Biology subjects

Rogers, M. F.

Publications and source records attributed to Rogers, M. F..

4 recordsLinked to original sources

bioRxiv2025

The impact of testosterone on paraventricular nucleus gene expression in male and female spontaneously hypertensive rats

BackgroundHypertension is a polygenic, complex disease that impacts men and women differently; whilst the incidence of high blood pressure (BP) is roughly equal over a lifetime, men typically are at higher risk of developing the disease earlier in life, before 50 years of age. There is adequate evidence that the brain is critical for the BP setpoint. The paraventricular nucleus (PVN) of the hypothalamus is an integrative structure that can influence not only neurohumoral responses to blood pressure changes, but also sympathetic drive. Here we manipulate the androgenic status of both male and female spontaneously hypertensive rats (SHRs) to determine how this changes gene expression within the PVN of these animals. MethodsSHR (8-weeks old) were either sham-operated or orchiectomized, whereas all females were oophorectomized, half of which received 10mg testosterone propionate subcutaneously. Mean arterial pressure (MAP) and testosterone (T) were measured by carotid cannulation and ELISA respectively. Sequencing was performed on hand-punched PVN sections and subjected to robust bioinformatic analysis. ResultsIn total, 6,571 differentially regulated genes (DRGs) are regulated in the PVN of male and female rats. High T (endogenous or replaced) correlates with higher MAP in both sexes. Orchidectomy-induced T depletion resulted in the significant regulation of 5,104 genes, involved in thousands of biological roles, including ones related to hormone and sex-hormone signalling. In the female SHR, testosterone replacement in oophorectomized animals induced the regulation of 1,727 genes, sharing many biological functions with those in the high T males. We validated key genes by qPCR to determine false discovery rate. ConclusionsT status in hypertensive rats correlates with MAP, and consistent changes in PVN transcriptome

neuroscience↗

bioRxiv2023

KDM5-mediated activation of genes required for mitochondrial biology is necessary for viability in Drosophila

The precise coordination of gene expression is critical for developmental programs, and histone modifying proteins play important, conserved roles in fine-tuning transcription for these processes. One such family of proteins are KDM5 enzymes that interact with chromatin through demethylating H3K4me3 as well as demethylase-independent mechanisms that remain less understood. The single kdm5 ortholog in Drosophila is an essential gene that has crucial developmental roles in a neuroendocrine tissue, the prothoracic gland. To characterize the regulatory functions of KDM5, we examined its role in coordinating gene expression programs critical to cellular homeostasis and organismal viability in larval prothoracic gland cells. Utilizing targeted genetic experiments, we analyzed the relationship between critical cell signaling pathways, particularly MAPK, and the lethality caused by loss of kdm5. Integrating KDM5 genome binding and transcriptomic data revealed conserved and tissue-specific transcriptional programs regulated by KDM5. These experiments highlighted a role for KDM5 in regulating the expression of a set of genes critical for the function and maintenance of mitochondria. This gene expression program is key to the essential functions of KDM5, as expression of the mitochondrial biogenesis transcription factor Ets97D/Delg, the Drosophila homolog of GABP, in prothoracic gland cells suppressed the lethality of kdm5 null animals. Consistent with this, we observed morphological changes to mitochondria in the prothoracic gland of kdm5 null mutant animals. Together, these data establish KDM5-mediated cellular functions that are both important for normal development and could also contribute to KDM5-linked disorders when dysregulated.

genetics↗

bioRxiv2019

Genetic interactions derived from high-throughput phenotyping of 7,350 yeast cell cycle mutants

Over the last 30 years, computational biologists have developed increasingly realistic mathematical models of the regulatory networks controlling the division of eukaryotic cells. These models capture data resulting from two complementary experimental approaches: low-throughput experiments aimed at extensively characterizing the functions of small numbers of genes, and large-scale genetic interaction screens that provide a systems-level perspective on the cell division process. The former is insufficient to capture the interconnectivity of the genetic control network, while the latter is fraught with irreproducibility issues. Here, we describe a hybrid approach in which the genetic interactions between 36 cell-cycle genes are quantitatively estimated by high-throughput phenotyping with an unprecedented number of biological replicates. Using this approach, we identify a subset of high-confidence genetic interactions, which we use to refine a previously published mathematical model of the cell cycle. We also present a quantitative dataset of the growth rate of these mutants under six different media conditions in order to inform future cell cycle models.\n\nAuthor SummaryThe process of cell division, also called the cell cycle, is controlled by a highly complex network of interconnected genes. If this process goes awry, diseases such as cancer can result. In order to unravel the complex interactions within the cell cycle control network, computational biologists have developed mathematical models that describe how different cell cycle genes are related. These models are built using large datasets describing the effect of mutating one or more genes within the network. In this manuscript, we present a novel method for producing such datasets. Using our method, we generate 7,350 yeast mutants to explore the interactions between key cell cycle genes. We measure the effect of the mutations by monitoring the growth rate of the yeast mutants under different environmental conditions. We use our mutants to revise an existing model of the yeast cell cycle and present a dataset of [~]44,000 gene by environment combinations as a resource to the yeast genetics and modeling communities.

systems biology↗

bioRxiv2019

Maternal antioxidant treatment prevents behavioural and neural changes in offspring exposed to prenatal social stress

Maternal exposure to social stress during pregnancy is associated with an increased risk of psychiatric disorders in the offspring in later life. However, the mechanism through which the effects of maternal stress are transmitted to the foetus is unclear. Using a rat model, we explored the mechanisms by which maternal social stress is conveyed to the foetus and the potential for targeted treatment to prevent disease in the offspring. Maternal stress increased circulating corticosterone in the mother, but not the foetuses. Maternal stress also induced oxidative stress in the placenta, but not in the foetal brain, and this was prevented by administration of a nanoparticle-bound antioxidant. Moreover, antioxidant treatment prevented prenatal stress-induced anxiety-like behaviour in the adult male offspring, along with several stress-induced neuroanatomical, neurochemical and gene expression changes in the offspring brain. Importantly, many of these neural effects were mimicked in neuronal cultures by application of placental-conditioned medium or foetal plasma from stressed pregnancies. Both placental-conditioned medium and foetal plasma contained differentially abundant extracellular microRNAs following prenatal stress. The present study highlights the crucial role of the placenta, and the molecules it secretes, in foetal brain development and provides evidence of the potential for treatment that can prevent maternal stress-induced foetal programming of neurological disease.

neuroscience↗