High-throughput DNA sequence analysis elucidates novel insight into the genetic basis of adaptation in local sheep.

Understanding how evolutionary factors related to climate adaptation and human selection have influenced the genetic architecture of domesticated animals is of great interest in biology. In the current study, by using 304 whole genomes from different geographical regions (including Europe, north Africa, Southwest Asia, east Asia, west Africa, south Asia, east Africa, Australia and Turkey), We evaluate global sheep population dynamics in terms of genetic variation and population structure. We further conducted comparative population analysis to study the genetic underpinnings of climate adaption to local environments and also morphological traits. In order to identify genomic signals under selection, we applied fixation index (FST) and also nucleotide diversity (θπ) statistical measurements. Our results revealed several candidate genes on different chromosomes under selection for local climate adaptation (e.g. HOXC12, HOXC13, IRF1, FGD2 and GNAQ), body size (PDGFA, HMGA2, PDE3A) and also morphological related traits (RXFP2). The discovered candidate genes may offer newel insights into genetic underpinning of regional adaptation and commercially significant features in local sheep.

Population genetic analysis and scans for adaptation and contemporary selection footprints provide genomic insight into aus, indica and japonica rice cultivars diversification.

Following domestication, rice cultivars have been spread worldwide to different climates and have experienced selection pressures to improve desirable traits. This has resulted in diverse cultivars that display variations in phenotypic traits, such as stress tolerance, grain size, and yield. To better understand the genomic composition arising from cultivar's development and local adaptation, high-density genotypes (containing 286,183 single-nucleotide polymorphisms after the quality control) of 1284 rice cultivars of aus, indica, and temperate and tropical japonica were scanned for diversifying signatures by applying a pairwise comparison of fixation index (Fst) test. Each cultivar's population was investigated for contemporary selection using the integrated haplotype score test. Signatures of diversifying selection among the pairwise comparisons were found in genomic regions mainly involved in response to stress (pathogens, drought, heat, cold) and development and morphology of various structures, such as root, pollen, spikelet, and grain. The most significant diversification signal between indica and japonica cultivars was detected at the location of ROX2 gene. Aus with indica comparison detected the most divergent signal at important candidate genes of OsEXPA8 and OsEXPA9, whereas temperate with tropical japonica comparison resulted in two well-known candidate genes OsHCT4 and OsGpx4. Recent selection analysis detected different patterns of contemporary selection in genomic regions related to rice breeding standard criteria such as stress tolerance, seed germination, starch content, and flowering time. Our findings highlight the underlying molecular basis of adaptive divergence and propose that modern rice breeding may provide additional diversification among rice cultivars.

Genetic diversity and signatures of selection in four indigenous horse breeds of Iran.

Indigenous Iranian horse breeds were evolutionarily affected by natural and artificial selection in distinct phylogeographic clades, which shaped their genomes in several unique ways. The aims of this study were to evaluate the genetic diversity and genomewide selection signatures in four indigenous Iranian horse breeds. We evaluated 169 horses from Caspian (n = 21), Turkmen (n = 29), Kurdish (n = 67), and Persian Arabian (n = 52) populations, using genomewide genotyping data. The contemporary effective population sizes were 59, 98, 102, and 113 for Turkmen, Caspian, Persian Arabian, and Kurdish breeds, respectively. By analysis of the population genetic structure, we classified the north breeds (Caspian and Turkmen) and west/southwest breeds (Persian Arabian and Kurdish) into two phylogeographic clades reflecting their geographic origin. Using the de-correlated composite of multiple selection signal statistics based on pairwise comparisons, we detected a different number of significant SNPs under putative selection from 13 to 28 for the six pairwise comparisons (FDR < 0.05). The identified SNPs under putative selection coincided with genes previously associated with known QTLs for morphological, adaptation, and fitness traits. Our results showed HMGA2 and LLPH as strong candidate genes for height variation between Caspian horses with a small size and the other studied breeds with a medium size. Using the results of studies on human height retrieved from the GWAS catalog, we suggested 38 new putative candidate genes under selection. These results provide a genomewide map of selection signatures in the studied breeds, which represent valuable information for formulating genetic conservation and improved breeding strategies for the breeds.

Improving vascular access creation among hemodialysis patients: An agent-based modeling and simulation approach.

Chronic kidney disease is a worldwide public health problem, and vascular access is known as hemodialysis patients' lifeline. Hemodialysis is the most common treatment for kidney replacement. The choice of vascular access should be "patient-centered." However, the preferred or optimal type of vascular access that is generally recommended by clinical guidelines for hemodialysis patients is a native Arteriovenous Fistula (AVF). Despite the recommendations of the guidelines, unfortunately, many hemodialysis patients undergo dialysis through the catheter. Thus, this issue must be controlled by healthcare providers to reduce the adverse events of choosing this access for patients. As such, the prevalence of the concept of "first fistula, catheter last," identification of barriers to catheterization and effective factors in the use of native venous arterial fistula, as well as evaluating its impact on improving health and quality of life should be considered. To this aim, we have developed an agent-based simulation to investigate the effects of different agents on this process, as well as plan to achieve the desired status for improving and optimizing vascular access creation and maintenance. The decisions and behaviors of the stakeholders (agents) play a critical role in hemodialysis processes, so we have simulated their behaviors and decisions that are the most essential factor in establishing the system's status. To understand and evaluate the current situation, several experts, including nephrologists, surgeons, and dialysis nurses have been recruited to detect the factors influencing this process plus the relevant stakeholders, and their roles and effects. Our study has shown that agent-based modeling has a great potential in developing a simulation model to improve vascular access creation among hemodialysis patients.

Evaluating the antibacterial effect of synthesized herbal toothpastes and their efficacy for dentine tubule occlusion: Scanning electron microscopy and energy-dispersive X-ray spectroscopy analysis.

The tubule occlusion of two newly developed herbal toothpastes was examined. They were prepared based on the mixture of pomegranate peel and Equisetum arvense extracts with strontium acetate. The antimicrobial activity of pomegranate peel and E. arvense were determined using minimum inhibitory concentration (MIC). Then, 30 mid-coronal dentin discs from the human third molars were etched for 30 s with the lemon juice (pH = 2.4). The specimens divided into the three groups. While the control group had 6 specimens, Groups 1 and 2 were including 12 specimens. Group 1 brushed with toothpaste containing 10% strontium acetate and 5% hydroalcoholic extracts of pomegranate peel, and Group 2 brushed with 5% strontium acetate, 5% hydroalcoholic extracts of E. arvense, and 5% hydroalcoholic extracts of pomegranate peel. Brushing was simulated for 6 months with 2 N loading. Then, 50% of discs in each group were immersed in lemon juice for 1 min. Moreover, specimens in control group were brushed with distilled water. Finally, all 30 discs were analyzed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDXS). The occluded dentin tubules were counted and statistically evaluated. It was found that the number of open dentin tubules decreases significantly after brushing with both tested toothpastes compared with control group (p < .001). Moreover, a significant difference was observed between two toothpastes before and after acid immersion process (p < .001). The SEM micrographs confirmed the dentin tubule occlusion of both herbal dentifrices. Besides, EDXS analysis approved the strontium and silica presence on the dentin tubules for the toothpaste which was based on E. arvense.

Prediction of biological age and evaluation of genome-wide dynamic methylomic changes throughout human aging.

The use of DNA methylation signatures to predict chronological age and aging rate is of interest in many fields, including disease prevention and treatment, forensics, and anti-aging medicine. Although a large number of methylation markers are significantly associated with age, most age-prediction methods use a few markers selected based on either previously published studies or datasets containing methylation information. Here, we implemented reproducing kernel Hilbert spaces (RKHS) regression and a ridge regression model in a Bayesian framework that utilized phenotypic and methylation profiles simultaneously to predict chronological age. We used over 450,000 CpG sites from the whole blood of a large cohort of 4409 human individuals with a range of 10-101 years of age. Models were fitted using adjusted and un-adjusted methylation measurements for cell heterogeneity. Un-adjusted methylation scores delivered a significantly higher prediction accuracy than adjusted methylation data, with a correlation between age and predicted age of 0.98 and a root mean square error (RMSE) of 3.54 years in un-adjusted data, and 0.90 (correlation) and 7.16 (RMSE) years in adjusted data. Reducing the number of predictors (CpG sites) through subset selection improved predictive power with a correlation of 0.98 and an RMSE of 2.98 years in the RKHS model. We found distinct global methylation patterns, with a significant increase in the proportion of methylated cytosines in CpG islands and a decreased proportion in other CpG types, including CpG shore, shelf, and open sea (P < 5e-06). Epigenetic drift seemed to be a widespread phenomenon as more than 97% of the age-associated methylation sites had heteroscedasticity. Apparent methylomic aging rate (AMAR) had a sex-specific pattern, with an increase in AMAR in females with age related to males.

The effect of hydroalcoholic extract of Teucrium polium L. on the inflammatory markers and lipid profile in hypercholesterolemic rats.

BACKGROUND: Cardiovascular diseases are among the most common causes of mortality worldwide. Therefore, it is necessary to control the risk factors of these patients. Since the level of inflammatory markers and lipid profiles has increased in cardiovascular diseases and due to the increasing role of plants in the treatment of diseases, the current study aimed to investigate the effect of hydroalcoholic extract of Teucrium polium on inflammatory markers and lipid profile in hypercholesterolemic rats. MATERIALS AND METHODS: A total of 24 adult male Wistar rats were randomly divided into four groups of six each and treated with oral administration for 8 weeks. The control group received normal diet, the sham group received high-cholesterol diet and experimental groups 1 and 2 received high-cholesterol diet in the 8 weeks and doses of 85 and 170 mg/kg, respectively, of the T. polium hydroalcoholic extract (TPHAE) in the second 4 weeks. At the beginning and the end of the study, rats were examined for biochemical parameters. The mean level of variables for each group was presented as mean ± standard error of mean. RESULTS: The results of this study showed that, after administration of TPHAE, there was a significant decrease in the mean of inflammatory markers in all groups compared to sham group (P<0.001). Also, administration of the extract significantly reduced the serum levels of triglyceride, cholesterol and LDL-cholesterol and significantly increased the serum HDL-cholesterol levels. In addition, the 170 mg/kg dose of TPHAE was the most effective in reducing serum levels of inflammatory and lipid markers. CONCLUSION: Treatment with TPHAE caused dose-dependent decrease in serum levels of inflammatory markers and lipid profile in hypercholesterolemic rats. Therefore, it can be applied as a natural product for the management of cardiovascular diseases.

Effects of Vitamin D Deficiency on Incidence Risk of Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis.

INTRODUCTION: Proper nutrition is important for overall health, and it reduces healthcare costs associated with malnutrition. Many studies have investigated vitamin D deficiency and its role in gestational diabetes and controversial data have reported. A comprehensive consideration of articles in this field provides the possibility of a general study of this relationship. This meta-analysis is an evaluation of the relationship between vitamin D deficiency and gestational diabetes. MATERIAL AND METHODS: Different databases (such as PubMed, Science Information Institute, EmBase, Scopus, and the Cochrane Library) were searched for studies and eligible English articles published before February 2017 that have reported the risk of gestational diabetes in relation to vitamin D deficiency. This relationship was measured using odds ratios (ORs) with a confidence interval (CI) of 95%. The influence of each study was measured through sensitivity analysis. Funnel plots, Egger regression tests, and the Begg-Mazumdar correlation test were used to determine bias or publication bias. STATA (version 11.2) was used for all analyses. RESULTS: Twenty-six studies were selected as eligible for this research and included in the final analysis. In general, vitamin D deficiency among mothers may be related to an increased risk of gestational diabetes (OR = 1.18; 95% CI, 1.01-1.35; p < 0.001). The serum level of 25(OH)D is less meaningful in people with gestational diabetes than in those who have normal glucose tolerance. Subgroup analysis showed that the results concerning this association may vary with study design but do not change with country of origin. CONCLUSION: Some evidence has shown that vitamin D deficiency may increase the risk of gestational diabetes.

Fracture risk in patients with type 2 diabetes mellitus and possible risk factors: a systematic review and meta-analysis.

AIM: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of bone fractures. A variable increase in fracture risk has been reported depending on skeletal site, diabetes duration, study design, insulin use, and so on. The present meta-analysis aimed to investigate the association between T2DM with fracture risk and possible risk factors. METHODS: Different databases including PubMed, Institute for Scientific Information, and Scopus were searched up to May 2016. All epidemiologic studies on the association between T2DM and fracture risk were included. The relevant data obtained from these papers were analyzed by a random effects model and publication bias was assessed by funnel plot. All analyses were done by R software (version 3.2.1) and STATA (version 11.1). RESULTS: Thirty eligible studies were selected for the meta-analysis. We found a statistically significant positive association between T2DM and hip, vertebral, or foot fractures and no association between T2DM and wrist, proximal humerus, or ankle fractures. Overall, T2DM was associated with an increased risk of any fracture (summary relative risk =1.05, 95% confidence interval: 1.04, 1.06) and increased with age, duration of diabetes, and insulin therapy. CONCLUSION: Our findings strongly support an association between T2DM and increased risk of overall fracture. These findings emphasize the need for fracture prevention strategies in patients with diabetes.