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Journal of Clinical Investigation
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#1Lin Liu (NU: Nanjing University)H-Index: 4
#2C.-Y. Ding (NU: Nanjing University)
Last. Zongchao Sun (NU: Nanjing University)
view all 20 authors...
Skeletal muscle depends on the precise orchestration of contractile and metabolic gene expression programs to direct fiber type specification and to ensure muscle performance. Exactly how such fiber type-specific patterns of gene expression are established and maintained remains unclear, however. Here, we demonstrate that histone mono-methyltransferase MLL4 (KMT2D), an enhancer regulator enriched in slow myofibers, plays a critical role in controlling muscle fiber identity as well as muscle perf...
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#1Maud Gratuze (WashU: Washington University in St. Louis)H-Index: 2
#2Cheryl E. G. Leyns (WashU: Washington University in St. Louis)H-Index: 5
Last. Marco Colonna (WashU: Washington University in St. Louis)H-Index: 119
view all 12 authors...
Alzheimer's disease (AD) is characterized by amyloid-β-containing plaques and neurofibrillary tangles composed of aggregated, hyperphosphorylated tau. Beyond tau and Aβ, evidence suggests that microglia play an important role in AD pathogenesis. Rare variants in the microglial-expressed triggering receptor expressed on myeloid cells 2 (TREM2) gene increase AD risk 2-4-fold. It is likely that these TREM2 variants increase AD risk by decreasing the response of microglia to Aβ and its local toxicit...
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#1Florence Enjalbert (QMUL: Queen Mary University of London)
#2Priya Dewan (QMUL: Queen Mary University of London)
Last. E. A. O Toole (QMUL: Queen Mary University of London)H-Index: 35
view all 8 authors...
The biology of harlequin ichthyosis (HI), a devastating skin disorder, caused by loss of function mutations in the gene ABCA12, is poorly understood and to date no satisfactory treatment has been developed. We sought to investigate pathomechanisms of HI which could lead to the identification of new treatments to improve patients' quality of life. In this study, RNA-Seq and functional assays were performed to define the effects of loss of ABCA12, using HI patient skin samples and an engineered CR...
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#1Xinxia Zhu (OHSU: Oregon Health & Science University)H-Index: 16
#2Michael F. Callahan (Monsanto)H-Index: 24
Last. Daniel L. Marks (OHSU: Oregon Health & Science University)H-Index: 43
view all 5 authors...
Cachexia, a devastating wasting syndrome characterized by severe weight loss with specific losses of muscle and adipose tissue, is driven by reduced food intake, increased energy expenditure, excess catabolism, and inflammation. Cachexia is associated with poor prognosis and high mortality, and frequently occurs in patients with cancer, chronic kidney disease, infection, and many other illnesses. There is no effective treatment for this condition. Hypothalamic melanocortins have a potent and lon...
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#1Shashank R. Ganatra (Texas Biomedical Research Institute)
#2Allison N. Bucsan (Tulane University)H-Index: 3
Last. Riti Sharan (Texas Biomedical Research Institute)
view all 17 authors...
While the advent of combination antiretroviral therapy (ART) has significantly improved survival, tuberculosis (TB) remains the leading cause of death in the HIV-infected population. We employed Mtb/Simian Immunodeficiency Virus (SIV) co-infected macaques to model Mtb/HIV co-infection and study the impact of ART on TB reactivation due to HIV-infection. While ART significantly reduced viral loads and increased CD4+ T cell counts in whole blood and BAL samples, it did not reduce the relative risk ...
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#1Daniela Puzzo (University of Catania)H-Index: 22
#2Elentina K. Argyrousi (Columbia University)H-Index: 2
Last. Claudio Grassi (CUA: The Catholic University of America)H-Index: 32
view all 14 authors...
The amyloid hypothesis posits that the amyloid-beta (Aβ) protein precedes and requires microtubule-associated protein tau in a sort of trigger-bullet mechanism leading to Alzheimer's disease (AD) pathology. This sequence of events has become dogmatic in the AD field and is used to explain clinical trial failures due to a late start of the intervention when Aβ already activated tau. Here, using a multidisplinary approach combining molecular biological, biochemical, histopathological, electrophysi...
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#1O. Emre Onat (Bilkent University)H-Index: 1
#2M. Ece Kars (Bilkent University)
Last. Arianna GoracciH-Index: 12
view all 18 authors...
Attention deficit/hyperactivity disorder (ADHD) is a common and heritable phenotype frequently accompanied by insomnia, anxiety, and depression. Here, using a reverse phenotyping approach, we report heterozygous coding variations in the core circadian clock gene cryptochrome 1 in 15 unrelated multigenerational families with combined ADHD and insomnia. The variants led to functional alterations in the circadian molecular rhythms, providing a mechanistic link to the behavioral symptoms. One varian...
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Pediatric cancers, particularly high-risk solid tumors, urgently need effective and specific therapies. Their outlook has not appreciably improved in decades. Immunotherapies such as immune checkpoint inhibitors offer much promise, but most are only approved for use in adults. Though several hundred clinical trials have tested immune-based approaches in childhood cancers, few have been guided by biomarkers or clinical-grade assays developed to predict patient response and, ultimately, to help se...
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#1Taotao Han (Peking Union Medical College)H-Index: 1
#2Xiao-Hui Jing (Peking Union Medical College)
Last. Jiazeng Sun (Peking Union Medical College)H-Index: 3
view all 11 authors...
Chronic infections can lead to carcinogenesis through inflammation-related mechanisms. Chronic infection of the human gastric mucosa with Helicobacter pylori is a well-known risk factor for gastric cancer. However, the mechanisms underlying H. pylori-induced gastric carcinogenesis are incompletely defined. We aimed to screen and clarify the functions of long noncoding RNAs (lncRNAs) that are differentially expressed in H. pylori-related gastric cancer. We found that lncRNA SNHG17 was upregulated...
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#1Shaohua Xiao (UofU: University of Utah)
#2Daisuke Shimura (UofU: University of Utah)
Last. TingTing Hong (Cedars-Sinai Medical Center)H-Index: 14
view all 11 authors...
Connexin 43 (Cx43) gap junctions provide intercellular coupling which ensures rapid action potential propagation and synchronized heart contraction. Altered Cx43 localization and reduced gap junction coupling occur in failing hearts, contributing to ventricular arrhythmias and sudden cardiac death. Recent reports have found that an internally translated Cx43 isoform, GJA1-20k, is an auxiliary subunit for the trafficking of Cx43 in heterologous expression systems. Here, we have created a mouse mo...
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