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Controlling enzyme activity by mutagenesis and metal exchange to obtain crystal structures of stable substrate complexes of Class 3 l-asparaginase.
FEBS J
January 2025
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
Rhizobium etli is a nitrogen-fixing bacterium that encodes two l-asparaginases. The structure of the inducible R. etli asparaginase ReAV has been recently determined to reveal a protein with no similarity to known enzymes with l-asparaginase activity, but showing a curious resemblance to glutaminases and β-lactamases.
View Article and Find Full Text PDFPharmacological targeting of caspase-8/c-FLIP heterodimer enhances complex II assembly and elimination of pancreatic cancer cells.
Commun Biol
January 2025
Translational Inflammation Research, Medical Faculty, Otto von Guericke University (OvGU), Magdeburg, Magdeburg, Germany.
Extrinsic apoptotic network is driven by Death Ligand (DL)-mediated activation of procaspase-8. Recently, we have developed the first-in class small molecule, FLIPinB, which specifically targets the key regulator of extrinsic apoptosis, the protein c-FLIP, in the caspase-8/c-FLIP heterodimer. We have shown that FLIPinB enhances DL-induced caspase-8 activity and apoptosis.
View Article and Find Full Text PDFFcRn-guided antigen trafficking enhances cancer vaccine efficacy.
Cancer Immunol Immunother
January 2025
Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, People's Republic of China.
The development of tumor vaccines represents a significant focus within cancer therapeutics research. Nonetheless, the efficiency of antigen presentation in tumor vaccine remains suboptimal. We introduce an innovative mRNA-lipid nanoparticle platform designed to express tumor antigenic epitopes fused with the transmembrane domain and cytoplasmic tail of the neonatal Fc receptor (FcRn).
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Massachusetts General Hospital, Boston, MA, USA.
Two broad classes of mechanisms have emerged for understanding the Amyloid-Related Imaging Abnormalities (ARIA) associated with anti-beta-amyloid immunotherapy. One set of mechanisms proposes that ARIA is driven by large-scale transfer of antibody-bound amyloid from brain parenchyma to the perivascular and vascular compartments. This class of mechanisms is indirectly supported by neuropathological evidence that immunotherapy substantially clears plaque amyloid while increasing vessel-associated amyloid, but has been difficult to directly demonstrate.
View Article and Find Full Text PDFClinical Manifestations.
Alzheimers Dement
December 2024
Amsterdam Neuroscience, Neurodegeneration, Amsterdam, Netherlands.
Background: With the increasing number of potential interventions for Alzheimer's Disease (AD), there is a growing need to detect meaningful cognitive changes early in the disease. Frequent passive monitoring of smartphone behaviour, such as typing speed and precision, can give insight into the cognitive changes in AD. In the 'A personalized Medicine Approach for AD' (ABOARD)-project we investigated the reliability and validity of typing behaviour to monitor cognition in people with and without AD.
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