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Master cell disease

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https://www.readbyqxmd.com/read/29778521/vasculature-on-the-clock-circadian-rhythm-and-vascular-dysfunction
#1
REVIEW
Sandra Crnko, Martin Cour, Linda W Van Laake, Sandrine Lecour
The master mammalian circadian clock (i.e. central clock), located in the suprachiasmatic nucleus of the hypothalamus, orchestrates the synchronization of the daily behavioural and physiological rhythms to better adapt the organism to the external environment in an anticipatory manner. This central clock is entrained by a variety of signals, the best established being light and food. However, circadian cycles are not simply the consequences of these two cues but are generated by endogenous circadian clocks...
May 17, 2018: Vascular Pharmacology
https://www.readbyqxmd.com/read/29778503/autoinflammatory-mutation-in-nlrc4-reveals-an-lrr-lrr-oligomerization-interface
#2
Fiona Moghaddas, Ping Zeng, Yuxia Zhang, Heike Schützle, Sebastian Brenner, Sigrun R Hofmann, Reinhard Berner, Yuanbo Zhao, Bingtai Lu, Xiaoyun Chen, Li Zhang, Suyun Cheng, Stefan Winkler, Kai Lehmberg, Scott W Canna, Peter E Czabotar, Ian P Wicks, Dominic De Nardo, Christian M Hedrich, Huasong Zeng, Seth L Masters
BACKGROUND: Monogenic autoinflammatory disorders are characterised by dysregulation of the innate immune system, for example by gain-of-function mutations in inflammasome forming proteins such as NLRC4. OBJECTIVE: Here we investigate the mechanism by which a novel mutation in the leucine rich repeat (LRR) domain of NLRC4 (c.G1965C, p.W655C) contributes to autoinflammatory disease. METHODS: We studied two unrelated patients with early onset macrophage activation syndrome (MAS) harboring the same de novo mutation in NLRC4...
May 17, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29773653/inhibition-of-protein-arginine-methyltransferase-5-enhances-hepatic-mitochondrial-biogenesis
#3
Lei Huang, Jehnan Liu, Xiao-Ou Zhang, Katelyn Sibley, Sonia M Najjar, Mary M Lee, Joae Qiong Wu
Protein arginine methyltransferase 5 (PRMT5) regulates gene expression either transcriptionallyly by symmetric dimethylation of arginine residues on histones H4R3, H3R8 and H2AR3, or at the post-translational level by methylation of non-histone target proteins. While emerging evidence suggests that PRMT5 functions as an oncogene, its role in metabolic diseases is not well defined. We investigated the role of PRMT5 in promoting high fat-induced hepatic steatosis. High fat diet up-regulated PRMT5 levels in the liver, but not in other metabolically relevant tissues such as skeletal muscle or white and brown adipose tissue...
May 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29769719/klhl22-activates-amino-acid-dependent-mtorc1-signalling-to-promote-tumorigenesis-and-ageing
#4
Jie Chen, Yuhui Ou, Yanyan Yang, Wen Li, Ye Xu, Yuntao Xie, Ying Liu
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that responds to a diverse set of environmental cues, including amino acids1,2 . Deregulation of mTORC1 has been linked with metabolic diseases, cancer and ageing2-4 . In response to amino acids, mTORC1 is recruited by the Rag GTPases to the lysosome, its site of activation5,6 . The GATOR1 complex, consisting of DEPDC5, NPRL3 and NPRL2, displays GAP activity to inactivate Rag GTPases under amino-acid-deficient conditions 7 ...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29769440/elevated-hepatic-expression-of-h19-long-noncoding-rna-contributes-to-diabetic-hyperglycemia
#5
Na Zhang, Tingting Geng, Zhangsheng Wang, Ruling Zhang, Tiefeng Cao, Joao Paulo Camporez, Shi-Ying Cai, Ya Liu, Luisa Dandolo, Gerald I Shulman, Gordon G Carmichael, Hugh S Taylor, Yingqun Huang
Excessive hepatic glucose production (HGP) contributes significantly to the hyperglycemia of type 2 diabetes; however, the molecular mechanism underlying this dysregulation remains poorly understood. Here, we show that fasting temporally increases the expression of H19 long noncoding RNA (lncRNA) in nondiabetic mouse liver, whereas its level is chronically elevated in diet-induced diabetic mice, consistent with the previously reported chronic hepatic H19 increase in diabetic patients. Importantly, liver-specific H19 overexpression promotes HGP, hyperglycemia, and insulin resistance, while H19 depletion enhances insulin-dependent suppression of HGP...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29768688/ppar-%C3%AE-in-innate-and-adaptive-lung-immunity
#6
REVIEW
Samuel Philip Nobs, Manfred Kopf
The transcription factor PPAR-γ (peroxisome proliferator-activated receptor-γ) is a key regulator of lung immunity exhibiting multiple cell type specific roles in controlling development and function of the lung immune system. It is strictly required for the generation of alveolar macrophages by controlling differentiation of fetal lung monocyte precursors. Furthermore, it plays an important role in lung allergic inflammation by licensing lung dendritic cell t helper 2 (Th2) priming capacity as well as acting as a master transcription factor for pathogenic Th2 cells...
May 16, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29768212/mtor-senses-environmental-cues-to-shape-the-fibroblast-like-synoviocyte-response-to-inflammation
#7
Thomas Karonitsch, Richard K Kandasamy, Felix Kartnig, Barbara Herdy, Karolina Dalwigk, Birgit Niederreiter, Johannes Holinka, Florian Sevelda, Reinhard Windhager, Martin Bilban, Thomas Weichhart, Marcus Säemann, Thomas Pap, Günter Steiner, Josef S Smolen, Hans P Kiener, Giulio Superti-Furga
Accumulating evidence suggests that metabolic master regulators, including mTOR, regulate adaptive and innate immune responses. Resident mesenchymal tissue components are increasingly recognized as key effector cells in inflammation. Whether mTOR also controls the inflammatory response in fibroblasts is insufficiently studied. Here, we show that TNF signaling co-opts the mTOR pathway to shift synovial fibroblast (FLS) inflammation toward an IFN response. mTOR pathway activation is associated with decreased NF-κB-mediated gene expression (e...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29768134/mtor-signalling-jack-of-all-trades
#8
Yassine El Hiani, Emmanuel E Egom, Xian-Ping Dong
The mechanistic target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that senses and integrates environmental information into cellular regulation and homeostasis. Accumulating evidence has suggested a master role of mTOR signaling in many fundamental aspects of cell biology and organismal development. mTOR deregulation is implicated in a broad range of pathological conditions, including diabetes, cancer, neurodegenerative diseases, myopathies, inflammatory, infectious and autoimmune conditions...
May 16, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29764842/role-of-the-hepcidin-ferroportin-axis-in-pathogen-mediated-intracellular-iron-sequestration-in-human-phagocytic-cells
#9
Rodrigo Abreu, Frederick Quinn, Pramod K Giri
Upon infection, pathogen and host compete for the same iron pool, because this trace metal is a crucial micronutrient for all living cells. Iron dysregulation in the host is strongly associated with poor outcomes in several infectious diseases, including tuberculosis, AIDS, and malaria, and inefficient iron scavenging by pathogens severely affects their virulence. Hepcidin is the master regulator of iron homeostasis in vertebrates, responsible for diminishing iron export from macrophages during iron overload or infection...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29757590/imbalance-of-peripheral-blood-t-helper-type-17-responses-in-patients-with-vitiligo
#10
Farinaz Behfarjam, Parvine Mansouri, Zohreh Jadali
There is growing evidence to suggest that Th cells play pivotal roles in a variety of chronic inflammatory diseases, including vitiligo. However, the exact role of different subsets of Th cells in the pathogenesis of vitiligo is still a question. The purpose of present study was to determine the mRNA expression level of Th17 master transcription factor retinoic acid receptor-related orphan receptors gamma (RORɣt) and cytokine mRNA and protein expression profiles of Th17 cells. 22 patients with vitiligo and 22 normal subjects were enrolled in the study...
April 2018: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29754775/in-situ-gene-therapy-via-aav-crispr-cas9-mediated-targeted-gene-regulation
#11
Ana M Moreno, Xin Fu, Jie Zhu, Dhruva Katrekar, Yu-Ru V Shih, John Marlett, Jessica Cabotaje, Jasmine Tat, John Naughton, Leszek Lisowski, Shyni Varghese, Kang Zhang, Prashant Mali
Development of efficacious in vivo delivery platforms for CRISPR-Cas9-based epigenome engineering will be critical to enable the ability to target human diseases without permanent modification of the genome. Toward this, we utilized split-Cas9 systems to develop a modular adeno-associated viral (AAV) vector platform for CRISPR-Cas9 delivery to enable the full spectrum of targeted in situ gene regulation functionalities, demonstrating robust transcriptional repression (up to 80%) and activation (up to 6-fold) of target genes in cell culture and mice...
April 25, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29748137/the-hidden-potential-of-lysosomal-ion-channels-a-new-era-of-oncogenes
#12
REVIEW
Andra M Sterea, Shekoufeh Almasi, Yassine El Hiani
Lysosomes serve as the control centre for cellular clearance. These membrane-bound organelles receive biomolecules destined for degradation from intracellular and extracellular pathways; thus, facilitating the production of energy and shaping the fate of the cell. At the base of their functionality are the lysosomal ion channels which mediate the function of the lysosome through the modulation of ion influx and efflux. Ion channels form pores in the membrane of lysosomes and allow the passage of ions, a seemingly simple task which harbours the potential of overthrowing the cell's stability...
March 10, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29742422/a-general-framework-for-interrogation-of-mrna-stability-programs-identifies-rna-binding-proteins-that-govern-cancer-transcriptomes
#13
Gabrielle Perron, Pouria Jandaghi, Shraddha Solanki, Maryam Safisamghabadi, Cristina Storoz, Mehran Karimzadeh, Andreas I Papadakis, Madeleine Arseneault, Ghislaine Scelo, Rosamonde E Banks, Jorg Tost, Mark Lathrop, Simon Tanguay, Alvis Brazma, Sidong Huang, Fadi Brimo, Hamed S Najafabadi, Yasser Riazalhosseini
Widespread remodeling of the transcriptome is a signature of cancer; however, little is known about the post-transcriptional regulatory factors, including RNA-binding proteins (RBPs) that regulate mRNA stability, and the extent to which RBPs contribute to cancer-associated pathways. Here, by modeling the global change in gene expression based on the effect of sequence-specific RBPs on mRNA stability, we show that RBP-mediated stability programs are recurrently deregulated in cancerous tissues. Particularly, we uncovered several RBPs that contribute to the abnormal transcriptome of renal cell carcinoma (RCC), including PCBP2, ESRP2, and MBNL2...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29738634/grp78-mediated-antioxidant-response-and-abc-transporter-activity-confers-chemoresistance-to-pancreatic-cancer-cells
#14
Patricia Dauer, Nikita S Sharma, Vineet K Gupta, Alice Nomura, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee
Chemoresistance is a major therapeutic challenge that plays a role in the poor statistical outcomes in pancreatic cancer. Unfolded Protein Response or UPR is one of the homeostasis mechanisms in cancer cells that have been correlated with chemoresistance in a number of cancers including pancreatic cancer. In the current study, we show that modulating glucose regulatory protein 78 (GRP78), the master regulator of the UPR, can have a profound effect on multiple pathways that mediate chemoresistance. Our study showed for the first time that silencing GRP78 can diminish efflux activity of ATP-binding cassette (ABC) transporters, and it can decrease the antioxidant response resulting in an accumulation of reactive oxygen species (ROS)...
May 8, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29737267/role-of-ampk-in-diabetic-cardiovascular-complications-an-overview
#15
Ashutosh Kumar, Karthika Nellaiappan, Veera Ganesh Yerra
Macrovascular complications of diabetes like cardiovascular diseases appear to be one of the leading causes of mortality. Current therapies aimed at counteracting the adverse effects of diabetes on cardiovascular system are found to be inadequate. Hence, there is growing need in search of novel targets. Adenosine monophosphate activated protein kinase (AMPK) is one such promising target, as a plethora of evidences point to its cardioprotective role in pathological milieu like cardiac hypertrophy, atherosclerosis and heart failure...
May 7, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29723294/probing-the-role-of-ppar%C3%AE-in-the-regulation-of-late-onset-alzheimer-s-disease-associated-genes
#16
Julio Barrera, Shobana Subramanian, Ornit Chiba-Falek
Peroxisome proliferator-activated receptor-γ (PPARγ), is a transcription factor that governs pathways, such as lipid metabolism and immune response, that have been implicated in the etiology of LOAD. Previously, we established HepG2-derived cell-lines with stable knockdown of PPARγ gene, and showed an increase in mRNA levels of genes mapped in the APOE linkage disequilibrium (LD) region on chromosome 19q13.32, with the greatest effect observed for APOE-mRNA. Here, we extended the analysis using our PPARγ knockdown model system and investigated the broader effect on expression changes of genes implicated in LOAD via genome wide association studies (GWAS)...
2018: PloS One
https://www.readbyqxmd.com/read/29712653/direct-activation-of-adenosine-monophosphate-activated-protein-kinase-ampk-by-pf-06409577-inhibits-flavivirus-infection-through-modification-of-host-cell-lipid-metabolism
#17
Nereida Jiménez de Oya, Ana-Belén Blázquez, Josefina Casas, Juan-Carlos Saiz, Miguel A Martín Acebes
Mosquito-borne flaviviruses are a group of RNA viruses that constitute global threats for human and animal health. Replication of these pathogens is strictly dependent on cellular lipid metabolism. We have evaluated the effect of the pharmacological activation of Adenosine Monophosphate-activated Protein Kinase (AMPK), a master regulator of lipid metabolism, on the infection of three medically relevant flaviviruses: West Nile virus (WNV), Zika virus (ZIKV) and dengue virus (DENV). WNV is responsible for recurrent outbreaks of meningitis and encephalitis affecting humans and horses worldwide...
April 30, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29708533/a-simple-and-efficient-method-for-in-vivo-cardiac-specific-gene-manipulation-by-intramyocardial-injection-in-mice
#18
Yanan Fu, Wenlong Jiang, Yichao Zhao, Yuli Huang, Heng Zhang, Hongju Wang, Jun Pu
Gene manipulation specifically in the heart significantly potentiate the investigation of cardiac disease pathomechanisms and their therapeutic potential. In vivo cardiac-specific gene delivery is commonly achieved by either systemic or local delivery. Systemic injection via tail vein is easy and efficient in manipulating cardiac gene expression by using recombinant adeno-associated virus 9 (AAV9). However, this method requires a relatively high amount of vector for efficient transduction, and may result in nontarget organ gene transduction...
April 16, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29706633/a-pathogenic-role-for-germline-pten-variants-which-accumulate-into-the-nucleus
#19
Janire Mingo, Isabel Rodríguez-Escudero, Sandra Luna, Teresa Fernández-Acero, Laura Amo, Amy R Jonasson, Roberto T Zori, José I López, María Molina, Víctor J Cid, Rafael Pulido
The PTEN gene encodes a master regulator protein that exerts essential functions both in the cytoplasm and in the nucleus. PTEN is mutated in the germline of both patients with heterogeneous tumor syndromic diseases, categorized as PTEN hamartoma tumor syndrome (PHTS), and a group affected with autism spectrum disorders (ASD). Previous studies have unveiled the functional heterogeneity of PTEN variants found in both patient cohorts, making functional studies necessary to provide mechanistic insights related to their pathogenicity...
April 30, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29704532/mdm2-controls-nrf2-antioxidant-activity-in-prevention-of-diabetic-kidney-disease
#20
Weiying Guo, Dan Tian, Ye Jia, Wenlin Huang, Mengnan Jiang, Junnan Wang, Weixia Sun, Hao Wu
Oxidative stress and P53 contribute to the pathogenesis of diabetic kidney disease (DKD). Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular antioxidant defense system, is negatively regulated by P53 and prevents DKD. Recent findings revealed an important role of mouse double minute 2 (MDM2) in protection against DKD. However, the mechanism remained unclear. We hypothesized that MDM2 enhances NRF2 antioxidant signaling in DKD given that MDM2 is a key negative regulator of P53...
April 25, 2018: Biochimica et Biophysica Acta
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