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| http://dx.doi.org/10.1073/pnas.1700685114 | DOI Listing |
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Glioma-induced alterations in excitatory neurons are reversed by mTOR inhibition.
Neuron
January 2025
Department of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Neurological Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address:
Gliomas are aggressive neoplasms that diffusely infiltrate the brain and cause neurological symptoms, including cognitive deficits and seizures. Increased mTOR signaling has been implicated in glioma-induced neuronal hyperexcitability, but the molecular and functional consequences have not been identified. Here, we show three types of changes in tumor-associated neurons: (1) downregulation of transcripts encoding excitatory and inhibitory postsynaptic proteins and dendritic spine development and upregulation of cytoskeletal transcripts via neuron-specific profiling of ribosome-bound mRNA, (2) marked decreases in dendritic spine density via light and electron microscopy, and (3) progressive functional alterations leading to neuronal hyperexcitability via in vivo calcium imaging.
View Article and Find Full Text PDFDiscovery of a DNA methylation profile in individuals with Sifrim-Hitz-Weiss syndrome.
Am J Hum Genet
January 2025
Genetics Institute, Rambam Health Care Campus, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Electronic address:
Pathogenic heterozygous variants in CHD4 cause Sifrim-Hitz-Weiss syndrome, a neurodevelopmental disorder associated with brain anomalies, heart defects, macrocephaly, hypogonadism, and additional features with variable expressivity. Most individuals have non-recurrent missense variants, complicating variant interpretation. A few were reported with truncating variants, and their role in disease is unclear.
View Article and Find Full Text PDFDiscovery of Rezatapopt (PC14586), a First-in-Class, Small-Molecule Reactivator of p53 Y220C Mutant in Development.
ACS Med Chem Lett
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Discovery Biology, PMV Pharmaceuticals, Inc., 400 Alexander Park Drive, Suite 301, Princeton, New Jersey 08540, United States.
p53 is a potent transcription factor that is crucial in regulating cellular responses to stress. Mutations in the gene are found in >50% of human cancers, predominantly occurring in the DNA-binding domain (amino acids 94-292). The Y220C mutation accounts for 1.
View Article and Find Full Text PDFEvaluation of rapid evaporative ionization mass spectrometry (REIMS) for the prediction of slice shear force and quality grades in beef longissimus lumborum steaks.
Meat Sci
January 2025
Department of Animal and Food Sciences, Texas Tech University, Lubbock, TX 79409, USA. Electronic address:
Steak samples were collected from the longissimus lumborum muscles of beef carcasses (Canada AA, n = 1505; Canada AAA, n = 1363) over a 3-year period. Steaks were aged for 14 d, and tenderness was determined by slice shear force (SSF). Metabolomic profiling of beef samples was performed using rapid evaporative ionization mass spectrometry (REIMS) (N = 2853).
View Article and Find Full Text PDFNatural Molecule-Derived Nanogels from Hematoxylin and l-lysine for Biomedical Use with Antimicrobial Properties.
Int J Mol Sci
December 2024
Department of Chemistry, Faculty of Sciences, Canakkale Onsekiz Mart University, Terzioglu Campus, 17100 Canakkale, Turkey.
Hematoxylin (HT) is a natural staining dye used in histopathology, often combined with Eosin for H&E staining. A poly(hematoxylin-co-l-lysine) (p(HT-co-l)) nanonetwork was synthesized through a one-step Mannich condensation reaction using formaldehyde as a linking agent. The resulting p(HT-co-l) nanogels had an average size of about 200 nm and exhibited a smooth surface and desirable functional groups such as -OH, -NH, and -COOH, as recognized by FT-IR analysis.
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