Enhancers play a critical role in regulating precise gene expression patterns essential for development and cellular identity; however, how gene-enhancer specificity is encoded within the genome is not clearly defined. To investigate how this specificity arises within topologically associated domains (TAD), we performed allele-specific genome editing of sequences surrounding the Lefty1 and Lefty2 paralogs in mouse embryonic stem cells. The Lefty genes arose from a tandem duplication event and these genes interact with each other in chromosome conformation capture assays which place these genes within the same TAD.
View Article and Find Full Text PDFWhile macrophage heterogeneity during metabolic dysfunction-associated steatohepatitis (MASH) has been described, the fate of these macrophages during MASH regression is poorly understood. Comparing macrophage heterogeneity during MASH progression vs regression, we identified specific macrophage subpopulations that are critical for MASH/fibrosis resolution. We elucidated the restorative pathways and gene signatures that define regression-associated macrophages and establish the importance of TREM2 macrophages during MASH regression.
View Article and Find Full Text PDFIntroduction: Patients with chronic kidney disease (CKD) are at increased risk of developing tuberculosis (TB). These patients may also be at higher risk of developing antitubercular treatment (ATT)-associated adverse drug reactions (ADRs). Although dose modification has been recommended, data regarding the impact of impaired kidney function on ATT-associated ADRs is sparse.
View Article and Find Full Text PDFThe uterine muscular layer, or myometrium, undergoes profound changes in global gene expression during its progression from a quiescent state during pregnancy to a contractile state at the onset of labor. In this study, we investigate the role of SOX family transcription factors in myometrial cells and provide evidence for the role of SOX4 in regulating labor-associated genes. We show that Sox4 has elevated expression in the murine myometrium during a term laboring process and in two mouse models of preterm labor.
View Article and Find Full Text PDFContext: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB), are presently the major infectious diseases imposing a consequential public health threat and their coinfection has a significant impact on the outcome.
Aims: To evaluate the clinical features and outcomes of COVID-19-TB coinfected cases compared to solely COVID-19-infected cases.
Settings And Design: A retrospective observational study was conducted between August 1, 2020, to February 28, 2022, at a tertiary care hospital.