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Nieto, J.

Publications and source records attributed to Nieto, J..

5 recordsLinked to original sources

Epileptogenesis dynamics driven by peritumoral circuit rewiring in gangliogliomas

Gangliogliomas (GGs) are emblematic low-grade epilepsy-associated tumors, yet the developmental mechanisms underlying their epileptogenicity remain unclear. Here, we investigated how tumor-network interactions evolve across postnatal maturation using an in-utero electroporated BRAFV600E-driven mouse model combining multiscale electrophysiology with histology, single-nucleus RNA sequencing, and complementary analyses in human GG tissue. We show that GGs induce early and evolutive modification of cortical organization and glioneuronal architecture. Despite glioneuronal preservation, seizure initiation shifted from distal cortical regions at postnatal stages to tumor-adjacent areas in adult networks. In both mouse and human, GG slices exhibited seizure activity localized to the peritumoral cortex. At the cellular level, neurons exhibited a developmental arrest of intrinsic electrophysiological maturation from postnatal to adult stages. Transcriptomic profiling identified stage-specific neuronal remodeling, with early alterations in inhibitory neurons and later changes affecting excitatory populations. Such developmental spatial seizure dynamics were associated with a pharmacological shift as NKCC1 inhibition with bumetanide selectively reduced seizure-like activity in neonatal but not mature tumor networks, indicating a restricted window of chloride-dependent epileptogenesis relevant to GABAergic maturation. Together, our results demonstrate that GG-associated epileptogenesis arises from developmentally regulated tumor-network interactions, highlighting distinct cellular and molecular mechanisms across maturation and revealing potential age-specific therapeutic targets.

neuroscience↗

Artificial intelligence-driven morphology-based enrichment of malignant cells from body fluid

Cell morphology is a fundamental feature used to evaluate patient specimens in pathological analysis. However, traditional cytopathology analysis of patient effusion samples is limited by low tumor cell abundance coupled with high background of non-malignant cells, restricting the ability for downstream molecular and functional analyses to identify actionable therapeutic targets. We applied the Deepcell platform that combines microfluidic sorting, brightfield imaging, and real-time deep learning interpretations based on multi-dimensional morphology to enrich carcinoma cells from malignant effusions without cell staining or labels. Carcinoma cell enrichment was validated with whole genome sequencing and targeted mutation analysis, which showed higher sensitivity for detection of tumor fractions and critical somatic variant mutations that were initially at low-levels or undetectable in pre-sort patient samples. Combined, our study demonstrates the feasibility and added value of supplementing traditional morphology-based cytology with deep learning, multi-dimensional morphology analysis, and microfluidic sorting.

pathology↗

We think what we eat: Animal-based diet influences cerebral and microbiota networks connectivity in early ages. A study case of an indigenous community in Mexico.

We are not individuals, we are much better described as ecosystems due to trillions of bacteria and other microorganisms that inhabit us. We now know that gut microbiota can greatly influence many physiological parameters that in turn may impact several cognitive functions, such as learning, memory, and decision making processes. This mutualistic symbiotic relation known as the gut-brain axis is also constrained by external factors such as dietary habits such as animal protein and lipids intake. Using a novel combination of Machine Learning and Network Theory techniques, we provide evidence from an indigenous population in Guerrero Mexico, that both brain and gut-microbiota connectivity, evaluated by Minimum Spanning Tree as the critical backbone of information flow, diminish under either low protein or lipids intake. We discuss then how this loss of connectivity may translate into a reduction of the individuals capacity to cope with perturbations as loss of connectivity may be linked with losses in antifragility.

neuroscience↗

Human gut microbiota networks disturbance by parasites in indigenous communities: Effect on bacteria genera related to depression incidence subnetworks

If you think you are in control of your behavior, think again. Evidence suggests that behavioral modifications, as development and persistence of depression, may be the consequence of a complex network of communication between macro (i.e. parasites) and micro-organisms capable of modifying the physiological axis of the host. Some parasites cause significant nutritional deficiencies for the host and impair the effectiveness of cognitive processes such as memory, teaching or non-verbal intelligence. Bacterial communities mediate the establishment of parasites and vice versa but this complexity approach remains little explored. We study the gut microbiota-parasite interactions using novel techniques of network analysis using data of individuals from two indigenous communities in the state of Guerrero, Mexico. Our results suggest that A. Lumbricoides, induce a gut microbiota perturbation affecting subnetworks of key species related to depression, consisting in the loss of network features such as path length, heterogeneity, number of nodes and neighbors; and especially by the loss of information emergence. Emergence is related with adaptability that has been linked to the concept of health as a critical balance between (adaptability) and self-organization (robustness). In this way, the loss of emergence means a depart from criticality and ultimately loss of health.

ecology↗

Self-reported Health is Related to Body Height and Waist Circumference in Rural Indigenous and Urbanized Latin-American Populations

Body height is a life-history component. It involves important costs for its expression and maintenance, which may originate trade-offs on other costly components such as reproduction or immunity. Although previous evidence has supported the idea that human height could be a sexually selected trait, the explanatory mechanisms that underlie this selection are poorly understood. Despite extensive studies on the association between height and attractiveness, the role of immunity in linking this relation is scarcely studied, particularly in non-Western populations. Here, we tested whether human height is related to health measured by self-perception, and relevant nutritional and health anthropometric indicators in three Latin-American populations that widely differ in socioeconomic and ecological conditions: two urbanised populations from Bogota (Colombia) and Mexico City (Mexico), and one isolated indigenous population (MePhaa, Mexico). Results showed that self-reported health is best predicted by an interaction between height and waist circumference, and the costs associated with large waist circumference are height-dependent, affecting taller people more than shorter individuals. If health and genetic quality cues play an important role in human mate-choice, and height and waist interact to signal health, its evolutionary consequences, including cognitive and behavioural effects, should be addressed in future research.

evolutionary biology↗