The development of the single-strand conformation polymorphism (SSCP) technique to assess sequence level variation within the major histocompatibility complex (MHC) DRB1 gene in four South African buffalo (Syncerus caffer) populations

Includes bibliographical references.This thesis reports the development of Single-Strand Conformation Polymorphism (SSCP) technique to assess sequence level variation within the Major Histocompatibility Complex (MHC) DRB1 gene in four South African buffalo populations. MHC gene products are involved in the immune response, and so variation within these genes provides information on the immunological fitness of the population under study. The aims of this study were: (i) to develop the SSCP technique; (ii) to investigate the level of genetic variation at the peptide binding region (PBR) of the DRB1 gene in four South African buffalo populations. (iii) This data was then compared to data generated previously in a study on the same populations using microsatellite DNA, (iv) the statistical comparisons were used to assess the appropriateness of SSCP data for population genetic analysis. Levels of heterozygosity, allelic diversity and population differentiation were quantified using MHC DRB1 gene. The amplified region (Exon 2 of the DRB1 gene) showed high levels of variability, with 77 alleles found in the 84 individuals examined using SSCP analyses

Traduire dans l’univers de la mode ou comment mettre son premier pied, délicatement chaussé, dans la porte

La vie d’une traductrice (ou d’un traducteur !) dans le domaine de la mode, quoi de plus sexy, me direz-vous. Et, soyons honnêtes, elle est sympa cette vie. La chance de donner libre cours à son esprit de créativité sur des thèmes variés et d’avoir carte blanche dans la rédaction d’articles percutants et de textes au goût du jour : le rêve du traducteur, n’est-ce pas ? Sans oublier que le secteur brasse des sommes importantes, et qui dit argent dit normalement exigence de qualité assortie d’u..

MicroRNAs in cardiac arrhythmia: DNA sequence variation of MiR-1 and MiR-133A in long QT syndrome.

Long QT syndrome (LQTS) is a genetic cardiac condition associated with prolonged ventricular repolarization, primarily a result of perturbations in cardiac ion channels, which predisposes individuals to life-threatening arrhythmias. Using DNA screening and sequencing methods, over 700 different LQTS-causing mutations have been identified in 13 genes worldwide. Despite this, the genetic cause of 30-50% of LQTS is presently unknown. MicroRNAs (miRNAs) are small (∼ 22 nucleotides) noncoding RNAs which post-transcriptionally regulate gene expression by binding complementary sequences within messenger RNAs (mRNAs). The human genome encodes over 1800 miRNAs, which target about 60% of human genes. Consequently, miRNAs are likely to regulate many complex processes in the body, indeed aberrant expression of various miRNA species has been implicated in numerous disease states, including cardiovascular diseases. MiR-1 and MiR-133A are the most abundant miRNAs in the heart and have both been reported to regulate cardiac ion channels. We hypothesized that, as a consequence of their role in regulating cardiac ion channels, genetic variation in the genes which encode MiR-1 and MiR-133A might explain some cases of LQTS. Four miRNA genes (miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2), which encode MiR-1 and MiR-133A, were sequenced in 125 LQTS probands. No genetic variants were identified in miR-1-1 or miR-133a-1; but in miR-1-2 we identified a single substitution (n.100A> G) and in miR-133a-2 we identified two substitutions (n.-19G> A and n.98C> T). None of the variants affect the mature miRNA products. Our findings indicate that sequence variants of miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2 are not a cause of LQTS in this cohort

Long QT syndrome — a cause of sudden death.

Sindrom dugog QT intervala (LQTS) je primarni aritmijski poremećaj koji može dovesti do pojave malignih ventrikularnih aritmija tipa torsades de pointe (TdP) i iznenadne srčane smrti. Obilježja u elektrokardiogramu (EKG) uključuju produljenje korigiranog QT intervala i abnormalnosti T-vala. Do danas identificirana genetska osnova za LQTS uključuje trinaest podložnih gena za LQTS: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, SNTA1, i KCNJ5. Najčešći genotip su mutacije KCNQ1 te gotovo polovica pacijenata ima tu vrstu mutacije. Navedeni geni kodiraju ionske kanale i regulatorne proteine koji su uključeni u modulaciju struja srčanog akcijskog potencijala. Stečeni oblici LQTS-a mogu također biti uzrokovani genetskim mutacijama, u tim slučajevima nositelji mutacija razvijaju aritmije isključivo u određenim uvjetima (npr. uporaba određenih lijekova). Trenutna terapija uključuje primjenu beta-blokatora, ugradnju implantabilnog kardioverter defibrilatora (ICD) te simpatičku denervaciju srca. LQTS mutacije povezane su s iznenadnom srčanom smrti kod mladih i veoma mladih; a post-mortem genetska testiranja LQTS gena mogu biti korisna kod procjene uzroka iznenadne neobjašnjive smrti (sudden unexplained death). Kaskadni probir koristan je za identificiranje asimptomatskih članova obitelji koji mogu biti pod povećanim rizikom od iznenadne smrti. U ovom preglednom članku prikazali smo gene povezane s LQTS-om zajedno s opisom povezanih patofizioloških mehanizama.Long QT syndrome (LQTS) is a primary arrhythmic disorder that may lead to the precipitation of torsades de pointe (TdP) and sudden death. Electrocardiogram (ECG) features include prolongation of the corrected QT interval and T-wave abnormalities. The genetic basis of LQTS identified to date includes thirteen susceptibility genes for LQTS: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, SNTA1, and KCNJ5. Mutations in KCNQ1 are by far the most frequent genotype with nearly half of the patients carrying KCNQ1 mutations. These genes code for ion channels and regulatory proteins that are involved in the modulation of the currents of the cardiac action potential (AP). Acquired forms of LQTS may also have underlying genetic mutations, in these cases mutation carriers develop arrhythmias only under certain conditions (e.g. use of certain medications). Current therapies include use of beta-blockers, implantable cardioverter defibrillators (ICD) and left cardiac sympathetic denervation. LQTS mutations have been associated with sudden death in the young and very young; and postmortem genetic testing in LQTS genes can be useful when assessing the cause of a sudden unexplained death. Cascade screening is also useful to identify asymptomatic family members that may be at risk of sudden death. Here we have reviewed the genes associated with LQTS along with the description of the related pathophysiological mechanisms

Fc Gamma Receptor IIIB (FcɣRIIIB) Polymorphisms Are Associated with Clinical Malaria in Ghanaian Children

The original publication is available at http://www.plosone.orgPlasmodium falciparum malaria kills nearly a million people annually. Over 90% of these deaths occur in children under five years of age in sub-Saharan Africa. A neutrophil mediated mechanism, the antibody dependent respiratory burst (ADRB), was recently shown to correlate with protection from clinical malaria. Human neutrophils constitutively express Fc gamma receptor-FcɣRIIA and FcɣRIIIB by which they interact with immunoglobulin (Ig) G (IgG)-subclass antibodies. Polymorphisms in exon 4 of FCGR2A and exon 3 of FCGR3B genes encoding FcɣRIIA and FcɣRIIIB respectively have been described to alter the affinities of both receptors for IgG. Here, associations between specific polymorphisms, encoding FcɣRIIA p.H166R and FcɣRIIIB-NA1/NA2/SH variants with clinical malaria were investigated in a longitudinal malaria cohort study. FcɣRIIA-p.166H/R was genotyped by gene specific polymerase chain reaction followed by allele specific restriction enzyme digestion. FCGR3B-exon 3 was sequenced in 585 children, aged 1 to 12 years living in a malaria endemic region of Ghana. Multivariate logistic regression analysis found no association between FcɣRIIA-166H/R polymorphism and clinical malaria. The A-allele of FCGR3B-c.233C>A (rs5030738) was significantly associated with protection from clinical malaria under two out of three genetic models (additive: p = 0.0061; recessive: p = 0.097; dominant: p = 0.0076) of inheritance. The FcɣRIIIB-SH allotype (CTGAAA) containing the 233A-allele (in bold) was associated with protection from malaria (p = 0.049). The FcɣRIIIB-NA2*03 allotype (CTGCGA), a variant of the classical FcɣRIIIB-NA2 (CTGCAA) was associated with susceptibility to clinical malaria (p = 0.0092). The present study is the first to report an association between a variant of FcɣRIIIB-NA2 and susceptibility to clinical malaria and provides justification for further functional characterization of variants of the classical FcɣRIIIB allotypes. This would be crucial to the improvement of neutrophil mediated functional assays such as the ADRB assay aimed at assessing the functionality of antibodies induced by candidate malaria vaccines.European and Developing Countries Clinical Trials Partnership (www.edctp.org) (TA.2007.40200.012)European Vaccine Initiative (www.euvaccine.eu) (08-2007)African Malaria Network Trust (www.amanet-trust.org) (008/2008AIA)Publisher's versio

The perinatal health challenges of emerging and re-emerging infectious diseases: A narrative review

The world has seen numerous infectious disease outbreaks in the past decade. In many cases these outbreaks have had considerable perinatal health consequences including increased risk of preterm delivery (e.g., influenza, measles, and COVID-19), and the delivery of low birth weight or small for gestational age babies (e.g., influenza, COVID-19). Furthermore, severe perinatal outcomes including perinatal and infant death are a known consequence of multiple infectious diseases (e.g., Ebola virus disease, Zika virus disease, pertussis, and measles). In addition to vaccination during pregnancy (where possible), pregnant women, are provided some level of protection from the adverse effects of infection through community-level application of evidence-based transmission-control methods. This review demonstrates that it takes almost 2 years for the perinatal impacts of an infectious disease outbreak to be reported. However, many infectious disease outbreaks between 2010 and 2020 have no associated pregnancy data reported in the scientific literature, or pregnancy data is reported in the form of case-studies only. This lack of systematic data collection and reporting has a negative impact on our understanding of these diseases and the implications they may have for pregnant women and their unborn infants. Monitoring perinatal health is an essential aspect of national and global healthcare strategies as perinatal life has a critical impact on early life mortality as well as possible effects on later life health. The unpredictable nature of emerging infections and the potential for adverse perinatal outcomes necessitate that we thoroughly assess pregnancy and perinatal health implications of disease outbreaks and their public health interventions in tandem with outbreak response efforts. Disease surveillance programs should incorporate perinatal health monitoring and health systems around the world should endeavor to continuously collect perinatal health data in order to quickly update pregnancy care protocols as needed