Biology subjects

Camacho, M.

Publications and source records attributed to Camacho, M..

6 recordsLinked to original sources

bioRxiv2026

The Canadian Pediatric Imaging Platform (C-PIP) Reference Sample: Neuroimaging Protocol and Cross-site Validation for Harmonized Multimodal Pediatric Imaging

Understanding how the human brain matures from infancy through adolescence is essential for identifying factors that influence health outcomes. Magnetic resonance imaging (MRI) provides powerful tools for characterizing structural, microstructural, functional, and metabolic aspects of brain development; however, many pediatric imaging studies are constrained by small sample sizes, limited geographic diversity, lack of longitudinal measurement, restricted age ranges, and heterogeneous acquisition protocols. While recent large-scale neuroimaging consortia have begun to address these challenges, such resources remain limited in the Canadian context, creating a critical gap. The Canadian Pediatric Imaging Platform (C-PIP) has developed a multisite neuroimaging framework across three of Canada's largest pediatric hospitals: Alberta Children's Hospital (Calgary), Centre Hospitalier Universitaire Sainte-Justine (Montreal), and the Hospital for Sick Children (Toronto). These three sites were united through a national initiative, leveraging high-performance MRI systems to accelerate Canadian neurodevelopmental research. In addition, C-PIP has implemented a centralized data sharing infrastructure to facilitate open science and collaborative research across institutions. Here, we describe the development and implementation of a multimodal MRI acquisition protocol designed to support multimodal longitudinal studies of typical and atypical brain development spanning infancy through adolescence. Within-site stability and cross-site stability of C-PIP core MRI sequences were evaluated using a travelling-participant study. The C-PIP MRI protocol establishes a harmonized, multisite imaging framework that supports large-scale investigations of pediatric brain development and disorders.

neuroscience↗

bioRxiv2025

Associations between amygdala connectivity and experienced discrimination in children

Discrimination is a chronic stressor linked to adverse health outcomes, particularly in racial and ethnic minorities. Understanding associations between early discrimination and the brain in childhood may help identify mechanisms through which discrimination impacts future health. Data from 4512 children (ages 9-11) and a subsample of Black, Indigenous, and People of Color (BIPOC; N = 1567) from the Adolescent Brain and Cognitive Development (ABCD) Study(R) was used to create linear mixed-effects models that evaluated associations between Perceived Discrimination (PD) and amygdala resting-state fMRI connectivity (AC) to the salience network (SN), default mode network (DMN), and thalamus. PD was measured using the youth self-reported PD Scale. Results indicated that greater PD significantly predicted greater AC to the right thalamus in our full sample. In secondary analyses, environmental and behavioral factors were evaluated as potential moderators for associations significant at least at a trend level in both our full sample and BIPOC subsample. In our BIPOC subsample, traumatic events experienced moderated the relationship between PD and AC to the anterior cingulate cortex (ACC; SN), such that greater traumatic experiences predicted stronger positive associations between PD and this connection. Results suggest PD impacts neural connections in early life, highlighting the need to consider the impact of discrimination on risk for psychopathology.

neuroscience↗

bioRxiv2025

Restoring Cholesterol Efflux in Vascular Smooth Muscle Cells Transitioning into Foam Cells Through Liver X Receptor Activation

ObjectiveMacrophage foam cells derived from vascular smooth muscle cells (VSMCs) account for 30-70% of foam cells in atherosclerotic lesions. Liver X receptor (LXR) agonists promote high-density lipoprotein (HDL)-mediated cholesterol efflux from macrophages. This study aimed to investigate the effects of LXR activation on the reverse cholesterol transport (RCT) rate from VSMCs to feces in vivo. Approach and ResultsCholesterol efflux induced by serum and HDL was evaluated in human and mouse VSMCs treated with the LXR agonist T090137 before and after methyl-{beta}-cyclodextrin (MBD)-cholesterol loading. Additional experiments included treatment with an acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitor. Cholesterol-radiolabeled VSMCs were injected into the peritoneal cavity of mice, and RCT was assessed by measuring radiolabeled cholesterol in serum, liver, and feces over 48 hours. Serum and HDL induced cholesterol efflux at similar levels in both human and mouse VSMCs. Cholesterol efflux was significantly reduced following MBD-cholesterol loading; however, treatment with the LXR agonist significantly enhanced efflux. Radiolabeled foam-like VSMCs injected into mice exhibited impaired cholesterol transfer to serum, HDL, and feces compared to non-lipid-laden VSMCs. Pre-treatment with the LXR agonist increased radiolabeled cholesterol levels in serum and HDL and doubled its fecal excretion. Additionally, LXR activation restored RCT from MBD-cholesterol-loaded VSMCs to feces, reaching levels comparable to those of non-lipid-laden cells. Treatment with an ACAT inhibitor fully restored RCT rates in foam-like VSMCs, and the combination of the ACAT inhibitor and the LXR agonist further enhanced RCT. ConclusionsHDL-mediated cholesterol efflux is significantly impaired in VSMCs during their transition into foam cells. Pharmacological activation of LXR enhances RCT from VSMCs to feces in vivo and restores the impaired RCT from transitioning VSMCs. The combination of LXR agonists and ACAT inhibitors holds promise as a synergistic therapeutic approach to restoring cholesterol homeostasis in lipid-laden VSMCs, offering potential strategies to mitigate atherosclerosis. HighlightsO_LILXR activation enhances cholesterol efflux in VSMCs in vitro, even after their transition into foam cells. C_LIO_LIVSMCs transitioning into foam cells exhibit reduced cholesterol transfer to HDL and feces in mice. C_LIO_LILXR agonist treatment enhances reverse cholesterol transport (RCT) from VSMCs to feces in vivo. C_LIO_LISelective ACAT inhibition restores RCT in foam-like VSMCs, with further enhancement observed upon LXR activation. C_LI

biochemistry↗

bioRxiv2024

Extinction potential from invasive alien species

Biological invasions threaten biodiversity, ecosystem services, human health, and cultural heritage, yet their impacts are often underappreciated, leading to insufficient management efforts and suboptimal conservation results. We argue that the lack of quantitative, continuous metrics of impact of invasive alien species (IAS) contribute this lack of appreciation. To bridge this knowledge-action gap, we propose the Extinction Potential Metric (EPM), a suite of quantitative metrics designed to assess the ecological damage caused by IAS. The EPM score of an IAS is the number of current and future species extinctions attributable to this IAS over the next 50 years under a business-as-usual scenario. EPM includes three variants: EPM-A (absolute EPM), EPM-R (relative EPM, which accounts for other anthropogenic pressures), and EPM-U (EPM for Unique species, adjusted for phylogenetic uniqueness of impacted native species), to capture different dimensions of IAS impacts. We applied EPM to evaluate the impact of IAS on 2178 amphibians, 920 birds, 865 reptiles, and 473 mammals. Our analyses revealed that the impact of the worst IAS was between 90 and 380 times higher than any IAS with an impact of 1 extinct native species. Importantly, several of the most impactful IAS disproportionately affect evolutionarily unique native species. The EPM framework offers a standardised approach for measuring ecological impacts of IAS but also other anthropogenic pressures at different spatial, temporal, and taxonomic scales. EPM could also guide the development of standardised indicators for assessing the impacts of other anthropogenic stressors. Ultimately, EPM will pave the way to answer ecological questions important to design better conservation policies, to enhance the management of biological invasions and reach global biodiversity conservation goals.

ecology↗

bioRxiv2021

Control of neurotransmitter release and presynaptic plasticity by re-orientation of membrane-bound Munc13-1

Munc13-1 plays a central role in neurotransmitter release through its conserved C-terminal region, which includes a diacyglycerol (DAG)-binding C1 domain, a Ca2+/PIP2-binding C2B domain, a MUN domain and a C2C domain. Munc13-1 was proposed to bridge synaptic vesicles to the plasma membrane in two different orientations mediated by distinct interactions of the C1C2B region with the plasma membrane: i) one involving a polybasic face that yields a perpendicular orientation of Munc13-1 and hinders release; and ii) another involving the DAG-Ca2+-PIP2-binding face that induces a slanted orientation and facilitates release. Here we have tested this model and investigated the role of the C1C2B region in neurotransmitter release. We find that K603E or R769E point mutations in the polybasic face severely impair synaptic vesicle priming in primary murine hippocampal cultures, and Ca2+-independent liposome bridging and fusion in in vitro reconstitution assays. A K720E mutation in the polybasic face and a K706E mutation in the C2B domain Ca2+-binding loops have milder effects in reconstitution assays and do not affect vesicle priming, but enhance or impair Ca2+-evoked release, respectively. The phenotypes caused by combining these mutations are dominated by the K603E and R769E mutations. Our results show that the C1-C2B region of Munc13-1 plays a central role in vesicle priming and support the notion that re-orientation of Munc13-1 controls neurotransmitter release and short-term presynaptic plasticity.

neuroscience↗

bioRxiv2019

Rational programming of history-dependent logic in cellular populations.

Genetic programs operating in an history-dependent fashion are ubiquitous in nature and govern sophisticated processes such as development and differentiation. The ability to systematically and predictably encode such programs would advance the engineering of synthetic organisms and ecosystems with rich signal processing abilities. Here we implement robust, scalable history-dependent programs by distributing the computational labor across a cellular population. Our design is based on recombinase-driven DNA scaffolds expressing different genes according to the order of occurrence of inputs. These multicellular computing systems are highly modular and any program can be built by differential composition of strains containing well-characterized logic scaffolds. We developed an automated workflow that researchers can use to streamline program design and optimization. We anticipate that the history-dependent programs presented here will support many applications using cellular populations for material engineering, biomanufacturing and healthcare.\n\nOne Sentence SummarySystematic and automated frameworks for implementing robust history-dependent genetic programs in cellular populations.

synthetic biology↗