Functional analysis of the mouse RBBP6 gene using Interference RNA

Philosophiae Doctor - PhDThe aim of this thesis was to investigate the cellular role of the mouse RBBP6 gene using the interference RNA (RNAi) gene targeting technology and also to understand the relevance of two promoters for the RBBP6 gene.South Afric

Changes in subcutaneous adipose tissue microRNA expression in response to exercise training in African women with obesity

The mechanisms that underlie exercise-induced adaptations in adipose tissue have not been elucidated, yet, accumulating studies suggest an important role for microRNAs (miRNAs). This study aimed to investigate miRNA expression in gluteal subcutaneous adipose tissue (GSAT) in response to a 12-week exercise intervention in South African women with obesity, and to assess depot-specific differences in miRNA expression in GSAT and abdominal subcutaneous adipose tissue (ASAT). In addition, the association between exercise-induced changes in miRNA expression and metabolic risk was evaluated. Women underwent 12-weeks of supervised aerobic and resistance training (n = 19) or maintained their regular physical activity during this period (n = 12). Exercise-induced miRNAs were identified in GSAT using Illumina sequencing, followed by analysis of differentially expressed miRNAs in GSAT and ASAT using quantitative real-time PCR. Associations between the changes (pre- and postexercise training) in miRNA expression and metabolic parameters were evaluated using Spearman’s correlation tests

Identification of biomarkers for the accurate and sensitive diagnosis of three bacterial pneumonia pathogens using in silico approaches

: Pneumonia ranks as one of the main infectious sources of mortality among kids under 5 years of age, killing 2500 a day; late research has additionally demonstrated that mortality is higher in the elderly. A few biomarkers, which up to this point have been distinguished for its determination lack specificity, as these biomarkers fail to build up a differentiation between pneumonia and other related diseases, for example, pulmonary tuberculosis and Human Immunodeficiency Infection (HIV). There is an inclusive global consensus of an improved comprehension of the utilization of new biomarkers, which are delivered in light of pneumonia infection for precision identification to defeat these previously mentioned constraints. Antimicrobial peptides (AMPs) have been demonstrated to be promising remedial specialists against numerous illnesses. This research work sought to identify AMPs as biomarkers for three bacterial pneumonia pathogens such as Streptococcus pneumoniae, Klebsiella pneumoniae, Acinetobacter baumannii using in silico technology. Hidden Markov Models (HMMER) was used to identify putative anti-bacterial pneumonia AMPs against the identified receptor proteins of Streptococcus pneumoniae, Klebsiella pneumoniae, and Acinetobacter baumannii. The physicochemical parameters of these putative AMPs were computed and their 3-D structures were predicted using I-TASSER. These AMPs were subsequently subjected to docking interaction analysis against the identified bacterial pneumonia pathogen proteins using PATCHDOCK

Building HMM and molecular docking analysis for the sensitive detection of anti-viral pneumonia antimicrobial peptides (AMPs)

Pneumonia is the main reason for mortality among children under five years, causing 1.6 million deaths every year; late research has exhibited that mortality is increasing in the elderly. A few biomarkers used for its diagnosis need specificity and precision, as they are related to different infections, for example, pulmonary tuberculosis and Human Immunodeficiency Virus. There is a quest for new biomarkers worldwide to diagnose the disease to defeat these previously mentioned constraints. Antimicrobial peptides (AMPs) are promising indicative specialists against infection. This research work used AMPs as biomarkers to detect viral pneumonia pathogens, for example, Respiratory syncytial virus, Influenza A and B viruses utilizing in silico technologies, such as Hidden Markov Model (HMMER). HMMER was used to distinguish putative anti-viral pneumonia AMPs against the recognized receptor proteins of Respiratory syncytial virus, Influenza A, and B viruses. The physicochemical parameters of these putative AMPs were analyzed, and their 3-D structures were determined utilizing I-TASSER. Molecular docking interaction of these AMPs against the recognized viral pneumonia proteins was carried out using the PATCHDOCK and HDock servers. The results demonstrated 27 anti-viral AMPs ranked based on their E values with significant physicochemical parameters in similarity with known experimentally approved AMPs. The AMPs additionally had a high anticipated binding potential to the pneumonia receptors of these microorganisms sensitively. The tendency of the putative anti-viral AMPs to bind pneumonia proteins showed that they would be promising applicant biomarkers to identify these viral microorganisms in the point-of-care (POC) pneumonia diagnostics. The high precision observed for the AMPs legitimizes HMM’s utilization in the disease diagnostics’ discovery proces

Functional prediction of candidate micrornas for CRC management using in silico approach

Approximately 30–50% of malignant growths can be prevented by avoiding risk factors and implementing evidence-based strategies. Colorectal cancer (CRC) accounted for the second most common cancer and the third most common cause of cancer death worldwide. This cancer subtype can be reduced by early detection and patients’ management. In this study, the functional roles of the identified microRNAs were determined using an in silico pipeline. Five microRNAs identified using an in silico approach alongside their seven target genes from our previous study were used as datasets in this study. Furthermore, the secondary structure and the thermodynamic energies of the microRNAs were revealed by Mfold algorithm. The triplex binding ability of the oligonucleotide with the target promoters were analyzed by Trident. Finally, evolutionary stage-specific somatic events and co-expression analysis of the target genes in CRC were analyzed by SEECancer and GeneMANIA plugin in Cytoscape. Four of the five microRNAs have the potential to form more than one secondary structure. The ranges of the observed/expected ratio of CpG dinucleotides of these genes range from 0.60 to 1.22

PZQ Therapy: How close are we in the development of effective alternative anti-schistosomal drugs?

Today schistosomiasis, caused mainly by the three major schistosome species (S. mansoni, S. haematobium and S. japonicum), has for many decades and still continues to be on a rapid and swift rise globally, claiming thousands of lives every year and leaving 800 million people at the risk of infection. Due to the high prevalence of this disease and the steady increase in the infection rates, praziquantel (PZQ) remains the only effective drug against this acute disease although it has no effect on the juvenile schistosome parasite. However, no significant approaches have been made in recent years in the discovery of new or alternative drugs and unfortunately, resistance to this drug has been reported in some parts of the world. Therefore, it is imperative to develop a new drug for this debilitating disease. In this review, a brief history of past, present, and new promising anti-schistosomal drugs is presented

Antibacterial activity of rationally designed antimicrobial peptides.

Many infectious diseases are still prevalent in the world’s populations since no effective treatments are available to eradicate them. e reasons may either be the antibiotic resistance towards the available therapeutic molecules or the slow rate of producing adequate therapeutic regimens to tackle the rapid growth of new infectious diseases, as well as the toxicity of current treatment regimens. Due to these reasons, there is a need to seek and develop novel therapeutic regimens to reduce the rapid scale of bacterial infections. Antimicrobial Peptides (AMPs) are components of the first line of defense for prokaryotes and eukaryotes and have a wide range of activities against Gram-negative and Gram-positive bacteria, fungi, cancer cells, and protozoa, as well as viruses. In this study, peptides which were initially identified for their HIV inhibitory activity were further screened for antibacterial activity through determination of their kinetics as well as their cytotoxicity. From the results obtained, the MICs of two AMPs (Molecule 3 and Molecule 7) were 12.5 μg/ml for K. pneumoniae (ATCC 700603) and 6.25 μg/ml for P. aeruginosa (ATCC 22108). e two AMPs killed these bacteria rapidly in vitro, preventing bacterial growth within few hours of treatment. Furthermore, the cytotoxic activity of these two peptides was significantly low, even at an AMP concentration of 100 μg/ml. ese results revealed that Molecule 3 and 7 have great potential as antibacterial drugs or could serve as lead compounds in the design of therapeutic regimens for the treatment of antibiotic-resistant bacteria

Dietary effects of antimicrobial peptides in therapeutics

The notable increase in drug-resistant infections and the failure of the most potent antibiotics to establish their curative effect without side effect have presented a serious need for the discovery of new therapeutic agent and the study of dietary implications on the mode of entry of these therapeutic agents in the human system. This review provides insight into the forms and modes of action, and roles of beneficial but limited and underutilized antimicrobial peptides for use in dietary formulations, with particular focus on the technologies employed for their discovery as well as their dietary efficacy. The wide spectrum of activities of these peptides will allow the opportunity to explore their benefits as dietary supplements and additives

Fire-arm Related Homicides in Gauteng

This fact sheet reports on firearm-related homicide, recorded by the National Injury Mortality Surveillance System (NIMSS), at nine forensic pathology services in the province of Gauteng for 2011, the latest year for which NIMSS data are available. NIMSS is managed and co-ordinated by the Safety and Peace Promotion Research Unit of the Medical Research Council and University of South Africa (MRC-UNISA SAPPRU). NIMSS aims to: provide comprehensive information about deaths due to external causes, establish a permanent comprehensive automated system that will timeously register all injury deaths that occur in all nine provinces of South Africa, and inform initiatives for the prevention of non-natural fatalities. NIMSS provides information on the major causes of non-natural deaths and their related demographic, seasonal and circumstantial factors. Presently, NIMSS focuses on the provinces of Gauteng and Mpumalanga in South Africa

In silico prediction of new antimicrobial peptides and proteins as druggable targets towards alternative anti-schistosomal therapy

Schistosomiasis is a debilitating disease caused by a parasitic flatworm found in fresh- water. With the exponential increase in prevalence, Praziquantel (PZQ) remains the only effective treatment drug, however, resistance to PZQ has been reported recently. There- fore, it is imperative to develop effective alternative anti-schistosomal compounds using bioinformatics-based tools utilizing the broad-spectrum therapeutic capabilities of antimi- crobial peptides (AMPs). AMPs are essential components of the innate immune system and are responsible for complete destruction and immunomodulatory effects in the host defence against pathogens. Here, Hidden Markov model was used to identify six anti- microbial peptides (TAK1–TAK6) with potential anti-schistosomal capabilities. Also, glyco- syltransferase and axonemal dynein intermediate chain protein were identified as impor- tant druggable Schistosome proteins. The 3-D structures of the AMPs and proteins were modelled using I-TASSER and it was shown that the six putative anti-schistosomal AMPs and the two proteins had low C-score, possibly due to lack of available templates for their modelling. Finally, PatchDock was employed to ascertain the interaction between the schis- tosome proteins and the putative AMPs