ABSTRACT
GAGA associated factor (GAF) is a sequence-specific DNA binding transcription factor that is evolutionarilyconserved from flies to humans. Emerging evidence shows a context-dependent function of vertebrate GAF(vGAF, a.k.a. ThPOK) in multiple processes like gene activation, repression, and enhancer-blocking. Wehypothesize that context-dependent interaction of vGAF with a diverse set of proteins forms the basis for themultifunctional nature of vGAF. To this end, we deciphered the protein–protein interactome of vGAF andshow that vGAF interacts with chromatin remodelers, RNA metabolic machinery, transcriptional activators/repressors, and components of DNA repair machinery. We further validated the biological significance of ourprotein–protein interaction data with functional studies and established a novel role of vGAF in DNA repairand cell-survival after UV-induced DNA damage. One of the major risk factors for skin cutaneous melanoma isprolonged exposure of UV and subsequent DNA damage. vGAF is highly expressed in normal skin tissue.Interestingly, our analysis of high-throughput RNA-sequencing data shows that vGAF is heavily downregulated across all major stages of skin cutaneous melanoma suggesting its potential as a diagnostic biomarker.Taken together, our study provides a plausible explanation for the diverse gene regulatory functions of vGAFand unravels its novel role in DNA repair.
ABSTRACT
Background: Diabetes is a chronic disease, leading to many complications include micro vascular (nephropathy, retinopathy, and neuropathy) and macro vascular (stroke, myocardial infarction, and coronary artery disease) with co morbidities leads to a substantial decrease in the patients' quality of life as well as socio-economic implications. It is a chronic disease with considerable impact on health status and quality of life and it is considered an urgent public health issue because it has a pandemic potential. Objectives:The main aim of this study was to determine diabetic complications and its associated factors. It also aimed to assess the knowledge of diabetic patients about the related complications. Material and Methods: Adescriptive, observational, cross sectional study was conducted in the diabetes clinic of Ram Manohar Lohia Combined Hospital, Lucknow. The study population included all the Type 2 diabetic subjects who attended the clinic from November 2017 to April 2018. 360 subjects were selected by systematic random sampling. A pre-designed and pre-tested schedule was used for data collection. Data were collected regarding socio-demographic characteristics and duration of diabetes.HbA1C levels were estimated. The data were analysed using statistical software SPSS 20.Proportions and Chi-square test were used for analysis. Results: Out of 360 diabetic patients, 140 (39%) had one or more complications while 220 (61%) did not have any complications. It was found that cardiovascular complications were present in 120 (33.3%) patients, cerebrovascular complications were present in 35 (9.7%) patients, peripheral vascular disease was present in 25 (7%) patients, while 50 (14%) patients were having diabetic nephropathy,130 (36.1%)patients were having diabetic neuropathy and 110 (30.5%) patients were suffering from diabetic retinopathy. Significant association was found between the complications with religion, socio-economic status, duration of diabetes, HbA1C.Also, significant association was found between duration of diabetes and HbA1C levels with each of the individual complications. Conclusion: Early diagnosis, periodic screening .and blood sugar control may help to reduce the complications of Type 2 diabetes.