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Biology subjects

White, E. L.

Publications and source records attributed to White, E. L..

4 recordsLinked to original sources

Early immune responses anticipate HIV rebound and precede viral control

Sustained viral suppression following antiretroviral treatment (ART) cessation is a major goal of HIV cure research1. Rare individuals mount immune responses able to control viral rebound without intervention2,3, however, the earliest moments in which these responses form remain poorly defined. We performed an intensively sampled, prospective analytical treatment interruption (ATI) to study the initial immune response to rebound and to understand its role in defining subsequent virus control. Profiling of peripheral blood mononuclear cells and plasma revealed consistent immune activation prior to systemic rebound, including upregulation of antiviral transcriptional pathways, expansion of CD16++ non-classical monocytes, and increases of inflammatory and antiviral soluble plasma proteins. Individuals with prior viral control (controllers) diverged from non-controllers with a slower slope of rebound, a longer period of immune activity prior to rebound, and engagement of a multifaceted immune program with less systemic inflammation. An intermediate immune signature emerged in a separate ATI cohort of individuals who experienced delayed rebound after receiving broadly neutralizing antibodies4, suggesting that immunotherapy can induce a potentially protective pre-rebound immune response. Together, these data resolve the earliest systemic host immune responses to HIV rebound and demonstrate broad immune differences associated with HIV control phenotypes.

immunology↗

ATRX Deficiency Drives Aberrant Type I Interferon Signalling Through cGAS-Dependent Transcriptional Dysregulation

The X-linked -thalassaemia intellectual disability syndrome (ATRX) protein is a chromatin remodeller involved in transcriptional regulation and genome stability. While the importance of ATRX in development and malignancy is well recognised, its role in innate immunity is less well defined. In two unrelated patients demonstrating cerebral white matter disease, learning difficulties and a persistent upregulation of interferon stimulated gene expression in whole blood, we identified the same Y1758C missense substitution in ATRX. Using patient-derived cells, engineered fibroblasts and neuronal models, we show that this substitution, and other loss of function mutations in ATRX, result in enhanced type I interferon signalling through a cGAS-dependent mechanism uncoupled from the DNA sensing activity of cGAS. Loss of ATRX function leads to alterations in the chromatin distribution of DAXX and H3.3, with cGAS essential for the changes in nucleosome composition and gene expression mediated by ATRX deficiency. Thus, our study highlights a previously unrecognized link between ATRX dysfunction and inflammation involving a non-canonical role of cGAS.

immunology↗

Fine-Scale Models of Bee Species Diversity and Habitat in New York State

Anthropogenic drivers of global change threaten bee diversity and the ecosystem services bees provide. Despite their importance, the conservation of bee pollinators is complicated by limited and often heavily biased occurrence data. A recent state-wide survey of insect pollinators across New York, United States generated a large spatial dataset of bee species occurrence records from community scientists, historical collections, and survey efforts. Using a combination of the state survey records with occurrence data from across the contiguous United States, we applied an ensemble modeling approach using balanced random forest and small bivariate generalized linear models to predict the distributions of most of the states bee species. We predicted the spatial distribution of bee species richness using a stacked species distribution model with climate, land cover, and soil covariates. To inform bee diversity conservation, we predicted spatial variation for each species and groups of species sharing similar life history traits. We also estimated statewide distribution of range-size rarity, ecological uniqueness, and climate exposure. We found that the richness of modeled species is high across the state, with the greatest richness in regions with low soil clay content and intermediate forest cover. The fine spatial scale and extent of our gridded data layers match the scale of conservation action in the state, providing an opportunity to incorporate wild bee diversity into broader statewide conservation planning. Conserving New York States bee pollinators is not straightforward, and decisions should be based on broader conservation priorities that incorporate bee biodiversity indicators into decision-making. Here, we encourage the inclusion of these vital pollinators in conservation decisions by leveraging the best available data and methods robust to small sample sizes to provide spatially explicit data products representing the distribution of bee diversity across the state of New York.

ecology↗

Insect Pollinators: The Time is Now for Identifying Species of Greatest Conservation Need

Severe declines in the abundance of insects, including economically and ecologically important pollinators are alarming conservationists and the public. Yet despite these increasingly well documented declines, relatively few pollinating insects other than some butterflies and bumble bees have appeared as Species of Greatest Conservation Need (SGCN) in State Wildlife Action Plans, decadal-scale blueprints for wildlife conservation efforts across the United States that require updating in 2025. Species absent from SGCN lists are ineligible for congressionally appropriated State Wildlife Grants that direct millions of dollars annually for their conservation. In the past, knowledge about the distribution and abundance of many insect pollinators was too poor to identify those meeting state guidelines for inclusion as SGCN. Using case studies from 4 northeastern states, we demonstrate that sufficient conservation status data now exists for many pollinators, including bees, butterflies, moths, beetles, and flower flies, to identify at-risk species meriting inclusion on SGCN lists in many states. Doing so will increase funding available for surveys, habitat protection and enhancement, and other conservation activities that will benefit this vitally important guild.

ecology↗