Detection and Neutralization of SARS-CoV-2 Using Non-conventional Variable Lymphocyte Receptor Antibodies of the Evolutionarily Distant Sea Lamprey

SARS-CoV-2 is a newly emerged betacoronavirus and the causative agent for the COVID-19 pandemic. Antibodies recognizing the viral spike protein are instrumental in natural and vaccine-induced immune responses to the pathogen and in clinical diagnostic and therapeutic applications. Unlike conventional immunoglobulins, the variable lymphocyte receptor antibodies of jawless vertebrates are structurally distinct, indicating that they may recognize different epitopes. Here we report the isolation of monoclonal variable lymphocyte receptor antibodies from immunized sea lamprey larvae that recognize the spike protein of SARS-CoV-2 but not of other coronaviruses. We further demonstrate that these monoclonal variable lymphocyte receptor antibodies can efficiently neutralize the virus and form the basis of a rapid, single step SARS-CoV-2 detection system. This study provides evidence for monoclonal variable lymphocyte receptor antibodies as unique biomedical research and potential clinical diagnostic reagents targeting SARS-CoV-2

Sleep quality in middle-aged and elderly Chinese: distribution, associated factors and associations with cardio-metabolic risk factors

Background Poor sleep quality has been associated with increased risk of heart disease, diabetes and mortality. However, limited information exists on the distribution and determinants of sleep quality and its associations with cardio-metabolic risk factors in Chinese populations. We aimed to evaluate this in the current study. Methods A cross-sectional survey conducted in 2005 of 1,458 men and 1,831 women aged 50–70 years from urban and rural areas of Beijing and Shanghai. Using a questionnaire, sleep quality was measured in levels of well, common and poor. Comprehensive measures of socio-demographical and health factors and biomarkers of cardio-metabolic disease were recorded. These were evaluated in association with sleep quality using logistic regression models. Results Half of the population reported good sleep quality. After adjusting for potential confounders, women and Beijing residents had almost half the probability to report good sleep quality. Good physical and mental health (good levels of self-rated health (OR 2.48; 95%CI 2.08 to 2.96) and no depression (OR 4.05; 95%CI 3.12 to 5.26)) related to an increased chance of reporting good sleep quality, whereas short sleep duration (<7 hrs OR 0.10; 95%CI 0.07 to 0.14)) decreased it substantially. There were significant associations between levels of sleep quality and concentrations of plasma insulin, total and LDL cholesterol, and index of insulin resistance. Conclusion Levels of good sleep quality in middle-age and elderly Chinese were low. Gender, geographical location, self-rated health, depression and sleep quantity were major factors associated with sleep quality. Prospective studies are required to distil the factors that determine sleep quality and the effects that sleep patterns exert on cardio-metabolic health

Association of PCSK1 rs6234 with Obesity and Related Traits in a Chinese Han Population

Background: Common variants in PCSK1 have been reported to be associated with obesity in populations of European origin. We aimed to replicate this association in Chinese. Methodology/Principal Findings: Two PCSK1 variants rs6234 and rs6235 (in strong LD with each other, r 2 = 0.98) were genotyped in a population-based cohort of 3,210 Chinese Hans. The rs6234 was used for further association analyses with obesity and related traits. We found no significant association of rs6234 with obesity, overweight, BMI, waist circumference, or body fat percentage (P.0.05) in all participants. However, the rs6234 G-allele showed a significant association with increased risk of combined phenotype of obesity and overweight (OR 1.21[1.03–1.43], P = 0.0193) and a trend toward association with obesity (OR 1.25[0.98–1.61], P = 0.08) in men, but not in women (P$0.29). Consistently, the rs6234 G-allele showed significant association with increased BMI (P = 0.0043), waist circumference (P = 0.008) and body fat percentage (P = 0.0131) only in men, not in women (P$0.24). Interestingly, the rs6234 G-allele was significantly associated with increased HOMA-B (P = 0.0059) and decreased HOMA-S (P = 0.0349) in all participants. Conclusion/Significance: In this study, we found modest evidence for association of the PCSK1 rs6234 with BMI and overweight in men only but not in women, which suggested that PCSK1 rs6234 might not be an important contributor t

Parental educational level and cardiovascular disease risk factors in schoolchildren in large urban areas of Turkey: Directions for public health policy

BACKGROUND: It is widely accepted that the development of atherosclerosis starts at an early age. However, there are very few studies evaluating the prevalence of the common clinical and behavioral cardiovascular disease (CVD) risk factors among children, especially in developing countries. The aim of the present cross-sectional survey was to evaluate the distribution of blood lipid profile and various behavioral (i.e. dietary habits, physical activity status) factors related to CVD risk and its relationships to paternal (PEL) and maternal educational level (MEL) among primary schoolchildren in Turkey. METHODS: In three major metropolises in Turkey (Istanbul, Ankara and Izmir), a random sample of 1044 children aged 12 and 13 years old was examined. ANOVA was applied to evaluate the tested hypothesis, after correcting for multiple comparisons (Tukey correction). RESULTS: After controlling for energy and fat intake, physical activity status and Body Mass Index (BMI), it was found that mostly PEL had a significant positive effect for most of the subgroups examined (Lower vs. Higher and Medium vs. Higher) on TC and HDL-cholesterol and a negative effect on TC/HDL ratio for both genders. Furthermore, both boys and girls with higher PEL and MEL were found to have higher energy intake derived from fat and protein than their counterparts with Medium and Lower PEL and MEL, while the opposite was observed for the percentage of energy derived from carbohydrates. CONCLUSIONS: Our study provides indications for a possible association between an adverse lipid profile, certain dietary patterns and Higher PEL and MEL among schoolchildren in Turkey. These findings underline the possible role of social status, indicated by the degree of education of both parents, in developing certain health behaviors and health indices among Turkish children and provide some guidance for Public Health Policy

Effects of Body Fat on the Associations of High-Molecular-Weight Adiponectin, Leptin and Soluble Leptin Receptor with Metabolic Syndrome in Chinese

BACKGROUND: Little is known regarding the associations between high-molecular-weight (HMW-) adiponectin, leptin and soluble leptin receptor (sOB-R) and metabolic syndrome (MetS) in Chinese. Also few studies elucidate the effects of inflammation and body fat mass on the relations. METHODS: Plasma HMW-adiponectin, leptin and sOB-R were measured among 1055 Chinese men and women (35∼54 yrs). Whole body and trunk fat mass were determined by Dual-energy X-ray absorptiometry. MetS was defined by the updated NCEP/ATPIII criterion for Asian-Americans. RESULTS: HMW-adiponectin was inversely associated with MetS in multivariate model including fat mass index (FMI), inflammatory markers, leptin and sOB-R (OR in the highest quartile= 0.30, 95%CI 0.18∼0.50, P<.0001). Plasma sOB-R was also inversely associated with MetS independent of body fatness and inflammatory markers, whereas the association was somewhat attenuated after adjusting HMW-adiponectin (OR for the highest quartile = 0.78, 95%CI 0.47∼1.32, P = 0.15). In contrast, leptin was associated with increased odds of MetS independent of inflammatory markers, HMW-adiponectin, and sOB-R (OR for the highest quartile= 2.64, 95%CI 1.35∼5.18, P = 0.006), although further adjustment for FMI abolished this association. CONCLUSIONS: HMW-adiponectin exhibited strong inverse associations with MetS independent of body composition, inflammation, leptin and sOB-R; while the associations of leptin and sOB-R were largely explained by fat mass or HMW-adiponectin, respectively

Structural Insights into TIR Domain Specificity of the Bridging Adaptor Mal in TLR4 Signaling

MyD88 adaptor-like protein (Mal) is a crucial adaptor that acts as a bridge to recruit the MyD88 molecule to activated TLR4 receptors in response to invading pathogens. The specific assembly of the Toll/interleukin-1 receptor (TIR) domains of TLR4, Mal and MyD88 is responsible for proper signal transduction in the TLR4 signaling pathway. However, the molecular mechanism for the specificity of these TIR domains remains unclear. Here, we present the crystal structure of the TIR domain of the human Mal molecule (Mal-TIR) at a resolution of 2.4 Å. Unexpectedly, Mal-TIR exhibits an extraordinarily long AB loop, but no αB helix or BB loop, distinguishing it from other TIR domains. More importantly, the Mal-TIR AB loop is capable of mediating direct binding to the TIR domains of TLR4 and MyD88 simultaneously. We also found that Mal-TIR can form a back-to-back dimer that may resemble the dimeric assembly of the entire Mal molecule. Our data demonstrate the bridge role of the Mal-TIR domain and provide important information about TIR domain specificity

Characterization of miRNAs in Response to Short-Term Waterlogging in Three Inbred Lines of Zea mays

Waterlogging of plants leads to low oxygen levels (hypoxia) in the roots and causes a metabolic switch from aerobic respiration to anaerobic fermentation that results in rapid changes in gene transcription and protein synthesis. Our research seeks to characterize the microRNA-mediated gene regulatory networks associated with short-term waterlogging. MicroRNAs (miRNAs) are small non-coding RNAs that regulate many genes involved in growth, development and various biotic and abiotic stress responses. To characterize the involvement of miRNAs and their targets in response to short-term hypoxia conditions, a quantitative real time PCR (qRT-PCR) assay was used to quantify the expression of the 24 candidate mature miRNA signatures (22 known and 2 novel mature miRNAs, representing 66 miRNA loci) and their 92 predicted targets in three inbred Zea mays lines (waterlogging tolerant Hz32, mid-tolerant B73, and sensitive Mo17). Based on our studies, miR159, miR164, miR167, miR393, miR408 and miR528, which are mainly involved in root development and stress responses, were found to be key regulators in the post-transcriptional regulatory mechanisms under short-term waterlogging conditions in three inbred lines. Further, computational approaches were used to predict the stress and development related cis-regulatory elements on the promoters of these miRNAs; and a probable miRNA-mediated gene regulatory network in response to short-term waterlogging stress was constructed. The differential expression patterns of miRNAs and their targets in these three inbred lines suggest that the miRNAs are active participants in the signal transduction at the early stage of hypoxia conditions via a gene regulatory network; and crosstalk occurs between different biochemical pathways

Identifying Consensus Disease Pathways in Parkinson's Disease Using an Integrative Systems Biology Approach

Parkinson's disease (PD) has had six genome-wide association studies (GWAS) conducted as well as several gene expression studies. However, only variants in MAPT and SNCA have been consistently replicated. To improve the utility of these approaches, we applied pathway analyses integrating both GWAS and gene expression. The top 5000 SNPs (p<0.01) from a joint analysis of three existing PD GWAS were identified and each assigned to a gene. For gene expression, rather than the traditional comparison of one anatomical region between sets of patients and controls, we identified differentially expressed genes between adjacent Braak regions in each individual and adjusted using average control expression profiles. Over-represented pathways were calculated using a hyper-geometric statistical comparison. An integrated, systems meta-analysis of the over-represented pathways combined the expression and GWAS results using a Fisher's combined probability test. Four of the top seven pathways from each approach were identical. The top three pathways in the meta-analysis, with their corrected p-values, were axonal guidance (p = 2.8E-07), focal adhesion (p = 7.7E-06) and calcium signaling (p = 2.9E-05). These results support that a systems biology (pathway) approach will provide additional insight into the genetic etiology of PD and that these pathways have both biological and statistical support to be important in PD

A Genome-Wide Characterization of MicroRNA Genes in Maize

MicroRNAs (miRNAs) are small, non-coding RNAs that play essential roles in plant growth, development, and stress response. We conducted a genome-wide survey of maize miRNA genes, characterizing their structure, expression, and evolution. Computational approaches based on homology and secondary structure modeling identified 150 high-confidence genes within 26 miRNA families. For 25 families, expression was verified by deep-sequencing of small RNA libraries that were prepared from an assortment of maize tissues. PCR–RACE amplification of 68 miRNA transcript precursors, representing 18 families conserved across several plant species, showed that splice variation and the use of alternative transcriptional start and stop sites is common within this class of genes. Comparison of sequence variation data from diverse maize inbred lines versus teosinte accessions suggest that the mature miRNAs are under strong purifying selection while the flanking sequences evolve equivalently to other genes. Since maize is derived from an ancient tetraploid, the effect of whole-genome duplication on miRNA evolution was examined. We found that, like protein-coding genes, duplicated miRNA genes underwent extensive gene-loss, with ∼35% of ancestral sites retained as duplicate homoeologous miRNA genes. This number is higher than that observed with protein-coding genes. A search for putative miRNA targets indicated bias towards genes in regulatory and metabolic pathways. As maize is one of the principal models for plant growth and development, this study will serve as a foundation for future research into the functional roles of miRNA genes