1,720,957 research outputs found
Screening for disease-causing genes in black South African patients with Parkinson’s disease
Get PDFThesis (MScMedSc)--Stellenbosch University, 2015.ENGLISH ABSTRACT: Please see fulltext for abstractAFRIKAANSE OPSOMMING: Parkinson se siekte ( PD ) is 'n toenemend algemene neurodegeneratiewe siekte wat die progressiewe verlies van dopaminergiese neurone in die substantia nigra pars compacta behels, wat lei tot die ontwrigting van die motororiese senuweestelsel. ’n Neuronale verlies van meer as 50% van die normale vlakke is nodig vir die ontwikkeling van die kliniese simptome, insluitende bewing, spier rigiditeit, bradykinesia, en posturale onstabiliteit. Alhoewel beskikbare medikasies vir PD wel simptome onderdruk, is dit nie in staat om die siekte te voorkom of vordering daarvan te verhoed nie. Een van die mees bedeidende risikofaktore vir PD is toenemende ouderdom. Huidige epidemiologiese studies voorspel ‘n toename in populasie ouderdom wat belangrike implikasies vir die voorkoms van PD kan inhou.
Die molekulere meganismes onderliggend aan die neurale agteruitgang in PD is steeds onbekend, maar dit blyk dat ‘n aantal genetiese faktore (in kombinasie met omgewingsfaktore) bydra tot die komplekse patogeniese agteruitgang van die siekte. Agt bevestigde gene is gevind om direk betrokke te wees by die etiologie van PD, naamlik: parkin, PINK1, DJ-1, ATP13A2, SNCA, LRRK2, VPS35, en EIF4G1. Hierdie gene is oorwegend geïdentifiseer en bestudeer in die Europese, Noord-Amerikaanse en Asiatiese bevolkings; terwyl die bestudering van Sub -Sahara- Afrika (SSA) bevolkings, veral dié van Swart Afrika afkoms, onderverteenwoordig bly in genetiese studies. Siende dat resultate verkry vanaf ander bevolkings nie verwant is aan die SSA bevolking nie, en ook nie ‘n voorspelling van wereldwye toename van die siekte kan verteenwoordig nie, is dit van belang dat omvattende genetiese studies uitgevoer word op hierdie onderbestudeerde bevolkings van SSA.
Desnieteenstaande, die doel van die studie was om die molekulere etiologie van PD in ‘n groep Swart Suid-Afrikaanse (SA) PD pasiente te ondersoek. ‘n Totaal van 47 pasiente is gewerf vir die studie waarvan 26% ‘n famielie geskiedenis het vir die afwyking. Die gemiddelde ouderdom van aanvang vir die pasiente was 55.3 ± 11.2 jaar. Mutasie volgorderbepaling vir alle bekende PD gene is uitgevoer. Addisionele mutasie volgorderbepaling vir die GBA is ook uitgevoer siende dat heterosigotiese mutasies in die geen dien as ‘n sterk risikofaktor vir die ontwikkeling van PD. ‘n Verskeidenheid mutasie volgordebepalingstegnieke is geinkorporeer vir die studie, naamlik: Sanger volgordebepaling en hoë resolusie smelt tegniek (vir die identifisering van missense mutasies asook kleinskaalse invoegings of weglatings), en multiplex-afbinding afhanklike ondersoek versterkingstoets (vir die opsporing van veranderinge in kopiegetal). Verder is volgende generasie volgordebepaling gebruik vir die sistematiese ondersoek van die bekende PD gene, asook vir 160 kandidaat gene wat vooraf bepaal is. Fluoreserend-geetiketeerde polymerase ketting reaksie primers is gebruik vir genotipering van CAG herhalings uitbreidings in die ataxin-2 (SCA2) en die ataxin-7 (SCA7) gene, gevolg deur elektroforese met behulp van die “ABI 3130x1 Genetic Analyzer”.
Mutasie volgordebepaling het voor die lig gebring dat die bekende PD gene klaarblyklik nie ‘n beduidende oorsaaklike rol speel in die patogenese van die siekte in die huidige groep Swart SA pasiente nie, want slegs 2 uit die 47 (43%) pasiente koester mutasies in parkin. Een van die pasiente besit ‘n heterosigotiese duplikasie van ekson 2 en ‘n heterosigotiese weglating van ekson 9; in die ander pasient is ‘n heterosigotiese ekson 4 weglating en ‘n heterosigotiese G430D mutasie geïdentifiseer. Verder is ‘n Q311K verandering in parkin gevind asook vier nuwe variante (I610T, H1758P, N2133S en T2423S) in die LRRK2 geen. Die patogenisiteit van hierdie variante moet egter nog bepaal word. Geen patogeniese herhaalings uitbreidings is gevind in die SCA2 en SCA7 lokusse nie, en die moontlikheid van die twee spinocerebellar ataksie subtipes as genetiese bepalers vir PD is uitgekanselleer. Geen patogeniese mutasies is gevind in enige van die oorblywende bekende PD gene nie, dit is dus waarskeinlik dat die pasiente wel mutasies in nuwe PD-geassosieerde gene besit. Hierdie is die eerste molekulere genetiese studie uitgevoer op uitsluitlik Swart SA PD pasiente, en ook die eerste omvattende ondersoek van al die bekende PD gene in ‘n SSA bevolking. Die algemene patogeniese mutasies in gene, wat voorheen bewys is as siekte veroorsakend in ‘n aantal Europese bevolkings, is nie bespeur in die huidige studie nie en kan dus nie verantwoordelik gehou word vir die voorkoms van PD in hierdie pasiente nie. Maar, siende dat die steekproefgrootte in hierdie studie relatief klein was, kan addisionele volgordebepaling van ‘n groter pasient groep voordelig wees in die bepaal van nuwe siekte-veroorsakende gene wat die potensiaal het om huidige hipoteses, dat die genetiese etiologie van PD duidelik verskil oor verskeie etniese groepe wereldwyd, te weerlê of bevestig. Die voortsetting van genetiese ondersoeke onder hierdie groep pasiente kan bydra tot insig met betrekking tot bevolking-spesifieke genetiese bepalers, en uiteindelik tot die identifisering van nuwe teikens vir medikasies teen die siekte
The effects of on chaperone-mediated autophagy in human HepG₂ liver cancer cells
No full textDissertation (MMed.Sc.((Physiology))--University of the Free State, 2023: The impact of hepatocellular carcinoma (HCC) is most significant in developing countries, including South Africa. Emerging evidence suggests that the cell survival mechanism, chaperone-mediated autophagy (CMA), promotes HCC tumour progression and chemotherapeutic drug resistance. Current treatment approach for HCC is guided by the Barcelona Clinic Liver Treatment Strategy (BCLTS), which recommends different treatment approaches depending on the level of tumour progression. Despite their efficacy, currently available chemotherapeutic options have numerous limitations such acquired resistance, recurrence, and hypertension. To address these limitations, phytochemical extracts are increasingly being investigated for the anti-cancer potential. The phytochemical extracts of the medicinal plant, Moringa oleifera (MO) have been shown to induce apoptosis of HCC cells. MO leaves have the greatest abundance of phytochemicals displaying anticancer potential. Investigating the interplay between all-trans-retinoic acid (ATRA), a potential inhibitor of CMA, and MO regarding their effects on CMA holds potential in identifying adjuvant therapeutic approaches for treatment modalities for HCC.
: This study aimed to investigate the effects of MO aqueous leaf extract on CMA activity in human HepG₂ cancer cells.
: HepG₂ cells were cultured and exposed to MO and ATRA for 24 hours. Thereafter, a cell viability assay was performed and an inhibition concentration 50 (IC50) was determined which was used for all subsequent experiments. The cells were allocated to three treatment groups: MO, ATRA and a combination group of MO and ATRA. A Caspase-Glo™ cell death assay and western blot analysis were also conducted to evaluate changes in lysosome-associated membrane protein type 2A (LAMP2A) and hexokinase II (HK2) protein expression levels.
: The cell viability assay results displayed a concentration-dependent decline in reductive capacity following MO and ATRA exposures. An IC₅₀ of 1415 μM (ATRA) and 2198 μg/mL (MO) were observed. The cell death assay revealed decreased caspase-9 activity following the respective treatment exposures. There was a corresponding decline in caspase-3/7 activity following respective treatment exposures, except for MO, where an increase in caspase-3/7 activity was observed. Western blot analysis showed a decline in the expression of LAMP2A and a corresponding increase in the expression of the CMA cargo protein HK2.
: The results revealed that MO and ATRA could inhibit the growth and proliferation of HCC cells, offering a promising adjuvant therapeutic approach against HCC. Further investigation into these compounds and their underlying mechanisms of action may contribute to developing novel treatment modalities for HCC
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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