ORCID Profile
0000-0002-1615-7331
Current Organisation
Colorado State University
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Publisher: Elsevier BV
Date: 2022
Publisher: Cold Spring Harbor Laboratory
Date: 17-08-2020
DOI: 10.1101/2020.08.13.249813
Abstract: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. We conducted the largest to date genome-wide genotype–by–sex (GxS) interaction of risk for these disorders, using 85,735 cases (33,403 SCZ, 19,924 BIP, 32,408 MDD) and 109,946 controls from the Psychiatric Genomics Consortium (PGC) and iPSYCH. Across disorders, genome-wide significant SNP-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815 p =3.2×10 −8 ), that interacts with sodium otassium-transporting ATPase enzymes implicating neuronal excitability. Three additional loci showed evidence ( p ×10 −6 ) for cross-disorder GxS interaction (rs7302529, p =1.6×10 −7 rs73033497, p =8.8×10 −7 rs7914279, p =6.4×10 −7 ) implicating various functions. Gene-based analyses identified GxS interaction across disorders ( p =8.97×10 −7 ) with transcriptional inhibitor SLTM . Most significant in SCZ was a MOCOS gene locus (rs11665282 p =1.5×10 −7 ), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509 p =1.1×10 −7 ) in a locus containing IDO2 , a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant GxS of genes regulating vascular endothelial growth factor (VEGF) receptor signaling in MDD ( p FDR .05). In the largest genome-wide GxS analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development, immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway enrichment levels.
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.GEP.2009.03.004
Abstract: The tescalcin gene (Tesc) encodes an EF-hand calcium-binding protein that interacts with the sodium/hydrogen exchanger, NHE1. Previous studies indicated that Tesc was expressed in mouse embryonic testis, but not in ovary, during the critical period of testis and ovary determination. In this paper we compared the expression of Tesc in embryonic tissues of chicken and mouse. Tesc expression was sexually dimorphic in the embryonic gonads of both mouse and chicken. Tescalcin (TESC) was detected in both Sertoli cells and germ cells. In the embryonic brain of both mouse and chicken, Tesc was highly expressed in the nasal placode and in fibers extending from the olfactory epithelium to the primordial olfactory bulb. Tesc was expressed in the embryonic heart of both chicken and mouse. In mouse Tesc expression was also detected in embryonic adrenal. These studies indicate very specific expression of Tesc in various tissues in chicken and mouse during embryologic development, and conservation of Tesc expression in both species.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.BIOS.2018.04.009
Abstract: The ability to view biological events in real time has contributed significantly to research in the life sciences. While video capture of real time changes in anatomical relationships is important, it is equally important to visualize real time changes in the chemical communications that drive cell behaviors. This paper describes an electrochemical imaging system capable of capturing changes in chemical gradients in live tissue slices. The system consists of a CMOS microchip with 8192 configurable Pt surface electrodes, on-chip potentiostat, on-chip control logic, and a microfluidic device designed to interface with the CMOS chip to support ex vivo tissue experimentation. All data processing and visualization methods, sensor calibrations, microfluidics fabrication, and tissue preparation and handling procedures are described. Using norepinephrine as a target analyte for proof of concept, the system is capable of differentiating concentrations of norepinephrine as low as 8 µM and up to 1024 µM with a linear response and a spatial resolution of 25.5 µm × 30.4 µm. Electrochemical imaging was tested using murine adrenal tissue as a biological model and successfully showed caffeine-stimulated release of catecholamines from live slices of adrenal tissue with temporal sensitivity. This system successfully demonstrates the use of a high-density microelectrode array for electrochemical analysis with high spatiotemporal resolution to gather chemical gradient information in parallel with optical microscopy recordings.
Location: United States of America
No related grants have been discovered for Stuart Tobet.