Biology subjects

Vasquez, G.

Publications and source records attributed to Vasquez, G..

5 recordsLinked to original sources

bioRxiv2026

Tuning siRNA Specificity through Seed Region Incorporation of Deoxyribonucleotide Stereoisomers

Precise chemical design continues to drive advances in RNA-based therapeutics. Here, we report the synthesis and site-specific incorporation of four canonical phosphoramidites (U, C, A, and G), each bearing non-natural nucleoside configurations: {beta}-D-2'-deoxyxylonucleosides and -L-2'-deoxyribonucleosides. These stereochemically distinct nucleoside analogs were introduced at positions 6 and 7 within siRNA seed regions. When applied to siRNAs targeting Ttr, ACTN1, and Marc1, these modifications reduced off-target gene repression in functional assays and, in several cases, in transcriptome-wide differential expression analyses, while preserving robust on-target activity. In vivo, Marc1-targeting siRNAs containing these modified nucleosides showed decreased hepatotoxicity, as evidenced by reduced serum ALT and AST levels. Collectively, these findings establish {beta}-D-2'-deoxyxylonucleoside and -L-2'-deoxyribonucleoside analogs as promising chemical tools for enhancing the specificity and safety of siRNA therapeutics. This work underscores the power of integrating rational nucleoside design with comprehensive functional and in vivo evaluation to advance drug development based on RNA interference (RNAi). GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=83 SRC="FIGDIR/small/699368v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@10e6e8aorg.highwire.dtl.DTLVardef@7b2797org.highwire.dtl.DTLVardef@1643f44org.highwire.dtl.DTLVardef@75a0a4_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2021

Evolution of Knockdown Resistance Haplotypes in Response to Pyrethroid Selection in Aedes aegypti

This study describes the evolution of knockdown resistance (kdr) haplotypes in Aedes aegypti in response to pyrethroid insecticide use over the course of 18 years in Iquitos, Peru. Based on the duration and intensiveness of sampling ([~]10,000 samples), this is the most thorough study of kdr population genetics in Ae. aegypti to date within a city. We provide evidence for the direct connection between programmatic citywide pyrethroid spraying and the increase in frequency of specific kdr haplotypes by identifying two evolutionary events in the population. The relatively high selection coefficients, even under infrequent insecticide pressure, emphasizes how quickly populations can evolve. The observed rapid increase in frequency of resistance alleles might have been aided by the incomplete dominance of resistance-conferring alleles over corresponding susceptibility alleles. In addition to dramatic temporal shifts, spatial suppression experiments reveal that genetic heterogeneity existed not only at the citywide scale, but also on a very fine scale within the city.

evolutionary biology↗

bioRxiv2018

Antimicrobial, Antioxidant and Anti-Inflammatory Activities of Proteins of Phaseoulus lunatus (Fabaceae) Baby Lima Beans Produced in Ecuador

Phaseoulus lunatus L., a variety of baby lima bean, which is produced in the coastal region of Ecuador, is a profitable crop of that country. Various cultivars of this common bean are considered a sources for nutraceutical compounds, such as bioactive peptides. To assess the potential biologic activities of protein isolates and hydrolysates of P. lunatus baby lima beans, this study evaluates the proteins antimicrobial, antioxidant and anti-inflammatory activities. Antioxidant activity was measured by the TBARS method. In-vitro anti-inflammatory activity was measured by the inhibition of denatured protein as well as a diffusion method, according with CLSI guidelines by antimicrobial activity. Both fractions (isolate and hydrolysates) showed anti-inflammatory and antioxidant activity. However, protein hydrolysates (pH 5) had a better performance than protein isolates. The same effect was observed in antimicrobial activity, when protein hydrolysates had a broad-spectrum antimicrobial activity against Gram-negative and Gram-positive bacteria. These preliminary studies suggest that P. lunatus baby lima beans could have a considerable biological activity for nutraceutical applications.

microbiology↗

bioRxiv2017

Efficacy of Aedes aegypti control by indoor Ultra Low Volume (ULV) insecticide spraying in Iquitos, Peru

BackgroundAedes aegypti is a primary vector of dengue, chikungunya, Zika, and urban yellow fever viruses. Indoor, ultra low volume (ULV) space spraying with pyrethroid insecticides is the main approach used for Ae. aegypti emergency control in many countries. Given the widespread use of this method, the lack of large-scale experiments or detailed evaluations of municipal spray programs is problematic.\n\nMethodology/Principal FindingsTwo experimental evaluations of non-residual, indoor ULV pyrethroid spraying were conducted in Iquitos, Peru. In each, a central sprayed sector was surrounded by an unsprayed buffer sector. In 2013, spray and buffer sectors included 398 and 765 houses, respectively. Spraying reduced the mean number of adults captured per house by ~83 percent relative to the pre-spray baseline survey. In the 2014 experiment, sprayed and buffer sectors included 1,117 and 1,049 houses, respectively. Here, the sprayed sectors number of adults per house was reduced ~64 percent relative to baseline. Parity surveys in the sprayed sector during the 2014 spray period indicated an increase in the proportion of very young females. We also evaluated impacts of a 2014 citywide spray program by the local Ministry of Health, which reduced adult populations by ~60 percent. In all cases, adult densities returned to near-baseline levels within one month.\n\nConclusions/SignificanceOur results demonstrate that densities of adult Ae. aegypti can be reduced by experimental and municipal spraying programs. The finding that adult densities return to approximately pre-spray densities in less than a month is similar to results from previous, smaller scale experiments. Our results demonstrate that ULV spraying is best viewed as having a short-term entomological effect. The epidemiological impact of ULV spraying will need evaluation in future trials that measure capacity of insecticide spraying to reduce disease transmission.

epidemiology↗

bioRxiv2017

Deep profiling of mouse splenic architecture with CODEX multiplexed imaging.

A highly multiplexed cytometric imaging approach, termed CO-Detection by indEXing (CODEX), is used here to create multiplexed datasets of normal and lupus (MRL/lpr) murine spleens. CODEX iteratively visualizes antibody binding events using DNA barcodes, fluorescent dNTP analogs, and an insitu polymerization-based indexing procedure. An algorithmic pipeline for single-cell antigen quantification in tightly packed tissues was developed and used to overlay well-known morphological features with de novo characterization of lymphoid tissue architecture at a single-cell and cellular neighborhood levels. We observed an unexpected, profound impact of the cellular neighborhood on the expression of protein receptors on immune cells. By comparing normal murine spleen to spleens from animals with systemic autoimmune disease (MRL/lpr), extensive and previously uncharacterized splenic cell interaction dynamics in the healthy versus diseased state was observed. The fidelity of multiplexed spatial cytometry demonstrated here allows for quantitative systemic characterization of tissue architecture in normal and clinically aberrant samples.

systems biology↗