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Hit II

Aditi Gupta, Garima Juyal, Ajit Sood, Vandana Midha, Keiko Yamazaki, Arnau Vich Vila, Motohiro Esaki, Toshiyuki Matsui, Atsushi Takahashi, Michiaki Kubo, Rinse K Weersma, B K Thelma
The first ever genome-wide association study (GWAS) of ulcerative colitis in genetically distinct north Indian population identified two novel genes namely CFB and SLC44A4. Considering their biological relevance, we investigated allelic/genetic heterogeneity in these genes among ulcerative colitis cohorts of north Indian, Japanese and Dutch origin using high-density ImmunoChip case-control genotype data. Comparative linkage disequilibrium profiling and test of association were performed. Of the 28 CFB SNPs, similar strength of association was observed for rs4151657 (novel ulcerative colitis GWAS SNP) in north Indians (P=1...
October 19, 2016: European Journal of Human Genetics: EJHG
Raquel T Lima, Diana Sousa, Ana M Paiva, Andreia Palmeira, João Barbosa, Madalena Pedro, Madalena M Pinto, Emília Sousa, M Helena Vasconcelos
(1) Background: Our previous studies unveiled the hit thioxanthone TXA1 as an inhibitor of P-glycoprotein (drug efflux pump) and of human tumor cells growth, namely of melanoma cells. Since TXA1 is structurally similar to lucanthone (an autophagy inhibitor and apoptosis inducer) and to N(10)-substituted phenoxazines (isosteres of thioxanthones, and autophagy inducers), this study aimed at further assessing its cytotoxic mechanism and evaluating its potential as an autophagy modulator in A375-C5 melanoma cells; (2) Methods: Flow cytometry with propidium iodide (PI) for cell cycle profile analysis; Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, flow cytometry with Annexin V/PI labeling and Western blot for apoptosis analysis were conducted...
October 10, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ralf Ulrich Trappe, Marianne Sinn, Hanno Riess
There is only limited data for the use of direct oral anticoagulants (DOACs) in tumor patients and no data from prospective randomised trials comparing DOACs to the current standard care: low molecular weight heparine (LMWH). Therefore, DOACs must be used with caution and should be restricted to tumor patients with (1) contraindications for LMWH (e.g. HIT II, phobia of syringe) or (2) to the situations of prolonged anticoagulation after initial therapy with LMWH. Cancer-associated disorders as well as side effects of chemotherapy as nausea and emesis have to be considered as well as potential substance-specific interactions...
September 2016: Deutsche Medizinische Wochenschrift
Thomas C A Smith, Antony M Carr, Adam C Eyre-Walker
Across independent cancer genomes it has been observed that some sites have been recurrently hit by single nucleotide variants (SNVs). Such recurrently hit sites might be either (i) drivers of cancer that are postively selected during oncogenesis, (ii) due to mutation rate variation, or (iii) due to sequencing and assembly errors. We have investigated the cause of recurrently hit sites in a dataset of >3 million SNVs from 507 complete cancer genome sequences. We find evidence that many sites have been hit significantly more often than one would expect by chance, even taking into account the effect of the adjacent nucleotides on the rate of mutation...
2016: PeerJ
Angélique Vétillard, Wafa Bouzid
Animal venoms are complex mixtures containing simple organic molecules, proteins, peptides, and other bioactive elements with extraordinary biological properties associated with their ability to act on a number of molecular receptors in the process of incapacitating their target organisms. In such a context, arthropod venoms are invaluable sources of bioactive substances, with therapeutic interest but the limited availability of some venom such as those from ants, has restricted the potential that these biomolecules could represent...
2016: Biologie Aujourd'hui
Laszlo A Erdodi, Chantalle L Pelletier, Robert M Roth
Elevations on certain Conners' CPT-II scales are known to be associated with invalid responding. However, scales and cutoffs vary across studies. In addition, the methodology behind developing performance validity tests (PVTs) has been challenged for mistaking true impairment for noncredible presentation. Using ability-based tests as a PVT makes clinicians especially vulnerable to this criticism. The present study examined the ability of CPT-II to dissociate effort from impairment in 47 adults clinically referred for neuropsychological assessment...
September 23, 2016: Applied Neuropsychology. Adult
Cong Ma, Xiao Yang, Peter J Lewis
Bacterial transcription is a proven target for antibacterial research. However, most of the known inhibitors targeting transcription are from natural extracts or are hits from screens where the binding site remains unidentified. Using an RNA polymerase holoenzyme homology structure from the model Gram-positive organism Bacillus subtilis, we created a pharmacophore model and used it for in silico screening of a publicly available library for compounds able to inhibit holoenzyme formation. The hits demonstrated specific affinity to bacterial RNA polymerase and excellent activity using in vitro assays and showed no binding to the equivalent structure from human RNA polymerase II...
January 8, 2016: ACS Infectious Diseases
Ohad Cohen, William Valentine
BACKGROUND: Continuous subcutaneous insulin infusion (CSII) is used less for type 2 than for type 1 diabetes because of inconsistencies in evidence of effectiveness. We reviewed published guidelines on intensive insulin therapy in type 2 diabetes to assess whether updating of guidance is needed with respect to evidence used and recommendations for CSII in diabetes management. METHODS: A literature review was performed to identify published national and international guidelines on type 2 diabetes management...
September 12, 2016: Journal of Diabetes Science and Technology
Beatriz López-Luengo, Alejandro González-Andrade, Miguel García-Cobo
OBJECTIVE: This study analyzed attentional performance in patients with schizophrenia during a continuous performance task requiring a high response rate. METHOD: The Conners' Continuous Performance Test-II (CPT-II) was administered to 64 patients with schizophrenia and 64 healthy comparison subjects. A cross-sectional design was used in order to allow analysis of the means between patients and healthy subjects. Differences in performance were assessed for significance using ANCOVA...
September 12, 2016: Archives of Clinical Neuropsychology: the Official Journal of the National Academy of Neuropsychologists
Cristian Álvarez, Rodrigo Ramírez-Campillo, Cristian Martínez, Mauricio Castro-Sepúlveda, Johnattan Cano-Montoya, Rodrigo Mancilla, Marcelo Flores-Opazo
BACKGROUND: The aim of this study was to assess the effects of three exercise training program in the adaptation of the heart rate recovery of patients with insulin resistance. METHODS: We studied 43 women with insulin resistance, which were assigned to three training groups: i) high intensity interval training (HIT, age 39.0 ± 10 y), ii) strength training (ST, age 33.9 ± 9.4 y), iii) mixed training of HIT+ST (MIXT, age 43.3 ± 8.1 y), and iv) and control group (CG, age 40...
September 8, 2016: Journal of Sports Medicine and Physical Fitness
Damien Restagno, Fabienne Venet, Christian Paquet, Ludovic Freyburger, Bernard Allaouchiche, Guillaume Monneret, Jeanne-Marie Bonnet, Vanessa Louzier
Sepsis is characterized by pro- and anti-inflammatory responses following infection. While inflammation is responsible for widespread organ damage, anti-inflammatory mediators lead to immunoparalysis increasing susceptibility to secondary infections (nosocomial pneumonia). We aimed to investigate the impact of bacterial load on survival and cytokine release in a two-hit murine (C57BL/6J) model of CLP followed by P. aeruginosa pneumonia. Plasmatic TNFα, IL-6, IL-10, sTNFr I and II were quantified until 13 days...
2016: PloS One
Qosay A Al-Balas, Mohammad A Hassan, Nizar A Al-Shar'i, Nizar M Mhaidat, Ammar M Almaaytah, Fatima M Al-Mahasneh, Israa H Isawi
BACKGROUND: The glyoxalase system including two thiol-dependent enzymes, glyoxalase I (Glo-I) and glyoxalase II, plays an important role in a ubiquitous metabolic pathway involved in cellular detoxification of cytotoxic 2-oxoaldehydes. Tumor cells have high glycolytic activity, leading to increased cellular levels of these toxic metabolites. The increased activity of the detoxification system in cancerous cells makes this pathway a viable target for developing novel anticancer agents...
2016: Drug Design, Development and Therapy
Alvaro Cortes Cabrera, Daniel Lucena-Agell, Mariano Redondo-Horcajo, Isabel Barasoain, J Fernando Díaz, Bernhard Fasching, Paula M Petrone
Predicting the cellular response of compounds is a challenge central for the discovery of new drugs. Compound biological signatures have risen as a way of representing the perturbation produced by a compound in the cell. However, their ability to encode specific phenotypic information and generating tangible predictions remains unknown, mainly because of the inherent noise in such data sets. In this work, we statistically aggregate signal from several biological signatures to find compounds that produce a desired phenotype in the cell...
August 26, 2016: ACS Chemical Biology
Fábio Caetano Oliveira Leme, Eduardo Toshiyuki Moro, Alexandre Alberto Fontana Ferraz
BACKGROUND AND OBJECTIVES: Peribulbar anesthesia (PBA) has emerged as a safer option compared with intraconal retrobulbar block. Still, PBA may not be considered without risk. Numerous complications have been described when performing this technique. This report aims to describe a rare case of amaurosis and contralateral paralysis while attempting to perform a PBA. CASE REPORT: Male patient, 75-year old, physical status ASA II, undergoing cataract surgery by phacoemulsification with intraocular lens implantation...
August 20, 2016: Revista Brasileira de Anestesiologia
Benedict C S Cross, Steffen Lawo, Caroline R Archer, Jessica R Hunt, Joanne L Yarker, Alessandro Riccombeni, Annette S Little, Nicola J McCarthy, Jonathan D Moore
Components of the type II CRISPR-Cas complex in bacteria have been used successfully in eukaryotic cells to facilitate rapid and accurate cell line engineering, animal model generation and functional genomic screens. Such developments are providing new opportunities for drug target identification and validation, particularly with the application of pooled genetic screening. As CRISPR-Cas is a relatively new genetic screening tool, it is important to assess its functionality in a number of different cell lines and to analyse potential improvements that might increase the sensitivity of a given screen...
2016: Scientific Reports
Rodolfo I Meneguette, Geraldo P R Filho, Daniel L Guidoni, Gustavo Pessin, Leandro A Villas, Jó Ueyama
Intelligent Transportation Systems (ITS) rely on Inter-Vehicle Communication (IVC) to streamline the operation of vehicles by managing vehicle traffic, assisting drivers with safety and sharing information, as well as providing appropriate services for passengers. Traffic congestion is an urban mobility problem, which causes stress to drivers and economic losses. In this context, this work proposes a solution for the detection, dissemination and control of congested roads based on inter-vehicle communication, called INCIDEnT...
2016: PloS One
Nuno A L Pereira, Francesc X Sureda, Maria Pérez, Mercedes Amat, Maria M M Santos
Enantiopure tryptophanol is easily obtained from the reduction of its parent natural amino acid trypthophan (available from the chiral pool), and can be used as chiral auxiliary/inductor to control the stereochemical course of a diastereoselective reaction. Furthermore, enantiopure tryptophanol is useful for the syntheses of natural products or biological active molecules containing the aminoalcohol functionality. In this communication, we report the development of a small library of indolo[2,3-a]quinolizidines and evaluation of their activity as N-Methyl d-Aspartate (NMDA) receptor antagonists...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Posen Lee, Hung-Yu Lin, Chin-Hsuan Liu, Wen-Shian Lu, Ching-Lin Hsieh
OBJECTIVE: The Conners' Continuous Performance Test II (CCPT-II) is one of the most commonly used tests of sustained attention in schizophrenia. To manage and monitor sustained attention deficits in schizophrenia, clinicians have to reliably assess the degree of attention impairment. The purpose of our study was to determine the relative and absolute reliability of the CCPT-II in schizophrenia. METHOD: The final sample was a total of 108 patients with schizophrenia...
August 9, 2016: Archives of Clinical Neuropsychology: the Official Journal of the National Academy of Neuropsychologists
Yoshinori Hasegawa, Takashi Watanabe, Masaki Takazawa, Osamu Ohara, Shin Kubota
In most animals, aging is an irreversible process; however the species Turritopsis sp. has been observed to undergo a rejuvenation process as many as 14 times. In the present study, we used multiplexed RNA libraries to obtain the transcriptome from four developmental stages (St) of Turritopsis sp., including (I) immature medusa, (II) dumpling, (III) dumpling with a short stolon, and (IV) polyp, which had recently rejuvenated. A total of 4.02 billion paired-end reads were assembled de novo, yielding 90,327 contigs...
August 2016: Zoological Science
Tiago Turnes, Rafael Alves de Aguiar, Rogério Santos de Oliveira Cruz, Felipe Domingos Lisbôa, Kayo Leonardo Pereira, Fabrizio Caputo
PURPOSE: Although high-intensity interval training (HIT) seems to promote greater improvements in aerobic parameters than continuous training, the influence of exercise intensity on [Formula: see text] on-kinetics remains under investigation. METHODS: After an incremental test, twenty-one recreationally trained cyclists performed several time-to-exhaustion tests to determine critical power (CP), and the highest intensity (I HIGH), and the lowest exercise duration (T LOW) at which [Formula: see text] is attained during constant exercise...
October 2016: European Journal of Applied Physiology
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