Bewertung der Wirkungen des Histone H3.2 durch die mikrophthalmische Mausmutante Aey69

Aey69, a micropthalmic mouse mutant was found to result from a mutation in H3.2 coding genes, Hist2h3c1. Using a combination of different immunohistochemical markers, a timeline of microphthalmic pathology was charted, with particular focus on lens and retinal pathological changes. In addition, using CRISPR/CAS9 a transgenic mouse line expressing the fusion protein H3.2-GFP was established and characterized. Analysis of incorporation sites of H3.2 in transgenic embryos, illustrated a novel role of H3.2 in ocular development.Die dominante Mausmutante Aey69 ist durch eine Mikrophthalmie charakterisiert, die durch eine c.358A->C Mutation (Ile120Leu) im Hist2h3c1 Gen verursacht wird, das für ein Histon H3.2 kodiert. Die Mutation führt in der Embryonalentwicklung zum Abbau des Linsenbläschens und zur Hyperproliferation der Retina. Es wurde eine transgene Mauslinie etabliert, die für ein H3.2-GFP-Fusionsprotein kodiert. Die CHiP-Seq-Analyse deutet darauf hin, dass der Ephrin-Signalweg durch das Histon H3.2 betroffen ist

Factors affecting the performance of small and medium enterprises in KwaZulu-Natal.

MBA University of KwaZulu-Natal, Durban 2014.Small and Medium Enterprises (SMEs) have an important role to play in the development of the country. A strong SME sector contributes highly to the economy, contributing to the Gross Domestic Product, by reducing the level of unemployment, reduction in poverty levels and promotion of entrepreneurship activity. Even though SMEs make a contribution to the economic growth and are of significant importance, SMEs globally, and in South Africa especially, are still faced with many challenges. In South Africa, the growth of SMEs and prevalence of SMEs is significantly low. Therefore, the aim of the study was to identify the internal and external factors affecting the performance of SMEs in KwaZulu-Natal, and to make recommendations to overcome these factors to improve the performance of SMEs. This was crosssectional survey conducted via online using anonymous questionnaire among the SMEs who were members of the Durban Chamber of Commerce. The results revealed technological advancement was a factor as 81.82% of the respondents, mentioned that would improve the performance of the business. With regards to challenge, 73.02% SME owners/managers viewed competition as a major challenge. Majority of the SME owners/managers, between 82.54% and 86.67% viewed all the macroeconomic factors studied as hindering factor. The factor crime and corruption was viewed by 88.89% as affecting business performance. However competition was the only factor, amongst the studied internal and external factors that revealed a significant association with the performance of SMEs in KwaZulu-Natal (p=0.011). No other variable were found to be associated with the performance of SMEs in KwaZulu-Natal. SMEs in Kwa-Zulu Natal are faced with competition which is impacting the performance of the business negatively. SMEs are finding it difficult to maintain their market share and position, due to the competition from local competitors as well as international competitors. SMEs need to recognize they must prepare for both domestic and international competition. Collaboration between SMEs could be a way for SMEs to confront competition. By entering into joint ventures, the opportunity to combine strengths, information and technological capabilities to increase sales or to enhance their customer base exist

Factors affecting the performance of small and medium enterprises in KwaZulu-Natal, South Africa

Small and medium enterprises (SMEs) have an important role to play in the development of the country. A strong SME sector contributes highly to the economy, contributing to the gross domestic product, by reducing the level of unemployment, reduction in poverty levels and promotion of entrepreneurship activity. In South Africa (SA), the growth of SMEs and prevalence of SMEs is significantly low. Therefore, the aim of the study is to identify the internal and external factors affecting the performance of SMEs in KwaZulu-Natal, SA. This was a cross-sectional study conducted among 74 SMEs owners/managers who were members of the Durban Chamber of Commerce via online using anonymous questionnaire. The results revealed technological advancement would improve the performance of the business. With regards to challenge, the majority of the respondents viewed competition as a major challenge. Almost all the respondent indicated that crime and corruption affecting business performance. Competition was the only factor amongst the studied internal and external factors that revealed a significant association with the performance of SMEs in KwaZulu-Natal (p = 0.011). SMEs need to recognize they must prepare for both domesti

Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A consensus statement

Líquido cefalorraquídeo; Consenso; Esclerosis múltipleLíquid cefaloraquidi; Consens; Esclerosi múltipleCerebrospinal fluid; Consensus; Multiple sclerosisCerebrospinal fluid (CSF) analysis is of utmost importance for diagnosis and differential diagnosis of patients with suspected multiple sclerosis (MS). Evidence of intrathecal immunoglobulin G (IgG) synthesis proves the inflammatory nature of the disease, increases diagnostic certainty and substitutes for dissemination in time according to current diagnostic criteria. The gold standard to determine intrathecal IgG synthesis is the detection of CSF-restricted oligoclonal bands (OCBs). However, advances in laboratory methods brought up κ-free light chains (FLCs) as a new biomarker, which are produced in excess over intact immunoglobulins and accumulate in CSF in the case of central nervous system-derived inflammation. Overwhelming evidence showed a high diagnostic accuracy of intrathecal κ-FLC synthesis in MS with sensitivity and specificity of approximately 90% similar to OCB. κ-FLCs have advantages as its detection is fast, easy, cost-effective, reliable, rater-independent and returning quantitative results which might also improve the value of predicting MS disease activity. An international panel of experts in MS and CSF diagnostics developed a consensus of all participants. Six recommendations are given for establishing standard CSF evaluation in patients suspected of having MS. The panel recommended to include intrathecal κ-FLC synthesis in the next revision of MS diagnostic criteria as an additional tool to measure intrathecal immunoglobulin synthesis

A rare presentation of atypical demyelination: tumefactive multiple sclerosis causing Gerstmann's syndrome

r. KS has been supported by a Higher Education Funding Council for England (HEFCE) Clinical Senior Lectureshi

Cryptococcal meningitis in apparently immunocompetent patients: association with idiopathic CD4+ lymphopenia.

We present two cases of cryptococcal meningitis in people subsequently diagnosed with idiopathic CD4+ lymphopenia. Both presented with new onset headaches without sinister features and were sent home on multiple occasions from emergency departments. Cryptococcal meningitis in HIV-negative patients poses major diagnostic and management problems; the associated mortality is 9%-27%. We suggest performing blood and cerebrospinal fluid cryptococcal antigen tests in all people with lymphocytic meningitis

The role of iron in calciphylaxis—a current review

Calcific uraemic arteriolopathy (CUA), also known as calciphylaxis, is a rare and often fatal condition, frequently diagnosed in end-stage renal disease (ESRD) patients. Although exact pathogenesis remains unclear, iron supplementation is suggested as a potential risk factor. Iron and erythropoietin are the main stay of treatment for anaemia in ESRD patients. Few observational studies support the role of iron in the pathogenesis of calciphylaxis although data from the pivotal trial was not strongly supportive of this argument, i.e., no difference in incidence of calciphylaxis between the low-dose and high-dose iron treatment arms. Elevated levels of vascular cell adhesion molecules in association with iron excess were postulated to the pathogenesis of CUA by causing inflammation and calcification within the microvasculature. In-addition, oxidative stress generated because of iron deposition in cases of systemic inflammation, such as those seen in ESRD, may play a role in vascular calcification. Despite these arguments, a direct correlation between cumulative iron exposure with CUA incidence is not clearly demonstrated in the literature. Consequently, we do not have evidence to recommend iron reduction or cessation in ESRD patients that develop CUA

PPARG dysregulation as a potential molecular target in adrenal Cushing's syndrome

BACKGROUND We performed a transcriptomic analysis of adrenal signaling pathways in various forms of endogenous Cushing's syndrome (CS) to define areas of dysregulated and druggable targets. METHODOLOGY Next-generation sequencing was performed on adrenal samples of patients with primary bilateral macronodular adrenal hyperplasia (PBMAH, n=10) and control adrenal samples (n=8). The validation groups included cortisol-producing adenoma (CPA, n=9) and samples from patients undergoing bilateral adrenalectomy for Cushing's disease (BADX-CD, n=8). In vivo findings were further characterized using three adrenocortical cell-lines (NCI-H295R, CU-ACC2, MUC1). RESULTS Pathway mapping based on significant expression patterns identified PPARG (peroxisome proliferator-activated receptor gamma) pathway as the top hit. Quantitative PCR (QPCR) confirmed that PPARG (l2fc<-1.5) and related genes - FABP4 (l2fc<-5.5), PLIN1 (l2fc<-4.1) and ADIPOQ (l2fc<-3.3) - were significantly downregulated (p<0.005) in PBMAH. Significant downregulation of PPARG was also found in BADX-CD (l2fc<-1.9, p<0.0001) and CPA (l2fc<-1.4, p<0.0001). In vitro studies demonstrated that the PPARG activator rosiglitazone resulted in decreased cell viability in MUC1 and NCI-H295R (p<0.0001). There was also a significant reduction in the production of aldosterone, cortisol, and cortisone in NCI-H295R and in Dihydrotestosterone (DHT) in MUC1 (p<0.05), respectively. OUTCOME This therapeutic effect was independent of the actions of ACTH, postulating a promising application of PPARG activation in endogenous hypercortisolism