Biology subjects

Ozkul, Y.

Publications and source records attributed to Ozkul, Y..

5 recordsLinked to original sources

bioRxiv2023

From Data to Insights: Machine Learning Empowers Prognostic Biomarker Prediction in Autism

Autism Spectrum Disorder (ASD) poses significant challenges to society and science due to its impact on communication, social interaction, and repetitive behaviour patterns in affected children. The Autism and Developmental Disabilities Monitoring (ADDM) Network continuously monitors ASD prevalence and characteristics. In 2020, ASD prevalence was estimated at one in 36 children, with higher rates than previous estimates. This study focuses on ongoing ASD research conducted by Erciyes University. Serum samples from 45 ASD patients and 21 unrelated control participants were analysed to assess the expression of 372 microRNAs (miRNAs). Six miRNAs (miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p, and miR-499a-5p) exhibited significant downregulation in all ASD patients compared to healthy controls. The current study endeavours to identify dependable diagnostic biomarkers for ASD, addressing the pressing need for non-invasive, accurate, and cost-effective diagnostic tools, as current methods are subjective and time intensive. A pivotal discovery in this study is the potential diagnostic value of miR-126-3p, offering the promise of earlier and more accurate ASD diagnoses, potentially leading to improved intervention outcomes. Leveraging machine learning, such as the K-nearest neighbours (KNN) model, presents a promising avenue for precise ASD diagnosis using miRNA biomarkers.

genomics↗

bioRxiv2023

RNA activities of trans species: RNA from the sperm of the father of an autistic child programs glial cells and behavioral disorders in mice.

Recently, we described the alteration of six miRNAs in the serum of autistic children, their fathers, mothers, siblings and in the sperm of autistic mouse models. Studies in model organisms suggest that noncoding RNAs participate in transcriptional modulation pathways. Using mice, approaches to alter the amount of RNA in fertilized eggs enable invivo intervention at an early stage of development. Noncoding RNAs are very numerous in spermatozoa. Our study aims to address a fundamental question: Can the transfer of RNA content from sperm to eggs result in changes in phenotypic traits, such as autism? To explore this, we utilized RNA from the sperm of a father with autistic children and microinjected it into fertilized mouse eggs, thus creating mouse models for autism. Here, we induced in a single step by microinjection of sperm RNA into fertilized eggs the transformation of glial cells into cells capable of developing `autism-like` disorders in mice born from these alterations.

animal behavior and cognition↗

bioRxiv2023

Experimental alteration of the microRNA profile of the mouse embryo: heritable phenotypes in the adult

We previously identified a unique genetic feature of Autism Spectrum Disorder (ASD) in human patients and established mouse models, namely the low to very low level of six microRNAs, miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p and miR-499a-5p. We attempted to interfere experimentally with the expression in the mouse of two of them, miR19a-3p and miR499a-5p by microinjecting into the one-cell embryo either the complementary sequence or an excess of the microRNA. Both approaches resulted in low levels in the somatic tissues and sperm of the targeted microRNAs (nascent) and their pri and pre precursors. The altered miRNA profiles were inherited by progenies of crosses with untreated partners together with behavior alterations partly characteristic of ASD patients and animal models. An excess of miRNA in the eggs leads to a specific downregulation, we propose variations of single-stranded miRNA, as effectors of its own transcription in eukaryotes.

molecular biology↗

bioRxiv2022

Progressive decline in the levels of six miRNAs from parents to children in autism

The growing burden of a gradual increase in births of children with autism has placed it at the center of the concerns of major laboratories. We have previously detected a decrease in the levels of six miRNAs (miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p, and miR-499a-5p) in parents and their children inherited at a lower level. Here, we suggest that down-regulation of each of these six miRNAs inherited from parents contributes to the development of children with autism. We compare their levels of distribution in each family between the autistic child and siblings. We find that the distribution of levels of these miRNAs in siblings (undiagnosed as autism) is not always higher than in autistic children, but it is at varying levels. These data support a model in which autistic behavior relies on low levels of the six miRNAs expressed in children potentially associated with autistic syndrome (ASD). The intimate link between miRNAs levels and behavioral characteristics suggests possibilities for understanding the basic circuitry involved in autism and thus advancing partial knowledge of brain functions. An early diagnosis of autism helps provide children an environment conducive to their development. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/512859v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@176d6f4org.highwire.dtl.DTLVardef@11a4ebforg.highwire.dtl.DTLVardef@280f67org.highwire.dtl.DTLVardef@b3659_HPS_FORMAT_FIGEXP M_FIG C_FIG

genetics↗

bioRxiv2019

HLA class II polymorphism influences the immune response to protective antigen and susceptibility to Bacillus anthracis

The causative agent of anthrax, Bacillus anthracis, evades the host immune response and establishes infection through the production of binary exotoxins composed of Protective Antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). The majority of vaccination strategies have focused upon the antibody response to the PA subunit. We have used a panel of humanised HLA class II transgenic mouse strains to define HLA-DR-restricted and HLA-DQ-restricted CD4+ T cell responses to the immunodominant epitopes of PA. This was correlated with the binding affinities of epitopes to HLA class II molecules, as well as the responses of two human cohorts: individuals vaccinated with the Anthrax Vaccine Precipitated (AVP) vaccine (which contains PA and trace amounts of LF), and patients recovering from cutaneous anthrax infections. The infected and vaccinated cohorts expressing different HLA types were found to make CD4+ T cell responses to multiple and diverse epitopes of PA. The effects of HLA polymorphism were explored using transgenic mouse lines, which demonstrated differential susceptibility, indicating that HLA-DR1 and HLA-DQ8 alleles conferred protective immunity relative to HLA-DR15, HLA-DR4 and HLA-DQ6. The HLA transgenics enabled a reductionist approach, allowing us to better define CD4+ T cell epitopes. Appreciating the effects of HLA polymorphism on the variability of responses to natural infection and vaccination will be vital in planning protective strategies against anthrax. Author SummaryThe bacterium responsible for causing the disease anthrax, Bacillus anthracis, produces a binary toxin composed of Protective Antigen (PA) and either Lethal Factor (LF) or Edema Factor (EF). Previous vaccination strategies have focused upon the antibody response to the PA subunit. However, within the field of bacterial immunity, there is a growing appreciation of the importance of the adaptive immune response, specifically led by CD4+ T cells. We identified long-term CD4+ T cell responses to PA epitopes following cutaneous human anthrax infection and vaccination, indicating that this toxin component is a principle B. anthracis antigen. To characterise the impact of polymorphism in HLA class II alleles at DR and DQ loci, we used transgenic mice to map the immunodominant epitopes from PA. This was correlated with survival in the transgenic lines following live anthrax challenge. We were able to demonstrate the differential impact of HLA class II alleles upon the CD4+ T cell immunodominant epitopes which shaped the immune hierarchy and therefore susceptibility to anthrax infection.

immunology↗