1,720,963 research outputs found
Characterization of the co-chaperones of Hsp70 and Hsp90 in Trypanosoma brucei and their potential partnerships
Get PDFAfrican Trypanosomiasis, which is caused by Trypanosoma brucei, is one of the crippling agents of social and economic development in Africa. T. brucei cycles between the cold-blooded insect vector, the tsetse fly (Glossina spp), and warm-blooded mammalian hosts. T. brucei, T. cruzi and L. major are mammal infecting kinetoplastid parasites that are collectively referred to as TriTryps. These parasites experience extreme environments as they move between their warm-blooded mammalian hosts and cold-blooded insect vectors which trigger extensive morphological transformations during the life-cycle of the parasite. Molecular chaperones have been implicated in parasite differentiation. TriTryps display significant expansions and diversity in the gene complements encoding molecular chaperones, especially J-proteins. Generally, J-proteins function as co-chaperones of Hsp70s, forming part of vital protein homeostasis processes. Hsp70s show a high degree of conservation, while J-proteins appear to be an extreme case of taxonomic radiation. Although several studies have focused on the molecular and cell biology of Hsp70s in some kinetoplastid parasites, knowledge is still lacking pertaining to J-proteins and their partnerships with Hsp70s. This thesis focused on the classification of kinetoplastid Jproteins into the four types by examining the domain organizations using T. brucei as a guide. The potential partnership of J-proteins and Hsp70s were postulated based on predicted subcellular localization. Kinetoplastid parasites, particularly T. brucei, have evolved an expanded and specialized J-protein machinery, likely to be a consequence of an evolutionary fitness/trait to adapt to diverse environment present in hosts and vectors. These analyses will yield insight into the process of parasite differentiation as well as provide new leads for chemotherapeutic treatments. The presence of the STI1 mediated Hsp90 hetero-complex formation has not been confirmed in T. brucei. To this end, in silico and biochemical techniques were used to characterize the role of TbSTI1, as an adaptor protein of Hsp70 and Hsp90. Through domain architecture analysis, sequence alignments, phylogenetic analysis and three-dimensional structure prediction, TbSTI1 was demonstrated to be the most conserved TPR containing co-chaperone of Hsp70 and Hsp83 in T. brucei and also shown to be highly similar to its eukaryotic homologues. Recombinant TbSTI1 was overproduced and purified in E.coli cells and subsequently shown to associate with TcHsp70 in a concentration dependent manner and associate weakly with TbHsp70.4. TbSTI1 and TbHsp83 were also demonstrated to be expressed and upregulated upon exposure to heat shock at the bloodstream stage of parasite development. In conclusion, this study is the first to report the interaction of TbSTI1 with a chaperone. Interactions between TbSTI1 and Hsp70s were demonstrated and therefore, the formation of the hetero-complex is predicted based the similarity of TbSTI1 to other STI1 proteins
Malarial drug targets cysteine proteases as hemoglobinases
Get PDFMalaria has consistently been rated as the worst parasitic disease in the world. This disease affects an estimated 5 billion households annually. Malaria has a high mortality rate leading to distorted socio-economic development of the world at large. The major challenge pertaining to malaria is its continuous and rapid spread together with the emergence of drug resistance in Plasmodium species (vector agent of the disease). For this reason, researchers throughout the world are following new leads for possible drug targets and therefore, investigating ways of curbing the spread of the disease. Cysteine proteases have emerged as potential antimalarial chemotherapeutic targets. These particular proteases are found in all living organisms, Plasmodium cysteine proteases are known to degrade host hemoglobin during the life cycle of the parasite within the human host. The main objective of this study was to use various in silico methods to analyze the hemoglobinase function of cysteine proteases in P. falciparum and P. vivax. Falcipain-2 (FP2) of P. falciparum is the best characterized of these enzymes, it is a validated drug target. Both the three-dimensional structures of FP2 and its close homologue falcipain-3 (FP3) have been solved by the experimental technique X-ray crystallography. However, the homologue falcipain-2 (FP2’)’ and orthologues from P.vivax vivapain-2 (VP2) and vivapain-3 (VP3) have yet to be elucidated by experimental techniques. In an effort to achieve the principal goal of the study, homology models of the protein structures not already elucidated by experimental methods (FP2’, VP2 and VP3) were calculated using the well known spatial restraint program MODELLER. The derived models, FP2 and FP3 were docked to hemoglobin (their natural substrate). The protein-protein docking was done using the unbound docking program ZDOCK. The substrate-enzyme interactions were analyzed and amino acids involved in binding were observed. It is anticipated that the results obtained from the study will help focus inhibitor design for potential drugs against malaria. The residues found in both the P. falciparum and P. vivax cysteine proteases involved in hemoglobin binding have been identified and some of these are proposed to be the main focus for the design of a peptidomimetric inhibitor
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Telomerase activity in response to RBBP6- Cannabidiol co-treatment in cervical cancer
Get PDFMSc (Biochemistry), North-West University, Mafikeng CampusCervical cancer ranks as the 4th most cited reason for mortalities amongst women across the globe. Accordingly, in 2018, 570 000 new individuals were diagnosed of cervical cancer. Early screening, detection and treatment can reduce cervical cancer incidences by 50%, however, developing countries lack resources, trained personnel and education in the general population limits the implementation of these routine testing programs in developing countries of sub-Saharan Africa. Cheaper and alternative therapeutic options to the otherwise expensive current interventions of chemotherapy, radiation and surgical resections are urgently required.
Retinoblastoma binding protein 6, which interacts with tumour suppressor p53, is highly abundant and expressed in many cancers such as cervical cancer. Taken together, the enhanced expression of RBBP6 and association with p53, has opened up interesting research possibilities exploring the RBBP6 biomolecule as both as therapeutic agent and biomarker for cancer. Gene therapy is associated with toxic effects. Hence, the present study proposes combination therapy which relies on the use of natural anticancer agents such as cannabidiol (CBD) found in a medicinal plant, along with gene-targeted therapeutics such as RBBP6 as a novel and cost-effective strategy for eradication of advanced stages of cancer. The exact molecular mechanism by which CBD mediates anticancer effects remains to be fully elucidated. There is a speculation that CBD induces apoptosis in cervical cancer, hence, current study was commenced to elucidate whether the possible apoptotic mechanisms involved in the chemotherapeutic properties of CBD in combination with targeted gene therapy maybe resulting in decreased telomerase activity.
Co-treatment of cervical cancer cells with a silenced of RBBP6 and CBD was used to assess telomerase activity. Once telomeres lose their function, they become rearranged and unstable. This results in genetic instability and leads to an increase in telomerase activity. It is then possible that telomerase activity can be explored as a molecular biomarker for early screening prevention of cervical cancer. To explore this possibility, ME-180 cervical cancer cells were maintained and subjected to treatment with the anticancer agent, CBD. The MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) viability assay was conducted to evaluate CBD effects on the viability of ME-180 cells. Furthermore, apoptotic response of cervical cancer cells to siRBBP6 and co-
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treatment with CBD was evaluated by DNA fragmentation and microscopy. Gene expression levels of RBBP6, MDM2 and p53 relative to GAPDH were evaluated by quantitative real-time PCR (qPCR). The effect of siRBBP6 and co-treatment was assessed using telomerase repeated amplification protocol (TRAP) assay.
It was found that CBD (0.5μg/ml) significantly reduces the viability of ME-180 cells, possibly by eliciting the apoptosis pathway. This was supported by observation of DNA fragmentation indicating both smearing that indicates necrosis in the combinational treatment. Microscopy revealed morphological features of apoptosis in cells treated with CBD alone and in-combination with siRBBP6. RBBP6 was successfully silenced and the combination therapy resulted in a down-regulation of RBBP6 and MDM2 expression levels and in contrast, p53 expression was found to be up-regulated. This study showed that RBBP6 promotes p53 degradation and that the p53 most likely central in telomerase activity. The likelihood that p53-dependent apoptosis is not related to telomerase activity in cervical cancer is being suggested based on the results obtained in the study. Overall, future endeavours should explore the cost effective and promising combination therapy as a powerful tool for halting cervical cancerMaster
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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