Biology subjects

Bermudez, S.

Publications and source records attributed to Bermudez, S..

7 recordsLinked to original sources

bioRxiv2025

Detection and phylogenetic characterization of Jingmen tick virus in Amblyomma mixtum ticks from Costa Rica

Jingmenvirus is a group of segmented flaviviruses detected in arthropods and vertebrates that has attracted growing public health interest due to the recognition of some members as emerging human arboviral pathogens. As part of a study aimed at deciphering the virome of medically and veterinary important ticks in Costa Rica, we detected Jingmen tick virus (JMTV) in engorged Amblyomma mixtum ticks collected from horses. We assembled three complete genome segments and one partial segment from tick pools. Phylogenetic analyses revealed that JMTV from Costa Rica (JMTV Costa Rica) shares a common viral ancestor with JMTV viruses identified in ticks from the Caribbean and Latin America, with putative reassortment events detected across segments. Two distinct clades of Jingmen viruses were identified in the American continent, suggesting two distinct introductions: one from Europe/Asia and the other from Africa/Asia. Of note, JMTV Costa Rica falls in the same clade as viruses from Europe and Turkey, including sequences found in humans. Our study constitutes the first report of JMTV associated with Amblyomma mixtum. This tick species feeds on a wide range of hosts, including wildlife, domestic animals, and frequently parasitizes humans in Central America. Further research involving the detection of active or past infections in humans and horses after tick bites are needed to evaluate the risk of JMTV-associated arboviral infection in Central America, including Costa Rica. ImportanceJingmenviruses are flaviviruses detected in arthropods and vertebrates reported in several countries worldwide. Some members cause disease and infections in humans; therefore, they are considered emergent human arboviruses. In Costa Rica and Central America, there is no information on tick-associated viruses or the role of ticks as putative vectors of viruses. Here, we report the first regional detection of Jingmen tick virus (JMTV) in Amblyomma mixtum ticks collected from horses. We assembled three complete and one partial viral segment from tick pools. Phylogenetic analysis revealed that the JTMV detected in Costa Rica is closely related to other detections from Latin America and the Caribbean and is located in the same clade as viruses reported in humans. Additionally, we detected two separate introductions of JMTV to Latin America. To determine whether this JMTV is an emergent arbovirus, research on past or active infections in humans is required.

microbiology↗

bioRxiv2025

Activation of transposable elements is linked to a region- and cell-type-specific interferon response in Parkinson's disease

Parkinsons disease (PD) is a neurodegenerative disorder involving a neuroinflammatory response, the cause of which remains unclear. Transposable elements (TE) have been linked to inflammation, but their potential role in PD remains unexplored. Using bulk- and single-nuclei RNAseq of postmortem brain tissue from four brain regions, we studied TE transcription and its correlation with PD neuroinflammation. Over a thousand TEs, including LINE-1s and ERVs, were expressed in a cell-type and region-specific manner in the human brain. Increased TE expression was found in microglia and neurons in the substantia nigra and putamen of PD brains, but not amygdala or prefrontal cortex, compared to controls. This TE activation correlated with an innate immune response in the same brain regions. The link between an interferon response and TE activation was mechanistically confirmed using human pluripotent stem cell-derived microglia and neurons. Our findings provide insights into TE transcription in the PD brain and suggest TEs may contribute to neuroinflammation and pathological progression in PD. Teaser: Transposable elements are linked to a cell type specific inflammatory state in Parkinsons Disease.

neuroscience↗

bioRxiv2024

Translational control of microglial inflammatory and neurodegenerative responses

In Alzheimers Disease (AD), activation of the mechanistic target of rapamycin (mTOR) pathway is essential for microglia neuroprotective roles, but it is unclear which mTOR effectors promote these neuroprotective functions. The mTOR complex 1 (mTORC1) inactivates the translation suppressors eukaryotic translation Initiation Factor 4E (eIF4E)-Binding Proteins (4E-BP) to promote mRNA translation. We show that 4E-BP1 inactivation is impaired in microglia under AD-relevant conditions. Depleting 4E-BPs in microglia increases mitochondrial metabolism, suppresses the pro-inflammatory profile, and mitigates amyloid-induced apoptosis. Furthermore, in the cerebrospinal fluid of patients with amyloid pathology, there was a positive association between microglia activation and neurodegeneration, which increases along 4E-BP1 levels. Thus, we propose the engagement mTORC1-4E-BP1 axis as a neuroprotective mechanism and a therapeutic target or biomarker for microglia modulation in AD.

neuroscience↗

bioRxiv2023

A Complex Containing the Na+/K+ ATPase Regulates Epileptogenesis in Drosophilamelanogaster

Epileptogenesis, the process through which the brain becomes seizure-prone, is not well understood. Previous work identified a novel gene in Drosophila, julius seizure (jus), that when mutated or developmentally knocked down, leads to epilepsy in adult Drosophila, providing a useful model for dissecting epileptogenesis. Here we report that when a GFP-tagged version of Jus was used as bait in a co-immunoprecipitation (co-IP) assay, a complex of 23 associated proteins was identified that included ATPalpha and Nervana 3, two subunits of the Na+/K+ ATPase. RNAi-mediated knockdown of ATPalpha, Nervana 3, or any of 8 additional complex proteins enhanced seizure susceptibility. The critical period of Jus expression in epileptogenesis was further defined, occurring between pupal stages P4-7; remarkably, the jus seizure phenotype could be rescued by increasing neural activity of jus-expressing neurons during these mid-pupal stages, suggesting that altered neural activity in these neurons may contribute to the seizure phenotype. Our data support a model that, in wild type flies, a protein complex containing Na+/K+ ATPase and Jus prevents epileptogenesis, possibly by regulating neural activity.

neuroscience↗

bioRxiv2023

Stimulation of mRNA translation rescues hippocampal synaptic plasticity and memory in mouse models of Alzheimer's disease

Impaired synaptic plasticity and progressive memory deficits are major hallmarks of Alzheimers disease (AD). Hippocampal mRNA translation, required for memory consolidation, is defective in AD. Here, we show that systemic treatment with (2R,6R)- hydroxynorketamine (HNK), an active metabolite of the antidepressant ketamine, prevented deficits in hippocampal mRNA translation, long-term potentiation (LTP) and memory induced by AD-linked amyloid-{beta} oligomers (A{beta}Os) in mice. HNK activated hippocampal extracellular signal-regulated kinase 1/2 (ERK1/2), mechanistic target of rapamycin (mTOR), and p70S6 kinase 1 (S6K1)/ribosomal protein S6 (S6), which promote protein synthesis and synaptic plasticity. Stimulation of S6 phosphorylation by HNK was mTORC1-dependent, while rescue of hippocampal LTP and memory in HNK-treated A{beta}O-infused mice was ERK1/2-dependent and, partially, mTORC1- dependent. Remarkably, treatment with HNK corrected LTP and memory deficits in aged APP/PS1 mice. Transcriptomic analysis further showed that HNK rescued signaling pathways that are aberrant in APP/PS1 mice, including inflammatory and hormonal responses, and programmed cell death. Taken together, our findings demonstrate that HNK induces signaling and transcriptional responses that correct deficits in hippocampal synaptic plasticity and memory in AD mouse models. These results raise the prospect that HNK could serve as a therapeutic to prevent or reverse memory decline in AD.

neuroscience↗

bioRxiv2019

CpG-creating Mutations are Costly in Many Human Viruses

Mutations can occur throughout the virus genome and may be beneficial or deleterious. We are interested in mutations that yield a C next to a G, producing CpG sites. CpG sites are rare in eukaryotic and viral genomes. For the eukaryotes, it is thought that CpG sites are rare because they are prone to mutation when methylated. In viruses, we know less about why CpG sites are rare. A previous study in HIV suggested that CpG-creating transition mutations are more costly that similar non-CpG-creating mutations. To determine if this is the case in other viruses, we analyzed the allele frequencies of CpG-creating and non-CpG-creating mutations across various strains, subtypes, and genes of viruses using existing data obtained from Genbank, HIV Databases, and Virus Pathogen Resource. Our results suggest that CpG sites are costly for most viruses. By understanding the cost of CpG sites, we can obtain further insights into the evolution and adaptation of viruses.

evolutionary biology↗

bioRxiv2018

Revealing an extended critical window of recovery post-stroke

The impact of rehabilitation on post-stroke motor recovery and its dependency on the patients chronicity remain unclear. The existence and regularity of a, so called, proportional recovery rule across a range of functional deficits and therapies supports the notion that functional interventions have little or no impact beyond spontaneous recovery rates in a critical window of recovery which lasts from 3 to 6 months post-stroke. In this meta-analysis, we apply a bootstrap analysis method to assess the overall impact of a specific VR-based rehabilitation protocol for the upper extremities on a homogeneous sample of 219 individuals with hemiparesis at various stages post stroke. Our analysis uncovers a precise gradient of sensitivity to treatment that expands more than one year beyond the limits of the so-called critical window of recovery. These findings redefine the limits of the so-called critical window of recovery and suggest that stroke-derived plasticity mechanisms do facilitate functional recovery even at the chronic and late chronic stage.

neuroscience↗