Biology subjects

Allen, C. E.

Publications and source records attributed to Allen, C. E..

4 recordsLinked to original sources

bioRxiv2026

Distinct EBV-Associated Phenotypes Due to a Novel Homozygous Missense Variant in CD27.

Biallelic deficiencies of CD27 and its ligand CD70 underlie selective susceptibility to Epstein-Barr virus (EBV) infection and its acute and chronic complications, underscoring their non-redundant roles in anti-EBV immunity. To date, 16 pathogenic CD27 variants have been reported. Here, we describe three patients from two unrelated families, homozygous for a novel loss-of-function (LOF) CD27 variant, resulting in substitution of serine 70 with proline (S70P). All three patients presented with EBV viremia and lymphoproliferative disease, with variable immune dysregulation or recurrent otosinopulmonary infections. One patient developed EBV-associated Hodgkin lymphoma. Functional studies demonstrated that the S70P variant impaired surface expression of CD27 and abolished CD70 binding, rendering complete LOF. Together, S70P represents a novel pathogenic CD27 variant causing autosomal recessive (AR) CD27 deficiency, characterized by a unified susceptibility to EBV yet variable clinical manifestations, ranging from chronic viremia to malignancy.

immunology↗

bioRxiv2023

Circulating senescent myeloid cells drive blood brain barrier breakdown and neurodegeneration

Neurodegenerative diseases (ND) are characterized by progressive loss of neuronal function. Mechanisms of ND pathogenesis are incompletely understood, hampering the development of effective therapies. Langerhans cell histiocytosis (LCH) is an inflammatory neoplastic disorder caused by hematopoietic progenitors expressing MAPK activating mutations that differentiate into senescent myeloid cells that drive lesion formation. Some patients with LCH subsequently develop progressive and incurable neurodegeneration (LCH-ND). Here, we show that LCH-ND is caused by myeloid cells that are clonal with peripheral LCH cells. We discovered that circulating BRAFV600E+ myeloid cells cause the breakdown of the blood-brain barrier (BBB), enhancing migration into the brain parenchyma where they differentiate into senescent, inflammatory CD11a+ macrophages that accumulate in the brainstem and cerebellum. Blocking MAPK activity and senescence programs reduced parenchymal infiltration, neuroinflammation, neuronal damage and improved neurological outcome in preclinical LCH-ND. MAPK activation and senescence programs in circulating myeloid cells represent novel and targetable mechanisms of ND.

cell biology↗

bioRxiv2023

Evolution of horn length and lifting strength in the Japanese rhinoceros beetle Trypoxylus dichotomus

Rhinoceros beetle (Trypoxylus dichotomus) males have pitchfork-shaped head horns, which they use to pry rival males from the trunks of trees. In the largest males these horns can be three times the length of horns in the two closest sister species. Because this weapon functions as a lever, longer horns should lift with less force than shorter horns (the paradox of the weakening combatant) unless other elements of the weapon system (e.g., input lever length, muscle mass) evolve to compensate. We used next-generation sequencing approaches to consolidate 23 sample locations into 8 genetically distinguishable populations, reconstructing their historical relationships and providing a comprehensive picture of the evolution of this horn lever system. We show that head horns likely increased in length independently in the Northern and Southern lineages. In both instances this resulted in weaker lifting forces, but this mechanical disadvantage was later ameliorated, to some extent and in some locations, by subsequent reductions to horn length, changes in muscle size, or by an increase in input lever length (head height). Our results reveal an exciting geographic mosaic of differences in weapon size, weapon force, and in the extent and nature of mechanical compensation. Reconstructing the evolution of this weapon system offers critical insights towards meaningfully linking mating system dynamics, selection patterns, and diversity in sexually selected traits.

evolutionary biology↗

bioRxiv2020

Neighboring colonies influence uptake of thermotolerant endosymbionts in threatened Caribbean coral recruits

Intervention strategies to enhance coral resilience include manipulating the association between corals and their algal endosymbionts. While hosting thermotolerant Durusdinium trenchii can increase bleaching thresholds in adults, its effects remain largely unknown during the early life stages of Caribbean corals. Here, we tested if Orbicella faveolata recruits could establish symbiosis with D. trenchii supplied by nearby "donor" colonies and examined the resulting ecological trade-offs to evaluate early Symbiodiniaceae manipulation as a scalable tool for reef restoration. We exposed aposymbiotic recruits to 29{degrees}C or 31{degrees}C and to fragments of either Montastraea cavernosa (containing Cladocopium) or Siderastrea siderea (containing D. trenchii). After 60 days, recruits reared with D. trenchii donors hosted nearly three times more D. trenchii than those with Cladocopium donors, suggesting that recruits can acquire Symbiodiniaceae from nearby corals of different species. Temperature did not affect D. trenchii uptake. Next, donor colonies were removed and surviving recruits were maintained for three months at ambient temperatures, after which a subset was exposed to a 60-day heat stress trial. Recruits previously reared at 31{degrees}C survived twice as long at 34{degrees}C as those reared at 29{degrees}C, suggesting that pre-exposure to heat can prime recruits to withstand future thermal stress. In addition, recruits hosting primarily D. trenchii survived twice as long at 34{degrees}C as those hosting little or no D. trenchii. However, the proportion of D. trenchii hosted was negatively correlated with polyp size and symbiont density, indicating a trade-off between growth (of both host and symbiont) and heat tolerance. These findings suggest that, while donor colonies may be effective sources for seeding coral recruits with thermotolerant symbionts, practitioners will need to balance the likely benefits and costs of these approaches when designing restoration strategies.

ecology↗