Examining Geographic and Social Barriers to HIV Treatment Adherence in Kampala, Uganda

With the rapid expansion of HIV treatment programs across sub-Saharan Africa, substantial progress has been made towards universal treatment accessibility in Uganda; however, new healthcare challenges have been emerging, such as the development of drug-resistant HIV, which threaten to undermine achievements made thus far. In order for HIV treatment to be effective, people living with HIV (PLWH) must be highly adherent without missing a single dose, which can be challenging for those also facing difficulties such as financial insecurity. In the context of Kampala, Uganda’s urban capital, it has been suggested that healthcare accessibility is made difficult by several physical and social barriers. However, knowledge of the extent to which such barriers, especially geographical barriers might influence HIV treatment success is lacking. This is a mixed methods study which examines geographical barriers to adherence within the socio-economic context of Kampala. Using data from a survey administered to individuals on treatment at the Joint Clinical Research Center (JCRC) in Kampala (n=149), the study employs logistic regression to examine the association between geographical barriers and treatment outcomes. Semi-structured interviews (n=30) were also conducted to deepen our understanding of lived experiences with HIV treatment. Results were unexpected, suggesting that participants living more than two hours away from the treatment facility were actually less likely to miss their daily dose of medication (OR = 0.33, p \u3c 0.05), compared to those living in proximity to the treatment center. Findings from the interviews helped to explain these paradoxical findings, as it was reported that PLWH prefer clinics further from their home to avoid being recognized. The effect of HIV stigma was reported to further impact adherence at home and in workspaces, as PLWH felt pressured to take medication in secrecy. The results of our regression suggested that high-income employment (OR = 3.82, p \u3c 0.05) and partnered relationship status (OR = 4.28, p \u3c 0.05) were predicted to increase the probability of missing doses. Challenges to HIV treatment adherence such as stigmatization and transportation costs must therefore be considered in conjunction with one another, as determinants of health are overlapping and inextricable

Removal of Carcinogens from Drinking Water: A Cost-Benefit Analysis

This study is an analysis is of the costs and benefits of implementing the amendment to the interim primary drinking water regulations proposed by the Environmental Protection Agency in January, 1978 (EPA, 1978). Specifically, the study will consider the benefits and costs involved for those water supply systems which would be required to remove organic contaminants by installing granular activated carbon (GAC) as a post-filtration adsorbent

A case for developmental genetics to increase yield of oilseed rape

B. napus is a widely-grown crop and its uses are widespread. The seeds used mostly for oil production are contained within cylindrical fruits called pods. These strongly resemble the well-studied fruiting structures of the model plant Arabidopsis, in which patterning genes, hormones and cellular growth dynamics are well characterized. The ovary of the fruit is partitioned into two valves separated by the replum and the valve margin, which is required for fruit opening and seed dispersal. On the inside are the ovules, which post-fertilization develop into seeds. Of benefit for B. napus crop improvement would be the production of larger seeds as well as more seeds per pod. The aim of this work was to improve yield of oilseed rape by targeting fruit growth. To this end, the growth of the B. napus pod was described in detail. This formed the basis of the study as it is imperative to understand the entire fruiting structure before attempting any improvements. Fruit length correlated consistently with seed number, making it a valuable trait to study. A correlation between stomata density and fruit length was investigated using several members of the Brassicaceae. Next, to identify new genes contributing to pod growth, a genome-wide association study (GWAS) was carried out on a diverse B. napus population. This yielded DPb, a cell-cycle gene. Further analysis lead to the identification of TSN1, a gene with similar expression levels as the former. Functions of the DP/E2F family with TSN1 and TSN2 were then studied in detail in the Arabidopsis fruit. Results uncovered an overlapping function in seed development and fruit growth of these previously not associated genes. Overall, this work thus demonstrates how findings in a crop species can be translated to the model to increase the fundamental knowledge of biological processes

Removal of Carcinogens from Drinking Water: A Cost-Benefit Analysis

This study is an analysis is of the costs and benefits of implementing the amendment to the interim primary drinking water regulations proposed by the Environmental Protection Agency in January, 1978 (EPA, 1978). Specifically, the study will consider the benefits and costs involved for those water supply systems which would be required to remove organic contaminants by installing granular activated carbon (GAC) as a post-filtration adsorbent

The Aquatic Toxicity of Organic Compounds to Embryo-Larval Stages of Fish and Amphibians

Aquatic toxicity tests were conducted on 11 organic compounds considered hazardous to water resources. The toxicity of each compound was evaluated using embryo-larval stages of two to eight fish and amphibian species. Exposure was initiated at fertilization and maintained through 4 days posthatching. The animal test species exhibited varying degrees of sensitivity to the selected toxicants. Combined frequencies for mortality and teratogenesis at 4 days posthatching gave LC50 ranges of 3.66 to 8.25 mg/L for benzene, 1.16 to 22.42 mg/L for carbon tetrachloride, 0.11 to 1.20 mg/L for chlorobenzene, 2.03 to \u3e 68 mg/L for chloroform, 3.01 to 5.56 mg/L for 1,2-dichlorobenzene, 2.54 to .34 mg/L for 1,2-dichloroethane, 13.16 to \u3e 48 mg/L for methylene chloride, 0.002 to 0.64 mg/L for nitrobenzene, 0.04 to .32 mg/L for phenol, 0.02 to 0.85 mg/L for toluene, and 3.53 to 3.77 mg/L for m-xylene. The species which exhibited the greatest susceptibility to organic compounds were the rainbow trout, Rana pipiens, and Rana temporaria. The more sensitive amphibian species generally were those which normaly are restricted to aquatic or moist terrestrial habitats, whereas the more tolerant amphibians included those semi-aquatic and terrestrial species which appear to be more broadly adapted ecologically. Of the 11 test compounds, nitrobenzene, toluene, chlorobenzene, and phenol were the most toxic. The least toxic organics included dichloroethane and methylene chloride. For three chlorinated alkanes, including methylene chloride (CH2Cl2), chloroform (CHCl3), and carbon tetrachloride (CCl4), toxicity was found to 1ncrease with the degree of chlorination. Concerning several aromatic hydrocarbons, benzene always was found to be less toxic than its monosubstituted analogs. Toxicity of the 11 compounds was further evaluated by calculating toxicant concentrations which produced embryo-larval mortality and/or teratogenesis at frequencies of 10% (LC10) and 1% (LC1). The LC values, used to estimate toxicity thresholds, ranged from \u3c 0.l for nitrobenzene to 69.9 μg/L for methylene chloride. A limited number of toxicity tests were performed to determine whether embryo-larval bioassays are suitable to assess effects of transitory chemical exposures, such as those resulting from intermittent discharges or accidental spills of chemicals into water resources. Results indicated that Rana pipiens embryos were sufficiently sensitive to quantify effects produced by short-term exposures to chloroform. Animals tested during the earliest embryonic stage appeared to be less tolerant than organisms exposed later in development

Molecular analysis of the distribution and phylogeny of the soxB gene among sulfur-oxidizing bacteria - evolution of the Sox sulfur-oxidizing enzyme system

The soxB gene encodes the SoxB component of the periplasmic thiosulfate-oxidizing Sox enzyme complex, which has been proposed to be widespread among the various phylogenetic groups of sulfur-oxidizing bacteria (SOB) that convert thiosulfate to sulfate with and without the formation of sulfur globules as intermediate. Indeed, the comprehensive genetic and genomic analyses presented in the present study identified the soxB gene in 121 phylogenetically and physiologically divergent SOB, including several species for which thiosulfate utilization has not been reported yet. In first support of the previously postulated general involvement of components of the Sox enzyme complex in the thiosulfate oxidation process of sulfur-storing SOB, the soxB gene was detected in all investigated photo- and chemotrophic species that form sulfur globules during thiosulfate oxidation (Chromatiaceae, Chlorobiaceae, Ectothiorhodospiraceae, Thiothrix, Beggiatoa, Thiobacillus, invertebrate symbionts and free-living relatives). The SoxB phylogeny reflected the major 16S rRNA gene-based phylogenetic lineages of the investigated SOB, although topological discrepancies indicated several events of lateral soxB gene transfer among the SOB, e.g. its independent acquisition by the anaerobic anoxygenic phototrophic lineages from different chemotrophic donor lineages. A putative scenario for the proteobacterial origin and evolution of the Sox enzyme system in SOB is presented considering the phylogenetic, genomic (sox gene cluster composition) and geochemical data

Export of functional Streptomyces coelicolor alditol oxidase to the periplasm or cell surface of Escherichia coli and its application in whole-cell biocatalysis

Streptomyces coelicolor A3(2) alditol oxidase (AldO) is a soluble monomeric flavoprotein in which the flavin cofactor is covalently linked to the polypeptide chain. AldO displays high reactivity towards different polyols such as xylitol and sorbitol. These characteristics make AldO industrially relevant, but full biotechnological exploitation of this enzyme is at present restricted by laborious and costly purification steps. To eliminate the need for enzyme purification, this study describes a whole-cell AldO biocatalyst system. To this end, we have directed AldO to the periplasm or cell surface of Escherichia coli. For periplasmic export, AldO was fused to endogenous E. coli signal sequences known to direct their passenger proteins into the SecB, signal recognition particle (SRP), or Twin-arginine translocation (Tat) pathway. In addition, AldO was fused to an ice nucleation protein (INP)-based anchoring motif for surface display. The results show that Tat-exported AldO and INP-surface-displayed AldO are active. The Tat-based system was successfully employed in converting xylitol by whole cells, whereas the use of the INP-based system was most likely restricted by lipopolysaccharide LPS in wild-type cells. It is anticipated that these whole-cell systems will be a valuable tool for further biological and industrial exploitation of AldO and other cofactor-containing enzymes.

Alternative splicing of Tcf7l2 transcripts generates protein variants with differential promoter-binding and transcriptional activation properties at Wnt/β-catenin targets

Alternative splicing can produce multiple protein products with variable domain composition from a single gene. The mouse Tcf7l2 gene is subject to alternative splicing. It encodes TCF4, a member of the T-cell factor (TCF) family of DNA-binding proteins and a nuclear interaction partner of β-catenin which performs essential functions in Wnt growth factor signalling. Multiple TCF4 isoforms, potentially exhibiting cell-type-specific distribution and differing in gene regulatory properties, could strongly influence tissue-specific Wnt responses. Therefore, we have examined mouse Tcf7l2 splice variants in neonatal tissues, embryonic stem cells and neural progenitors. By polymerase chain reaction amplification, cloning and sequencing, we identify a large number of alternatively spliced transcripts and report a highly flexible combinatorial repertoire of alternative exons. Many, but not all of the variants exhibit a broad tissue distribution. Moreover, two functionally equivalent versions of the C-clamp, thought to represent an auxiliary DNA-binding domain, were identified. Depending upon promoter context and precise domain composition, TCF4 isoforms exhibit strikingly different transactivation potentials at natural Wnt/β-catenin target promoters. However, differences in C-clamp-mediated DNA binding can only partially explain functional differences among TCF4 variants. Still, the cell-type-specific complement of TCF4 isoforms is likely to be a major determinant for the context-dependent transcriptional output of Wnt/β-catenin signalling