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Biology subjects

Kaya, H.

Publications and source records attributed to Kaya, H..

5 recordsLinked to original sources

Sex chromosomes shape the transcriptional landscape of the preimplantation mouseembryo

Sex chromosomes are emerging as key regulators of adult health and disease in males (XY) and females (XX), but their impact on embryo development is poorly understood. Using single-cell RNA sequencing (scRNA-seq) on wild type and aneuploid mouse embryos, we show that sex chromosomes significantly shape the preimplantation embryo transcriptional landscape. A hierarchy of effects are identified, distinctly mediated by the Y chromosome, the dosage of X chromosomes, X-chromosome imprinting, and by Xist, the non-coding RNA that initiates X-inactivation. The sex chromosomes have strong trans effects on autosomal gene expression throughout preimplantation development. The Y chromosome has an unexpectedly pronounced impact on the trophectoderm, the precursor of the placenta, and this property is shared with genes expressed from the inactive X chromosome. The paternal and maternal X chromosomes differentially promote preimplantation growth, and we identify multiple novel candidate X-linked imprinted genes mediating this effect. Our findings show that sex chromosomes impact the embryo from the beginning of life, long before the appearance of overt sex differences.

developmental biology↗

Neutralizing antibody levels and epidemiological information of patients with breakthrough COVID-19 infection in Toyama, Japan

Breakthrough infection (BI) after coronavirus disease 2019 (COVID-19) vaccination has exploded owing to the emergence of various SARS-CoV-2 variants and has become a major problem at present. In this study, we analyzed the epidemiological information and possession status of neutralizing antibodies in patients with BI using SARS-CoV-2 pseudotyped viruses (SARS-CoV-2pv). Analysis of 44 specimens diagnosed with COVID-19 after two or more vaccinations showed high inhibition of infection by 90% or more against the Wuhan strain and the Alpha and Delta variants of pseudotyped viruses in 40 specimens. In contrast, almost no neutralizing activity was observed against the Omicron BA.1 variant. Many cases without neutralizing activity or BI were immunosuppressed individuals. The results of this study show that BI occurs even when there are sufficient neutralizing antibodies in the blood due to exposure to close contacts at the time of infection. Thus, even after vaccination, sufficient precautions must be taken to prevent infection.

microbiology↗

TAF4b transcription networks regulating early oocyte differentiation

Establishment of a healthy ovarian reserve is contingent upon numerous regulatory pathways during embryogenesis. Previously, mice lacking TBP-associated factor 4b (Taf4b) were shown to exhibit a diminished ovarian reserve. However, potential oocyte-intrinsic functions of TAF4b have not been examined. Here we use a combination of gene expression profiling and chromatin mapping to characterize the TAF4b gene regulatory network in mouse oocytes. We find that Taf4b-deficient oocytes display inappropriate expression of meiotic, chromatin, and X-linked genes, and unexpectedly we found a connection with Turner Syndrome pathways. Using Cleavage Under Targets and Release Using Nuclease (CUT&RUN), we observed TAF4b enrichment at genes involved in meiosis and DNA repair, some of which are differentially expressed in Taf4b-deficient oocytes. Interestingly, TAF4b target genes were enriched for Sp/KLF family motifs rather than TATA-box, suggesting an alternate mode of promoter interaction. Together, our data connects several gene regulatory nodes that contribute to the ovarian reserve.

developmental biology↗

Impaired expression of chloroplast HSP90C chaperone activates plant defense responses leading to a disease symptom-like phenotype

RNA-seq analysis of a transgenic tobacco plant, i-hpHSP90C, in which chloroplast HSP90C genes can be silenced in an artificially inducible manner resulting in the development of chlorosis, revealed the up- and down-regulation of 2746 and 3490 genes, respectively. Gene Ontology analysis of these differentially expressed genes indicated the upregulation of ROS-responsive genes, the activation of the innate immunity and cell death pathways, and the downregulation of genes involved in photosynthesis, plastid organization, and cell cycle. Cell death was confirmed by trypan blue staining and electrolyte leakage assay and the H2O2 production by diaminobenzidine staining. The upregulation of ER stress-responsive genes suggested the interplay between ER protein quality control and chloroplast or immune response. The results collectively suggest that the reduced levels of HSP90C chaperone leads the plant to develop chlorosis primarily through the global downregulation of chloroplast and photosynthesis-related genes and additionally through the light-dependent production of ROS, followed by the activation of immune responses including the cell death. HighlightInduced silencing of HSP90C gene caused the upregulation of stress-responsive genes and the activation of innate immune response, which resulted in the chlorosis development accompanying cell death.

plant biology↗

Glucocorticoid receptor gene polymorhisms and breast cancer: significant association in cancerous tissue samples from Turkish patients

Background and Aims: Glucocorticoid receptor (GR) has been postulated to serve an important role in normal breast and breast carcinoma. On the other hand, studies on its common polymorphisms with breast cancer are very limited. In this study, we aimed to assess the presence and frequency of 4 common polymorphisms of the GR gene in the cancerous tissue samples from breast cancer patients in the Turkish population and compare them with healthy individuals. Methods: DNA samples from 86 Turkish female breast cancer patients and 86 healthy controls analysed for BclI, Tth111I, N363S and ER22/23EK polymorphisms of GR gene by PCR-RFLP. Results: N363S polymorphism was not observed in study samples. Frequency of BclI polymorphism did not differ between cases and controls but it associated with family history of cancer. The polymorphic allele frequency of Tth111I and ER22/23EK was found to be higher in cases compared to healthy samples (p<0.05). Also, a haplotype containing polymorphic variants of these two polymorphisms found to be associated with breast cancer. Conclusion: The data presented here suggest that polymorphisms of GR gene may be an important risk factor for breast cancer predisposition.

cancer biology↗