Biology subjects

Wolfe, B.

Publications and source records attributed to Wolfe, B..

7 recordsLinked to original sources

bioRxiv2025

Biological Sex Differences after High and Low Doses of Influenza A Virus Infection in a Diet-induced Obesity Mouse Model

Obesity is an independent risk factor for influenza A virus (IAV) pathogenesis. In non-obese hosts, following IAV infection, adult females develop more severe disease than males. Limited research on biological sex differences following IAV infection in individuals with obesity forms the basis for this study. Male and female C57BL/6J mice were treated with high-fat or low-fat diets to obtain mice with or without obesity. They were inoculated intranasally with a high (103) or low dose (101.5 TCID50) of mouse-adapted A/California/04/2009 H1N1 IAV and followed for 21 days post-infection (dpi) for morbidity. Subsets of mice were euthanized at different dpi to measure lung virus titers, histopathological changes, cellular infiltration, and cytokine induction. After a high-dose infection, females with obesity demonstrated shorter median survival time, greater parenchymal inflammation, and heightened induction of inflammatory markers than males with obesity. After a low-dose infection, females than males, and mice with obesity than the non-obese mice, exhibited severe morbidity. Female mice with obesity exhibited the greatest disease severity, where 25% (2/8) reached humane endpoint. Delayed but persistent inflammatory changes were observed in females with obesity, characterized by relatively lower pathological changes, lesser induction of cytokines and chemokines, and reduced myeloid and lymphoid infiltration in the lungs at 3 dpi followed by sustained pathological changes and cytokine and chemokine induction at 21 dpi. Our study suggests that the biological sex difference following IAV infection persists during obesity. Females with obesity experience greater influenza disease severity than males, possibly driven by more severe dysregulation of inflammatory responses. ImportanceThe prevalence of obesity is increasing worldwide. The risk of developing severe disease following influenza virus infection is higher in individuals with obesity. Males and females with obesity differ in terms of fat deposition and inflammatory and metabolic biomarkers. These differences can alter the outcomes of influenza-induced disease pathogenesis. The observation of sex differences in IAV pathogenesis among non-obese hosts underscores the importance of determining whether similar differences occur in the context of obesity. Indeed, our study suggested that females with obesity experience greater disease severity than males with obesity after IAV infection. Understanding the immunological mechanisms of such differences will advance precision medicine approaches to develop safer and more effective preventive and therapeutic strategies against influenza for the high-risk populations with obesity.

immunology↗

bioRxiv2025

Females with Obesity Exhibit Greater Influenza Vaccine-induced Immunity and Protection than Males in a Mouse Model

IntroductionObesity is increasing globally, and it negatively impacts influenza vaccine efficacy. Although sex differences in influenza vaccine responses are studied in non-obese hosts, studies investigating sex differences in influenza vaccine-induced immunity and protection during obesity are limited. Materials and methodsUsing the C57BL/6J mouse model of high-fat diet (HFD)-induced obesity or low-fat diet controls, we investigated sex differences in influenza vaccine-induced immunity and protection during obesity. Male and female mice with or without obesity were vaccinated intramuscularly twice at a 3-week interval with an inactivated 2009 H1N1 influenza A virus (IAV) vaccine. At 35 days post-vaccination (dpv), antibody responses in plasma and B- and T-cell responses in spleen and bone marrow were quantified. At 42 dpv, mice were intranasally challenged with a drift variant of the H1N1 IAV, and disease severity was assessed by monitoring the change in body mass up to 21 days post-challenge (dpc). Subsets of mice were euthanized at 3 dpc to determine pulmonary virus replication (TCID50 assay), histopathology (H&E staining), and cytokine/chemokine responses (multiplex ELISA). ResultsFemale mice, irrespective of diet and obesity status, developed higher antibody responses and were better protected compared to males. Vaccinated males with obesity mounted the poorest antibody responses, experienced a more severe disease, were unable to clear replicating virus from the lungs effectively, and demonstrated heightened pulmonary inflammation. Despite these differences, splenic B- and T-cell frequencies were comparable, suggesting the inefficiency of B cells to produce antibodies in males but not in females with obesity. DiscussionOur findings suggest that sex differences is observed in influenza vaccine-induced immunity and protection during obesity, where males are more severely affected. These findings highlight the importance of considering biological sex and obesity status in influenza vaccine design and testing.

immunology↗

bioRxiv2024

Pairwise interactions and serial bottlenecks help explain species composition in a multi-species microbial community

Characterizing the processes that drive microbial community assembly remains a key challenge in ecology. Several recent studies have argued that pairwise interactions may be insufficient to explain co-occurrence patterns in complex microbial communities, but most such studies have focused on synthetic communities not found in nature or microbes grown in contexts that differ widely from their natural environment. Moreover, most models of pairwise interactions rely on equilibrium assumptions that are not relevant to all natural communities, such as gut microbiomes or species in fluctuating environments. Inclusion of appropriate demographic factors into models of pairwise interactions could be a potential approach to better capture patterns of community assembly. In this study, we investigated whether multi-species co-occurrence patterns can be predicted from pairwise interactions for microbes isolated from sourdough starters. Interaction parameters inferred from pairwise growth trajectories were suggestive of widespread coexistence between pairs of microbes in our species pool. In communities of up to nine species, most species presence and relative abundance could be reliably predicted based on a model of pairwise interactions. The inclusion of nonequilibrium demography in our model further improved the accuracy of our pairwise model. Our work contributes to the broader debate on the processes underlying community assembly by showing that pairwise interactions are predictive of community structure in a system of moderate species complexity.

ecology↗

bioRxiv2023

Overexpression of Alpha-1 Antitrypsin Increases the Proliferation of Mesenchymal Stem Cells by Upregulation of Cyclin D1 and is Independent of the Wnt Signaling Pathway

Alaph-1 antitrypsin overexpressing mesenchymal stromal/stem cells (AAT-MSCs) showed improved innate properties with a faster proliferation rate when studied for their protective effects in mouse models of diseases. Here, we investigated the potential mechanism(s) by which AAT gene insertion increases MSC proliferation. Human bone marrow-derived primary or immortalized MSCs (iMSCs) or AAT-MSCs (iAAT-MSCs) were used in the study. Cell proliferation was measured by cell counting and cell cycle analysis. Possible pathways involved in the pro-proliferation effect of AAT were investigated by measuring mRNA and protein expression of key cell cycle genes. Interval cell counting showed increased proliferation in AAT-MSCs or iAAT-MSCs compared to their corresponding MSC controls. Cell cycle analysis revealed more cells progressing into the S and G2/M phases in iAAT-MSCs, with a notable increase in the cell cycle protein, Cyclin D1. Moreover, treatment with Cyclin D1 inhibitors showed that the increase in proliferation is due to Cyclin D1 and that the AAT protein is upstream and a positive regulator of Cyclin D1. Furthermore, AATs effect on Cyclin D1 is independent of the Wnt signaling pathway as there were no differences in the expression of regulatory proteins, including GSK3{beta} and {beta}-Catenin in iMSC and iAAT-MSCs. In summary, our results indicate that AAT gene insertion in an immortalized MSC cell line increases cell proliferation and growth by increasing Cyclin D1 expression and consequently causing cells to progress through the cell cycle at a significantly faster rate.

cell biology↗

bioRxiv2019

Native and invasive populations of the ectomycorrhizal death cap Amanita phalloides are highly sexual but dispersal limited

The authors have withdrawn this manuscript and do not wish it to be cited. As we have moved more deeply into population genomics, we have discovered the analyses we initially used do not answer our questions well. We are recalibrating and intend to submit a new manuscript in the future. If you have any questions, please contact the corresponding author.

microbiology↗

bioRxiv2019

Rapid phenotypic and metabolomic domestication of wild Penicillium molds on cheese

Fermented foods provide novel ecological opportunities for natural populations of microbes to evolve through successive recolonization of resource-rich substrates. Comparative genomic data have reconstructed the evolutionary histories of microbes adapted to food environments, but experimental studies directly demonstrating the process of domestication are lacking for most fermented food microbes. Here we show that during the repeated colonization of cheese, phenotypic and metabolomic traits of wild Penicillium molds rapidly change to produce mutants with properties similar to industrial cultures used to make Camembert and other bloomy rind cheeses. Over a period of just a few weeks, populations of wild Penicillium strains serially passaged on cheese resulted in the reduction or complete loss of pigment, spore, and mycotoxin production. Mutants also had a striking change in volatile metabolite production, shifting from production of earthy or musty volatile compounds (e.g. geosmin) to fatty and cheesy volatiles (e.g. 2-nonanone, 2-undecanone). RNA-sequencing demonstrated a significant decrease in expression of 356 genes in domesticated mutants, with an enrichment of many secondary metabolite production pathways in these downregulated genes. By manipulating the presence of neighboring microbial species and overall resource availability, we demonstrate that the limited competition and high nutrient availability of the cheese environment promote rapid trait evolution of Penicillium molds.\n\nIMPORTANCEIndustrial cultures of filamentous fungi are used to add unique aesthetics and flavors to cheeses and other microbial foods. How these microbes adapted to live in food environments is generally unknown as most microbial domestication is unintentional. Our work demonstrates that wild molds closely related to the starter culture Penicillium camemberti can readily lose undesirable traits and quickly shift toward producing desirable aroma compounds. In addition to experimentally demonstrating a putative domestication pathway for P. camemberti, our work suggests that wild Penicillium isolates could be rapidly domesticated to produce new flavors and aesthetics in fermented foods.

microbiology↗

bioRxiv2017

Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques

Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals clear viremia within 10-12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection.

pathology↗