Common biological networks underlie genetic risk for alcoholism in African‐ and European‐American populations

Alcohol dependence (AD) is a heritable substance addiction with adverse physical and psychological consequences, representing a major health and economic burden on societies worldwide. Genes thus far implicated via linkage, candidate gene and genome‐wide association studies (GWAS) account for only a small fraction of its overall risk, with effects varying across ethnic groups. Here we investigate the genetic architecture of alcoholism and report on the extent to which common, genome‐wide SNPs collectively account for risk of AD in two US populations, African‐Americans (AAs) and European‐Americans (EAs). Analyzing GWAS data for two independent case–control sample sets, we compute polymarker scores that are significantly associated with alcoholism (P = 1.64 × 10^–3 and 2.08 × 10^–4 for EAs and AAs, respectively), reflecting the small individual effects of thousands of variants derived from patterns of allelic architecture that are population specific. Simulations show that disease models based on rare and uncommon causal variants (MAF < 0.05) best fit the observed distribution of polymarker signals. When scoring bins were annotated for gene location and examined for constituent biological networks, gene enrichment is observed for several cellular processes and functions in both EA and AA populations, transcending their underlying allelic differences. Our results reveal key insights into the complex etiology of AD, raising the possibility of an important role for rare and uncommon variants, and identify polygenic mechanisms that encompass a spectrum of disease liability, with some, such as chloride transporters and glycine metabolism genes, displaying subtle, modifying effects that are likely to escape detection in most GWAS designs.     

Low-density lipoprotein-associated variables and the severity of coronary artery disease: an untreated Chinese cohort study

Abstract

Background and aims: Elevated low-density lipoprotein cholesterol (LDL-C) is causal risk for coronary artery disease (CAD) and LDL-associated variables including LDL-C, apolipoprotein B (apoB), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein a [Lp(a)], small dense LDL (sd-LDL), and oxidized LDL (ox-LDL) have been widely used for predicting the risk of CAD. This study was aimed to compare the values of six LDL-related variables for predicting the severity of CAD using untreated patients undergoing coronary angiography (CAG).

Methods: A group of 1977 individuals were consecutively enrolled and divided into CAD (n?=?1151) and non-CAD groups (n?=?826) according to the results of CAG. LDL-C, apoB, non-HDL-C, Lp(a), sd-LDL and ox-LDL were measured, respectively. The numbers of stenotic arteries and Gensini Scores (GS) were used to calculate the severity of CAD and the associations of six variables with the severity of CAD and predicting value of these parameters were simultaneously examined.

Results: CAD patients had significantly higher concentrations of LDL-related variables than non-CAD ones (all p?<?0.05). Importantly, all variables rose with the increase in the severity of CAD. The predicting value of CAD manifested as sd-LDL?>?ox-LDL?>?apoB?>?non-HDL-C?>?LDL-C?>?Lp(a) [area under curve (AUC): sd-LDL 0.641; ox-LDL 0.640; apoB 0.611; non-HDL-C 0.587; LDL-C 0.583; Lp(a) 0.554; respectively]. In multivariate logistic analysis, all variables showed as independent risk factors for the severity of CAD [odds ratio (OR): ox-LDL?>?sd-LDL?>?apoB?>?non-HDL-C?>?LDL-C?>?Lp(a)].

Conclusions: All of LDL-related variables could be useful marker for predicting the severity of CAD but sd-LDL and ox-LDL appeared to litter better. Further study may be needed to validate our results.     

耐药大环内酯类肺炎支原体肺炎患儿外周血HMGB1表达与预后转归的关系

摘要 目的：探讨耐药大环内酯类肺炎支原体(Mycoplasma pneumoniae,MP)肺炎患儿外周血高迁移率族蛋白 B1(high mobility group protein B1,HMGB1)表达与预后转归的关系。方法：2017年1月-2019年12月选择在新疆维吾尔自治区人民医院诊治的耐药大环内酯类肺炎支原体肺炎患儿78例、非耐药大环内酯类肺炎支原体肺炎患儿78例与健康儿童78例分别作为耐药组、非耐药组与对照组,检测三组外周血HMGB1表达水平,调查耐药组患儿的急性生理与慢性健康(Acute Physiology and Chronic Health Evaluation,APACHEⅡ)评分与随访预后并进行相关性分析。结果：耐药组、非耐药组的血清HMGB1水平高于对照组(P<0.05),耐药组高于非耐药组(P<0.05)。随着入院时间的增加,耐药组患儿的APACHEⅡ评分逐渐降低,对比差异有统计学意义(P<0.05)。随访到2020年5月1日,耐药组患儿死亡2例,死亡率为2.6 %。在耐药组中,Pearson相关分析显示外周血HMGB1与APACHEⅡ评分、发热持续时间、住院时间、肺部病变个数存在相关性(P<0.05)。受试者工作特征(receiver operating characteristic,ROC)曲线分析显示外周血HMGB1、APACHEⅡ评分预测患儿死亡的最大截面积为0.872(95 %CI：0.729-0.878)和0.889(95 %CI：0.813-0.941)。结论：耐药大环内酯类肺炎支原体肺炎患儿外周血HMGB1呈现高表达状况,与患儿的APACHEⅡ评分呈现正相关性,以上结果有助于预测患儿的随访预后,并为进一步明确该病的发生机制提供一定的借鉴。     

Sow behaviour and piglet weight gain after late cross-fostering in farrowing crates and pens

Determining best practices for managing free farrowing systems is crucial for uptake. Cross-fostering, the exchange of piglets between litters, is routinely performed amongst crate-housed sows. However, cross-fostering can increase fighting amongst the litter and may be more challenging within free farrowing systems as sows have more freedom to respond to cross-fostered piglets. This study compared the effect of either cross-fostering (FOS), or a control of sham-fostering (CON), of four focal piglets per litter on Day 6 postpartum in crates (CRATE) and free farrowing pens (PEN). The post-treatment behavioural responses of sows were recorded (Day 6 = 60 min; Day 7 = 300 min; n = 48), as were the average daily gain (ADG; g/day), total weight gain (TWG; kg) and body lesion scores of focal piglets and their littermates throughout lactation (Day 6, Day 8, Day 11 and Day 26; n = 539) and the post-weaning period (Day 29, Day 32 and Day 60; n = 108). On Day 6, though post-reunion latency to nursing did not differ, latency to successful nursing was longer amongst FOS than CON litters (P < 0.001), more so amongst CRATE FOS than PEN FOS (P < 0.01). On Day 7, PEN FOS sows had fewer successful nursing bouts (P < 0.05) and exhibited decreased lateral (P < 0.01) and increased ventral lying frequencies (P < 0.01) compared to all other housing and treatment combinations. Focal piglet ADG was lower for FOS than CON in the CRATE during Day 6 to Day 8 (P < 0.01) and lower in the PEN during Day 6 to Day 8 (P < 0.001), Day 8 to Day 11 (P < 0.01) and Day 11 to Day 26 (P < 0.05). The TWG of pre-weaned focal piglets (Day 6 to Day 26) was higher amongst CON than FOS litters (P = 0.01). Post-weaning, piglet ADG was higher for PEN than CRATE during Day 26 to Day 29 (P < 0.01) and higher for FOS than CON during Day 26 to Day 29 (P < 0.05), Day 29 to Day 32 (P < 0.001) and Day 32 to Day 60 (P < 0.01); thus, TWG was higher for FOS than CON during the weaner (P = 0.001) and the combined lactation and weaner periods (P = 0.09). In conclusion, sow behaviour was disrupted by cross-fostering in the crates and pens and continued to be disturbed on the following day amongst penned sows. FOS piglets exhibited reduced ADG after cross-fostering, which extended throughout lactation in the pens. However, the increased post-weaning weight gain of FOS piglets meant that their TWG was higher than CON piglets, irrespective of the farrowing system used.     

Comparative virulence of Pyrenophora teres f. teres from Syria and Tunisia and screening for resistance sources in barley: implications for breeding

Aims: The aim of this study is to investigate the pathogenic diversity and virulence groups among Pyrenophora teres f. teres isolates, sampled from Syria and Tunisia, and to identify the most effective source of resistance in barley that could be used in breeding programmes to control net blotch in both countries. Methods and Results: One hundred and four isolates of P. teres f. teres were collected from barley in different agroecological zones of Tunisia and Syria. Their virulence was evaluated using 14 barley genotypes as differential hosts. The upgma clustering identified high pathogenic variability; the isolates were clustered onto 20 pathotypes that were sheltered under three virulence groups, with high, intermediate and low disease scores. According to susceptibility/resistance frequencies and mean disease ratings, CI05401 cultivar ranked as the best differential when inoculated with the Syrian isolates. However, CI09214 cultivar was classified as the best effective source of resistance in Tunisia. Conclusions: All P. teres f. teres isolates were differentially pathogenic. CI09214 and CI05401 cultivars were released as the most effective sources of resistance in Syria and Tunisia. Significance and Impact of the Study: National and international barley breeding programmes that seek to develop resistance against P. teres f. teres in barley should strongly benefit from this study. This resistance cannot be achieved without the proper knowledge of the pathogen virulence spectrum and the sources of host resistance.     

Selective constraints in yeast genes with differential expressivity: codon pair usage and mRNA stability perspectives

Protein translation has been elucidated to be dictated by evolutionary constraints, namely, variations in tRNA availabilities and/or variations in codon-anticodon binding that is manifested in biased codon usage. Taking advantage of publicly available mRNA expression and protein abundance data for Saccharomyces cerevisiae, we have performed a comprehensive analysis of the diverse factors guiding translation leading to desired protein levels irrespective of the corresponding high or low mRNA levels. It has been elucidated in this study that different combinations of most abundant/non abundant tRNA isoacceptors are selected for in S. cerevisiae that helps in achieving the optimum speed and accuracy in the protein translation process. This is also accompanied by the strategic location of codon pairs in coherence to mRNA secondary structure folding stability for the above mentioned combinations of tRNA isoacceptors. We thus find that codon pair contextual effects; in addition to tRNA abundance and mRNA folding stability during translation elongation process play plausible roles in maintaining translation accuracy and speed that can achieve desired protein levels.     

Hydrodynamic behaviors in fermentative hydrogen bioreactors by pressure fluctuation analysis

Three bioreactor configurations were employed in these investigations, which consisted of working volumes of 10, 1.2 and 1.2 L. Power spectrum diagrams of bed pressure fluctuation were used with hydraulic retention times (HRT) and geometric factors to identify the flow regimes in the bioreactors, where HRT varied from 8 to 1 h. It was found that the flow regimes in the bioreactors changed from a dispersed regime to coalesced and slugging regimes, when the biogas production rate (BPR) increased, as a result of decreasing the operating HRT. The flow regime was a dispersed bubble regime when the HRT was higher than 4 h in the bioreactor, whereas when the HRT was 2 h the coalesced bubble phenomena occurred in the bioreactor. A slugging regime was found when the HRT was lower than 1 h in thinner bioreactor.     

Profound Perturbation of the Metabolome in Obesity Is Associated with Health Risk

1. Download high-res image (253KB)
2. Download full-size image

     

Grades of undernutrition and socioeconomic status influence cognitive development in school children of Kolkata

Cognitive development of children is influenced by different environmental factors like nutritional and socio‐economic status. The objectives of the present study were to determine the influence of grades of undernutrition and socio‐economic status (SES) on the cognitive development of school children of Kolkata. Five hundred sixty six (566) school children having 5–12 years of age were selected from different schools of Kolkata. The cognitive development was measured by the scores of Raven's colored progressive matrices (RCPM). The chronic and acute nutritional statuses were measured from height‐for‐age (HAZ) and weight‐for‐age (WAZ) Z scores respectively with reference to the values of WHO. SES was determined by updated Kuppuswamy scale. The prevalences of undernutrition in the observed children were 57.95% (according to HAZ) and 52.82% (according to WAZ). The age dependent growth curve of RCPM scores of the observed children remains in between the 10th and 25th centile of British children. The children belonging to superior and intellectual deficit IQ classes were 21.55 and 36.40%, respectively of the total subjects. Most of the subjects belong to lower middle (39.93%) and upper middle (36.40%) class of SES. RCPM scores of school children were gradually decreased with the grades of undernutrition and SES. RCPM scores were significantly correlated with HAZ, WAZ, SES, age, and sex (P < 0.001) and strongly associated with HAZ, SES, age, and sex (P < 0.001, P < 0.05). Present study indicates that cognitive development of school children of Kolkata is influenced by the grade of undernutrition and SES. Am J Phys Anthropol 156:274–285, 2015. © 2014 Wiley Periodicals, Inc.