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https://www.readbyqxmd.com/read/28102837/precise-and-efficient-scarless-genome-editing-in-stem-cells-using-correct
#1
Dylan Kwart, Dominik Paquet, Shaun Teo, Marc Tessier-Lavigne
CRISPR/Cas9 is a promising tool for genome-editing DNA in cells with single-base-pair precision, which allows novel in vitro models of human disease to be generated-e.g., in pluripotent stem cells. However, the accuracy of intended sequence changes can be severely diminished by CRISPR/Cas9's propensity to re-edit previously modified loci, causing unwanted mutations (indels) alongside intended changes. Here we describe a genome-editing framework termed consecutive re-guide or re-Cas steps to erase CRISPR/Cas-blocked targets (CORRECT), which, by exploiting the use of highly efficacious CRISPR/Cas-blocking mutations in two rounds of genome editing, enables accurate, efficient and scarless introduction of specific base changes-for example, in human induced pluripotent (iPS) stem cells...
February 2017: Nature Protocols
https://www.readbyqxmd.com/read/28101863/lessons-from-animal-models-of-cytoplasmic-intermediate-filament-proteins
#2
Jamal-Eddine Bouameur, Thomas M Magin
Cytoplasmic intermediate filaments (IFs) represent a major cytoskeletal network contributing to cell shape, adhesion and migration as well as to tissue resilience and renewal in numerous bilaterians, including mammals. The observation that IFs are dispensable in cultured mammalian cells, but cause tissue-specific, life-threatening disorders, has pushed the need to investigate their function in vivo. In keeping with human disease, the deletion or mutation of murine IF genes resulted in highly specific pathologies...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28098181/profiling-single-guide-rna-specificity-reveals-a-mismatch-sensitive-core-sequence
#3
Ting Zheng, Yingzi Hou, Pingjing Zhang, Zhenxi Zhang, Ying Xu, Letian Zhang, Leilei Niu, Yi Yang, Da Liang, Fan Yi, Wei Peng, Wenjian Feng, Ying Yang, Jianxin Chen, York Yuanyuan Zhu, Li-He Zhang, Quan Du
Targeting specificity is an essential issue in the development of CRISPR-Cas technology. Using a luciferase activation assay, off-target cleavage activity of sgRNA was systematically investigated on single nucleotide-mismatched targets. In addition to confirming that PAM-proximal mismatches are less tolerated than PAM-distal mismatches, our study further identified a "core" sequence that is highly sensitive to target-mismatch. This sequence is of 4-nucleotide long, located at +4 to +7 position upstream of PAM, and positioned in a steric restriction region when assembled into Cas9 endonuclease...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097911/design-synthesis-and-docking-study-of-novel-coumarin-ligands-as-potential-selective-acetylcholinesterase-inhibitors
#4
Fatih Sonmez, Belma Zengin Kurt, Isil Gazioglu, Livia Basile, Aydan Dag, Valentina Cappello, Tiziana Ginex, Mustafa Kucukislamoglu, Salvatore Guccione
New coumaryl-thiazole derivatives with the acetamide moiety as a linker between the alkyl chains and/or the heterocycle nucleus were synthesized and in vitro tested as acetylcholinesterase (AChE) inhibitors. 2-(diethylamino)-N-(4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl)acetamide (6c, IC50 value of 43 nM) was the best AChE inhibitor with a selectivity index of 4151.16 over BuChE. Kinetic study of AChE inhibition revealed that 6c was a mixed-type inhibitor. Moreover, the result of H4IIE hepatoma cell toxicity assay for 6c showed negligible cell death...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28097217/amylose-recognition-and-ring-size-determination-of-amylomaltase
#5
Christian Roth, Nicole Weizenmann, Nicola Bexten, Wolfram Saenger, Wolfgang Zimmermann, Timm Maier, Norbert Sträter
Starch is a major carbon and energy source throughout all kingdoms of life. It consists of two carbohydrate polymers, branched amylopectin and linear amylose, which are sparingly soluble in water. Hence, the enzymatic breakdown by glycoside hydrolases (GHs) is of great biological and societal importance. Amylomaltases (AMs) are GHs specialized in the hydrolysis of α-1,4-linked sugar chains such as amylose. They are able to catalyze an intramolecular transglycosylation of a bound sugar chain yielding polymeric sugar rings, the cycloamyloses (CAs), consisting of 20 to 100 glucose units...
January 2017: Science Advances
https://www.readbyqxmd.com/read/28097058/determining-virus-host-interactions-and-glycerol-metabolism-profiles-in-geographically-diverse-solar-salterns-with-metagenomics
#6
Abraham G Moller, Chun Liang
Solar salterns are excellent model ecosystems for studying virus-microbial interactions because of their low microbial diversity, environmental stability, and high viral density. By using the power of CRISPR spacers to link viruses to their prokaryotic hosts, we explored virus-host interactions in geographically diverse salterns. Using taxonomic profiling, we identified hosts such as archaeal Haloquadratum, Halorubrum, and Haloarcula and bacterial Salinibacter, and we found that community composition related to not only salinity but also local environmental dynamics...
2017: PeerJ
https://www.readbyqxmd.com/read/28096836/coronary-artery-spasm-following-on-pump-coronary-artery-bypass-grafting-with-20-months-follow-up
#7
Adam R Kowalówka, Marcin Malinowski, Magdalena Onyszczuk, Marek Deja
We report on a 69-year-old woman who demonstrated native coronary artery and grafted vessel spasm following on-pump coronary artery bypass grafting (CABG). Despite intraaortic balloon pump (IABP) insertion, electrocardiogram (ECG) abnormalities did not disappear. Emergency coronary angiography (CAG) was performed. The patient was successfully treated with systemic and intracoronary injection of vasodilator agents. ECG changes disappeared, with normalized and stable hemodynamic function. Intraaortic balloon pump was maintained for 48 h...
December 2016: Kardiochirurgia i Torakochirurgia Polska, Polish Journal of Cardio-Thoracic Surgery
https://www.readbyqxmd.com/read/28096221/efficient-crispr-cas9-assisted-gene-targeting-enables-rapid-and-precise-genetic-manipulation-of-mammalian-neural-stem-cells
#8
Raul Bardini Bressan, Pooran Singh Dewari, Maria Kalantzaki, Ester Gangoso, Mantas Matjusaitis, Claudia Garcia-Diaz, Carla Blin, Vivien Grant, Harry Bulstrode, Sabine Gogolok, William C Skarnes, Steven M Pollard
Mammalian neural stem (NS) cell lines provide a tractable model for discovery across stem cell and developmental biology, regenerative medicine and neuroscience. They can be derived from foetal or adult germinal tissues and continuously propagated in vitro as adherent monolayers. NS cells are clonally expandable, genetically stable, and easily transfectable - experimental attributes compatible with targeted genetic manipulations. However, gene targeting - so critical for functional studies of embryonic stem cells - has not been exploited to date in NS cells...
January 17, 2017: Development
https://www.readbyqxmd.com/read/28094166/carotid-stenting-prior-to-coronary-bypass-surgery-an-updated-systematic-review-and-meta-analysis
#9
REVIEW
K I Paraskevas, S Nduwayo, A N Saratzis, A R Naylor
OBJECTIVES: The aim was to determine 30-day outcomes in patients with concurrent carotid and cardiac disease who underwent carotid artery stenting (CAS) followed by coronary artery bypass grafting (CABG). METHODS: This was a systematic review with searches of PubMed/Medline, Embase, and Cochrane databases. "Same-day" procedures involved CAS + CABG being performed on the same day, and "staged" interventions involved at least 1 day's delay between undergoing CAS and then CABG...
January 13, 2017: European Journal of Vascular and Endovascular Surgery
https://www.readbyqxmd.com/read/28093797/adverse-reactions-to-dietary-supplements-containing-red-yeast-rice-assessment-of-cases-from-the-italian-surveillance-system
#10
Gabriela Mazzanti, Paola Angela Moro, Emanuel Raschi, Roberto Da Cas, Francesca Menniti-Ippolito
AIMS: Red yeast rice (RYR) is contained in dietary supplements for patients with dyslipidemia. RYR supplements contain monacolin K, which is chemically identical to lovastatin, a licensed drug with a well-known risk profile. We aim to describe the safety profile of RYR by analysing spontaneous reports of suspected adverse reactions (ARs). METHODS: Within the Italian Surveillance System of Natural Health Products, suspected ARs were collected and evaluated by a multidisciplinary group of experts to assess causality using the WHO-UMC system or the CIOMS/RUCAM score, for hepatic reactions...
January 17, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28092970/surgery-of-anterior-skull-base-lesions-in-children
#11
Thomas Karl Hoffmann, Marc Oliver Scheithauer, Fabian Sommer, Jörg Lindemann, Ernst-Johannes Haberl, Ulrike Friebe-Hoffmann, Marie-Nicole Theodoraki
INTRODUCTION: Lesions affecting the anterior skull base represent a rare group of craniofacial pathologies. A tumor of the facial midline, meningitis, or rhinoliquorrhea may be indicative of malformations like dermoid cysts, gliomas, encephaloceles, or nasal fistulas. METHODS: We present a case series of 13 children (4 months to 12 years; 8 males, 5 females) with lesions involving the anterior skull base, which were treated surgically in an interdisciplinary setting...
January 1, 2017: Annals of Otology, Rhinology, and Laryngology
https://www.readbyqxmd.com/read/28092963/mathematical-modeling-of-continuous-and-intermittent-androgen-suppression-for-the-treatment-of-advanced-prostate-cancer
#12
Alacia M Voth, John G Alford, Edward W Swim
Prostate cancer is one of the most prevalent types of cancer among men. It is stimulated by the androgens, or male sexual hormones, which circulate in the blood and diffuse into the tissue where they stimulate the prostate tumor to grow. One of the most important treatments for advanced prostate cancer has become androgen deprivation therapy (ADT). In this paper we present three different models of ADT for prostate cancer: continuous androgen suppression (CAS), intermittent androgen suppression (IAS), and periodic androgen suppression...
June 1, 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/28092918/complete-sequence-and-organization-of-pfr260-the-bacillus-thuringiensis-inta-fr7-4-plasmid-harboring-insecticidal-genes
#13
Laura E Navas, Ariel F Amadio, Elio M Ortiz, Diego H Sauka, Graciela B Benintende, Marcelo F Berretta, Rubén O Zandomeni
We report the complete sequence and analysis of pFR260, a novel megaplasmid of 260,595 bp from the Bacillus thuringiensis strain INTA Fr7-4 isolated in Argentina. It carries 7 insecticidal genes: 3 cry8 copies previously reported, 2 vip1, and 2 vip2. Also, it carries a gene encoding a putative atypical Cry protein. These genes are arranged in a region of approximately 105 kbp in size with characteristics of a pathogenicity island with a potential coleopteran-specific insecticide profile. DNA strand composition asymmetry, as determined by GC skew analysis, and the presence of a Rep protein involved in the initiation of replication suggest a bidirectional theta mechanism of replication...
January 17, 2017: Journal of Molecular Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28092230/octamethylcyclotetrasiloxane-d4
#14
(no author information available yet)
Octamethylcyclotetrasiloxane (D4; CAS No. 556-67-2) is used as a monomer in the manufacture of polymeric materials, which are widely used in various industrial and/or medical applications, such as breast implants. D4 has a relatively low order of toxicity following acute administration via the oral, dermal, and inhalation routes of exposure and is not considered to be a dermal or eye irritant or to be a dermal sensitizer. There is no appreciable dermal absorption of D4 based on results from in vivo and in vitro studies...
January 2017: Toxicology and Industrial Health
https://www.readbyqxmd.com/read/28092229/decamethylcyclopentasiloxane-d5
#15
(no author information available yet)
Decamethylcyclopentasiloxane (D5; CAS No. 541-02-6) is a precursor in the production of siloxane polymers for industry and medicine and is a carrier ingredient in many toiletries and cosmetics. D5 has a relatively low order of toxicity following acute administration via the oral, dermal, and inhalation routes of exposure. It is not considered to be a dermal or eye irritant or a dermal sensitizer. There is no appreciable dermal absorption of D5 based on results from in vivo and in vitro studies. It has not been shown to be genotoxic/mutagenic when tested in a number of short-term in vitro and in vivo assays and did not cause reproductive or developmental toxicity in rats...
January 2017: Toxicology and Industrial Health
https://www.readbyqxmd.com/read/28088532/comparison-of-an-anaerobic-feed-and-split-anaerobic-aerobic-feed-on-granular-sludge-development-performance-and-ecology
#16
Benjamin J Thwaites, Petra Reeve, Nirmala Dinesh, Michael D Short, Ben van den Akker
The retrofitting of existing wastewater sequencing batch reactors (SBRs) to select for rapid-settling aerobic granular sludge (AGS) over floc-based conventional activated sludge (CAS), could be a viable option to decrease reactor cycle time and increase hydraulic capacity. Successful CAS-to-AGS conversion has previously been shown to be highly dependent on having a dedicated anaerobic feed, which presents additional engineering challenges when retrofitting SBRs. In this study we compared the performance of a split anaerobic-aerobic (An-Aer) feed with that of a traditional dedicated anaerobic feed regarding AGS formation and stability, nitrogen removal performance and microbial ecology...
December 29, 2016: Chemosphere
https://www.readbyqxmd.com/read/28087399/advances-with-using-crispr-cas-mediated-gene-editing-to-treat-infections-with-hepatitis-b-virus-and-hepatitis-c-virus
#17
REVIEW
Buhle Moyo, Kristie Bloom, Tristan Scott, Abdullah Ely, Patrick Arbuthnot
Chronic infections with hepatitis B and hepatitis C viruses (HBV and HCV) account for the majority of cases of cirrhosis and hepatocellular carcinoma. Current therapies for the infections have limitations and improved efficacy is necessary to prevent complications in carriers of the viruses. In the case of HBV persistence, the replication intermediate comprising covalently closed circular DNA (cccDNA) is particularly problematic. Licensed therapies have little effect on cccDNA and HBV replication relapses following treatment withdrawal...
January 10, 2017: Virus Research
https://www.readbyqxmd.com/read/28081148/characterization-of-multi-drug-resistant-enterococcus-faecalis-isolated-from-cephalic-recording-chambers-in-research-macaques-macaca-spp
#18
Stephanie E Woods, Mia T Lieberman, Francois Lebreton, Elise Trowel, César de la Fuente-Núñez, Joanne Dzink-Fox, Michael S Gilmore, James G Fox
Nonhuman primates are commonly used for cognitive neuroscience research and often surgically implanted with cephalic recording chambers for electrophysiological recording. Aerobic bacterial cultures from 25 macaques identified 72 bacterial isolates, including 15 Enterococcus faecalis isolates. The E. faecalis isolates displayed multi-drug resistant phenotypes, with resistance to ciprofloxacin, enrofloxacin, trimethoprim-sulfamethoxazole, tetracycline, chloramphenicol, bacitracin, and erythromycin, as well as high-level aminoglycoside resistance...
2017: PloS One
https://www.readbyqxmd.com/read/28079352/the-way-forward-in-italy-for-iodine
#19
Antonella Olivieri, Caterina DI Cosmo, Simona DE Angelis, Roberto DA Cas, Paolo Stacchini, Augusto Pastorelli, Paolo Vitti
Italy is dealing with iodine deficiency since ancient times. Indeed, iodine deficiency disorders, specifically goiter and cretinism, have been reported in some regions of Northern Italy already in the first century AD. However, a clear relationship between endemic goiter and endemic cretinism was recognized only in 1848 by an "ad hoc" committee appointed by the king of Sardinia, which identified extensive areas afflicted by these disorders in Piedmont, Liguria and Sardinia. With the identification in the early 20th century of iodine deficiency as the cause of endemic goiter1 many epidemiological studies were conducted in Italy...
January 12, 2017: Minerva Medica
https://www.readbyqxmd.com/read/28078914/appropriate-patient-selection-for-carotid-revascularization-procedures-is-urgently-needed
#20
Kosmas I Paraskevas, Frank J Veith, Dimitri P Mikhailidis, Christos D Liapis
The identification/selection of appropriate patient subgroups with asymptomatic carotid artery stenosis and the performance of prophylactic carotid endarterectomy (CEA)/carotid artery stenting (CAS) exclusively on these asymptomatic patient subgroups is currently one of the "hottest" topics in vascular surgery. It is now clear that offering CEA/CAS to asymptomatic carotid patients based only on the degree of carotid stenosis is unjustified and scientifically flawed. On the other hand, offering only best medical therapy to every asymptomatic patient, irrespective of certain high-risk criteria (such as the detection of microemboli by transcranial Doppler, intraplaque hemorrhage, silent embolic infarcts on brain computed tomography/magnetic resonance imaging, elevated biomarkers, family history), is equally wrong...
January 1, 2017: Angiology
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