Biology subjects

Karatas, M.

Publications and source records attributed to Karatas, M..

5 recordsLinked to original sources

bioRxiv2025

A comparative study on promoter DNA methylation status of the CDO1 tumor suppressor gene in chronic gastritis and gastric cancer: The role of Helicobacter pylori infection

Silencing of the Cysteine dioxygenase-1 (CDO1) tumor suppressor gene by aberrant DNA methylation contributes to gastric carcinogenesis. Despite earlier data indicating that Helicobacter pylori (H. pylori) infection induces aberrant DNA methylation in the gastric mucosa, the CDO1 methylation level has not been studied in H. pylori-positive (HPP) patients with chronic gastritis. This study aimed to investigate the CDO1 methylation level in patients with chronic gastritis who have and do not have H. pylori infection, in comparison to gastric tumours. The quantitative analysis of the promoter methylation of the CDO1 gene and CDO1 immunopositivity was determined in 45 primary gastric tumors, 17 biopsy samples of HPP- chronic gastritis, 23 H. pylori-negative (HPN) chronic gastritis, and 15 normal mucosa as the control. CDO1 expression levels were measured by immunohistochemical staining, and the methylation level of the promoter region was determined by quantitative methylation-specific PCR after bisulfite conversion. CDO1 gene promoter methylation levels were significantly higher in the gastric cancer (GC) group compared to the HPN-chronic gastritis and control groups (P = 0.000). There was no significant difference between the GC group and the HPP- chronic gastritis group. The CDO1 gene promoter methylation levels were higher in the HPP- chronic gastritis group than in the HPN-chronic gastritis group (P = 0.049). There was no significant difference between the study groups for the CDO1 immunopositivity score. The CDO1 gene promoter methylation levels are increased in GC and HPP-chronic gastritis patients. The CDO1 methylation, regardless of differences in protein expression, may be a promising non-invasive marker for early diagnosis of GC in HPP-chronic gastritis patients.

biochemistry↗

bioRxiv2022

The basolateral amygdala-anterior cingulate pathway contributes to depression and its comorbidity with chronic pain

While depression and chronic pain are frequently comorbid, underlying neuronal circuits, and their relevance for the understanding of psychopathology, remain poorly defined. Here we show in mice that hyperactivity of the neuronal pathway linking the basolateral amygdala to the anterior cingulate cortex is essential for chronic pain-induced depression. In naive animals, we demonstrate that activation of this pathway is sufficient to trigger depressive-like behaviors, as well as transcriptomic alterations that recapitulate core molecular features of depression in the human brain. These alterations notably impact gene modules related to myelination and the oligodendrocyte lineage. Among these, we show that Sema4a, a hub gene significantly upregulated in both mice and humans in the context of altered mood, is necessary for the emergence of depressive-like behaviors. Overall, these results place the BLA-ACC pathway at the core of pain and depression comorbidity, and unravel the role of impaired myelination and Sema4a in mood control.

neuroscience↗

bioRxiv2020

Enzyme Kinetics and Inhibition parameters of Human Leukocyte Glucosylceramidase

Glucosylceramidase (GCase) is a lysosomal enzyme that catalyzes the cleavage of {beta}-glucosidic linkage of glucocerebroside (GC) into glucose and ceramide; thereby, plays an essential function in the degradation of complex lipids and the turnover of cellular membranes. The growing list of 460 mutations in the gene coding for it--glucosylceramidase beta acid 1 (GBA1)--is reported to abolish its catalytic activity and decrease its enzyme stability, associating it with severe health conditions such as Gaucher disease (GD), Parkinson Disease and Dementia with Lewy bodies. Although the three-dimensional structure of wild type glucosylceramidase is elucidated, little is known about its features in human cells. Moreover, alternative sources of GCase that prove to be effective in the treatment of diseases with enzyme treatment therapies, impose the need for simple and cost-effective procedures to study the enzyme behaviour. This work, for the first time, shows a well established, yet simple, cost- and time-efficient protocol for the study of GCase enzyme in human leukocytes by the artificial substrate PNPG. Characterization of the enzyme in human leukocytes for activation parameters (optimal pH, Km, and Vmax) and enzyme inhibition, was done. The results indicate that the optimum pH of GCase enzyme with PNPG is 5.1. The Km and Vmax values were 12.6mM and 333 U/mg, respectively. Gluconolactone successfully inhibits GCase in a competitive manner, with a Ki value of 0.023 mM and IC 50 of 0.047 mM. Glucose inhibition was uncompetitive with a Ki of 1.94 mM and IC50 of 55.3 mM. This is the first report for the inhibitory effect of glucose, {delta}-gluconolactone on leukocyte GCase activity.

biochemistry↗

bioRxiv2019

Mapping the living mouse brain neural architecture: strain specific patterns of brain structural and functional connectivity

Mapping the structural and functional brain connectivity fingerprints became an essential approach in neurology and experimental neuroscience because network properties can underlie behavioral phenotypes. In mouse models, revealing strain related patterns of brain wiring have a tremendous importance, since these animals are used to answer questions related to neurological or neuropsychiatric disorders. C57BL/6 and BALB/cJ inbred strains are primary \"genetic backgrounds\" for brain disease modelling and for testing therapeutic approaches. Nevertheless, extensive literature describes basal differences in the behavioral, neuroanatomical and neurochemical profiles of the two strains, which raises the question whether the observed effects are pathology specific or depend on the genetic background. Here we performed a systematic comparative exploration of brain structure and function of C57BL/6 and BALB/cJ mice via Magnetic Resonance Imaging (MRI). We combined voxel-based morphometry (VBM), diffusion MRI and high resolution fiber mapping (hrFM) and resting state functional MRI (rs-fMRI) and depicted brain-wide dissimilarities in the morphology and \"connectome\" features in the two strains. Particularly C57BL/6 animals show bigger and denser frontal cortical areas, cortico-striatal tracts and thalamic and midbrain pathways, and higher density of fibers in the genu and splenium of the corpus callosum. These features are fairly reflected in the functional connectograms that emphasize differences in \"hubness\", frontal cortical and basal forbrain connectivity. We demonstrate strongly divergent reward-aversion circuitry patterns and some variations of the default mode network features. Inter-hemispherical functional connectivity showed flexibility and adjustment regarding the structural patterns in a strain specific manner. We further provide high-resolution tractograms illustrating also inter-individual variability across inter-hemispherical callosal pathways in the BALB/cJ strain.

neuroscience↗

bioRxiv2019

Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis

Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories world-wide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline. Despite prominent cross-laboratory differences in equipment and imaging procedures, we report the reproducible identification of several large-scale resting-state networks (RSN), including a murine default-mode network, in the majority of datasets. A combination of factors was associated with enhanced reproducibility in functional connectivity parameter estimation, including animal handling procedures and equipment performance. Our work describes a set of representative RSNs in the mouse brain and highlights key experimental parameters that can critically guide the design and analysis of future rodent rsfMRI investigations.

neuroscience↗