To investigate the evolution and genetic characteristics of Coxsackievirus A6 (CVA6) which acted as the predominant pathogen of hand, foot and mouth disease (HFMD) in children in Beijing, China, ...2017–2019.
Throat swab specimens were collected for general Enterovirus (EV), enterovirus A71 (EV-A71) and CVA16 detection by Real-time PCR. These general EV-positive samples were identified by semi-nested RT-PCR method and sequencing. The CVA6 VP1 gene and genome sequences were amplified and sequenced. The phylogenetic, variation and recombination analyses were performed.
A total of 1721 HFMD patients were enrolled in this study, with the male to female ratio of 1.62:1. The majority of cases were less than five years, which accounted for 73.50%. The overall detection rate of EV was 88.32% (1520/1721). A total of 8 EV types were identified, including CVA6 (55.86%), CVA16 (26.32%), EV-A71 (2.24%), CVA10 (2.04%), CVA4 (1.05%), CVA5 (0.59%), CVA2 (0.33%), and CVA8 (0.07%), while 175 (11.51%) EV were untyped. The main pathogen of HFMD was CVA6 from 2017 to 2018, while CVA6 and CVA16 were the main causative pathogens in 2019. The nucleotide and amino acid sequence identities of the 120 CVA6 complete VP1 gene sequences in this study were 91.2%–100.0% and 97.7%–100.0%, respectively. Compared with the prototype strain (Gdula) of CVA6, the nucleotide and amino acid sequence identities were 81.7%–84% and 94.7%–96.3%, respectively. The phylogenetic tree indicated that all 120 CVA6 sequences belonged to sub-genotype D3, while 119 CVA6 sequences belonged to evolutionary branch D3a, except one from 2017 belonged to D3b. Recombination analysis based on the complete genome sequences showed that potential multiple recombination may have occurred in 2B and 3D protein coding regions with EV-A114.
The main pathogens of HFMD were CVA6 and CVA16 in Beijing, China, 2017–2019; while these CVA6, as recombination strains, belonged to the D3a evolutionary branch.
•The predominant serotypes of HFMD were CVA6 and CVA16 in Beijing, 2017−2019.•CVA6 D3a was the predominant sub-genotype caused HFMD in Beijing.
Oxytocin and its target receptor (oxytocin receptor, OXTR) exert important roles in the regulation of complex social behaviors and cognition. The oxytocin/OXTR system in the brain could activate and ...transduce several intracellular signaling pathways to affect neuronal functions or responses and then mediate physiological activities. The persistence and outcome of the oxytocin activity in the brain are closely linked to the regulation, state, and expression of OXTR. Increasing evidence has shown that genetic variations, epigenetic modification states, and the expression of OXTR have been implicated in psychiatric disorders characterized by social deficits, especially in autism. Among these variations and modifications, OXTR gene methylation and polymorphism have been found in many patients with psychiatric disorders and have been considered to be associated with those psychiatric disorders, behavioral abnormalities, and individual differences in response to social stimuli or others. Given the significance of these new findings, in this review, we focus on the progress of OXTR's functions, intrinsic mechanisms, and its correlations with psychiatric disorders or deficits in behaviors. We hope that this review can provide a deep insight into the study of OXTR-involved psychiatric disorders.
Skin colour and vitamin D: An update Hanel, Andrea; Carlberg, Carsten
Experimental dermatology,
September 2020, 2020-09-00, 20200901, Letnik:
29, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Homo sapiens evolved in East Africa and had dark skin, hair, and eyes, in order to protect against deleterious consequences of intensive UV radiation at equatorial latitudes. Intensive skin ...pigmentation was thought to bear the risk of inefficient vitamin D3 synthesis in the skin. This initiated the hypothesis that within the past 75 000 years, in which humans migrated to higher latitudes in Asia and Europe, the need for vitamin D3 synthesis served as an evolutionary driver for skin lightening. In this review, we summarize the recent archeogenomic reconstruction of population admixture in Europe and demonstrate that skin lightening happened as late as 5000 years ago through immigration of lighter pigmented populations from western Anatolia and the Russian steppe but not primarily via evolutionary pressure for vitamin D3 synthesis. We show that variations in genes encoding for proteins being responsible for the transport, metabolism and signalling of vitamin D provide alternative mechanisms of adaptation to a life in northern latitudes without suffering from consequences of vitamin D deficiency. This includes hypotheses explaining differences in the vitamin D status and response index of European populations.
Water scarcity is a global dilemma, and rice crop needs plenty of water for optimum growth and yield. In the current climate change scenario, developing a broad-based gene pool of rice to help the ...crop breeders develop high-yielding cultivars needs dire action. This study assessed the genetic variation among 10 diversified parents and their 15 F5 populations developed under limited water supply for various morphological traits. Parents and F5 populations showed significant differences at 5% and 1% for most of the studied maturity and yield traits. F5 population ‘Dokri-Basmati/DR-92’ exhibited earliest for days to heading (93) with the highest culm length (85.5 cm). Maximum flag leaf area (34.67 cm2) resulted for the F5 population ‘DR-83/NIAB-IRRI-8.’ On the other hand, the F5 population ‘DR-83/DR-92’ excelled in performance for the number of primary branches panicle-1 (11). F5 population ‘IR-8/NIAB-IRRI-9’ displayed the longest panicle (28.70 cm) with the highest number of secondary branches panicle-1 (38). Three of the F5 populations ‘DR-92/DR-83,’ ‘DR-83/NIAB-IRRI-8,’ and ‘NIAB-IRRI-9/IR-8,’ displayed maximum heritability for panicle length (0.82), the number of primary branches (0.80), and secondary branches panicle-1 (0.94), respectively, offering the prospects for development of potentially high-yielding variety. The highest genetic advance for panicle length (9.87%) emerged from the F5 population ‘DR-92/DR-83,’ which also had the highest heritability for this trait. F5 population ‘DR-83/DR-92’ manifested maximum genetic advance (3.32%) for primary branches panicle-1, while ‘NIAB-IRRI-9/IR-8’ revealed the highest genetic advance (6.26%) for secondary branches panicle-1. Both of these populations may be suitable for developing the spreading type of rice germplasm with the potential water stress. F5 populations displayed differential responses for the studied traits, with none of the segregating populations excelling for studied maturity and yield traits. However, the germplasm pool created can serve as a better collection for improving existing populations from a production traits perspective under water-stress conditions or developing new cultivars focusing these traits for the target water stress region(s).
Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein(a). Increased Lp(a) levels are an independent, heritable causal risk factor for ...atherosclerotic cardiovascular disease (ASCVD) as they are largely determined by variations in the Lp(a) gene (LPA) locus encoding apo(a). Lp(a) is the preferential lipoprotein carrier for oxidized phospholipids (OxPL), and its role adversely affects vascular inflammation, atherosclerotic lesions, endothelial function and thrombogenicity, which pathophysiologically leads to cardiovascular (CV) events. Despite this crucial role of Lp(a), its measurement lacks a globally unified method, and, between different laboratories, results need standardization. Standard antilipidemic therapies, such as statins, fibrates and ezetimibe, have a mediocre effect on Lp(a) levels, although it is not yet clear whether such treatments can affect CV events and prognosis. This narrative review aims to summarize knowledge regarding the mechanisms mediating the effect of Lp(a) on inflammation, atherosclerosis and thrombosis and discuss current diagnostic and therapeutic potentials.
Folate is a micronutrient essential for DNA synthesis, cell division, fetal growth and development. Folate deficiency leads to genomic instability. Inadequate intake of folate during conception may ...lead to neural tube defects (NTDs) in the offspring. Folate influences the DNA methylation, histone methylation and homocysteine mediated gene methylation. DNA methylation influences the expression of microRNAs (miRNAs). Folate deficiency may be associated with miRNAs misregulation leading to NTDs. Mitochondrial epigenetics and folate metabolism has proved to be involved in embryogenesis and neural tube development. Folate related genetic variants also cause the occurrence of NTDs. Unmetabolized excessive folate may affect health adversely. Hence estimation of folate levels in the blood plays an important role in high-risk cases.
•Folate plays an important role in DNA homeostasis, stability, and repair.•Defective folate intake increases the risk for neural tube defects under the influence of epigenetic modifications.•Mitochondria plays a crucial role in folate dependent one carbon metabolism.•Gene polymorphism caused by folate deficiency may also result in the development of neural tube defects during conception.•Blood folate levels need to be monitored in high risk cases since both deficiency and excess are harmful.
The bioavailability of β-carotene, the main dietary provitamin A carotenoid, varies among individuals. It is not known whether this variability can affect long-term β-carotene, and hence vitamin A, ...status.
We hypothesized that variations in genes involved in β-carotene absorption and postprandial metabolism could at least partially explain the high interindividual variability in β-carotene bioavailability. Thus, the main objectives of this study were to identify associated single-nucleotide polymorphisms (SNPs), and to estimate whether populations with different allele frequencies at these SNPs could have different abilities to absorb provitamin A carotenoids.
In this single-group design, 33 healthy, nonobese adult men were genotyped with the use of whole-genome microarrays. After an overnight fast, they consumed a test meal containing 100 g tomato puree providing 0.4 mg β-carotene. The postprandial plasma chylomicron β-carotene concentration was then measured at regular time intervals over 8 h. Partial least squares (PLS) regression was used to identify the best combination of SNPs in or near candidate genes (54 genes representing 2172 SNPs) that was associated with the postprandial chylomicron β-carotene response (incremental β-carotene area-under-the-curve concentration over 8 h in chylomicrons).
The postprandial chylomicron β-carotene response was highly variable (CV = 105%) and was positively correlated with the fasting plasma β-carotene concentration (r = 0.78; P < 0.0001). A significant (P = 6.54 × 10(-3)) multivalidated PLS regression model, which included 25 SNPs in 12 genes, explained 69% of the variance in the postprandial chylomicron β-carotene response, i.e., β-carotene bioavailability.
Interindividual variability in β-carotene bioavailability appears to be partially modulated by a combination of SNPs in 12 genes. This variability likely affects the long-term blood β-carotene status. A theoretic calculation of β-carotene bioavailability in 4 populations of the international HapMap project suggests that populations with different allele frequencies in these SNPs might exhibit a different ability to absorb dietary β-carotene. This trial was registered at clinicaltrials.gov as NCT02100774.
Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and ...psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop accurate diagnostic tools for treatment recommendations and preventive strategies, and for disease prognosis and prediction, is an important step toward precision medicine. However, for complex diseases, precision medicine is associated with several challenges. There is a significant heterogeneity between patients of a specific disease-both with regards to symptoms and underlying causal mechanisms-and the number of underlying genetic and nongenetic risk factors is often high. Here, we summarize precision medicine approaches for complex diseases and highlight the current breakthroughs as well as the challenges. We conclude that genomic-based precision medicine has been used mainly for patients with highly penetrant monogenic disease forms, such as cardiomyopathies. However, for most complex diseases-including psychiatric disorders and allergies-available polygenic risk scores are more probabilistic than deterministic and have not yet been validated for clinical utility. However, subclassifying patients of a specific disease into discrete homogenous subtypes based on molecular or phenotypic data is a promising strategy for improving diagnosis, prediction, treatment, prevention, and prognosis. The availability of high-throughput molecular technologies, together with large collections of health data and novel data-driven approaches, offers promise toward improved individual health through precision medicine.
Mosaic loss of chromosome Y (mLOY) is the most common structure somatic event that related to increased risks of various diseases and mortality. Environmental pollution and genetic susceptibility ...were important contributors to mLOY. We aimed to explore the associations of polycyclic aromatic hydrocarbons (PAHs) exposure, as well as their joint effects with age, smoking, and genetic variants on peripheral blood mLOY. A total of 1005 male coke-oven workers were included in this study and their internal PAHs exposure levels of 10 urinary PAH metabolites and plasma benzoapyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts were measured. mLOY was defined by the median log R ratio(mLRR) of 1480 probes in male-specific region of chromosome-Y from genotyping array. We found that the PAHs exposure levels were linearly associated with mLOY. A 10-fold increase in urinary 1-hydroxynaphthalene (1-OHNa), 1-hydroxyphenanthrene (1-OHPh), 2-OHPh, 1-hydroxypyrene (1-OHP), ΣOH-PAHs, and plasma BPDE-Alb adducts could generate 0.0111, 0.0085, 0.0069, 0.0103, 0.0134, and 0.0152 decrease in mLRR-Y, respectively. Additionally, mLOY accelerated with age, smoking pack-years, and TCL1A rs1122138-C allele, and we observed the most severe mLOY among subjects carrying more than 3 of the above risk factors. Our results revealed the linear dose-effect associations between PAHs exposure and mLOY. Elder male smokers carrying rs1122138CC genotype were the most susceptible subpopulations to mLOY, who should be given protections for PAHs exposure induced chromosome-Y aberration.
Display omitted
•Increased levels of PAHs exposure were associated with more severe mLOY.•PAHs, age, smoking pack-years, and TCL1A rs1122138CC had joint effects on mLOY.•Take precautions against mLOY among elder smokers exposed to PAHs and rs1122138CC.
Increased levels of PAHs exposure were associated with more severe mLOY. There were interactive and joint effects of PAHs, age, smoking pack-years, and TCL1A rs1122138CC on mLOY.
PDF
