Biology subjects

Gomez, A. C.

Publications and source records attributed to Gomez, A. C..

4 recordsLinked to original sources

bioRxiv2025

Old growth attributes by chain saw: how between-patch heterogeneity changes the metacommunities of beetles in temperate forests

Metacommunity theory has expanded our understanding of how spatial dynamics and local interactions influence species communities. Different assembly archetypes, reflecting different roles of species differences, habitat differences, and dispersal have been described, but we lack empirical studies specifically in terrestrial habitats testing which archetype is most important. In a replicated design we experimentally enhanced structural between-patch heterogeneity in homogeneous production forests and developed a statistical framework controlling for sample incompleteness to detect different metacommunity processes. Meta-analyses on >100K individuals of >1.3K beetle species showed an increase of [~]60 species in heterogenized forests at {gamma}-level promoted by increasing -diversity consistent with the mass-effect and an increase of {beta}-diversity by [~]10% supporting species-sorting. Additionally, we tested {beta}-deviations from random assembly as a proxy of neutral processes. Findings indicate that enhancing structural heterogeneity can shift forests from patch-dynamics dominance towards mass-effect and species-sorting, offering a promising pathway to restore biodiversity in managed landscapes.

ecology↗

bioRxiv2025

Sirtuin 1 Activation Mitigates Murine Vasculitis Severity by Promoting Autophagy and Mitophagy

BACKGROUNDSirtuin 1 (SIRT1), a NAD+-dependent protein deacetylase, regulates cardiovascular inflammation by modulating cellular stress, inhibiting NLRP3 activation, and promoting the clearance of damaged mitochondria. However, its precise role in the pathogenesis of Kawasaki disease (KD), a pediatric systemic vasculitis and the leading cause of acquired heart disease in children, remains unclear. METHODSUsing the Lactobacillus casei cell wall extract (LCWE) murine model of KD, we evaluated the severity of vasculitis in mice supplemented with NAD+ precursors, as well as transgenic mice overexpressing SIRT1, and mice with specific deletion of Sirt1 in vascular smooth muscle cells (VSMCs) and myeloid cells. Proteomics analysis was performed on the abdominal aortas of WT and SIRT1-overexpressing mice. We performed immunofluorescent staining of cardiovascular tissues to assess the expression of proteins related to the autophagy/mitophagy pathway and the pathogenic switch of VSMCs. Western blot analysis was performed on primary VSMCs and cardiovascular tissues to determine the impact of SIRT1 on autophagic flux. The production of pro-inflammatory cytokines was measured in bone marrow-derived macrophages and peritoneal lavage of transgenic mice using ELISAs. RESULTSSIRT1 expression was downregulated in cardiovascular lesions of LCWE-injected mice, which was associated with a significant reduction of circulating levels of nicotinamide. Supplementation of mice with NAD+ precursors or genetic overexpression of SIRT1 significantly reduced the development of LCWE-induced KD, while the specific deletion of Sirt1 in VSMCs or myeloid cells exacerbated vasculitis. Proteomics analysis indicated impaired mitophagy/autophagy and the pathogenic synthetic switch of VSMCs in LCWE-injected mice, which was rescued with SIRT1 overexpression and associated with reduced production of proinflammatory cytokines. CONCLUSIONSThis study reveals the presence of an impaired NAD+-SIRT1 axis in the pathogenesis of LCWE-induced KD vasculitis and the therapeutic potential of targeting this axis to reduce cardiovascular lesions and inflammation.

immunology↗

bioRxiv2024

The intestinal microbiota contributes to the development of immune-mediated cardiovascular inflammation and vasculitis in mice.

Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease (KD), an acute pediatric vasculitis, remains unclear. We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking KD vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Oral supplementation with either of these live or pasteurized individual bacteria, or with short-chain fatty acids (SCFAs) produced by them, attenuated cardiovascular inflammation. Treatment with Amuc_1100, the TLR-2 signaling outer membrane protein from A. muciniphila, also decreased the severity of vascular inflammation. This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in KD vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins acting on gut barrier function. IN BRIEFIt remains unclear whether changes in the intestinal microbiota composition are involved in the development of cardiovascular lesions associated with Kawasaki disease (KD), an immune-mediated vasculitis. Jena et al. observe alterations in the intestinal microbiota composition of mice developing vasculitis, characterized by reduced A. muciniphila and F. prausnitzii. Oral supplementation with either of these bacteria, live or pasteurized, or with bacteria-produced short-chain fatty acids (SCFAs) or Amuc_1100, the TLR-2 signaling outer membrane protein of A. muciniphila, was sufficient to alleviate the development of cardiovascular lesions in mice by promoting intestinal barrier function. HIGHLIGHTSO_LIAbsence or depletion of the microbiota decreases the severity of vasculitis in a murine model mimicking KD vasculitis. C_LIO_LISupplementation of B. wadsworthia and B. fragilis promotes murine KD vasculitis. C_LIO_LIDecreased abundances of F. prausnitzii and A. muciniphila are associated with the development of cardiovascular lesions in mice. C_LIO_LISupplementation with either live or pasteurized A. muciniphila and F. prausnitzii, or the TLR-2 signaling Amuc_1100, reduces the severity of vasculitis by promoting gut barrier function. C_LI

immunology↗

bioRxiv2018

Genome-encoded Cytoplasmic Double-Stranded RNAs, Found in C9ORF72 ALS-FTD Brain, Provoke Propagated Neuronal Death

Innate immune signaling activation and DNA damage are pathological hallmarks of aging that may herald multiple adult-onset neurodegenerative diseases. Here, we report that both cell autonomous and non-autonomous neuronal death are triggered by the production of cytoplasmic double-stranded RNA (cdsRNA) from a regulated, disarticulated transgene in the setting of type I interferon (IFN-I) signaling. CdsRNA is a pathogen associated molecular pattern that induces IFN-I in many cell types. Transfection of a dsRNA mimetic into cultured human neurons also induces IFN-I signaling and cell death in a dose-dependent manner. Direct relevance to human disease is found in neurons of ALS-FTD patients carrying C9ORF72 intronic hexanucleotide expansions; cdsRNA isolated from these tissues is comprised of repeat sequences. Together, these findings implicate cdsRNA generated from genomic sequences in neurons as a trigger for sterile, viral-mimetic IFN-I induction and propagated neuronal death within in a neural circuit in the aging nervous system.

neuroscience↗