Trapping redox partnerships in oxidant-sensitive proteins with a small, thiol-reactive cross-linker

A broad range of redox-regulated proteins undergo reversible disulfide bond formation on oxidation-prone cysteine residues. Heightened reactivity of the thiol groups in these cysteines also increases susceptibility to modification by organic electrophiles, a property that can be exploited in the study of redox networks. Here, we explored whether divinyl sulfone (DVSF), a thiol-reactive bifunctional electrophile, cross-links oxidant-sensitive proteins to their putative redox partners in cells. To test this idea, previously identified oxidant targets involved in oxidant defense (namely, peroxiredoxins, methionine sulfoxide reductases, sulfiredoxin, and glutathione peroxidases), metabolism, and proteostasis were monitored for cross-link formation following treatment of Saccharomyces cerevisiae with DVSF. Several proteins screened, including multiple oxidant defense proteins, underwent intermolecular and/or intramolecular cross-linking in response to DVSF. Specific redox-active cysteines within a subset of DVSF targets were found to influence cross-linking; in addition, DVSF-mediated cross-linking of its targets was impaired in cells first exposed to oxidants. Since cross-linking appeared to involve redox-active cysteines in these proteins, we examined whether potential redox partners became cross-linked to them upon DVSF treatment. Specifically, we found that several substrates of thioredoxins were cross-linked to the cytosolic thioredoxin Trx2 in cells treated with DVSF. However, other DVSF targets, like the peroxiredoxin Ahp1, principally formed intra-protein cross-links upon DVSF treatment. Moreover, additional protein targets, including several known to undergo S-glutathionylation, were conjugated via DVSF to glutathione. Our results indicate that DVSF is of potential use as a chemical tool for irreversibly trapping and discovering thiol-based redox partnerships within cells

Social factors influencing child health in Ghana

Objectives Social factors have profound effects on health. Children are especially vulnerable to social influences, particularly in their early years. Adverse social exposures in childhood can lead to chronic disorders later in life. Here, we sought to identify and evaluate the impact of social factors on child health in Ghana. As Ghana is unlikely to achieve the Millennium Development Goals’ target of reducing child mortality by two-thirds between 1990 and 2015, we deemed it necessary to identify social determinants that might have contributed to the non-realisation of this goal. Methods ScienceDirect, PubMed, MEDLINE via EBSCO and Google Scholar were searched for published articles reporting on the influence of social factors on child health in Ghana. After screening the 98 articles identified, 34 of them that met our inclusion criteria were selected for qualitative review. Results Major social factors influencing child health in the country include maternal education, rural-urban disparities (place of residence), family income (wealth/poverty) and high dependency (multiparousity). These factors are associated with child mortality, nutritional status of children, completion of immunisation programmes, health-seeking behaviour and hygiene practices. Conclusions Several social factors influence child health outcomes in Ghana. Developing more effective responses to these social determinants would require sustainable efforts from all stakeholders including the Government, healthcare providers and families. We recommend the development of interventions that would support families through direct social support initiatives aimed at alleviating poverty and inequality, and indirect approaches targeted at eliminating the dependence of poor health outcomes on social factors. Importantly, the expansion of quality free education interventions to improve would-be-mother’s health knowledge is emphasised

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance

SOME ASPECTS OF THE BIOLOGY AND CONTROL OF CALLOSOBRUCHUS MACULATUS (F.) ON SOME STORED SOYABEAN GLYCINE MAX (L.) MERR VARIETIES

Pulses include all the legume crops that are grown for dried seeds such as soya beans. Due to their comparative high protein contents, ease of handling, transportation and storage, pulses are of great importance in their role in the diet of Africans. However, pulses are subject to attack by many groups of biodeteriorative agents, of which bruchids are the most important. In Ghana, soya beans have recently become a very important pulse. Even though soya bean is considered to be relatively resistant to attack by bruchids, not much is known about its susceptibility to the cowpea weevil, Callosobruchus maculatus (F.), a major pest of pulses in Africa and what available non-chemical control measures to use against the pest. In the present study, some aspects of the biology: oviposition, development, survival, fecundity and damage caused by C. maculatus on six stored soya bean, Glycine max (L) Merr. varieties, and control of the weevil, using plant materials such as neem, Azadirachta indica A. Juss (Meliaceae) and sweet orange, Citrus sinensis (Linn.) Osbeck (Rutaceae) powders were studied under ambient laboratory conditions (temperature range 28 – 300C and 59 – 75 % relative humidity). Developmental period of C. maculatus was found to differ with the different varieties suggesting differences in the suitability of the varieties as food source. Based on the length of the developmental period of C. maculatus, damage caused, number of eggs laid and number of emerged adults, variety TGX 1473-2D was the most resistant. TGX 1025-8E appeared to be equally resistant but for the shorter developmental period of C. maculatus on it. Of the remaining varieties: TGX 923 – 2E, TGX 1150-6D, TGX 1118 – 1D and LM, the local variety LM was the most susceptible. TGX 923-2E was the most preferred for oviposition. The plant materials, Azadirachta indica seed powder and Citrus sinensis peel powder were found to be effective as seed protectants over a three month period. A. indica seed powder was found to have ovicidal and larvicidal properties. It is effective for use to suppress Callosobruchus maculates for short periods. Key Words: Callosobruchus maculatus, developmental period, soya bean, Azadirachta indica, Citrus sinensis ASPECTS DE LA BIOLOGIE ET DU CONTROLE DU CALLOSOBRUCHUS MACULATUS (F.) SUR LA CONSERVATION DES GRAINES DE SOJA DES VARIETES GLYCINE MAX (L.) MERR NOTE DE SYNTHESE Les légumes à cosse comprennent toutes les légumineuses cultivées pour leurs graines sèches, telles que les graines de soja. En raison de leur haute teneur en protéines, de leur résistance à la manutention, au transport et à la conservation, les légumes à cosse sont d\'une grande importance. En outre, ils jouent un rôle essentiel dans le régime alimentaire des africains. Toutefois, ils sont sujets à bon nombre de groupes d\'agents de détérioration biologique dont les principaux sont les bruches. Au Ghana, les graines de soja connaissent depuis peu une importance croissante. Toutefois, même si la graine de soja résiste relativement à l\'attaque des bruches, très peu est connu sur sa vulnérabilité au charançon du niélé, Callosobruchus maculatus (F.), principal ravageur des légumes à cosse en Afrique. De même, on dispose de très peu d\'informations sur les mesures de contrôle non-chimique disponibles pour lutter contre cet insecte. L\'étude préliminaire a examiné certains aspects de la biologie dans des conditions ambiantes de laboratoire (température variant entre 28 – 300C et humidité relative de 59 – 75%). Elle a porté entre autres sur la ponte, le développement, la survie, la fécondité et les dégâts causés par le C. maculatus sur six graines de soya conservées, des variétés Glycine max (L) Merr. Elle a également analysé la lutte contre le charançon, en utilisant des substances végétales telles que le neem, Azadirachta indica A. Juss (Meliaceae) et l\'orange sucrée, Citrus sinensis (Linn.) et les poudres Osbeck (Rutaceae). Il a été constaté que la période de croissance du C. maculatus était différente selon les diverses variétés de graines de soja, ce qui laisse supposer des différences dans la convenance des variétés en tant que source alimentaire. Compte tenu de la durée de croissance du C. maculatus, des dégâts causés, du nombre d\'œufs pondus et du nombre de nouveaux adultes en croissance, la variété de graine de soja TGX 1473-2D est la plus résistante. Le type TGX 1025-8E semble également être résistant mais pendant la courte période de croissance du C. maculatus sur ce type de graine de soja . Parmi les variétés restantes, notamment TGX 923 – 2E, TGX 1150-6D, TGX 1118 – 1D et LM, la variété locale LM est la plus prédisposée à l\'attaque du C. maculatus. Ce charançon préfère le type TGX 923-2E pour la ponte. Il a été constaté que les matières végétales, notamment la poudre pour le traitement des semences Azadirachta indica ainsi que la poudre pour la protection de la pelure Citrus sinensis sont efficaces dans la protection des graines sur une période de trois mois. Ainsi, la préférence est accordée à la poudre pour le traitement des semences A. indica, du fait qu\'elle contient des propriétés qui tuent les œufs et les larves. Mots-clés: Callosobruchus maculatus, période de croissance, graine de soja, Azadirachta indica, Citrus sinensis AJFAND Vol.4(2) 200

INSECT AND MYCOFLORA INTERACTIONS IN MAIZE FLOUR

Maize flour treated with or without Tribolium castaneum was investigated for the presence of some fungi. Fusarium moniliforme had the highest occurrence of 36.7%, 28.1% and 33.3% while Aspergillus flavus/parasiticus had a frequency of 3.2%, 3.1% and 3% on primary isolation media of czapek dox agar (CDA), potato dextrose agar (PDA) and sabouraud dextrose agar (SDA) respectively, in maize flour without T. castaneum. The frequency of F. moniliforme reduced in maize flour with T. castaneum to 11.1%, 12.1% and 18.8% on CDA, PDA and SDA while A. flavus/parasiticus increased in occurrence after introducing T. castaneum to 22.2%, 18.2% and 12.3% on the three respective media. Fourteen and 7 fungal genera were isolated from maize flour with and without F. castaneum respectively. Two fungal species isolated from maize flour without T. castaneum were Cladosporium cladosporioides and C. lunata. Ten species isolated from maize flour with T. castaneum were A. pullulans, Auxarthron spp., C. herbarum, Eurotium sp., Phoma glomerata, Neosauorya spp., Scopulariopsis brevicaulis, Rhizopus oryzae, R. stolonifer and Wallemia sebi. These results suggest an association and a synergistic interaction between important spoilage and mycotoxigenic fungi with T. castaneum such as A. flavus/parasiticus and some mildly parasitic fungal colonies but an antagonistic interaction with F. moniliforme. Key words: Tribolium castaneum, storage fungi, synergistic/antagonistic interactions, mycotoxins (Af. J. Food and Nutritional Sciences: 2001 1(1): 3-8

Visual impairment and amblyopia in Malaysian pre-school children - The SEGPAEDS study

Daniel Reidpath - ORCID: 0000-0002-8796-0420 https://orcid.org/0000-0002-8796-0420Item is not available in this repository.Introduction: Little is known regarding the extent of visual impairment amongst pre-school children in Malaysia. Objective: To determine the prevalence of visual impairment and amblyopia in Malaysian preschool children. Methodology: A cross-sectional, population-based study was conducted on children aged four to six years from 51 participating kindergartens in the district of Segamat, Johor, Malaysia from 20 March 2016 to 6 April 2016. All subjects had initial eye screening consisting of LogMar visual acuity, orthoptics examination and Spot vision screener assessment. Subjects who failed the initial eye screening were invited for a formal eye assessment consisting of cycloplegic refraction and a comprehensive ocular examination. Definitions of visual impairment and amblyopia were based on the Multi-Ethnic Pediatric Eye Disease Study criteria. Results: A total of 1287 children were recruited. Mean subject age was 5.03 (SD:0.77) and males represented 52.3% of subjects. Subjects by ethnicity were Malay (54.8%), Chinese (27.7%), Indian (15.6%) and Orang Asli (1.9%). Formal eye assessment was required for 221 subjects and 88.8% required ophthalmic intervention. Refractive error, representing 95.4% of diagnosed ocular disorders, comprised of astigmatism (84%), myopia (9%) and hypermetropia (6.9%). With-the-rule astigmatism was present in 93.4% of the subjects with astigmatism. Visual impairment was present in 12.5% of our subjects, with 61% having bilateral visual impairment. Of the subjects with visual impairment, 59.1% had moderate visual impairment. The prevalence of amblyopia was 7.53%, and 66% of the amblyopic subjects had bilateral amblyopia. Conclusion: Our study highlights an urgent need for initiation of preschool vision screening in Malaysia.https://www.e-mjm.org/2018/v73n1/visual-impairment-and-amblyopia.pdf73pubpub