Biology subjects

Cardenas, F.

Publications and source records attributed to Cardenas, F..

4 recordsLinked to original sources

bioRxiv2026

Breaking the link between demyelination and axon loss: SARM1 inhibition as a neuroprotective strategy for multiple sclerosis

Axonal degeneration is a principal driver of irreversible neurological disability in multiple sclerosis (MS), yet current treatments fail to target this neurodegenerative phase directly. Sterile alpha and TIR domain-containing protein 1 (SARM1) has emerged as an executioner of programmed axon destruction and is overexpressed in grey and white matter MS tissue, making its inhibition a promising therapeutic strategy. However, the effects of SARM1 inhibition on localized neurodegeneration versus systemic and central inflammation remain poorly understood in complex autoimmune environments like MS. Here, we investigated SARM1 pathology using global SARM1-/- knockout (SARM1-/-) mice, AAV-mediated CRISPR knockdown and overexpression of SARM1 in retinal ganglion cells (RGCs), and the small-molecule SARM1 inhibitor 5-iodoisoquinoline (5IIQ), across optic nerve crush (ONC) and experimental autoimmune encephalomyelitis (EAE) models. While global SARM1-/- did not alter the overall clinical course of EAE, it revealed a complex phenotype characterized by an altered peripheral inflammatory cytokine profile and persistent CNS immune infiltration, alongside preserved axonal and myelin integrity. RGC-restricted SARM1 knockdown partially preserved RGCs and axons during EAE, whereas SARM1 overexpression worsened both retinal function and axonal injury. Pharmacological inhibition with 5IIQ preserved axonal integrity and restored visual function in both the ONC and EAE models, as confirmed by electrophysiology, and reduced serum neurofilament light chain (NfL) in EAE, without affecting demyelination. Together, these findings demonstrate that SARM1 inhibition uncouples axonal self-destruction from demyelination and gross neuroinflammation while providing robust structural and functional neuroprotection. This study establishes SARM1 as a viable target for neuroprotective co-therapies designed to complement existing immunomodulatory and remyelinating regimens in MS and related neurodegenerative disorders.

neuroscience↗

bioRxiv2026

Into new depths: climate-driven habitat expansion of the endangered skate Dipturus chilensis (Chondrichthyes, Rajiformes)

The yellownose skate (Dipturus chilensis) is an endangered skate with a narrow distribution in the southeastern Pacific, facing intense fishing pressure and potential climate threats. Using a species distribution model, we projected the current and future distribution of D. chilensis under contrasting climate change scenarios (SSP1-2.6, SSP2-4.5, and SSP5-8.5) for mid-century (2050) and end-of-century (2100). Our models, which demonstrated robust predictive performance significantly better than random expectations, identified maximum temperature and minimum oxygen as the primary environmental drivers of habitat suitability. Projections revealed a consistent poleward range shift towards the Channels and Fjords of Southern Chile ecoregion across all scenarios. While localized habitat loss was projected in Central Chile and Araucanian ecoregions, particularly under high emissions (SSP5-8.5), these losses were outweighed by southern expansions, leading to a net increase in total suitable habitat by 2100. These findings underscore the critical need for climate-adaptive management strategies, including the protection of emerging southern refugia and dynamic fisheries regulations, to ensure the long-term persistence of D. chilensis.

ecology↗

bioRxiv2023

Modulation of functional phosphorylation sites by basic residues in the Unique domain of c-Src

In contrast to the well-studied canonical regulatory mechanisms, the way by which the recently discovered Src N-terminal regulatory element (SNRE) modulates Src activity is not yet well understood. Phosphorylation of serine and threonine residues modulate the charge distribution along the disordered region of the SNRE and may affect a fuzzy complex with the SH3 domain that is believed to act as an information transduction element. The preexisting positively charged sites can interact with the newly introduced phosphate groups by modulating their acidity, introducing local conformational restrictions, or coupling various phosphosites into a functional unit. In this paper we use pH dependent NMR measurements combined with single point mutations to identify the interactions of basic residues with physiologically important phosphorylated residues and to characterize the effect of these interactions in neighbor residues, thus providing insight on the electrostatic network in the isolated disordered regions and in the entire SNRE. From a methodological point of view, the linear relationship observed between the mutation induced pKa changes of the phosphate groups of phosphoserine and phosphothreonine and the pH induced chemical shifts of the NH groups of these residues provides a very convenient alternative to identify interacting phosphate groups without the need to introduce point mutations on specific basic residues.

biophysics↗

bioRxiv2017

Degradation of benzene by the heavy-metal resistant bacterium Cupriavidus metallidurans CH34 reveals its catabolic potential for aromatic compounds

Benzene, toluene, ethylbenzene and the three xylene isomers are monoaromatic contaminants widely distributed on polluted sites. Some microorganisms have developed mechanisms to degrade these compounds, but their aerobic and anaerobic degradation is inhibited in presence of heavy metals, such as mercury or lead. In this report, the degradation of benzene and other aromatic compounds catalyzed by the metal resistant bacterium Cupriavidus metallidurans CH34 was characterized. A metabolic reconstruction of aromatic catabolic pathways was performed based on bioinformatics analyses. Functionality of the predicted pathways was confirmed by growing strain CH34 on benzene, toluene, o-xylene, p-cymene, 3-hydroxybenzoate, 4-hydroxybenzoate, 3-hydroxyphenylacetate, 4-hydroxyphenylacetate, homogentisate, catechol, naphthalene, and 2-aminophenol as sole carbon and energy sources. Benzene catabolic pathway was further characterized. Results showed that firstly benzene is transformed into phenol and, thereafter, into catechol. Benzene is degraded under aerobic conditions via a combined pathway catalyzed by three Bacterial Multicomponent Monooxygenases: a toluene-2-monoxygenase (TomA012345), a toluene-4-monooxygenase (TmoABCDEF) and a phenol-2-hydroxylase (PhyZABCDE). A catechol-2,3-dioxygenase (TomB) expressed at early exponential phase cleaves the catechol ring in meta-position; an ortho-cleavage of catechol is accomplished by a catechol-1,2-dioxygenase (CatA) at late exponential phase instead. This study additionally shows that C. metallidurans CH34 is capable of degrading benzene in presence of heavy metals, such as Hg(II) or Pb(II). This capability of degrading aromatic compounds in presence of heavy metals is rather unusual among environmental bacteria; therefore, C. metallidurans CH34 seems to be a promising candidate for developing novel bioremediation process for multi-contaminated environments.\n\nHIGHLIGHTSO_LIThe strain Cupriavidus metallidurans CH34 is capable to degrade benzene aerobically\nC_LIO_LIBenzene oxydation is mediated by bacterial multicomponent monoxygenases\nC_LIO_LIStrain CH34 is able to grow using a broad range of aromatic compounds as sole carbon and energy source\nC_LIO_LIBenzene degradation occurs even in presence of heavy metals such as mercury and lead\nC_LI

microbiology↗