Biology subjects

Eby, H.

Publications and source records attributed to Eby, H..

3 recordsLinked to original sources

bioRxiv2026

Sex-Specific Modulation of Gene Expression by 17beta-Estradiol in Human Meniscal Cells: Pathways to Targeted Osteoarthritis Therapies

Osteoarthritis (OA) disproportionately affects women, and estrogen has been implicated in cartilage and joint homeostasis, yet its effects on meniscal fibrochondrocytes (MFCs), and whether those effects differ by sex, remain poorly defined. We reanalyzed a publicly available RNA-sequencing dataset (Gene Expression Omnibus, GSE199087) comprising human MFCs from a male and a female donor treated with 17{beta}-estradiol (E2) or vehicle. Differential expression, Gene Set Enrichment Analysis, Enrichr, and iLINCS were integrated to identify the transcriptional programs modulated by E2 in each sex. In female MFCs, E2 upregulated pathways governing DNA replication, cell-cycle progression, and genomic maintenance (e.g., MCM8, BRCA1, RAD51), while downregulating inflammatory and extracellular matrix-degrading genes, including MMP1, IL12A, CXCL12, and MYD88. In male MFCs, E2 instead upregulated chromatin remodeling and developmental signaling programs, led by SRCAP, ERCC6, and NOTCH1, and downregulated antigen presentation and mitochondrial genes. These divergent responses indicate that E2 engages distinct, sex-specific transcriptional programs in MFCs, with the female profile favoring proliferation and matrix preservation. Although derived from a limited sample and therefore hypothesis-generating, these findings nominate candidate mechanisms underlying sex differences in meniscal biology and OA susceptibility, and warrant validation in larger, sex-balanced cohorts. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/740612v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@16026fforg.highwire.dtl.DTLVardef@1a048acorg.highwire.dtl.DTLVardef@3246corg.highwire.dtl.DTLVardef@4c598b_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2023

Neuronal alterations in AKT isotype expression in schizophrenia

Schizophrenia is characterized by substantial alterations in brain function, and previous studies suggest insulin signaling pathways, particularly involving AKT, are implicated in the pathophysiology of the disorder. This study demonstrates elevated mRNA expression of AKT1-3 in neurons from schizophrenia subjects, contrary to unchanged or diminished total AKT protein expression reported in previous postmortem studies, suggesting a potential decoupling of transcript and protein levels. Sex-specific differential AKT activity was observed, indicating divergent roles in males and females with schizophrenia. Alongside AKT, upregulation of PDK1, a critical component of the insulin signaling pathway, and several protein phosphatases known to regulate AKT were detected. Moreover, enhanced expression of the transcription factor FOXO1, a regulator of glucose metabolism, hints at possible compensatory mechanisms related to insulin signaling dysregulation. Findings were largely independent of antipsychotic medication use, suggesting inherent alterations in schizophrenia. These results highlight the significance of AKT and related signaling pathways in schizophrenia, proposing that these changes might represent a compensatory response to a primary defect of insulin signaling. This research underscores the need for a detailed understanding of these signaling pathways for the development of effective therapeutic strategies.

neuroscience↗

bioRxiv2020

Kaleidoscope: A New Bioinformatics Pipeline Web Application for In Silico Hypothesis Exploration of Omics Signatures

BackgroundIn silico data exploration is a key first step of exploring a research question. There are many publicly available databases and tools that offer appealing features to help with such a task. However, many applications lack exposure or are constrained with unfriendly or outdated user interfaces. Thus, it follows that there are many resources that are relevant to investigation of medical disorders that are underutilized. ResultsWe developed an R Shiny web application, called Kaleidoscope, to address this challenge. The application offers access to several omics databases and tools to let users explore research questions in silico. The application is designed to be user- friendly with a unified user interface, while also scalable by offering the option of uploading user-defined datasets. We demonstrate the application features with a starting query of a single gene (Disrupted in schizophrenia 1, DISC1) to assess its protein-protein interactions network. We then explore expression levels of the gene network across tissues and cell types in the brain, as well as across 34 schizophrenia versus control differential gene expression datasets. ConclusionKaleidoscope provides easy access to several databases and tools under a unified user interface to explore research questions in silico. The web application is open-source and freely available at https://kalganem.shinyapps.io/Kaleidoscope/. This application streamlines the process of in silico data exploration for users and expands the efficient use of these tools to stakeholders without specific bioinformatics expertise.

bioinformatics↗