-
作者：Chen, Yan Q.; Yang, Ye; Zhen, Eugene Y.; Beyer, Thomas P.; Li, Hongxia; Wen, Yi; Ehsani, Mariam; Jackson, Nicholas; Xie, Katherine; Jung, Hyesoo; Scheithauer, Julia L.; Kumari, Anni; Birrane, Gabriel; Russell, Anna M.; Balasubramaniam, Deepa; Liao, Zhongping; Siegel, Robert W.; Qian, Yuewei; Ploug, Michael; Young, Stephen G.; Konrad, Robert J.
作者单位：Eli Lilly; Lilly Research Laboratories; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of Copenhagen; Copenhagen University Hospital; Rigshospitalet; University of Copenhagen; Copenhagen University Hospital; Rigshospitalet; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center
摘要：Apolipoprotein AV (APOA5) lowers plasma triglyceride (TG) levels by binding to the binding sites within capillaries. However, the sequences in APOA5 that are required for suppressing ANGPTL3/8 activity have never been defined. A clue to the identity of those sequences was the presence of severe hypertriglyceridemia in two patients harboring an APOA5 mutation that truncates APOA5 by 35 residues (APOA5A35). We found that wild- type (WT) human APOA5, but not APOA5A35, suppressed ANGPTL3/8's abili...
-
作者：Arvanitaki, Ermioni S.; Goulielmaki, Evi; Gkirtzimanaki, Katerina; Niotis, George; Tsakani, Edisona; Nenedaki, Electra; Rouska, Iliana; Kefalogianni, Mary; Xydias, Dionysios; Kalafatakis, Ilias; Psilodimitrakopoulos, Sotiris; Karagogeos, Domna; Schumacher, Bjoern; Stratakis, Emmanuel; Garinis, George A.
作者单位：University of Crete; Foundation for Research & Technology - Hellas (FORTH); University of Crete; Foundation for Research & Technology - Hellas (FORTH); University of Crete; University of Crete; University of Cologne; University of Cologne
摘要：DNA damage and neurodegenerative disorders are intimately linked but the underlying mechanism remains elusive. Here, we show that persistent DNA lesions in tissue- resident macrophages carrying an XPF-ERCC1 DNA repair defect trigger neuroinflammation and neuronal cell death in mice. We find that microglia accumulate dsDNAs and chromatin fragments in the cytosol, which are sensed thereby stimulating a viral - like immune response in Er1Cx/- and naturally aged murine brain. Cytosolic DNAs are pa...
-
作者：Sachdev, Aradhana; Gill, Kamaljot; Sckaff, Maria; Birk, Alisha M.; Arogundade, Olubankole Aladesuyi; Brown, Katherine A.; Chouhan, Runvir S.; Issagholian-Lewin, Patrick Oliver; Patel, Esha; Watry, Hannah L.; Bernardi, Mylinh T.; Keough, Kathleen C.; Tsai, Yu-Chih; Smith, Alec Simon Tulloch; Conklin, Bruce R.; Clelland, Claire Dudley
作者单位：University of California System; University of California San Francisco; The J David Gladstone Institutes; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco
摘要：Efforts to genetically reverse C9orf72 pathology have been hampered by our incomplete understanding of the regulation of this complex locus. We generated five different genomic excisions at the C9orf72 locus in a patient - derived induced pluripotent stem cell (iPSC) line and a non - diseased wild - type (WT) line (11 total isogenic lines), and examined gene expression and pathological hallmarks of C9 frontotemporal dementia/amyotrophic lateral sclerosis in motor neurons differentiated from th...
-
作者：Diao, Fengqiu; Vasudevan, Deeptha; Heckscher, Ellie S.; White, Benjamin H.
作者单位：National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH); University of Chicago
摘要：The Trojan exon method, which makes use of intronically inserted T2A - Gal4 cassettes, has been widely used in Drosophila to create thousands of gene - specific Gal4 driver lines. These dual - purpose lines provide genetic access to specific cell types based on their expression of a native gene while simultaneously mutating one allele of the gene to enable loss - of - function analysis in homozygous animals. While this dual use is often an advantage, the truncation mutations produced by Trojan...
-
作者：Mclean, Iona R.; Erkelens, Ian M.; Cooper, Emily A.
作者单位：University of California System; University of California Berkeley; University of California System; University of California Berkeley
摘要：Vision can provide useful cues about the geometric properties of an object, like its size, distance, pose, and shape. But how the brain merges these properties into a complete sensory representation of a three- dimensional object is poorly understood. To address this gap, we investigated a visual illusion in which humans misperceive the shape of an object due to a small change in one eye's retinal image. We first show that this illusion affects percepts of a highly familiar object under comple...
-
作者：Singh, Pradeep Kumar; Pires, Elisa Nicoloso Simoes-; Chen, Zu- Lin; Torrente, Daniel; Calvano, Marissa; Sharma, Anurag; Strickland, Sidney; Norris, Erin H.
作者单位：Rockefeller University; Rockefeller University
摘要：Proteinaceous brain inclusions, neuroinflammation, and vascular dysfunction are common pathologies in Alzheimer's disease (AD). Vascular deficits include a compromised blood-brain barrier, which can lead to extravasation of blood proteins like fibrinogen into the brain. Fibrinogen's interaction with the amyloid-beta (A beta) peptide is known to worsen thrombotic and cerebrovascular pathways in AD. Lecanemab, an FDA-approved antibody therapy for AD, clears A beta plaque from the brain and slows...
-
作者：Thomas, Mekha A.; Naik, Pooja; Wang, Hong; Giles, Jon T.; Girgis, Alexander A.; Kim, Seok - Young; Johnson, Tory P.; Curran, Ashley M.; Crawford, Jonathan D.; Jahanbani, Shaghayegh; Bingham, Clifton O.; Robinson, William H.; Na, Chan Hyun; Darrah, Erika
作者单位：Johns Hopkins University; Columbia University; Johns Hopkins University; Johns Hopkins University; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); Stanford University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto Health Care System
摘要：Although anti- citrullinated protein autoantibodies (ACPAs) are a hallmark serological feature of rheumatoid arthritis (RA), the mechanisms and cellular sources behind the generation of the RA citrullinome remain incompletely defined. Peptidylarginine deiminase IV (PAD4), one of the key enzymatic drivers of citrullination in the RA joint, is expressed by granulocytes and monocytes; however, the subcellular localization and contribution of monocyte- derived PAD4 to the generation of citrullinat...
-
作者：Carlsson, Fredric; Raberg, Lars
作者单位：Lund University
摘要：The germ theory states that pathogenic microorganisms are responsible for causing infectious diseases. The theory is inherently microbe- centric and does not account for variability in disease severity among individuals and asymptomatic carriership-two phenomena indicating an important role for host variability in infection outcome. The basic tenet of the germ theory was recently challenged, and a radically host- centric paradigm referred to as the full- blown host theory was proposed. Accordi...
-
作者：Chen, Gang; Han, Qingxia; Li, Wan - Xiang; Hai, Rong; Ding, Shou- Wei; Palese, Peter
作者单位：University of California System; University of California Riverside
摘要：Global control of infectious diseases depends on the continuous development and deployment of diverse vaccination strategies. Currently available live - attenuated and killed virus vaccines typically take a week or longer to activate specific protection by the adaptive immunity. The mosquito - transmitted Nodamura virus (NoV) is attenuated in mice by mutations that prevent expression of the B2 viral suppressor of RNA interference (VSR) and consequently, drastically enhance in vivo production o...
-
作者：Costanza, Massimo; Ciotti, Arianna; Consonni, Alessandra; Cipelletti, Barbara; Cattalini, Alessandro; Cagnoli, Cinzia; Baggi, Fulvio; de Curtis, Marco; Colciaghi, Francesca
摘要：The development of seizures in epilepsy syndromes associated with malformations of cortical development (MCDs) has traditionally been attributed to intrinsic cortical alterations resulting from abnormal network excitability. However, recent analyses at single - cell resolution of human brain samples from MCD patients have indicated the possible involvement of adaptive immunity in the pathogenesis of these disorders. By exploiting the MethylAzoxyMethanol (MAM)/pilocarpine (MP) rat model of drug...
