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https://www.readbyqxmd.com/read/28212463/efficacy-and-tolerability-of-an-inhaled-selective-glucocorticoid-receptor-modulator-azd5423-in-copd-patients-phase-ii-study-results
#1
Piotr Kuna, Magnus Aurivillius, Carin Jorup, Susanne Prothon, Ziad Taib, Staffan Edsbäcker
AZD5423 is a novel, inhaled, selective glucocorticoid receptor modulator (SGRM), which in an allergen challenge model in asthmatics improved lung function and airway hyper-reactivity. In the current trial, AZD5423 was for the first time tested in patients with chronic obstructive pulmonary disease (COPD). In this double-blind, randomised and parallel group study, we examined airway and systemic effects of two doses of AZD5423, inhaled via Turbuhaler for 12 weeks, in 353 symptomatic COPD patients (average pre-bronchodilator forced expiratory volume in one second (FEV1) at screening was 50-52% of predicted normal)...
February 17, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28212410/a-high-throughput-genetic-screen-identifies-previously-uncharacterized-borrelia-burgdorferi-genes-important-for-resistance-against-reactive-oxygen-and-nitrogen-species
#2
Meghan E Ramsey, Jenny A Hyde, Diana N Medina-Perez, Tao Lin, Lihui Gao, Maureen E Lundt, Xin Li, Steven J Norris, Jon T Skare, Linden T Hu
Borrelia burgdorferi, the causative agent of Lyme disease in humans, is exposed to reactive oxygen and nitrogen species (ROS and RNS) in both the tick vector and vertebrate reservoir hosts. B. burgdorferi contains a limited repertoire of canonical oxidative stress response genes, suggesting that novel gene functions may be important for protection of B. burgdorferi against ROS or RNS exposure. Here, we use transposon insertion sequencing (Tn-seq) to conduct an unbiased search for genes involved in resistance to nitric oxide, hydrogen peroxide, and tertiary-butyl hydroperoxide in vitro...
February 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28211974/whole-exome-sequencing-identified-1-base-pair-novel-deletion-in-bcl2-associated-athanogene-3-bag3-gene-associated-with-severe-dilated-cardiomyopathy-dcm-requiring-heart-transplant-in-multiple-family-members
#3
Muhammad Arshad Rafiq, Ayeshah Chaudhry, Melanie Care, Danna A Spears, Chantal F Morel, Robert M Hamilton
Dilated cardiomyopathy (DCM) is characterized by dilation and impaired contraction of the left ventricle or both ventricles. Among hereditary DCM, the genetic causes are heterogeneous, and include mutations encoding cytoskeletal, nucleoskeletal, mitochondrial, and calcium-handling proteins. We report three severely affected males, in a four-generation pedigree, with DCM phenotype who underwent cardiac transplant. Cardiomegaly with marked biventricular dilation and fibrosis were noticeable histopathological findings...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28211900/amyloid-%C3%AE-oligomers-interact-with-neurexin-and-diminish-neurexin-mediated-excitatory-presynaptic-organization
#4
Yusuke Naito, Yuko Tanabe, Alfred Kihoon Lee, Edith Hamel, Hideto Takahashi
Alzheimer's disease (AD) is characterized by excessive production and deposition of amyloid-beta (Aβ) proteins as well as synapse dysfunction and loss. While soluble Aβ oligomers (AβOs) have deleterious effects on synapse function and reduce synapse number, the underlying molecular mechanisms are not well understood. Here we screened synaptic organizer proteins for cell-surface interaction with AβOs and identified a novel interaction between neurexins (NRXs) and AβOs. AβOs bind to NRXs via the N-terminal histidine-rich domain (HRD) of β-NRX1/2/3 and alternatively-spliced inserts at splicing site 4 of NRX1/2...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211892/high-throughput-in-situ-cell-electroporation-microsystem-for-parallel-delivery-of-single-guide-rnas-into-mammalian-cells
#5
Shengtai Bian, Yicen Zhou, Yawei Hu, Jing Cheng, Xiaofang Chen, Youchun Xu, Peng Liu
Arrayed genetic screens mediated by the CRISPR/Cas9 technology with single guide RNA (sgRNA) libraries demand a high-throughput platform capable of transfecting diverse cell types at a high efficiency in a genome-wide scale for detection and analysis of sophisticated cellular phenotypes. Here we developed a high-throughput in situ cell electroporation (HiCEP) microsystem which leveraged the superhydrophobic feature of the microwell array to achieve individually controlled conditions in each microwell and coupled an interdigital electrode array chip with the microwells in a modular-based scheme for highly efficient delivery of exogenous molecules into cells...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211844/a-tool-named-iris-for-versatile-high-throughput-phenotyping-in-microorganisms
#6
George Kritikos, Manuel Banzhaf, Lucia Herrera-Dominguez, Alexandra Koumoutsi, Morgane Wartel, Matylda Zietek, Athanasios Typas
Advances in our ability to systematically introduce and track controlled genetic variance in microorganisms have, in the past decade, fuelled high-throughput reverse genetics approaches. When coupled to quantitative readouts, such approaches are extremely powerful at elucidating gene function and providing insights into the underlying pathways and the overall cellular network organization. Yet, until now, all efforts to quantify microbial macroscopic phenotypes have been restricted to monitoring growth in a small number of model microorganisms...
February 17, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28211522/structure-and-polymorphisms-of-the-major-histocompatibility-complex-in-the-oriental-stork-ciconia-boyciana
#7
Hiroki Tsuji, Yukio Taniguchi, Shintaro Ishizuka, Hirokazu Matsuda, Takahisa Yamada, Kazuaki Naito, Hiroaki Iwaisaki
The major histocompatibility complex (MHC) is highly polymorphic and plays a central role in the vertebrate immune system. Despite its functional consistency, the MHC genomic structure differs substantially among organisms. In birds, the MHCs of Galliformes and the Japanese crested ibis (Pelecaniformes) are well-characterized, but information about other avian MHCs remains scarce. The Oriental stork (Ciconia boyciana, order Ciconiiformes) is a large endangered migrant. The current Japanese population of this bird originates from a few founders; thus, understanding the genetic diversity among them is critical for effective population management...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211456/learning-from-data-to-design-functional-materials-without-inversion-symmetry
#8
Prasanna V Balachandran, Joshua Young, Turab Lookman, James M Rondinelli
Accelerating the search for functional materials is a challenging problem. Here we develop an informatics-guided ab initio approach to accelerate the design and discovery of noncentrosymmetric materials. The workflow integrates group theory, informatics and density-functional theory to uncover design guidelines for predicting noncentrosymmetric compounds, which we apply to layered Ruddlesden-Popper oxides. Group theory identifies how configurations of oxygen octahedral rotation patterns, ordered cation arrangements and their interplay break inversion symmetry, while informatics tools learn from available data to select candidate compositions that fulfil the group-theoretical postulates...
February 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28211264/genetics-diagnosis-and-clinical-features-of-congenital-hypodysfibrinogenaemia-a-systematic-literature-review-and-report-of-a-novel-mutation
#9
A Casini, T Brungs, C Lavenu-Bombled, R Vilar, M Neerman-Arbez, P de Moerloose
BACKGROUND: Hypodysfibrinogenaemia is a rare disease characterised by decreased levels of a dysfunctional fibrinogen. It shares features with both hypo- and dysfibrinogenaemia, although with specific molecular patterns and clinical phenotypes. OBJECTIVES: To better define the genetics, the diagnosis and the clinical features of hypodysfibrinogenaemia. PATIENTS/METHODS: A systematic literature search led to 167 records. After removal of duplicates, abstract screening and full-text reviewing, 56 molecular and/or clinical studies were analysed, including a novel FGB missense mutation in a woman with a mild bleeding phenotype...
February 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28210761/the-evolutionary-loss-of-rnai-key-determinants-in-kinetoplastids-as-a-multiple-sporadic-phenomenon
#10
Andrey V Matveyev, João M P Alves, Myrna G Serrano, Vladimir Lee, Ana M Lara, William A Barton, André G Costa-Martins, Stephen M Beverley, Erney P Camargo, Marta M G Teixeira, Gregory A Buck
We screened the genomes of a broad panel of kinetoplastid protists for genes encoding proteins associated with the RNA interference (RNAi) system using probes from the Argonaute (AGO1), Dicer1 (DCL1), and Dicer2 (DCL2) genes of Leishmania brasiliensis and Crithidia fasciculata. We identified homologs for all the three of these genes in the genomes of a subset of these organisms. However, several of these organisms lacked evidence for any of these genes, while others lacked only DCL2. The open reading frames encoding these putative proteins were structurally analyzed in silico...
February 16, 2017: Journal of Molecular Evolution
https://www.readbyqxmd.com/read/28210256/transcriptomic-analysis-of-the-innate-antiviral-immune-response-in-porcine-intestinal-epithelial-cells-influence-of-immunobiotic-lactobacilli
#11
Leonardo Albarracin, Hisakazu Kobayashi, Hikaru Iida, Nana Sato, Tomonori Nochi, Hisashi Aso, Susana Salva, Susana Alvarez, Haruki Kitazawa, Julio Villena
Lactobacillus rhamnosus CRL1505 and Lactobacillus plantarum CRL1506 are immunobiotic strains able to increase protection against viral intestinal infections as demonstrated in animal models and humans. To gain insight into the host-immunobiotic interaction, the transcriptomic response of porcine intestinal epithelial (PIE) cells to the challenge with viral molecular associated pattern poly(I:C) and the changes in the transcriptomic profile induced by the immunobiotics strains CRL1505 and CRL1506 were investigated in this work...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28209807/blast-injury-of-the-ear-by-massive-explosion-a-review-of-41-cases
#12
Stanislas Ballivet de Régloix, A Crambert, O Maurin, Q Lisan, S Marty, Y Pons
BACKGROUND: Blast injuries in modern warfare are common, and the ear is often affected as it is an effective pressure transducer. This study aimed to evaluate military blast injuries of the ear. METHODS: From May 2002 to October 2014, all patients referred to two military hospitals near Paris, France following exposure to massive explosions were analysed. RESULTS: Among the 41 patients (82 ears), 36 of them reported tinnitus, 25 hearing loss, 14 earache and 8 vertigo...
February 16, 2017: Journal of the Royal Army Medical Corps
https://www.readbyqxmd.com/read/28209778/role-for-dithiolopyrrolones-in-disrupting-bacterial-metal-homeostasis
#13
Andrew N Chan, Anthony L Shiver, Walter J Wever, Sayyeda Zeenat A Razvi, Matthew F Traxler, Bo Li
Natural products harbor unique and complex structures that provide valuable antibiotic scaffolds. With an increase in antibiotic resistance, natural products once again hold promise for new antimicrobial therapies, especially those with unique scaffolds that have been overlooked due to a lack of understanding of how they function. Dithiolopyrrolones (DTPs) are an underexplored class of disulfide-containing natural products, which exhibit potent antimicrobial activities against multidrug-resistant pathogens...
February 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28209762/identification-of-genes-in-saccharomyces-cerevisiae-that-are-haploinsufficient-for-overcoming-amino-acid-starvation
#14
Nancy S Bae, Andrew P Seberg, Leslie P Carroll, Mark J Swanson
The yeast Saccharomyces cerevisiae responds to amino acid deprivation by activating a pathway conserved in eukaryotes to overcome the starvation stress. We have screened the entire yeast heterozygous deletion collection to identify strains haploinsufficient for growth in the presence of sulfometuron methyl, which causes starvation for isoleucine and valine. We have discovered that cells devoid of MET15 are sensitive to sulfometuron methyl, and loss of heterozygosity at the MET15 locus can complicate screening the heterozygous deletion collection...
February 16, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28209494/effect-of-early-onset-preeclampsia-on-cardiovascular-risk-in-the-fifth-decade-of-life
#15
Anouk Bokslag, Pim W Teunissen, Constantijn Franssen, Floortje van Kesteren, Otto Kamp, Wessel Ganzevoort, Walter J Paulus, Christianne J M de Groot
BACKGROUND: Women with hypertensive disorders in pregnancy, in particular early-onset preeclampsia, are at increased risk of developing cardiovascular disease later in life. These women have a more than two-fold increased risk to die from cardiovascular diseases. Most studies focused on identification of risk factors shortly after pregnancy. Less is known on the prevalence of risk factors or actual signs of cardiovascular disease 5 - 20 years later. The presence of hypertension or metabolic syndrome can be seen as an opportunity for preventive interventions to reduce the development of severe cardiovascular diseases like myocardial infarction and stroke...
February 13, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28209186/identification-of-immune-protective-genes-of-eimeria-maxima-through-cdna-expression-library-screening
#16
XinChao Yang, MengHui Li, JianHua Liu, YiHong Ji, XiangRui Li, LiXin Xu, RuoFeng Yan, XiaoKai Song
BACKGROUND: Eimeria maxima is one of the most prevalent Eimeria species causing avian coccidiosis, and results in huge economic loss to the global poultry industry. Current control strategies, such as anti-coccidial medication and live vaccines have been limited because of their drawbacks. The third generation anticoccidial vaccines including the recombinant vaccines as well as DNA vaccines have been suggested as a promising alternative strategy. To date, only a few protective antigens of E...
February 16, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28209174/mouse-genomic-screen-reveals-novel-host-regulator-of-metastasis
#17
Toni Celià-Terrassa, Yibin Kang
Tumor cells have to overcome challenges in the host tissue microenvironment to metastasize successfully to distant organs. In a recent Nature study, a genome-wide functional screen demonstrated that deficiency of the sphingosine-1-phoshate (S1P) transporter gene Spns2 in endothelium increased immune-mediated cell killing by T cells and natural killer (NK) cells, thereby suppressing metastatic colonization.
February 16, 2017: Genome Biology
https://www.readbyqxmd.com/read/28209040/-establishment-and-application-effect-appraisement-of-community-chronic-obstructive-pulmonary-disease-integrated-management-system
#18
D X Zhao, S Y Chen, Y M Zhou, X C Li, W F Zou, X M Chen, P X Ran
Objective: To establish the COPD community integrated management system suitable for our national situation and assess its effects in the prevention and treatment for COPD. Methods: The COPD community integrated management system based on the electronic management system was established, including the functional modules of preliminary screening for COPD, electronic health record, grading management and dual referral system, ect. Two townships were randomly selected from the rural areas in north Guangdong as Observational Community and Control Community, respectively...
February 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28208946/the-impact-of-intimate-male-partner-violence-on-women-s-sexual-function-a-study-in-iran
#19
Safieh Jamali, Shohreh Javadpour
INTRODUCTION: Sexuality is an integral part of a woman's life. A variety of factors can affect a woman's sexuality, among them physical disorders, social-religious beliefs, age, psychological factors, depression, mental tension, disbelief, an unfulfilling relationship with one's spouse and emotional and physical violence. AIM: The present study aimed to explore the rate of domestic violence against women and its impact on women's sexuality. MATERIALS AND METHODS: This cross-sectional study was conducted on 813 women referring to the gynaecology clinics of Jahrom, Iran, from April to October 2015...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28208801/atomic-force-microscopy-a-powerful-tool-to-address-scaffold-design-in-tissue-engineering
#20
Marica Marrese, Vincenzo Guarino, Luigi Ambrosio
Functional polymers currently represent a basic component of a large range of biological and biomedical applications including molecular release, tissue engineering, bio-sensing and medical imaging. Advancements in these fields are driven by the use of a wide set of biodegradable polymers with controlled physical and bio-interactive properties. In this context, microscopy techniques such as Atomic Force Microscopy (AFM) are emerging as fundamental tools to deeply investigate morphology and structural properties at micro and sub-micrometric scale, in order to evaluate the in time relationship between physicochemical properties of biomaterials and biological response...
February 13, 2017: Journal of Functional Biomaterials
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