Biology subjects

Lopez, A.

Publications and source records attributed to Lopez, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Pharmacologic inhibition of OLIG2 by CT-179 disrupts mitotic progression and enhances standard-of-care chemoradiotherapy in glioblastoma

Background: Glioblastoma (GBM) remains uniformly fatal. The basic helix-loop-helix transcription factor OLIG2 is universally expressed in diffuse glioma, sustains the tumor-propagating stem-like fraction, and opposes p53-mediated genotoxic responses, but has historically been considered undruggable. We characterized CT-179, a brain-penetrant small-molecule OLIG2 inhibitor, as a candidate therapeutic for GBM. Methods: Target engagement was assessed by cellular thermal shift assay, differential scanning fluorimetry, crosslinking, and electrophoretic mobility shift assay. Anti-tumor activity was evaluated across eleven patient-derived GBM cell lines, in zebrafish oligodendrocyte precursor cell (OPC)-derived tumors, and orthotopic and subcutaneous GBM models, including combinations with radiotherapy plus temozolomide and with selective Bcl-2 family inhibitors. Results: CT-179 engaged OLIG2 and altered the conformation of dimerized OLIG2 on chromatin without preventing dimerization or fully displacing OLIG2 from DNA. CT-179 reduced OLIG2-positive OPCs and OPC-derived tumors in zebrafish and inhibited proliferation across all eleven GBM lines (IC50 < 360 nM), depleting the stem-like fraction and inducing apoptosis through mitotic catastrophe, mitotic slippage, or a hybrid response. RNA-seq across three patient-derived glioma stem cell lines identified {beta}-tubulin gene isoforms as the most strongly CT-179-down-regulated transcripts at the early time point and showed correlated {beta}-tubulin and OLIG2 expression in TCGA glioblastoma specimens. Combination with the Mcl-1 inhibitor S63845 or the Bcl-2/Bcl-xL/Bcl-w inhibitor ABT-737 produced greater-than-additive cytotoxicity. Oral CT-179 crossed the blood-brain barrier and extended median survival as a single agent across two independent adult orthotopic patient-derived backgrounds (GBM8 and G06); intraperitoneal CT-179 was associated with reduced intratumoral OLIG2 and Ki-67 staining in GBM8 orthotopic xenografts. Combination of CT-179 with radiotherapy and temozolomide eliminated all GBM8 and 7 of 8 GBM4 subcutaneous xenografts without weight loss and significantly extended survival when combined with radiotherapy in MGMT-unmethylated GBM6 orthotopic xenografts (CT-179 administered intraperitoneally). Conclusions: CT-179 is a brain-penetrant inhibitor of an established GBM driver with single-agent and combination activity across several orthotopic models, supporting clinical development for GBM and translational evaluation in other OLIG2-dependent CNS malignancies.

cancer biology↗

bioRxiv2026

Mycobacterium tuberculosis inactivates host oxysterols to impair macrophage cholesterol homeostasis

Host oxysterols coordinate macrophage cholesterol homeostasis and antimicrobial defense, but whether pathogens directly target oxysterol signaling is unknown. Here, we identify pathogen-mediated enzymatic oxysterol inactivation as a mechanism by which Mycobacterium tuberculosis (Mtb) subverts host cholesterol metabolism. Mtb oxidizes the endogenous oxysterols 27-hydroxycholesterol (27-HC) and 3{beta}-hydroxycholest-5-enoic acid (3{beta}-HCA) into 3-oxo-{Delta}4 metabolites. Sputum lipidomics across TB cohorts on three continents revealed an active-disease signature characterized by 27-HC depletion and accumulation of 27-hydroxycholest-4-en-3-one (27-HCO) and 3-oxocholest-4-enoic acid (3O-CA), which normalized with treatment. In infected human macrophages, Mtb 3{beta}-hydroxysteroid dehydrogenase (3{beta}-Hsd) generated 27-HCO. Unlike their parent oxysterols, 27-HCO and 3O-CA did not activate liver X receptor (LXR), and 3O-CA failed to suppress sterol regulatory element-binding protein 2 (SREBP2) target genes. Accordingly, 3{beta}-Hsd-deficient Mtb did not induce macrophage cholesterol retention, a phenotype restored by LXR antagonism. Thus, Mtb enzymatically inactivates host oxysterols, disrupting macrophage cholesterol homeostasis and generating treatment-responsive metabolic signatures in human TB.

microbiology↗

bioRxiv2026

Reciprocal control of the stomach and intestine by viscerosensory neurons in caudal brainstem

Digestion requires precisely timed transit of food through the gastrointestinal tract. Here we show that emptying of food from the stomach occurs in discrete pulses, separated by pauses that allow the proximal duodenum to clear before the next bolus arrives. By combining X-ray fluoroscopy of the gut with calcium imaging of the brainstem, we identify a population of neurons defined by expression of neuropeptide FF (NPFF) that tracks these duodenal dynamics. Stimulation of NPFF neurons induces a coordinated response that inhibits gastric emptying and accelerates intestinal transit, thereby clearing the proximal intestine for the next bolus of food. These neurons also bidirectionally control food intake through cholinergic signaling in the gut. These findings reveal a mechanism by which brainstem transforms the sensory detection of nutrients in the duodenum into the opposing control of the stomach and intestine. They also establish an experimental approach for dissecting gut-brain signaling in behaving animals.

neuroscience↗

bioRxiv2026

Body condition as an indicator of long-term ecosystem change: evidence from common dolphins

As climate change continues to disrupt marine ecosystems, reliable body condition indices (BCIs) for sentinel megafauna species such as dolphins will become increasingly important tools for long-term ecosystem monitoring. We developed novel BCIs from routinely collected morphometric measurements and applied them to a 22-year dataset (1998-2019) of 597 stranded common dolphins (Delphinus delphis) from Northwest Spain. BCIs were calculated as residuals from Generalized Additive Models relating body length to girth and blubber thickness measurements, thereby controlling for body size effects. The indices were first validated against visually assessed nutritional status and then used to investigate long-term trends and potential environmental and trophic drivers of body condition. The girth-based BCI outperformed the blubber thickness-based index in predicting nutritional status. The indices differed in their sensitivity to confounding variables. Both indices revealed an increase in male body condition until 2009-2010 followed by a sustained decline through 2019, whereas no long-term trend was detected in females. By integrating data on climate variability (North Atlantic Oscillation), oceanographic conditions (upwelling intensity, sea surface temperature, chlorophyll-a), prey availability, and prey quality, we found evidence that changes in body condition was associated with climate- and oceanography-driven changes in prey communities and reductions in the quality of prey available to dolphins. Our findings suggest that body condition in common dolphins integrates signals across multiple components of marine ecosystems and can serve as a sensitive indicator of ecosystem change. Given growing reports of declining body condition in marine predators worldwide, the approach presented here provides a practical and transferable framework for long-term ecosystem monitoring using existing stranding network datasets.

ecology↗

bioRxiv2026

Elevated cholesterol in APOE4 astrocytes drives mitochondrial cristae collapse and ATP synthase dysfunction

Cholesterol imbalance is a hallmark of major human diseases, including atherosclerosis and Alzheimers disease, both of which are also associated with mitochondrial dysfunction, yet the mechanistic links between cholesterol and mitochondria remain poorly understood. Here we show that elevated intracellular cholesterol in murine astrocytes expressing the Alzheimers disease risk variant APOE4 disrupts the inner mitochondrial membrane, manifesting as sparse, truncated cristae alongside an excess of cristae junction complexes. These structural abnormalities are accompanied by loss of respiratory chain complexes I and IV, and reduced respiration; nevertheless, low proton leak and reverse ATP synthase activity combine to generate an elevated mitochondrial membrane potential. Strikingly, APOE4 astrocytes are hypersensitive to the ATP synthase inhibitor oligomycin, demonstrating a profound dysfunction of the enzyme, and cholesterol sequestration with methyl-{beta}-cyclodextrin abrogates this toxicity, establishing elevated cholesterol as its proximate cause. Another method of targeting ATP synthase, epicatechin, which prevents the enzyme operating in reverse, attenuated both cholesterol- and respiratory chain inhibitor-induced cell death. Reciprocally, reducing intracellular cholesterol via nutrient restriction restored cristae architecture and partially rescued respiratory chain complex abundance. These findings identify mitochondrial cholesterol as a critical determinant of cristae architecture and ATP synthase function and suggest that cholesterol-driven mitochondrial dysfunction may be a unifying feature of cholesterol-related disorders from neurodegeneration to atherosclerosis. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/742391v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@2e80a1org.highwire.dtl.DTLVardef@fecd32org.highwire.dtl.DTLVardef@51ba3corg.highwire.dtl.DTLVardef@199f3c6_HPS_FORMAT_FIGEXP M_FIG Elevated intracellular cholesterol in APOE4 astrocytes disrupts the inner mitochondrial membrane and ATP synthase, resulting in sparse cristae, increased ATP hydrolysis and heightened oligomycin sensitivity. The vulnerability to oligomycin is abrogated by cholesterol sequestration with cyclodextrin, indicating causality. These findings position cholesterol as a key determinant of the cristae landscape and ATP synthase function, highlighting the importance of the emerging field of mitochondrial-cholesterol crosstalk. C_FIG

cell biology↗

bioRxiv2026

Rapid and dynamic reprogramming within the tumor microenvironment drives EDA-CAR-T dysfunction and compromised therapeutic efficacy in solid tumors

BackgroundChimeric antigen receptor (CAR)-T cell therapies efficacy in solid tumors remains limited, largely due to the profoundly immunosuppressive tumor microenvironment (TME) which drives CAR-T cells to dysfunction and poor persistence. A comprehensive understanding of the dynamic interplay between CAR-T cells and the TME is therefore critical for the rational design of more effective CAR-T strategies for solid cancers. MethodsHere, we performed single-cell RNA sequencing of tumor samples from immunocompetent mice treated with stroma-targeting EDA-CAR-T cells, profiling CAR-T cell states and TME programs at the peak of antitumor response and during subsequent tumor progression. ResultsOur analysis revealed a marked temporal remodeling of EDA-CAR-T cells within the TME, where early antitumor efficacy is associated with concurrent expansion of cytotoxic effector CD8 CAR-T cells and activation of memory CD4 CAR-T subsets. Moreover, EDA-CAR-T cells effectively engaged the myeloid compartment, resulting in strengthened communication networks involving T cell activation. However, by tumor progression, EDA-CAR-T cells suffered a widespread transcriptional reprogramming towards dysfunction, characterized by loss of effector programs alongside induction of exhaustion and immunoregulatory pathways within the TME, including PD-L1/PD-L2 and TGF{beta} signaling, which impairs sustained immune responses. Notably, early CAR-T cell activation led to increased susceptibility to TME-mediated immunosuppression, revealing EDA-CAR-T-specific soluble galectin-mediated cell-to-cell interaction networks. ConclusionsTogether, this works offers a high-resolution view of CAR-T cell dynamics within the solid TME, uncovering cellular and molecular mechanisms of rapid functional decline and identifying regulatory pathways within the TME that can be exploited to improve CAR-T cell therapy efficacy in solid tumors. KEY MESSAGES OF THE ARTICLEO_ST_ABSWhat is already known on this topicC_ST_ABSThe determinants of CAR-T cell therapeutic efficacy in solid tumors remain poorly defined, largely due to the complexity of the immunosuppressive tumor microenvironment. In this effort, it is necessary to perform comprehensive and detailed mechanistic studies that capture CAR-T cell dynamics within the solid tumor microenvironment to understand treatment failure. What this study addsWe performed single-cell profiling of stroma-targeting EDA-CAR-T cells, revealing their dynamic reprogramming toward dysfunction within the solid tumor microenvironment. We dissected CAR-T cell states and their cell-to-cell interactions with the tumor microenvironment across response and tumor progression and identified mechanisms linking CAR-T cell functionality and therapeutic failure. How this study might affect research, practice or policyThis study provides comprehensive mechanistic insights from an immunocompetent model that can be leveraged to identify shared determinants of CAR-T cell functionality in solid tumors and potentially guide the rational development of improved CAR-T cell therapies.

genomics↗

bioRxiv2026

Wind history shapes olfactory search response in free flying Drosophila melanogaster

The ability of flying insects to locate distant food and mates by tracking odor plumes through turbulent and unsteady flow represents a remarkable feat of sensorimotor integration. Successful navigation requires not only extracting a reliable directional estimate from an intermittent olfactory signal, but also contending with the challenging dynamics of variable winds. While prior work has established that insects integrate the history of odor encounters to shape search decisions, whether they also retain a working memory of recently experienced wind conditions has remained unknown. Here, we use optogenetics combined with controlled wind perturbations in a free-flight wind tunnel to investigate how wind history modulates the olfactory search behavior of Drosophila melanogaster. By introducing lateral "gust" flow via auxiliary fans and independently delivering olfactory stimuli, we show that the wind experienced during an olfactory stimulus shapes both the immediate surge response and the subsequent spatial search. Flies that received an olfactory stimulus while being displaced by a crosswind gust were significantly more likely to return to the gust zone during the post-stimulus search phase compared to flies that received the same odor cue in steady laminar flow. Meanwhile, surge responses and course directions exhibited during search indicate that moment-to-moment flight kinematics may be driven more by instantaneous flow. These results reveal that wind experience is tracked in addition to olfactory experience, and provide evidence that Drosophila maintain a short-term working memory of ambient wind conditions to guide olfactory navigation.

animal behavior and cognition↗

bioRxiv2026

Kinetics of local C3 production orchestrates neutrophil recruitment in lung injury

Complement component 3 (C3) is crucial for host defense against bacteria. While the liver is the primary source of circulating C3, local C3 production at barrier surfaces such as the lung is key in early responses. Yet, how local complement-mediated responses are initiated at mucosal barriers is unknown. This study investigates the kinetics and necessity of lung-derived C3 during the initial hours of an infection. Using models of bacterial pneumonia in ex vivo-perfused human lungs and mice deficient in liver-derived C3, we demonstrate that intrapulmonary C3 production and activation precedes the accumulation of circulating C3 into the bronchoalveolar space. Utilizing mice deficient in lung-derived C3, we demonstrate that epithelial cell-derived C3 is required for early neutrophil recruitment in pneumonia. Transcriptomic and proteomic analyses reveal that neutrophil chemotactic pathways such as C5a and CXCL2 depend on lung epithelial cell-derived C3. These findings demonstrate how lung epithelial-derived C3 influences early mucosal responses to infection via both canonical (direct) and non-canonical (indirect) pathways. SUMMARYAlburquerque et al show an initial, entirely local phase of complement-mediated mucosal protection before a subsequent, systemic response occurs in the setting of barrier disruption. Their work suggests that complement component C3 derived locally at a barrier from the epithelium influences early responses to infection by recruiting neutrophils via multiple pathways independent of circulating C3.

immunology↗

bioRxiv2026

D-Methionine Improves Spatial Navigation and Attenuates Oxidative Stress and Amyloid Pathology in a Sex-Specific Manner

BackgroundOxidative stress and maladaptive neuroimmune activation contribute to cognitive decline in Alzheimers disease (AD) and represent therapeutic targets beyond amyloid-centered approaches. ObjectiveTo determine whether oral D-methionine (D-Met), a redox-active amino acid, reduces amyloid pathology and lipid peroxidation and confers disease-modifying benefits in AD mouse models. MethodsMale and female APP/PS1 and APPNL-F mice with advanced AD pathology received oral D-Met or vehicle. Behavioral assessments included locomotor activity and hippocampal-dependent spatial learning and memory. Amyloid burden, lipid peroxidation, peripheral metabolic and inflammatory markers, and hippocampal microglial phenotypes were evaluated using biochemical and histological analyses. ResultsD-Met did not alter locomotor or exploratory behavior but improved spatial memory recall in both sexes of APP/PS1 mice and in female APPNL-F mice. APPNL-F males exhibited improved learning during Morris water maze (MWM) acquisition. Amyloid pathology was modestly and region-specifically reduced, including decreased hippocampal plaque size in male APPNL-F mice, reduced cortical plaque size in female APP/PS1 mice, and lower soluble amyloid-{beta} (A{beta})42 in male APP/PS1 mice. Lipid peroxidation, assessed by malondialdehyde, was reduced only in female APPNL-F mice. D-Met induced pronounced sex-dependent peripheral effects, increasing adiposity and pro-inflammatory adipose signaling in males, while reducing perigonadal white adipose tissue (pgWAT) IL-6 expression in female APPNL-F mice. In the hippocampus, D-Met remodeled microglial signatures, with female APPNL-F mice showing reduced Iba1 and disease-associated microglial (DAM) markers and increased Axl expression. ConclusionShort-term D-Met acts as a metabolic and redox modulator with modest amyloid-lowering effects mediated by improved microglial function. Therapeutic efficacy is strongly sex- and model-dependent, with the greatest benefit observed in female APPNL-F mice.

neuroscience↗

bioRxiv2026

From cognitive abstraction to adaptive behavior: neural bases of concept learning in autistic adolescents

BACKGROUNDLearned knowledge does not consistently generalize to new contexts in autistic individuals, limiting potential for adapting to real-world demands. This challenge is hypothesized to stem from difficulties with forming abstract representations, potentially arising from perceptual processing that favors local details over the gestalt. We tested the prediction that generalization would be primarily based on exemplar-specific representations in autistic youth using computational modelling coupled with neuroimaging. METHODSSixty-four autistic adolescents without intellectual disability (69% males; ages 14-18 years) completed a category generalization task during functional magnetic resonance imaging at two time points. Computational models estimated abstract (prototype-based) and specific (exemplar-based) representations and underlying neural correlates. We further examined associations with adaptive functioning and moderation by autistic traits. RESULTSContrary to predictions, we observed a consistent prototype-dominant majority, a subgroup who generalized without consistent representational reliance, and a small minority who failed to acquire category structure. Prototypes were represented in bilateral ventromedial prefrontal cortex (VMPFC), inferior parietal lobule (IPL), right frontal pole, and right lateral occipital cortex, while exemplars were represented in bilateral cuneus. Better generalization predicted better real-world adaptive functioning. Moreover, greater prototype-related activation in left IPL predicted better adaptive functioning in participants with higher autistic traits. CONCLUSIONSThese findings challenge the prevailing view that concept learning in autism relies primarily on hyper-specific perceptual processing, identify meaningful variability in representational strategies, and reveal neural pathways through which abstract representation may support real-world adaptive behavior.

neuroscience↗

bioRxiv2026

Lethal epistasis maintains strong linkage disequilibrium between unlinked supergenes

Linkage disequilibrium (LD) between adaptive gene combinations is typically maintained through physical linkage and suppressed recombination. Although epistatic interactions can maintain LD between unlinked loci, this mechanism is rarely documented in nature. Supergenes, regions of suppressed recombination containing tightly linked loci, typically exemplify the first mechanism, in which genomic rearrangements lock together coadapted alleles. Here, we demonstrate a rare case of epistasis-driven LD between two supergenes on different chromosomes in the European ant Formica cinerea: one controlling colony queen number (chromosome 3) and another determining sexual body size (chromosome 9). We show that these supergenes assort independently according to Mendelian expectations during meiosis, yet exhibit high LD between the multi-queen haplotype P2 and the miniaturizing haplotype 9r, with small queens and males occurring exclusively in multi-queen colonies. Mismatched genotype combinations (P2 without 9r and vice versa) are severely underrepresented among all adult castes, with mismatched males experiencing complete mortality. We show that this pattern cannot be explained by meiotic drive or maternal-effect killing, assortative mating, or extrinsic selection on adults, indicating strong postzygotic epistatic selection maintaining the observed LD. The fitness costs of these epistatic interactions are substantial but critically depend on mating combinations: heterozygous small queens achieve 1.5-2.5 times higher fitness (based on offspring genotype viability) when mated to small males (P2-9r) compared to large males. Our findings provide empirical evidence for epistatic interactions between unlinked supergenes maintaining LD in the absence of physical linkage.

evolutionary biology↗

bioRxiv2025

Historic Overexploitation, Genetic Erosion and Local extinction: Palaeogenomic Insights into the Decline of Eubalaena glacialis in the Northeast Atlantic

The North Atlantic right whale (Eubalaena glacialis) was the primary target for early industrial whalers, particularly the Basques. Once widespread across temperate and subpolar waters on both sides of the North Atlantic, the species is now functionally extinct in the Northeast Atlantic and listed as critically endangered by the IUCN. Despite their fragmentary remains, bones are abundant in the archaeological and historical records and reveal a long history and extensive tradition connected to the exploitation of these marine resources. Using state-of-the-art ancient DNA techniques, here we aimed at genetically characterizing the lost Northeast Atlantic population. We sequenced 17 genomes from historical specimens collected in the Cantabrian Sea, dating from the 13th-18th century, and compared them with available genomes for 12 individuals from the surviving Northwest Atlantic population. Our analyses reveal a historically panmictic population and document a dramatic decline in genetic diversity from the Middle Ages to the present. These findings illuminate the profound impact of centuries of whaling, which eradicated the Northeast Atlantic population and severely depleted genetic diversity in the remnant population.

evolutionary biology↗

bioRxiv2025

A database of biological thermal performances

We built a database of thermal performance curves that includes different variables --mostly population growth rates --for species in representative groups across major domains, including viruses, bacteria, archaea, unicellular eukaryotes (such as fungi), and multicellular eukaryotes (including plants and both invertebrates and vertebrates). To build the database, we integrated previous databases and compiled additional data from individual studies, all of which were normalized to the same units when corresponding. Our database contains data for 1300 curves across 1125 different species and 38 variable types. The database consists of four (.csv) tables and an R code that can be explored through an R package or a Shiny app. Applications of our dataset include providing a resource to studies in thermal ecology and integration with other types of data, such as geographic temperatures. This would allow us to make further predictions, such as potential species distributions based on their thermal tolerances and their changes with climate warming.

bioinformatics↗

bioRxiv2025

Scaling laws in biological thermal performances

Understanding the extent to which genetic correlations change in response to environmental factors, such as temperature, is a poorly explored question, despite the importance of understanding how different processes will change with climate warming. Despite correlations between thermal performance traits having been reported in the literature for a few taxa and performance tasks, such as population growth rate, a comprehensive global analysis of the entire tree of life and multiple performance tasks remains an open challenge. To advance in this open question, we compile a database of 1,300 thermal response curves, encompassing 38 variable types related to individuals performance (including per capita population growth rate, photosynthetic rate, among others) and 1,125 different species, ranging from viruses to mammals, encompassing all major lineages of the tree of life. Our analysis reveals that among all possible relationships between traits and optimal performance, four traits form a line with a high goodness-of-fit, while the remaining traits exhibit a polygonal pattern, either a triangle or a tetrahedron. We derive a thermodynamic framework that explains the relationships described by a curve or line (as opposed to a surface or polygon), highlighting the linear relationship between maximum and minimum temperatures, as well as between maximum and optimum temperatures. We also discuss other generic trait evolution models, which could account for the other significant sublinear relationships, as well as the more general model, Pareto optimality theory, which could account for relationships in the form of lines or polygons. Our theoretical framework and empirical evidence suggest that, based on a single data point (e.g., minimum temperature), all critical temperature limits and maximum performance boundaries can be predicted using the estimated parameter from this study. Our results reveal universal scaling relationships in thermal performance, which could be useful for predicting changes in performance under scenarios of climate warming.

biophysics↗

bioRxiv2025

Exploring the Repetitive DNA Diversity in Solanum betaceum (Solanaceae)

The Solanaceae family, known for its diverse and economically important crops, includes the genus Solanum, which comprises 1,245 species. Solanum betaceum (tree tomato), native to the Andes and cultivated globally, is a promising species due to its nutritional value and market potential. The Cyphomandra clade, which includes the tree tomato, is characterized by huge genomes and chromosomes, with repetitive DNA elements (e.g., retrotransposons and satellite DNA) playing crucial roles in genomic and evolutionary studies. Despite its importance, genetic research on S. betaceum remains limited. This study addresses this knowledge gap by characterizing the repetitive DNA fraction to better understand intraspecific variation and develop molecular markers. Samples from five populations in northwestern Argentina were cultivated, and genome size was assessed via flow cytometry. Illumina HiSeq sequencing combined with RepeatExplorer analysis was used to identify repetitive DNA elements. Cytogenetic techniques, including CMA/DAPI staining and fluorescence in situ hybridization (FISH), were employed to detect satellite DNA patterns. Genome size analysis revealed slight variation among populations. Repetitive DNA accounted for 63.5% of the genome, with Ty3-gypsy retrotransposons being the most abundant (51.44%). Satellite DNA and rDNA were less prevalent, comprising 0.93% and 0.30% of the genome, respectively. Population comparisons showed consistent proportions of repetitive DNA overall, with notable differences in Ty3-gypsy-Tekay and satellite DNA fractions. This study provides a detailed profile of the repetitive DNA landscape in S. betaceum, uncovering intraspecific differences and delivering valuable genomic insights for future breeding and conservation efforts.

genomics↗

bioRxiv2025

Cross-species analysis identifies genotype-driven vulnerabilities in lung adenocarcinoma

While three major genetic alteration subsets, characterized by mutations in STK11, KRAS, and EGFR, are seminal in driving tumorigenesis in LUAD, their distinct effects on tumor cells and the tumor microenvironment are not fully understood. Here, we map critical oncogenic subset-specific vulnerabilities by identifying conserved cell-type-specific reprogrammings between human and mouse LUAD. Through harmonized scRNA-seq analysis of 57 human and 18 mouse specimens, we unveil that genetic alterations impose genotype-specific immune imprints on the tumor microenvironment: KRAS is associated with a transitional immune state, whereas STK11 and EGFR mutations define discrete and contrasting immune phenotypes. We find that STK11-mutant tumors exhibit complement and interferon-rich immune microenvironments while EGFR-mutant tumors harbor a naive T cell-rich phenotype accompanied by a global HLA downregulation, stress-responsive alveolar macrophages marked by MARCO. In the epithelial compartments, cross-species analysis reveals metabolic dependencies, including OGDH in EGFR- and PDE4D in STK11-mutant cells. Statement of SignificanceThis study delineates oncogenotype-specific molecular and immune imprints in lung adenocarcinoma, revealing STK11-, KRAS-, and EGFR-mutated tumors as transcriptionally and immunologically discrete ecosystems. By mapping epithelial vulnerabilities alongside immune imprints, we unveil genotype-imposed dependencies that inform the rational development of precision therapies with direct translational relevance.

cancer biology↗

bioRxiv2025

The Crunchometer: A Low-Cost, Open-Source Acoustic Analysis of Feeding Microstructure

Elucidating the neuronal circuits that govern appetite requires precise, high-resolution monitoring of the microstructure of solid food consumption, a need unmet by existing tools, which are either costly or lack the temporal resolution to align feeding events with neuronal activity. To overcome this, we developed the Crunchometer, a low-cost, open-source acoustic system that uses computational algorithms to generate high-resolution feeding ethograms from the sounds produced during solid food consumption. Validation across energy states (hunger/satiety) confirmed its sensitivity to changes in feeding microstructure, and the system reliably detected semaglutide-induced suppression of intake and reduced preference for a high-fat diet. Leveraging its seamless integration with in vivo recordings in freely behaving mice, we paired the Crunchometer with lateral hypothalamus (LH) electrophysiology to identify "meal-related" neurons that track entire meals rather than individual bouts. Calcium imaging further revealed that distinct subsets of LH GABAergic and glutamatergic neurons were tuned to feeding only, to licking only, or to both behaviors. Thus, LH neuronal ensembles differentially encode the consumption of solid food versus liquid sucrose. These findings demonstrate that the Crunchometer is a robust, accessible platform for dissecting the neural correlates of feeding behavior at the resolution of a single bite. Significance statementThe Crunchometer is a low-cost, open-source technology that democratizes feeding analysis, enabling the precise dissection of neuronal circuits involved in appetite to advance therapies for obesity and eating disorders.

neuroscience↗

bioRxiv2025

PHYSICOCHEMICAL PROPERTIES OF ENHANCED AND RECOVERED VENEZUELAN CRUDE OIL TREATED WITH BIOCOMPATIBLE PHARMACEUTICAL FORMULATION: SIMULATION OF THE ROLE OF WATER AND IONIC CONTENT.

In this work, the hydrogen bonding interaction of water and ethanol with Polysorbate 80 (P-80, Tween 80) is simulated, in relation to its role in oil upgrading and recovery, using real theoretical and experimental studies. The theoretical physicochemical results obtained were compared with other experimental results derived from the treatment of improved and recovered oil after mixing Biocompatible Pharmaceutical Formulations (BPF) of these three compounds and oil produced in Venezuela. The Spartan 16 program was used to build the molecular structures and simulate the interactions with the semi-empirical PM3 method, to compare them with two real experiments. These two experiments were performed as follows: in the first, the mixture consists of a surfactant, (Z)-Sorbitan mono-9-octadecenoate poly(oxy-1,2-ethanediyl) or polyoxoethylene (20) sorbitan mono-oleate (Polysorbate 80), which is mixed with the hydrocarbon, and then completely fluidized with the addition of ethyl alcohol or ethanol.Water and ions (<100 ppm) present in this experiment are contained in oil and ethanol as contaminants (approximately 1.73-1.30% of total water). In the second experiment, the BPF ratios were 10:5:0.1:0.01 for oil:water with 17,800 ppm NaCl:P-80:ethanol (approximately 33.09% of total water and 1.78% w/v NaCl). The simulations were performed taking into account both real experiments. The simulated interactive products were characterized by the following parameters: energy, minimum conformational energy, solvation energy, aqueous energy, HOMO energy, LUMO energy, {Delta}E, dipole moment, polarizability, electrostatic potential map (EPM) and electron density.A theoretical parametric relationship (sio Index, "stability in oil Index") is developed to evaluate the stability of the molecular forms generated within the hydrocarbon. The following theoretical experiments were performed: First, successive interactions of water with P-80 from position 1 to position 21. Second, successive interactions from position 1 to position 21 of P-80 of water and ethanol, 1 to 1. Third, successive interactions with P-80 of 21 ethanol molecules on the final product of the first experiment. These theoretical results were compared with some experimental results obtained using Oil Mixtures. The results obtained and compared in both experimental series (theoretical and real) allow to distinguish the role of P-80, Ethanol, Water and ions for the improvement and recovery of the treated oil. It is concluded that the formulation that does not contain added water and sodium chloride is supposed to use the contaminating water present in the petroleum and the water contained in the ethanol (<5%).This formulation has very little effect on the resulting Density of the improved Oil, but it greatly decreases the resulting Viscosity in the Crude Oil. The formulation that contains more than 30% added Water decreases the Density while the Viscosity of the Crude Oil responds proportionally to the Water retained in it. This difference in the results could be interpreted as a different proportion and chemical composition as a consequence of a different structural relationship between these components and a different conformation of the nanoparticle generated within the Oil, in each case. In this sense, the hypothesis is established that there would be an intermediate molecular form that could improve both Viscosity and Density.

biophysics↗