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Biology subjects

Saravia, A.

Publications and source records attributed to Saravia, A..

3 recordsLinked to original sources

Differential effects of postpartum sleep restriction on maternal and offspring immunity in the rat

Backgroundsleep disturbances can trigger a wide range of physiological consequences, affecting hormonal regulation, metabolism, cognitive function, and immune responses. Human mothers worldwide frequently experience sleep restriction and fragmentation, a pattern also observed in other mammalian mothers, such as rats. These alterations may add to sleep disturbances unrelated to motherhood. Considering this, we wondered about the impact of sleep restriction in postpartum mother rats on their immunological status. Furthermore, given that early-life experiences can shape the immune system and that even subtle parental changes can influence offspring development, we hypothesized that maternal sleep loss might also exert detrimental effects on the pups. In this study, we investigated the effects of acute and chronic maternal sleep restriction during the postpartum period on immune parameters in both mother rats and their offspring by analyzing antibody titers and systemic inflammation. Methodsmother rats were surgically implanted with electrodes for polysomnographic recordings and for sleep deprivation (deep electrodes targeting the mesopontine wake-promoting area). From postpartum day 5 to day 9, lactating dams were randomly assigned to one of three groups: chronic sleep restriction (CSR; 6 h of sleep deprivation per day for five consecutive days), acute sleep restriction (ASR; 6 h of sleep deprivation only on postpartum day 9), or control (undisturbed). On postpartum day 9, mothers were milked, and blood samples from both mothers and pups were subsequently collected. ELISA assays quantified IL-17A, IL-6, IgG, and IgG2a in maternal serum; IgG and IgG2a in milk; and IgG in pup serum. Hematological parameters, including leukocyte profiles, were also assessed in peripheral blood of dams and pups. Resultsmaternal immune parameters analyzed remained unaffected by sleep restriction. IgG levels were lower in male pups from mothers subjected to ASR (5560 {+/-} 734 {micro}g/mL) compared with the control group (8666 {+/-} 463 {micro}g/mL; p = 0.025), whereas female pups showed no significant changes. Additionally, both female (4.10 {+/-} 0.58) and male (3.81 {+/-} 0.42) pups from dams subjected to CSR exhibited higher absolute lymphocytes counts relative to the control group (females: 2.28 {+/-} 0.25, p = 0.004; males: 2.44 {+/-} 0.25; p = 0.029). ConclusionsChronic and acute maternal sleep restriction had distinct impacts on offspring immunity, altering serum antibody and leukocyte profiles, while leaving maternal parameters unaffected. These results indicate that maternal sleep loss can influence the offspring even in the absence of detectable maternal immune alterations, with male pups being especially susceptible.

immunology↗

Population analysis and immunologic landscape of melanoma in people living with HIV

PurposeTo dissect the clinical and immunological features of people living with HIV (PLWH) diagnosed with melanoma, who have consistently shown worse outcomes than HIV-negative individuals (PLw/oH) with the same cancer. Experimental DesignWe analyzed electronic health records from 1,087 PLWH and 394,437 PLw/oH with melanoma. Demographic and clinical characteristics were compared. Spatial immune transcriptomics (72 immune-related genes) was performed on melanoma tumor samples (n=11), with downstream validation using multiplex immunofluorescence (n=15 PLWH, n=14 PLw/oH). ResultsPLWH were diagnosed at a younger age, had greater representation of Hispanic and Black individuals, and showed reduced survival. They also had a markedly increased risk of brain metastases. PLWH experienced significant delays in initiating immune checkpoint inhibitor (ICI) therapy and had worse post-ICI survival, even after balancing covariates. Spatial transcriptomics revealed a more immunosuppressive tumor microenvironment in PLWH, with increased transcription of immune checkpoints (PD1, LAG3) and reduced antigen-presentation markers (HLA-DRB, B2M), with distinct spatial distributions in tumors and surrounding microenvironments. Multiplex immunofluorescence demonstrated features of an exhausted CD8 T cell compartment, including enrichment of PD1intLAG3- and PD1intLAG3 subpopulations, and a significant accumulation of myeloid-derived suppressor cells (CD11b HLA-DR- CD33). ConclusionsMelanoma in PLWH is associated with distinct clinical and immunological features, including delayed ICI treatment, reduced survival, and an immunosuppressive microenvironment with exhausted CD8 T cells and expanded myeloid-derived suppressor cells. These findings suggest that chronic HIV infection may impair antitumor immunity in melanoma. Targeting the pathways identified here may improve therapeutic responses and outcomes in this population. Statement of translational relevanceThis study reveals critical barriers to effective melanoma treatment in people living with HIV (PLWH). Despite receiving immune checkpoint inhibitors (ICIs), PLWH face delayed therapy initiation, a greater likelihood of brain metastases, and significantly higher long-term mortality, even after adjusting for demographic covariates. Transcriptional immune profiling further uncovers a tumor microenvironment enriched in immunosuppressive myeloid-derived suppressor cells and CD8 T cell populations with features of exhaustion. These findings suggest that poorer outcomes in PLWH stem not only from delayed care, but also from distinct targetable mechanisms of immune dysfunction. For example, strategies to reverse MDSC accumulation in the tumor or tailored ICI regimens could enhance immune responsiveness and improve treatment efficiency. By defining the clinical and immunological features of this population, this work highlights opportunities for precision immunotherapy tailored to PLWH with melanoma, with direct implications for improving survival and reducing disparities.

cancer biology↗

Diversity and seasonality of horse flies (Diptera: Tabanidae) in Uruguay

Horse flies (Diptera: Tabanidae) are hematophagous insects that cause direct and indirect losses in livestock production and are important vectors of pathogens. The aim of this study was to determine the diversity and seasonality of horse fly species at an experimental farm in Tacuarembo and the diversity of species in different departments of Uruguay. For 20 months, systematic collections were performed using Nzi and Malaise traps in two different environments at the experimental farm. Temperature, humidity and rainfall were recorded using a local climatological station. In addition, nonsystematic collections were made at farms located in the departments of Paysandu, Tacuarembo and Colonia. A total of 3,666 horse flies were collected, allowing the identification of 16 species. Three species were recorded for the first time in Uruguay: Dasybasis ornatissima (Brethes), Dasybasis missionum (Macquart), and Tabanus aff. platensis Brethes. A species that had not been previously taxonomically described was identified (Tabanus sp.1). In the systematic captures, the most abundant species were Tabanus campestris Brethes, T. aff. platensis and D. missionum, representing 77.6% of the collected specimens. The environment was an important factor related to the abundance of horse flies, as well as the mean temperature. The horse fly season in Tacuarembo started in September and ended in May, with three evident peaks, the most important one during summer. No horse flies were caught during winter. Variations in the prevalence of species in the different departments were observed, indicating the need to carry out new sampling efforts in different areas.

ecology↗