Biology subjects

Guevara, C.

Publications and source records attributed to Guevara, C..

6 recordsLinked to original sources

bioRxiv2026

Efficacy of an attractive lethal ovitrap to reduce populations of Aedes mosquitoes: a controlled trial in Iquitos, Peru

IntroductionDengue, one of the most important arboviral infections worldwide, is transmitted primarily by the mosquito Aedes aegypti, a vector closely associated with human habitations. Because vector control is the primary prevention strategy for this disease novel tools are urgently needed. We evaluated an Attractive Lethal OviTrap (ALOT) that targets epidemiologically relevant gravid female mosquitoes for public health impact against dengue disease. MethodsWe conducted a proof-of-concept field efficacy trial in the Amazonian city of Iquitos, Peru, to quantify the reduction of vector density, parity, and sex ratio and symptomatic human dengue infection over a 3.5 year follow-up period. After three baseline entomological surveys in core (753 houses), and buffer (1,549 houses) areas where traps were placed in and around homes, and a control (1,233 houses) area without traps, entomological surveys were carried out every 2 months, and household residents were monitored for dengue disease 3 times a week. Trap maintenance was conducted at 2-3 week intervals by study staff during the first 2.5 years and by residents in the final year. ResultsTotal and female Ae. aegypti abundance demonstrated a strong initial effect with 52% and 47% fewer mosquitoes after trap placement, respectively (Total: RR = 0.48, 95% CI: 0.40 - 0.58, p < 0.001; Females: RR = 0.53, 95% CI: 0.43 - 0.66, p < 0.001). The effect diminished significantly, however, over the study period (interaction coefficient = 0.035 per month, p < 0.001; interaction coefficient = 0.030 per month, p < 0.001). Female-to-male ratio decreased after trap deployment and impact on non-Aedes abundance was like that of Aedes. Cumulative symptomatic dengue incidence was 1.40% (95% CI: 1.00%-1.70%) in the ALOT area versus 3.20% (95% CI: 2.60%-3.80%) in the control area, a 56% relative reduction (log-rank {chi}{superscript 2}=30.0, p<0.001). Restricted mean survival time analysis showed participants in the intervention area on average remained dengue-free for 15.5 additional days (95% CI: 11.1-20.0, p<0.001). ConclusionsThe ALOT strategy functioned as predicted, decreasing but not eliminating female vector densities, with a clear public health impact, lowering dengue disease in areas where traps were deployed. Our study also illustrates the challenges associated with conducting large-scale vector control trials and the need to consider programmatic implementation early in the process of bringing a new product to market. Author SummaryDengue is one of the most important mosquito transmitted infections worldwide. Aedes aegypti, the most important species involved, has a unique biology living in containers associated with households. New methods to control this mosquito are needed and we present our evaluation of a novel trap called the Attractive Lethal OviTrap (ALOT) that targets older female mosquitoes that are the most important for dengue disease transmission. We conducted a trial in the Amazonian city of Iquitos, Peru, to measure reductions in mosquito numbers, age, and sex ratio and symptomatic human dengue infections over a 3.5 years. After baseline entomological surveys prior to placing ALOT traps in homes in a treatment area, which included a central core area with 753 houses and a protective buffer area with 1,549 houses areas. We also had a control area without any traps in 1,233 houses. Mosquito surveys were carried out every 2 months, and household residents were monitored for dengue disease 3 times per week. Trap maintenance was conducted at 2 - 3 week intervals by study staff during the first 2.5 years and by residents in the final year. The number of all Ae. aegypti were initially reduced by 52% after trap placement whereas females were reduced by 47%. The effect diminished significantly, however, over the study period. Female-to-male ratio decreased after trap deployment and impact on other mosquito species was like that of Aedes. Dengue incidence was 56% less in the area with traps compared to the control area, estimating that participants in the intervention area on average remained dengue-free for 15.5 additional days. The ALOT strategy functioned as predicted, decreasing but not eliminating female mosquitos and had a clear public health impact, lowering dengue disease in areas where traps were deployed. Our study also illustrates the challenges associated with conducting large-scale vector control trials and the need to consider programmatic implementation early in the process of bringing a new product to market.

ecology↗

bioRxiv2025

Sleep controls peroxisomal abundance to reduce wake-induced brain oxidation

Sleep is increasingly linked to the regulation of Reactive Oxygen Species (ROS) and lipid metabolism. However, the mechanisms underlying this interaction are underexplored. Here, we use Drosophila melanogaster to report a bidirectional relationship between sleep and peroxisomes, cellular organelles that process lipids and alleviate ROS. Of the genes that change expression after sleep deprivation in the dorsal fan-shaped body, knockdown of the peroxisomal biogenesis factor Pex16 results in decreased sleep. Pex16 acts in several brain regions to modulate sleep amount, with ellipsoid body neurons (EB) producing the highest sleep reduction of the sleep-promoting regions. Consistent with a general role for peroxisomes, knockdown of other peroxisomal enzymes relevant for lipid import and synthesis also decreases sleep. Whole-brain peroxisomal numbers increase with wake, which is supported by lipidomic analysis indicating that peroxisomal-derived phospholipids are the major contributors to phospholipid changes after wake or sleep deprivation. Peroxisomal proliferation in the EB is driven by neuronal activity and increased oxidation, suggesting that these mediate the effect of wake/sleep loss. In turn, peroxisomes alleviate the oxidation accumulated during wake, such that loss of Pex16 in the EB works non-cell autonomously to increase lipid peroxidation brain-wide. This likely contributes to sleep loss, as sleep is rescued with an antioxidant. Together, these results position peroxisomes as key players in sleep, regulating ROS and thereby maintaining normal cycles.

neuroscience↗

bioRxiv2025

Sleep-dependent clearance of brain lipids by peripheral blood cells

Sleep is typically viewed through a brain-centric lens, with little known about the role of the periphery. Here, we identify a sleep function for peripheral macrophage-like cells (hemocytes) in the Drosophila circulation, showing that hemocytes track to the brain during sleep and take up lipids accumulated in cortex glia due to wake-associated oxidative damage. Through a screen of phagocytic receptors expressed in hemocytes, we discovered that knockdown of eater, a member of the Nimrod receptor family, reduces sleep. Loss of eater also disrupts hemocyte adhesion to the brain and lipid uptake, which results in increased brain levels of Acetyl CoA and acetylated proteins, including mitochondrial proteins PGC1 and DRP1. Dysregulation of mitochondria, reflected in high oxidation and reduced NAD+, is accompanied by impaired memory and lifespan. Thus, peripheral blood cells, which we suggest are precursors of mammalian microglia, perform a daily function of sleep to maintain brain function and fitness.

molecular biology↗

bioRxiv2023

Chemokine receptor 5 signaling in PFC mediates stress susceptibility in female mice

Chronic stress induces changes in the periphery and the central nervous system (CNS) that contribute to neuropathology and behavioral abnormalities associated with psychiatric disorders. In this study, we examined the impact of peripheral and central inflammation during chronic social defeat stress (CSDS) in female mice. Compared to male mice, we found that female mice exhibited heightened peripheral inflammatory response and identified C-C motif chemokine ligand 5 (CCL5), as a stress-susceptibility marker in females. Blocking CCL5 signaling in the periphery promoted resilience to CSDS. In the brain, stress-susceptible mice displayed increased expression of C-C chemokine receptor 5 (CCR5), a receptor for CCL5, in microglia in the prefrontal cortex (PFC). This upregulation was associated with microglia morphological changes, their increased migration to the blood vessels, and enhanced phagocytosis of synaptic components and vascular material. These changes coincided with neurophysiological alterations and impaired blood-brain barrier (BBB) integrity. By blocking CCR5 signaling specifically in the PFC were able to prevent stress-induced physiological changes and rescue social avoidance behavior. Our findings are the first to demonstrate that stress-mediated dysregulation of the CCL5-CCR5 axis triggers excessive phagocytosis of synaptic materials and neurovascular components by microglia, resulting in disruptions in neurotransmission, reduced BBB integrity, and increased stress susceptibility. Our study provides new insights into the role of cortical microglia in female stress susceptibility and suggests that the CCL5-CCR5 axis may serve as a novel sex-specific therapeutic target for treating psychiatric disorders in females.

animal behavior and cognition↗

bioRxiv2023

A glia cell dependent mechanism at a peripheral nerve plexus critical for target-selective axon regeneration

A critical step for functional recovery from peripheral nerve injury is for regenerating axons to connect with their pre-injury targets. Reestablishing pre-injury target specificity is particularly challenging for limb-innervating axons as they encounter a plexus, a network where peripheral nerves converge, axons from different nerves intermingle, and then re-sort into target-specific bundles. Here, we examine this process at a plexus located at the base of the zebrafish pectoral fin, equivalent to tetrapod forelimbs. Using live cell imaging and sparse axon labeling, we find that regenerating motor axons from three nerves coalesce into the plexus. There, they intermingle and sort into distinct branches, and then navigate to their original muscle domains with high fidelity that restores functionality. We demonstrate that this regeneration process includes selective retraction of mistargeted axons, suggesting active correction mechanisms. Moreover, we find that Schwann cells are enriched and associate with axons at the plexus, and that Schwann cell ablation during regeneration causes profound axonal mistargeting. Our data provide the first real time account of regenerating vertebrate motor axons navigating a nerve plexus and reveal a previously unappreciated role for Schwann cells to promote axon sorting at a plexus during regeneration.

neuroscience↗

bioRxiv2020

Nucleolar disruption, activation of P53 and premature senescence in POLR3A-mutated Wiedemann-Rautenstrauch Syndrome fibroblasts

Recently, mutations in the RNA polymerase III subunit 3A (POLR3A) have been described as the cause of the neonatal progeria or Wiedemann-Rautenstrauch syndrome (WRS). POLR3A have important roles in the regulation of transcription of small RNAs, including tRNA, 5S rRNA and U6 snRNA. We aim to describe cellular and molecular features of WRS fibroblasts. Cultures of primary fibroblasts from one WRS patient [monoallelic POLR3A variant c.3772_3773delCT (p.Leu1258Glyfs*12)] and one control were grown. Mutation in POLR3A causes a decreased in the expression of POLR3A mRNA and protein and a sharp increased of mutant protein. In addition, there was an increased in its nuclear localization. These changes were associated to an increase number and area of nucleoli, a significantly larger nuclear area, and a high increased in the expression of pP53 and pH2AX. All these changes were associated to premature senescence. The present observations add to our understanding of the differences between HGPS and WRS, and opens new alternatives to study cell senesce and human aging.

cell biology↗