Estimation of Inbreeding Coefficients Using Pedigree and Microsatellite Markers and Its Effects on Economic Traits of Shirvan Kordi Sheep

INTRODUCTION Intensive selection within a single population of finite size reduces the genetic variability and increases the rate of inbreeding KEY WORDS Research Article Estimation of Inbreeding Coefficients in Shirvan Kordi Sheep In the overdominance hypothesis, inbreeding depression is attributable to higher fitness of heterozygotes for the loci in question. For the partial recessive hypothesis, negative fitness consequences are due to the fixation of recessive or partially recessive deleterious alleles Microsatellites has been widely used as reliable molecular markers to study the genetic relationship of different populations and for indirect measures of inbreeding. They are codominant, highly polymorphic, highly abundant, heritable, locus specific, and easily analyzed and therefore suitable for studies on population phylogenesis constitution This study was carried out using microsatellite markers because they are powerful tools for tracking alleles through a population and to estimate genetic variability and inbreeding Marker data collected provides information on population structure, relatedness and inbreeding MATERIALS AND METHODS Data Pedigree information from 1989 to 2009 of a flock of Kordi sheep maintained at Shirvan Sheep Breeding Station was used. Pedigree file contained information on individual identification number, sex, type of birth, dam and sire as well as birth date and included 7170 registered animals (3332 males and 3838 females), progeny of177 sires and 2182 dams. Pedigree analysis Inbreeding coefficients of the animals were computed using the CFC program Microsatellite method Blood samples (5 mL) of 100 animals were collected from the jugular vein and transferred into vacutainer tubes containing 0.5 molar EDTA as anticoagulant and frozen at -20 ˚C. Total DNA was isolated from blood samples using the Diatom DNA Kit, according to the manufacturer instructions. The quantity and quality of the isolated DNA was determined using both spectrophotometry and by 0.8% agarose gel electrophoresis. Characteristics of the microsatellite markers used in this study are listed in Approximately, 100 ng DNA (adjusted concentration) was used as template for polymerase chain reaction (PCR). The PCR reaction cycle was carried out in a the rmocycler (Biorad) by denaturation at 95 ˚C for 4 min, denaturation at 95 ˚C for 45 sec, primer annealing for 45 sec at the desired temperature (55-60 ˚C) and an extension for 1 min at 72 ˚C, repeating the cycle 35 times. The final extension step was at 72 ˚C for 4 min. The PCR amplification was conducted in a 12 μL volume. PCR products were analyzed by vertical electrophoresis in 6% non-denaturing polyacrylamide gel (170 V, 3-4 h) and bands visualized by rapid silver staining Molecular data analysis Molecular data were analysed using the POPGENE V1.32 RESULTS AND DISCUSSION Pedigree analysis The analysis of pedigree revealed that mean level of inbreeding (F) of all animals acrossall years (1989-2009) was 0.668%. Moreover, the minimum and maximum coefficientsof inbreeding for the animals in the flock was 0 and 31.25%, respectively. The low average coefficient of inbreeding could be ascribed to breeding strategies at the station for preventing mating of relatives. Totally, 23.26% of the animals (1668 out of 7170) were inbred with a mean inbreeding coefficient of 2.87%. In the pedigree, 3332 and 3838 of the animals were males and females with mean inbreeding coefficients of 0.693% and 0.646%, respectively. Out of all, 1668 animals were inbred. These included 823 males and 845 females having average inbreeding coefficient of 2.81% and 2.93%, respectively. These results indicated that fewmatings of close relatives have occurred. Descriptive statistics for inbreeding coefficients for the entire population and the inbred portion of the population are shown in 135 Estimation of Inbreeding Coefficients in Shirvan Kordi Sheep Mean of all traits decreased and increased irregularly by increasing inbreeding coefficients. This could be due to fewer records in the numerically higher classes of inbreeding. Inbreeding depression Details of the data used for the estimation of inbreeding depression are given in Regression coefficients and their standard errors on inbreeding coefficients were -0.0013 ± 0.0003 kg for BWT, 0.080 ± 0.015 kg for WWT, 0.001 ± 0.0009 kg for BW6M, -0.065 ± 0.055 kg for BW9M, -0.092 ± 0.063 kg for BW12M, 0.008 ± 0.0066kg for Wool and -0.023 ± 0.012 lambs for LS. Pre-weaning growth traits BWT: birth weight trait; WWT: weaning weight trait; BW6M: body weight at 6 months of age trait; BW9W: body weight at 9 months of age trait; BW12M: body weight at 12 months of age trait; Wool: wool produced annually and LS: number of lambs per ewe lambing. Changes for every one percent increase in inbreeding coefficient for BWT and WWT were -0.0131 and 0.0795 kg, respectively. Regression coefficient estimate for BWT Regression coefficients for BW in the 9 th and 12 th month were more than all the other studied traits. Estimates of -0.0653 and -0.0921 kg per 1% increase in inbreeding coefficient for BW in 9 th month and BW in 12 th month, were more than the values reported in other studies. Annual wool production and number of lambs per ewe lambing The effect of inbreeding on wool produced annually and the number of lambs per ewe lambing amounted to 0.0083 kg and -0.023 lambs, respectively. For the annual wool production, the linear effect of individual inbreeding, regression was positive but non-significant. On the average, an increase in 1 percent in individual inbreeding increased the wool produced annually by 0.0083 kg. A review b

Design of a Customized Neck Orthosis for FDM Manufacturing with a New Sustainable Bio-composite

The interest in developing customized external orthopaedic devices, thanks to the advent of Additive Manufacturing (AM), has grown in recent years. Greater attention was focused on upper limb casts, while applications to other body’s parts, such as the neck, were less investigated. In this paper the computer aided design (CAD) modelling, assessment and 3D printing with fused deposition modelling (FDM) of a customized neck orthosis are reported. The modelling, based on anatomic data of a volunteer subject, was aimed to obtain a lightweight, ventilated, hygienic and comfortable orthosis compared to the produced medical devices generally used for neck injuries. CAD models with different geometrical patterns, introduced for lightening and improving breathability, were considered, specifically, a honeycomb pattern and an elliptical holes pattern. These models were structurally assessed by means of finite elements analysis (FEA). Furthermore, an innovative composite material was considered for 3D printing. The material, Hemp Bio-Plastic® (HBP), composed by polylactic acid (PLA) and hemp shives, offers different advantages including lightweight, improved superficial finish and antibacterial properties. The results obtained in terms of design methodology and manufacturing by 3D printing of a prototype have shown the feasibility to develop customized cervical orthoses, with potentially improved performance with respect to cervical collars available on the market also thanks to the use of the innovative composite material

Bio-nanotechnology application in wastewater treatment

The nanoparticles have received high interest in the field of medicine and water purification, however, the nanomaterials produced by chemical and physical methods are considered hazardous, expensive, and leave behind harmful substances to the environment. This chapter aimed to focus on green-synthesized nanoparticles and their medical applications. Moreover, the chapter highlighted the applicability of the metallic nanoparticles (MNPs) in the inactivation of microbial cells due to their high surface and small particle size. Modifying nanomaterials produced by green-methods is safe, inexpensive, and easy. Therefore, the control and modification of nanoparticles and their properties were also discussed

Low fingertip temperature rebound measured by digital thermal monitoring strongly correlates with the presence and extent of coronary artery disease diagnosed by 64-slice multi-detector computed tomography

Previous studies showed strong correlations between low fingertip temperature rebound measured by digital thermal monitoring (DTM) during a 5 min arm-cuff induced reactive hyperemia and both the Framingham Risk Score (FRS), and coronary artery calcification (CAC) in asymptomatic populations. This study evaluates the correlation between DTM and coronary artery disease (CAD) measured by CT angiography (CTA) in symptomatic patients. It also investigates the correlation between CTA and a new index of neurovascular reactivity measured by DTM. 129 patients, age 63 ± 9 years, 68% male, underwent DTM, CAC and CTA. Adjusted DTM indices in the occluded arm were calculated: temperature rebound: aTR and area under the temperature curve aTMP-AUC. DTM neurovascular reactivity (NVR) index was measured based on increased fingertip temperature in the non-occluded arm. Obstructive CAD was defined as ≥50% luminal stenosis, and normal as no stenosis and CAC = 0. Baseline fingertip temperature was not different across the groups. However, all DTM indices of vascular and neurovascular reactivity significantly decreased from normal to non-obstructive to obstructive CAD [(aTR 1.77 ± 1.18 to 1.24 ± 1.14 to 0.94 ± 0.92) (P = 0.009), (aTMP-AUC: 355.6 ± 242.4 to 277.4 ± 182.4 to 184.4 ± 171.2) (P = 0.001), (NVR: 161.5 ± 147.4 to 77.6 ± 88.2 to 48.8 ± 63.8) (P = 0.015)]. After adjusting for risk factors, the odds ratio for obstructive CAD compared to normal in the lowest versus two upper tertiles of FRS, aTR, aTMP-AUC, and NVR were 2.41 (1.02–5.93), P = 0.05, 8.67 (2.6–9.4), P = 0.001, 11.62 (5.1–28.7), P = 0.001, and 3.58 (1.09–11.69), P = 0.01, respectively. DTM indices and FRS combined resulted in a ROC curve area of 0.88 for the prediction of obstructive CAD. In patients suspected of CAD, low fingertip temperature rebound measured by DTM significantly predicted CTA-diagnosed obstructive disease

Trends in HIV/AIDS morbidity and mortality in Eastern Mediterranean countries, 1990–2015: findings from the Global Burden of Disease 2015 study

OBJECTIVES: We used the results of the Global Burden of Disease 2015 study to estimate trends of HIV/AIDS burden in Eastern Mediterranean Region (EMR) countries between 1990 and 2015. METHODS: Tailored estimation methods were used to produce final estimates of mortality. Years of life lost (YLLs) were calculated by multiplying the mortality rate by population by age-specific life expectancy. Years lived with disability (YLDs) were computed as the prevalence of a sequela multiplied by its disability weight. RESULTS: In 2015, the rate of HIV/AIDS deaths in the EMR was 1.8 (1.4–2.5) per 100,000 population, a 43% increase from 1990 (0.3; 0.2–0.8). Consequently, the rate of YLLs due to HIV/AIDS increased from 15.3 (7.6–36.2) per 100,000 in 1990 to 81.9 (65.3–114.4) in 2015. The rate of YLDs increased from 1.3 (0.6–3.1) in 1990 to 4.4 (2.7–6.6) in 2015. CONCLUSIONS: HIV/AIDS morbidity and mortality increased in the EMR since 1990. To reverse this trend and achieve epidemic control, EMR countries should strengthen HIV surveillance, and scale up HIV antiretroviral therapy and comprehensive prevention services

Estimates, trends, and drivers of the global burden of type 2 diabetes attributable to PM2·5 air pollution, 1990–2019: an analysis of data from the Global Burden of Disease Study 2019

Background: Experimental and epidemiological studies indicate an association between exposure to particulate matter (PM) air pollution and increased risk of type 2 diabetes. In view of the high and increasing prevalence of diabetes, we aimed to quantify the burden of type 2 diabetes attributable to PM2·5 originating from ambient and household air pollution. Methods: We systematically compiled all relevant cohort and case-control studies assessing the effect of exposure to household and ambient fine particulate matter (PM2·5) air pollution on type 2 diabetes incidence and mortality. We derived an exposure–response curve from the extracted relative risk estimates using the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. The estimated curve was linked to ambient and household PM2·5 exposures from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, and estimates of the attributable burden (population attributable fractions and rates per 100 000 population of deaths and disability-adjusted life-years) for 204 countries from 1990 to 2019 were calculated. We also assessed the role of changes in exposure, population size, age, and type 2 diabetes incidence in the observed trend in PM2·5-attributable type 2 diabetes burden. All estimates are presented with 95% uncertainty intervals. Findings: In 2019, approximately a fifth of the global burden of type 2 diabetes was attributable to PM2·5 exposure, with an estimated 3·78 (95% uncertainty interval 2·68–4·83) deaths per 100 000 population and 167 (117–223) disability-adjusted life-years (DALYs) per 100 000 population. Approximately 13·4% (9·49–17·5) of deaths and 13·6% (9·73–17·9) of DALYs due to type 2 diabetes were contributed by ambient PM2·5, and 6·50% (4·22–9·53) of deaths and 5·92% (3·81–8·64) of DALYs by household air pollution. High burdens, in terms of numbers as well as rates, were estimated in Asia, sub-Saharan Africa, and South America. Since 1990, the attributable burden has increased by 50%, driven largely by population growth and ageing. Globally, the impact of reductions in household air pollution was largely offset by increased ambient PM2·5. Interpretation: Air pollution is a major risk factor for diabetes. We estimated that about a fifth of the global burden of type 2 diabetes is attributable PM2·5 pollution. Air pollution mitigation therefore might have an essential role in reducing the global disease burden resulting from type 2 diabetes. Funding: Bill & Melinda Gates Foundation

Redirection to the bone marrow improves T cell persistence and antitumor functions

A key predictor for the success of gene-modified T cell therapies for cancer is the persistence of transferred cells in the patient. The propensity of less differentiated memory T cells to expand and survive efficiently has therefore made them attractive candidates for clinical application. We hypothesized that redirecting T cells to specialized niches in the BM that support memory differentiation would confer increased therapeutic efficacy. We show that overexpression of chemokine receptor CXCR4 in CD8+ T cells (TCXCR4) enhanced their migration toward vascular-associated CXCL12+ cells in the BM and increased their local engraftment. Increased access of TCXCR4 to the BM microenvironment induced IL-15–dependent homeostatic expansion and promoted the differentiation of memory precursor–like cells with low expression of programmed death-1, resistance to apoptosis, and a heightened capacity to generate polyfunctional cytokine-producing effector cells. Following transfer to lymphoma-bearing mice, TCXCR4 showed a greater capacity for effector expansion and better tumor protection, the latter being independent of changes in trafficking to the tumor bed or local out-competition of regulatory T cells. Thus, redirected homing of T cells to the BM confers increased memory differentiation and antitumor immunity, suggesting an innovative solution to increase the persistence and functions of therapeutic T cells

Mapping subnational HIV mortality in six Latin American countries with incomplete vital registration systems

Background: Human immunodeficiency virus (HIV) remains a public health priority in Latin America. While the burden of HIV is historically concentrated in urban areas and high-risk groups, subnational estimates that cover multiple countries and years are missing. This paucity is partially due to incomplete vital registration (VR) systems and statistical challenges related to estimating mortality rates in areas with low numbers of HIV deaths. In this analysis, we address this gap and provide novel estimates of the HIV mortality rate and the number of HIV deaths by age group, sex, and municipality in Brazil, Colombia, Costa Rica, Ecuador, Guatemala, and Mexico. Methods: We performed an ecological study using VR data ranging from 2000 to 2017, dependent on individual country data availability. We modeled HIV mortality using a Bayesian spatially explicit mixed-effects regression model that incorporates prior information on VR completeness. We calibrated our results to the Global Burden of Disease Study 2017. Results: All countries displayed over a 40-fold difference in HIV mortality between municipalities with the highest and lowest age-standardized HIV mortality rate in the last year of study for men, and over a 20-fold difference for women. Despite decreases in national HIV mortality in all countries—apart from Ecuador—across the period of study, we found broad variation in relative changes in HIV mortality at the municipality level and increasing relative inequality over time in all countries. In all six countries included in this analysis, 50% or more HIV deaths were concentrated in fewer than 10% of municipalities in the latest year of study. In addition, national age patterns reflected shifts in mortality to older age groups—the median age group among decedents ranged from 30 to 45 years of age at the municipality level in Brazil, Colombia, and Mexico in 2017. Conclusions: Our subnational estimates of HIV mortality revealed significant spatial variation and diverging local trends in HIV mortality over time and by age. This analysis provides a framework for incorporating data and uncertainty from incomplete VR systems and can help guide more geographically precise public health intervention to support HIV-related care and reduce HIV-related deaths