Biology subjects

Lopez, V.

Publications and source records attributed to Lopez, V..

12 recordsLinked to original sources

bioRxiv2026

YfiM is a lipid-linked oligosaccharide pyrophosphatase

Lipid-linked oligosaccharides (LLO), such as Lipid II and O-antigen precursors in bacteria, and dolichol-linked oligosaccharides (DLO) in eukaryotes, are universal metabolic intermediates required for cell wall assembly and protein glycosylation across all domains of life. The oligosaccharide moiety of LLO is synthesized through the sequential addition of various monosaccharides, a process catalyzed by a series of glycosyltransferases, to form the final mature structure. However, the existence of a homeostasis and quality control mechanism to degrade surplus and aberrant LLO has long remained a mystery. Although we recently identified the yeast LLP1 as an LLO pyrophosphatase involved in the homeostasis and quality control of DLO in fungi, the corresponding mechanism in bacteria and plants has remained elusive. Here, we identify YfiM and AT1G15900 as LLO pyrophosphatases in Escherichia coli and Arabidopsis thaliana, respectively. Phylogenetic profiling revealed that while YfiM is broadly conserved among Gram-negative bacilli, its plant ortholog displays a unique lineage-specific distribution shaped by selective gene loss. In vitro, purified YfiM and AT1G15900 exhibit LLO pyrophosphatase activity. In vivo, deletion mutant of yfiM caused vancomycin sensitivity in E. coli. Conversely, overexpression of YfiM triggered osmotic lysis under hypotonic conditions. Moreover, overexpression of YfiM in an outer membrane-compromised strain partially rescued detergent-chelator sensitivity, revealing a compensatory envelope stress response. Together, our findings uncover an ancient, conserved cross-kingdom system for LLO quality control bridging prokaryotes and plants.

microbiology↗

bioRxiv2026

Developmental Chlorpyrifos Exposure Disrupts Tectal Circuit Formation and Behavior in Xenopus laevis

Developmental exposure to organophosphate pesticides has been associated with adverse neurodevelopmental outcomes, but the circuit-level mechanisms underlying these effects remain poorly understood. Here, we examined how low-level chlorpyrifos (CPF) exposure affects neural circuit maturation and behavior in Xenopus laevis tadpoles. Tadpoles were exposed to 1 {micro}M CPF from developmental stage 42 to stage 49, spanning a critical period of synaptogenesis and circuit refinement. CPF-exposed tadpoles displayed abnormal schooling behavior, characterized primarily by impaired body-axis alignment despite preserved group aggregation, as well as altered spontaneous swimming marked by reduced looping and increased seizure-like activity. Whole-cell recordings from tectal neurons revealed persistent reductions in inhibitory synaptic drive, consistent with altered excitation-inhibition balance. Although acute CPF exposure transiently increased intrinsic excitability of tectal neurons as well as baseline swimming activity, this effect was not maintained after chronic exposure. Morphological analysis of GFP-labeled tectal neurons revealed altered dendritic branching distribution despite no change in total dendritic length or branch number. Together, these findings suggest that developmental CPF exposure disrupts tectal circuit maturation, leading to abnormal neural connectivity and maladaptive behavioral outcomes relevant to neurodevelopmental dysfunction.

neuroscience↗

bioRxiv2026

Direct and Indirect Entomological Efficacy of Targeted Indoor Residual Spraying against Aedes aegypti in Iquitos, Peru

BackgroundControl of Aedes aegypti, the primary vector of dengue and other Aedes-borne viruses, is challenged by insecticide resistance, limited efficacy of existing tools and the large and widespread epidemics. Targeted Indoor Residual Spraying (TIRS), a modification of traditional indoor residual spraying focused on Ae. aegypti resting sites, has demonstrated promising results, yet its indirect community-wide effects remain underexplored. Methodology/Principal FindingsWe conducted an entomological cluster-randomized controlled trial in Iquitos, Peru, to evaluate the direct and indirect entomological impacts of TIRS using pirimiphos-methyl. Thirty clusters were randomized to receive either TIRS (15 clusters, 898 structures) or standard Ministry of Health vector control activities (15 clusters, 1,018 structures). Aedes aegypti indoor densities were assessed in the 45 days pre-intervention and at four time points up to 255 days post-intervention using Prokopack aspiration. Generalized linear mixed models with a negative binomial link were used to estimate incidence rate ratios (IRRs) and calculate efficacy (1-IRR) for houses that received TIRS (direct effect) and untreated houses in TIRS clusters (indirect effect). Direct efficacy reached 96% at 15 days post-spraying and remained significant (40%) at 255 days post-spraying. Indirect efficacy reached 69% at 15 days and declined to 7% by 255 days post-spraying. Despite only 57% household-level TIRS coverage, both direct and indirect impacts on Ae. aegypti were significant during early post-intervention surveys, and after 8 months in TIRS clusters. Conclusions/SignificanceTIRS provided substantial and sustained reductions in indoor Ae. aegypti density, including measurable indirect effects in untreated homes within intervention clusters. These findings demonstrate the entomological value of TIRS even at moderate coverage levels and highlight its potential for both preventive and reactive vector control programs and should be considered for implementation by Ministries of Health in dengue-endemic urban settings as well as by the U.S. military when deployed to tropical or subtropical locations.

ecology↗

bioRxiv2026

CYCLON is a nucleolar protein that regulates pan-cancer cell fitness through ribosome biogenesis

Tumor progression is driven by cancer cell fitness, defined as the capacity of malignant cells to maintain growth, adapt to stress and withstand therapy Cellular fitness is fundamentally governed by nucleolar processes, which act as central regulators by integrating RNA processing with ribosome biogenesis to support protein synthesis and stress adaptation. The nuclear protein CYCLON, containing a large intrinsically disordered region (IDR) could be implicated in mediating biomolecular condensates and regulatory plasticity, which are key elements of nucleolar biology. CYCLON also emerged as a candidate regulator of cancer cell fitness, as it is frequently overexpressed across tumor types. Inducible silencing and cell biology approaches have shown that CYCLON maintains nucleolar integrity, controls nucleoli size and number, nucleolin and Ki-67 distribution and prevents nucleolar stress. CYCLON contributes to ribosome biogenesis by binding ribosomal RNA (rRNA) and regulating 32S and 21S pre-rRNA processing, ultimately influencing ribosomal subunit production and global protein synthesis. Its depletion impairs proliferation and clonogenic capacity by prolonging both interphase and mitosis, leading to slowed cell cycle progression. The impact of CYCLON on cellular fitness has been consistently observed across cancer models, reinforcing its essential role in the regulation of nucleolar biology.

cancer biology↗

bioRxiv2026

Microglia Rank signaling regulates GnRH function and the Hypothalamic-Pituitary-Gonadal axis

The hypothalamic-pituitary-gonadal axis (HPG) controls pubertal development, sexual maturation, and fertility. We hereby demonstrate a new role of hypothalamic microglia in controlling the HPG axis through Rank signaling, a pathway known for its role in bone and mammary gland biology. Whole-body and microglia Rank depletion leads to hypogonadotropic hypogonadism (HH) resulting from an alteration in gonadotropin-releasing hormone (GnRH) function. In addition, we identify rare gene variants of RANK in patients with HH. Transcriptional profiling upon pubertal Rank loss reveals defective microglia activation and morphological alterations in the median eminence (ME), decreasing the contacts and engulfment of GnRH terminal projections and impairing GnRH responses to kisspeptin. Overall, our data uncovers the crucial role of microglia in regulating GnRH function through Rank signaling, with implications for reproductive maturation and fertility. One-Sentence SummaryMicroglia regulates GnRH function through RANK signaling

cell biology↗

bioRxiv2025

Copy number variation in the genome of four South American camelid species

Copy number variation (CNV), a type of structural genomic variant, has been widely studied in humans, plants, and livestock. CNVs may contribute to phenotypic variation and traits of economic importance. Evaluating CNVs in domestic populations and their wild ancestors can reveal genetic changes associated with phenotypic differences that have emerged during domestication. In this study, whole-genome data from sixteen alpacas, six llamas, one guanaco, and one vicuna were used to investigate CNVs. A total of 4,247 CNVs were identified through genome-wide analysis. Functional analysis of Gene Ontology (GO) groups indicated that CNVs in alpacas are mainly related to immune-related genes, olfactory receptor genes, and keratinization. Species-level differences were observed, with the vicuna showing the least variation and the alpaca the most. This study provides the first CNV map for camelids and contributes to expanding knowledge of CNV diversity across the four South American camelid species.

genomics↗

bioRxiv2024

Oral Exposure to Benzalkonium Chlorides in Male and Female Mice Reveals Sex-Dependent Alteration of the Gut Microbiome and Bile Acid Profile

Benzalkonium chlorides (BACs) are commonly used disinfectants in a variety of consumer and food-processing settings, and the COVID-19 pandemic has led to increased usage of BACs. The prevalence of BACs raises the concern that BAC exposure could disrupt the gastrointestinal microbiota, thus interfering with the beneficial functions of the microbes. We hypothesize that BAC exposure can alter the gut microbiome diversity and composition, which will disrupt bile acid homeostasis along the gut-liver axis. In this study, male and female mice were exposed orally to d7-C12- and d7-C16-BACs at 120 {micro}g/g/day for one week. UPLC-MS/MS analysis of liver, blood, and fecal samples of BAC-treated mice demonstrated the absorption and metabolism of BACs. Both parent BACs and their metabolites were detected in all exposed samples. Additionally, 16S rRNA sequencing was carried out on the bacterial DNA isolated from the cecum intestinal content. For female mice, and to a lesser extent in males, we found that treatment with either d7-C12- or d7-C16-BAC led to decreased alpha diversity and differential composition of gut bacteria with notably decreased actinobacteria phylum. Lastly, through a targeted bile acid quantitation analysis, we observed decreases in secondary bile acids in BAC-treated mice, which was more pronounced in the female mice. This finding is supported by decreases in bacteria known to metabolize primary bile acids into secondary bile acids, such as the families of Ruminococcaceae and Lachnospiraceae. Together, these data signify the potential impact of BACs on human health through disturbance of the gut microbiome and gut-liver interactions.

pharmacology and toxicology↗

bioRxiv2024

Effect of dataset partitioning strategies for evaluating out-of-distribution generalisation for predictive models in biochemistry

AO_SCPLOWBSTRACTC_SCPLOWQuantifying model generalization to out-of-distribution data has been a longstanding challenge in machine learning. Addressing this issue is crucial for leveraging machine learning in scientific discovery, where models must generalize to new molecules or materials. Current methods typically split data into train and test sets using various criteria -- temporal, sequence identity, scaffold, or random cross-validation -- before evaluating model performance. However, with so many splitting criteria available, existing approaches offer limited guidance on selecting the most appropriate one, and they do not provide mechanisms for incorporating prior knowledge about the target deployment distribution(s). To tackle this problem, we have developed a novel metric, AU-GOOD, which quantifies expected model performance under conditions of increasing dissimilarity between train and test sets, while also accounting for prior knowledge about the target deployment distribution(s), when available. This metric is broadly applicable to biochemical entities, including proteins, small molecules, nucleic acids, or cells; as long as a relevant similarity function is defined for them. Recognizing the wide range of similarity functions used in biochemistry, we propose criteria to guide the selection of the most appropriate metric for partitioning. We also introduce a new partitioning algorithm that generates more challenging test sets, and we propose statistical methods for comparing models based on AU-GOOD. Finally, we demonstrate the insights that can be gained from this framework by applying it to two different use cases: developing predictors for pharmaceutical properties of small molecules, and using protein language models as embeddings to build biophysical property predictors.

bioinformatics↗

bioRxiv2023

AutoPeptideML: Automated Machine Learning for Building Trustworthy Peptide Bioactivity Predictors

MotivationAutomated machine learning (AutoML) solutions can bridge the gap between new computational advances and their real-world applications by enabling experimental scientists to build their own custom models. We examine different steps in the development life-cycle of peptide bioactivity binary predictors and identify key steps where automation can not only result in a more accessible method, but also more robust and interpretable evaluation leading to more trustworthy models. ResultsWe present a new automated method for drawing negative peptides that achieves better balance between specificity and generalisation than current alternatives. We study the effect of homology-based partitioning for generating the training and testing data subsets and demonstrate that model performance is overestimated when no such homology correction is used, which indicates that prior studies may have overestimated their performance when applied to new peptide sequences. We also conduct a systematic analysis of different protein language models as peptide representation methods and find that they can serve as better descriptors than a naive alternative, but that there is no significant difference across models with different sizes or algorithms. Finally, we demonstrate that an ensemble of optimised traditional machine learning algorithms can compete with more complex neural network models, while being more computationally efficient. We integrate these findings into AutoPeptideML, an easy-to-use AutoML tool to allow researchers without a computational background to build new predictive models for peptide bioactivity in a matter of minutes. AvailabilitySource code, documentation, and data are available at https://github.com/IBM/AutoPeptideML and a dedicated webserver at http://peptide.ucd.ie/AutoPeptideML.

bioinformatics↗

bioRxiv2020

Behavioral assays to study neural development in Xenopus laevis tadpoles

Escape responses, orienting reflexes, and social behaviors in Xenopus laevis tadpoles have been well documented in the literature (Lee et al. 2010; Roberts et al. 2000; Simmons et al. 2004; Katz et al. 1981; Villinger and Waldman 2012). In this article, we describe several behavioral protocols that together allow researchers efficiently (in terms of financial cost and time investment) and effectively assess developmental abnormalities in pre-metamorphic Xenopus tadpoles.

neuroscience↗

bioRxiv2017

Immediate effects of psychosocial stress on attention depend on subjective experience and not directly on stress-related physiological changes

Acute psychosocial stress is associated with physiological, subjective and cognitive changes. In particular, attention, which is considered one of the main processes driving cognition, has been related to different stress outcomes, such as anxiety, cortisol levels and autonomic responses, individually. Nonetheless, their specific contributions to and association with attention is still not fully understood. To study this association, 42 male participants were asked to perform an attentional task just before and immediately after being exposed to either an experimental treatment designed to induce psychosocial stress using the Trier Social Stress Test (TSST) or a matching stress-free control condition. The salivary cortisol concentration, heart rate, and self-reported anxiety were measured to assess the physiological response to stress and the subjective experience during the protocol. As expected, psychosocial stress induced increases in heart rate, salivary cortisol levels and anxiety. The behavioral analysis revealed that members of the control group performed better on the attentional task after the protocol, while members of the TSST group showed no changes. Moreover, after dividing the stress group into sub-groups of participants with high and low anxiety, we observed that participants in the high-anxiety group not only failed to perform better but also performed worse. Finally, after testing several single-level mediation models, we found that anxiety is sufficient to explain the changes in attention and that it mediates the effects between heart rate and cortisol levels on attention. Our results suggest that the immediate effects of acute psychosocial stress on attention are highly dependent on the participants subjective experience, which, in turn, is affected and can mediate stress-related physiological changes.

neuroscience↗

bioRxiv2017

Non-canonical aberrant DNA hypermethylation in glioma

Aberrant DNA hypermethylation is a hallmark of cancer although the underlying molecular mechanisms are still poorly understood. To study the possible role of 5-hydroxymethylcytosine (5hmC) in this process we analyzed the global and locus-specific genome-wide levels of 5hmC in primary samples from 54 gliomas and 72 colorectal cancer patients. Levels of 5hmC in colorectal cancer were very low and no consistent changes were detected between control tissues and tumors. As expected, levels of 5hmC in non-tumoral brain samples were high and significantly reduced at the 49,601 CpG sites in gliomas. Strikingly, hypo-hydroxymethylation at 4,627 (9.3%) of these CpG sites was associated with aberrant DNA hypermethylation. The DNA regions containing these CpG sites were enriched in H3K4me2, and presented a different genuine chromatin signature to that characteristic of the genes classically aberrantly hypermethylated in cancer. We conclude that this data identifies a novel 5hmC-dependent non-canonical class of aberrant DNA hypermethylation in glioma.

cancer biology↗