Biology subjects

Wang, Y.-S.

Publications and source records attributed to Wang, Y.-S..

3 recordsLinked to original sources

bioRxiv2022

Elevated HLA-E and NKG2A as a consequence of chronic immune activation defines resistance to M. bovis BCG immunotherapy in Non-Muscle-Invasive Bladder Cancer

Mycobacterium bovis Bacillus Calmette-Guerin (BCG), the first-line treatment for non-muscle invasive bladder cancer (NMIBC), promotes the production of inflammatory cytokines, particularly interferon (IFN)-{gamma}. Prolonged inflammation and IFN-{gamma} exposure are known to cause an adaptive immune response, enabling immune escape and proliferation by tumor cells. We investigated HLA-E and NKG2A, a novel T and NK cell checkpoint pathway, as a driver of adaptive resistance in BCG unresponsive NMIBC. We observed ubiquitous inflammation in all patients after BCG immunotherapy, regardless of recurrence status. IFN-{gamma} was shown to drive tumor expression of HLA-E and PD-L1. Further, NKG2A-expressing NK and CD8 T cells were enriched in BCG unresponsive tumors and with enhanced capacity for cytolytic functions. Strikingly, in situ spatial analyses revealed that HLA-EHIGH tumors are activated to recruit NK and T cells via chemokine production, potentially sparing HLA-ELOW tumors that would otherwise be susceptible to lysis. Finally, blood-derived NK cells retained anti-tumor functions at the time of tumor recurrence. These data support combined NKG2A and PD-L1 blockade for BCG unresponsive disease.

immunology↗

bioRxiv2021

Structure-activity relationships of B.1.617 and other SARS-CoV-2 spike variants

The surge of COVID-19 infection cases is spurred by emerging SARS-CoV-2 variants such as B.1.617. Here we report 38 cryo-EM structures, corresponding to the spike protein of the Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Kappa (B.1.617.1) variants in different functional states with and without its receptor, ACE2. Mutations on the N-terminal domain not only alter the conformation of the highly antigenic supersite of the Delta variant, but also remodel the glycan shield by deleting or adding N-glycans of the Delta and Gamma variants, respectively. Substantially enhanced ACE2 binding was observed for all variants, whose mutations on the receptor binding domain modulate the electrostatics of the binding interfaces. Despite their abilities to escape host immunity, all variants can be potently neutralized by three unique antibodies.

biophysics↗

bioRxiv2021

FMRI multi-scale cortical spontaneous activity: 7T vs. 3T

This paper describes the use of the Human Connectome Project (HCP) data for mapping the distribution of spontaneous activity in the human brain across different spatial scales, magnets and individuals. Specifically, the resting-state functional MRI signals acquired under the HCP 3 tesla (T) and 7T magnet protocols were measured by computational methods at multiple spatial scales across the cerebral cortex using: 1) an amplitude metric on a single measuring unit (ALFF), 2) a functional homogeneity metric on a set of neighboring measuring units (ReHo) and 3) a homotopic functional connectivity metric on pairs of symmetric measuring units between the two hemispheres (VMHC). Statistical assessments on these measurements revealed that all the raw metrics were enhanced by the higher magnetic field, highlighting their dependence on magnet field strength. Measurement reliability of these global measurements were moderate to high and comparable between between 3T and 7T magnets. The differences in these measurements introduced by the higher magnetic field were spatially dependent and varied according to specific cortical regions. Specifically, the spatial contrasts of ALFF were enhanced by the 7T magnet within the anterior cortex while weakened in the posterior cortex. This is opposite for ReHo and VMHC. This scale-dependent phenomena also held true for measurement reliabilities, which were enhanced by the 7T magnet for ReHo and VMHC and weakened for ALFF. These reliability differences were primarily located in high-order associate cortex, reflecting the corresponding changes of individual differences: higher between-subject variability and lower within-subject variability for ReHo and VMHC, lower between-subject variability and higher within-subject variability for ReHo and VMHC with respect to higher magnetic field strength. Our work, for the first time, demonstrates the spatial-scale dependence of spontaneous cortical activity measurements in the human brain and their test-retest reliability across different magnet strengths, and discussed about the statistical implications for experimental design using resting-state fMRI.

neuroscience↗