Multiple sclerosis risk variants alter expression of co-stimulatory genes in B cells.

The increasing evidence supporting a role for B cells in the pathogenesis of multiple sclerosis prompted us to investigate the influence of known susceptibility variants on the surface expression of co-stimulatory molecules in these cells. Using flow cytometry we measured surface expression of CD40 and CD86 in B cells from 68 patients and 162 healthy controls that were genotyped for the multiple sclerosis associated single nucleotide polymorphisms (SNPs) rs4810485, which maps within the CD40 gene, and rs9282641, which maps within the CD86 gene. We found that carrying the risk allele rs4810485*T lowered the cell-surface expression of CD40 in all tested B cell subtypes (in total B cells P ≤ 5.10 × 10-5 in patients and ≤4.09 × 10-6 in controls), while carrying the risk allele rs9282641*G increased the expression of CD86, with this effect primarily seen in the naïve B cell subset (P = 0.048 in patients and 5.38 × 10-5 in controls). In concordance with these results, analysis of RNA expression demonstrated that the risk allele rs4810485*T resulted in lower total CD40 expression (P = 0.057) but with an increased proportion of alternative splice-forms leading to decoy receptors (P = 4.00 × 10-7). Finally, we also observed that the risk allele rs4810485*T was associated with decreased levels of interleukin-10 (P = 0.020), which is considered to have an immunoregulatory function downstream of CD40. Given the importance of these co-stimulatory molecules in determining the immune reaction that appears in response to antigen our data suggest that B cells might have an important antigen presentation and immunoregulatory role in the pathogenesis of multiple sclerosis

The Association of Depressive Symptoms with Inflammatory Factors and Adipokines in Middle-Aged and Older Chinese

Studies in Western populations find that depression is associated with inflammation and obesity. The present study aimed to evaluate the relation of depressive symptoms with inflammatory factors and adipose-derived adipokines in middle-aged and older Chinese.Data were from 3289 community residents aged 50-70 from Beijing and Shanghai who participated in the Nutrition and Health of Aging Population in China project. Depressive symptoms were defined as a Center for Epidemiological Studies of Depression Scale (CES-D) score of 16 or higher. Plasma concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), adiponectin, resistin, plasminogen activator inhibitor-1 (PAI-1) and retinol binding protein 4 (RBP4) were measured. Of the 3289 participants, 312 (9.5%) suffered from current depressive symptoms. IL-6 level was higher in participants with depressive symptoms compared to their counterparts in the crude analyses (1.17 vs. 1.05 pg/mL, p = 0.023) and this association lost statistical significance after multiple adjustments (1.13 vs. 1.10 pg/mL, p = 0.520). Depressive symptoms were not associated with increased mean levels of any other inflammatory factors or adipokines in the unadjusted or adjusted analyses.We found no evidence that depressive symptoms were associated with inflammatory factors and adipokines in the middle-aged and older Chinese populations. Prospective studies and studies in clinically diagnosed patients are needed to confirm our results and clarify the relation of depression with inflammatory factors and adipokines

Effects of a Flaxseed-Derived Lignan Supplement in Type 2 Diabetic Patients: A Randomized, Double-Blind, Cross-Over Trial

Flaxseed consumption has been shown to improve blood lipids in humans and flaxseed-derived lignan has been shown to enhance glycemic control in animals. The study aimed to investigate the effect of a flaxseed-derived lignan supplement on glycemic control, lipid profiles and insulin sensitivity in type 2 diabetic patients.This was a randomized, double-blind, placebo-controlled, cross-over trial and it was conducted between April and December 2006 in Shanghai, China. Seventy-three type 2 diabetic patients with mild hypercholesterolemia were enrolled into the study. Patients were randomized to supplementation with flaxseed-derived lignan capsules (360 mg lignan per day) or placebo for 12 weeks, separated by an 8-week wash-out period. HbA1c, lipid profiles, insulin resistance index and inflammatory factors were measured. Sixty-eight completed the study and were included in the analyses. The lignan supplement significantly improved glycemic control as measured by HbA(1c) (-0.10+/-0.65 % vs. 0.09+/-0.52 %, P = 0.001) compared to placebo; however, no significant changes were observed in fasting glucose and insulin concentrations, insulin resistance and blood lipid profiles. Urinary excretion of lignan metabolites (enterodiol and enterolactone) was significantly higher after the lignan supplement intervention compared to baseline (14.2+/-18.1 vs. 1.2+/-2.4 microg/mL, P<0.001). Data also suggested minimal competition between lignan and isoflavones for bioavailability when measured by the excretion concentrations.Daily lignan supplementation resulted in modest, yet statistically significant improvements in glycemic control in type 2 diabetic patients without apparently affecting fasting glucose, lipid profiles and insulin sensitivity. Further studies are needed to validate these findings and explore the efficacy of lignans on type 2 diabetes.ClinicalTrials.gov NCT00363233

A population-based phenome-wide association study of cardiac and aortic structure and function

Differences in cardiac and aortic structure and function are associated with cardiovascular diseases and a wide range of other types of disease. Here we analyzed cardiovascular magnetic resonance images from a population-based study, the UK Biobank, using an automated machine-learning-based analysis pipeline. We report a comprehensive range of structural and functional phenotypes for the heart and aorta across 26,893 participants, and explore how these phenotypes vary according to sex, age and major cardiovascular risk factors. We extended this analysis with a phenome-wide association study, in which we tested for correlations of a wide range of non-imaging phenotypes of the participants with imaging phenotypes. We further explored the associations of imaging phenotypes with early-life factors, mental health and cognitive function using both observational analysis and Mendelian randomization. Our study illustrates how population-based cardiac and aortic imaging phenotypes can be used to better define cardiovascular disease risks as well as heart–brain health interactions, highlighting new opportunities for studying disease mechanisms and developing image-based biomarkers

Cadmium pollution status and assessment of potential risk to human health of commercial aquatic products

Objective To understand the cadmium pollution in aquatic products of fish, shellfish, shrimp and crab, analyze the seasonal difference of cadmium content in the above aquatic products, classify the level of cadmium pollution and assess the health risks. Methods Totally 1 554 samples of commercial aquatic products were collected and the cadmium content in aquatic products was determined by graphite furnace atomic absorption spectrometry. The difference of cadmium concentration between seasons were compared through descriptive analysis. Pollution index (Pi) methodology was employed to evaluate the pollution level of aquatic products. The provisional tolerable monthly intake (PTMI) of cadmium was taken as the reference value to assess the health risks of aquatic products. Results The average concentration of cadmium in 1 554 aquatic products was 0.116 4 mg/kg. The total detection rate was 45.56% (708/1 554), including 86.26% (496/575) of shellfish, 66.43% (93/140) of crabs, 32.48% (102/314) of shrimps and 3.24% (17/525) of fish. The total violation rate was 1.74% (27/1 554), of which crabs were 7.86% (11/140), shrimps were 2.87% (9/314), shellfish were 1.22% (7/575), fish were 0.00% (0/525). The result of pollution index indicated that crabs were lightly polluted in autumn (Pi=0.36), moderately polluted in spring and winter (Pi were 0.70 and 0.89 respectively), and the other aquatic products were clean in each season. The result of health risk assessment showed that at the general intake level, the maximum percentage of estimated monthly intake (EMI) in PTMI of various aquatic products in different seasons was 0.35%, while at the high intake level, the maximum percentage was 49.33%. Conclusion There were some differences of the violation rate of cadmium in aquatic products between seasons. The cadmium pollution was the lightest in summer. Except for crabs, which had light or moderate pollution level, the other kinds of aquatic products were clean. Either at the general level or high level of intake, the health risks of cadmium exposure caused by taking aquatic products was relatively low

Significance of paleo-fluid in the Ordovician–Silurian detachment zone to the preservation of shale gas in western Hunan–Hubei area

The studies on the paleo-fluid in the Ordovician–Silurian detachment zone in the Middle–Upper Yangtze area focus on the origin of high-density methane inclusions and the evolution process of formation pressure, but rarely deal with the significance of paleo-fluid to shale gas preservation. In this paper, the relationship between fracture formation and detachment zone was analyzed by observing the Ordovician–Silurian outcrops in western Hunan–Hubei area and by investigating the geological characteristics of fracture veins in the drilling cores. Then, the significance of paleo-fluid forming environment and detachment zone to shale gas preservation was studied by using inclusion compositions of fracture veins and homogenization temperature test data. Finally, accumulation–dispersion modes of shale gas in the detachment zone were established. The following results were obtained. First, the detachment zone is lithologically composed of silicite with intercalated shale at the Ordovician–Silurian interface. In the detachment zone, rocks are broken and small crumples are developed. The conjugate-vertical joints are relatively developed in the silicite above and below the detachment zone. Second, multi-stage and multi-type inclusions, especially the aqueous inclusions, are developed in the veins of the detachment zone. Third, the infiltration depth of ancient meteoric water along the detachment zone in the study area is over 4000 m. High-density overpressure methane inclusions were captured in the detachment zone during early stage, while normal-pressure methane and nitrogen inclusions were captured during late stage. Fourth, the ionic constituents of inclusions recording the fluid activity during the late stage was characterized by high sodium-chloride coefficient, high desulfurization coefficient and low metamorphic coefficient, and it is indicated that the sealing capacity of the shale in the detachment zone gets worse. Fifth, the accumulation and dispersion of shale gas in the detachment zone within the study area is divided into three modes, i.e., syncline, broad anticline and closed anticline. In conclusion, the detachment zone in the study area is permeable. Synclines and closed anticlines developed in detachment structures are unfavorable for the accumulation of shale gas, while broad anticlines are favorable. Keywords: Western Hunan–Hubei area, Ordovician, Silurian, Detachment zone, Paleo-fluid, Inclusions, Homogenization temperature, Ionic constituent, Shale gas, Preservation conditio

Rubella outbreak and outbreak management in a school setting, China, 2014

Background: An active response to a rubella outbreak may interrupt disease transmission, and outbreak response immunization (ORI) can increase immunity among persons who might otherwise not be protected. On March 17, 2014, a rubella outbreak was reported in a middle school in Guangzhou city, China. We conducted an investigation to assess impact of a policy of exclusion of cases from school and of ORI. Methods: Active surveillance was used to find cases of rubella. Investigators interviewed teachers and reviewed the absentee records to determine implementation details of school exclusion. ORI was recommended on 2 occasions during the outbreak, one small-scale and one large-scale. Laboratory confirmation tests included serum IgM and IgG measurements to distinguish between acute infection and immunity. A serological survey in 4 classes was used to determine immunity status and identify symptomatic and asymptomatic cases. Results: From February 17 to May 23, 2014, 162 rubella cases (24 laboratory-confirmed and 138 epidemiologically linked) were detected among 1,621 students. Cases ultimately occurred in 27 classes (72.97%) across 37 classes. In 11 classes in which exclusion from school was delayed by 1 or more days, the secondary attack rate was 12.30%, compared with 2.35% in 15 classes with immediate exclusion. ORI increased vaccine coverage from 25.83 % to 86.92%, and the final case of the epidemic was reported one month later. A serological survey of 91 students in 4 classes identified 15 cases, 6 of which were asymptomatic. Conclusions: The outbreak happened in school with low rubella-containing vaccination coverage. Exclusion from school upon rash/fever onset was associated with lowering the secondary attack rate, but school exclusion alone was not able to stop this outbreak – a large ORI was needed. Assuring complete vaccination upon entry to school is likely to be necessary to ensure coverage is above the herd immunity threshold and prevent outbreaks from happening

Scientific analysis of tie luo, a Qing Dynasty calligraphy artifact in the Palace Museum, Beijing, China

Abstract Tie luo (affixed hanging) was an expressive form of traditional Chinese calligraphy or paintings, and popular in the imperial palaces for interior decorations in Qing Dynasty (1644–1911 C.E.). A piece of calligraphic tie luo, written by an eminent calligrapher Gu Gao (1763–1832 C.E.), was restored recently in the Palace Museum, Beijing, China. The paper with pigment coating specially made for this calligraphic piece was named as fenjian. This article presented results from materials identification prior to the restoration. Multianalysis with scientific approaches revealed how tie luo was manufactured. It could be concluded that the investigated tie luo used a paper made from bast fibers of mulberry trees. And the decorative ground layer for the piece was also studied, which indicated that a type of organic red pigments were used for the masterpiece. White lead was considered as the main pigment, mixed with a red dye extracted from sappanwood. Meanwhile, animal glue, drying oils and beeswax were confirmed as the organic binding media. In dye analysis, protosappanin B and brazilin as well as brazilein were identified, which implied that sappanwood was used for the organic manufacture of pigments. In addition, both Nowik type A and C were found in the research, which were characteristic of sappanwood for identification

Transcription Regulation of Cell Cycle Regulatory Genes Mediated by NtrX to Affect <i>Sinorhizobium</i> <i>meliloti</i> Cell Division

The cell division of the alfalfa symbiont, Sinorhizobium meliloti, is dictated by a cell cycle regulatory pathway containing the key transcription factors CtrA, GcrA, and DnaA. In this study, we found that NtrX, one of the regulators of nitrogen metabolism, can directly regulate the expression of ctrA, gcrA, and dnaA from the cell cycle pathway. Three sets of S. meliloti ntrX mutants showed similar cell division defects, such as slow growth, abnormal morphology of some cells, and delayed DNA synthesis. Transcription of ctrA and gcrA was upregulated, whereas the transcription of dnaA and ftsZ1 was downregulated in the insertion mutant and the strain of Sm1021 expressing ntrXD53E. Correspondingly, the inducible transcription of ntrX activates the expression of dnaA and ftsZ1, but represses ctrA and gcrA in the depletion strain. The expression levels of CtrA and GcrA were confirmed by Western blotting. The transcription regulation of these genes requires phosphorylation of the conserved 53rd aspartate in the NtrX protein that binds directly to the promoter regions of ctrA, gcrA, dnaA, and ftsZ1 by recognizing the characteristic sequence CAAN2-5TTG. Our findings suggest that NtrX affects S. meliloti cell division by regulating the transcription of the key cell cycle regulatory genes