Biology subjects

Cheney, J. A.

Publications and source records attributed to Cheney, J. A..

4 recordsLinked to original sources

bioRxiv2026

CD8 T cells with classical and NK-like cytotoxic gene expression programs mediate control of HBV replication and functional cure

Chronic hepatitis B is characterized by a decades-long evolving engagement between host immunity and the hepatitis B virus (HBV). Understanding the molecular characteristics of HBV-specific CD8 T cells linked to control of viral replication and antigenemia is essential to design effective immunotherapeutic modalities. Here we show that HBV-specific CD8 T cells, even during infection stages with extremely high viral loads, lack the features of terminally exhausted CD8 T cells observed in chronic HCV and HIV infection or cancer. Instead, we observe emerging gene expression programs over disease stages that correlate with increasing HBV control, which include a bona fide cytotoxic and T-cell localization program associated with low levels of viral replication, and a second NK-like T-cell program that combines expression of classical NK markers (KIRs, KLRs, FCGR3A, TYROBP, IKZF2) with cytotoxic genes (GZMB, GNLY, PRF1), which emerges with complete control of HBV viremia and antigenemia. We also found enrichment of both CD8 T-cell programs in HIV-specific CD8 T cells from HIV elite controllers, supporting a conserved role in controlling persistent viral infections with viral reservoirs.

immunology↗

bioRxiv2022

Dynamics of hinged wings in strong upward gusts

A birds wings are articulated to its body via highly mobile shoulder joints. The wings possess an impressive range of motion, which allows for movements that can modulate the production of aerodynamic load in flight. This is crucial for stability and control--particularly in gusty or turbulent environments. In this study, we develop a dynamics model to examine how a bird-scale gliding aircraft can use wing-root hinges (analogous to avian shoulder joints) to reject the initial impact of a strong upward gust. Our idea requires that the spanwise centre of pressure and the centre of percussion of the hinging wing start, and stay, in good initial alignment (the centre of percussion here is related to the idea of a sweet spot on a bat, as in cricket or baseball). We propose a method for achieving this rejection passively, for which the essential ingredients are: (i) well-considered lift and mass distributions; (ii) constant-torque hinges; and (iii) a wing whose sections stall softly. When configured correctly, the gusted wings will first pivot on their hinges without disturbing the fuselage of the aircraft, affording time for other corrective actions to engage. We expect this system to enhance the control of aircraft that fly in gusty conditions.

bioengineering↗

bioRxiv2021

Differentiation of exhausted CD8 T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory

T cell exhaustion is associated with failure to clear chronic infections and malignant cells. Defining the molecular mechanisms of T cell exhaustion and reinvigoration is essential to improving immunotherapeutic modalities. Analysis of antigen-specific CD8+ T cells before and after antigen removal in human hepatitis C virus (HCV) infection confirmed pervasive phenotypic, functional, and transcriptional differences between exhausted and memory CD8+ T cells. After viral cure, we observed broad phenotypic and transcriptional changes in clonally stable exhausted T-cell populations suggesting differentiation towards a memory-like profile. However, functionally, the cells showed little improvement and critical transcriptional regulators remained in the exhaustion state. Notably, T cells from chronic HCV infection that were exposed to antigen for shorter periods of time because of viral escape mutations were functionally and transcriptionally more similar to memory T cells from spontaneously resolved acute HCV infection. Thus, duration of T cell stimulation impacts the ability to recover from exhaustion, as antigen removal after long-term T cell exhaustion is insufficient for the development of key T cell memory characteristics.

immunology↗

bioRxiv2020

From wing shape to fluid dynamics in the barn owl (Tyto alba)

Birds morph their wings and tail in order to glide under a wide range of aerodynamic conditions. Gross wing morphing has been described in a multitude of studies, but the finer details of wing morphing are still unknown. Here, we measured the changes in wing shape and pose in a barn owl, Tyto alba, when gliding across a range of fifteen self-selected speeds. We found that T. alba does not use fine-wing shape control to glide at slow speeds in steady conditions, with the measured wing shapes being highly consistent across all flights. Instead, T. alba relied upon wing postural control (gross pitch) and changes in both tail shape and pose to modulate aerodynamic force. A consistent wing shape provides an exceptional aerodynamic tool for understanding gliding flight in birds through postural change and tail morphing. This geometry was used as the basis for computational fluid dynamics simulations which gave very similar wake measurements and weight support to those measured in flight. This geometry is provided here to assist other researchers interested in exploring the fluid dynamics behind gliding flight in birds.Competing Interest StatementThe authors have declared no competing interest.View Full Text

zoology↗