Biology subjects

Peralta, R.

Publications and source records attributed to Peralta, R..

4 recordsLinked to original sources

bioRxiv2026

Hypothalamic oligodendrocytes regulate systemic energy balance through Notch-dependent state transitions

The central mechanisms through which glial cells regulate whole-body metabolism remain poorly understood. Here, we identify Notch signaling in hypothalamic oligodendrocyte lineage cells as a previously unrecognized regulator of systemic energy homeostasis. Pharmacological inhibition of the Notch ligands Jagged1 (Jag1) and Jagged2 (Jag2) induces rapid and reversible weight loss across diverse physiological and metabolic contexts independently of toxicity or caloric intake. Single-nucleus transcriptomic analyses identify hypothalamic oligodendrocyte precursor cells (OPCs) as the principal Notch-responsive population following systemic Jag1/2 inhibition and reveal expansion of a metabolically specialized GPR17 intermediate state characterized by enhanced oxidative metabolism and increased predicted communication with hypothalamic neurons. This glial remodeling is accompanied by fasting-like transcriptional reprogramming of AgRP neurons, reorganization of melanocortin-autonomic circuit activity, and activation of peripheral catabolic programs. Importantly, selective deletion of Notch1/2 in hypothalamic OPCs recapitulates the major physiological and metabolic effects of systemic Jag1/2 inhibition, establishing oligodendrocyte Notch signaling as a causal regulator of whole-body metabolism. Together, our findings establish Notch-dependent oligodendrocyte state transitions as a previously unrecognized mechanism linking glial plasticity to systemic energy homeostasis.

physiology↗

bioRxiv2026

Limited Volumetric Separation Across CDR Groups in OASIS-1

Clinical Dementia Rating (CDR) scores are used to classify the cognitive state of patients and are provided within neuroimaging datasets. This is achieved through a standardized clinical assessment that evaluates participants cognitive and functional abilities in everyday life, after which they are given a score ranging from 0 to 3. Where 0 represents no signs of dementia and three represents severe dementia1. These scores are then used to track the progression of dementia over time2. This study explored if these CDR labels within the OASIS-1 dataset produced consistent volumetric separation across the hippocampus, amygdala, and cortex.

neuroscience↗

bioRxiv2021

Altered costimulatory signals and hypoxia support chromatin landscapes limiting the functional potential of exhausted T cells in cancer

Immunotherapy has changed cancer treatment with major clinical successes, but response rates remain low due in part to elevated prevalence of dysfunctional, terminally exhausted T cells. However, the mechanisms promoting progression to terminal exhaustion remain undefined. We profiled the histone modification landscape of tumor-infiltrating CD8 T cells throughout differentiation, finding terminally exhausted T cells possessed chromatin features limiting their transcriptional potential. Active enhancers enriched for bZIP/AP-1 transcription factor motifs lacked correlated gene expression, which were restored by immunotherapeutic costimulatory signaling. Epigenetic repression was also driven by an increase in histone bivalency, which we linked directly to hypoxia exposure. Our study is the first to profile the precise epigenetic changes during intratumoral differentiation to exhaustion, highlighting their altered function is driven by both improper costimulatory signals and environmental factors. These data suggest even terminally exhausted T cells remain poised for transcription in settings of increased costimulatory signaling and reduced hypoxia.

immunology↗

bioRxiv2017

Modeling the dynamics of progression of chromosomal alterations in cervical cancer: a computational model

Computational modeling has been applied to simulate the heterogeneity of cancer behavior. The development of Cervical Cancer (CC) is a process in which the cell acquires dynamic behavior among non-deleterious and deleterious mutations, exhibiting chromosomal alterations as a manifestation of this dynamic. To further determine the progression of chromosomal alterations in precursor lesions and CC, we introduce a computational model to study the dynamic of deleterious and non-deleterious mutations as an outcome of tumor progression. Analysis of chromosomal alterations mediated by our model reveals that multiple deleterious mutations are more frequent in precursor lesions than in CC. Cells with lethal deleterious mutations would be eliminated, which would mitigate cancer progression; on the other hand, cells with non-deleterious mutations would become dominant, which could predispose to cancer progression. The study of somatic alterations by computer simulations during cancer progression provides a feasible pathway for insights into the transformation of cell mechanisms in humans. During cancer progression, tumors may acquire new phenotype traits, such as the ability to invade and metastasize or to become clinically important when they develop drug resistance. Chromosomal alterations non deleterious contributes to this progression.

systems biology↗