Serologic assays used to detect antibodies to nonstructural proteins (NSPs) of foot-and-mouth disease virus (FMDV) are used for disease surveillance in endemic countries, and are essential to providing evidence for freedom of the disease with or without vaccination and to recover the free status of a country after an outbreak. In a 5-site inter-laboratory study, we compared the performance of 2 commercial NSP ELISA kits (ID Screen FMD NSP ELISA single day [short] and overnight protocols, ID.Vet; PrioCHECK FMDV NS antibody ELISA, Thermo Fisher Scientific).
View Article and Find Full Text PDFAim: To evaluate the association between loss-of-function (LOF) variants (A433T/rs28362263 and C679X/rs28362286) and biomarkers of cardiometabolic risk, specifically fasting glucose and low density lipoprotein cholesterol (LDL-C) concentrations.
Methods: Our study comprised 757 male and female black South African adolescents (mean age 18.0 ± 0.
Background: Ninety-seven independent single nucleotide polymorphisms (SNPs) are robustly associated with adult body mass index (BMI kg/m) in Caucasian populations. The relevance of such variants in African populations at different stages of the life course (such as childhood) is unclear. We tested whether a genetic risk score composed of the aforementioned SNPs was associated with BMI from infancy to early adulthood.
View Article and Find Full Text PDFObjective: The latest genome-wide association studies of obesity-related traits have identified several genetic loci contributing to body composition (BC). These findings have not been robustly replicated in African populations, therefore, this study aimed to assess whether European BC-associated gene loci played a similar role in a South African black population.
Methods: A replication and fine-mapping study was performed in participants from the Birth to Twenty cohort (N = 1,926) using the Metabochip.
The aim of this special issue is to understand better the many changes in adolescent psychopathology have taken place over the last decades. The factors associated with adjustment problems and psychopathology in adolescence today are not necessarily the same as the factors that predicted problems and psychopathology in the past. But the basic strategies for connecting negative experiences with adolescent psychopathology remain as important today as they were for understanding adolescent psychopathology decades ago.
View Article and Find Full Text PDFBackground: Cardiovascular diseases (CVDs) are the leading cause of non-communicable disease deaths globally, with hypertension being a major risk factor contributing to CVDs. Blood pressure is a heritable trait, with relatively few genetic studies having been performed in Africans. This study aimed to identify genetic variants associated with variance in systolic (SBP) and diastolic (DBP) blood pressure in black South Africans.
View Article and Find Full Text PDFThe H3ABioNet pan-African bioinformatics network, which is funded to support the Human Heredity and Health in Africa (H3Africa) program, has developed node-assessment exercises to gauge the ability of its participating research and service groups to analyze typical genome-wide datasets being generated by H3Africa research groups. We describe a framework for the assessment of computational genomics analysis skills, which includes standard operating procedures, training and test datasets, and a process for administering the exercise. We present the experiences of 3 research groups that have taken the exercise and the impact on their ability to manage complex projects.
View Article and Find Full Text PDFObjectives: HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection, and it is often painful. Tumor necrosis factor (TNF)-α is implicated in neuropathic pain, but associations between neuropathic pain and polymorphisms in the TNFA gene have not been identified. The "TNF block" is a region of high linkage disequilibrium within the central major histocompatability complex that contains several genes involved in the regulation of inflammation, including TNFA.
View Article and Find Full Text PDFWe are somewhat critical of the concept of emerging adulthood as a new developmental stage in modern industrial societies, and prefer the idea of systemic mechanisms and processes as the forces and factors that influence the transitions and transformations of human change across the life course. For this reason, we are pleased to see this volume is entirely dedicated to the life-phase of emerging adulthood in Mediterranean countries, suggesting that researchers are not convinced that the characteristics of emerging adulthood would be the same for young people from different cultures. While we are very positive towards this series of articles showing that emerging adulthood in Mediterranean countries has similarities, and, yet differences to other cultures, and appreciate the diverse findings of these research projects, we would want to suggest some new and more radical strategies for future developmental research.
View Article and Find Full Text PDFHIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection. The TNF block is a region within the central MHC that contains many immunoregulatory genes. Polymorphisms and haplotypes of the TNF block have been associated with increased risk of HIV-SN in Asians and whites.
View Article and Find Full Text PDFKCNS1 and GCH1 were investigated for their association with pain intensity in black Southern Africans with HIV-associated sensory neuropathy. Previously associated single nucleotide polymorphisms (SNPs) were supplemented with population-specific tagSNPs. No SNPs in KCNS1 were individually associated with pain intensity.
View Article and Find Full Text PDFThis qualitative interview study explored and examined the transitions surrounding emerging adulthood within the family from the parents' perspective. Interviews conducted with a purposive sample of parents (N = 59) revealed the perceived difficulties parents have in 'letting go' of their grown-up children, and in acknowledging their developing autonomy; and demonstrated a range of perceived parental strategies in response to young people's growing independence. The significance of these intertwined elements of perceived dependency, emotional tensions, and interactive behaviours for relationships in the family, and the implications for 'emerging adulthood', was discussed.
View Article and Find Full Text PDFA molecular guidance system useful in drug design is described in which nuclear receptors position ligands in intercalation sites in responsive genes. Evidence is based upon positions of agonists in receptors and the transcriptional activity of a designed estrogen that is 3 times more potent than the steroid hormone estradiol.
View Article and Find Full Text PDFThe brucellosis surveillance scheme in Great Britain includes the serological testing of approximately 1 million bovine samples per year. These are screened by iELISA, positives going forward for confirmatory testing by CFT and SAT. Samples positive by confirmatory testing prompt substantial field investigations and interventions, but the animals involved are usually uninfected.
View Article and Find Full Text PDFThe binding of small molecules to double stranded DNA including intercalation between base pairs has been a topic of research for over 40 years. For the most part, however, intercalation has been of marginal interest given the prevailing notion that binding of small molecules to protein receptors is largely responsible for governing biological function. This picture is now changing with the discovery of nuclear enzymes, e.
View Article and Find Full Text PDFSTAT (signal transducer and activator of transcription) proteins are critical regulators of cytokine-induced cell proliferation, differentiation and survival. STAT functional activity can be variably regulated by post-translational modifications, including phosphorylation, acetylation, methylation and sumoylation. Additionally, limited proteolytic digestion of full-length STAT proteins (STATalpha) generates C-terminally truncated forms (STATgamma) in different cell lineages, which have significantly reduced transcriptional activity due to the lack of the transactivation domain.
View Article and Find Full Text PDFWe have previously noted that the Physicians' Desk Reference (PDR) contains over 80 instances in which a drug elicited a positive genotoxic response in one or more in vitro assays, despite having no obvious structural features predictive of covalent drug/DNA interactive potential or known mechanistic basis. Furthermore, in most cases, these drugs were "missed" by computational genotoxicity-predicting models such as DEREK, MCASE and TOPKAT. We have previously reported the application of a V79 cell-based model and a 3D DNA docking model for predicting non-covalent chemical/DNA interactions.
View Article and Find Full Text PDFMycosis fungoides and its leukemic variant, Sezary syndrome, are the most common primary cutaneous T-cell lymphomas (CTCLs). In an ex vivo study, we investigated the percentage, phenotype, and suppressive function of CD4+CD25+ regulatory T cells (Tregs) from peripheral blood of CTCL patients. The percentage of Tregs did not differ significantly between patients and controls.
View Article and Find Full Text PDFThe energy of interaction of antiestrogenic ligands bound to DNA derived from molecular modeling was compared to the capacity of the ligands to directly inhibit the transcriptional activity of an estrogen responsive gene. 3-Phenylacetylamino-2,6-piperidinedione (A10) and related compounds were intercalated into a partially unwound DNA site in a canonical estrogen response element (ERE). The piperidinedione/ERE complexes were subjected to energy minimization and the strength of interaction of the ligands with the DNA was measured.
View Article and Find Full Text PDFDNA intercalation by small chemical molecules can result in frameshift mutagenesis and chromosomal breakage. With evidence mounting that broadly diverse structures are capable of intercalating between DNA base pairs, it becomes important to better define those structural features that enhance intercalation strength and those that confer genotoxicity particularly among those intercalators that do not have the classical planar tricyclic fused ring structure. A chemical substituent that is present on many pharmaceutical and other biologically active molecules is the N-dialkyl group.
View Article and Find Full Text PDFThe item-order hypothesis suggests that under certain conditions increased item processing can lead to deficits in order processing, and that this produces a dissociation in performance between item and order tasks. The generation effect is one such example. The word length effect is seen as another instance where this trade-off might be observed.
View Article and Find Full Text PDFNoncovalent DNA interactions, e.g., DNA intercalation and DNA groove-binding, have not been well studied relative to covalent interactions largely due to the inability of predicting and detecting such events in intact cells.
View Article and Find Full Text PDFInteraction of cytokines with their cognate receptors leads to the activation of latent transcription factors, the signal transducer and activator of transcription (STAT) proteins. Numerous studies have identified the critical roles played by STAT proteins in regulating cell proliferation, differentiation and survival. Consequently, the activity of STAT proteins is negatively regulated by a variety of different mechanisms, which include alternative splicing, covalent modifications, protein-protein interactions with negative regulatory proteins and proteolytic processing by proteases.
View Article and Find Full Text PDFA regimen combining fludarabine, cyclophosphamide and mitoxantrone (FCM) was used to treat 29 patients with relapsed or refractory chronic lymphocytic leukemia (CLL, N = 24) and low-grade non-Hodgkin's lymphoma (NHL, N = 5) based on evidence suggesting synergism between the 3 drugs. Patients were treated with mitoxantrone 5mg/m2 i.v.
View Article and Find Full Text PDFTo what extent noncovalent chemical-DNA interactions, in particular weak nonbonded DNA intercalation, contribute to genotoxic responses in mammalian cells has not been fully elucidated. Moreover, with the exception of predominantly flat, multiple-fused-ring structures, our ability to predict intercalation ability of novel compounds is nearly completely lacking. Computational programs such as DEREK and MCASE recognize primarily those molecules that can form irreversible covalent adducts with DNA since their learning sets, for the most part, have not been populated by compounds for which a relationship between noncovalent interaction and genotoxicity exists.
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