Biology subjects

Morales, I.

Publications and source records attributed to Morales, I..

6 recordsLinked to original sources

bioRxiv2026

Opioid addiction vs. sugar addiction: Mesocorticolimbic stimulation controls motivation for remifentanil or alternative reward

Addiction is characterized by intense incentive motivation that becomes narrowly focused on particular targets. Laboratory studies have modeled intensification, directional targeting, and narrowing of the focus of incentive motivation using paired optogenetic stimulation of central amygdala CeA circuitry, which can create addictive-like motivation focused on either cocaine or on sucrose, as directed by experimenters. However, opioid drugs have been suggested to be different from cocaine in both reward and addictive effects, to be less dependent on mesolimbic incentive salience circuitry, and so may be potentially exempt from such control. To test if opoioid motivation is subject to similar control, CeA ChR2 rats were allowed to freely choose between intravenous remifentanil (2 ug/kg) or sucrose. One group had CeA stimulation selectively paired with earning sucrose, while the other group had stimulation paired with remifentanil. The sucrose-paired CeA ChR2 rats came to nearly exclusively pursue sucrose, ignoring remifentanil. By contrast, remifentanil-paired CeA ChR2 rats specifically pursued remifentanil, ignoring sucrose (control eYFP rats had no overall preference). To confirm whether CeA ChR2 pairing also intensified incentive motivation for remifentanil, as well as controlling its target, a separate CeA ChR2 group chose between two remifentanil options: one paired with CeA Stimulation, and the other unpaired. CeA ChR2 stimulation both focused pursuit specifically on laser-paired remifentanil, and escalated breakpoint for laser-paired remifentanil in a progressive ratio test of motivation intensity. Despite this ability to control motivation for opioid or sucrose, CeA ChR2 laser on its own had only low to moderate incentive value. For example, some CeA ChR2 rats above completely failed to self-stimulate CeA laser by itself. It appears that amygdala-related recruitment of mesocorticolimbic circuitry can transform the incentive salience of opioid drugs, similar to that for cocaine or sucrose, and gate the induction of intense but narrowly focused wanting in an addictive-like fashion.

neuroscience↗

bioRxiv2026

A Modular Chromosomally Integrated Yeast Surface Display Platform for Quantitative Serology and Immune Profiling

Precise quantification of antigen-specific antibodies is essential for assessing immune status and fundamental to both clinical and research settings. However, current serological platforms remain limited in their ability to combine quantitative performance, flexibility, and scalability. Here, we present a chromosomally integrated yeast surface display (YSD) system engineered for stable, quantitative, and scalable antibody profiling. Genomic integration of the YSD cassette supports uniform antigen presentation without continuous selective pressure, reducing variability associated with plasmid-based systems. Two distinct cell-wall anchoring strategies are implemented within a modular synthetic framework that enables rapid, cloning-free strain construction. Coupled with flow-cytometric readout, the system provides sensitive detection of antigen-specific antibodies with single-cell normalization for antigen expression. In addition, the combination of barcoded YSD strain libraries with fluorescence-activated cell sorting and next-generation sequencing enables multiplexed serological profiling across multiple samples and antigens. As a proof of concept, we demonstrate quantitative antibody detection against SARS-CoV-2 and extend the approach to hepatitis virus antigens, highlighting the utility of this platform as a flexible framework for serological assay development and immune profiling.

bioengineering↗

bioRxiv2026

Hydrogel formulation controls size-dependent accumulation of proteins and nanoparticles in PEG microparticles

Hydrogels are widely used in sensing, delivery, and tissue engineering because their transport properties can be tuned through material design. However, while hydrogel permeability is often characterized using small molecules, many practical applications depend on the uptake and retention of much larger species, including protein conjugates and nanoparticles. Here, we systematically investigate how polyethylene glycol (PEG)-acrylate hydrogel microparticle formulation influences accumulation of signal-generating probes spanning a broad size range. We fabricated particles across a 36-condition design space varying nominal PEG-acrylate molecular weight, polymer weight percent, and UV crosslinking dose, and related formulation-dependent probe accumulation to particle swelling behavior. Increasing nominal PEG-acrylate molecular weight and decreasing polymer weight percent produced more highly swollen particles and strongly enhanced accumulation of fluorescent streptavidin conjugates, with the largest effects observed for bulky labels such as allophycocyanin and phycoerythrin. Gold nanoparticle accumulation was even more formulation-restricted, with detectable colorimetric signal observed primarily in the most permissive formulations. These findings establish design rules linking PEG hydrogel formulation to size-dependent accumulation and show that formulations suitable for small probes may be inadequate for larger reporters. More broadly, this framework may inform the design of hydrogels for particle-based assays as well as other applications where transport of macromolecules or nanoscale materials is important.

bioengineering↗

bioRxiv2025

Sealable capped nanovials for high-throughput screening of cell growth and function

Millions of modular nanoliter-scale compartments that isolate functionally rich single-cell and cell-to-cell communication data can scale biological discovery for the age of AI. Here, we introduce capped nanovials--suspendable, sealable microscale compartments formed by the docking of hydrogel capping particles into bowl-shaped nanovials--as a versatile system for culturing, analyzing, and sorting single cells and small colonies. This two-particle architecture enables localized confinement of cells and secreted products while maintaining compatibility with standard laboratory workflows such as wash and reagent exchange steps, fluorescence microscopy, and flow cytometry. Crucially, these compartments are formed via simple pipetting and centrifugation steps, making the platform highly democratized. We demonstrate the ability of capped nanovials to compartmentalize single mammalian, bacterial, and yeast cells and support growth into colonies, enabling selection based on proliferation and bioproduction. We further show that capped nanovials enhance single-cell secretion assays by reducing molecular crosstalk and increasing signal-to-noise ratios. Importantly, we demonstrate functional co-culture assays by permitting stable confinement of cell pairs, enabling detection and enrichment of antibody-secreting cells based on the ability of their secreted antibodies to activate co-encapsulated reporter T cells, achieving a signal-to-noise ratio of >30 and up to 100% selection purity. By combining the simplicity of standard lab handling with the resolution and throughput of traditional microfluidic compartmentalization approaches, capped nanovials provide a new class of scalable, accessible test tubes for modern single-cell biology.

bioengineering↗

bioRxiv2024

Optogenetic hedonic hotspots in orbitofrontal cortex and insula: causing enhancement of sweetness liking

Hedonic hotspots are brain subregions that causally amplify the hedonic impact of palatable tastes, measured as increases in affective orofacial liking reactions to sweetness. Previously, two cortical hedonic hotspots in orbitofrontal cortex and insula were identified by neurochemical stimulation using opioid or orexin microinjections. Here we used optogenetic stimulation in rats as an independent neurobiological technique for activating cortical hedonic hotspots to identify hedonic functions and map boundaries. We report that channelrhodopsin stimulations within rostral orbitofrontal and caudal insula hotspots doubled the number of hedonic liking reactions elicited by sucrose taste. This independently confirms their robust functional identity as causal amplifiers of hedonic liking and confirms their anatomical boundaries. Additionally, we confirmed an intervening suppressive hedonic coldstrip, to stretching from caudal orbitofrontal cortex to rostral insula. By contrast to localized hedonic hotspots for liking enhancement, motivational wanting for reward, measured as laser self-stimulation, was mediated by more widely distributed anatomical sites.

neuroscience↗

bioRxiv2017

Epidemic establishment and cryptic transmission of Zika virus in Brazil and the Americas

Zika virus (ZIKV) transmission in the Americas was first confirmed in May 2015 in Northeast Brazil1. Brazil has the highest number of reported ZIKV cases worldwide (>200,000 by 24 Dec 20162) as well as the greatest number of cases associated with microcephaly and other birth defects (2,366 confirmed cases by 31 Dec 20162). Following the initial detection of ZIKV in Brazil, 47 countries and territories in the Americas have reported local ZIKV transmission, with 22 of these reporting ZIKV-associated severe disease3. Yet the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of such information for interpreting past trends in reported microcephaly. To address this we generated 53 complete or partial ZIKV genomes, mostly from Brazil, including data generated by the ZiBRA project - a mobile genomics lab that travelled across Northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Joint analyses of viral genomes with ecological and epidemiological data estimate that the ZIKV epidemic first became established in NE Brazil by March 2014 and likely disseminated from there, both nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates of the international spread of ZIKV from Brazil coincide with periods of high vector suitability in recipient regions and indicate the duration of pre-detection cryptic transmission in those regions. NE Brazils role in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the virus basic reproduction number.\n\nOne Sentence SummaryVirus genomes reveal the establishment of Zika virus in Northeast Brazil and the Americas, and provide an appropriate timeframe for baseline (pre-Zika) microcephaly in different regions.

genomics↗