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https://www.readbyqxmd.com/read/28441427/programmable-type-iii-a-crispr-cas-dna-targeting-modules
#1
H Travis Ichikawa, John C Cooper, Leja Lo, Jason Potter, Rebecca M Terns, Michael P Terns
The CRISPR-Cas systems provide invader defense in a wide variety of prokaryotes, as well as technologies for many powerful applications. The Type III-A or Csm CRISPR-Cas system is one of the most widely distributed across prokaryotic phyla, and cleaves targeted DNA and RNA molecules. In this work, we have constructed modules of Csm systems from 3 bacterial species and heterologously expressed the functional modules in E. coli. The modules include a Cas6 protein and a CRISPR locus for crRNA production, and Csm effector complex proteins...
2017: PloS One
https://www.readbyqxmd.com/read/28441230/cochlear-implantation-in-adults-with-asymmetric-hearing-loss-benefits-of-bimodal-stimulation
#2
Maarten Caspar van Loon, Cas Smits, Conrad F Smit, Erik F Hensen, Paul Merkus
OBJECTIVE: This study addresses the outcome of cochlear implantation in addition to hearing aid use in patients with asymmetric sensorineural hearing loss. STUDY DESIGN: Prospective longitudinal study. SETTING: Tertiary referral center. PATIENTS: Seven adults with asymmetric sensorineural hearing loss, i.e., less than 30% aided speech recognition in their worst hearing ear and 60 to 85% speech recognition in their best hearing ear...
April 24, 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28440027/the-crispr-cas9-system-their-delivery-in-vivo-and-ex-vivo-applications-and-clinical-development-by-startups
#3
REVIEW
Minjung Song
The CRISPR/Cas9 gene editing system was originally derived from the prokaryotic adaptive immune system mediated by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated proteins (Cas). The system has been successfully applied to genome editing in eukaryotes and has contributed to remarkable advances in the life sciences, in areas ranging from agriculture to genetic disease therapies. For efficient editing and extending the influence of this system, proper delivery of its components is crucial...
April 25, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28439853/crispr-cas-mediated-in-planta-gene-targeting
#4
Simon Schiml, Friedrich Fauser, Holger Puchta
The recent emergence of the CRISPR/Cas system has boosted the possibilities for precise genome engineering approaches throughout all kingdoms of life. The most common application for plants is targeted mutagenesis, whereby a Cas9-mediated DNA double-strand break (DSB) is repaired by mutagenic nonhomologous end joining (NHEJ). However, the site-specific alteration of a genomic sequence or integration of a transgene relies on the precise repair by homologous recombination (HR) using a suitable donor sequence: this poses a particular challenge in plants, as NHEJ is the preferred repair mechanism for DSBs in somatic tissue...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28439213/a-clinical-perspective-on-the-utility-of-alpha-1-antichymotrypsin-for-the-early-diagnosis-of-calcific-aortic-stenosis
#5
Tatiana Martin-Rojas, Laura Mourino-Alvarez, Felix Gil-Dones, Fernando de la Cuesta, Esther Rosello-Lleti, Carlos M Laborde, Miguel Rivera, Luis Fernando Lopez-Almodovar, Juan Antonio Lopez, Finn Akerstrom, Luis R Padial, Maria G Barderas
BACKGROUND: Calcific aortic stenosis (CAS) is the most common heart valve disease in the elderly, representing an important economic and social burden in developed countries. Currently, there is no way to predict either the onset or progression of CAS, emphasizing the need to identify useful biomarkers for this condition. METHODS: We performed a multi-proteomic analysis on different kinds of samples from CAS patients and healthy donors: tissue, secretome and plasma...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28438998/cas1-and-the-csy-complex-are-opposing-regulators-of-cas2-3-nuclease-activity
#6
MaryClare F Rollins, Saikat Chowdhury, Joshua Carter, Sarah M Golden, Royce A Wilkinson, Joseph Bondy-Denomy, Gabriel C Lander, Blake Wiedenheft
The type I-F CRISPR adaptive immune system in Pseudomonas aeruginosa (PA14) consists of two CRISPR loci and six CRISPR-associated (cas) genes. Type I-F systems rely on a CRISPR RNA (crRNA)-guided surveillance complex (Csy complex) to bind foreign DNA and recruit a trans-acting nuclease (i.e., Cas2/3) for target degradation. In most type I systems, Cas2 and Cas3 are separate proteins involved in adaptation and interference, respectively. However, in I-F systems, these proteins are fused into a single polypeptide...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438939/emergence-and-evolution-of-multidrug-resistant-klebsiella-pneumoniae-with-both-blakpc-and-blactx-m-integrated-in-chromosome
#7
Weihua Huang, Guiqing Wang, Robert Sebra, Jian Zhuge, Changhong Yin, Maria E Aguero-Rosenfeld, Audrey N Schuetz, Nevenka Dimitrova, John T Fallon
The extended-spectrum β-lactamase (ESBL)- and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae represent serious and urgent threats to public health. In a retrospective study of multidrug-resistant K. pneumoniae, we identified three clinical isolates, CN1, CR14 and NY9, carrying both blaCTX-M and blaKPC genes. The complete genomes of these three K. pneumoniae isolates were de novo assembled by using both short- and long-read whole-genome sequencing. In CR14 and NY9, blaCTX-M and blaKPC were carried on two different plasmids...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28438299/can-gene-editing-and-silencing-technologies-play-a-role-in-the-treatment-of-head-and-neck-cancer
#8
REVIEW
Mushfiq H Shaikh, Daniel T W Clarke, Newell W Johnson, Nigel A J McMillan
Conventional treatment strategies have done little to improve the prognosis or disease-free survival in head and neck cancer (HNC) patients. Recent progress in our understanding of molecular aspects of head and neck squamous cell carcinoma (HNSCC) has provided insights into the potential use of molecular targeted therapies in combination with current treatment strategies. Here we review the current understanding of treatment modalities for both HPV-positive and HPV-negative HNSCCs with the potential to use gene editing and silencing technologies therapeutically...
May 2017: Oral Oncology
https://www.readbyqxmd.com/read/28438207/large-scale-validation-of-an-efficient-crispr-cas-based-multi-gene-editing-protocol-in-escherichia-coli
#9
Francesca Zerbini, Ilaria Zanella, Davide Fraccascia, Enrico König, Carmela Irene, Luca F Frattini, Michele Tomasi, Laura Fantappiè, Luisa Ganfini, Elena Caproni, Matteo Parri, Alberto Grandi, Guido Grandi
BACKGROUND: The exploitation of the CRISPR/Cas9 machinery coupled to lambda (λ) recombinase-mediated homologous recombination (recombineering) is becoming the method of choice for genome editing in E. coli. First proposed by Jiang and co-workers, the strategy has been subsequently fine-tuned by several authors who demonstrated, by using few selected loci, that the efficiency of mutagenesis (number of mutant colonies over total number of colonies analyzed) can be extremely high (up to 100%)...
April 24, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28436315/restenosis-after-carotid-artery-stenting
#10
Zhengze Dai, Gelin Xu
As a common etiology for ischemic stroke, atherosclerotic carotid stenosis has been targeted by vascular surgery since 1950s. Compared with carotid endarterectomy, carotid angioplasty and stenting (CAS) is almost similarly efficacious and less invasive. These advantages make CAS an alternative in treating carotid stenosis. However, accumulative evidences suggested that the long-term benefit-risk ratio of CAS may be decreased or even neutralized by the complications related to in-stent restenosis (ISR). Therefore, investigating the mechanisms and identifying the influential factors of ISR are of vital importance for improving the long-term outcomes of CAS...
January 1, 2017: Vascular
https://www.readbyqxmd.com/read/28435892/dramatic-improvement-of-crispr-cas9-editing-in-candida-albicans-by-increased-single-guide-rna-expression
#11
Henry Ng, Neta Dean
The clustered regularly interspaced short palindromic repeat system with CRISPR-associated protein 9 nuclease (CRISPR/Cas9) has emerged as a versatile tool for genome editing in Candida albicans. Mounting evidence from other model systems suggests that the intracellular levels of single guide RNA (sgRNA) limit the efficiency of Cas9-dependent DNA cleavage. Here, we tested this idea and describe a new means of sgRNA delivery that improves previously described methods by ~10-fold. The efficiency of Cas9/sgRNA-dependent cleavage and repair of a single-copy yeast enhanced monomeric red fluorescent protein (RFP) gene was measured as a function of various parameters that are hypothesized to affect sgRNA accumulation, including transcriptional and posttranscriptional processing...
March 2017: MSphere
https://www.readbyqxmd.com/read/28434807/claimed-effects-outcome-variables-and-methods-of-measurement-for-health-claims-proposed-under-european-community-regulation-1924-2006-in-the-framework-of-protection-against-oxidative-damage-and-cardiovascular-health
#12
REVIEW
D Martini, S Rossi, B Biasini, I Zavaroni, G Bedogni, M Musci, C Pruneti, G Passeri, M Ventura, S Di Nuzzo, D Galli, P Mirandola, M Vitale, A Dei Cas, R C Bonadonna, D Del Rio
BACKGROUND AND AIMS: The high number of negative opinions from the European Food Safety Authority (EFSA) to the requests for authorization of health claims is largely due to the design of human intervention studies, including the inappropriate choice of outcome variables (OVs) and of their methods of measurement (MMs). The present manuscript reports the results of an investigation aimed to collect, collate and critically analyse the information in relation to claimed effects, OVs and MMs, in the context of protection against oxidative damage and cardiovascular health compliant with Regulation 1924/2006...
February 13, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28434254/association-of-gstt1-null-xpd-751%C3%A2-cc-and-xpc-939%C3%A2-cc-genotypes-with-increased-levels-of-genomic-damage-among-hospital-pathologists
#13
Alfredo Santovito, Marta Delsoglio, Eleonora Manitta, Giulia Picco, Giulia Meschiati, Michela Chiarizio, Claudio Gendusa, Piero Cervella
CONTEXT: Hospital workers are at risk for genotoxic damage following occupationally exposure to xenobiotics. Pathologists are exposed to chemicals during their use in health care environments, particularly throughout inhalation of airborne agents, absorption through skin or contact with the patient's body fluids. OBJECTIVE: We evaluated the level of genomic damage in a sample of 61 hospital pathologists (occupationally exposed to antineoplastic drugs and sterilizing agents) and 60 control subjects...
April 24, 2017: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/28433007/alternative-definition-of-excitation-amplitudes-in-multi-reference-state-specific-coupled-cluster
#14
Yann Garniron, Emmanuel Giner, Jean-Paul Malrieu, Anthony Scemama
A central difficulty of state-specific Multi-Reference Coupled Cluster (MR-CC) in the multi-exponential Jeziorski-Monkhorst formalism concerns the definition of the amplitudes of the single and double excitation operators appearing in the exponential wave operators. If the reference space is a complete active space (CAS), the number of these amplitudes is larger than the number of singly and doubly excited determinants on which one may project the eigenequation, and one must impose additional conditions. The present work first defines a state-specific reference-independent operator T∼^(m) which acting on the CAS component of the wave function |Ψ0(m)⟩ maximizes the overlap between (1+T∼^(m))|Ψ0(m)⟩ and the eigenvector of the CAS-SD (Singles and Doubles) Configuration Interaction (CI) matrix |ΨCAS-SD(m)⟩...
April 21, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28432519/carotid-plaque-with-expansive-arterial-remodeling-is-a-risk-factor-for-ischemic-complication-following-carotid-artery-stenting
#15
Daina Kashiwazaki, Naoya Kuwayama, Naoki Akioka, Kyo Noguchi, Satoshi Kuroda
BACKGROUND: Carotid artery stenting (CAS) is associated with a higher risk of periprocedural stroke than carotid endarterectomy. For better patient selection, more accurate risk factors should be identified. The aim of this study was to determine whether expansive arterial remodeling can predict ischemic complications in patients undergoing CAS. METHODS: This retrospective study included 82 patients with carotid stenosis treated by CAS. The plaque component was evaluated using MR plaque imaging before the procedure...
April 21, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/28431926/multiple-repair-pathways-mediate-cellular-tolerance-to-resveratrol-induced-dna-damage
#16
Ying Liu, Xiaohua Wu, Xiaoqing Hu, Ziyuan Chen, Hao Liu, Shunichi Takeda, Yong Qing
Resveratrol (RSV) has been reported to exert health benefits for the prevention and treatment of many diseases, including cancer. The anticancer mechanisms of RSV seem to be complex and may be associated with genotoxic potential. To better understand the genotoxic mechanisms, we used wild-type (WT) and a panel of isogenic DNA-repair deficient DT40 cell lines to identify the DNA damage effects and molecular mechanisms of cellular tolerance to RSV. Our results showed that RSV induced significant formation of γ-H2AX foci and chromosome aberrations (CAs) in WT cells, suggesting direct DNA damage effects...
April 18, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28431308/hyperexcitability-of-inferior-colliculus-and-acoustic-startle-reflex-with-age-related-hearing-loss
#17
Binbin Xiong, Ana'am Alkharabsheh, Senthilvelan Manohar, Guang-Di Chen, Ning Yu, Xiaoming Zhao, Richard Salvi, Wei Sun
Chronic tinnitus and hyperacusis often develop with age-related hearing loss presumably due to aberrant neural activity in the central auditory system (CAS) induced by cochlear pathologies. However, the full spectrum of physiological changes that occur in the CAS as a result age-related hearing loss are still poorly understood. To address this issue, neurophysiological measures were obtained from the cochlea and the inferior colliculus (IC) of 2, 6 and 12 month old C57BL/6J mice, a mouse model for early age-related hearing loss...
March 27, 2017: Hearing Research
https://www.readbyqxmd.com/read/28431233/a-compendium-of-rna-binding-proteins-that-regulate-microrna-biogenesis
#18
Thomas Treiber, Nora Treiber, Uwe Plessmann, Simone Harlander, Julia-Lisa Daiß, Norbert Eichner, Gerhard Lehmann, Kevin Schall, Henning Urlaub, Gunter Meister
During microRNA (miRNA) biogenesis, two endonucleolytic reactions convert stem-loop-structured precursors into mature miRNAs. These processing steps can be posttranscriptionally regulated by RNA-binding proteins (RBPs). Here, we have used a proteomics-based pull-down approach to map and characterize the interactome of a multitude of pre-miRNAs. We identify ∼180 RBPs that interact specifically with distinct pre-miRNAs. For functional validation, we combined RNAi and CRISPR/Cas-mediated knockout experiments to analyze RBP-dependent changes in miRNA levels...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28430820/cardiovascular-safety-of-tiotropium-respimat-vs-handihaler-in-the-routine-clinical-practice-a-population-based-cohort-study
#19
Francesco Trotta, Stefania Spila-Alegiani, Roberto Da Cas, Maja Rajevic, Valentino Conti, Mauro Venegoni, Mariangela Rossi, Giuseppe Traversa
The cardiovascular safety of tiotropium Respimat formulation in the routine clinical practice is still an open issue. Our aim was to compare the risk of acute myocardial infarction and heart rhythm disorders in incident users of either tiotropium Respimat or HandiHaler. The study population comprises patients aged ≥45 years, resident in two Italian regions with a first prescription of tiotropium (HandiHaler or Respimat) between 01/07/2011-30/11/2013. The cohort was identified through the database of prescriptions reimbursed by the Italian National Health Service...
2017: PloS One
https://www.readbyqxmd.com/read/28430423/hafnium-based-contrast-agents-for-x-ray-computed-tomography
#20
Markus Berger, Marcus Bauser, Thomas Frenzel, Christoph Stephan Hilger, Gregor Jost, Silvia Lauria, Bernd Morgenstern, Christian Neis, Hubertus Pietsch, Detlev Sülzle, Kaspar Hegetschweiler
Heavy-metal-based contrast agents (CAs) offer enhanced X-ray absorption for X-ray computed tomography (CT) compared to the currently used iodinated CAs. We report the discovery of new lanthanide and hafnium azainositol complexes and their optimization with respect to high water solubility and stability. Our efforts culminated in the synthesis of BAY-576, an uncharged hafnium complex with 3:2 stoichiometry and broken complex symmetry. The superior properties of this asymmetrically substituted hafnium CA were demonstrated by a CT angiography study in rabbits that revealed excellent signal contrast enhancement...
April 21, 2017: Inorganic Chemistry
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