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https://www.readbyqxmd.com/read/28205648/identification-of-a-novel-nampt-inhibitor-by-crispr-cas9-chemogenomic-profiling-in-mammalian-cells
#1
David Estoppey, Jeffrey W Hewett, Chantale T Guy, Edmund Harrington, Jason R Thomas, Markus Schirle, Rachel Cuttat, Annick Waldt, Bertran Gerrits, Zinger Yang, Sven Schuierer, Xuewen Pan, Kevin Xie, Walter Carbone, Judith Knehr, Alicia Lindeman, Carsten Russ, Elizabeth Frias, Gregory R Hoffman, Malini Varadarajan, Nadire Ramadan, John S Reece-Hoyes, Qiong Wang, Xin Chen, Gregory McAllister, Guglielmo Roma, Tewis Bouwmeester, Dominic Hoepfner
Chemogenomic profiling is a powerful and unbiased approach to elucidate pharmacological targets and the mechanism of bioactive compounds. Until recently, genome-wide, high-resolution experiments of this nature have been limited to fungal systems due to lack of mammalian genome-wide deletion collections. With the example of a novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitor, we demonstrate that the CRISPR/Cas9 system enables the generation of transient homo- and heterozygous deletion libraries and allows for the identification of efficacy targets and pathways mediating hypersensitivity and resistance relevant to the compound mechanism of action...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28192235/high-hcv-subtype-heterogeneity-in-a-chronically-infected-general-population-revealed-by-high-resolution-hcv-subtyping
#2
Francisco Rodriguez-Frias, Leonardo Nieto, Josep Gregori, Damir Garcia-Cehic, Rosario Casillas, David Tabernero, Maria Homs, Maria Blasi, Marta Vila, Qian Chen, Victor Vargas, Lluís Castells, Lluís Viladomiu, Joan Genesca, Beatriz Minguez, Salvador Augustin, Judit Carbonell, Celia Perales, Maria Eugenia Soria, Miriam Asensio, Meritxell Llorens, Laura Ordeig, Cristina Godoy, Maria Buti, Rafael Esteban, Tomas Pumarola, Juan Ignacio Esteban, Josep Quer
OBJECTIVES: Accurately characterize the chronically-infected general HCV population in the Barcelona area by a highly sensitive subtyping method able to identify the 67 recognized hepatitis C virus (HCV) subtypes, and to discriminate mixed infections in a single individual. This information has strong implications on patient management, in deciding the optimal combination of direct-acting antivirals (DAAs) for each patient. METHODS: HCV subtyping by UDPS. All HCV patients who attended Vall d'Hebron Hospital outpatient clinics from February 2015 to May 2016 (N=1473) were included...
February 10, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28191913/treatment-with-the-glucagon-receptor-antagonist-ly2409021-increases-ambulatory-blood-pressure-in-patients-with-type-2-diabetes
#3
Christof M Kazda, Juan Frias, Irene Foga, Xuewei Cui, Cristina B Guzman, Parag Garhyan, Cory Heilmann, Jihui Anne Yang, Thomas A Hardy
AIMS: To assess the effect of LY2409021 on systolic blood pressure (SBP) in patients with type 2 diabetes. MATERIALS AND METHODS: This 6-week, randomized, crossover study evaluated the effects of once-daily administration of LY2409021 20 mg vs those of placebo on SBP, diastolic BP (DBP), and mean arterial pressure (MAP) using 24-hour ambulatory BP monitoring (ABPM) in 270 subjects treated with diet/exercise ± metformin. Other measures included changes in glycemic control, serum lipids, and hepatic safety markers...
February 13, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28174048/the-effects-of-particulate-matter-on-inflammation-of-respiratory-system-differences-between-male-and-female
#4
Kelly Yoshizaki, Jôse Mára Brito, Luiz Fernando Silva, Adriana Lino-Dos-Santos-Franco, Daniela Perroni Frias, Renata Calciolari Rossi E Silva, Luís Fernando Amato-Lourenço, Paulo Hilário Nascimento Saldiva, Iolanda de Fátima Lopes Calvo Tibério, Thais Mauad, Mariangela Macchione
Air pollution is known to exacerbate respiratory diseases and epidemiological studies have shown that women present more chronic respiratory symptoms than man exposed to traffic pollution, however, the reason why is unclear. This study evaluated the inflammatory differences in BALB/c mouse males (n=34) and females (n=111) in three phases of the estrous cycle that were exposed to ambient air (AA) or concentrated ambient particles (CAPs). Tracheal hyperreactivity to methacholine, bronchoalveolar lavage fluid (BALF) and immunohistochemical of airways and lung parenchyma were studied...
February 4, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28153658/first-trimester-alcohol-exposure-alters-placental-perfusion-and-fetal-oxygen-availability-affecting-fetal-growth-and-development-in-a-non-human-primate-model
#5
Jamie O Lo, Matthias C Schabel, Victoria H J Roberts, Xiaojie Wang, Katherine S Lewandowski, Kathleen A Grant, Antonio E Frias, Christopher D Kroenke
BACKGROUND: Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol that links altered placental function to impaired fetal development remain areas of active research. OBJECTIVE: Recently, we developed magnetic resonance imaging techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T2* and perfusion using dynamic contrast-enhanced magnetic resonance imaging...
January 30, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28150814/p-selectin-preserves-immune-tolerance-in-mice-and-is-reduced-in-human-cutaneous-lupus
#6
Rafael González-Tajuelo, Javier Silván, Alicia Pérez-Frías, María de la Fuente-Fernández, Reyes Tejedor, Marina Espartero-Santos, Esther Vicente-Rabaneda, Ángeles Juarranz, Cecilia Muñoz-Calleja, Santos Castañeda, Carlos Gamallo, Ana Urzainqui
Mice deficient in P-Selectin presented altered immunity/tolerance balance. We have observed that the absence of P-Selectin promotes splenomegaly with reduced naïve T cell population, elevated activated/effector T cell subset, increased germinal center B and Tfh populations and high production of autoreactive antibodies. Moreover, 1.5-3-month-old P-selectin KO mice showed reduced IL-10-producing leukocytes in blood and a slightly reduced Treg population in the skin. With aging and, coinciding with disease severity, there is an increase in the IL17(+) circulating and dermal T cell subpopulations and reduction of dermal Treg...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28120014/a-bacterial-gh6-cellobiohydrolase-with-a-novel-modular-structure
#7
Liliana Cerda-Mejía, Susana Valeria Valenzuela, Cristina Frías, Pilar Diaz, F I Javier Pastor
Cel6D from Paenibacillus barcinonensis is a modular cellobiohydrolase with a novel molecular architecture among glycosyl hydrolases of family 6. It contains an N-terminal catalytic domain (family 6 of glycosyl hydrolases (GH6)), followed by a fibronectin III-like domain repeat (Fn31,2) and a C-terminal family 3b cellulose-binding domain (CBM3b). The enzyme has been identified and purified showing catalytic activity on cellulosic substrates and cellodextrins, with a marked preference for phosphoric acid swollen cellulose (PASC)...
January 25, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28116776/a-phase-3-efficacy-and-safety-study-of-ertugliflozin-monotherapy-in-patients-with-type-2-diabetes-mellitus-inadequately-controlled-with-diet-and-exercise-alone
#8
Steven G Terra, Kristen Focht, Melanie Davies, Juan Frias, Giuseppe Derosa, Amanda Darekar, Gregory Golm, Jeremy Johnson, Didier Saur, Brett Lauring, Sam Dagogo-Jack
AIMS: A Phase 3 study to evaluate the efficacy and safety of ertugliflozin monotherapy in patients with type 2 diabetes. MATERIALS AND METHODS: This was a 52-week, double-blind, multi-center, randomized, parallel-group study with a 26-week, placebo-controlled treatment period (Phase A) followed by a 26-week active-controlled treatment period (Phase B) in 461 men and women, ≥18 years of age and inadequate glycaemic control (HbA1c 7.0-10.5% [53-91 mmol/mol], inclusive) despite diet and exercise...
January 24, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28113804/scalable-semi-automatic-annotation-for-multi-camera-person-tracking
#9
Jorge Nino, Andres Frias-Velazquez, Nyan Bo Bo, Maarten Slembrouck, Junzhi Guan, Glen Debard, Bart Vanrumste, Tinne Tuytelaars, Wilfried Philips
This paper proposes a generic methodology for semi-automatic generation of reliable position annotations for evaluating multi-camera people-trackers on large video datasets. Most of the annotation data is computed automatically, by estimating a consensus tracking result from multiple existing trackers and people detectors and classifying it as either reliable or not. A small subset of the data, composed of tracks with insufficient reliability is verified by a human using a simple binary decision task, a process faster than marking the correct person position...
March 29, 2016: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
https://www.readbyqxmd.com/read/28107169/genetic-diagnosis-of-%C3%AE-1-antitrypsin-deficiency-using-dna-from-buccal-swab-and-serum-samples
#10
Irene Belmonte, Miriam Barrecheguren, Cristina Esquinas, Esther Rodríguez, Marc Miravitlles, Francisco Rodríguez-Frías
BACKGROUND: α1-Antitrypsin deficiency (AATD) is associated with a high risk of developing lung and liver disease. Despite being one of the most common hereditary disorders worldwide, AATD remains under-diagnosed and prolonged delays in diagnosis are usual. The aim of this study was to validate the use of buccal swab samples and serum circulating DNA for the complete laboratory study of AATD. METHODS: Sixteen buccal swab samples from previously characterized AATD patients were analyzed using an allele-specific genotyping assay and sequencing method...
January 20, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28096449/specific-glucoside-transporters-influence-septal-structure-and-function-in-the-filamentous-heterocyst-forming-cyanobacterium-anabaena-sp-strain-pcc-7120
#11
Mercedes Nieves-Morión, Sigal Lechno-Yossef, Rocío López-Igual, José E Frías, Vicente Mariscal, Dennis J Nürnberg, Conrad W Mullineaux, C Peter Wolk, Enrique Flores
: When deprived of combined nitrogen, some filamentous cyanobacteria contain two cell types: vegetative cells that fix CO2 through oxygenic photosynthesis and heterocysts that are specialized in N2 fixation. In the diazotrophic filament, the vegetative cells provide the heterocysts with reduced carbon (mainly in the form of sucrose) and heterocysts provide the vegetative cells with combined nitrogen. Septal junctions traverse peptidoglycan through structures known as nanopores, and appear to mediate intercellular molecular transfer that can be traced with fluorescent markers, including the sucrose analog esculin (a coumarin glucoside) that is incorporated into the cells...
January 17, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28077520/hepatitis-e-virus-infection-in-anti-hev-igg-carryinfing-patients-after-successful-hcv-treatment-reactivation-or-reinfection
#12
Antonio Rivero-Juarez, Mario Frias, Pedro Lopez-Lopez, María de Los Angeles Risalde, Teresa Brieva, Isabel Machuca, Angela Camacho, Antonio Martinez-Peinado, Jose Carlos Gomez-Villamandos, Antonio Rivero
Although Hepatitis E (HEV) is regarded asa self-limiting infection and anti-HEV antibodies seem toprotect against reinfection, its pathogenesis is not well established. We describe two cases of acute symptomatic HEV infection after Hepatitis C therapy in patients carrying anti-HEV IgG antibodies raising two major questions: reactivation or reinfection?
January 11, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28074043/correction-dasatinib-a-src-inhibitor-sensitizes-liver-metastatic-colorectal-carcinoma-to-oxaliplatin-in-tumors-with-high-levels-of-phospho-src
#13
Marco Perez, Antonio Lucena-Cacace, Luis Miguel Marín-Gómez, Javier Padillo-Ruiz, Maria Jose Robles-Frias, Carmen Saez, Rocio Garcia-Carbonero, Amancio Carnero
No abstract text is available yet for this article.
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/28069920/folding-but-not-surface-area-expansion-is-associated-with-cellular-morphological-maturation-in-the-fetal-cerebral-cortex
#14
Xiaojie Wang, Colin Studholme, Peta L Grigsby, Antonio E Frias, Verginia C Cuzon Carlson, Christopher D Kroenke
: Altered macroscopic anatomical characteristics of the cerebral cortex have been identified in individuals affected by various neurodevelopmental disorders. However, the cellular developmental mechanisms that give rise to these abnormalities are not understood. Recently, advances in image reconstruction of diffusion magnetic resonance imaging (diffusion MRI) have made possible high resolution in utero measurements of water diffusion anisotropy in the fetal brain. Here, diffusion anisotropy within the developing fetal cerebral cortex is longitudinally characterized in the rhesus macaque, focusing on gestation days (G) 85 through G135 of the 165 day term...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28067990/familial-hepatitis-e-outbreak-linked-to-wild-boar-meat-consumption
#15
A Rivero-Juarez, M Frias, A Martinez-Peinado, M A Risalde, D Rodriguez-Cano, A Camacho, I García-Bocanegra, F Cuenca-Lopez, J C Gomez-Villamandos, A Rivero
An HIV-infected patient was diagnosed with acute hepatitis E infection in our hospital. An epidemiological inquiry was performed to collect demographic, food and animal exposure variables in order to identify the potential route of transmission. The patient reported that his family traditionally hunted wild boar for food. All family members were analysed for hepatitis E virus infection. Additionally, route of transmission by wild boar meat consumption and prevalence of HEV infection among wild boar from the same hunting area were investigated...
January 9, 2017: Zoonoses and Public Health
https://www.readbyqxmd.com/read/28066799/the-study-protocol-for-a-non-randomized-controlled-clinical-trial-using-a-genotype-guided-strategy-in-a-dataset-of-patients-who-undergone-percutaneous-coronary-intervention-with-stent
#16
Cristina Lucía Dávila-Fajardo, Jesús Sánchez-Ramos, Xando Diaz- Villamarín, Luis Javier Martínez-González, Pablo Toledo Frías, Susana Martínez Huertas, Francisco Burillo Gómez, Juan Caballero Borrego, Alicia Bautista Pavés, Mª Carmen Marín Guzmán, José Antonio Ramirez Hernández, Concepción Correa Vilches, Jose Cabeza Barrera
This article contains data related to the research article entitled "Results of genotype-guided antiplatelet therapy in patients undergone percutaneous coronary intervention with stent" (J. Sánchez-Ramos, C.L. Dávila-Fajardo, P. Toledo Frías, X. Díaz Villamarín, L.J. Martínez-González, S. Martínez Huertas, F. Burillo Gómez, J. Caballero Borrego, A. Bautista Pavés, M.C. Marín Guzmán, J.A. Ramirez Hernández, C. Correa Vilches, J. Cabeza Barrera, 2016) (1). This data article reports, for the first time, about the non-randomized clinical trial protocol that check if CYP2C19/ABCB1 genotype-guided strategy in which the choice of antiplatelet therapy is based on the genetic test, reduces the rates of cardiovascular events and bleeding compared to a non-tailored strategy in patients undergone percutaneous coronary intervention (PCI) with stent...
February 2017: Data in Brief
https://www.readbyqxmd.com/read/28062871/-chronic-diarrhea-in-the-diabetic-a-review-of-the-literature
#17
Juan Sebastián Frías Ordoñez, William Otero Regino
The association of diarrhea with diabetes mellitus has been known for more than 70 years. In diabetic patients its prevalence is around 20%.Its clinical manifestations are diverse, and represents a diagnostic and therapeutic challenge.There are certain diagnoses of higher prevalence in diabetic patients than in the general population.The different related etiologies can be adequately diagnosed through the clinical history and complementary diagnostic tests.The medications used by the diabetic patient to manage their disease often cause chronic diarrhea, so the pharmacological background should be studied at the time of the study of diarrhea...
October 2016: Revista de Gastroenterología del Perú: órgano Oficial de la Sociedad de Gastroenterología del Perú
https://www.readbyqxmd.com/read/28051797/%C3%A2-sofosbuvir-and-daclatasvir-in-mono-and-hiv-coinfected-patients-with-recurrent-hepatitis-c-after-liver-transplant
#18
Lluís Castells, Jordi Llaneras, Isabel Campos-Varela, Itxarone Bilbao, Manel Crespo, Oscar Len, Francisco Rodríguez-Frías, Ramon Charco, Teresa Salcedo, Juan Ignacio Esteban, Rafael Esteban-Mur
:  Background and aims. Pegylated interferon (Peg-INF) and ribavirin (RBV) based therapy is suboptimal and poorly tolerated. We evaluated the safety, tolerability and efficacy of a 24-week course of sofosbuvir plus daclatasvir without ribavirin for the treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) in both HCV-monoinfected and human immunodeficiency virus (HIV)-HCV coinfected patients. MATERIAL AND METHODS: We retrospectively evaluated 22 consecutive adult LT recipients (16 monoinfected and 6 coinfected with HIV) who received a 24-week course of sofosbuvir plus daclatasvir treatment under an international compassionate access program...
January 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28040474/deep-sequencing-in-the-management-of-hepatitis-virus-infections
#19
REVIEW
Josep Quer, Francisco Rodríguez-Frias, Josep Gregori, David Tabernero, Maria Eugenia Soria, Damir García-Cehic, Maria Homs, Albert Bosch, Rosa María Pintó, Juan Ignacio Esteban, Esteban Domingo, Celia Perales
The hepatitis viruses represent a major public health problem worldwide. Procedures for characterization of the genomic composition of their populations, accurate diagnosis, identification of multiple infections, and information on inhibitor-escape mutants for treatment decisions are needed. Deep sequencing methodologies are extremely useful for these viruses since they replicate as complex and dynamic quasispecies swarms whose complexity and mutant composition are biologically relevant traits. Population complexity is a major challenge for disease prevention and control, but also an opportunity to distinguish among related but phenotypically distinct variants that might anticipate disease progression and treatment outcome...
December 28, 2016: Virus Research
https://www.readbyqxmd.com/read/28025823/hla-alleles-are-genetic-markers-for-susceptibility-and-resistance-towards-leprosy-in-a-mexican-mestizo-population
#20
Maribel Aguilar-Medina, Monica Escamilla-Tilch, Luis Octavio Frías-Castro, Geovanni Romero-Quintana, Iris Estrada-García, Sergio Estrada-Parra, Julio Granados, Eliakym Arambula Meraz, Guzman Sánchez-Schmitz, Shabaana Abdul Khader, Javier Rangel-Moreno, Rosalío Ramos-Payán
Despite the use of multidrug therapy, leprosy remains endemic in some countries. The association of several human leucocyte antigen (HLA) alleles and gene polymorphisms with leprosy has been demonstrated in many populations, but the major immune contributors associated to the spectrum of leprosy have not been defined yet. In this study, genotyping of HLA-A, -B, -DR, and -DQ alleles was performed in leprosy patients (n = 113) and control subjects (n = 117) from the region with the highest incidence for the disease in México...
December 27, 2016: Annals of Human Genetics
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