A small library of 19 compounds was designed based on unique structural features of PTP1b. Utilizing electrospray ionization mass spectrometry (ESI-MS) to provide binding information about complexes of enzyme and small molecule ligands, two classes of lead compounds were discovered.
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http://dx.doi.org/10.1016/j.bmcl.2003.10.058 | DOI Listing |
HGG Adv
January 2025
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett's esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (A) known/plausible links to BE/EAC pathogenesis (n=493) or (B) prior evidence of biological interactions (n=4,196).
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
DP Technology, Beijing, 100080, China.
Powder X-ray diffraction (PXRD) is a prevalent technique in materials characterization. While the analysis of PXRD often requires extensive human manual intervention, and most automated method only achieved at coarse-grained level. The more difficult and important task of fine-grained crystal structure prediction from PXRD remains unaddressed.
View Article and Find Full Text PDFActa Neuropathol Commun
January 2025
Department of Biological Sciences, Purdue University, 915 Mitch Daniels Blvd, West Lafayette, IN, USA.
Dementia refers to an umbrella phenotype of many different underlying pathologies with Alzheimer's disease (AD) being the most common type. Neuropathological examination remains the gold standard for accurate AD diagnosis, however, most that we know about AD genetics is based on Genome-Wide Association Studies (GWAS) of clinically defined AD. Such studies have identified multiple AD susceptibility variants with a significant portion of the heritability unexplained and highlighting the phenotypic and genetic heterogeneity of the clinically defined entity.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi, China
Background: Clear cell renal cell carcinoma (ccRCC) is the most common histologic type of RCC. However, the spatial and functional heterogeneity of immunosuppressive cells and the mechanisms by which their interactions promote immunosuppression in the ccRCC have not been thoroughly investigated.
Methods: To further investigate the cellular and regional heterogeneity of ccRCC, we analyzed single-cell and spatial transcriptome RNA sequencing data from four patients, which were obtained from samples from multiple regions, including the tumor core, tumor-normal interface, and distal normal tissue.
Adv Biol Regul
December 2024
Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpönkatu 34, 33014, Finland; Institute of Biotechnology, HiLIFE, University of Helsinki, P.O. Box 56, 00014, Finland; Department of Microbiology, Fimlab Laboratories, P.O.Box 66, 33013, Tampere, Finland. Electronic address:
Janus kinases (JAK1-3, TYK2) are critical mediators of cytokine signaling and their role in hematological and inflammatory and autoimmune diseases has sparked widespread interest in their therapeutic targeting. JAKs have unique tandem kinase structure consisting of an active tyrosine kinase domain adjacent to a pseudokinase domain that is a hotspot for pathogenic mutations. The development of JAK inhibitors has focused on the active kinase domain and the developed drugs have demonstrated good clinical efficacy but due to off-target inhibition cause also side-effects and carry a black box warning limiting their use.
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