72 research outputs found

    Community Perception of Cultural Identity of Heritage Sites for Determining Local Participation in their Management and Conservation: The Case of Thimlich Ohinga and Seme-Kaila in Kenya

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    The study investigated the significance of cultural identity of prehistoric settlements in establishing community participation in their conservation and management for ecotourism promotion. This was accomplished using both qualitative and quantitative methods of data collection and analyzed using descriptive and inferential statistics, as well as, content analysis. The research employed value theory to interpret the data and provide clarity of the research findings. The study concluded that there is a significant relationship between community perception of cultural identity of the sites and community participation in their conservation and management for ecotourism promotion. High level of community perception of cultural identity of Thimlich Ohinga indicates high community participation in the conservation and management of the site. Low level of community perception of cultural identity of Seme-Kaila shows low community participation in the conservation and management of the site. KEY WORDS: Cultural identity, community perception, community participation, management, conservation, heritage site

    Introducing a multi-site program for early diagnosis of HIV infection among HIV-exposed infants in Tanzania

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    <p>Abstract</p> <p>Background</p> <p>In Tanzania, less than a third of HIV infected children estimated to be in need of antiretroviral therapy (ART) are receiving it. In this setting where other infections and malnutrition mimic signs and symptoms of AIDS, early diagnosis of HIV among HIV-exposed infants without specialized virologic testing can be a complex process. We aimed to introduce an Early Infant Diagnosis (EID) pilot program using HIV DNA Polymerase Chain Reaction (PCR) testing with the intent of making EID nationally available based on lessons learned in the first 6 months of implementation.</p> <p>Methods</p> <p>In September 2006, a molecular biology laboratory at Bugando Medical Center was established in order to perform HIV DNA PCR testing using Dried Blood Spots (DBS). Ninety- six health workers from 4 health facilities were trained in the identification and care of HIV-exposed infants, HIV testing algorithms and collection of DBS samples. Paper-based tracking systems for monitoring the program that fed into a simple electronic database were introduced at the sites and in the laboratory. Time from birth to first HIV DNA PCR testing and to receipt of test results were assessed using Kaplan-Meier curves.</p> <p>Results</p> <p>From October 2006 to March 2007, 510 HIV-exposed infants were identified from the 4 health facilities. Of these, 441(87%) infants had an HIV DNA PCR test at a median age of 4 months (IQR 1 to 8 months) and 75(17%) were PCR positive. Parents/guardians for a total of 242(55%) HIV-exposed infants returned to receive PCR test results, including 51/75 (68%) of those PCR positive, 187/361 (52%) of the PCR negative, and 4/5 (80%) of those with indeterminate PCR results. The median time between blood draw for PCR testing and receipt of test results by the parent or guardian was 5 weeks (range <1 week to 14 weeks) among children who tested PCR positive and 10 weeks (range <1 week to 21 weeks) for those that tested PCR negative.</p> <p>Conclusions</p> <p>The EID pilot program successfully introduced systems for identification of HIV-exposed infants. There was a high response as hundreds of HIV-exposed infants were registered and tested in a 6 month period. Challenges included the large proportion of parents not returning for PCR test results. Experience from the pilot phase has informed the national roll-out of the EID program currently underway in Tanzania.</p

    Impaired Nuclear Nrf2 Translocation Undermines the Oxidative Stress Response in Friedreich Ataxia

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    BACKGROUND: Friedreich ataxia originates from a decrease in mitochondrial frataxin, which causes the death of a subset of neurons. The biochemical hallmarks of the disease include low activity of the iron sulfur cluster-containing proteins (ISP) and impairment of antioxidant defense mechanisms that may play a major role in disease progression. METHODOLOGY/PRINCIPAL FINDINGS: We thus investigated signaling pathways involved in antioxidant defense mechanisms. We showed that cultured fibroblasts from patients with Friedreich ataxia exhibited hypersensitivity to oxidative insults because of an impairment in the Nrf2 signaling pathway, which led to faulty induction of antioxidant enzymes. This impairment originated from previously reported actin remodeling by hydrogen peroxide. CONCLUSIONS/SIGNIFICANCE: Thus, the defective machinery for ISP synthesis by causing mitochondrial iron dysmetabolism increases hydrogen peroxide production that accounts for the increased susceptibility to oxidative stress

    In silico pathway reconstruction: Iron-sulfur cluster biogenesis in Saccharomyces cerevisiae

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    BACKGROUND: Current advances in genomics, proteomics and other areas of molecular biology make the identification and reconstruction of novel pathways an emerging area of great interest. One such class of pathways is involved in the biogenesis of Iron-Sulfur Clusters (ISC). RESULTS: Our goal is the development of a new approach based on the use and combination of mathematical, theoretical and computational methods to identify the topology of a target network. In this approach, mathematical models play a central role for the evaluation of the alternative network structures that arise from literature data-mining, phylogenetic profiling, structural methods, and human curation. As a test case, we reconstruct the topology of the reaction and regulatory network for the mitochondrial ISC biogenesis pathway in S. cerevisiae. Predictions regarding how proteins act in ISC biogenesis are validated by comparison with published experimental results. For example, the predicted role of Arh1 and Yah1 and some of the interactions we predict for Grx5 both matches experimental evidence. A putative role for frataxin in directly regulating mitochondrial iron import is discarded from our analysis, which agrees with also published experimental results. Additionally, we propose a number of experiments for testing other predictions and further improve the identification of the network structure. CONCLUSION: We propose and apply an iterative in silico procedure for predictive reconstruction of the network topology of metabolic pathways. The procedure combines structural bioinformatics tools and mathematical modeling techniques that allow the reconstruction of biochemical networks. Using the Iron Sulfur cluster biogenesis in S. cerevisiae as a test case we indicate how this procedure can be used to analyze and validate the network model against experimental results. Critical evaluation of the obtained results through this procedure allows devising new wet lab experiments to confirm its predictions or provide alternative explanations for further improving the models

    Exercise-induced recurrent myoglobinuria: Defective activity of inner carnitine palmitoyltransferase in muscle mitochondria of two patients

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    In carnitine palmitoyltransferase (CPT) deficiency, it is not known whether the outer (CPT-I) and the inner (CPT-II) mitochondrial activities are equally altered. By two different assays, we found that CPT activity in fresh intact mitochondria of two patients was normal or increased, indicating an active outer CPT. In controls and in one of the two patients, the isotope-exchange assay was also evaluated after disruption of mitochondria by sonication: in controls the activity almost doubled because of the contribution of inner CPT to the assay, but in the patients it did not increase, indicating absence of the CPT-II activity. After further disruption of mitochondria by freezing and all-glass homogenization, CPT activity in patients decreased to 36% and 10% of control. These data suggest that CPT deficiency was limited to the inner mitochondrial activity. The alteration could be explained by mutation of the membrane factor that determines in situ differences between CPT-I and II. \ua9 1987 American Academy of Neurology
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