Biology subjects

Jou, C.

Publications and source records attributed to Jou, C..

6 recordsLinked to original sources

bioRxiv2026

mRNA deep sequencing profiling and integrative miRNA-mRNA network analysis in pediatric Burkitt leukemia and lymphoma

Background: Although the genomic alterations in Burkitt leukemia and lymphoma (BL) have been extensively studied, data on genome-wide dysregulation of messenger RNA (mRNA) and microRNA (miRNA) in Burkitt leukemia (BuAL) and Burkitt lymphoma (BuLY) are scarce. The aim of this study was to analyze mRNA and miRNA expression profiles in pediatric BuAL/BuLY to identify dysregulated mRNA-miRNA networks. Methods: Total RNA from fresh tumor samples of 13 pediatric BL patients (BuAL n=7, BuLY n=6) and 4 pediatric normal control lymphoid tissue (NCLT) samples was included for mRNA-deep sequencing and miRNA-microarrays studies. Differential expression (DE) analysis of mRNAs and miRNAs as well as gene set and functional enrichment analysis were performed. The multiMiR R package was used to identify the validated target genes for the dysregulated miRNAs. miRNA-mRNA target interaction analysis was performed combining DE, validated targets observed among the inverse-significant miRNA-mRNA correlations, with evidence statistics retained (p[≤]-0.5 and Benjamini-Hochberg (BH) -adjusted correlation p-value< 0.05). Results: BL showed 1965 DE genes (DEG) compared to NCLT (1214 upregulated, 751 downregulated) (p-adj<0.05, log2FC>0.5) and 11 DE miRNAs (three upregulated and eight downregulated) (FC>1.5, p-adj<0.05). The transcriptional differences observed between BL and normal lymphoid tissue inferred by functional enrichment analysis identified along a MYC-driven proliferative backbone with strong E2F4 and MYB pathway activity, activation of the MAPK, PI3K and the G2/M checkpoint signaling pathways and repression of the JAK-STAT, NFkB, TP53, TRAIL and hypoxia pathways (p-adj<0.05). Functional enrichment analysis highlighted an upregulation of proliferative and metabolic pathways accompanied by an attenuated inflammatory and immunosurveillance signaling in BL compared to NCLT. Correlated miRNA-mRNA expression analysis identified DE dysregulated miRNAs and their validated target genes. DE downregulated miRNAs (hsa-miR-150-5p, hsa-miR-342-3p and hsa-miR-450-5p, among others) inversely correlated with upregulated mRNA targets showing pathway enrichment related to transcriptional activity and nuclear organization modules. mRNA targets of DE upregulated miRNAs (hsa-miR-106a-5p, hsa-miR-17-5p and hsa-miR-7-5p) were enriched in downregulated pathways related to immune response processes. Conclusions: Overall, this pilot study provides new insights on key proliferative, metabolic and cytokine-mediated immune signaling pathways in BL and highlights miRNA-mRNA networks influencing transcriptional activity and immune surveillance, paving the way for experimental validation models.

cancer biology↗

bioRxiv2023

On the results of causal optogenetic engram manipulations

Hippocampal neurons encoding memories discharge in sparsely-distributed patterns; they can be optogenetically tagged, then photostimulated to elicit conditioned behavior, potentially generating a synthetic memory trace, "engram". We investigated mouse hippocampal population responses to the photostimulation of memory-tagged neurons to determine if memory-associated discharge is mimicked in hippocampus, a network with non-linear and homeostatic interactions. Both memory-tagged and not-tagged CA1 cells adjusted firing during photostimulation without altering place cell firing fields. Cell-pair cofiring relationships also maintain during photostimulation, indicating a low-dimensional, dynamical structure-preserving, homeostatic network response instead of the photostimulated pattern. Photostimulating neurons that were tagged during place-avoidance memory elicits similar place-avoidance memory in control conditions. Thus artificial photostimulation elicits natural, stored, homeostatic neuronal network cofiring patterns to elicit memory, establishing mimicry evidence for the engram.

neuroscience↗

bioRxiv2023

Decoding Duchenne muscular dystrophy transcriptome to single nuclei level reveals clinical-genetic correlations

The cellular and molecular consequences of lack of dystrophin in humans are only partially known, which is crucial for the development of new therapies aiming to slow or stop the progression Duchenne and Becker muscular dystrophies. We analyzed muscle biopsies of DMD patients and controls using single nuclei RNA sequencing (snRNAseq) and correlated the results with clinical data. DMD samples displayed an increase in regenerative fibers, satellite cells and fibro-adipogenic progenitor cells (FAPs) and a decrease in slow fibers and smooth muscle cells. Samples from patients with stable mild weakness were characterized by an increase in regenerative fibers, while those from patients with progressive weakness had fewer muscle fibers and increased FAPs. DMD muscle fibers displayed a strong regenerative signature, while DMD FAPs upregulated genes producing extracellular matrix and molecules involved in several signaling pathways. An analysis of intercellular communication profile identified FAPs as a key regulator of cell signaling in DMD samples. We show significant differences in the gene expression profiled of the different cell populations present in DMD muscle samples compared to controls.

bioinformatics↗

bioRxiv2023

A Photoactivated Protein Degrader for Optical Control of Synaptic Function

Hundreds of proteins determine the function of synapses, and synapses define the neuronal circuits that subserve myriad brain, cognitive, and behavioral functions. It is thus necessary to precisely manipulate specific proteins at specific sub-cellular locations and times to elucidate the roles of particular proteins and synapses in brain function. We developed PHOtochemically TArgeting Chimeras (PHOTACs) as a strategy to optically degrade specific proteins with high spatial and temporal precision. PHOTACs are small molecules that, upon wavelength-selective illumination, catalyze ubiquitylation and degradation of target proteins through endogenous proteasomes. Here we describe the design and chemical properties of a PHOTAC that targets Ca2+/calmodulin-dependent protein kinase II alpha (CaMKII), which is abundant and crucial for baseline synaptic function of excitatory neurons. We validate the PHOTAC strategy, showing that the CaMKII-PHOTAC is effective in mouse brain tissue. Light activation of CaMKII-PHOTAC removed CaMKII from regions of the mouse hippocampus only within 25 m of the illuminated brain surface. The optically-controlled degradation decreases synaptic function within minutes of light activation, measured by the light-initiated attenuation of evoked field excitatory postsynaptic potential (fEPSP) responses to physiological stimulation. The PHOTACs methodology should be broadly applicable to other key proteins implicated in synaptic function, especially for evaluating their precise roles in the maintenance of long-term potentiation and memory within subcellular dendritic domains.

neuroscience↗

bioRxiv2021

Antibody Conversion rates to SARS-CoV-2 in Saliva from Children Attending Summer Schools in Barcelona, Spain

Surveillance tools to estimate infection rates in young populations are essential to guide recommendations for school reopening and management during viral epidemics. Ideally, field-deployable non-invasive, sensitive techniques are required to detect low viral load exposures among asymptomatic children. We determined SARS-CoV-2 antibody conversion by high-throughput Luminex assays in saliva samples collected weekly in 1,509 children and 396 adults in 22 Summer schools and 2 pre-schools in 27 venues in Barcelona, Spain, from June 29th to July 31st 2020, between the first and second COVID-19 pandemic waves. Saliva antibody conversion defined as [≥]4-fold increase in IgM, IgA and/or IgG levels to SARS-CoV-2 antigens between two visits over a 5-week period was 3.22% (49/1518), or 2.36% if accounting for potentially cross-reactive antibodies, six times higher than the cumulative infection rate (0.53%) by weekly saliva RT-PCR screening. IgG conversion was higher in adults (2.94%, 11/374) than children (1.31%, 15/1144) (p=0.035), IgG and IgA levels moderately increased with age, and antibodies were higher in females. Most antibody converters increased both IgG and IgA antibodies but some augmented either IgG or IgA, with a faster decay over time for IgA than IgG. Nucleocapsid rather than spike was the main antigen target. Anti-spike antibodies were significantly higher in individuals not reporting symptoms than symptomatic individuals, suggesting a protective role against COVID-19. To conclude, saliva antibody profiling including three isotypes and multiplexing antigens is a useful and more user-friendly tool for screening pediatric populations to determine SARS-CoV-2 exposure and guide public health policies during pandemics.

immunology↗

bioRxiv2020

A self-initiated cue-reward learning procedure for neural recording in rodents

BackgroundSingle-unit recording in Pavlovian conditioning tasks requires the use of within-subject designs as well as sampling a considerable number of trials per trial type and session, which increases the total trial count. Pavlovian conditioning, on the other hand, requires a long average intertrial interval (ITI) relative to cue duration for cue-specific learning to occur. These requirements combined can make the session duration unfeasibly long. New MethodTo circumvent this issue, we developed a self-initiated variant of the Pavlovian magazine-approach procedure in rodents. Unlike the standard procedure, where the animals passively receive the trials, the self-initiated procedure grants animals agency to self-administer and self-pace trials from a predetermined, pseudorandomized list. Critically, whereas in the standard procedure the typical ITI is in the order of minutes, our procedure uses a much shorter ITI (10 s). ResultsDespite such a short ITI, discrimination learning in the self-initiated procedure is comparable to that observed in the standard procedure with a typical ITI, and superior to that observed in the standard procedure with an equally short ITI. Comparison with Existing Method(s)The self-initiated procedure permits delivering 100 trials in a [~]1-h session, almost doubling the number of trials safely attainable over that period with the standard procedure. ConclusionsThe self-initiated procedure enhances the collection of neural correlates of cue-reward learning while producing good discrimination performance. Other advantages for neural recording studies include ensuring that at the start of each trial the animal is engaged, attentive and in the same location within the conditioning chamber.

neuroscience↗