Biology subjects

Martinez, K.

Publications and source records attributed to Martinez, K..

9 recordsLinked to original sources

bioRxiv2026

Integrating social-ecological dimensions of fisheries non-compliance in a stochastic framework

Non-compliance with regulations threatens the sustainability of fisheries worldwide. Understanding the interconnected feedbacks of this complex social-ecological problem is key for sustainability but rarely integrated into fisheries management. We provide an adaptive stochastic modelling framework that integrates economic, social behavior, and ecological aspects of the Chilean kelp fishery, which plays a critical economic and ecological role in coastal social-ecological ecosystem. High levels of non-compliance is threatening sustainability, fishers well-being, and ecosystem health. Our model considers inherent environmental uncertainties and enables the assessment of different harvesting and compliance scenarios and the role of market-based economic incentives in reducing non-compliance. Results show that, unlike the sustainability obtained under an idealized full-compliance scenario, under dynamic compliance the social, economic, and ecological feedbacks leads to system collapse. Importantly, price premiums can promote compliance and sustainability, but the probability of collapse, albeit small, still exist. Our generalizable stochastic modeling framework evidenced that accounting for inherent uncertainty in natural resource management is key to designing interventions for sustainability.

ecology↗

bioRxiv2025

Multiomic profiling reveals pericyte and smooth muscle cell contributions to CADASIL pathology in cell-specific Notch3 mutant mice

Cerebral ischemic small vessel disease (SVD) is the leading cause of vascular dementia and a major contributor to stroke. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of familial SVD. CADASIL is caused by dominant missense mutations in Notch3, a receptor expressed in mural cells, including smooth muscle cells (SMCs) and pericytes. However, the cell-type specific contributions driving the CADASIL pathology remain unknown due to lack of animal models. Here, we generated two conditional knock-in mouse models carrying the CADASIL-causing Notch3R170C mutation selectively in SMC and brain pericytes. Both Notch3R170Cmodels showed perivascular accumulation of the NOTCH3 extracellular domain, yet developed distinct neurovascular changes depending on the affected cell type. Pericyte-specific Notch3R170C mice displayed pronounced region-selective microglial activation and vascular changes, whereas SMC-specific Notch3R170C mice showed localized perivascular gliosis with minimal vascular remodeling. Proteomic profiling of isolated brain vessels revealed largely unique cell-specific responses. Pericytes Notch3R170C expression dysregulated metabolic pathways, whereas SMC Notch3R170C expression induced immune signaling related pathways. Integration with single-cell RNA-seq data revealed that many of the proteomic and phosphoproteomic shifts might also include brain endothelial cells, including metabolic changes in the presence of pericyte Notch3R170C and inflammatory signaling in the presence of SMC-Notch3R170C. Together, these findings define mural cell-specific mechanisms that contribute to the CADASIL-associated vascular pathology.

neuroscience↗

bioRxiv2025

Specific and versatile monoclonal antibodies for hantavirus research

Rodent-borne hantaviruses pose a continual public health threat to humans through zoonotic transmission, with case fatality rates of up to 50% in some cases. Human infections can lead to hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardio-pulmonary syndrome (HCPS), depending on the viral species. Despite the morbidity and mortality associated with this family of viruses, no anti-viral therapeutics or vaccines are available to treat and prevent hantavirus disease. The relative shortage of commercially available reagents to study hantavirus infections in vitro and in vivo likely contributes to the challenges in developing viral countermeasures. This report describes the generation of a panel of mouse monoclonal antibodies that collectively recognize the four viral proteins of Seoul virus (Orthohantavirus seoulense), an Old World hantavirus with worldwide distribution and the causative agent of HFRS. We have validated the specificity and versatility of these antibodies against a subset of Old World and New World hantaviruses in assays relying on antigen recognition in denatured or native conformations. We present several antibodies that specifically recognize the Seoul virus nucleoprotein and polymerase protein in Western blotting and immunostaining assays. We also identified three novel antibodies directed against the glycoprotein complex that are capable of binding to the N-terminal glycoprotein of all hantaviruses tested. These antibodies are freely available to all hantavirus researchers to add to the small, but growing, collection of reliable and available reagents to be used to study hantavirus biology, identify novel antiviral compounds, and measure viral prevalence in the laboratory and the field. ImportancePathogenic hantaviruses cause severe hemorrhagic disease and pose a significant public health threat world-wide. Insufficient research into the biology of these viruses has slowed the development of effective direct-acting antivirals and vaccines. Here, we describe the generation and validation of novel, specific monoclonal antibodies for the detection of Seoul virus proteins in vitro. These reagents can be used to fill in critical gaps in knowledge regarding hantavirus entry, protein expression, and particle generation.

microbiology↗

bioRxiv2025

Functional diversity of Arabidopsis late embryogenesis abundant proteins in response to changes in the physicochemical environment

Some desiccation-tolerant organisms accumulate intrinsically disordered proteins (IDPs), such as Late Embryogenesis Abundant (LEA) proteins, which help protect other proteins from inactivation and/or aggregation during desiccation. Like other IDPs, LEA proteins adopt ensembles of extended conformations that shift in response to environmental changes. Desiccation causes dramatic changes in the cellular environment, but it is unclear how the structural malleability of LEAs is related to their protective function. In this work, we measured the in vitro protective function and structural sensitivity to changes in the environment of four Arabidopsis thaliana LEA proteins from different families. We found that all LEAs showed different protection efficiencies of the labile enzyme lactate dehydrogenase under desiccation in vitro. In line with this, we identified distinct ensemble structural changes when these LEA proteins were exposed to different physicochemical environments. Specifically, AtEM1, AtLEA7, and AtLEA4-5 showed compaction when the solution was crowded with polymers, whereas AtLEA6-2.2 showed larger structural changes when salt concentrations were increased. Furthermore, the ensembles of AtEM1, AtLEA7, and AtLEA4-5 gained helicity under desiccated conditions, while that of AtLEA6-2.2 remained largely disordered. Our results highlight how ensemble properties of LEA proteins contribute to their distinct functional activities in vitro. This work advances our understanding of the molecular features that contribute to functional diversity in desiccation-related IDPs.

biophysics↗

bioRxiv2024

Seoul orthohantavirus evades innate immune activation inreservoir endothelial cells

Pathogenic hantaviruses are maintained world-wide within wild, asymptomatic rodent reservoir hosts, with increasingly frequent human spillover infections resulting in severe hemorrhagic fever disease. With no approved therapeutics or vaccines, research has, until recently, focused on understanding the drivers of immune-mediated pathogenesis. An emerging body of work is now investigating the mechanisms that allow for asymptomatic, persistent infections of mammalian reservoir hosts with highly pathogenic RNA viruses. Despite limited experimental data, several hypotheses have arisen to explain limited or absent disease pathology in reservoir hosts. In this study, we directly tested two leading hypotheses: 1) that reservoir host cells induce a generally muted response to viral insults, and 2) that these viruses employ host-specific mechanisms of innate antiviral antagonism to limit immune activation in reservoir cells. We demonstrate that, in contrast to human endothelial cells which mount a robust antiviral and inflammatory response to pathogenic hantaviruses, primary Norway rat endothelial cells do not induce antiviral gene expression in response to infection with their endemic hantavirus, Seoul orthohantavirus (SEOV). Reservoir rat cells do, however, induce strong innate immune responses to exogenous stimulatory RNAs, type I interferon, and infection with Hantaan virus, a closely related hantavirus for which the rat is not a natural reservoir. We also find that SEOV-infected rat endothelial cells remain competent for immune activation induced by exogenous stimuli or subsequent viral infection. Importantly, these findings support an alternative model for asymptomatic persistence within hantavirus reservoir hosts: that efficient viral replication within reservoir host cells prevents the exposure of critical motifs for cellular antiviral recognition and thus limits immune activation that would otherwise result in viral clearance and/or immune-mediated disease. Defining the mechanisms that allow for infection tolerance and persistence within reservoir hosts will reveal novel strategies for viral countermeasures and inform rational surveillance programs. Author SummaryDespite the significant, and continual, threat to human health, limited experimental evidence explains the mechanisms that underly asymptomatic zoonotic RNA virus persistence within natural, mammalian reservoir hosts. Here, we investigated whether reservoir host target cells for hantavirus infection are competent for antiviral activation and tested the hypothesis that, through long-term co-evolution, Seoul orthohantavirus actively antagonizes innate antiviral signaling pathways to limit immune induction and prevent viral clearance in primary reservoir cells. While we find no evidence to support these hypotheses, our findings do support an alternative hypothesis that viral replication within the natural reservoir cells may not result in the production of immune-stimulating by-products. The factors that determine viral persistence within the reservoirs may include efficient use of host co-factors for efficient genome replication and/or packaging and warrant further investigation.

microbiology↗

bioRxiv2024

Insights into the Contribution of Type VI Secretion Towards AHPND Pathogenesis

The Type VI Secretion System (T6SS) is a contractile injection apparatus which delivers effector toxins in a contact-dependent manner, and has drawn considerable attention as a determinant of pathogenicity and environmental fitness in diverse bacterial taxa. Past reports have noted that many strains of Vibrio parahaemolyticus which cause Acute Hepatopancreatic Necrosis Disease (AHPND) in shrimp harbor two functional T6SSs (T6SS1 and T6SS2), leading to speculation that these systems may contribute to virulence. Here, we evaluate the involvement of Type VI Secretion (T6S) as a pathogenicity factor during shrimp infection by two geographically distinct isolates of AHPND-causing V. parahaemolyticus (VpAHPND). Combining in vitro contact-killing assays with comparative genomic analysis, we demonstrate that these strains -- 13-306/D4 (Mexico) and 12-297/B (Vietnam) -- leverage overlapping yet distinct effector arsenals to antagonize bacterial and fungal prey under warm, high-salinity conditions. Moreover, our in silico analyses reveal a predicted T6SS effector/immunity (E/I) module encoded in proximity to the pirAB-Tn903 composite transposon on pVA1-type plasmids. We demonstrate that acquisition of a plasmid expressing this module allows the non-AHPND isolate V. parahaemolyticus BB22OP to antagonize its parental strain in a T6SS1-dependent fashion. In turn, prey equipped with a plasmid expressing only the immunity gene gain protection against BB22OP attackers armed with the full E/I module. Employing an immersion bioassay, we show that both D4 and 297B require T6S functionality for full virulence against whiteleg shrimp (Litopenaeus vannamei) postlarvae under warm, marine-like conditions, and provide preliminary evidence that T6SS-dependent interactions with host-associated bacteria may contribute to virulence. Our findings offer empirical evidence supporting the involvement of T6S in AHPND pathogenesis under conditions relevant to commercial aquaculture, inviting further studies to decipher the role/s of T6S as a virulence determinant.

microbiology↗

bioRxiv2022

Long-term, super-resolution HIDE imaging of the inner mitochondrial membrane in live cells with a cell-permeant lipid probe

The densely packed inner mitochondrial membrane (IMM) is vital for bioenergy generation and its dynamics control mitochondrial health and cellular homeostasis. IMM structure is complex, however, and imaging its dynamics with high temporal and spatial resolution is complicated by the photosensitivity of IMM-resident enzymes. Here we describe the cell-permeant, lipid-like acridine orange derivative MAO-N3 and use it to assemble high-density, environmentally sensitive (HIDE) probes that selectively label and image the IMM in live cells. MAO-N3 pairs with multiple SPAAC-reactive fluorophores to support HIDE imaging via confocal, Structured Illumination, Single Molecule Localization, and Stimulated Emission Depletion microscopy, all with significantly improved resistance against photobleaching. The HIDE probes generated using MAO-N3 require no genetic manipulations, are non-toxic in model cell lines and primary cardiomyocytes, even under conditions that amplify the effects of mitochondrial toxins, and visualize the IMM for up to 12.5 hours with unprecedented spatial and temporal resolution.

cell biology↗

bioRxiv2020

Longitudinal profiling of the macaque vaginal microbiome reveals similarities to diverse human vaginal communities: implications for use as a pre-clinical model for bacterial vaginosis

The vaginal microbiota plays an important role in womens reproductive and urogenital health. Disturbances in this microbial community can lead to several adverse outcomes including pelvic inflammatory disease, bacterial vaginosis (BV) as well as increased susceptibility to sexually transmitted infections, miscarriage, and pre-term births. It is now well accepted that while the microbiome of healthy women in the developed world is dominated by Lactobacillus species, vaginal communities in asymptomatic women, especially those in the developing world, can be comprised of a diverse set of micro-organisms. The presence of a diverse vaginal microbiome has been associated with increased susceptibility to HIV infection but their implications for womens health remain poorly understood. Rhesus macaques are an excellent translational animal model due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from 16 reproductive age female rhesus macaques. Many animals showed hallmarks of BV, including Nugent scores above 7 and high vaginal pH. At both the taxonomic and functional level, the rhesus macaque vaginal microbiome was most similar to that of women who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Specifically, rhesus macaque vaginal microbiomes harbored a diverse set of anaerobic gram-negative bacteria, including; Snethia, Prevotella, Porphyromonas, and Mobilluncus. Interestingly, some animals were transiently colonized by Lactobacillus and some with Gardnerella. Our in-depth and comprehensive analysis highlights the importance of the model to test interventions for manipulating the vaginal microbiome. IMPORTANCEIt is widely accepted that the "healthy" vaginal microbiome of the majority of women in the developed world is dominated by Lactobacillus species. However, in the developing world, a majority of women are colonized by diverse microbial communities, typically associated with bacterial vaginosis, but remain asymptomatic. Many questions remain about the drivers of this disparity and potential interventions to alter the vaginal microbiome. Rhesus macaques provide an excellent translational model due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from a large cohort of reproductive age rhesus macaques. At the taxonomic, genomic, and functional level, the rhesus macaque vaginal microbiome was most similar to that of humans who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Our in-depth and comprehensive analysis highlights the utility of macaques to test interventions for manipulating the vaginal microbiome.

microbiology↗

bioRxiv2020

Development of early-stage type 1 diabetes in germ-free interleukin-10 deficient mice

Several experimental models demonstrate a role for gut microbiota in the progression of type 1 diabetes (T1D) in genetically prone hosts. While the association between disturbances in gut microbiota, or microbial dysbiosis, and complex immune diseases such as inflammatory bowel diseases (IBD) are well established, less is known about its role in T1D pathogenesis. In IBD-prone interleukin-10 deficient (IL-10 KO) mice, the absence of gut microbiota under germ-free (GF) conditions prevents IBD development. However, in aged GF IL-10 KO mice (>6-months of age), polyuria and pancreatic lymphocytic infiltration resembling T1D lesions was observed. Approximately 50% of male and female mice above 6-months of age develop pancreatic immune cell infiltration, as compared to none in conventionally-raised and fecal microbiota transplanted (FMT) IL-10 KO counterparts. Immunofluorescence staining of islet infiltrates was positive for adaptive and innate immunological markers, including lymphoid and myeloid cell markers, which typically characterize autoimmune T1D lesions. A subset of GF IL-10 KO mice was also positive for insulin autoantibodies (IAA), but the majority of mice did not become diabetic. Our findings of early stage lymphocytic infiltrates in the pancreas and IAA in the absence of overt diabetes in GF IL-10 KO mice embody the early stages of T1D pathogenesis. As such, we propose that the presence of gut microbiota play a protective role against immune infiltration in the pancreas of genetically prone hosts. Moreover, our model provides an opportunity to better understand the role of the microbiota in the early stages of immune pathogenesis and perhaps conceive the development of microbe-mediated prophylactic strategies to treat or even prevent T1D.

physiology↗