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Time persistence of the fMRI resting-state functional brain networks.
J Neurosci
January 2025
The Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan, 52900, Israel
Time persistence is a fundamental property of many complex physical and biological systems; thus understanding the phenomenon in the brain is of high importance. Time persistence has been explored at the level of stand-alone neural time-series, but since the brain functions as an interconnected network, it is essential to examine time persistence at the network level. Changes in resting-state networks have been previously investigated using both dynamic (i.
View Article and Find Full Text PDFEndogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.
Proc Natl Acad Sci U S A
February 2025
Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.
Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1) are associated with familial Parkinson's disease (PD). LRRK2 phosphorylates Rab guanosine triphosphatase (GTPases) within the Switch II domain while PINK1 directly phosphorylates Parkin and ubiquitin (Ub) and indirectly induces phosphorylation of a subset of Rab GTPases. Herein we have crossed LRRK2 [R1441C] mutant knock-in mice with PINK1 knock-out (KO) mice and report that loss of PINK1 does not impact endogenous LRRK2-mediated Rab phosphorylation nor do we see significant effect of mutant LRRK2 on PINK1-mediated Rab and Ub phosphorylation.
View Article and Find Full Text PDFSuppressing APOE4-induced neural pathologies by targeting the VHL-HIF axis.
Proc Natl Acad Sci U S A
February 2025
Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158.
The ε4 variant of human apolipoprotein E () is a key genetic risk factor for neurodegeneration in Alzheimer's disease and elevated all-cause mortality in humans. Understanding the factors and mechanisms that can mitigate the harmful effects of has significant implications. In this study, we find that inactivating the VHL-1 (Von Hippel-Lindau) protein can suppress mortality, neural and behavioral pathologies caused by transgenic human in .
View Article and Find Full Text PDFSplicing accuracy varies across human introns, tissues, age and disease.
Nat Commun
January 2025
UK Dementia Research Institute, University of Cambridge, Cambridge, United Kingdom.
Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we investigate splicing accuracy using RNA-sequencing data from >14k control samples and 40 human body sites, focusing on split reads partially mapping to known transcripts in annotation.
View Article and Find Full Text PDFPgpP is a broadly conserved phosphatase required for phosphatidylglycerol lipid synthesis.
Proc Natl Acad Sci U S A
February 2025
Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115.
The cytoplasmic membrane of bacteria is composed of a phospholipid bilayer made up of a diverse set of lipids. Phosphatidylglycerol (PG) is one of the principal constituents and its production is essential for growth in many bacteria. All the enzymes required for PG biogenesis in have been identified and characterized decades ago.
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