Biology subjects

Bonilla, H.

Publications and source records attributed to Bonilla, H..

3 recordsLinked to original sources

bioRxiv2026

Widespread occurrence of XXY females in Drosophila mojavensis and related species

Bridges first reported that XXY individuals are fertile females in Drosophila melanogaster, arising at low frequency (~1/2000) through errors in chromosome segregation (BRIDGES 1914; BRIDGES 1916). Although widely used in genetic studies, XXY females are seldom found in wild-type strains or natural populations, presumably because natural selection keeps them at very low frequency. Here we show that many wild-type strains of D. mojavensis and its close relatives D. arizonae, D. navojoa, and D. wheeleri carry XXY and XXYY females at frequencies of up to 88%; males from these strains are frequently XYY or XYYY. Although field collections were hampered by population declines and safety concerns, we found one XXY female (out of 87) and one XYY male (out of 36) in a natural population of D. mojavensis, indicating that these genotypes also occur at appreciable frequencies in nature. XXY females are expected to produce XY-bearing and X-bearing eggs in equal proportions; instead, we found a 57:43 ratio. Mathematical modeling shows that this meiotic-drive advantage is sufficient to explain high frequencies of XXY females. It is universally accepted that Y evolution responds exclusively to male selection, yet in XXY-bearing species it also responds to female fitness.

evolutionary biology↗

bioRxiv2024

Sex differences and immune correlates of Long COVID development, persistence, and resolution

Sex differences have been observed in acute COVID-19 and Long COVID (LC) outcomes, with greater disease severity and mortality during acute infection in males and a greater proportion of females developing LC. We hypothesized that sex-specific immune dysregulation contributes to the pathogenesis of LC. To investigate the immunologic underpinnings of LC development and persistence, we used single-cell transcriptomics, single-cell proteomics, and plasma proteomics on blood samples obtained during acute SARS-CoV-2 infection and at 3 and 12 months post-infection in a cohort of 45 patients who either developed LC or recovered. Several sex-specific immune pathways were associated with LC. Specifically, males who would develop LC at 3 months had widespread increases in TGF-{beta} signaling during acute infection in proliferating NK cells. Females who would develop LC demonstrated increased expression of XIST, an RNA gene implicated in autoimmunity, and increased IL1 signaling in monocytes at 12 months post infection. Several immune features of LC were also conserved across sexes. Both males and females with LC had reduced co-stimulatory signaling from monocytes and broad upregulation of NF-{kappa}B transcription factors. In both sexes, those with persistent LC demonstrated increased LAG3, a marker of T cell exhaustion, reduced ETS1 transcription factor expression across lymphocyte subsets, and elevated intracellular IL-4 levels in T cell subsets, suggesting that ETS1 alterations may drive an aberrantly elevated Th2-like response in LC. Altogether, this study describes multiple innate and adaptive immune correlates of LC, some of which differ by sex, and offers insights toward the pursuit of tailored therapeutics. One Sentence SummaryThis multi-omic analysis of Long COVID reveals sex differences and immune correlates of Long COVID development, persistence, and resolution.

immunology↗

bioRxiv2024

Oxidative Stress is a shared characteristic of ME/CFS and Long COVID

More than 65 million individuals worldwide are estimated to have Long COVID (LC), a complex multisystemic condition, wherein patients of all ages report fatigue, post-exertional malaise, and other symptoms resembling myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). With no current treatments or reliable diagnostic markers, there is an urgent need to define the molecular underpinnings of these conditions. By studying bioenergetic characteristics of peripheral blood lymphocytes in over 16 healthy controls, 15 ME/CFS, and 15 LC, we find both ME/CFS and LC donors exhibit signs of elevated oxidative stress, relative to healthy controls, especially in the memory subset. Using a combination of flow cytometry, bulk RNA-seq analysis, mass spectrometry, and systems chemistry analysis, we also observed aberrations in ROS clearance pathways including elevated glutathione levels, decreases in mitochondrial superoxide dismutase levels, and glutathione peroxidase 4 mediated lipid oxidative damage. Critically, these changes in redox pathways show striking sex-specific trends. While females diagnosed with ME/CFS exhibit higher total ROS and mitochondrial calcium levels, males with an ME/CFS diagnosis have normal ROS levels, but larger changes in lipid oxidative damage. Further analyses show that higher ROS levels correlates with hyperproliferation of T cells in females, consistent with the known role of elevated ROS levels in the initiation of proliferation. This hyperproliferation of T cells can be attenuated by metformin, suggesting this FDA-approved drug as a possible treatment, as also suggested by a recent clinical study of LC patients. Thus, we report that both ME/CFS and LC are mechanistically related and could be diagnosed with quantitative blood cell measurements. We also suggest that effective, patient tailored drugs might be discovered using standard lymphocyte stimulation assays.

immunology↗