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Biology subjects

Vasquez, L.

Publications and source records attributed to Vasquez, L..

6 recordsLinked to original sources

Human exploitation of shellfish in the Atacama desert coast and environmental variability: a trans-Holocene perspective

The Humboldt upwelling ecosystem has been intensively harvested by people since the early Holocene. Understanding past and present human choices under climatic variability in these productive environments may hold key insights for its future sustainability by unraveling different adaptive pathways. To this end, we studied shellfish exploitation and climate patterns in the Taltal region of the Atacama desert coast (25{whitebullet}S) from the early Holocene until today using a compilation of archaeological, and modern benthic fisheries data together with direct ecological surveys. In addition we obtained satellite sea surface temperature (SST) and published{delta} 18O SST for the study region. The archaeological record and the modern rocky shore assemblage were dominated by herbivorous gastropods -Fissurella spp., Enoplochiton spp., Tegula spp.-and the carnivorous whelk Concholepas concholepas. Functional composition from the early Holocene to the present was remarkably stable. Using SST as a latent variable, we examined changes in functional composition across the Holocene and in a 16-year series of artisanal fisheries landings using bayesian ordination. The analysis identified functional groups characteristic of kelp ecosystems in association with cooler SST conditions during the Holocene and the present. Changes in functional composition during warm and cold periods of the Holocene broadly mirrored effects of interannual SST variability in the modern fisheries. The archaeological record suggests two cross-Holocene transitions social-ecological transitions. The generalized shoreline harvesting strategy that prevailed during the cold early Holocene shifted to a specialized maritime economy towards the warmer mid-Holocene. The maritime technological and cultural adaptions remained, but were part of more diversified lifestyles in the cooler and more variable late Holocene. The latter emerged at the same time as the modern El Nino climate pattern. Our insights from the direct analysis of human choices and SST variability highlight the role of flexibility and agency under a changing environment. The broad range of human decisions in the past, inform current regulatory frameworks for benthic artisanal fisheries. Marine resources and the livelihoods that depend on them are integrated into coupled coastal socioecological systems; their future sustainability hinges on fostering the different dimension of their adaptive capacity.

ecology↗

Drug-Eluting, Radiopaque, Tumor-Casting Hydrogels for Endovascular Locoregional Therapy of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. For patients with unresectable disease, locoregional therapies, such as transarterial chemoembolization (TACE), are the standard of care. However, even with this treatment, the average survival rate is only 27% at 5 years. Recent studies have demonstrated the potential of novel approaches to improve responses through more complete embolization and targeting ischemia-induced molecular dependencies. To build on these findings, we developed an injectable chitosan-based hydrogel system (AuNP-Lys05-gel) that we hypothesized might be a more effective embolic material by (i) enabling a more complete filling of tumor feeding blood vessels in a cast-like manner, (ii) encapsulating Lys05, a potent autophagy inhibitor, and (iii) providing X-ray contrast for direct visualization of the embolization. Chitosan hydrogels of varying composition were formed and characterized. We found that Lys05 could be loaded in this type of hydrogel and that it was released gradually over 7 days. We found that AuNP was better retained by the hydrogel than iopamidol, an FDA-approved contrast agent, indicating that AuNP would provide longer-lasting CT monitoring. In a rat model of HCC, AuNP-Lys05-gel reduced tumor growth and resulted in a 67% objective response rate vs 26% for a clinically used particle embolic. Histology indicated effective vascular occlusion by the gel. These findings indicate that AuNP-Lys05-gel merits further investigation as a treatment for HCC.

cancer biology↗

Environmentally-induced DNA methylation is inherited across generations in an aquatic keystone species (Daphnia magna)

Environmental stress can result in epigenetic modifications that are passed down several generations. Such epigenetic inheritance can have significant impact on eco-evolutionary dynamics, but the phenomenon remains controversial in ecological model systems. Here, we used whole-genome bisulfite sequencing on individual water fleas (Daphnia magna) to assess whether environmentally-induced DNA methylation can persist for up to four generations. Genetically identical females were exposed to a control treatment, one of three natural stressors (high temperature, zinc, microcystin), or the methylation-inhibitor 5-azacytidine. After exposure, lines were propagated clonally for four generations under control conditions. We identified between 70 and 225 differentially methylated CpG positions (DMPs) between controls and F1 individuals whose mothers (and therefore they themselves as germ cells) were exposed to one of the three natural stressors. Between 46% and 58% of these environmentally-induced DMPs persisted until generation F4 without attenuation in their magnitude of differential methylation. DMPs were enriched in exons and largely stressor-specific, suggesting a possible role in environment-dependent gene regulation. In contrast, treatment with the compound 5-azacytidine demonstrated that pervasive hypo-methylation upon exposure is reset almost completely after a single generation. These results suggest that environmentally-induced DNA methylation is non-random and stably inherited across generations in Daphnia, making epigenetic inheritance a putative factor in the eco-evolutionary dynamics of fresh-water communities. Author summaryWater fleas are important keystone species mediating eco-evolutionary dynamics in lakes and ponds. It is currently an open question in how far epigenetic inheritance contributes to the ability of Daphnia populations to adapt to environmental stress. Using a range of naturally occurring stressors and a multi-generational design, we show that environmentally-induced DNA methylation variants are stably inherited for at least four generations in Daphnia magna. The induced variation in DNA methylation are stressor-specific and almost exclusively found in exons, bearing the signatures of functional adaptations. Our findings imply that ecological adaptations of Daphnia to seasonal fluctuations can be underpinned by epigenetic inheritance of DNA methylation without changes in gene frequencies.

evolutionary biology↗

Genetic associations at regulatory phenotypes improve fine-mapping of causal variants for twelve immune-mediated diseases

The identification of causal genetic variants for common diseases improves understanding of disease biology. Here we use data from the BLUEPRINT project to identify regulatory quantitative trait loci (QTL) for three primary human immune cell types and use these to fine-map putative causal variants for twelve immune-mediated diseases. We identify 340 unique, non major histocompatibility complex (MHC) disease loci that colocalise with high (>98%) posterior probability with regulatory QTLs, and apply Bayesian frameworks to fine-map associations at each locus. We show that fine-mapping applied to regulatory QTLs yields smaller credible set sizes and higher posterior probabilities for candidate causal variants compared to disease summary statistics. We also describe a systematic under-representation of insertion/deletion (INDEL) polymorphisms in credible sets derived from publicly available disease meta-analysis when compared to QTLs based on genome-sequencing data. Overall, our findings suggest that fine-mapping applied to disease-colocalising regulatory QTLs can enhance the discovery of putative causal disease variants and provide insights into the underlying causal genes and molecular mechanisms.

genomics↗

PATHWAYS ANALYZER: Design of a Tool for the Synthetic Assembly of Escherichia Coli K-12 MG1655 Bacteria for Biofuel Production

SummaryDue to the impact of environmental pollution, the importance of producing high quality biofuels and to leverage organic waste that normally would have no use has increased over time. Through synthetic biology, it is possible to improve existing organisms to process waste that is traditionally not used for biofuel production, such as whey.\n\nWith the redesign of metabolic pathways, it is possible to create connections for the implementation of new organisms that carry out functions that are normally not present in nature.\n\nFrom a computational point of view, metabolic pathways, which can be found in data sources as KEGG, can be converted to a graph data structure. These transformations enable the use of well-known algorithms, which enables the optimization of the analyses required to achieve the assembly of new organisms.\n\nThe present work aims to design a tool for the transformation of metabolic pathways and the development of path finding algorithms that establish relevant links between compounds that are essential to the biofuel production process.\n\nAs a result, a catalog of biobricks is created from the analysis of a subset of paths which can be used in the design stage of the synthetic assembly of the E. coli bacteria. The assemblys structure and functions are characterized according to the pieces used.\n\nFinally, new constructions are visualized with the goal of demonstrating and supporting the analysis processes, thus assisting people that work in the field of Synthetic Biology.\n\nAvailabilityPathways Analyzer is accessible at: https://gitlab.com/lvasquezcr/pathways-analyzer/

synthetic biology↗

Variation in PU.1 binding and chromatin looping at neutrophil enhancers influences autoimmune disease susceptibility

Neutrophils play fundamental roles in innate inflammatory response, shape adaptive immunity1, and have been identified as a potentially causal cell type underpinning genetic associations with immune system traits and diseases2,3 The majority of these variants are non-coding and the underlying mechanisms are not fully understood. Here, we profiled the binding of one of the principal myeloid transcriptional regulators, PU.1, in primary neutrophils across nearly a hundred volunteers, and elucidate the coordinated genetic effects of PU.1 binding variation, local chromatin state, promoter-enhancer interactions and gene expression. We show that PU.1 binding and the associated chain of molecular changes underlie genetically-driven differences in cell count and autoimmune disease susceptibility. Our results advance interpretation for genetic loci associated with neutrophil biology and immune disease.

genetics↗