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https://www.readbyqxmd.com/read/29334376/positively-selected-enhancer-elements-endow-osteosarcoma-cells-with-metastatic-competence
#1
James J Morrow, Ian Bayles, Alister P W Funnell, Tyler E Miller, Alina Saiakhova, Michael M Lizardo, Cynthia F Bartels, Maaike Y Kapteijn, Stevephen Hung, Arnulfo Mendoza, Gursimran Dhillon, Daniel R Chee, Jay T Myers, Frederick Allen, Marco Gambarotti, Alberto Righi, Analisa DiFeo, Brian P Rubin, Alex Y Huang, Paul S Meltzer, Lee J Helman, Piero Picci, Henri Versteeg, John Stamatoyannopolus, Chand Khanna, Peter C Scacheri
Metastasis results from a complex set of traits acquired by tumor cells, distinct from those necessary for tumorigenesis. Here, we investigate the contribution of enhancer elements to the metastatic phenotype of osteosarcoma. Through epigenomic profiling, we identify substantial differences in enhancer activity between primary and metastatic human tumors and between near isogenic pairs of highly lung metastatic and nonmetastatic osteosarcoma cell lines. We term these regions metastatic variant enhancer loci (Met-VELs)...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29299238/is-there-plasticity-in-developmental-instability-the-effect-of-daily-thermal-fluctuations-in-an-ectotherm
#2
Øystein Nordeide Kielland, Claus Bech, Sigurd Einum
Diversified bet-hedging (DBH) by production of within-genotype phenotypic variance may evolve to maximize fitness in stochastic environments. Bet-hedging is generally associated with parental effects, but phenotypic variation may also develop throughout life via developmental instability (DI). This opens for the possibility of a within-generation mechanism creating DBH during the lifetime of individuals. If so, DI could in fact be a plastic trait itself; if a fluctuating environment indicates uncertainty about future conditions, sensing such fluctuations could trigger DI as a DBH response...
December 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/29297501/t-bet-independent-th1-response-induces-intestinal-immunopathology-during-toxoplasma-gondii-infection
#3
Américo H López-Yglesias, Elise Burger, Alessandra Araujo, Andrew T Martin, Felix Yarovinsky
Coordinated production of IFN-γ by innate and adaptive immune cells is central for host defense, but can also trigger immunopathology. The investigation of the lymphoid cell-specific contribution to the IFN-γ-mediated intestinal pathology during Toxoplasma gondii infection identified CD4+ T cells as a key cell population responsible for IFN-γ-dependent intestinal inflammation and Paneth cell loss, where T-bet-dependent group 1 innate lymphoid cells have a minor role in driving the parasite-induced immunopathology...
January 3, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29275836/a-cellular-and-molecular-view-of-t-helper-17%C3%A2-cell-plasticity-in-autoimmunity
#4
REVIEW
Ralph Stadhouders, Erik Lubberts, Rudi W Hendriks
Since the original identification of the T helper 17 (Th17) subset in 2005, it has become evident that these cells do not only contribute to host defence against pathogens, such as bacteria and fungi, but that they are also critically involved in the pathogenesis of many autoimmune diseases. In contrast to the classic Th1 and Th2 cells, which represent rather stably polarized subsets, Th17 cells display remarkable heterogeneity and plasticity. This has been attributed to the characteristics of the key transcription factor that guides Th17 differentiation, retinoic acid receptor-related orphan nuclear receptor gamma (RORγ)...
December 21, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29247138/bet-2-nsais-and-chickenpox
#5
Karen Stone, Emma Tackley, Sandra Weir
A shortcut review was carried out to establish whether non-steroidal anti-inflammatory drugs (NSAIDs) is safe to prescribe in patients with chicken pox. 66 unique papers were found in CINAHL, Medline, Embase and Cochrane using the reported searches of which 6 presented the best evidence to answer the clinical question. The author, date and country of publication; patient group studied; study type; relevant outcomes; results and study weaknesses of these best papers are tabulated. It is concluded that, pending further research, it is advisable to avoid NSAID use in cases of primary varicella due to the potential increased risk of severe bacterial skin infections...
January 2018: Emergency Medicine Journal: EMJ
https://www.readbyqxmd.com/read/29247136/bet-1-continuous-flow-insufflation-of-oxygen-in-out-of-hospital-cardiac-arrest
#6
Pierre-Alexandre LeBlanc, Alexandra Nadeau
A short cut review was carried out to establish whether continuous flow insufflation of oxygen (CFIO) is better than standard ventilation strategies at improving outcome in adults who have suffered an out-of-hospital cardiac arrest (OHCA). Papers were found in Medline and Embase using the reported searches of which four presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated...
January 2018: Emergency Medicine Journal: EMJ
https://www.readbyqxmd.com/read/29246955/a-bet-bromodomain-inhibitor-suppresses-adiposity-associated-malignant-transformation
#7
Debrup Chakraborty, Vanessa Benham, Vladislav Jdanov, Blair Bullard, Ana S Leal, Karen T Liby, Jamie J Bernard
Almost half a million of all new cancers have been attributed to obesity and epidemiological evidence implicates visceral adipose tissue (VAT) and high-fat diets (HFD) in increasing cancer risk. We demonstrated that VAT-derived fibroblast growth factor 2 (FGF2) from mice fed a HFD or obese individuals stimulates the malignant transformation of epithelial cells. Mechanism-based strategies to prevent this VAT-enhanced tumorigenesis have not been explored. Clinical studies have indicated that bromodomain inhibitors have considerable potential as therapeutic agents for cancer by inhibiting the activity of several oncogenes including c-Myc however, their chemopreventive activity is unknown...
December 15, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29218570/pure-correlates-of-exploration-and-exploitation-in-the-human-brain
#8
Tommy C Blanchard, Samuel J Gershman
Balancing exploration and exploitation is a fundamental problem in reinforcement learning. Previous neuroimaging studies of the exploration-exploitation dilemma could not completely disentangle these two processes, making it difficult to unambiguously identify their neural signatures. We overcome this problem using a task in which subjects can either observe (pure exploration) or bet (pure exploitation). Insula and dorsal anterior cingulate cortex showed significantly greater activity on observe trials compared to bet trials, suggesting that these regions play a role in driving exploration...
December 7, 2017: Cognitive, Affective & Behavioral Neuroscience
https://www.readbyqxmd.com/read/29171228/-molecular-cloning-bacterial-expression-analysis-and-functional-characterization-of-pathogenesis-related-pr10-2-gene-in-panax-notoginseng
#9
Dan Yang, Yi Bao, Li-Mei Chen, Xiu-Ming Cui, Kun-Zhi Li
Base on the transcriptome analysis and RT-PCR techniques,a pathogenesis-related protein 10 gene was isolated from Panax notoginseng root and named as PnPR10-2. Bioinformatics and phylogenetic trees analysis revealed that open reading frame (ORF) of PnPR10-2 was 465 bp in length,encoding 154 amino acids,containing one typical conserved domain of pathogenesis related protein Bet v I family, and showed high similarity with that from P. ginseng. The recombinant expressed plasmid pET32a(+)-PnPR10-2 was expressed in Escherichia coli BL21...
August 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29170712/chemical-probes-and-inhibitors-of-bromodomains-outside-the-bet-family
#10
REVIEW
Moses Moustakim, Peter G K Clark, Duncan A Hay, Darren J Dixon, Paul E Brennan
In the last five years, the development of inhibitors of bromodomains has emerged as an area of intensive worldwide research. Emerging evidence has implicated a number of non-BET bromodomains in the onset and progression of diseases such as cancer, HIV infection and inflammation. The development and use of small molecule chemical probes has been fundamental to pre-clinical evaluation of bromodomains as targets. Recent efforts are described highlighting the development of potent, selective and cell active non-BET bromodomain inhibitors and their therapeutic potential...
December 7, 2016: MedChemComm
https://www.readbyqxmd.com/read/29170296/towards-evidence-based-emergency-medicine-best-bets-from-the-manchester-royal-infirmary
#11
Katherine Wylie
No abstract text is available yet for this article.
December 2017: Emergency Medicine Journal: EMJ
https://www.readbyqxmd.com/read/29137609/a-comparative-content-analysis-of-media-reporting-of-sports-betting-in-australia-lessons-for-public-health-media-advocacy-approaches
#12
Jennifer L David, Samantha L Thomas, Melanie Randle, Steven J Bowe, Mike Daube
BACKGROUND: Harmful gambling is a significant public health issue. There has been widespread discussion in the Australian media about the extent and impact of sports betting on the Australian community, particularly relating to young men and children. Given the role that the media plays in influencing policy change and political agendas, and the acknowledgement that media based advocacy is a fundamental component of successful advocacy campaigns, this research aimed to investigate how different stakeholder groups discuss sports betting within the Australian print media...
November 14, 2017: BMC Public Health
https://www.readbyqxmd.com/read/29113796/the-bet-brd-inhibitor-jq1-attenuates-diabetes-induced-cognitive-impairment-in-rats-by-targeting-nox4-nrf2-redox-imbalance
#13
Ershun Liang, Min Ma, Lei Wang, Xue Liu, Jinfeng Xu, Mingxiang Zhang, Ruixue Yang, Yuxia Zhao
Diabetes-induced oxidative damage is believed to play an important role in the development of cognitive dysfunction. In this study, the involvement of the Nox4-Nrf2 redox imbalance was investigated. STZ-induced diabetic rats exhibited obvious oxidative stress and apoptosis in the hippocampus assessed by augmentation of lipid peroxidation, positive TUNEL staining, elevated ratio of Bax/Bcl-2 and increased caspase 3 activity. Furthermore, hyperglycemia markedly increased Nox4 activity and reduced the activation of Nrf2 by suppressing its up-stream regulatory Akt as well as down-stream target HO-1...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29104468/extensively-disturbance-of-regulatory-t-cells-th17-cells-balance-in-stage-ii-pulmonary-sarcoidosis
#14
Jingjing Ding, Jinghong Dai, Hourong Cai, Qian Gao, Yanting Wen
BACKGROUND: Sarcoidosis is a systemic inflammatory disorder characterized by granulomas. Not enough evidences correlate the derangement of CD4+ T subsets, which have an impact on the therapeutic effects of corticosteroids, with the radiographical staging of sarcoidosis. Here we show the disturbance of CD4+ T subsets in newly diagnosed stage II pulmonary sarcoidosis, which is the most common stage in which corticosteroids treatment is used. MATERIALS AND METHODS: 39 newly diagnosed and treatment-naïve patients and 9 subjects after corticosteroids treatment were included...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29081776/innate-lymphoid-cells-in-intestinal-inflammation
#15
REVIEW
Alessandra Geremia, Carolina V Arancibia-Cárcamo
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine that encompasses Crohn's disease (CD) and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC) in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29061878/bet-2-should-children-with-sport-related-concussion-observe-strict-physical-rest-until-symptom-free
#16
Andrew C Kline
A short cut review was carried out to establish whether strict physical rest following sports related concussion in children is better than normal activity in reducing post-concussional symptoms. two recent systematic reviews presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. It is concluded that children who present with a sport-related concussion should have a brief period of cognitive and physical rest followed by a gradual increase in activity...
November 2017: Emergency Medicine Journal: EMJ
https://www.readbyqxmd.com/read/29061876/bet-1-does-the-use-of-emollients-prevent-frostbite-to-the-face
#17
Emmy De Buck
A short cut review was carried out to establish whether routine use of emollients on the face reduced the incidence of frostbite in cold environments. 126 papers were found using the reported searches, of which three presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. It is concluded that the use of emollients on the face is not a good protection against frostbite and may even result in a higher risk...
November 2017: Emergency Medicine Journal: EMJ
https://www.readbyqxmd.com/read/29044821/what-do-children-observe-and-learn-from-televised-sports-betting-advertisements-a-qualitative-study-among-australian-children
#18
Hannah Pitt, Samantha L Thomas, Amy Bestman, Mike Daube, Jeffrey Derevensky
OBJECTIVE: To explore children's awareness of sports betting advertising and how this advertising may influence children's attitudes, product knowledge and desire to try sports betting. METHODS: Semi-structured qualitative interviews were conducted with 48 children (8-16 years) from Melbourne, Victoria. The interview schedule explored children's recall and interpretations of sports betting advertising, strategies within advertisements that may appeal to children, children's product knowledge and understanding of betting terminology, and factors that may encourage gambling...
October 18, 2017: Australian and New Zealand Journal of Public Health
https://www.readbyqxmd.com/read/29033951/sphingosine-1-phosphate-receptor-5-modulates-early-stage-processes-during-fibrogenesis-in-a-mouse-model-of-systemic-sclerosis-a-pilot-study
#19
Katrin G Schmidt, Martina Herrero San Juan, Sandra Trautmann, Lucija Berninger, Anja Schwiebs, Florian M Ottenlinger, Dominique Thomas, Frank Zaucke, Josef M Pfeilschifter, Heinfried H Radeke
Systemic sclerosis (SSc) is a rare multi-organ autoimmune disease characterized by progressive skin fibrosis. Inflammation, type 2 immunity, and fibrogenic processes are involved in disease development and may be affected by sphingolipids. However, details about early-stage pathophysiological mechanisms and implicated mediators remain elusive. The sphingolipid sphingosine-1-phosphate (S1P) is elevated in the sera of SSc patients, and its receptor S1P5 is expressed in skin tissue. Nevertheless, almost nothing is known about the dermatological contribution of S1P5 to inflammatory and pro-fibrotic processes leading to the pathological changes seen in SSc...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28991225/super-enhancers-define-a-proliferative-pgc-1%C3%AE-expressing-melanoma-subgroup-sensitive-to-bet-inhibition
#20
K A Gelato, L Schöckel, O Klingbeil, T Rückert, R Lesche, J Toedling, E Kalfon, M Héroult, P Lejeune, U Mönning, A E Fernández-Montalván, S Bäurle, S Siegel, B Haendler
Metabolic changes are linked to epigenetic reprogramming and play important roles in several tumor types. PGC-1α is a transcriptional coactivator controlling mitochondrial biogenesis and is linked to oxidative phosphorylation. We provide evidence that melanoma models with elevated PGC-1α levels are characteristic of the proliferative phenotype and are sensitive to bromodomain and extra-terminal domain (BET) inhibitor treatment. A super-enhancer region highly occupied by the BET family member BRD4 was identified for the PGC-1α gene...
October 9, 2017: Oncogene
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