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Zaid, M.

Publications and source records attributed to Zaid, M..

3 recordsLinked to original sources

Simple Models For Neuroscience Research Discoveries: How Often Are These Models Used In Africa

Simple animal model systems such as Drosophila, Zebrafish, and C. Elegans have enabled numerous breakthroughs in understanding human health and disease. Their conserved biological processes, ever-expanding established procedures for handling, and amenability for molecular and genetic manipulation, in addition to the minimal ethical concerns, have made these models preferred choices in several life science disciplines globally. Owing to their cheap maintenance cost, adopting these model systems will help bridge the research gap between Africa and the Global North and contribute to advancing scientific knowledge in African universities through practical sessions. However, the extent to which these models are used across Africa is unknown. Here, we analysed the use of Drosophila, Zebrafish, and C. elegans model systems in scientific publications from African laboratories from the year 2000 to 2021. Of 1851 PubMed-indexed publications in which at least one simple animal model was mentioned, 168 used at least one of these models for the actual investigation. With an average of 21 articles per country, South Africa, Nigeria, Kenya, Egypt, Morocco, and Tunisia contributed 75% of these studies. The remaining 25% were contributed by seven other countries at 2-7 articles per country. From here, we extracted and analysed information on funding and international collaboration. This revealed that 24.4 % of the studies were exclusively funded locally, 28.57 % exclusively funded internationally, 15.5% received both local and international funding, and the rest (31.5%) were unfunded, revealing that there is satisfactory access to funds for simple animal model studies, especially from external funders. By analysing the pattern of collaborations, we show that most of these studies had international collaborations, while very few collaborated within Africa. Our work provides data on the current state of research using simple model systems in African laboratories and argues that incorporating these models will advance biomedical science research in Africa.

neuroscience↗

Loss of Rnf43 accelerates Kras-mediated neoplasia and remodels the tumor immune microenvironment in pancreatic adenocarcinoma

RNF43 is an E3 ubiquitin ligase that is recurrently mutated in pancreatic ductal adenocarcinoma (PDAC) and precursor cystic neoplasms of the pancreas. The impact of RNF43 mutations on PDAC is poorly understood and autochthonous models have not been sufficiently characterized. In this study we describe a genetically engineered mouse model (GEMM) of PDAC with conditional expression of oncogenic Kras and deletion of the catalytic domain of Rnf43 (KRC) in exocrine cells. We demonstrate that Rnf43 loss results in an increased incidence of high-grade cystic lesions of the pancreas and PDAC. Importantly, KRC mice have a significantly decreased survival compared to mice containing only an oncogenic Kras mutation. By use of single cell RNA sequencing we demonstrated that KRC tumor progression is accompanied by a decrease in macrophages, as well as an increase in T and B lymphocytes with evidence of increased immune checkpoint molecule expression and affinity maturation, respectively. This was in stark contrast to the tumor immune microenvironment observed in the Kras/Tp53 driven PDAC GEMM. Furthermore, expression of the chemokine, CXCL5, was found to be specifically decreased in KRC cancer cells by means of epigenetic regulation and emerged as a putative candidate for mediating the unique KRC immune landscape. This GEMM establishes RNF43 as a bona fide tumor suppressor gene in PDAC and puts forth a rationale for an immunotherapy approach in this subset of PDAC cases.

cancer biology↗

Comparing the metabolic fates of BALB/c mice maintained on cafeteria-style diets with differential nutritive values

Cafeteria (CAF) diet-fed rodents are shown to provide a robust model of metabolic syndrome and human obesity. The carbohydrate/fat-rich food-items provided to the CAF-diet-model more closely approximate the ultra-processed human diet. However, most of the previous studies applied the commercially available rodent chow-diet for the comparative analyses and labeled it as a healthy-diet. The presented work aims to extend the knowledge on CAF-diet model by exposing the mice to human foods with different nutritional values. Our major goal was to study the metabolic fates of mice maintained on human food-items, which depending upon on their macronutrient compositions are categorized as healthy or unhealthy. BALB/c mice were randomly allocated to one of the three dietary intervention groups, standard chow diet; high-sugar/high-fat-cafeteria (HSHF-CAF) diet; or low-sugar/low-fat-cafeteria (LSLF-CAF) diet, for 5 weeks. The differences in multiple metabolic parameters (including food-/energy /macronutrient-intake, body-weight gain rate, organ-to-body weight ratios, plasma lipid profiles, adipocyte physiology, lipid deposition in metabolic tissues and ectopic fat storage in heart and kidney) were compared among the three intervention groups. We did not observe hyperphagia in mice maintained on CAF-diets. Nonetheless, the CAF-diet-fed mice displayed increased weight-gain-rate, adiposity, and adipocyte hypertrophy when compared to the chow-fed mice. However, the mice maintained on the two cafeteria-style diets displayed similar metabolic profiles, with HSHF-CAF-group displaying slightly higher weight-gain-rate. The HSHF-CAF-and LSLF-CAF-diet induced comparable adiposity in BALB/c mice. Further studies, with longer dietary intervention periods, are required to elucidate the effects of differential CAF-diets on the metabolic health of mice.

biochemistry↗