Biology subjects

Reyes, G.

Publications and source records attributed to Reyes, G..

5 recordsLinked to original sources

bioRxiv2026

Area-level context and functional brain organization across the lifespan

The neighborhoods children grow up in are associated with cognitive and mental health outcomes across the lifespan. Yet how neighborhood-level factors are quantified, and how they relate to large-scale functional brain connectivity, remains an emerging area of investigation. This scoping review synthesizes empirical evidence on associations between area-level factors and resting-state functional brain connectivity and network organization. We included studies assessing resting-state fMRI functional connectivity or rs-fMRI-derived intrinsic activity in relation to validated area-level deprivation indices guided by Trinidad et al.s (2022) inventory, the Opportunity Atlas, or geocoded crime exposure from the Uniform Crime Reporting program. Of the 28 studies meeting inclusion criteria, the evidence base was unevenly distributed across the lifespan; 25 of 28 (89.3%) examined perinatal, childhood, or adolescent samples, while only one examined adults exclusively. The literature was also methodologically non-independent, over half drew on the Adolescent Brain and Cognitive Development (ABCD) Study, and the Area Deprivation Index was the most commonly used measure (k = 16, 57.1%). Therefore, apparent convergence partly reflects shared data and instruments rather than independent replication. Where directions could be compared, higher area-level disadvantage was associated predominantly with lower within-network connectivity in association and control systems and higher connectivity in somatomotor systems, with several findings attenuating once area-level exposure was isolated from household socioeconomic status. Geographic resolution varied but was rarely justified. Progress will require greater theoretical intentionality in selecting area-level measures, transparent justification of geographic resolution, treatment of dataset and measure non-independence, and investment in understudied developmental periods and non-US contexts.

neuroscience↗

bioRxiv2026

Designed Minibinders Rewire Receptor Signaling to Enable Functional Human Myogenic Reprogramming

Sarcopenia, loss of muscle mass is a considerable health burden that demands immediate societal attention. Direct myogenic somatic cell reprogramming, a potential muscle regeneration method is constrained by an inability to control the signaling logic that governs cell fate. Here, we show that this barrier can be overcome using AI-designed receptor modulators. Screening de novo minibinders, we identify a synthetic protein cocktail, C6-DPC, that drives efficient human fibroblast-to-muscle transdifferentiation with robust structural and metabolic maturation. C6-DPC reprograms extracellular signaling by activating pro-myogenic FGFR1/2c pathways while suppressing anti-myogenic inputs through ALK1 and TGFBR2; targeted depletion of ALK1 is sufficient to lower the reprogramming barrier. Inflammatory signaling via gp130 emerges as a dominant checkpoint, and its inhibition further enhances conversion. Engineered tissues generate high twitch and tetanic forces in both wild-type and dystrophin-deficient human cells. These findings demonstrate that programmable synthetic ligands can rewrite receptor-level signaling to direct cell fate and enable functional tissue regeneration.

biochemistry↗

bioRxiv2024

1 Microbiome determinants of productivity in whiteleg shrimp aquaculture

Aquaculture holds immense promise for addressing the food needs of our growing global population. Yet, a quantitative understanding of the factors that control its efficiency and productivity has remained elusive. In this study, we address this knowledge gap by focusing on the microbiome determinants of productivity, more specifically animal survival and growth, for one of the most predominant animal species in global aquaculture, whiteleg shrimp (Penaeus vannamei). Through analysis of the shrimp-associated microbiome from 610 aquaculture samples across Asia and Latin America, we established the presence of core phylogenetic groups, widely prevalent across aquaculture conditions in disparate geographic locations and including both pathogenic and beneficial microbes. Focusing on early stages of growth (larval hatcheries), we showed that the composition of the microbiome alone can predict approximately 50% of the variation in shrimp larvae survival rates. Taxa associated with high survival rates share recently acquired genes that appear to be specific to aquaculture conditions. These genes are involved in the biosynthesis of growth factors and in protein degradation, underscoring the potential role of beneficial microorganisms in nutrient assimilation. In contrast, the predictability of the microbiome on the adult shrimp weight in grow-out farms is weaker (10-20%), akin to observations in the context of livestock. In conclusion, our study unveils a novel avenue for predicting productivity in shrimp aquaculture based on microbiome analysis. This paves the way for targeted manipulation of the microbiome as a strategic approach to enhancing aquaculture efficiency from the earliest developmental stages.

microbiology↗

bioRxiv2023

Maintenance of pig brain function under extracorporeal pulsatile circulatory control (EPCC)

Selective vascular access to the brain is desirable in metabolic tracer, pharmacological and other studies aimed to characterize neural properties in isolation from somatic influences from chest, abdomen or limbs. However, current methods for artificial control of cerebral circulation can abolish pulsatility-dependent vascular signaling or neural network phenomena such as the electrocorticogram even when preserving individual neuronal activity. Thus, we set out to mechanically render cerebral hemodynamics fully regulable to replicate or modify native pig brain perfusion. To this end, blood flow to the head was surgically separated from the systemic circulation and full extracorporeal pulsatile circulatory control (EPCC) delivered via a modified aorta or brachiocephalic artery. This control relied on a computerized algorithm that maintained, for several hours, blood pressure, flow and pulsatility at near-native values individually measured before EPCC. Continuous electrocorticography and brain depth electrode recordings were used to evaluate brain activity relative to the standard offered by awake human electrocorticography. Under EPCC, this activity remained unaltered or minimally perturbed compared to the native circulation state, as did cerebral oxygenation, pressure, temperature and microscopic structure. Thus, our approach enables the study of neural activity and its circulatory manipulation in independence of most of the rest of the organism.

neuroscience↗

bioRxiv2019

Mitochondrial protein interaction landscape of SS-31

Mitochondrial dysfunction underlies the etiology of a broad spectrum of diseases including heart disease, cancer, neurodegenerative diseases, and the general aging process. Therapeutics that restore healthy mitochondrial function hold promise for treatment of these conditions. The synthetic tetrapeptide, elamipretide (SS-31), improves mitochondrial function, but mechanistic details of its pharmacological effects are unknown. Reportedly, SS-31 primarily interacts with the phospholipid cardiolipin in the inner mitochondrial membrane. Here we utilize chemical cross-linking with mass spectrometry to identify protein interactors of SS-31 in mitochondria. The SS-31-interacting proteins, all known cardiolipin binders, fall into two groups, those involved in ATP production through the oxidative phosphorylation pathway and those involved in 2-oxoglutarate metabolic processes. Residues cross-linked with SS-31 reveal binding regions that in many cases, are proximal to cardiolipin-protein interacting regions. These results offer the first glimpse of the protein interaction landscape of SS-31 and provide new mechanistic insight relevant to SS-31 mitochondrial therapy. Significance StatementSS-31 is a synthetic peptide that improves mitochondrial function and is currently undergoing clinical trials for treatments of heart failure, primary mitochondrial myopathy, and other mitochondrial diseases. SS-31 interacts with cardiolipin which is abundant in the inner mitochondrial membrane, but mechanistic details of its pharmacological effects are unknown. Here we apply a novel chemical cross-linking/mass spectrometry method to provide the first direct evidence for specific interactions between SS-31 and mitochondrial proteins. The identified SS-31 interactors are functional components in ATP production and 2-oxoglutarate metabolism and signaling, consistent with improved mitochondrial function resultant from SS-31 treatment. These results offer the first glimpse of the protein interaction landscape of SS-31 and provide new mechanistic insight relevant to SS-31 mitochondrial therapy.

systems biology↗