Biology subjects

Andres, M.

Publications and source records attributed to Andres, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Odors Smell Like Their Components: A Linear Framework for Predicting Olfactory Mixture Perception

Most smells, whether in food, perfume, or the environment, are complex mixtures of many odor molecules. A principled framework for modeling natural mixtures has been considered intractable because mixtures are widely assumed to generate nonlinear perceptual interactions that mirror nonlinear responses at the receptor and neural levels. We quantified perceptual interactions across 432 mixtures composed of 144 component odorants using a trained human panel, and nearly all mixtures were explained by a linear average of their component quality profiles. Within this linear modeling framework, averaging component profiles predicted mixture perception significantly better than the previous state-of-the-art and approached the ceiling set by measurement noise. Even mixtures previously reported to exhibit emergence were equally well predicted. These results suggest that the main challenge in modeling odor perception is characterizing individual components, rather than exhaustively mapping odor-odor interactions. Just as additive color mixing enabled colorimetry, linear mixing in olfaction opens the door to quantitative odorimetry, allowing mixtures to be predicted, reconstructed, and optimized computationally.

neuroscience↗

bioRxiv2026

An auditory advantage of Rdl-resistant mosquitoes may promote its persistence in urban environments

Despite dieldrin being discontinued, resistance mutations in the GABA-gated chloride channel RDL (Resistance to dieldrin) continue at high frequencies in natural malaria mosquitoes, suggesting a selective advantage. We showed that RDL modulates the mosquito auditory sensitivity. Because acoustic recognition is essential for mate acquisition, we hypothesized that resistance mutations confer a pleiotropic effect on mating success, with potential consequences for sexual selection. We provide laboratory evidence that resistance mutations enhance auditory and mating behaviours. We then conduct field collections in the city of Bangui (Central African Republic) and rural areas, revealing an association between Rdl resistance genotypes and urban settings, and within the city, with the noisiest locations. We also show decreased mating success of susceptible females with increasing noise levels, suggesting detrimental effects. Together, our findings support that Rdl resistance mutations enhance auditory function and mating success. We propose that this auditory advantage may contribute, together with other selective pressures such as cross-selection by other insecticides, to the persistence of these alleles in nature and may facilitate urban colonization by malaria vectors.

evolutionary biology↗

bioRxiv2026

Odor Sampling Bags Enable Reliable Delivery of Controlled Odor Concentrations

Precise control of odorant concentration is essential for reliable olfactory research, yet existing odorant delivery methods often suffer from solvent interactions and dilution from ambient air, limiting stimulus consistency in olfactory research. We developed an odor sampling bag system using Nalophan plastic to create a closed headspace with air as the carrier medium, eliminating solvent-related variability and ambient air dilution. In two independent experiments, 15 trained panelists each rated the perceived intensity of seven concentrations of benzaldehyde and 2-heptanone using both gas-sampling bags and glass jars. Bags produced higher maximum perceptual intensities (p < 0.001) and greater test-retest reliability than jars (Experiment 1: r = 0.89 vs. 0.81, p < 0.001; Experiment 2: r = 0.86 vs. 0.72, p < 0.001). Notably, the two tested odorants showed different maximum intensities in bags (p < 0.001) but not jars (p = 0.85), suggesting bags better preserve odorant-specific concentration differences. Photoionization detector measurements confirmed stable headspace concentrations over time, comparable to industry-standard Tedlar bags. This cost-effective approach offers improved stimulus control for olfactory psychophysics research.

neuroscience↗

bioRxiv2025

Distortion rules: audibility creation in the mosquito ear

Hearing begins when ears convert sound into neuronal excitation. The hearing organs of male Anopheles mosquitoes rank amongst the most sensitive ears evolved. Males use them to detect faint female flight tones within noisy mating swarms, but female flight tones largely lie above the males hearing range. We report a mechanism by which inaudible higher-frequency primary tones become audible through intrinsically generated, lower-frequency distortion tones. Distortion-evoked responses show [~]10-times greater sensitivity and 45% higher temporal precision than those of same-frequency primary tones. Moreover, self-sustained oscillations of the males ear dramatically reshape auditory frequency tuning and neuronal recruitment. By one mechanism, mosquito ears thus create audible signals and isolate these from the most salient frequencies of background noise. In audiology, distortions are used for diagnostics; their biological relevance, however, is unknown. Our results suggest that distortions are not mere by-products of the auditory process, but integral to its signaling logic.

neuroscience↗

bioRxiv2025

Controlling malaria mosquito reproduction via the octopamine beta2 receptor

Mosquito reproduction in a broad sense involves multiple steps from acoustic recognition of mating partners to egg hatching. We show that the octopamine receptor AgOct{beta}2R controls different aspects of this process in a sexually dimorphic manner. AgOct{beta}2R knockout males present auditory defects that impair their ability to inseminate females, whilst knockout females are sterile. These phenotypes suggest AgOct{beta}2R as a target to impair mosquito reproduction at multiple levels. We test the reproductive effects of the insecticide amitraz, an AgOct{beta}2R agonist, showing that amitraz exposure reduces insemination in the lab but not in the field and has no effects on female sterility, excluding its applicability as a mating disruptor. Pharmacological assays reveal that AgOct{beta}2R sensitivity to amitraz is reduced compared to other arthropods, but its responses can be altered by modifying residues in the binding pocket. Together, our results establish AgOct{beta}2R as a promising target to disrupt mosquito reproduction but emphasize the necessity of developing new tools to exploit this approach.

neuroscience↗

bioRxiv2025

A quantitative framework for predicting odor intensity across molecule and mixtures

In vision and hearing, standardized units such as lumens (for brightness) and decibels (for loudness) allow consistent quantification of stimulus intensity, enabling precise control of sensory experiences. Olfaction, by contrast, currently lacks a robust quantitative framework linking physical stimulus properties directly to perceived odor intensity, complicating efforts to accurately characterize and manipulate aromas. To bridge this gap, we used a precisely controlled odor delivery system combined with deep learning models to predict the intensity of both single molecules and mixtures from physical properties. These models allowed us to develop an automated, quantitative method that accurately identifies which volatile components meaningfully contribute to aroma perception, overcoming the limitations of traditional heuristic approaches such as odor activity values and demonstrating practical utility in complex naturalistic odors.

neuroscience↗

bioRxiv2025

cAMP-related second messenger pathways modulate hearing function in Aedes aegypti mosquitoes

The powerful ears of male Aedes aegypti mosquitoes facilitate identification and localization of mating partners via detection of female flight tones. Male hearing function is modulated by the efferent release of neurotransmitters, though the secondary mechanisms underlying this modulation remain unclear. Here, we investigated these mechanisms using octopamine as a model, as octopamine modulates hearing function and the erection status of fibrillar hairs lining male ears. We found that pharmacological interference with octopamine receptors alters hearing function at multiple levels and identified the second messenger cAMP as likely mediating these changes. Furthermore, the erection status of male ear fibrillar hairs could be altered by targeting specific sub-types of octopamine receptors, but these changes were not linked to changes in ear frequency tuning. Finally, we suggest that octopamine 2 receptors linked to fibrillar hair erection may not always produce functional proteins across species, with downstream implications for hearing behaviors. HighlightsO_LIOctopamine and its receptors are found throughout Aedes aegypti mosquito ears C_LIO_LIPharmacological interference with octopamine receptors modulates hearing function C_LIO_LIModulating levels of the second messenger cAMP also alters hearing function C_LIO_LIEar frequency tuning does not correlate with the erection of hairs lining male ears C_LI

neuroscience↗

bioRxiv2025

Using a female-specific isoform of doublesex to explore male-specific hearing in mosquitoes

Animal reproduction relies on elaborate divisions of labour and multiple dimorphisms between the sexes. Primary dimorphisms affect core elements of reproduction, secondary dimorphisms affect more indirect traits, including complex behaviours. In disease-transmitting mosquitoes, males locate females acoustically prior to copulation (phonotaxis). No comparable acoustic behaviour is known for females. As a result, the males ears - and hearing performance - have evolved to become substantially more complex. Sex-specific hearing in mosquitoes is in part controlled by the doublesex (dsx) gene. Intriguingly, dsx forms a linker between primary and secondary dimorphisms: spermatogenesis and ear morphogenesis share considerable molecular overlap and both depend on dsx expression patterns. We have combined transcriptomics with functional-anatomical analyses to dissect dsx-dependent hearing in the malaria mosquito Anopheles gambiae. By cross-linking our auditory findings to the genetic bases of spermatogenesis we advance the molecular understanding of sex-specific hearing mechanisms in insects, highlighting the special roles of ciliary factors therein. HighlightsO_LIDisruption of the female-specific exon of the doublesex gene alters hearing in female Anopheles gambiae mosquitoes C_LIO_LIFemale mutant ears are anatomically and functionally distinct from both wild-type male and female; they show a substantial, but incomplete, masculinisation C_LIO_LIContrary to males, and similarly to females, the flagella of female mutants do not exhibit Self-Sustained Oscillations (SSOs) C_LIO_LITranscriptomic comparisons of ears uncovered molecular bases of auditory maleness, these were closely linked to molecular machinery of ciliary function C_LIO_LIComparisons with existing transcriptome from male testes revealed a substantial overlap between male ear and testicular ciliary motility machineries C_LI

neuroscience↗

bioRxiv2025

Differential regulation of histone H1 subtypes by N6-methyladenosine RNA methylation.

Histone H1 is involved in the regulation of chromatin structure and gene expression. Up to seven H1 subtypes or variants are expressed in human somatic cells. The H1 complement, defined as the subtype composition and proportions in each cell, is highly variable depending on the cell type, cell cycle stage, developmental context, and several diseases such as cancer. This variability results from the combined action of multiple regulatory processes. Epitranscriptomic modifications have emerged as a new regulatory layer capable of controlling all aspects of mRNA metabolism. In this work, we examined the role of the most prevalent mRNA modification, N6 methyladenosine (m6A), in the regulation of H1 subtypes. MeRIP-seq showed that H1-0 and H1-4 are enriched in m6A, whereas H1-2 displays intermediate levels of this mark. Integration of the functional studies involving m6A inhibition and partial depletion of these m6A readers led us to propose the first model of the differential regulation of H1 subtypes by m6A. In this model, m6A promotes the degradation of H1-0 mRNA mediated by YTHDF2, while it enhances the stability of H1-2 mRNA through IGF2BP1 binding and its translation by the combined action of IGF2BP1 and hnRNPD. In the case of H1-4, m6A promotes its transcription and stimulates its translation via hnRNPD binding. These findings suggest that m6A participates in the subtype-specific regulation of H1 variants, adding another layer to their complex regulation and contributing to the variability of the H1 complement in cancer. KeypointsO_LIHistone transcripts have different levels of m6A. C_LIO_LIWe analyzed the function of m6A in H1-0, H1-2, and H1-4 and identified its readers. C_LIO_LIWe propose the first model of the role of m6A in the subtype-specific regulation of histone H1. C_LI

molecular biology↗

bioRxiv2024

Pupil size variations reveal Bayesian inference in cognitive arithmetic

The assumption that the brain relies on Bayesian inference has been successful in accounting for many behavioural and neurophysiological observations, but to date, dependence on such mechanism has not been assessed in the context of arithmetic. Bayesian inference implies the representation of uncertainty and reliance on prior beliefs. In arithmetic problem solving, it would consist in refining prior knowledge about the response range as the system progressively integrates the numerical information conveyed by the operands. Within this framework, the amount of information needed to progress from a prior to a posterior probability distribution over responses can be quantified by the information gain, which would relate to the cognitive workload of the task. To test this hypothesis, we designed three experiments in which participants computed the sum of two numbers presented one after another through headphones. In each experiment, the information about response predictability conveyed by the first operand was manipulated. The first operand was either highly informative and contributed to narrow down the response range, or poorly informative and conveyed little information about a plausible response. Throughout all experiments, we found that pupil-related arousal signalled the information gain associated with the first operand, indicating that participants already updated the probability distribution of possible responses upon hearing that first stimulus. This finding shows that Bayesian inference is central to arithmetic problem solving and that information gains consecutive to the integration of the operands can be tracked over time through pupillometry. Public significance statement- This study suggests that when we do arithmetic, our brain uses Bayesian inference, a method similar to how scientists update their theories based on new evidence. This means that when doing math, we start with hypotheses about the result and progressively narrow down possible solutions. - By observing the eye of the participants while they were solving arithmetic problems, the authors showed that their pupil size increased in proportion to the amount of processed information. - The authors also found that when participants received more informative first operands in the math problem, and when their pupil size increased more during this presentation, they were also faster to respond, indicating that greater initial information processing facilitated quicker problem-solving.

neuroscience↗

bioRxiv2024

The GABAA receptor RDL modulates the auditory sensitivity of malaria mosquitoes.

Malaria mosquitoes mate in crowded, and noisy, swarms. A vital stage of their precopulatory behaviour involves detecting the faint flight tone of a mating partner amidst the noise from hundreds of other mosquitoes. This exquisite sensory performance is enabled by a complex auditory system with remarkable features. One such feature is their vast efferent control system, which provides the mosquito ear with the required plasticity to adapt to various external and internal changes. In this paper, we study the auditory role of GABA, one of the main efferent signalling molecules in the mosquito ear, and its interactions with octopamine, another neurotransmitter of the efferent network. We show that GABA is released in the malaria mosquito auditory nerve and that GABA receptors are expressed in the ear, including the GABAA receptor Resistance to Dieldrin (RDL), a target for the evolution of insecticide resistance. Using picrotoxin to antagonize RDL receptors, we discovered multiple auditory effects of GABA at the mechanical and electrical level. At the mechanical level, blocking RDL promotes the erection of antennal fibrillae and the cessation of flagellar self-sustained oscillations. These effects are not observed in knockouts of the octopamine receptor AgOct{beta}2, suggesting that RDL auditory mechanical effects are mediated through octopamine release in the mosquito ear. Electrically, picrotoxin injection increases the spontaneous firing of auditory neurons and direct current (DC) responses of the nerve to mechanical stimulation both in wildtype and AgOct{beta}2 mutants, indicating that RDL may also modulate auditory sensitivity via octopamine-independent pathways. In summary, our experiments uncover distinct auditory roles of GABA, as well as synergistic roles with octopamine. The data show a fundamental role of RDL in controlling the auditory function of malaria mosquitoes and implicate RDL signalling in mating of natural malaria mosquito populations.

neuroscience↗

bioRxiv2024

Quantification of histone H1 subtypes using targeted proteomics.

Histone H1 is involved in the regulation of chromatin structure. Human somatic cells express up to seven subtypes. The variability in the proportions of somatic H1s (H1 complement) is one evidence supporting their functional specificity. Alterations in the protein levels of different H1 subtypes have been observed in cancer, suggesting their potential as biomarkers and that they might play a role in disease development. We have developed a mass spectrometry based (MS) parallel reaction monitoring (PRM) assay suitable for the quantification of H1 subtypes. Our PRM method is based on the quantification of unique peptides for each subtype, providing high specificity. Evaluation of the PRM performance on three human cell lines showed high reproducibility and sensitivity. Quantification values agreed with the electrophoretic and Western blot data, indicating the accuracy of the method. We used PRM to quantify the H1 complement in peripheral blood samples of healthy individuals and chronic myeloid leukemia (CML) patients. Our preliminary data revealed differences in the H1 complement between responders and non-responder CML patients and suggest that the H1 content could help predicting imatinib response.

biochemistry↗

bioRxiv2023

Generation of a Plasmodium falciparum reporter line for studies of parasite biology throughout the life cycle

Fluorescence reporter strains of human malaria parasites are powerful tools to study the interaction of the parasites with both human and mosquito hosts. However, low fluorescence intensity in transmission-relevant parasite stages and the choice of insertion loci that cause parasite developmental defects in the mosquito largely limits usefulness of currently available lines. To overcome these limitations, we used a CRISPR-Cas9-mediated approach to generate PfOBC13GFP, a novel selection marker-free reporter parasite in the background of the African NF54 Plasmodium falciparum line. As docking site, we selected the OBC13 locus that is dispensable for asexual and sexual development in vitro. PfOBC13GFP parasites encode GFP flanked by hsp70 UTRs that drive strong fluorescence reporter expression throughout blood and mosquito stages, enabling parasite detection by such high throughput methods as flow cytometry. When compared to the parental line, PfOBC13GFP parasites showed normal development during blood and mosquito stages, and they efficiently infected the main African vector Anopheles coluzzii, overcoming one of the limitations of the previously developed fluorescent reporter lines based on the Pfs47 locus. PfOBC13GFP constitutes a potent tool enabling host-pathogen studies throughout Plasmodium life cycle. ImportanceFluorescence reporter strains have been very useful in malaria research, however, up to date they had limitations in mosquito infectivity and fluorescence intensity. Here we report the generation of PfOBC13GFP, a new fluorescent parasite strain of the human malaria parasite P. falciparum. PfOBC13GFP parasites are highly fluorescent throughout the life cycle, making them an ideal tool for the study the parasite progression through blood and mosquito stages. They efficiently infect the African mosquito vector A. coluzzii, allowing the study of this African parasite in its biological background. Moreover, strong parasite fluorescence enables flow cytometry and live microscopy characterization of all parasite stages, especially those involved in transmission.

microbiology↗

bioRxiv2022

A Principal Odor Map Unifies Diverse Tasks in Human Olfactory Perception

Mapping molecular structure to odor perception is a key challenge in olfaction. Here, we use graph neural networks (GNN) to generate a Principal Odor Map (POM) that preserves perceptual relationships and enables odor quality prediction for novel odorants. The model is as reliable as a human in describing odor quality: on a prospective validation set of 400 novel odorants, the model-generated odor profile more closely matched the trained panel mean (n=15) than did the median panelist. Applying simple, interpretable, theoretically-rooted transformations, the POM outperformed chemoinformatic models on several other odor prediction tasks, indicating that the POM successfully encoded a generalized map of structure-odor relationships. This approach broadly enables odor prediction and paves the way toward digitizing odors. One-Sentence SummaryAn odor map achieves human-level odor description performance and generalizes to diverse odor-prediction tasks.

neuroscience↗

bioRxiv2022

A novel beta-adrenergic like octopamine receptor modulates the audition of malaria mosquitoes and serves as insecticide target

Hearing is an essential sense in the life cycle of malaria mosquitoes. Within large swarms formed transiently at dusk, mosquitoes acoustically recognize their mating partners by their wingbeats. Indeed, malaria mosquitoes only respond to the flight tones of mating partners during swarm time. This phenomenon implies a sophisticated context- and time-dependent modulation of mosquito audition, the mechanisms of which are still largely unknown. Using transcriptomics, we identify a complex network of candidate neuromodulators regulating mosquito hearing. Among them, octopamine stands out as regulator of the auditory performance during swarm time. To explore octopamines roles in mosquito hearing, we carried out an in-depth analysis of octopamine-mediated effects on auditory function. We found that octopamine affects the properties of the mosquito ear on multiple levels: it modulates the tuning and stiffness of the flagellar sound receiver and it controls the erection of antennal fibrillae in males. We found that two different receptors are driving octopamines auditory roles, including a novel beta octopamine receptor. We also demonstrate that the octopaminergic auditory control system can be targeted by insecticides. Our findings identify octopamine signalling as a key component of hearing and mating partner detection in malaria mosquitoes, and as a potential novel target for mosquito control.

neuroscience↗

bioRxiv2021

Flight-tone mediated circadian control of audibility in mating swarms of Anopheles mosquitoes

Mating swarms of malaria mosquitoes form every day at sunset throughout the tropical world, they typically last less than 30 minutes. Activity patterns must thus be highly synchronized between the sexes. Moreover, males must be able to identify the few sporadically entering females by detecting the females faint flight tones. We here show that the Anopheles circadian clock ensures a tight synchrony of male and female activity and -importantly - also retunes the males acoustic detection system: by lifting their own flight tones at dusk, males actively enhance the audibility of females. The reported phenomenon of harmonic convergence is a random by-product of the mosquitoes flight tone variance. Intriguingly, flight tones of individual mosquitoes occupy narrow -partly non-overlapping-frequency ranges, suggesting that the audibility of individual females varies across males. One Sentence SummaryMale mosquitoes sharpen their hearing at sunset.

neuroscience↗

bioRxiv2020

Towards understanding the regulation of histone H1 somatic subtypes with OMICs.

BackgroundHistone H1 is involved in the regulation of chromatin higher-order structure and compaction. In humans, histone H1 is a multigene family with seven subtypes differentially expressed in somatic cells. Which are the regulatory mechanisms that determine the variability of the H1 complement is a long-standing biological question regarding histone H1. We have used a new approach based on the integration of OMICs data to address this question. ResultsWe have examined the 3D-chromatin structure, the binding of transcription factors (TFs), and the expression of somatic H1 genes in human cell lines, using data from public repositories, such as ENCODE. Analysis of Hi-C, ChIP-seq, and RNA-seq data, have shown that transcriptional control has a greater impact on H1 regulation than previously thought. Somatic H1 genes located in TADs show higher expression than in boundaries. H1 genes are targeted by a variable number of transcription factors including cell cycle-related TFs, and tissue-specific TFs, suggesting a finetuned, subtype-specific transcriptional control. We describe, for the first time, that all H1 somatic subtypes are under transcriptional co-regulation. The replication-independent subtypes, which are encoded in different chromosomes, isolated from other histone genes are also co-regulated with the rest of the somatic H1 genes, indicating that transcriptional co-regulation extends beyond the histone cluster. ConclusionsTranscriptional control and transcriptional co-regulation explain, at least in part, the variability of H1 complement, the fluctuations of H1 subtypes during development, and also the compensatory effects observed, in model systems, after perturbation of one or more H1 subtypes.

molecular biology↗

bioRxiv2020

Typical lipreading and audiovisual speech perception without motor simulation

All it takes is a face to face conversation in a noisy environment to realize that viewing a speakers lip movements contributes to speech comprehension. Following the finding that brain areas that control speech production are also recruited during lip reading, the received explanation is that lipreading operates through a covert unconscious imitation of the observed speech movements in the observers own speech motor system - a motor simulation. However, motor effects during lipreading do not necessarily imply simulation or a causal role in perception. In line with this alternative, we report here that some individuals born with lip paralysis, who are therefore unable to covertly imitate observed lip movements, have typical lipreading abilities and audiovisual speech perception. This constitutes existence proof that typically efficient lipreading abilities can be achieved without motor simulation. Although it remains an open question whether this conclusion generalizes to typically developed participants, these findings demonstrate that alternatives to motor simulation theories are plausible and invite the conclusion that lip-reading does not involve motor simulation. Beyond its theoretical significance in the field of speech perception, this finding also calls for a re-examination of the more general hypothesis that motor simulation underlies action perception and interpretation developed in the frameworks of the motor simulation and mirror neuron hypotheses.

neuroscience↗