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https://www.readbyqxmd.com/read/28651017/crystal-structure-of-middle-east-respiratory-syndrome-coronavirus-helicase
#1
Wei Hao, Justyna Aleksandra Wojdyla, Rong Zhao, Ruiyun Han, Rajat Das, Ivan Zlatev, Muthiah Manoharan, Meitian Wang, Sheng Cui
Middle East respiratory syndrome coronavirus (MERS-CoV) remains a threat to public health worldwide; however, effective vaccine or drug against CoVs remains unavailable. CoV helicase is one of the three evolutionary most conserved proteins in nidoviruses, thus making it an important target for drug development. We report here the first structure of full-length coronavirus helicase, MERS-CoV nsp13. MERS-CoV helicase has multiple domains, including an N-terminal Cys/His rich domain (CH) with three zinc atoms, a beta-barrel domain and a C-terminal SF1 helicase core with two RecA-like subdomains...
June 26, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28649747/synthesis-structure-and-biological-evaluation-of-a-platinum-carbazole-conjugate
#2
Young Cheun, Myong-Chul Koag, Youssef W Naguib, Hala Ouzon-Shubeita, Zhengrong Cui, Danaya Pakotiprapha, Seongmin Lee
Cisplatin resistance is caused, in part, by the efficient removal of the helix-distorting cisplatin 1,2-intrastrand crosslinks by nucleotide excision repair (NER) machinery. To make a platinum-DNA adduct that causes less helical distortion than the cisplatin 1,2-intrastrand adduct, we designed and synthesized a monofunctional platinum-carbazole conjugate (carbazoleplatin). The 2.5Å crystal structure of carbazoleplatin-DNA adduct revealed both the monoplatination of the N7 of a guanine (G) base and the intercalation into two G:C base pairs while causing a minor distortion of the DNA helix...
June 26, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28648153/-human-papillomavirus-and-oropharyngeal-cancer
#3
Michael Josiassen, Christian Grønhøj Larsen, Christel Bræmer Lajer, Birgitte Charabi, Christian von Buchwald
The prevalence of oropharyngeal cancer is increasing in the Western world, and human papillomavirus (HPV) is believed to play a role in this development. Patients with HPV-positive oropharyngeal cancer differ significantly from patients with HPV-negative cancer. They may present solely with a small cervical metastasis and thus undergo an extensive diagnostic workup. Treatment modalities include radiotherapy often in combination with chemotherapy. However, new surgical advances are now possible. In this review we discuss the changing epidemiology, virology, symptomatology and different treatment modalities...
June 19, 2017: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/28647126/mers-cov-infection-mind-the-public-knowledge-gap
#4
Amen Bawazir, Eman Al-Mazroo, Hoda Jradi, Anwar Ahmed, Motasim Badri
In August 2015, the Corona outbreak caused by Middle East respiratory syndrome coronavirus (MERS-CoV) was the 9th episode since June 2012 in Saudi Arabia. Little is known about the public awareness toward the nature or prevention of the disease. The aim of this work was to assess the knowledge of the adult population in Riyadh toward the MERS-CoV. In this cross-sectional survey, a self-administrated questionnaire was distributed to randomly selected participants visiting malls in Riyadh. The questionnaire contained measurable epidemiological and clinical MERS-CoV knowledge level variables and relevant source of information...
June 21, 2017: Journal of Infection and Public Health
https://www.readbyqxmd.com/read/28645043/in-vitro-and-in-vivo-behavior-of-dna-tetrahedrons-as-tumor-targeting-nanocarriers-for-doxorubicin-delivery
#5
Ji Hee Kang, Kyoung-Ran Kim, Hyukjin Lee, Dae-Ro Ahn, Young Tag Ko
Deoxyribonucleic acid (DNA) is a versatile material with high applicability and inherent biocompatibility. L-DNA, the perfect mirror form of the naturally occurring D-DNA, has been used in DNA nanotechnology. It has thermodynamically identical properties to D-DNA, is capable of self-assembly and bio-orthogonal base-pairing, and is resistant to nuclease activity. We previously constructed an L-DNA tetrahedron (L-Td) and found that this nanostructure has remarkably higher capacity for cell penetration than its natural counterpart (D-Td)...
June 16, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28643248/computational-prediction-of-crispr-cas9-target-sites-reveals-potential-off-target-risks-in-human-and-mouse
#6
Qingbo Wang, Kumiko Ui-Tei
The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system is a prominent genome engineering technology. In the CRISPR/Cas system, the RNA-guided endonuclease Cas protein introduces a DNA double-stranded break at the genome position recognized by a guide RNA (gRNA) based on complementary base-pairing of about 20-nucleotides in length. The 8- or 12-mer gRNA sequence in the proximal region is especially important for target recognition, and the genes with sequence complementarity to such regions are often disrupted...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28643204/host-factors-in-coronavirus-replication
#7
Adriaan H de Wilde, Eric J Snijder, Marjolein Kikkert, Martijn J van Hemert
Coronaviruses are pathogens with a serious impact on human and animal health. They mostly cause enteric or respiratory disease, which can be severe and life threatening, e.g., in the case of the zoonotic coronaviruses causing severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in humans. Despite the economic and societal impact of such coronavirus infections, and the likelihood of future outbreaks of additional pathogenic coronaviruses, our options to prevent or treat coronavirus infections remain very limited...
June 23, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28642467/targeting-coronaviral-replication-and-cellular-jak2-mediated-dominant-nf-%C3%AE%C2%BAb-activation-for-comprehensive-and-ultimate-inhibition-of-coronaviral-activity
#8
Cheng-Wei Yang, Yue-Zhi Lee, Hsing-Yu Hsu, Chuan Shih, Yu-Sheng Chao, Hwan-You Chang, Shiow-Ju Lee
Tylophorine-based compounds exert broad spectral, potent inhibition of coronaviruses. NF-κB activation is a common pro-inflammatory response of host cells to viral infection. The aims of this study were to (i) find an effective combination treatment for coronaviral infections through targeting of the virus per se and cellular NF-κB activity; and (ii) to study the underling mechanisms. We found that tylophorine-based compounds target the TGEV viral RNA and effectively inhibit TGEV replication. NF-κB inhibition also leads to anti-TGEV replication...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28640218/studies-on-the-two-thymine-residues-in-the-catalytic-core-of-10-23-dnazyme-the-impact-on-the-catalysis-of-their-5-substituted-functional-groups
#9
Pengyu Li, Shanshan Du, Yang Li, Junlin He
In the 15-mer catalytic core of 10-23 DNAzyme, each residue contributes to the catalytic conformation differently. Here, the critically conserved T4 and the least conserved T8 were modified on their 5-position with hydroxyl, imidazolyl, and amino groups with a hydrogen-bonding ability. These external functional groups induced new interactions within the catalytic core, resulting in both negative and positive effects on the catalytic activity of 10-23 DNAzyme, and the different linkages could be used to modulate the effect of the functional groups...
June 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28638792/immunotherapy-in-pancreatic-cancer-unleash-its-potential-through-novel-combinations
#10
REVIEW
Songchuan Guo, Merly Contratto, George Miller, Lawrence Leichman, Jennifer Wu
Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States, with poor response to current standard of care, short progression-free and overall survival. Immunotherapies that target cytotoxic T lymphocyte antigen-4, programmed cell death protein-1, and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma, renal cell carcinoma, and non-small cell lung cancer due to high numbers of somatic mutations, combined with cytotoxic T-cell responses...
June 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28638649/crystal-structure-of-5-chloro-n-1-5-phenyl-1h-pyrazol-3-yl-benzene-1-2-di-amine
#11
Yegor Yartsev, Vitaliy Palchikov, Alexandr Gaponov, Svitlana Shishkina
The title compound, C15H13ClN4, crystallizes with two independent mol-ecules (A and B) in the asymmetric unit, which are far from planar as a result of steric repulsion between the rings. The benzene and phenyl rings are inclined to the central pyrazole ring by 46.64 (10) and 17.87 (10)° in mol-ecule A, and by 40.02 (10) and 14.18 (10)° in mol-ecule B. The aromatic rings are inclined to one another by 58.77 (9)° in mol-ecule A, and 36.95 (8)° in mol-ecule B. In the crystal, the A and B mol-ecules are linked by two pairs of N-H⋯N hydrogen bonds forming A-B dimers...
June 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28637340/an-analysis-of-the-use-of-multichannel-microelectrode-recording-during-deep-brain-stimulation-surgeries-at-a-single-center
#12
Steven Falowski, James Dierkes
BACKGROUND: Microelectrode recording (MER) can be used to map out the target nucleus and identify ideal lead placement. OBJECTIVE: To assess the use of multichannel MER to increase the efficiency of lead placement without compromising patient safety. METHODS: Analysis of a single center's technique for utilizing multichannel MER with 3 consistent anterior-to-posterior simultaneous passes that include an evaluation of the location of final lead placement, patient diagnosis, target nuclei, and additional work involved for refinement of targeting...
June 14, 2017: Operative Neurosurgery (Hagerstown, Md.)
https://www.readbyqxmd.com/read/28636980/a-multiplex-liquid-chip-assay-based-on-luminex-xmap-technology-for-simultaneous-detection-of-six-common-respiratory-viruses
#13
Yong Yan, Jian-Yong Luo, Yin Chen, Heng-Hui Wang, Guo-Ying Zhu, Pei-Yan He, Jin-Lei Guo, Yong-Liang Lei, Zhong-Wen Chen
We utilized one-step multiplex reverse transcription-PCR (RT-PCR) and Luminex xMAP technology to develop a respiratory multiplex liquid-chip assay (rMLA) for simultaneous detection of 6 common respiratory viruses, including influenza virus type A (FluA) and type B (FluB), para-influenza virus type 3 (PIV-3), respiratory syncytial virus (RSV), human metapneumovirus (MPV) and a threatening virus to China, Middle East Respiratory Syndrome coronavirus (MERS-CoV). Performance of rMLA was evaluated by comparing with real-time RT-PCR...
June 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634746/screening-and-identification-of-a-specific-peptide-binding-to-cervical-cancer-cells-from-a-phage-displayed-peptide-library
#14
Chunyan Li, Ning Gao, Qinqin Xue, Ni Ma, Yuqin Hu, Jianfang Zhang, Biliang Chen, Yingchun Hou
OBJECTIVES: To screen and identify the probe markers specifically binding to human cervical cancer, a phage-displayed 12-mer peptide library was used for biopanning of SiHa cells. RESULTS: After four rounds of whole-cell subtraction biopanning, the phage recovery was 21-fold higher (from 3.9 × 10(-5) to 8.3 × 10(-4)) than that of the first round, and specific phage clones were significantly enriched. 57 randomly selected phage clones were tested by ELISA, and 36 phage clones were identified as positive clones...
June 20, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28634355/longitudinal-study-of-middle-east-respiratory-syndrome-coronavirus-infection-in-dromedary-camel-herds-in-saudi-arabia-2014-2015
#15
Maged Gomaa Hemida, Abdulmohsen Alnaeem, Daniel Kw Chu, Ranawaka Apm Perera, Samuel Ms Chan, Faisal Almathen, Emily Yau, Brian Cy Ng, Richard J Webby, Leo Lm Poon, Malik Peiris
Two herds of dromedary camels were longitudinally sampled with nasal and rectal swabs and serum, between September 2014 and May 2015, and the samples were tested for Middle East Respiratory Syndrome (MERS) coronavirus RNA and antibodies. Evidence of MERS-CoV infection was confirmed in one herd on the basis of detection of virus RNA in nasal swabs from three camels and significant increases in the antibody titers from three others. The three viruses were genetically identical, thus indicating introduction of a single virus into this herd...
June 21, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28633891/aids-avian-flu-sars-mers-ebola-zika%C3%A2-what-next
#16
REVIEW
Leslie A Reperant, Albert D M E Osterhaus
Emerging infections have threatened humanity since times immemorial. The dramatic anthropogenic, behavioral and social changes that have affected humanity and the environment in the past century have accelerated the intrusion of novel pathogens into the global human population, sometimes with devastating consequences. The AIDS and influenza pandemics have claimed and will continue to claim millions of lives. The recent SARS and Ebola epidemics have threatened populations across borders. The emergence of MERS may well be warning signals of a nascent pandemic threat, while the potential for geographical spread of vector-borne diseases, such as Zika, but also Dengue and Chikungunya is unprecedented...
June 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28633570/enantioselective-light-switch-effect-of-%C3%AE-and-%C3%AE-ru-phenanthroline-2-dipyrido-3-2-a-2-3-c-phenazine-2-bound-to-g-quadruplex-dna
#17
Jin Ha Park, Hyun Suk Lee, Myung Duk Jang, Sung Wook Han, Seog K Kim, Young-Ae Lee
The interaction of Δ- and Λ-[Ru(phen)2DPPZ](2+) (DPPZ = dipyrido[3,2-a:2', 3'-c]phenazine, phen = phenanthroline) with a G-quadruplex formed from 5'-G2T2G2TGTG2T2G2-3'(15-mer) was investigated. The well-known enhancement of luminescence intensity (the 'light-switch' effect) was observed for the [Ru(phen)2DPPZ](2+) complexes upon formation of an adduct with the G-quadruplex. The emission intensity of the G-quadruplex-bound Λ-isomer was 3-fold larger than that of the Δ-isomer when bound to the G-quadruplex, which is opposite of the result observed in the case of double stranded DNA (dsDNA); the light switch effect is larger for the dsDNA-bound Δ-isomer...
June 20, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28633391/kmerpyramid-an-interactive-visualization-tool-for-nucleobase-and-k-mer-frequencies
#18
Jochen Kruppa, Erhard van der Vries, Wendy K Jo, Alexander Postel, Paul Becher, Albert Osterhaus, Klaus Jung
Summary: Bioinformatics methods often incorporate the frequency distribution of nulecobases or k -mers in DNA or RNA sequences, for example as part of metagenomic or phylogenetic analysis. Because the frequency matrix with sequences in the rows and nucleobases in the columns is multi-dimensional it is hard to visualize. We present the R-package 'kmerPyramid' that allows to display each sequence, based on its nucleobase or k -mer distribution projected to the space of principal components, as a point within a 3-dimensional, interactive pyramid...
June 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28630998/annals-consult-guys-syncope-how-do-i-figure-this-one-out
#19
Geno J Merli, Howard H Weitz
No abstract text is available yet for this article.
June 20, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28630747/global-patterns-in-coronavirus-diversity
#20
Simon J Anthony, Christine K Johnson, Denise J Greig, Sarah Kramer, Xiaoyu Che, Heather Wells, Allison L Hicks, Damien O Joly, Nathan D Wolfe, Peter Daszak, William Karesh, W I Lipkin, Stephen S Morse, Jonna A K Mazet, Tracey Goldstein
Since the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrom Coronavirus (MERS-CoV) it has become increasingly clear that bats are important reservoirs of CoVs. Despite this, only 6% of all CoV sequences in GenBank are from bats. The remaining 94% largely consist of known pathogens of public health or agricultural significance, indicating that current research effort is heavily biased towards describing known diseases rather than the 'pre-emergent' diversity in bats...
January 2017: Virus Evolution
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