Biology subjects

Gilbert-Jaramillo, J.

Publications and source records attributed to Gilbert-Jaramillo, J..

6 recordsLinked to original sources

bioRxiv2026

Acute Ethanol Exposure Induces Stage-Specific Bioenergetic, Mitochondrial and Neurodevelopmental Transcriptional Remodeling in Human Forebrain Progenitors

Prenatal alcohol exposure (PAE) is associated with long-term neurodevelopmental risk, yet how neuronal progenitor metabolism responds to alcohol across developmental stages remains unclear. Here, we integrated brain-isoform-focused analysis of public datasets with targeted transcriptional, translational, and functional mitochondrial assessments in human iPSC-derived cortical progenitor models representing distinct bioenergetic states. Re-analysis of prior PAE studies revealed broad metabolic gene downregulation in embryonic systems, whereas neurodevelopmental models showed limited and non-coherent transcriptional signatures. In vitro, acute ethanol exposure (AEE) induced stage-dependent transcriptional remodeling in iPSC-derived neuronal progenitor cells. Early progenitors exhibited selective upregulation of mitochondrial-associated transcripts alongside increased neuronal lineage markers. In contrast, late progenitors showed broader increases in glycolytic, lipid, and mitochondrial gene expression. Despite these transcriptional changes, mitochondrial ATP production and mitochondrial protein abundance remained unchanged in both models with altered dynamics being restricted to late progenitors. These findings indicate that ethanol exposure is associated with developmental stage-dependent neuronal remodeling of bioenergetic genes. Measurements of mitochondrial-neural frameworks after AEE showed no major alterations in either model. Overall, our results reveal a dissociation between transcriptional, translational, and functional bioenergetic outputs in models of early human neurodevelopment and highlight that transcriptional alterations of mitochondria and cellular bioenergetics under AEE should be interpreted in the context of developmental stage rather than in isolation as evidence of energetic dysfunction.

neuroscience↗

bioRxiv2026

Developmental Bioenergetic Reprogramming and Glycolytic Shift in Schizophrenia Vulnerability

Schizophrenia (SZ) arises from complex gene-environment interactions, yet how early insults shape later circuit vulnerability remains unclear. Here, we investigated whether bioenergetic states represent a convergent disease signature across genetic and environmental risk factors. We analyzed transcriptional profiles across neocortical development in murine models of maternal immune activation (polyIC MIA), and serine racemase deletion (Srr-/-), extending these analyses to juvenile stages in Srr-/- and interneuron-specific NMDA receptor deletion (Nkx2.1:Grin1fl/fl), highlighting cell-type-specific metabolic vulnerability across developmental stages. In MIA, early gestation (E12.5) revealed a transient bioenergetic shift likely driven by microglial and radial glial populations, suggesting metabolic priming rather than canonical inflammatory signaling. By late gestation (E17.5), MIA induced coordinated dysregulation of neuronal glycolytic isoforms alongside mitochondrial and lipid-associated metabolic pathways, suggesting coordinated metabolic remodeling involving lipid-linked processes. In contrast, Srr-/- mice showed minimal glycolytic alterations at E17.5, indicating that isolated genetic perturbation is insufficient to recapitulate this fetal metabolic state. However, at juvenile stages, region-specific bioenergetic adaptations emerged. Srr-/- mice exhibited global cortical increases in glycolytic gene expression, with hippocampal changes potentially enriched in neuronal populations. Conversely, Nkx2.1:Grin1fl/flinterneurons showed increased glycolytic and TCA cycle transcription in the hippocampus but opposing patterns in the medial prefrontal cortex. Together, these findings identify increased glycolytic activity, potentially linked to lactate metabolism, as a partially convergent developmental mechanism bridging prenatal perturbations and later circuit dysfunction in SZ, and suggest that downstream glycolysis-linked pathways may contribute to phenotypic heterogeneity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=174 SRC="FIGDIR/small/723970v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1dd1461org.highwire.dtl.DTLVardef@1651b65org.highwire.dtl.DTLVardef@e98bc8org.highwire.dtl.DTLVardef@d813a2_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Multiviral Quartet Nanocages Elicit Broad Anti-Coronavirus Responses for Proactive Vaccinology

Defending against future pandemics may require vaccine platforms that protect across a range of related pathogens. The presentation of multiple receptor-binding domains (RBDs) from evolutionarily-related viruses on a nanoparticle scaffold elicits a strong antibody response to conserved regions. Here we produce quartets of tandemly-linked RBDs from SARS-like betacoronaviruses coupled to the mi3 nanocage through a SpyTag/SpyCatcher spontaneous reaction. These Quartet Nanocages induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented on the vaccine. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increased the strength and breadth of an otherwise narrow immune response. Quartet Nanocages are a strategy with potential to confer heterotypic protection against emergent zoonotic coronavirus pathogens and facilitate proactive pandemic protection. One Sentence SummaryA vaccine candidate with polyprotein antigens displayed on nanocages induces neutralizing antibodies to multiple SARS-like coronaviruses.

immunology↗

bioRxiv2020

Potent SARS-CoV-2 neutralizing antibodies selected from a human antibody library constructed decades ago

Combinatorial antibody libraries not only effectively reduce antibody discovery to a numbers game, but enable documentation of the history of antibody responses in an individual. The SARS-CoV-2 pandemic has prompted a wider application of this technology to meet the public health challenge of pandemic threats in the modern era. Herein, we used a combinatorial human antibody library constructed 20 years before the COVID-19 pandemic to discover three highly potent antibodies that selectively bind SARS-CoV-2 spike protein and neutralize authentic SARS-CoV-2 virus. Compared to neutralizing antibodies from COVID-19 patients with generally low somatic hypermutation (SHM), these antibodies contain over 13-22 SHMs, many of which are involved in specific interactions in crystal structures with SARS-CoV-2 spike RBD. The identification of these somatically mutated antibodies in a pre-pandemic library raises intriguing questions about the origin and evolution of human immune responses to SARS-CoV-2.

microbiology↗

bioRxiv2020

Differentiation of Human induced Pluripotent Stem Cells to Authentic Macrophages using Fully Defined, Serum Free, Open Source Media

SummaryHuman iPSC and macrophages derived from them are increasingly popular tools for research into both infectious and degenerative diseases. However, as the field strives for greater modelling accuracy, it is becoming ever more challenging to justify the use of undefined and proprietary media for the culture of these cells. We describe here two fully defined, serum-free, open-source media for the culture of iPSC and differentiation of iPSC-derived macrophages. These media are equally capable of maintaining these cells compared to commercial alternatives. The macrophages differentiated in these defined media display improved terminally differentiated cell characteristics, reduced basal expression of induced anti-viral response genes, and improved polarisation capacity. We conclude that cells cultured in these media are an appropriate and malleable model for tissue resident macrophages, on which future differentiation techniques can be built.

immunology↗

bioRxiv2020

Plasmablast-derived antibody response to acute SARS-CoV-2 infection in humans

Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 13.0% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) and over half of anti-nucleocapsid (19 of 35) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-RBD, three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. At last, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.

microbiology↗