Biology subjects

Marquez, C.

Publications and source records attributed to Marquez, C..

13 recordsLinked to original sources

bioRxiv2026

Genome-wide within-host evolution during prolonged SARS-CoV-2 infection in a person with advanced HIV infection

Within-host evolution during prolonged SARS-CoV-2 infection can be extensive in immunocompromised individuals, but the consequences of mutations that emerge and change in frequency over time remain difficult to predict. We characterized an XBB.1.5.10 infection lasting nearly 90 days in a person with advanced human immunodeficiency virus (HIV) infection. Genome-wide tracking of allele frequencies in samples collected on study days 43, 48, and 70 revealed a Spike N-terminal domain (NTD) deletion spanning residues 138-145 at frequencies of 33%, 80%, and 96%, respectively. A receptor-binding domain (RBD) deletion-insertion spanning residues 373-378 was detected on days 43 and 48 but not on day 70, while nsp12 C464Y was detected at approximately 8% on day 48 and 86% on day 70. We reconstructed representative Spike and non-Spike mutation profiles from the longitudinal samples and tested their effects on cell entry and viral RNA replication. The representative Spike construct for days 43 and 48 increased entry relative to XBB.1.5. Comparison with a matched construct lacking the receptor-binding domain deletion-insertion showed that the deletion-insertion enhanced entry, although it was not detected in the day 70 sample. The day 48 non-Spike profile supported the highest RNA replication among the tested replicons. Together, allele-frequency tracking revealed both transient mutations and mutations detected at progressively higher frequencies across the sampled time points. Functional testing showed that increased entry or RNA replication in vitro did not necessarily predict persistence in vivo.

microbiology↗

bioRxiv2026

Building neuroanatomical resources for three-spined sticklebacks: Brain areas important for social behavior

IntroductionThree-spined stickleback fish are famous for their diversity and charismatic social behavior. However, there are few neuroanatomical resources for studying the neural and brain mechanisms underlying their fascinating behavior. Methods and ResultsWe identify 11 brain areas important for social behavior by referencing brain atlases for six other teleost fishes. Brain regions were identified via neuroanatomical landmarks and we characterized the presence / absence of tyrosine hydroxylase (TH), a key gene product of the dopaminergic system, in those regions. Comparing the neuroanatomical location of these regions in the stickleback brain and the expression of TH therein to that of other fish species highlights similarities and differences and the need for a brain atlas specific to sticklebacks. This resource serves as a map of the location of regions important for social behavior in the stickleback brain. ConclusionThis resource will help guide future studies connecting gene function to social behavior through the brain and will enable future work to understand the evolution of neural mechanisms that contribute to the diversity of social behavior in this emerging model organism.

neuroscience↗

bioRxiv2025

Reward-based prosocial choices in mice

Prosocial behaviors, actions that benefit others, are an essential part of the social life of humans and other animals, by promoting bonding and cohesion among individuals and groups. Here we present a new behavioural paradigm to assess prosociality in food foraging contexts in laboratory mice, based in our paradigm previously developed for rats. In this task, the decision-maker can choose between two options, one that will only provide rewards to itself (selfish choice) or one that will reward both itself and its cagemate (prosocial choice). Our work reveals that prosocial choices in male mice are not widespread and are only observed in a small proportion of animals. Using detailed analysis of behavior, we describe that recipients of help express different social cues in prosocial and selfish trials, but decision makers do not take them into account to guide their choices. Furthermore, we assess how the level of individual training and the physical layout of the paradigm might affect the performance in this social task. Only those mice with increased social attention (16% of the animals) display prosocial preferences, suggesting these to be rooted in similar behavioural factors and social interactions that we previously described in other work with rats.

neuroscience↗

bioRxiv2024

The GenPPI tool enhanced Protein Interaction Network Generation with Machine Learning-Based Protein Similarity Inference

AbstractO_ST_ABSBackgroundC_ST_ABSComputational prediction of protein-protein interactions (PPIs) is crucial for understanding cell biology and drug development, offering an alternative to costly experimental methods. The original GenPPi software advanced ab initio PPI network prediction from bacterial genomes but was limited by its reliance on high sequence similarity. This work introduces GenPPi 1.5 to enhance these predictive capabilities. ResultsGenPPi 1.5 incorporates a Random Forest (RF) algorithm, trained on 60 biophysical features from amino acid propensity indices, to classify protein similarity even in low sequence identity scenarios (targeting >65% identity). To manage computational complexity from the increased interactions generated by the RF model, especially in extensive conserved phylogenetic profiles, we developed and integrated the Reduced Interaction Sampling (RIS) algorithm. RIS stochastically samples interactions within these profiles, optimizing performance for complete genome analysis. Extensive simulations across various configurations validated the methodology. RF integration significantly broadened GenPPis predictive power; application to Buchnera aphidicola showed up to 62% overlap with STRING database interactions. Analysis of RIS demonstrated that while introducing some randomness, critical node identification remains robust, particularly for Top N values[≥] 100, indicating minimal compromise to network integrity. ConclusionThe combination of Machine Learning (RF) and the RIS algorithm in GenPPi 1.5 represents a significant advancement. It overcomes the highsimilarity dependency of the previous version while efficiently handling complex genomes. GenPPi 1.5 provides a robust and scalable alignment-free PPI prediction solution, enabling users to train custom models tailored to specific genomic contexts. GenPPi is freely available on our website https://genppi.facom.ufu.br/, its source code is hosted on GitHub https://github.com/santosardr/genppi, and it can be easily installed via the Python Package Index using the command pip install genppipy.

bioinformatics↗

bioRxiv2024

Cell Maps for Artificial Intelligence: AI-Ready Maps of Human Cell Architecture from Disease-Relevant Cell Lines

This article describes the Cell Maps for Artificial Intelligence (CM4AI) project and its goals, methods, standards, current datasets, software tools, status, and future directions. CM4AI is the Functional Genomics Data Generation Project in the U.S. National Institute of Healths (NIH) Bridge2AI program. Its overarching mission is to produce ethical, AI-ready datasets of cell architecture, inferred from multimodal data collected for human cell lines, to enable transformative biomedical AI research.

systems biology↗

bioRxiv2022

Multimodal cues displayed by submissive rats promote prosocial choices by dominants

Animals often display prosocial behaviours, performing actions that benefit others. Although prosociality is essential for social bonding and cooperation, we still know little about how animals integrate behavioural cues from those in need to make decisions that increase their wellbeing. To address this question, we used a two-choice task where rats can provide rewards to a conspecific in the absence of self-benefit, and interrogated which conditions promote prosociality by manipulating the social context of the interacting animals. While sex or degree of familiarity did not affect prosocial choices in rats, social hierarchy revealed to be a potent modulator, with dominant decision-makers showing faster emergence and higher levels of prosocial choices towards their submissive cage-mates. Leveraging quantitative analysis of multimodal social dynamics prior to choice, we identified that pairs with dominant decision-makers exhibited more proximal interactions. Interestingly, these closer interactions were driven by submissive animals that modulated their position and movement following their dominants and whose 50kHz vocalisation rate correlated with dominants prosociality. Moreover, Granger causality revealed stronger bidirectional influences in pairs with dominant focals and submissive recipients, indicating increased behavioural coordination. Finally, multivariate analysis highlighted body language as the main information dominants use on a trial-by-trial basis to learn that their actions have effects on others. Our results provide a refined understanding of the behavioural dynamics that rats use for action-selection upon perception of socially relevant cues and navigate social decision-making.

neuroscience↗

bioRxiv2021

SARS-CoV-2 Omicron Variant: ACE2 Binding, Cryo-EM Structure of Spike Protein-ACE2 Complex and Antibody Evasion

The newly reported Omicron variant is poised to replace Delta as the most rapidly spread SARS-CoV-2 variant across the world. Cryo-EM structural analysis of the Omicron variant spike protein in complex with human ACE2 reveals new salt bridges and hydrogen bonds formed by mutated residues R493, S496 and R498 in the RBD with ACE2. These interactions appear to compensate for other Omicron mutations such as K417N known to reduce ACE2 binding affinity, explaining our finding of similar biochemical ACE2 binding affinities for Delta and Omicron variants. Neutralization assays show that pseudoviruses displaying the Omicron spike protein exhibit increased antibody evasion, with greater evasion observed in sera obtained from unvaccinated convalescent patients as compared to doubly vaccinated individuals (8-vs 3-fold). The retention of strong interactions at the ACE2 interface and the increase in antibody evasion are molecular factors that likely contribute to the increased transmissibility of the Omicron variant.

biochemistry↗

bioRxiv2021

Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19

Type I interferon (IFN-I) neutralizing autoantibodies have been found in some critical COVID-19 patients; however, their prevalence and longitudinal dynamics across the disease severity scale, and functional effects on circulating leukocytes remain unknown. Here, in 284 COVID-19 patients, we found IFN-I autoantibodies in 19% of critical, 6% of severe and none of the moderate cases. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 COVID-19 patients, 15 non-COVID-19 patients and 11 non-hospitalized healthy controls, revealed a lack of IFN-I stimulated gene (ISG-I) response in myeloid cells from critical cases, including those producing anti-IFN-I autoantibodies. Moreover, surface protein analysis showed an inverse correlation of the inhibitory receptor LAIR-1 with ISG-I expression response early in the disease course. This aberrant ISG-I response in critical patients with and without IFN-I autoantibodies, supports a unifying model for disease pathogenesis involving ISG-I suppression via convergent mechanisms.

immunology↗

bioRxiv2021

pyControl: Open source, Python based, hardware and software for controlling behavioural neuroscience experiments.

Laboratory behavioural tasks are an essential research tool. As questions asked of behaviour and brain activity become more sophisticated, the ability to specify and run richly structured tasks becomes more important. An increasing focus on reproducibility also necessitates accurate communication of task logic to other researchers. To these ends we developed pyControl, a system of open source hardware and software for controlling behavioural experiments comprising; a simple yet flexible Python-based syntax for specifying tasks as extended state machines, hardware modules for building behavioural setups, and a graphical user interface designed for efficiently running high throughput experiments on many setups in parallel, all with extensive online documentation. These tools make it quicker, easier and cheaper to implement rich behavioural tasks at scale. As important, pyControl facilitates communication and reproducibility of behavioural experiments through a highly readable task definition syntax and self-documenting features. ResourcesDocumentation: https://pycontrol.readthedocs.io Repositories: https://github.com/pyControl User support: https://groups.google.com/g/pycontrol

neuroscience↗

bioRxiv2020

Novel Competition test for food rewards reveals stable dominance status in rats

Social hierarchy is a potent modulator of behavior, that is typically established through overt agonistic interactions between individuals in the group. Once established, social ranks are maintained through subtler interactions allowing the redirection of energy away from agonistic interactions towards other needs. The available tasks for assessing social rank in rats allow the study of the mechanisms by which social hierarches are formed in early phases but fail to assess the maintenance of established hierarchies between stable pairs of animals, which might rely on distinct neurobiological mechanisms. Here we present and validate a novel trial-based dominancy assay, the modified Food Competition test, where established social hierarchies can be identified in the home cage of non-food deprived pairs of male rats. In this task, we introduce a small conflict in the home cage, where access to a new feeder containing palatable pellets can only be gained by one animal at a time. We found that this subtle conflict triggered asymmetric social interactions and resulted in higher consumption of food by one of the animals in the pair, which reliably predicted hierarchy in other tests. Our findings reveal stable dominance status in pair-housed rats and provide a novel tool for the evaluation of established social hierarchies, the modified Food Competition test, that is robust and easy to implement.

neuroscience↗

bioRxiv2020

Programming effects of peripubertal stress on spatial learning

Exposure to adversity during early life can have profound influences on brain function and behavior later in life. The peripubertal period is emerging as an important time-window of susceptibility to stress, with substantial evidence documenting long-term consequences in the emotional and social domains. However, little is known about how stress during this period impacts subsequent cognitive functioning. Here, we assessed potential long-term effects of peripubertal stress on spatial learning and memory using the water maze task. In addition, we interrogated whether individual differences in stress-induced behavioral and endocrine changes are related to the degree of adaptation of the corticosterone response to repeated stressor exposure during the peripubertal period. We found that, when tested at adulthood, peripubertally stressed animals displayed a slower learning rate. Strikingly, the level of spatial orientation in the water maze completed on the last training day was predicted by the degree of adaptation of the recovery -and not the peak-of the corticosterone response to stressor exposure (i.e., plasma levels at 60 min post-stressor) across the peripubertal stress period. In addition, peripubertal stress led to changes in emotional and glucocorticoid reactivity to novelty exposure, as well as in the expression levels of the plasticity molecule PSA-NCAM in the hippocampus. Importantly, by assessing the same endpoints in another peripubertally stressed cohort tested during adolescence, we show that the observed effects at adulthood are the result of a delayed programming manifested at adulthood and not protracted effects of stress. Altogether, our results support the view that the degree of stress-induced adaptation of the hypothalamus-pituitary-adrenal axis responsiveness at the important transitional period of puberty relates to the long-term programming of cognition, behavior and endocrine reactivity.

neuroscience↗

bioRxiv2020

Cell-free DNA as a biomarker for prostate cancer: elevated concentration and decreased fragment size

PurposeProstate cancer is the most commonly diagnosed neoplasm in American men. Although existing biomarkers may detect localized prostate cancer, additional strategies are necessary for improving detection and identifying aggressive disease that may require further intervention. One promising, minimally invasive biomarker is cell-free DNA (cfDNA), which consist of short DNA fragments released into circulation by dying or lysed cells that may reflect underlying cancer. Here we investigated whether differences in cfDNA concentration and cfDNA fragment size could improve the sensitivity for detecting more advanced and aggressive prostate cancer. Materials and MethodsThis study included 268 individuals: 34 healthy controls, 112 men with localized prostate cancer who underwent radical prostatectomy (RP), and 122 men with metastatic castration-resistant prostate cancer (mCRPC). Plasma cfDNA concentration and fragment size were quantified with the Qubit 3.0 and the 2100 Bioanalyzer. The potential relationship between cfDNA concentration or fragment size and localized or mCRPC prostate cancer was evaluated with descriptive statistics, logistic regression, and area under the curve analysis with cross-validation. ResultsPlasma cfDNA concentrations were elevated in mCRPC patients in comparison to localized disease (OR5 ng/mL = 1.34, P = 0.027) or to being a control (OR5 ng/mL = 1.69, P = 0.034). Decreased average fragment size was associated with an increased risk of localized disease compared to controls (OR5bp = 0.77, P = 0.0008). ConclusionThis study suggests that cfDNA concentration and average cfDNA fragment size may provide a quick, cost-effective approach to help determine which patients will benefit most from further screening and/or disease monitoring to help improve prostate cancer outcomes.

cancer biology↗

bioRxiv2019

Freezing displayed by others is a learned cue of danger resulting from co-experiencing own-freezing and shock

Social cues of threat are widely reported [1-3], whether actively produced to trigger responses in others, such as the emission of alarm calls, or by-products of an encounter with a predator, like the defensive behaviors themselves, such as an escape flight [4-14]. Although the recognition of social alarm cues is often innate [15-17], in some instances it requires experience to trigger defensive responses [4,7]. One mechanism proposed for how learning from self-experience contributes to social behavior is that of auto-conditioning, whereby subjects learn to associate their own behaviors with the relevant trigger events. Through this process the same behaviors, now displayed by others, gain meaning. [18,19 but see: 20]. Although it has been shown that only animals with prior experience with shock display observational freezing [21-25] suggesting that auto-conditioning could mediate this process, evidence for this hypothesis was lacking. Previously we found that when a rat freezes, the silence that results from immobility triggers observational freezing in its cage-mate, provided the cage-mate had experienced shocks before [24]. Hence, in our study auto-conditioning would correspond to rats learning to associate shock with their own response to it - freezing. Using a combination of behavioral and optogenetic manipulations, here we show that freezing becomes an alarm cue by a direct association with shock. Our work shows that auto-conditioning can indeed modulate social interactions, expanding the repertoire of cues that mediate social information exchange, providing a framework to study how the neural circuits involved in the self-experience of defensive behaviors overlap with the ones involved in socially triggered defensive behaviors.

animal behavior and cognition↗