Two-dimensional analysis reveals that peptide–MHC class II tetramers underestimate the frequency of cytokine-producing antigen-specific CD4+ T cells in polyclonal responses.

Background: It has been suggested that gut microbiota is altered in Type 2 Diabetes Mellitus (T2DM) patients.Objective: This study was to evaluate the effect of the prebiotic xylooligosaccharide (XOS) on the gut microbiota in both healthy and prediabetic (Pre-DM) subjects, as well as impaired glucose tolerance (IGT) in Pre-DM.Subjects/Methods: Pre-DM (n = 13) or healthy (n = 16) subjects were randomized to receive 2 g/day XOS or placebo for 8-weeks. In Pre-DM subjects, body composition and oral glucose tolerance test (OGTT) was done at baseline and week 8. Stool from Pre-DM and healthy subjects at baseline and week 8 was analyzed for gut microbiota characterization using Illumina MiSeq sequencing.Results: We identified 40 Pre-DM associated bacterial taxa. Among them, the abundance of the genera Enterorhabdus, Howardella, and Slackia was higher in Pre-DM. XOS significantly decreased or reversed the increase in abundance of Howardella, Enterorhabdus, and Slackia observed in healthy or Pre-DM subjects. Abundance of the species Blautia hydrogenotrophica was lower in pre-DM subjects, while XOS increased its abundance. In Pre-DM, XOS showed a tendency to reduce OGTT 2-h insulin levels (P = 0.13), but had no effect on body composition, HOMA-IR, serum glucose, triglyceride, satiety hormones, and TNFα.Conclusion: This is the first clinical observation of modifications of the gut microbiota by XOS in both healthy and Pre-DM subjects in a pilot study. Prebiotic XOS may be beneficial in reversing changes in the gut microbiota during the development of diabetes.Clinical trial registration: NCT01944904 (https://clinicaltrials.gov/ct2/show/NCT01944904).

beta-NAD(+) is as abundant as ATP in neuronal cells. beta-NAD(+) functions not only as a coenzyme but also as a substrate. beta-NAD(+)-utilizing enzymes are involved in signal transduction. We focus on ADP-ribosyl cyclase/CD38 which synthesizes cyclic ADP-ribose (cADPR), a universal Ca(2+) mobilizer from intracellular stores, from beta-NAD(+). cADPR acts through activation/modulation of ryanodine receptor Ca(2+) releasing Ca(2+) channels. cADPR synthesis in neuronal cells is stimulated or modulated via different pathways and various factors. Subtype-specific coupling of various neurotransmitter receptors with ADP-ribosyl cyclase confirms the involvement of the enzyme in signal transduction in neurons and glial cells. Moreover, cADPR/CD38 is critical in oxytocin release from the hypothalamic cell dendrites and nerve terminals in the posterior pituitary. Therefore, it is possible that pharmacological manipulation of intracellular cADPR levels through ADP-ribosyl cyclase activity or synthetic cADPR analogues may provide new therapeutic opportunities for treatment of neurodevelopmental disorders.

Objective To design a simple model to assess the effectiveness of measures to prevent the spread of coronavirus disease 2019 (COVID-19) to different regions of mainland China. Methods We extracted data on population movements from an internet company data set and the numbers of confirmed cases of COVID-19 from government sources. On 23 January 2020 all travel in and out of the city of Wuhan was prohibited to control the spread of the disease. We modelled two key factors affecting the cumulative number of COVID-19 cases in regions outside Wuhan by 1 March 2020: (i) the total the number of people leaving Wuhan during 20-26 January 2020; and (ii) the number of seed cases from Wuhan before 19 January 2020, represented by the cumulative number of confirmed cases on 29 January 2020. We constructed a regression model to predict the cumulative number of cases in non-Wuhan regions in three assumed epidemic control scenarios. Findings Delaying the start date of control measures by only 3 days would have increased the estimated 30 699 confirmed cases of COVID-19 by 1 March 2020 in regions outside Wuhan by 34.6% (to 41 330 people). Advancing controls by 3 days would reduce infections by 30.8% (to 21 235 people) with basic control measures or 48.6% (to 15 796 people) with strict control measures. Based on standard residual values from the model, we were able to rank regions which were most effective in controlling the epidemic. Conclusion The control measures in Wuhan combined with nationwide traffic restrictions and self-isolation reduced the ongoing spread of COVID-19 across China. Research COVID-19 epidemic control measures, mainland China Zheming Yuan et al.