Biology subjects

Delgado, P.

Publications and source records attributed to Delgado, P..

7 recordsLinked to original sources

bioRxiv2026

Oxytocin and Vasopressin at Birth Prevent Hypoactivity and Excess Weight Gain in Vole Offspring Delivered by Cesarean Section

Birth occurs during a sensitive period in brain development wherein hormones facilitate the dramatic shift in physiology that accomplishes the transition to extrauterine homeostasis. The surge in birth signaling hormones is abridged in cases of delivery by cesarean section (CS), which accounts for 32% of all births in the U.S. Epidemiological studies have associated birth via CS with increased risk of obesity in later life. Here, we sought to investigate this association using an experimental preclinical animal model, the prairie vole. Subjects were delivered either via vaginal delivery (VD) or CS and then cross-fostered. CS delivery led to increased body weight across development, which could be prevented with hormone rescue of oxytocin (OXT) and arginine vasopressin (AVP), delivered to neonates immediately after CS. This weight gain could not be attributed to differences in birth weight, parenting, food consumption, or thermoregulation; however, CS subjects moved slower than VD subjects, which hormone rescue reversed. Hormone rescue also reduced adiposity in adulthood among CS subjects. The dopamine system was dysregulated in the caudate/putamen of CS offspring, suggesting a neural mechanism for the decreased locomotion. Hormone rescue of CS neonates restored dopamine synthesis in the caudate/putamen and increased spontaneous locomotor activity. These findings suggest CS can lead to increased weight gain in part through a reduction of locomotion driven by long-lasting changes in striatal dopamine regulation, all of which can be prevented by treating CS neonates with a single peripheral administration of two birth-signaling hormones, OXT and AVP.

neuroscience↗

bioRxiv2025

Viral soluble decoy receptor as a novel treatment for IFN-I triggered diseases

Besides its antiviral action, type I interferon (IFN-I) plays a key role in triggering the inflammatory response and immunopathology in a group of autoinflammatory disorders known as interferonopathies. Current therapies for these diseases focus on blocking IFN-I signaling at different levels, but with incomplete success. Throughout evolution, to counteract the host immune response, poxviruses have developed decoy receptors, soluble proteins secreted from infected cells during infection that bind and block key host cytokines. One of these, the poxvirus IFN-I binding protein (IFN{beta}BP) is a unique soluble receptor with the ability to block many IFN-I subtypes with broad species specificity. In addition, this protein interacts with glycosaminoglycans on the cell surface while binding IFN-I, which enhances its immunomodulatory potential by allowing the retention of this receptor around the site of infection. In this study, we have deepened into how the poxvirus IFN{beta}BP modulates IFN-I to apply this knowledge to the development of new anti-IFN-I therapeutics. With this purpose, a set of IFN{beta}BP-based recombinant proteins were generated and tested for their ability to neutralize IFN-I and bind to the cell surface in vitro, and their immunomodulatory action was tested in the mousepox model of pathogenesis. Finally, the therapeutic potential of some of these selected viral IFN-I inhibitors was validated in two different murine models of autoinflammatory disease, imiquimod-induced psoriasis and pristane-induced lupus.

immunology↗

bioRxiv2024

Ketomimetic Medium Promotes Metastatic Disposition and Chemoresistance in Breast Cancer Cells through Hypersialylation and Lipid Synthesis

While the triggers for the metastatic transformation of breast cancer (BC) cells remain unknown, recent evidence suggests that intrinsic cellular metabolism could be a crucial driver of migratory disposition and chemoresistance. Aiming to decode the molecular mechanisms involved in BC cell metabolic maneuvering, we study how a ketomimetic (ketone body-rich, low glucose) medium affects Doxorubicin (DOX) susceptibility and invasive disposition of BC cells. We quantified glycocalyx sialylation and found an inverse correlation with DOX-induced cytotoxicity and DOX internalization. These measurements were coupled with single-cell metabolic imaging, bulk migration studies, along with transcriptomic and metabolomic analyses. Our findings revealed that a ketomimetic medium enhances chemoresistance and invasive disposition of BC cells via two main oncogenic pathways: hypersialylation and lipid synthesis. We propose that the crosstalk between these pathways, juxtaposed at the synthesis of the glycan precursor UDP-GlcNAc, furthers advancement of a metastatic phenotype in BC cells under ketomimetic conditions.

cancer biology↗

bioRxiv2023

Polyploidy enhances desiccation tolerance in the grass Microchloa caffra

Desiccation tolerance evolved recurrently across diverse plant lineages to enable survival in water limited conditions. Many resurrection plants are polyploid and several groups have hypothesized that polyploidy enabled the evolution of desiccation tolerance. However, due to the vast evolutionary divergence between resurrection plant lineages, the rarity of desiccation tolerance, and the prevalence of polyploidy in plants, this hypothesis has been difficult to test. Here, we surveyed variation in morphological, reproductive, and desiccation tolerance traits across natural populations of a single species that has differing ploidies and tested for links between polyploidy and resilience. We sampled multiple populations of the resurrection grass Microchloa caffra across an environmental gradient ranging from mesic to xeric in South Africa. We describe two distinct ecotypes of M. caffra that occupy different ends of the environmental gradient and exhibit consistent differences in ploidy, morphological, reproductive, and desiccation tolerance traits in both field and common growth conditions. Interestingly, plants with more polyploid genomes were consistently more desiccation tolerant, less reproductive, and larger than plants with smaller genomes and lower ploidy. These data suggest that polyploidy enhances desiccation tolerance and that stronger selective pressures in increasingly xeric sites may play a role in maintaining and increasing desiccation tolerance.

plant biology↗

bioRxiv2022

The Main Themes and Experiences Shared with the Hashtag #BlackintheIvory: A Qualitative Analysis

BackgroundThe movement #BlackintheIvory gave Black academics an opportunity to connect through a social media platform allowing them to share common experiences in the pursuit of higher education. Through the analysis of Twitter posts, using the hashtag #BlackintheIvory, this study investigates the main themes identified among Black scholars in academia and their shared experiences with teaching, mentoring, collegiality, identity, service, and racism. MethodsUsing the Twitter API, we isolated all publicly available tweets, which can include text, images, and links to websites, posted with the hashtag #BlackintheIvory on the Twitter website (www.twitter.com) from the inception of the hashtag in June 2020 to the end of December 2020. To evaluate the tweets, we categorized the tweets inductively. Based on the content of the posts, we identified 6 themes: Teaching, Mentoring, Collegiality, Identity, Service, and Racism. ResultsOur search yielded a total of 12,538 original posts, including tweets between inception in June 2020 to December 2020 from profiles made public (excluding modified tweets and duplicate tweets). We selected and analyzed the top retweeted 2500 tweets, which is 20% (2500/12538) of the total number of downloaded tweets. The greatest percentage of posts were about Teaching (881; 35%), followed by Service (441; 18%) and Racism (414; 17%). The remaining tweets were categorized as Collegiality (388; 15%), Identity (210; 8%), and Mentoring (166; 7%) of the total number of tweets from June-December 2020. ConclusionThe experiences, perspectives, and narratives among the Black diaspora within #BlackintheIvory are not uniform. The commonality exists within the structural systemic racism which impacts Black academics within the ivory tower, this study is a resounding wake-up call for action. FundingThis study was not subject to any funding

scientific communication and education↗

bioRxiv2020

Interplay between UNG and AID governs intratumoral heterogeneity in mature B cell lymphoma

ABSTRACTMost B cell lymphomas originate from B cells that have germinal center (GC) experience and bear chromosome translocations and numerous point mutations. GCs B cells remodel their immunoglobulin (Ig) genes by somatic hypermutation (SHM) and class switch recombination (CSR) in their immunoglobulin (Ig) genes. Activation Induced Deaminase (AID) initiates CSR and SHM by generating U:G mismatches on Ig DNA that can then be processed by Uracyl-N-glycosylase (UNG). AID promotes collateral damage in the form of chromosome translocations and off-target SHM, however, the exact contribution of AID activity to lymphoma generation and progression is not completely understood. Here we show using a conditional knock-in strategy that AID supraactivity alone is not sufficient to generate B cell transformation. In contrast, in the absence of UNG, AID supra-expression increases SHM and promotes lymphoma. Whole exome sequencing revealed that AID heavily contributes to lymphoma SHM, promoting subclonal variability and a wider range of oncogenic variants. Thus, our data provide direct evidence that UNG is a brake to AID-induced intratumoral heterogeneity and evolution of B cell lymphoma.View Full Text

cancer biology↗

bioRxiv2020

Recreation of an antigen-driven germinal center in vitro by providing B cells with phagocytic antigen

Successful vaccines rely on activating a functional humoral response that results from generating class-switched high affinity immunoglobulins (Igs) with a superior capacity to neutralize infection. Key to this process is the germinal center (GC) reaction, in which B cells are selected in their search for antigen and T cell help. A major hurdle to understanding the mechanisms of B cell:T cell cooperation has been the lack of an in vitro system to recreate GCs in an antigen-specific manner. Here we report the generation of functional antigen-specific high affinity Igs of different isotypes in simple 2-cell type cultures of naive B and T cells. It is crucial for this process for B cells to take up antigen by a phagocytic mechanism, which results in stronger and more sustained BCR signals compared to stimulation with a soluble antigen. We also show the applicability of the system to generate antibodies of potential clinical interest.

immunology↗