The influence of hydrostatic pressure on the partial molar volume (PMV) of the protein apomyoglobin (AMb) was investigated by all-atom molecular dynamics (MD) simulations. Using the time-resolved Kirkwood-Buff (KB) approach, the dynamic behavior of the PMV was identified. The simulated time average value of the PMV and its reduction by 3000 bar pressurization correlated with experimental data. In addition, with the aid of the surficial KB integral method, we obtained the spatial distributions of the components of PMV to elucidate the detailed mechanism of the PMV reduction. New R-dependent PMV profiles identified the regions that increase or decrease the PMV under the high pressure condition. The results indicate that besides the hydration in the vicinity of the protein surface, the outer space of the first hydration layer also significantly influences the total PMV change. These results provide a direct and detailed picture of pressure induced PMV reduction.
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http://dx.doi.org/10.1021/jp1043267 | DOI Listing |
Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.
View Article and Find Full Text PDFPacing Clin Electrophysiol
January 2025
Department of Cardiology, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, UK.
Background: Pulmonary vein isolation (PVI) has been established as an effective management option for symptomatic paroxysmal atrial fibrillation (PAF). We aimed to explore the role of P-wave parameters in a 12-lead electrocardiogram (ECG) in predicting the success of repeat PAF ablation.
Methods: We enrolled consecutive patients who underwent a second AF ablation procedure for PAF in a UK tertiary center after an index ablation conducted between 2018 and 2019 and a repeat ablation up to 2021.
Proc Natl Acad Sci U S A
December 2024
The Francis Crick Institute, London NW1 1AT, United Kingdom.
The consequences of reactive oxygen species (ROS) in cancer cells are complex and have been shown to both promote and retard tumorigenesis in different models. In mouse models of pancreatic ductal adenocarcinoma (PDAC), loss of the antioxidant defense gene results in both a reduction in the development of early pancreatic intraepithelial neoplasia and an increase in invasive and metastatic capacity, accompanied by decreased survival of mice lacking pancreatic TIGAR. We previously demonstrated that increased ROS following loss of TIGAR promotes various cancer cell-intrinsic changes that contribute to metastatic capacity, including epithelial to mesenchymal transition, enhanced migration and invasion, and an increase in ERK signaling.
View Article and Find Full Text PDFSci Rep
October 2024
State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, China.
Snake venom C-type lectin-like proteins (CLPs) belong to the nonenzymatic proteins. To date, no CLP with both platelet and coagulation factors activating activities has been reported. In this study, a novel CLP, termed protocetin, with molecular weight of 29.
View Article and Find Full Text PDFbioRxiv
September 2024
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Viruses have evolved myriad strategies to exploit the translation machinery of host cells to potentiate their replication. However, how paramyxovirus (PMVs) modulate cellular translation for their own benefit has not been systematically examined. Utilizing puromycylation labeling, overexpression of individual viral genes, and infection with wild-type virus versus its gene-deleted counterpart, we found that PMVs significantly inhibit host cells' nascent peptide synthesis during infection, with the viral matrix being the primary contributor to this effect.
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