Search bioRxiv⌕ Search

Biology subjects

Olayinka, A.

Publications and source records attributed to Olayinka, A..

3 recordsLinked to original sources

N-Glycans on the extracellular domain of the Notch1 receptor control Jagged-1 induced Notch signalling and myogenic differentiation of S100β resident vascular stem cells

Notch signalling, critical for development and postnatal homeostasis of the vascular system, is highly regulated by several mechanisms including glycosylation. While the importance of O-linked glycosylation is widely accepted, the structure and function of N-glycans has yet to be defined. Here, we take advantage of lectin binding assays in combination with pharmacological, molecular, and site-directed mutagenetic approaches to study N-glycosylation of the Notch1 receptor. We find that several key oligosaccharides containing bisecting or core fucosylated structures decorate the receptor, control expression and receptor trafficking, and dictate Jagged-1 activation of Notch target genes and myogenic differentiation of multipotent S100{beta} vascular stem cells. N-glycans at asparagine (N) 1241 and 1587 protect the receptor from accelerated degradation, while the oligosaccharide at N888 directly affects signal transduction. Conversely, N-linked glycans at N959, N1179, N1489 do not impact canonical signalling but inhibit differentiation. Our work highlights a novel functional role for N-glycans in controlling Notch1 signalling and differentiation of vascular stem cells. TeaserA sweet development in Notch regulation of vascular smooth muscle cell differentiation

cell biology↗

Disease-relevant single cell photonic signatures identify S100β+ stem cells and their myogenic progeny in vascular lesions

A hallmark of subclinical atherosclerosis is the accumulation of vascular smooth muscle cell (SMC)-like cells leading to intimal thickening and lesion formation. While medial SMCs contribute to vascular lesions, the involvement of resident vascular stem cells (vSCs) remains unclear. We evaluated single cell photonics as a discriminator of cell phenotype in vitro before the presence of vSC within vascular lesions was assessed ex vivo using supervised machine learning and further validated using lineage tracing analysis. Using a novel lab-on-a-Disk (Load) platform, label-free single cell photonic emissions from normal and injured vessels ex vivo were interrogated and compared to freshly isolated aortic SMCs, cultured Movas SMCs, macrophages, B-cells, S100{beta}+ mVSc, bone marrow derived mesenchymal stem cells (MSC) and their respective myogenic progeny across five broadband light wavelengths ({lambda}465 - {lambda}670 {+/-} 20 nm). We found that profiles were of sufficient coverage, specificity, and quality to clearly distinguish medial SMCs from different vascular beds (carotid vs aorta), discriminate normal carotid medial SMCs from lesional SMC-like cells ex vivo following flow restriction, and identify SMC differentiation of a series of multipotent stem cells following treatment with transforming growth factor beta 1 (TGF-{beta}1), the Notch ligand Jaggedl, and Sonic Hedgehog using multivariate analysis, in part, due to photonic emissions from enhanced collagen III and elastin expression. Supervised machine learning supported genetic lineage tracing analysis of S100{beta}+ vSCs and identified the presence of S100{beta}+ vSC-derived myogenic progeny within vascular lesions. We conclude disease-relevant photonic signatures may have predictive value for vascular disease.

cell biology↗

HIV-MALARIA CO-INFECTION AND ITS DETERMINANTS AMONG PATIENTS ATTENDING ANTIRETROVIRAL TREATMENT CLINIC IN ZARIA, NORTH-WESTERN NIGERIA

IntroductionMalaria and HIV are two important global public health problems. Together, they cause more than two million deaths each year. In sub-Saharan Africa alone, more than 29 million people are living with HIV/AIDS and about 70% of population is at risk to malaria infection. Nigeria accounts for about a quarter of the global malaria cases and tenth of the global HIV cases. Recent theories suggested possibilities of high occurrence of HIV-malaria co-infection wherever there is geographical overlap of the two diseases. We therefore conducted this study to determine the prevalence of HIV-malaria co-infection and its determinants in a malaria endemic setting.\n\nMethodsWe conducted a cross-sectional study. Two hundred and sixty-two clients attending antiretroviral treatment (ART) clinic in Zaria, Kaduna State were enrolled between February and April 2018 using systematic sampling technique. Questionnaires were administered to collect information on respondents personal characteristics as well as their knowledge, perception and practices on malaria prevention. Venous blood samples were collected and analyzed for malaria parasite, viral load, CD4, and FBC using Giemsa stained light microscopy, COBAS TaqMan equipment, BD FACS flow cytometer, and Sysmex haematology analyser respectively. Descriptive and inferential statistics were performed, predictors of HIV-malaria co-infection were ascertained at multivariate analysis.\n\nResultsMedian age of the respondents was 33 years, 52% were females, 65% were married, 65% were employed, 57% lived in urban residence, and 34% had tertiary education. The prevalence of malaria co-infection among HIV patients was found to be 22.9%. Significant risk factors for the co-infection were high HIV viral load (aOR= 3.30, C.I = 1.15-9.45), being co-infected with TB (aOR= 5.60, C.I = 1.34-23.33), poor knowledge of malaria infection (aOR= 3.12, C.I = 1.27-7.72) and poor practice of malaria prevention (aOR= 13.30, C.I = 4.88-36.23).\n\nConclusionThe level of occurrence of malaria among HIV infected patients in this setting calls for attention. We recommended that health education on malaria should be a priority in malaria control programme; the programmes for control of HIV, malaria and TB should collaborate to ensure integrated service delivery and that people living with HIV/AIDS should be given special consideration for malaria prevention.

epidemiology↗