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https://www.readbyqxmd.com/read/28548080/discovery-of-first-in-class-reversible-dual-small-molecule-inhibitors-against-g9a-and-dnmts-in-hematological-malignancies
#1
Edurne San José-Enériz, Xabier Agirre, Obdulia Rabal, Amaia Vilas-Zornoza, Juan A Sanchez-Arias, Estibaliz Miranda, Ana Ugarte, Sergio Roa, Bruno Paiva, Ander Estella-Hermoso de Mendoza, Rosa María Alvarez, Noelia Casares, Victor Segura, José I Martín-Subero, François-Xavier Ogi, Pierre Soule, Clara M Santiveri, Ramón Campos-Olivas, Giancarlo Castellano, Maite Garcia Fernandez de Barrena, Juan Roberto Rodriguez-Madoz, Maria José García-Barchino, Juan Jose Lasarte, Matias A Avila, Jose Angel Martinez-Climent, Julen Oyarzabal, Felipe Prosper
The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favoured development of epigenetic drugs. In this study, we design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of haematological neoplasia (acute myeloid leukaemia-AML, acute lymphoblastic leukaemia-ALL and diffuse large B-cell lymphoma-DLBCL) with the lead compound CM-272, inhibits cell proliferation and promotes apoptosis, inducing interferon-stimulated genes and immunogenic cell death...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28542593/lack-of-the-pga-exopolysaccharide-in-salmonella-as-an-adaptive-trait-for-survival-in-the-host
#2
Maite Echeverz, Begoña García, Amaia Sabalza, Jaione Valle, Toni Gabaldón, Cristina Solano, Iñigo Lasa
Many bacteria build biofilm matrices using a conserved exopolysaccharide named PGA or PNAG (poly-β-1,6-N-acetyl-D-glucosamine). Interestingly, while E. coli and other members of the family Enterobacteriaceae encode the pgaABCD operon responsible for PGA synthesis, Salmonella lacks it. The evolutionary force driving this difference remains to be determined. Here, we report that Salmonella lost the pgaABCD operon after the divergence of Salmonella and Citrobacter clades, and previous to the diversification of the currently sequenced Salmonella strains...
May 24, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28529350/a-latent-profile-analysis-investigating-factors-impacting-latino-adolescents-attendance-in-treatment
#3
Karina A Gattamorta, Brian E McCabe, Maite P Mena, Daniel A Santisteban
In this study, we examined data from 200 families to investigate whether family functioning and adolescent psychiatric symptomatology were associated with differential attendance in a family-based or individually focused intervention for Latino adolescents. Latent profile analysis was used to identify families, and regression models were used to examine whether profiles exhibited differential attendance. Overall, three latent profiles were observed. The first described families where parents and adolescents reported discrepancies on psychiatric symptoms and family conflict...
August 2016: Counseling Psychologist
https://www.readbyqxmd.com/read/28528702/detailed-characterization-of-mesenchymal-stem-stromal-cells-from-a-large-cohort-of-aml-patients-demonstrates-a-definitive-link-to-treatment-outcomes
#4
Rafael Diaz de la Guardia, Belen Lopez-Millan, Jessie R Lavoie, Clara Bueno, Julio Castaño, Maite Gómez-Casares, Susana Vives, Laura Palomo, Manel Juan, Julio Delgado, Maria L Blanco, Josep Nomdedeu, Alberto Chaparro, Jose Luis Fuster, Eduardo Anguita, Michael Rosu-Myles, Pablo Menéndez
Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are key components of the hematopoietic niche thought to have a direct role in leukemia pathogenesis. BM-MSCs from patients with acute myeloid leukemia (AML) have been poorly characterized due to disease heterogeneity. We report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. Stable MSC cultures were successfully established and characterized from 40 of 46 AML patients irrespective of the risk subgroup...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28526582/mait-cells-a-tailor-made-mate-in-the-ancient-battle-against-infectious-diseases
#5
REVIEW
Marcela de Lima Moreira, Moriya Tsuji, Alexandra Jane Corbett, Márcio Sobreira Silva Araújo, Andréa Teixeira-Carvalho, Olindo Assis Martins-Filho, Vanessa Peruhype-Magalhães, Jordana Grazziela Coelho-Dos-Reis
It has been almost two decades since the discovery of mucosal-associated invariant T (MAIT)-cells. Several advances in the field have been made such as the discovery of the antimicrobial activity of MAIT-cells, the abundance of these cells in human mucosa and in liver and the discovery of ligands able to bind MR1 and activate MAIT-cells. MAIT-cells are a unique subset of innate-like T-cells that express a canonical T-cell receptor with the alpha chain containing hAV7S2 and AJ33 in humans (TCRVα7.2Jα33) and respond to bacterial/fungus vitamin B2 metabolites by an MR1-dependent pathway...
May 16, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28526460/semi-supervised-medical-entity-recognition-a-study-on-spanish-and-swedish-clinical-corpora
#6
Alicia Pérez, Rebecka Weegar, Arantza Casillas, Koldo Gojenola, Maite Oronoz, Hercules Dalianis
OBJECTIVE: The goal of this study is to investigate entity recognition within Electronic Health Records (EHRs) focusing on Spanish and Swedish. Of particular importance is a robust representation of the entities. In our case, we utilized unsupervised methods to generate such representations. METHODS: The significance of this work stands on its experimental layout. The experiments were carried out under the same conditions for both languages. Several classification approaches were explored: maximum probability, CRF, Perceptron and SVM...
May 16, 2017: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/28520640/twenty-four-month-follow-up-of-tocilizumab-therapy-for-refractory-uveitis-related-macular-edema
#7
Marina Mesquida, Blanca Molins, Victor Llorenç, María V Hernández, Gerard Espinosa, Maite Sainz de la Maza, Alfredo Adán
BACKGROUND: To report the 24-month efficacy and safety of the interleukin-6 receptor antagonist tocilizumab (TCZ) for refractory uveitis-related macular edema (ME). METHODS: Data were obtained by standardized chart review. Patients with quiescent uveitis seen at a single tertiary referral center, for whom ME was the principal cause of reduced visual acuity. OUTCOME MEASURES: Central foveal thickness measured by optical coherence tomography; degree of anterior and posterior chamber; inflammation (Standardization of Uveitis Nomenclature Working Group criteria); and visual acuity (Snellen and logarithm of the minimum angle of resolution) were recorded in all patients during TCZ therapy at months 1, 3, 6, 12, 18, and 24...
May 16, 2017: Retina
https://www.readbyqxmd.com/read/28518215/the-tlr9-signaling-pathway-regulates-mr1-mediated-bacterial-antigen-presentation-in-b-cells
#8
Jianyun Liu, Randy R Brutkiewicz
Mucosal-associated invariant T (MAIT) cells are conserved T cells that express a semi-invariant TCR (Vα7.2 in humans and Vα19 in mice). The development of MAIT cells requires the antigen (Ag) presenting MHC-related protein 1 (MR1), as well as commensal bacteria. The mechanisms that regulate the functional expression of MR1 molecules and their loading with bacterial Ag in APCs are largely unknown. We have found that treating B cells with the TLR9 agonist CpG increases MR1 surface expression. Interestingly, activation of TLR9 by CpG-A (but not CpG-B) enhances MR1 surface expression...
May 18, 2017: Immunology
https://www.readbyqxmd.com/read/28515343/kidney-heart-and-brain-three-organs-targeted-by-ageing-and-glycation
#9
REVIEW
Marie Frimat, Maité Daroux, Rachel Litke, Rémi Nevière, Frédéric J Tessier, Eric Boulanger
Advanced glycation end-product (AGE) is the generic term for a heterogeneous group of derivatives arising from a non-enzymatic reaction between reducing sugars and proteins. In recent years, evidence has accumulated that incriminates AGEs in pathogenic processes associated with both chronic hyperglycaemia and age-related diseases. Regardless of their exogenous or endogenous origin, the accumulation of AGEs and their derivatives could promote accelerated ageing by leading to protein modifications and activating several inflammatory signalling pathways via AGE-specific receptors...
June 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28513074/%C3%AE-myrtoxin-mp1a-is-a-helical-heterodimer-from-the-venom-of-the-jack-jumper-ant-with-antimicrobial-membrane-disrupting-and-nociceptive-activities
#10
Zoltan Dekan, Stephen J Heady, Martin Scanlon, Brian A Baldo, Tzong-Hsien Lee, Marie-Isabel Aguilar, Jennifer R Deuis, Irina Vetter, Alysha G Elliott, Maite Amado, Matthew A Cooper, Dianne Alewood, Paul Francis Alewood
Δ-Myrtoxin-Mp1a (Mp1a), a 49-residue heterodimeric peptide from the venom of Myrmecia pilosula is comprised of a 26-mer A chain and a 23-mer B chain connected by two disulfide bonds in an antiparallel arrangement. Combination of the individual synthetic chains via aerial oxidation remarkably resulted in the self-assembly of Mp1a as a homogenous product without the need for directed disulfide bond formation. NMR analysis revealed a well-defined, unique structure containing a pair of antiparallel α-helices...
May 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28498521/does-drought-stress-modify-the-effects-of-plant-growth-promoting-rhizobacteria-on-an-aboveground-chewing-herbivore
#11
Maite Fernández de Bobadilla, Julia Friman, Nurmi Pangesti, Marcel Dicke, Joop J A van Loon, Ana Pineda
Soil microbes have important effects on the interactions of plants with their environment, by promoting plant growth, inducing resistance to pests or by conferring tolerance to abiotic stress. However, their effects are variable and the factors responsible for this variation are mainly unknown. Our aim was to assess how drought stress modifies the effect of the non-pathogenic rhizobacterium Pseudomonas simiae WCS417r on plant growth and resistance against the generalist leaf-chewing caterpillar Mamestra brassicae...
May 12, 2017: Insect Science
https://www.readbyqxmd.com/read/28494326/mait-cells-and-mr1-antigen-recognition
#12
REVIEW
Andrew N Keller, Alexandra J Corbett, Jacinta M Wubben, James McCluskey, Jamie Rossjohn
Mucosal-associated invariant T cells (MAIT cells) are innate-like T cells that recognise antigens presented by the monomorphic MHC-I related molecule, MR1. Distinct from the conventional MHC-restricted T cell system, MR1 presents small-molecule precursors, derived from microbial biosynthesis of riboflavin, to activate the innate MAIT cell effector potential. Recent data demonstrates how: vitamin B precursors modulate intracellular trafficking of MR1 and impact on MAIT cell development; variation in the MAIT cell antigen receptor sequence impacts MR1-antigen recognition; and most notably, how MR1 can capture chemical identities distinct from riboflavin precursors, including drugs and drug-like molecules...
May 8, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28487696/natural-killer-cells-in-graft-versus-host-disease-after-allogeneic-hematopoietic-cell-transplantation
#13
REVIEW
Federico Simonetta, Maite Alvarez, Robert S Negrin
Allogeneic hematopoietic cell transplantation (HCT) is a well-established therapeutic modality effective for a variety of hematological malignancies but, unfortunately, is associated with significant morbidity and mortality related to cancer relapse as well as to transplant-related complications including graft-versus-host-disease (GvHD). Natural killer (NK) cells are the first donor-derived lymphocyte subset to recover after HCT, and their crucial role in protection against cancer relapse and infections is well established...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28487465/geriatric-assessment-predicts-survival-and-competing-mortality-in-elderly-patients-with-early-colorectal-cancer-can-it-help-in-adjuvant-therapy-decision-making
#14
Maite Antonio, Juana Saldaña, Alberto Carmona-Bayonas, Valentín Navarro, Cristian Tebé, Marga Nadal, Francesc Formiga, Ramon Salazar, Josep Maria Borràs
BACKGROUND: The challenge when selecting elderly patients with colorectal cancer (CRC) for adjuvant therapy is to estimate the likelihood that death from other causes will preclude cancer events from occurring. The aim of this paper is to evaluate whether comprehensive geriatric assessment (CGA) can predict survival and cancer-specific mortality in elderly CRC patients candidates for adjuvant therapy. MATERIAL AND METHODS: One hundred ninety-five consecutive patients aged ≥75 with high-risk stage II and stage III CRC were prospectively included from May 2008 to May 2015...
May 9, 2017: Oncologist
https://www.readbyqxmd.com/read/28485401/foxp3-regulatory-t-cells-maintain-the-bone-marrow-microenvironment-for-b-cell-lymphopoiesis
#15
Antonio Pierini, Hidekazu Nishikii, Jeanette Baker, Takaharu Kimura, Hye-Sook Kwon, Yuqiong Pan, Yan Chen, Maite Alvarez, William Strober, Andrea Velardi, Judith A Shizuru, Joy Y Wu, Shigeru Chiba, Robert S Negrin
Foxp3(+) regulatory T cells (Treg cells) modulate the immune system and maintain self-tolerance, but whether they affect haematopoiesis or haematopoietic stem cell (HSC)-mediated reconstitution after transplantation is unclear. Here we show that B-cell lymphopoiesis is impaired in Treg-depleted mice, yet this reduced B-cell lymphopoiesis is rescued by adoptive transfer of affected HSCs or bone marrow cells into Treg-competent recipients. B-cell reconstitution is abrogated in both syngeneic and allogeneic transplantation using Treg-depleted mice as recipients...
May 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28476285/is-heart-rate-variability-affected-by-distinct-motor-imagery-strategies
#16
Talita Peixoto Pinto, Maitê Mello Russo Ramos, Thiago Lemos, Claudia Domingues Vargas, Luis Aureliano Imbiriba
Although some studies have reported significant changes in autonomic responses according to the perspective-taking during motor imagery [first person perspective (1P) and third person perspective (3P)], investigations on how the strategies adopted to mentally simulate a given movement affect the heart rate variability (HRV) seem so far unexplored. Twenty healthy subjects mentally simulated the movement of middle-finger extension in 1P and 3P, while electrocardiogram was recorded. After each task, the level of easiness was self-reported...
May 2, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28474257/a-cumulative-effect-involving-malfunction-of-the-pth1r-and-atp4a-genes-explains-a-familial-gastric-neuroendocrine-tumor-with-hypothyroidism-and-arthritis
#17
Oriol Calvete, Maite Herraiz, Jose Reyes, Ana Patiño, Javier Benitez
BACKGROUND: Type I gastric neuroendocrine tumors (gNETs) classically arise because of hypergastrinemia and involve destruction of parietal cells, which are responsible for gastric acid secretion through the ATP4A proton pump and for intrinsic factor production. METHODS: By whole exome sequencing, we studied a family with three members with gNETs plus hypothyroidism and rheumatoid arthritis to uncover their genetic origin. RESULTS: A heterozygous missense mutation in the ATP4A gene was identified...
May 4, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28472591/association-between-personality-traits-and-escitalopram-treatment-efficacy-in-panic-disorder
#18
Ülle Võhma, Mait Raag, Innar Tõru, Anu Aluoja, Eduard Maron
BACKGROUND: There is strong evidence to suggest that personality factors may interact with the development and clinical expression of panic disorder (PD). A greater understanding of these relationships may have important implications for clinical practice and implications for searching reliable predictors of treatment outcome. AIMS: The study aimed to examine the effect of escitalopram treatment on personality traits in PD patients, and to identify whether the treatment outcome could be predicted by any personality trait...
May 4, 2017: Nordic Journal of Psychiatry
https://www.readbyqxmd.com/read/28470739/vitamin-d-treatment-modulates-immune-activation-in-cystic-fibrosis
#19
T Pincikova, D Paquin-Proulx, J K Sandberg, M Flodström-Tullberg, L Hjelte
Persistent inflammatory response in cystic fibrosis (CF) airways is believed to play a central role in the progression of lung damage. Anti-inflammatory treatment may slow lung disease progression, but adverse side effects have limited its use. Vitamin D has immunoregulatory properties. We randomized 16 CF patients to receive vitamin D2, vitamin D3 or to serve as controls, and investigated the effect of vitamin D supplementation on soluble immunological parameters, myeloid dendritic cells (mDCs) and T cell activation...
May 3, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28466149/potentially-modifiable-factors-contributing-to-sepsis-associated-encephalopathy
#20
Romain Sonneville, Etienne de Montmollin, Julien Poujade, Maïté Garrouste-Orgeas, Bertrand Souweine, Michael Darmon, Eric Mariotte, Laurent Argaud, François Barbier, Dany Goldgran-Toledano, Guillaume Marcotte, Anne-Sylvie Dumenil, Samir Jamali, Guillaume Lacave, Stéphane Ruckly, Bruno Mourvillier, Jean-François Timsit
PURPOSE: Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. METHODS: We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) <15 or when features of delirium were noted. Potentially modifiable risk factors for SAE at ICU admission and its impact on mortality were investigated using multivariate logistic regression analysis and Cox proportional hazard modeling, respectively...
May 2, 2017: Intensive Care Medicine
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