Biology subjects

Figueroa, C.

Publications and source records attributed to Figueroa, C..

7 recordsLinked to original sources

bioRxiv2026

HLA-DRB1*15:01 drives sex- and age-dependent microglial activation and neuroimmune signaling

IntroductionThe major histocompatibility complex class II (MHC-II) pathway is central to adaptive immunity and immune tolerance, and age-related erosion of these mechanisms is increasingly recognized as a driver of chronic neuroinflammation. The HLA-DRB1*15:01 allele--the strongest genetic risk factor for multiple sclerosis in Caucasians--has been implicated in shaping pathogenic CD4 T-cell responses and broader neuroimmune vulnerability, yet how this allele modulates age- and sex-dependent neuroimmune processes within the central nervous system (CNS) remains poorly defined. MethodsWe investigated the impact of HLA-DRB1*15:01 expression using a humanized mouse model (HLA mice) and wild-type (WT) controls. Male and female mice were analyzed at 6, 9, and 15 months of age, with endocrine stratification in females. Behavioral testing, flow cytometry, immunofluorescence, and multiplex cytokine analyses were used to assess cognitive performance, glial activation and oxidative stress, astrocyte-microglia IL-3/IL-3R signaling, endothelial activation, selective immune cell accumulation at CNS borders, tissue organization, and hippocampal cytokine profiles. ResultsHLA mice developed age- and sex-dependent cognitive impairment, most pronounced in aged females. HLA-DRB1*15:01 expression promoted progressive microglial activation, characterized by increased CD14 and CD68 expression, elevated mitochondrial oxidative stress, altered astrocyte phenotypes, and enhanced IL-3/IL-3R signaling. Hippocampal axonal and myelin organization was disrupted in aged HLA mice, and this disruption was spatially associated with increased microglial presence. At CNS interfaces, HLA mice exhibited selective immune remodeling, including increased accumulation of CD4 T cells and NK1.1CD3 natural killer T (NKT) cells, particularly in females, accompanied by endothelial activation, as evidenced by elevated ICAM-1 and E-selectin expression. Hippocampal cytokine profiling revealed selective, sex-biased alterations, including increased IL-12p70 and reduced IL-10 and IL-2, without broad induction of classical inflammatory cytokines. ConclusionTogether, these findings demonstrate that HLA-DRB1*15:01 drives a coordinated, age- and sex-dependent neuroinflammatory program linking behavioral dysfunction, glial activation and oxidative stress, selective immune cell recruitment, endothelial activation, tissue remodeling, and targeted cytokine imbalance. This integrated phenotype provides mechanistic insight into how this major MS risk allele confers vulnerability to chronic neuroinflammation during aging, with heightened impact in females.

neuroscience↗

bioRxiv2025

Functional Characterization of 123 Genes from Mycobacteriophage LeBron Uncovers Cytotoxic Gene Families in Cluster L1

Bacteriophages represent a vast reservoir of genetic diversity however, functional annotation remains a major challenge, as most predicted gene products lack detectable similarity to characterized gene families. Experimental approaches such as systematic overexpression screens provide an avenue for identifying phage genes that influence bacterial physiology. Here, we report an overexpression screen of all 123 predicted protein-coding genes from Cluster L1 mycobacteriophage LeBron, the first representative of this cluster to undergo genome-wide functional analysis. Expression assays in Mycobacterium smegmatis revealed that 39 genes (32%) impaired host growth, with nineteen of these toxic genes (49%) assigned no known function. The proportion of cytotoxic genes observed in LeBron is comparable to findings from Clusters K and F, despite minimal sequence conservation across clusters. Interestingly, a subset of LeBrons toxic genes appear to be functionally analogous to previously identified toxic genes in other clusters, suggesting conserved biological activities carried out by non-homologous proteins. Additionally, this analysis uncovered several novel gene families that elicit strong cytotoxic effects, expanding the known catalog of phage-derived bacterial growth inhibitors. These results provide new insights into phage gene functions and demonstrate the value of genome-wide expression screening for uncovering conserved and cluster-specific interactions between bacteriophages and their hosts.

microbiology↗

bioRxiv2023

Dynamics of the viral community on the cheese surface during maturation and persistence across production years

The surface of smear-ripened cheeses constitutes a dynamic microbial ecosystem resulting from the successive development of different microbial groups such as lactic acid bacteria, fungi and ripening bacteria. Recent studies indicate that a viral community, mainly composed of bacteriophages, also represents a common and substantial part of the cheese microbiome. However, the composition of this community, its temporal variations and associations between bacteriophages and their hosts remain poorly characterized. Here, we studied a French smear-ripened cheese by both viral metagenomics and 16S metabarcoding approaches to assess both the succession of phages and bacterial communities on the cheese surface during cheese ripening, and their temporal variations in ready-to-eat cheeses over the years of production. We observed a clear transition of the phage community structure during ripening with a decreased relative abundance of viral species (vOTUs) associated with Lactococcus phages, which were replaced by vOTUs associated with phages infecting ripening bacteria such as Brevibacterium, Glutamicibacter, Pseudoalteromonas and Vibrio. The dynamics of the phage community was strongly associated with bacterial successions observed on the cheese surface. Finally, while some variations in the distribution of phages were observed in ready-to-eat cheeses produced at different dates spanning more than 4 years of production, the most abundant phages were detected throughout. This result revealed the long-term persistence of the dominant phages in the cheese production environment. Together, these findings offer novel perspectives on the ecology of bacteriophages in smear-ripened cheese and emphasize the significance of incorporating bacteriophages in the microbial ecology studies of fermented foods. IMPORTANCEThe succession of diverse microbial populations is critical for ensuring the production of high-quality cheese. We observed a temporal succession of phages on the surface of a smear-ripened cheese, with new phage communities showing up at the time when ripening bacteria start covering this surface. Interestingly, the final phage community of this cheese is also consistent over large periods of time, as the same bacteriophages were found in cheese products from the same manufacturer made over 4-years. This research highlights the importance of considering these bacteriophages when studying the microbial life of fermented foods like cheese.

microbiology↗

bioRxiv2023

Social aging trajectories are sex-specific, sensitive to adolescent stress, and most robustly revealed during social tests with familiar stimuli

Social networks and support are integral to health and wellness across the lifespan, and social engagement may be particularly important during aging. However, social behavior and social cognition decline naturally during aging across species. Social behaviors are in part supported by the reward circuitry, a network of brain regions that develops during adolescence. We published that male and female rats undergo adolescent social development during sex-specific periods, pre-early adolescence in females and early-mid adolescence males. Although males and females have highly dimorphic development, expression, and valuation of social behaviors, there is relatively little data indicating whether social aging is the same or different between the sexes. Thus, we sought to test two hypotheses: (1) natural social aging will be sex-speciifc, and (2) social isolation stress restricted to sex-specific adolescent critical periods for social development would impact social aging in sex-specific ways. To do this, we bred male and female rats in-house, and divided them randomly to receive either social isolation for one week during each sexs respective critical period, or no manipulation. We followed their social aging trajectory with a battery of five tests at 3, 7, and 11 months of age. We observed clear social aging signatures in all tests administered, but sex differences in natural social aging were most robustly observed when a familiar social stimulus was included in the test. We also observed that adolescent isolation did impact social behavior, in both age-independent and age-dependent ways, that were entirely sex-specific. Please note, this preprint will not be pushed further to publication (by me, AMK), as I am leaving academia. So, its going to be written more conversationally.

neuroscience↗

bioRxiv2023

Morphine exposure during adolescence induces enduring social changes dependent on adolescent stage of exposure, sex, and social test

Drug exposure during adolescence, when the reward circuitry of the brain is developing, can permanently impact reward-related behavior. Epidemiological studies show that opioid treatment during adolescence, such as pain management for a dental procedure or surgery, increases the incidence of psychiatric illness including substance use disorders. Moreover, the opioid epidemic currently in the United States is affecting younger individuals raising the impetus to understand the pathogenesis of the negative effects of opioids. One reward-related behavior that develops during adolescence is social behavior. We previously demonstrated that social development occurs in rats during sex-specific adolescent periods: early to mid-adolescence in males (postnatal day (P)30-40) and pre-early adolescence in females (P20-30). We thus hypothesized that morphine exposure during the female critical period would result in adult sociability deficits in females, but not males, and morphine administered during the male critical period would result in adult sociability deficits in males, but not females. We found that morphine exposure during the female critical period primarily resulted in deficits in sociability in females, while morphine exposure during the male critical period primarily resulted in deficits in sociability primarily in males. However, depending on the test performed and the social parameter measured, social alterations could be found in both sexes that received morphine exposure at either adolescent stage. These data indicate that when drug exposure occurs during adolescence, and how the endpoint data are measured, will play a large role in determining the effects of drug exposures on social development.

neuroscience↗

bioRxiv2021

Morphine exposure bidirectionally alters c-Fos expression in a sex-, age-, and brain region-specific manner during adolescence

Drug and alcohol use during adolescence is common, and data in both humans and preclinical animal models clearly indicate drug exposure during adolescence increases the risk of substance use and other mental health disorders later in life. Adolescence is a period of social, emotional, and cognitive development, and is characterized by increased exploratory behavior, risk-taking, and peer-centered social interactions. These are thought to be behavioral manifestations of developmental plasticity in reward regions of the brain. Human data indicate that adolescence is not a unitary developmental period, but rather different neural and behavioral sequelae can be observed in early vs. late adolescence. However, most studies with rodent models examine a single adolescent age compared to a mature adult age, and often only in males. Herein, we sought to determine whether the acute response to the opioid morphine would also differ across adolescence, and by sex. By quantifying c-Fos positive cells, a proxy for neural activity, at different stages during adolescence (pre-, early, mid-, and late adolescence) and in multiple reward regions (prefrontal cortex, nucleus accumbens, caudate/putamen), we determined that acute morphine can either reduce or increase c-Fos expression dependent on adolescent age, sex, and brain region. These data suggest that heterogeneity in the consequences of adolescent opioid exposure may be due to the interaction between age- and sex-specific developmental profiles of reward processing in individual brain regions. In future studies, it will be important to add age within adolescence as an independent variable to fully capture the consequences of healthy or abnormal reward-related neural development.

neuroscience↗

bioRxiv2021

Commercial vaccines do not confer protection against two genetic strains of Piscirickettsia salmonis, LF-89-like and EM-90-like, in Atlantic salmon.

In Atlantic salmon, vaccines have failed to control and prevent Piscirickettsiosis, for reasons that remain elusive. In this study, we report the efficacy of a commercial vaccine developed with the Piscirickettsia salmonis isolate AL100005 against other two isolates which are considered highly and ubiquitously prevalent in Chile: LF-89-like and EM-90-like. Two cohabitation trials were performed to mimic real-life conditions and vaccine performance: 1) post smolt fish were challenged with a single infection of LF-89-like, 2) adults were coinfected with EM-90-like and a low coinfection of sea lice. In the first trial, the vaccine delayed smolt mortalities by two days; however, unvaccinated and vaccinated fish did not show significant differences in survival (unvaccinated: 60.3%, vaccinated: 56.7%; p = 0.28). In the second trial, mortality started three days later for vaccinated fish than unvaccinated fish. However, unvaccinated and vaccinated fish did not show significant differences in survival (unvaccinated: 64.6%, vaccinated: 60.2%, p= 0.58). Thus, we found no evidence that the evaluated vaccines confer effective protection against of LF-89-like or EM-90-like with estimated relative survival proportions (RPSs) of -9% and -12%, respectively. More studies are necessary to evaluate whether pathogen heterogeneity is a key determinant of the vaccine efficacy against P. salmonis.

immunology↗