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Xia Guo et al.
Journal of lipid research, 58(9), 1777-1784 (2017-07-19)
Obesity is the major risk factor for type 2 diabetes, cardiovascular disorders, and many other diseases. Adipose tissue inflammation is frequently associated with obesity and contributes to the morbidity and mortality. Dedicator of cytokinesis 2 (DOCK2) is involved in several...
Gaëlle Marenne et al.
Cell metabolism, 31(6), 1107-1119 (2020-06-04)
Obesity is genetically heterogeneous with monogenic and complex polygenic forms. Using exome and targeted sequencing in 2,737 severely obese cases and 6,704 controls, we identified three genes (PHIP, DGKI, and ZMYM4) with an excess burden of very rare predicted deleterious...
Veena Padmanaban et al.
Nature, 573(7774), 439-444 (2019-09-06)
Metastasis is the major driver of death in patients with cancer. Invasion of surrounding tissues and metastasis have been proposed to initiate following loss of the intercellular adhesion protein, E-cadherin1,2, on the basis of inverse correlations between in vitro migration...
Vincent P Schulz et al.
Cell reports, 28(11), 2996-3009 (2019-09-12)
Mammalian erythropoiesis yields a highly specialized cell type, the mature erythrocyte, evolved to meet the organismal needs of increased oxygen-carrying capacity. To better understand the regulation of erythropoiesis, we performed genome-wide studies of chromatin accessibility, DNA methylation, and transcriptomics using...
Wenxiang Hu et al.
Cell stem cell, 24(2), 299-308 (2019-01-15)
Thiazolidinedione drugs (TZDs) target the transcriptional activity of peroxisome proliferator activated receptor γ (PPARγ) to reverse insulin resistance in type 2 diabetes, but side effects limit their clinical use. Here, using human adipose stem cell-derived adipocytes, we demonstrate that SNPs...
Micaela Morgado et al.
Journal of cellular biochemistry, 118(1), 163-171 (2016-06-14)
CA125 is serum tumor marker consisting of an epitope carried by a portion of the extremely large (>3 MDa), heavily glycosylated cell surface transmembrane mucin, MUC16. In malignancies, membrane bound mucins lose their polarized distribution, become aberrantly over-expressed and protect tumor...
Sung Ho Lee et al.
Biochemical and biophysical research communications, 534, 864-870 (2020-11-11)
Bile acids have recently emerged as key metabolic hormones with beneficial impacts in multiple metabolic diseases. We previously discovered that hepatic bile acid overload distally modulates glucose and fatty acid metabolism in adipose tissues to exert anti-obesity effects. However, the...
Yuanyuan Zhu et al.
Cellular and molecular neurobiology, 40(5), 801-812 (2019-12-22)
Cerebral glycogen is principally localized in astrocytes rather than in neurons. Glycogen metabolism has been implicated in higher brain functions, including learning and memory, yet the distribution patterns of glycogen in different types of astrocytes have not been fully described....
Chuay-Yeng Koo et al.
Molecular cancer therapeutics, 16(11), 2410-2421 (2017-08-24)
Thousand-and-one amino acid kinases (TAOK) 1 and 2 are activated catalytically during mitosis and can contribute to mitotic cell rounding and spindle positioning. Here, we characterize a compound that inhibits TAOK1 and TAOK2 activity with IC50 values of 11 to...
Isaac S Chan et al.
The Journal of cell biology, 219(9) (2020-07-10)
Natural killer (NK) cells have potent antitumor and antimetastatic activity. It is incompletely understood how cancer cells escape NK cell surveillance. Using ex vivo and in vivo models of metastasis, we establish that keratin-14+ breast cancer cells are vulnerable to...
Ben J Wu et al.
Arteriosclerosis, thrombosis, and vascular biology, 39(6), 1160-1171 (2019-04-26)
Objective- Insulin resistance and inflammation in pregnancy are risk factors for gestational diabetes mellitus. Increased plasma HDL (high-density lipoprotein) and apo (apolipoprotein) A-I levels have been reported to improve glucose metabolism and inhibit inflammation in animals and humans. This study...
Wenjing Li et al.
Nucleic acids research, 48(9), 4827-4838 (2020-04-15)
NONO is a DNA/RNA-binding protein, which plays a critical regulatory role during cell stage transitions of mouse embryonic stem cells (mESCs). However, its function in neuronal lineage commitment and the molecular mechanisms of its action in such processes are largely...
A Cell-Autonomous Signature of Dysregulated Protein Phosphorylation Underlies Muscle Insulin Resistance in Type 2 Diabetes.
Batista, et al.
Cell Metabolism, 32, 844-859 (2021)
Fuu-Jen Tsai et al.
Oncotarget, 8(9), 15470-15489 (2017-01-19)
Evidence for long-term use of Chinese herbal medicine (CHM) as an adjuvant treatment in patients with type 2 diabetes (T2D) remains limited. This study aimed to assess the frequency of use, utilization patterns, and therapeutic effects of adjuvant CHM for...
Guoqiang Sun et al.
Cell reports. Medicine, 1(1), 100002-100002 (2020-11-19)
Although congenital infection by human cytomegalovirus (HCMV) is well recognized as a leading cause of neurodevelopmental defects, HCMV neuropathogenesis remains poorly understood. A major challenge for investigating HCMV-induced abnormal brain development is the strict CMV species specificity, which prevents the...
Andrea Cerquone Perpetuini et al.
Scientific reports, 10(1), 5363-5363 (2020-03-27)
Muscle resident fibro-adipogenic progenitors (FAPs), support muscle regeneration by releasing cytokines that stimulate the differentiation of myogenic stem cells. However, in non-physiological contexts (myopathies, atrophy, aging) FAPs cause fibrotic and fat infiltrations that impair muscle function. We set out to...
Simon Pecha et al.
Scientific reports, 9(1), 9831-9831 (2019-07-10)
Human iPSC-derived engineered heart tissue (hEHT) has been used to remuscularize injured hearts in a guinea pig infarction model. While beneficial effects on cardiac remodeling have been demonstrated, the arrhythmogenic potential of hEHTs is a major concern. We investigated whether...
Florian Beaumatin et al.
Molecular cell, 76(1), 163-176 (2019-09-08)
Sensing nutrient availability is essential for appropriate cellular growth, and mTORC1 is a major regulator of this process. Mechanisms causing mTORC1 activation are, however, complex and diverse. We report here an additional important step in the activation of mTORC1, which...
Xiao-Long Qi et al.
Poultry science, 97(12), 4415-4424 (2018-08-08)
The objective of this study consisting of 2 trials was to investigate the antioxidant role of conjugated linoleic acid (CLA) isomers (c9, t11-CLA and t10, c12-CLA) and the underlying mechanism by which they act in modulating redox status in a...
Christoph Malkmus et al.
PLoS neglected tropical diseases, 14(11), e0008503-e0008503 (2020-11-06)
Onchocerciasis also known as river blindness is a neglected tropical disease and the world's second-leading infectious cause of blindness in humans; it is caused by Onchocerca volvulus. Current treatment with ivermectin targets microfilariae and transmission and does not kill the...
Shaun Martin et al.
Acta neuropathologica, 139(6), 1001-1024 (2020-03-17)
Parkinson's disease (PD) is a progressive neurodegenerative brain disease presenting with a variety of motor and non-motor symptoms, loss of midbrain dopaminergic neurons in the substantia nigra pars compacta and the occurrence of α-synuclein-positive Lewy bodies in surviving neurons. Here...
Maria Teresa Dell'Anno et al.
Nature communications, 9(1), 3419-3419 (2018-08-26)
Traumatic spinal cord injury results in persistent disability due to disconnection of surviving neural elements. Neural stem cell transplantation has been proposed as a therapeutic option, but optimal cell type and mechanistic aspects remain poorly defined. Here, we describe robust...
E Comisso et al.
Oncogene, 36(30), 4253-4266 (2017-03-21)
OCT4 (Octamer-binding transcription factor 4) is essential for embryonic stem cell self-renewal. Here we show that OCT4 increases the aggressiveness of high-grade serous ovarian cancer (HG-SOC) by inactivating the Retinoblastoma tumor suppressor pathway and enhancing mitotic stability in cancer cells....
Sharmeen Uddin et al.
Cell cycle (Georgetown, Tex.), 19(17), 2158-2167 (2020-07-28)
G1 cell cycle progression is controlled largely by growth factors in early G1 indicating that it is appropriate to divide and by nutrients in late G1 indicating sufficient raw material for cell division. We previously mapped a late G1 cell...
Jason Pitt et al.
Molecular biology of the cell, 28(20), 2623-2636 (2017-10-01)
Synaptopathy underlying memory deficits in Alzheimer's disease (AD) is increasingly thought to be instigated by toxic oligomers of the amyloid beta peptide (AβOs). Given the long latency and incomplete penetrance of AD dementia with respect to Aβ pathology, we hypothesized...
Olga Spadaro et al.
Cell reports, 19(2), 225-234 (2017-04-14)
In concert with their phagocytic activity, macrophages are thought to regulate the host immunometabolic responses primarily via their ability to produce specific cytokines and metabolites. Here, we show that IL-4-differentiated, M2-like macrophages secrete IGF1, a hormone previously thought to be...
François Aguet et al.
Molecular biology of the cell, 27(22), 3418-3435 (2016-11-05)
Membrane remodeling is an essential part of transferring components to and from the cell surface and membrane-bound organelles and for changes in cell shape, which are particularly critical during cell division. Earlier analyses, based on classical optical live-cell imaging and...
Farinaz Ghodrati et al.
Scientific reports, 8(1), 8654-8654 (2018-06-07)
At times, it can be difficult to discern if a lack of overlap in reported interactions for a protein-of-interest reflects differences in methodology or biology. In such instances, systematic analyses of protein-protein networks across diverse paradigms can provide valuable insights....
Stephanie Dooves et al.
Cells, 10(1) (2021-01-16)
Tuberous sclerosis complex (TSC) is a genetic disease affecting the brain. Neurological symptoms like epilepsy and neurodevelopmental issues cause a significant burden on patients. Both neurons and glial cells are affected by TSC mutations. Previous studies have shown changes in...
Hee Chan Yoo et al.
Cell metabolism, 31(2), 267-283 (2019-12-24)
Glutamine is an essential nutrient that regulates energy production, redox homeostasis, and signaling in cancer cells. Despite the importance of glutamine in mitochondrial metabolism, the mitochondrial glutamine transporter has long been unknown. Here, we show that the SLC1A5 variant plays...
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