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https://www.readbyqxmd.com/read/27933180/serum-levels-of-immunoglobulins-and-severity-of-community-acquired-pneumonia
#1
Mari C de la Torre, Pere Torán, Mateu Serra-Prat, Elisabet Palomera, Estel Güell, Ester Vendrell, Joan Carles Yébenes, Antoni Torres, Jordi Almirall
INSTRUCTION: There is evidence of a relationship between severity of infection and inflammatory response of the immune system. The objective is to assess serum levels of immunoglobulins and to establish its relationship with severity of community-acquired pneumonia (CAP) and clinical outcome. METHODS: This was an observational and cross-sectional study in which 3 groups of patients diagnosed with CAP were compared: patients treated in the outpatient setting (n=54), patients requiring in-patient care (hospital ward) (n=173), and patients requiring admission to the intensive care unit (ICU) (n=191)...
2016: BMJ Open Respiratory Research
https://www.readbyqxmd.com/read/27923837/the-nci-60-methylome-and-its-integration-into-cellminer
#2
William C Reinhold, Sudhir Varma, Margot Sunshine, Vinodh Rajapakse, Augustin Luna, Kurt W Kohn, Holly Stevenson, Yonghong Wang, Holger Heyn, Vanesa Nogales, Sebastian Moran, David J Goldstein, James H Doroshow, Paul S Meltzer, Manel Esteller, Yves Pommier
A unique resource for systems pharmacology and genomic studies is the NCI-60 cancer cell line panel, which provides data for the largest publicly available library of compounds with cytotoxic activity (~21,000 compounds), including 108 FDA-approved and 70 clinical trial drugs as well as genomic data, including whole-exome sequencing, gene and microRNA transcripts, DNA copy number, and protein levels. Here we provide the first readily usable genome-wide DNA methylation database for the NCI-60, including 485,577 probes from the Infinium HumanMethylation450k BeadChip array, which yielded DNA methylation signatures for 17,559 genes integrated into our open access CellMiner version 2...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27918140/investigation-of-intrinsically-disordered-proteins-through-exchange-with-hyperpolarized-water
#3
Dennis Kurzbach, Estel Canet, Andrea G Flamm, Aditya Jhajharia, Emmanuelle M M Weber, Robert Konrat, Geoffrey Bodenhausen
Hyperpolarized water can selectively enhance NMR signals of rapidly exchanging protons in osteopontin (OPN), a metastasis-associated intrinsically disordered protein (IDP), at near-physiological pH and temperature. The transfer of magnetization from hyperpolarized water is limited to solvent-exposed residues and therefore selectively enhances signals in (1) H-(15) N correlation spectra. Binding to the polysaccharide heparin was found to induce the unfolding of preformed structural elements in OPN.
December 5, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27911230/bromodomain-inhibitors-and-cancer-therapy-from-structures-to-applications
#4
Montserrat Pérez-Salvia, Manel Esteller
Aberrations in the epigenetic landscape are a hallmark of cancer. Alterations in enzymes that are "writers", "erasers", or "readers" of histone modification marks are common. Bromodomains are "readers" that bind acetylated lysines in histone tails. Their most important function is the regulation of gene transcription by the recruitment of different molecular partners. Moreover, proteins containing bromodomains are also epigenetic regulators, although little is known about the specific function of these domains...
December 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27894957/dna-methylation-profiling-identifies-ptrf-cavin-1-as-a-novel-tumor-suppressor-in-ewing-sarcoma-when-co-expressed-with-caveolin-1
#5
Juan Huertas-Martínez, Franck Court, Santiago Rello-Varona, David Herrero-Martín, Olga Almacellas-Rabaiget, Miguel Sáinz-Jaspeado, Silvia Garcia-Monclús, Laura Lagares-Tena, Raquel Buj, Lourdes Hontecillas-Prieto, Ana Sastre, Daniel Azorin, Xavier Sanjuan, Roser López-Alemany, Sebastian Moran, Josep Roma, Soledad Gallego, Jaume Mora, Xavier García Del Muro, Paloma H Giangrande, Miquel A Peinado, Javier Alonso, Enrique de Alava, Dave Monk, Manel Esteller, Oscar M Tirado
Epigenetic modifications have been shown to be important in developmental tumors as Ewing sarcoma. We profiled the DNA methylation status of 15 primary tumors, 7 cell lines, 10 healthy tissues and 4 human mesenchymal stem cells lines samples using the Infinium Human Methylation 450k. Differential methylation analysis between Ewing sarcoma and reference samples revealed 1,166 hypermethylated and 864 hypomethylated CpG sites (Bonferroni p<0.05, δ-β-value with absolute difference of >0.20) corresponding to 392 and 470 genes respectively...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27881738/human-selenoprotein-p-and-s-variant-mrnas-with-different-numbers-of-secis-elements-and-inferences-from-mutant-mice-of-the-roles-of-multiple-secis-elements
#6
Sen Wu, Marco Mariotti, Didac Santesmasses, Kristina E Hill, Janinah Baclaocos, Estel Aparicio-Prat, Shuping Li, John Mackrill, Yuanyuan Wu, Michael T Howard, Mario Capecchi, Roderic Guigó, Raymond F Burk, John F Atkins
Dynamic redefinition of the 10 UGAs in human and mouse selenoprotein P (Sepp1) mRNAs to specify selenocysteine instead of termination involves two 3' UTR structural elements (SECIS) and is regulated by selenium availability. In addition to the previously known human Sepp1 mRNA poly(A) addition site just 3' of SECIS 2, two further sites were identified with one resulting in 10-25% of the mRNA lacking SECIS 2. To address function, mutant mice were generated with either SECIS 1 or SECIS 2 deleted or with the first UGA substituted with a serine codon...
November 2016: Open Biology
https://www.readbyqxmd.com/read/27875876/dissolution-dynamic-nuclear-polarization-of-deuterated-molecules-enhanced-by-cross-polarization
#7
Dennis Kurzbach, Emmanuelle M M Weber, Aditya Jhajharia, Samuel F Cousin, Aude Sadet, Sina Marhabaie, Estel Canet, Nicolas Birlirakis, Jonas Milani, Sami Jannin, Dmitry Eshchenko, Alia Hassan, Roberto Melzi, Stephan Luetolf, Marco Sacher, Marc Rossire, James Kempf, Joost A B Lohman, Matthias Weller, Geoffrey Bodenhausen, Daniel Abergel
We present novel means to hyperpolarize deuterium nuclei in (13)CD2 groups at cryogenic temperatures. The method is based on cross-polarization from (1)H to (13)C and does not require any radio-frequency fields applied to the deuterium nuclei. After rapid dissolution, a new class of long-lived spin states can be detected indirectly by (13)C NMR in solution. These long-lived states result from a sextet-triplet imbalance (STI) that involves the two equivalent deuterons with spin I = 1. An STI has similar properties as a triplet-singlet imbalance that can occur in systems with two equivalent I = 12 spins...
November 21, 2016: Journal of Chemical Physics
https://www.readbyqxmd.com/read/27874015/metabolic-sialic-acid-blockade-lowers-the-activation-threshold-of-modcs-for-tlr-stimulation
#8
Christian Büll, Estel Collado-Camps, Esther D Kers-Rebel, Torben Heise, Jonas N Søndergaard, Martijn H den Brok, Barbara M Schulte, Thomas J Boltje, Gosse J Adema
Sialic acid sugars cover the surface of dendritic cells (DCs) and have been suggested to impact several aspects of DC biology. Research into the role of sialic acids in DCs, however, is complicated by the limited number of tools available to modulate sialic acid expression. Here we report on a synthetic, fluorinated sialic acid mimetic, Ac53FaxNeu5Ac, which potently blocks sialic acid expression in human monocyte-derived DCs (moDCs). Sialic acid blockade enhanced the responsiveness of moDCs to Toll-like receptor (TLR) stimulation as measured by increased maturation marker expression and cytokine production...
November 22, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27821766/epigenetic-inactivation-of-the-p53-induced-long-noncoding-rna-tp53-target-1-in-human-cancer
#9
Angel Diaz-Lagares, Ana B Crujeiras, Paula Lopez-Serra, Marta Soler, Fernando Setien, Ashish Goyal, Juan Sandoval, Yutaka Hashimoto, Anna Martinez-Cardús, Antonio Gomez, Holger Heyn, Catia Moutinho, Jesús Espada, August Vidal, Maria Paúles, Maica Galán, Núria Sala, Yoshimitsu Akiyama, María Martínez-Iniesta, Lourdes Farré, Alberto Villanueva, Matthias Gross, Sven Diederichs, Sonia Guil, Manel Esteller
Long noncoding RNAs (lncRNAs) are important regulators of cellular homeostasis. However, their contribution to the cancer phenotype still needs to be established. Herein, we have identified a p53-induced lncRNA, TP53TG1, that undergoes cancer-specific promoter hypermethylation-associated silencing. In vitro and in vivo assays identify a tumor-suppressor activity for TP53TG1 and a role in the p53 response to DNA damage. Importantly, we show that TP53TG1 binds to the multifaceted DNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27810920/in-vivo-conditional-deletion-of-hdac7-reveals-its-requirement-to-establish-proper-b-lymphocyte-identity-and-development
#10
Alba Azagra, Lidia Román-González, Olga Collazo, Javier Rodríguez-Ubreva, Virginia G de Yébenes, Bruna Barneda-Zahonero, Jairo Rodríguez, Manuel Castro de Moura, Joaquim Grego-Bessa, Irene Fernández-Duran, Abul B M M K Islam, Manel Esteller, Almudena R Ramiro, Esteban Ballestar, Maribel Parra
Class IIa histone deacetylase (HDAC) subfamily members are tissue-specific gene repressors with crucial roles in development and differentiation processes. A prominent example is HDAC7, a class IIa HDAC that shows a lymphoid-specific expression pattern within the hematopoietic system. In this study, we explored its potential role in B cell development by generating a conditional knockout mouse model. Our study demonstrates for the first time that HDAC7 deletion dramatically blocks early B cell development and gives rise to a severe lymphopenia in peripheral organs, while also leading to pro-B cell lineage promiscuity...
November 14, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27804975/corrigendum-a-derl3-associated-defect-in-the-degradation-of-slc2a1-mediates-the-warburg-effect
#11
Paula Lopez-Serra, Miguel Marcilla, Alberto Villanueva, Antonio Ramos-Fernandez, Anna Palau, Lucía Leal, Jessica E Wahi, Fernando Setien-Baranda, Karolina Szczesna, Catia Moutinho, Anna Martinez-Cardus, Holger Heyn, Juan Sandoval, Sara Puertas, August Vidal, Xavier Sanjuan, Eva Martinez-Balibrea, Francesc Viñals, Jose C Perales, Jesper B Bramsem, Torben F Ørntoft, Claus L Andersen, Josep Tabernero, Ultan McDermott, Matthew B Boxer, Matthew G Vander Heiden, Juan Pablo Albar, Manel Esteller
No abstract text is available yet for this article.
November 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27776934/the-antiphospholipid-syndrome-in-patients-with-systemic-lupus-erythematosus
#12
Guillermo J Pons-Estel, Laura Andreoli, Francesco Scanzi, Ricard Cervera, Angela Tincani
The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the occurrence of venous and/or arterial thrombosis and pregnancy morbidity in the presence of pathogenic autoantibodies known as antiphospholipid antibodies (aPL). APS may be associated with other diseases, mainly systemic lupus erythematosus (SLE). The presence or absence of SLE might modify the clinical or serological expression of APS. Apart from the classical manifestations, APS patients with associated SLE more frequently display a clinical profile with arthralgias, arthritis, autoimmune hemolytic anemia, livedo reticularis, epilepsy, glomerular thrombosis, and myocardial infarction...
October 21, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27773016/fragmented-diagnoses
#13
Kumari Dissanayake, Jane Estell, Vivien Chen
No abstract text is available yet for this article.
February 2016: Pathology
https://www.readbyqxmd.com/read/27753208/formalising-multidisciplinary-peer-review-developing-a-haematological-malignancy-specific-electronic-proforma-and-standard-operating-procedure-to-facilitate-procedural-efficiency-and-evidence-based-clinical-practice
#14
J Trotman, J Trinh, Y L Kwan, J A Estell, J Fletcher, K Archer, K Lee, K Foo, J Curnow, A Bianchi, L Wignall, E Verner, R Gasiorowski, E Siedlecka, I Cunningham
BACKGROUND: Multidisciplinary Team (MDT) meetings aimed at facilitating peer review have become standard practice in oncology. However, there is scant literature on the optimal structure and conduct of such meetings. AIMS: We aimed to develop a process for formal peer review of patients with haematologic malignancies, and to audit any resulting changes made to the management recommendations of the treating physician. METHODS: A standard operating procedure (SOP) for MDT meetings was developed essentially to integrate clinical peer review with weekly pathology and radiology meetings...
October 18, 2016: Internal Medicine Journal
https://www.readbyqxmd.com/read/27746755/epigenetics-in-schizophrenia-a-pilot-study-of-global-dna-methylation-in-different-brain-regions-associated-with-higher-cognitive-functions
#15
Raúl Alelú-Paz, Francisco J Carmona, José V Sanchez-Mut, Ariel Cariaga-Martínez, Ana González-Corpas, Nadia Ashour, Maria J Orea, Ana Escanilla, Alfonso Monje, Carmen Guerrero Márquez, Jerónimo Saiz-Ruiz, Manel Esteller, Santiago Ropero
Attempts to discover genes that are involved in the pathogenesis of major psychiatric disorders have been frustrating and often fruitless. Concern is building about the need to understand the complex ways in which nature and nurture interact to produce mental illness. We analyze the epigenome in several brain regions from schizophrenic patients with severe cognitive impairment using high-resolution (450K) DNA methylation array. We identified 139 differentially methylated CpG sites included in known and novel candidate genes sequences as well as in and intergenic sequences which functions remain unknown...
2016: Frontiers in Psychology
https://www.readbyqxmd.com/read/27742776/germline-missense-pathogenic-variants-in-the-brca1-brct-domain-p-gly1706glu-and-p-ala1708glu-increase-cellular-sensitivity-to-parp-inhibitor-olaparib-by-a-dominant-negative-effect
#16
Tereza Vaclová, Nicholas T Woods, Diego Megías, Sergio Gomez-Lopez, Fernando Setién, José María García Bueno, José Antonio Macías, Alicia Barroso, Miguel Urioste, Manel Esteller, Alvaro N A Monteiro, Javier Benítez, Ana Osorio
BRCA1-deficient cells show defects in DNA repair and rely on other members of the DNA repair machinery, which makes them sensitive to PARP inhibitors (PARPi). Although carrying a germline pathogenic variant in BRCA1/2 is the best determinant of response to PARPi, a significant percentage of the patients do not show sensitivity and/or display increased toxicity to the agent. Considering previously suggested mutation-specific BRCA1 haploinsufficiency, we aimed to investigate whether there are any differences in cellular response to PARPi Olaparib depending on the BRCA1 mutation type...
October 13, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27732835/oncometabolite-accumulation-and-epithelial-to-mesenchymal-transition-the-turn-of-fumarate
#17
Maxime Janin, Manel Esteller
Mutations to the Krebs cycle enzyme fumarate hydratase in cancer cells leads to an accumulation of the oncometabolite fumarate. Sciacovelli et al. (2016) demonstrate an epigenetically dependent epithelial-to-mesenchymal transition mediated by modulation of the miR-200 cluster and TET demethylation in response to fumarate accumulation.
October 11, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27660998/theory-of-mind-in-euthymic-bipolar-patients-and-first-degree-relatives
#18
Josep Manel Santos, Esther Pousa, Estel Soto, Anna Comes, Pere Roura, Francesc X Arrufat, Jordi E Obiols
The present study analyzed the capacity for mentalization of patients with bipolar disorder (BD) and their first-degree relatives (FDR) and examined the implications of clinical variables and cognitive deficits. The study recruited 31 patients with type I BD, 18 FDR, and 31 paired healthy controls. Their capacity for mentalization was explored by means of first- and second-order false-belief tasks, the hinting task, and the Movie for the Assessment of Social Cognition (MASC). Patients and FDR were found to have a theory of mind (ToM) deficit when they were evaluated with the MASC, which was also related to a worse neurocognitive performance and to being a patient or FDR...
September 22, 2016: Journal of Nervous and Mental Disease
https://www.readbyqxmd.com/read/27645142/application-of-water-quality-index-to-evaluate-groundwater-quality-temporal-and-spatial-variation-of-an-intensively-exploited-aquifer-puebla-valley-mexico
#19
Edith R Salcedo-Sánchez, Sofía E Garrido Hoyos, Ma Vicenta Esteller Alberich, Manuel Martínez Morales
The spatial and temporal variation of water quality in the urban area of the Puebla Valley aquifer was evaluated using historical and present data obtained during this investigation. The current study assessed water quality based on the Water Quality Index developed by the Canadian Council of Ministers of the Environment (CCME-WQI), which provides a mathematical framework to evaluate the quality of water in combination with a set of conditions representing quality criteria, or limits. This index is flexible regarding the type and number of variables used by the evaluation given that the variables of interest are selected according to the characteristics and objectives of development, conservation and compliance with regulations...
December 0: Environmental Monitoring and Assessment
https://www.readbyqxmd.com/read/27616566/metformin-pharmacogenomics-a-genome-wide-association-study-to-identify-genetic-and-epigenetic-biomarkers-involved-in-metformin-anticancer-response-using-human-lymphoblastoid-cell-lines
#20
Nifang Niu, Tongzheng Liu, Junmei Cairns, Reynold C Ly, Xianglin Tan, Min Deng, Brooke L Fridley, Krishna R Kalari, Ryan P Abo, Gregory Jenkins, Anthony Batzler, Erin E Carlson, Poulami Barman, Sebastian Moran, Holger Heyn, Manel Esteller, Liewei Wang
Metformin is currently considered as a promising anticancer agent in addition to its anti-diabetic effect. To better individualize metformin therapy and explore novel molecular mechanisms in cancer treatment, we conducted a pharmacogenomic study using 266 lymphoblastoid cell lines (LCLs). Metformin cytotoxicity assay was performed using the MTS assay. Genome-wide association (GWA) analyses were performed in LCLs using 1.3 million SNPs, 485k DNA methylation probes, 54k mRNA expression probe sets, and metformin cytotoxicity (IC50s)...
September 11, 2016: Human Molecular Genetics
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