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https://www.readbyqxmd.com/read/28098181/profiling-single-guide-rna-specificity-reveals-a-mismatch-sensitive-core-sequence
#1
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/28098168/the-il-17a-rs2275913-single-nucleotide-polymorphism-is-associated-with-protection-to-tuberculosis-but-related-to-higher-disease-severity-in-argentina
#2
A Rolandelli, R E Hernández Del Pino, J M Pellegrini, N L Tateosian, N O Amiano, S de la Barrera, N Casco, M Gutiérrez, D J Palmero, V E García
Mycobacterium tuberculosis (Mtb) causes nearly 10 millions of new tuberculosis disease cases annually. However, most individuals exposed to Mtb do not develop tuberculosis, suggesting the influence of a human genetic component. Here, we investigated the association of the rs2275913 SNP (G → A) from IL-17A and tuberculosis in Argentina by a case-control study. Furthermore, we evaluated in vitro the functional relevance of this SNP during the immune response of the host against Mtb and analyzed its impact on clinical parameters of the disease...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098150/a-survey-of-sub-saharan-gene-flow-into-the-mediterranean-at-risk-loci-for-coronary-artery-disease
#3
Miguel M Álvarez-Álvarez, Daniela Zanetti, Robert Carreras-Torres, Pedro Moral, Georgios Athanasiadis
This study tries to find detectable signals of gene flow of Sub-Saharan origin into the Mediterranean in four genomic regions previously associated with coronary artery disease. A total of 366 single-nucleotide polymorphisms were genotyped in 772 individuals from 10 Mediterranean countries. Population structure analyses were performed, in which a noticeable Sub-Saharan component was found in the studied samples. The overall percentage of this Sub-Saharan component presents differences between the two Mediterranean coasts...
January 18, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28097776/molecular-mechanisms-underlying-deoxy-adp-pi-activation-of-pre-powerstroke-myosin
#4
Sarah G Nowakowski, Michael Regnier, Valerie Daggett
Myosin activation is a viable approach to treat systolic heart failure. We previously demonstrated that striated muscle myosin is a promiscuous ATPase that can use most nucleoside triphosphates as energy substrates for contraction. When 2-deoxy ATP (dATP) is used, it acts as a myosin activator, enhancing cross-bridge binding and cycling. In vivo, we have demonstrated that elevated dATP levels increase basal cardiac function and rescues function of infarcted rodent and pig hearts. Here we investigate the molecular mechanism underlying this physiological effect...
January 18, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28097715/c-di-amp-modulates-listeria-monocytogenes-central-metabolism-to-regulate-growth-antibiotic-resistance-and-osmoregulation
#5
Aaron T Whiteley, Nicholas E Garelis, Bret N Peterson, Philip H Choi, Liang Tong, Joshua J Woodward, Daniel A Portnoy
Cyclic di-adenosine monophosphate (c-di-AMP) is a conserved nucleotide second messenger critical for bacterial growth and resistance to cell wall-active antibiotics. In Listeria monocytogenes, the sole diadenylate cyclase, DacA, is essential in rich, but not synthetic media and ΔdacA mutants are highly sensitive to the β-lactam antibiotic cefuroxime. In this study, loss of function mutations in the oligopeptide importer (oppABCDF) and glycine betaine importer (gbuABC) allowed ΔdacA mutants to grow in rich medium...
January 18, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28097645/bacterial-subversion-of-camp-signalling-inhibits-cathelicidin-expression-which-is-required-for-innate-resistance-to-mycobacterium-tuberculosis
#6
Shashank Gupta, Kathryn Winglee, Richard Gallo, William R Bishai
Antimicrobial peptides such as cathelicidins are an important component of innate immune defence against inhaled microorganisms and have demonstrated antimicrobial activity against Mycobacterium tuberculosis with in vitro models. Despite this, little is known about the regulation and expression of cathelicidin during tuberculosis in vivo. We sought to determine whether the cathelicidin-related antimicrobial peptide (Cramp) gene, the murine functional homologue of the human cathelicidin gene (CAMP or LL-37), is required for regulating protective immunity during M...
January 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28097538/the-role-of-glutamine-synthetase-in-energy-production-and-glutamine-metabolism-during-oxidative-stress
#7
Nohaiah Aldarini, Azhar A Alhasawi, Sean C Thomas, Vasu D Appanna
Oxidative stress is known to severely impede aerobic adenosine triphosphate (ATP) synthesis. However, the metabolically-versatile Pseudomonas fluorescens survives this challenge by invoking alternative ATP-generating networks. When grown in a medium with glutamine as the sole organic nutrient in the presence of H2O2, the microbe utilizes glutamine synthetase (GS) to modulate its energy budget. The activity of this enzyme that mediates the release of energy stored in glutamine was sharply increased in the stressed cells compared to the controls...
January 17, 2017: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/28097058/determining-virus-host-interactions-and-glycerol-metabolism-profiles-in-geographically-diverse-solar-salterns-with-metagenomics
#8
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/28096879/association-between-mitofusin-2-gene-polymorphisms-and-late-onset-alzheimer-s-disease-in-the-korean-population
#9
Young Jong Kim, Jin Kyung Park, Won Sub Kang, Su Kang Kim, Changsu Han, Hae Ri Na, Hae Jeong Park, Jong Woo Kim, Young Youl Kim, Moon Ho Park, Jong-Woo Paik
OBJECTIVE: Mitochondrial dysfunction is a prominent and early feature of Alzheimer's disease (AD). The morphologic changes observed in the AD brain could be caused by a failure of mitochondrial fusion mechanisms. The aim of this study was to investigate whether genetic polymorphisms of two genes involved in mitochondrial fusion mechanisms, optic atrophy 1 (OPA1) and mitofusin 2 (MFN2), were associated with AD in the Korean population by analyzing genotypes and allele frequencies. METHODS: One coding single nucleotide polymorphism (SNP) in the MFN2, rs1042837, and two coding SNPs in the OPA1, rs7624750 and rs9851685, were compared between 165 patients with AD (83 men and 82 women, mean age 72...
January 2017: Psychiatry Investigation
https://www.readbyqxmd.com/read/28096862/does-nosema-ceranae-wipe-out-nosema-apis-in-turkey
#10
Rahşan Ivgin Tunca, Devrim Oskay, Ayhan Gosterit, Olgay Kaan Tekin
BACKGROUND: The aim of this study was to determine the prevalence of the Nosema ceranae and Nosema apis among apiaries using both spore counts and multiplex PCR and the replacement of N. apis by N. ceranae in some regions of Turkey. METHODS: A hundred honey bee samples were collected from 99 apiaries in 11 different locations in 2011-2012 in Turkey. Nosema infection degree from collected samples was determined using light microscope and molecular detection of Nosema spp...
April 2016: Iranian Journal of Parasitology
https://www.readbyqxmd.com/read/28096852/echinococcus-granulosus-sensu-stricto-in-dogs-and-jackals-from-caspian-sea-region-northern-iran
#11
Shirzad Gholami, Hefzallah Jahandar, Mahdi Abastabar, Abdolsatar Pagheh, Iraj Mobedi, Mitra Sharbatkhori
BACKGROUND: The aim of the present study was genotyping of Echinococcus granulosus isolates from dogs and jackals in Mazandaran Province, northern Iran, and using partial sequence of the mitochondrial cytochrome c oxidase subunit 1 gene (cox1). METHODS: E. granulosus isolates (n = 15) were collected from 42 stray dogs and 16 jackals found in south of the Caspian Sea in northern Iran. After morphological study, the isolates were genetically characterized using consensus sequences (366bp) of the cox1 gene...
April 2016: Iranian Journal of Parasitology
https://www.readbyqxmd.com/read/28096648/identification-of-genetic-and-epigenetic-variants-associated-with-breast-cancer-prognosis-by-integrative-bioinformatics-analysis
#12
Arunima Shilpi, Yingtao Bi, Segun Jung, Samir K Patra, Ramana V Davuluri
INTRODUCTION: Breast cancer being a multifaceted disease constitutes a wide spectrum of histological and molecular variability in tumors. However, the task for the identification of these variances is complicated by the interplay between inherited genetic and epigenetic aberrations. Therefore, this study provides an extrapolate outlook to the sinister partnership between DNA methylation and single-nucleotide polymorphisms (SNPs) in relevance to the identification of prognostic markers in breast cancer...
2017: Cancer Informatics
https://www.readbyqxmd.com/read/28096535/genetics-of-ancestry-specific-risk-for-relapse-in-acute-lymphoblastic-leukemia
#13
S E Karol, E Larsen, C Cheng, X Cao, W Yang, L B Ramsey, C A Fernandez, J R McCorkle, S W Paugh, R J Autry, E Lopez-Lopez, B Diouf, S Jeha, C-H Pui, E A Raetz, N J Winick, W L Carroll, S P Hunger, M L Loh, M Devidas, W E Evans, J J Yang, M V Relling
The causes of individual relapses in children with acute lymphoblastic leukemia (ALL) remain incompletely understood. We evaluated the contribution of germline genetic factors to relapse in 2225 children treated on Children's Oncology Group trial AALL0232. We identified 302 germline single nucleotide polymorphisms (SNPs) associated with relapse after adjusting for treatment and ancestry and 715 additional SNPs associated with relapse in an ancestry-specific manner. We tested for replication of these relapse-associated SNPs in external data sets of antileukemic drug pharmacokinetics and pharmacodynamics and an independent clinical cohort...
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28096519/the-nuclear-poly-a-binding-protein-of-mammals-but-not-of-fission-yeast-participates-in-mrna-polyadenylation
#14
Uwe Kühn, Juliane Buschmann, Elmar Wahle
The nuclear poly(A) binding protein (PABPN1) has been suggested, on the basis of biochemical evidence, to play a role in mRNA polyadenylation by strongly increasing the processivity of poly(A) polymerase. While experiments in metazoans have tended to support such a role, the results were not unequivocal, and genetic data show that the S. pombe orthologue of PABPN1, Pab2, is not involved in mRNA polyadenylation. The specific model that PABPN1 increases the rate of poly(A) tail elongation has never been examined in vivo...
January 17, 2017: RNA
https://www.readbyqxmd.com/read/28096484/evolutionary-dynamics-of-pandemic-methicillin-sensitive-staphylococcus-aureus-st398-and-its-international-spread-via-routes-of-human-migration
#15
Anne-Catrin Uhlemann, Paul R McAdam, Sean B Sullivan, Justin R Knox, Hossein Khiabanian, Raul Rabadan, Peter R Davies, J Ross Fitzgerald, Franklin D Lowy
: Methicillin-susceptible Staphylococcus aureus (MSSA) accounts for the majority of S. aureus infections globally, and yet surprisingly little is known about its clonal evolution. We applied comparative whole-genome sequencing (WGS) analyses to epidemiologically and geographically diverse ST398-MSSA, a pandemic lineage affecting both humans and livestock. Bayesian phylogenetic analysis predicted divergence of human-associated ST398-MSSA ~40 years ago. Isolates from Midwestern pigs and veterinarians differed substantially from those in New York City (NYC)...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28096473/vimentin-intermediate-filaments-control-actin-stress-fiber-assembly-through-gef-h1-and-rhoa
#16
Yaming Jiu, Johan Peränen, Niccole Schaible, Fang Cheng, John E Eriksson, Ramaswamy Krishnan, Pekka Lappalainen
The actin and intermediate filament cytoskeleltons contribute to numerous cellular processes, including morphogenesis, cytokinesis, and migration. These two cytoskeletal systems associate with each other, but the underlying mechanisms are incompletely understood. Here,we show that inactivation of vimentin leads to increased actin stress fiber assembly and contractility, and consequent elevation of myosin light chain phosphorylation and stabilization of tropomyosin-4.2. The vimentin knockout phenotypes can be rescued by re-expression of wild-type vimentin, but not by the non-filamentous 'unit length form' vimentin, demonstrating that intact vimentin intermediate filaments are required to facilitate the effects on the actin cytoskeleton...
January 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28096466/a-phosphoproteomic-screen-identifies-a-guanine-nucleotide-exchange-factor-for-rab3a-as-a-map-kinase-phosphatase-5-regulated-map-kinase-target-in-il-6-secretion-and-myogenesis
#17
Hojin Lee, Kisuk Min, Jae-Sung Yi, Hao Shi, Woochul Chang, Leandra Jackson, Anton M Bennett
The mitogen-activated protein kinases (MAPKs) have been shown to regulate skeletal muscle function. Previously, we showed that MAPK phosphatase-5 (MKP-5) negatively regulates myogenesis and regeneration of skeletal muscle through inhibition of p38 MAPK and c-Jun N-terminal kinase (JNK). However, the identity and contribution of MKP-5-dependent MAPK targets in the regulation of skeletal muscle function and regenerative myogenesis has not been established. In order to identify MKP-5-dependent MAPK substrates in skeletal muscle, we performed a global differential phospho-MAPK substrate screen in regenerating skeletal muscles of wild type and MKP-5-deficient mice...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096356/active-mlkl-triggers-the-nlrp3-inflammasome-in-a-cell-intrinsic-manner
#18
Stephanie A Conos, Kaiwen W Chen, Dominic De Nardo, Hideki Hara, Lachlan Whitehead, Gabriel Núñez, Seth L Masters, James M Murphy, Kate Schroder, David L Vaux, Kate E Lawlor, Lisa M Lindqvist, James E Vince
Necroptosis is a physiological cell suicide mechanism initiated by receptor-interacting protein kinase-3 (RIPK3) phosphorylation of mixed-lineage kinase domain-like protein (MLKL), which results in disruption of the plasma membrane. Necroptotic cell lysis, and resultant release of proinflammatory mediators, is thought to cause inflammation in necroptotic disease models. However, we previously showed that MLKL signaling can also promote inflammation by activating the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome to recruit the adaptor protein apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) and trigger caspase-1 processing of the proinflammatory cytokine IL-1β...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096345/the-nbs-lrr-architectures-of-plant-r-proteins-and-metazoan-nlrs-evolved-in-independent-events
#19
Jonathan M Urbach, Frederick M Ausubel
There are intriguing parallels between plants and animals, with respect to the structures of their innate immune receptors, that suggest universal principles of innate immunity. The cytosolic nucleotide binding site-leucine rich repeat (NBS-LRR) resistance proteins of plants (R-proteins) and the so-called NOD-like receptors of animals (NLRs) share a domain architecture that includes a STAND (signal transduction ATPases with numerous domains) family NTPase followed by a series of LRRs, suggesting inheritance from a common ancestor with that architecture...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096075/hpprna-a-snakemake-based-handy-parameter-free-pipeline-for-rna-seq-analysis-of-numerous-samples
#20
Dapeng Wang
RNA-Seq technology has been gradually becoming a routine approach for characterizing the properties of transcriptome in terms of organisms, cell types and conditions and consequently a big burden has been put on the facet of data analysis, which calls for an easy-to-learn workflow to cope with the increased demands from a large number of laboratories across the world. We report a one-in-all solution called hppRNA, composed of four scenarios such as pre-mapping, core-workflow, post-mapping and sequence variation detection, written by a series of individual Perl and R scripts, counting on well-established and preinstalled software, irrespective of single-end or paired-end, unstranded or stranded sequencing method...
January 17, 2017: Briefings in Bioinformatics
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