeostasis, and link high-fat feeding, obesity, and diabetes with perturbations in these gut-brain signaling pathways. We identify how lipids, carbohydrates, and proteins, initiate gut peptide release from the enteroendocrine cells through small intestinal sensing pathways, and how these peptides regulate food intake, glucose tolerance, and hepatic glucose production. Lastly, we highlight how the gut microbiota impact small intestinal nutrient-sensing in normal physiology, and in disease, pharmacological and surgical settings. Emerging evidence indicates that the molecular mechanisms of small intestinal nutrient sensing in metabolic homeostasis have physiological and pathological impact as well as therapeutic potential in obesity and diabetes.
Observations of low-frequency gravitational waves (GWs) will require the highest possible timing precision from an array of the most spin-stable pulsars. We can improve the sensitivity of a pulsar ...timing array (PTA) to different GW sources by observing pulsars with low timing noise over years to decades and distributed across the sky. We discuss observing strategies for a PTA focused on a stochastic GW background such as from unresolved supermassive black hole binaries as well as focused on single continuous-wave sources. First, we describe the method to calculate a PTA's sensitivity to different GW-source classes. We then apply our method to the 45 pulsars presented in the North American Nanohertz Observatory for the GW 11 year data set. For expected amplitudes of the stochastic background, we find that all pulsars contribute significantly over the timescale of decades; the exception is for very pessimistic values of the stochastic-background amplitude. For individual single sources, we find that a number of pulsars contribute to the sensitivity of a given source, but that which pulsars contribute is different depending on the source, or versus an all-sky metric. Our results seem robust to the presence of red noise in pulsar arrival times. It is critical to obtain more robust pulsar-noise parameters as they heavily affect our results. Our results show that it is also imperative to locate and time as many high-precision pulsars as possible, as quickly as possible, to maximize the sensitivity of next-generation PTA detectors.
While learning analytics (LA) practices have been shown to be practical and effective, most of them require a huge amount of data and effort. This paper reports a case study which demonstrates the ...feasibility of practising LA at a low cost for instructors to identify at-risk students in an undergraduate business quantitative methods course. Instead of using tracking data from a learning management system as predictive variables, this study utilised clicker responses as formative assessments, together with student demographic data and summative assessments. This LA practice makes use of free cloud services, Google Forms and Google Sheets in particular for collecting and analysing clicker data. Despite a small dataset being used, the LA implementation was effective in identifying at-risk students at an early stage. A systematic proactive advising approach is proposed as an intervention strategy based on students' at-risk probability estimated by a prediction model. The result shows that the intervention success rate increases correspondingly with the number of interventions and the intervention effects on peer groups are far more successful than on individual students. Overall, the students' pass rate in the study was 7% higher than that for the whole course. Practical recommendations and concerns about using linear regression and logistic regression for classification are also discussed.
A novel mitochondrion‐specific photoactivatable fluorescence turn‐on bioprobe, named as o‐TPE‐ON+, is designed and readily prepared, operating through a new photoactivatable mechanism of ...photocyclodehydrogenation. This bioprobe exhibits unique photoactivation behavior in cells, and is applied to super‐resolution imaging of mitochondrion and its dynamic investigation in both fixed and live cells under physiological conditions without any external additives.
The metabolic role of vagal afferent innervation Waise, T M Zaved; Dranse, Helen J; Lam, Tony K T
Nature reviews. Gastroenterology & hepatology,
10/2018, Letnik:
15, Številka:
10
Journal Article
Recenzirano
The regulation of energy and glucose balance contributes to whole-body metabolic homeostasis, and such metabolic regulation is disrupted in obesity and diabetes. Metabolic homeostasis is orchestrated ...partly in response to nutrient and vagal-dependent gut-initiated functions. Specifically, the sensory and motor fibres of the vagus nerve transmit intestinal signals to the central nervous system and exert biological and physiological responses. In the past decade, the understanding of the regulation of vagal afferent signals and of the associated metabolic effect on whole-body energy and glucose balance has progressed. This Review highlights the contributions made to the understanding of the vagal afferent system and examines the integrative role of the vagal afferent in gastrointestinal regulation of appetite and glucose homeostasis. Investigating the integrative and metabolic role of vagal afferent signalling represents a potential strategy to discover novel therapeutic targets to restore energy and glucose balance in diabetes and obesity.
Epidemiological studies have implicated obstructive sleep apnea (OSA) as an independent comorbid factor in cardiovascular and cerebrovascular diseases. It is postulated that recurrent episodes of ...occlusion of upper airways during sleep result in pathophysiological changes that may predispose to vascular diseases. Insulin resistance is a known risk factor for atherosclerosis, and we postulate that OSA represents a stress that promotes insulin resistance, hence atherogenesis. This study investigated the relationship between sleep-disordered breathing and insulin resistance, indicated by fasting serum insulin level and insulin resistance index based on the homeostasis model assessment method (HOMA-IR). A total of 270 consecutive subjects (197 male) who were referred for polysomnography and who did not have known diabetes mellitus were included, and 185 were documented to have OSA defined as an apnea-hypopnea index (AHI) > or =5. OSA subjects were more insulin resistant, as indicated by higher levels of fasting serum insulin (p = 0.001) and HOMA-IR (p < 0.001); they were also older and more obese. Stepwise multiple linear regression analysis showed that obesity was the major determinant of insulin resistance but sleep-disordered breathing parameters (AHI and minimum oxygen saturation) were also independent determinants of insulin resistance (fasting insulin: AHI, p = 0.02, minimum O(2), p = 0.041; HOMA-IR: AHI, p = 0.044, minimum O(2), p = 0.022); this association between OSA and insulin resistance was seen in both obese and nonobese subjects. Each additional apnea or hypopnea per sleep hour increased the fasting insulin level and HOMA-IR by about 0.5%. Further analysis of the relationship of insulin resistance and hypertension confirmed that insulin resistance was a significant factor for hypertension in this cohort. Our findings suggest that OSA is independently associated with insulin resistance, and its role in the atherogenic potential of sleep disordered breathing is worthy of further exploration.
There is growing interest in glutamatergic agents in depression, particularly ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. We aimed to assess the efficacy of ketamine in ...major depressive episodes.
We searched EMBASE, PsycINFO, CENTRAL, and Medline from 1962 to January 2014 to identify double-blind, randomized controlled trials with allocation concealment evaluating ketamine in major depressive episodes. Clinical remission, response and depressive symptoms were extracted by two independent raters. The primary outcome measure was clinical remission at 24 h, 3 days and 7 days post-treatment. Analyses employed a random-effects model.
Data were synthesized from seven RCTs employing an intravenous infusion and one RCT employing intranasal ketamine, representing 73 subjects in parallel arms and 110 subjects in cross-over designs n = 34 with bipolar disorder (BD), n = 149 with major depressive disorder (MDD). Ketamine was associated with higher rates of clinical remission relative to comparator (saline or midazolam) at 24 h OR 7.06, number needed to treat (NNT) = 5, 3 days (OR 3.86, NNT = 6), and 7 days (OR 4.00, NNT = 6), as well as higher rates of clinical response at 24 h (OR 9.10, NNT = 3), 3 days (OR 6.77, NNT = 3), and 7 days (OR 4.87, NNT = 4). A standardized mean difference of 0.90 in favor of ketamine was observed at 24 h based on depression rating scale scores, with group comparisons revealing greater efficacy in unipolar depression compared to bipolar depression (1.07 v. 0.68). Ketamine was associated with transient psychotomimetic effects, but no persistent psychosis or affective switches.
Our meta-analysis suggests that single administrations ketamine are efficacious in the rapid treatment of unipolar and bipolar depression. Additional research is required to determine optimal dosing schedules, route, treatment schedules, and the potential efficacy of other glutamatergic agents.
In keeping with emerging consumer trends, the food industry is continually searching for cheaper and healthier protein ingredients to replace those derived from animal sources (e.g., whey, casein, ...gelatin, and ovalbumin), gluten-based proteins (e.g., wheat), and soy. Pea protein shows promise in filling this niche because it is non-genetically modified organism (GMO), gluten-free, nutritious, and of low allergenicity. This review discusses structure-function relationships of pea protein isolates, the impact of extraction techniques used to produce the isolate, and the impact of cultivar and environment on ingredient performance in terms of solubility, water- and oil-holding capacities, emulsifying, foaming, and gelation properties.
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