Biology subjects

Carrillo, E.

Publications and source records attributed to Carrillo, E..

7 recordsLinked to original sources

bioRxiv2026

GluDs are ionotropic dopamine receptors tuned by G-proteins

Dopamine is a neurotransmitter essential for cognition, and its dysregulation is associated with neurological diseases1,2. Historically, dopamine has been understood to signal exclusively through metabotropic receptors3. Delta-type ionotropic glutamate receptors (GluDs), which have recently been established as ligand-gated ion channels4,5, are fundamental for synaptic maintenance, are implicated in neurological disorders, and co-localize with dopaminergic machinery. Here, we report that dopamine is a direct agonist of GluDs, eliciting ionotropic activity, as visualized by cryo-electron microscopy (cryo-EM), bilayer recordings, mutagenesis, and patch clamp recordings. Dopamine binds to the GluD ligand binding domain, inducing clamshell closure and channel activation through a distinct molecular interface. GluD channel activity is tightly regulated by G-proteins, which act as molecular switches to tune GluD activity: free G{beta}{gamma} inhibits ligand-gating, while G or inactive G-protein heterotrimers enable dopamine-induced GluD currents. This tuning of GluD activity by G-proteins is uncoupled in a point mutation associated with neurodegeneration. These findings expand mechanisms of neuronal dopaminergic signaling, uncover how G-proteins tune GluD channel activity, and provide a framework for targeting GluDs in neurological diseases.

biophysics↗

bioRxiv2025

Alkalinized Filtered Water Induces Changes in the Gut Microbiome in Inflammatory Bowel Disease.

ObjectiveThis study evaluated the effects of filtered, alkalinized water on inflammation and intestinal dysbiosis in individuals with inflammatory bowel disease (IBD). MethodsWe conducted a three-month, two-arm, randomized intervention study involving 46 patients with IBD in remission. Participants were divided into two groups: one consumed filtered water from an active filtering device, and the control group consumed water from a mock device. Blood and stool samples were collected before and after the intervention. We assessed antioxidant capacity and circulating cytokine levels from plasma. Gene expression levels of inflammatory mediators were determined using mRNA from peripheral blood mononuclear cells (PBMCs). The microbial composition of fecal samples was characterized by qPCR analysis using primers targeting 16S rRNA genes. ResultsConsumption of alkalinized filtered water significantly reduced IL1B gene expression in PBMCs. Furthermore, subjects drinking alkalinized filtered water exhibited a consistent, albeit not statistically significant, decrease in circulating IL-1{beta} and significantly lower levels of IL-4 than controls. Microbiome analysis revealed that the levels of the Bacteroides fragilis Group were significantly lower in subjects consuming tap water than in those consuming filtered water. ConclusionThese changes suggest that consuming alkalinized water for three months leads to an improved inflammatory status compared with consuming tap water.

pathology↗

bioRxiv2025

Could instructor talk drive CURE effectiveness? A comparative study of instructor talk in introductory lab courses

Course-based undergraduate research experiences (CUREs) are thought to enhance students motivation to continue in college, in science, and in research. Yet, how CUREs enhance student motivation is largely undefined. Theories of instructor immediacy, self-efficacy, and task values suggest that CURE instructors may talk in ways that influence students motivational beliefs. We characterized the non-content related talk of instructors teaching 48 introductory biology lab courses, half CUREs and half non-CUREs. We identified 14 types of instructor talk that fit these theoretical perspectives: fostering students closeness with their instructor (i.e., immediacy talk), building students confidence in their scientific abilities (i.e., self-efficacy talk), and promoting students sense of worth in their work (i.e., task value talk). Course type had a medium effect on talk type, with CURE instructors utilizing more immediacy, self-efficacy, and task values talk than non-CURE instructors but also showing more variation in these types of talk. Our results suggest that motivation-related instructor talk is more prevalent in CUREs than non-CUREs, but wide variation in CURE instructor talk indicates additional investigation is needed before non-content talk can be considered a mechanism for the motivational influences of CUREs. HIGHLIGHTThis study compares non-content instructor talk in CURE and non-CURE lab courses using immediacy, self-efficacy, and task value theories. CURE instructors use more talk than non-CURE instructors, but variation in CURE instructor talk leaves open the question of whether talk is a causal factor in the motivational influence of CURE instruction.

scientific communication and education↗

bioRxiv2024

Temperature Sensitive Glutamate Gating of AMPA-subtype iGluRs

Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that mediate the majority of excitatory neurotransmission1. iGluRs are gated by glutamate, where upon glutamate binding, they open their ion channels to enable cation influx into post-synaptic neurons, initiating signal transduction2. The structural mechanism of iGluR gating by glutamate has been extensively studied in the context of positive allosteric modulators (PAMs)3-15. A fundamental question has remained - are the PAM activated states of iGluRs representative of glutamate gating in the absence of PAMs? Here, using the -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype iGluR (AMPAR) we show that glutamate gating is unique from gating in the presence of PAMs. We demonstrate that glutamate gating is temperature sensitive, and through temperature-resolved cryo-electron microscopy (cryo-EM), capture all major glutamate gating states. Physiological temperatures augment channel activation and conductance. Activation by glutamate initiates ion channel opening that involves all ion channel helices hinging away from the pores axis in a motif that is conserved across all iGluRs. Desensitization occurs when the local dimer pairs decouple and enables closure of the ion channel below through restoring the channel hinges and refolding the channel gate. Our findings define how glutamate gates iGluRs, provide foundations for therapeutic design, and point to iGluR gating being temperature sensitive.

biophysics↗

bioRxiv2024

Memantine Inhibits Calcium-Permeable AMPA Receptors

Memantine is an US Food and Drug Administration (FDA) approved drug that selectively inhibits NMDA-subtype ionotropic glutamate receptors (NMDARs) for treatment of dementia and Alzheimers. NMDARs enable calcium influx into neurons and are critical for normal brain function. However, increasing evidence shows that calcium influx in neurological diseases is augmented by calcium-permeable AMPA-subtype ionotropic glutamate receptors (AMPARs). Here, we demonstrate that these calcium-permeable AMPARs (CP-AMPARs) are inhibited by memantine. Electrophysiology unveils that memantine inhibition of CP-AMPARs is dependent on their calcium permeability and the presence of their neuronal auxiliary subunit transmembrane AMPAR regulatory proteins (TARPs). Through cryo-electron microscopy we elucidate that memantine blocks CP-AMPAR ion channels in a unique mechanism of action from NMDARs. Furthermore, we demonstrate that memantine reverses a gain of function AMPAR mutation found in a patient with a neurodevelopmental disorder and inhibits CP-AMPARs in nerve injury. Our findings alter the paradigm for the memantine mechanism of action and provide a blueprint for therapeutic approaches targeting CP-AMPARs.

biophysics↗

bioRxiv2021

TRICLOSAN IS A KCNQ3 POTASSIUM CHANNEL ACTIVATOR

KCNQ channels participate in the physiology of several cell types. In neurons of the central nervous system, the primary subunits are KCNQ2, 3 and 5. Activation of these channels silence the neurons, limiting action potential duration and preventing high-frequency action potential burst. Mutation of the KCNQ genes are associated with a wide spectrum of phenotypes characterized by hyperexcitability. Activation of KCNQ channels is an attractive strategy to treat epilepsy and other hyperexcitability conditions as are the evolution of stroke and traumatic brain injury. In this work we show that triclosan, a bactericide widely used in personal care products, activates the KCNQ3 channels but not the KCNQ2. Triclosan induces a voltage shift in the activation, increases the conductance and slows the closing of the channel. The effect is independent of PIP2. The putative binding site is located in the pore region but is distinct from the binding site for retigabine. Our results indicate that triclosan is a new activator for KCNQ channels.

biophysics↗

bioRxiv2021

Alignment of multiple metabolomics LC-MS datasets from disparate diseases to reveal fever-associated metabolites

Acute febrile illnesses are still a major cause of mortality and morbidity globally, particularly in low to middle income countries. The aim of this study was to determine any possible metabolic commonalities of patients infected with disparate pathogens that cause fever. Three liquid chromatography-mass spectrometry (LC-MS) datasets investigating the metabolic effects of malaria, leishmaniasis and Zika virus infection were used. The retention time (RT) drift between the datasets was determined using landmarks obtained from the standard reference mixtures generally used in the quality control of the LC-MS experiments. We used fitted Gaussian Process models (GPs) to perform a high level correction of the RT drift between the experiments, followed by standard peakset alignment between the samples with corrected RTs of the three LC-MS datasets. Statistical analysis, annotation and pathway analysis of the integrated peaksets were subsequently performed. Metabolic dysregulation patterns common across the datasets were identified, with kynurenine pathway being the most affected pathway between all three fever-associated datasets.

bioinformatics↗