Epidermal growth factor (EGF) is involved in acute regulation of Na(+)/H(+) exchangers (NHEs), but the effect of chronic EGF administration on NHE gene expression is unknown. The present studies showed that EGF treatment increased NHE2-mediated intestinal brush-border membrane vesicle Na(+) absorption and NHE2 mRNA abundance by nearly twofold in 19-day-old rats. However, no changes were observed in renal NHE2 mRNA or intestinal and renal NHE3 mRNA abundance. To understand the mechanism of this regulation, we developed the rat intestinal epithelial (RIE) cell as an in vitro model to study the effect of EGF on NHE2 gene expression. EGF increased functional NHE2 activity and mRNA abundance in cultured RIE cells, and this stimulation could be blocked by actinomycin D (a transcriptional inhibitor). Additionally, NHE2 promoter reporter gene assays in transiently transfected RIE cells showed an almost twofold increase in promoter activity after EGF treatment. We conclude that rat NHE2 activity can be stimulated by chronic EGF treatment and that this response is at least partially mediated by gene transcription.
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http://dx.doi.org/10.1152/ajpcell.2001.281.2.C504 | DOI Listing |
Brief Bioinform
November 2024
Center for Artificial Intelligence Research, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States.
Pathway analysis plays a critical role in bioinformatics, enabling researchers to identify biological pathways associated with various conditions by analyzing gene expression data. However, the rise of large, multi-center datasets has highlighted limitations in traditional methods like Over-Representation Analysis (ORA) and Functional Class Scoring (FCS), which struggle with low signal-to-noise ratios (SNR) and large sample sizes. To tackle these challenges, we use a deep learning-based classification method, Gene PointNet, and a novel $P$-value computation approach leveraging the confusion matrix to address pathway analysis tasks.
View Article and Find Full Text PDFClin Cancer Res
January 2025
Stanford University, Palo Alto, CA, United States.
Purpose: After failing primary and secondary hormonal therapy, castration-resistant and neuroendocrine prostate cancer metastatic to the bone is invariably lethal, although treatment with docetaxel and carboplatin can modestly improve survival. Therefore, agents targeting biologically relevant pathways in PCa and potentially synergizing with docetaxel and carboplatin in inhibiting bone metastasis growth are urgently needed.
Experimental Design: Phosphorylated (activated) AXL expression in human prostate cancer bone metastases was assessed by immunohistochemical staining.
STAR Protoc
January 2025
Department of Statistics, University of Georgia, 310 Herty Drive, Athens, GA 30602, USA. Electronic address:
Spatial transcriptomics enhances our understanding of cellular organization by mapping gene expression data to precise tissue locations. Here, we present a protocol for using weighted ensemble method for spatial transcriptomics (WEST), which uses ensemble techniques to boost the robustness and accuracy of existing algorithms. We describe steps for preprocessing data, obtaining embeddings from individual algorithms, and ensemble integrating all embeddings as a similarity matrix.
View Article and Find Full Text PDFSci Transl Med
January 2025
Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Sci Transl Med
January 2025
Graduate Program in Human Genetics, University of Miami Miller School of Medicine, 1501 NW 10th Avenue (M-860), Miami, FL 33136, USA.
Primary mitochondrial disorders are most often caused by deleterious mutations in the mitochondrial DNA (mtDNA). Here, we used a mitochondrial DddA-derived cytosine base editor (DdCBE) to introduce a compensatory edit in a mouse model that carries the pathological mutation in the mitochondrial transfer RNA (tRNA) alanine (mt-tRNA) gene. Because the original m.
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