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https://www.readbyqxmd.com/read/27936513/probing-the-structural-dynamics-of-the-crispr-cas9-rna-guided-dna-cleavage-system-by-coarse-grained-modeling
#1
Wenjun Zheng
In the adaptive immune systems of many bacteria and archaea, the Cas9 endonuclease forms a complex with specific guide/scaffold RNA to identify and cleave complementary target sequences in foreign DNA. This DNA targeting machinery has been exploited in numerous applications of genome editing and transcription control. However, the molecular mechanism of the Cas9 system is still obscure. Recently, high-resolution structures have been solved for Cas9 in different structural forms (e.g., unbound forms, RNA-bound binary complexes, and RNA-DNA-bound tertiary complexes, corresponding to an inactive state, a pre-target-bound state, and a cleavage-competent or product state), which offered key structural insights to the Cas9 mechanism...
December 9, 2016: Proteins
https://www.readbyqxmd.com/read/27936511/znf208-polymorphisms-associate-with-ischemic-stroke-in-southern-chinese-han-population
#2
Jianzhong Yu, Feng Zhou, Dong Luo, Nianzhen Wang, Chong Zhang, Tianbo Jin, Xiongfei Liang, Dan Yu
BACKGROUND: Ischemic stroke is one of the most common diseases with a high burden of neurological deficits, disability and death. Zinc finger protein 208 (ZNF208) was found to be involved in coronary heart disease, but little information was about its association with ischemic stroke. We performed this case-control study to elucidate the association between single-nucleotide polymorphisms (SNPs) within ZNF208 and risk of ischemic stroke in southern Chinese Han population. METHODS: A total of 799 subjects (400 cases and 399 health controls) were enrolled in this study...
December 9, 2016: Journal of Gene Medicine
https://www.readbyqxmd.com/read/27936496/simultaneous-stimulation-of-the-sbpase-fbp-aldolase-and-the-photorespiratory-gdc-h-protein-increases-co2-assimilation-vegetative-biomass-and-seed-yield-in-arabidopsis
#3
Andrew J Simkin, Patricia E Lopez-Calcagno, Philip A Davey, Lauren R Headland, Tracy Lawson, Stefan Timm, Hermann Bauwe, Christine A Raines
In this paper we have altered the levels of three different enzymes involved in the Calvin Benson cycle and photorespiratory pathway. We have generated transgenic Arabidopsis plants with altered combinations of sedoheptulose 1,7-bisphosphatase (SBPase), fructose 1,6-bisphophate aldolase (FBPA) and the glycine decarboxylase H-protein (GDC-H) gene identified as targets to improve photosynthesis based on previous studies. Here, we show that increasing the levels of the three corresponding proteins, either independently or in combination, significantly increases the quantum efficiency of PSII...
December 9, 2016: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/27936494/five-new-c19-diterpenoid-alkaloids-from-delphinium-tianshanicum-w-t-wang
#4
By Ji-Fa Zhang, Lian-Hai Shan, Feng Gao, Shuai Huang, Xian-Li Zhou
Five new diterpenoid alkaloids tianshanitine A-E (1-5), along with ten known compounds (6-15), were isolated from the ethanolic extracts of the whole plant of Delphinium tianshanicum W. T. Wang. Their structures were determined based on extensive spectroscopic analyses, including 1D, 2D NMR, HRESIMS, and the structure of tianshanitine C (3) was confirmed by X-ray diffraction analysis. Tianshanitine A (1) is the first example of natural diterpenoid alkaloid containing a benzoyl group at C-1 position. Tianshanitine B (2) is a rare natural diterpenoid alkaloid including a hydroxyl group at C-16 position...
December 9, 2016: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/27936490/combining-ancestral-sequence-reconstruction-with-protein-design-to-identify-an-interface-hotspot-in-a-key-metabolic-enzyme-complex
#5
Alexandra Holinski, Kristina Heyn, Rainer Merkl, Reinhard Sterner
It is important to identify hotspot residues that determine protein-protein interactions in interfaces of macromolecular complexes. We have applied a combination of ancestral sequence reconstruction and protein design to identify hotspots within imidazole glycerol phosphate synthase (ImGPS). ImGPS is a key metabolic enzyme complex, which links histidine and de novo purine biosynthesis and consists of the cyclase subunit HisF and the glutaminase subunit HisH. Initial fluorescence titration experiments showed that HisH from Zymomonas mobilis (zmHisH) binds with high affinity to the reconstructed HisF from the last universal common ancestor (LUCA-HisF) but not to HisF from Pyrobaculum arsenaticum (paHisF), which differ by 103 residues...
December 9, 2016: Proteins
https://www.readbyqxmd.com/read/27936485/x-ray-crystal-structure-of-cytochrome-p450-monooxygenase-cyp101j2-from-sphingobium-yanoikuyae-strain-b2
#6
Birgit Unterweger, Nyssa Drinkwater, Priscilla Johanesen, Dena Lyras, Geoffrey J Dumsday, Sheena McGowan
The cytochrome P450 monooxygenases (P450s) catalyse a vast array of oxygenation reactions that can be useful in biocatalytic applications. CYP101J2 from Sphingobium yanoikuyae is a P450 that catalyses the hydroxylation of 1,8-cineole. Here we report the crystallisation and X-ray structure elucidation of recombinant CYP101J2 to 1.8 Å resolution. The CYP101J2 structure shows the canonical P450-fold and has an open conformation in the absence of substrate. Analysis of the structure revealed that CYP101J2, in the absence of substrate, forms a well-ordered substrate-binding channel that suggests a unique form of substrate guidance in comparison to other bacterial 1,8-cineole-hydroxylating P450 enzymes...
December 9, 2016: Proteins
https://www.readbyqxmd.com/read/27936481/patients-with-ultrasound-diagnosis-of-hepatic-steatosis-are-at-high-metabolic-risk
#7
J Kälsch, H Keskin, A Schütte, T Baars, H A Baba, L P Bechmann, A Canbay, J P Sowa
Background and aims: Hepatic steatosis is the basis of non-alcoholic fatty liver disease (NALFD). Mere fat accumulation within hepatocytes is considered the mild form of NAFLD, but can progress in some patients to advanced steatohepatitis (NASH), which may lead to fibrosis, cirrhosis or hepatocellular carcinoma. However, even hepatic steatosis alone may be a risk factor for cardiovascular disease (CVD). Patients and methods: In the present real life study 106 patients from the outpatient clinic of the Department for Gastroenterology and Hepatology with either NAFLD (n = 60) or other typical diagnoses (n = 46) were included...
December 2016: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/27936476/necrotizing-enterocolitis-and-growth-in-preterm-infants-fed-predominantly-maternal-milk-pasteurized-donor-milk-or-preterm-formula-a-retrospective-study
#8
Paula M Sisk, Tinisha M Lambeth, Mario A Rojas, Teisha Lightbourne, Maria Barahona, Evelyn Anthony, Sam T Auringer
Objective To evaluate the association between necrotizing enterocolitis (NEC), growth, and feeding. Methods This is a retrospective study of 551 infants (birth weight ≤ 1,500 g, ≤32 weeks' gestation). NEC, Bell's stage ≥ 2, was confirmed by independent review of sentinel radiographs. Feeding type was defined as ≥ 50% maternal milk (MM), pasteurized donor human milk (PDHM), or preterm formula (PF). Demographic and clinical characteristics including growth were compared between the three groups...
December 9, 2016: American Journal of Perinatology
https://www.readbyqxmd.com/read/27936470/ocular-delivery-of-pacap1-27-protects-the-retina-from-ischemic-damage-in-rodents
#9
Dora Werling, Dora Reglodi, William A Banks, Therese S Salameh, Krisztina Kovacs, Timea Kvarik, Alexandra Vaczy, Laszlo Kovacs, Flora Mayer, Bese Danyadi, Emese Lokos, Andrea Tamas, Gabor Toth, Zsolt Biro, Tamas Atlasz
Purpose: Pituitary adenylate cyclase activating polypeptide (PACAP) is neuroprotective in neuronal injuries. Bilateral common carotid artery occlusion (BCCAO) causes chronic hypoperfusion-induced degeneration in the rat retina, where we proved the retinoprotective effect of intravitreal PACAP. Although this route of administration is a common clinical practice in several diseases, easier routes are clinically important. Our aim was to investigate the potential retinoprotective effects of PACAP eye drops in BCCAO-induced ischemic retinopathy...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27936465/meta-analysis-of-transcatheter-arterial-chemoembolization-plus-radiofrequency-ablation-versus-transcatheter-arterial-chemoembolization-alone-for-hepatocellular-carcinoma
#10
De-Jun Yang, Kun-Lun Luo, Hong Liu, Bing Cai, Guo-Qing Tao, Xiao-Fang Su, Xiao-Juan Hou, Fei Ye, Xiang-Yong Li, Zhi-Qiang Tian
This meta-analysis was conducted to compare transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA) with TACE alone for hepatocellular carcinoma. We searched MEDLINE, EMBASE and CENTRAL for all relative randomized controlled trials (RCTs) and retrospective studies until October 31 2016. Tumor response, recurrence-free survival, overall survival and postoperative complications were the major evaluation indices. Review Manager (version 5.3) was used to analyze the data. Dichotomous data was calculated by odds ratio (OR) with 95% confidence intervals (CI)...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27936464/refractory-testicular-germ-cell-tumors-are-highly-sensitive-to-the-second-generation-dna-methylation-inhibitor-guadecitabine
#11
Costantine Albany, Mary P Hever-Jardine, Katherine M von Herrmann, Christina Y Yim, Janice Tam, Joshua M Warzecha, Leah Shin, Sarah E Bock, Brian S Curran, Aneeq S Chaudhry, Fred Kim, George E Sandusky, Pietro Taverna, Sarah J Freemantle, Brock C Christensen, Lawrence H Einhorn, Michael J Spinella
Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A substantial portion of TGCT patients are refractory to cisplatin. There are no effective therapies for these patients, many of whom die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. In prior in vitro studies we found that EC cells were highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). Here, as an initial step in bringing demethylation therapy to the clinic for TGCT patients, we evaluated the effects of the clinically optimized, second generation demethylating agent guadecitabine (SGI-110) on EC cells in an animal model of cisplatin refractory testicular cancer...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27936462/sinu-virus-a-novel-and-divergent-orthomyxovirus-related-to-members-of-the-genus-thogotovirus-isolated-from-mosquitoes-in-colombia
#12
María Angélica Contreras-Gutiérrez, Marcio R T Nunes, Hilda Guzman, Sandra Uribe, Juan Carlos Gallego Gómez, Juan David Suaza Vasco, Jedson F Cardoso, Vsevolod L Popov, Steven G Widen, Thomas G Wood, Nikos Vasilakis, Robert B Tesh
The genome and structural organization of a novel insect-specific orthomyxovirus, designated Sinu virus, is described. Sinu virus (SINUV) was isolated in cultures of C6/36 cells from a pool of mosquitoes collected in northwestern Colombia. The virus has six negative-sense ssRNA segments. Genetic analysis of each segment demonstrated the presence of six distinct ORFs encoding the following genes: PB2 (Segment 1), PB1, (Segment 2), PA protein (Segment 3), envelope GP gene (Segment 4), the NP (Segment 5), and M-like gene (Segment 6)...
December 6, 2016: Virology
https://www.readbyqxmd.com/read/27936453/biological-mechanisms-of-depression-following-treatment-with-interferon-for-chronic-hepatitis-c-a-critical-systematic-review
#13
REVIEW
Myrela O Machado, Giovanni Oriolo, Beatrice Bortolato, Cristiano A Köhler, Michael Maes, Marco Solmi, Iria Grande, Rocío Martín-Santos, Eduard Vieta, André F Carvalho
BACKGROUND: A significant subset of patients infected by the hepatitis C virus (HCV) develops a major depressive episode (MDE) during Interferon-alpha (IFN-α) based immunotherapy. We performed a systematic review of studies which examined biological mechanisms contributing to the onset of a MDE during IFN-α-based immunotherapy for HCV. METHODS: Major electronic databases were searched from inception up until 15th February 2016 for peer-reviewed prospective studies that had enrolled HCV infected patients who received IFN-α treatment...
November 27, 2016: Journal of Affective Disorders
https://www.readbyqxmd.com/read/27936442/label-free-colorimetric-detection-of-cancer-related-gene-based-on-two-step-amplification-of-molecular-machine
#14
Huo Xu, Dong Wu, Chen-Qiao Li, Zheng Lu, Xiao-Yun Liao, Jie Huang, Zai-Sheng Wu
Highly sensitive detection of K-ras gene is of great significance in biomedical research and clinical diagnosis. Here, we developed a colorimetric biosensing system for the detection of proto-oncogene K-ras based on enhanced amplification effect of DNA molecular machine, where dual isothermal circular strand-displacement amplification (D-SDA) occurs on two arms in one-to-one correspondence. Specifically, we designed a primer-locked hairpin probe (HP) and a primer-contained linear polymerization template (PPT)...
December 2, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27936439/symptoms-of-prolonged-grief-post-traumatic-stress-and-depression-after-loss-in-a-dutch-community-sample-a-latent-class-analysis
#15
A A A Manik J Djelantik, Geert E Smid, Rolf J Kleber, Paul A Boelen
Mental health problems following loss can manifest as heterogeneous symptomatology that may include symptoms of Prolonged Grief Disorder (PGD), Post-Traumatic Stress Disorder (PTSD), and Major Depressive Disorder (MDD). However, the co-occurrence of symptoms of these three disorders is still only partially explored. The aims of this study were to identify subgroups (i.e., classes) in a Dutch sample of bereaved individuals, based on severity and/or co-occurrence of symptoms and to identify predictors for these subgroups, taking into account all three disorders...
November 22, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27936436/spectroscopic-single-crystal-x-ray-hirshfeld-in-vitro-and-in-silico-biological-evaluation-of-a-new-series-of-potent-thiazole-nucleus-integrated-with-pyrazoline-scaffolds
#16
Vinutha V Salian, Badiadka Narayana, Balladka K Sarojini, Madan S Kumar, Govinahalli S Nagananda, Kullaiah Byrappa, Avinash K Kudva
In the present study, the spectroscopic characterization of a new series of substituted thiazole linked pyrazoline scaffolds 4a-l was performed. The formation of 4a-l from the intermediate 3-(4-chlorophenyl)-5-[4-(propan-2-yl)phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide 2 and substituted 2-bromo-1-phenylethanone 3a-l was evidenced through the changes in FTIR, (1)H NMR, (13)C NMR, LCMS data. The X-ray diffraction studies revealed that compound 2 and 4g crystallized in monoclinic crystal system with P21/n space group...
November 28, 2016: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/27936432/the-role-of-the-water-tankers-market-in-water-stressed-semi-arid-urban-areas-implications-on-water-quality-and-economic-burden
#17
Kinda Constantine, May Massoud, Ibrahim Alameddine, Mutasem El-Fadel
Population growth and development are associated with increased water demand that often exceeds the capacity of existing resources, resulting in water shortages, particularly in urban areas, where more than 60% of the world's population resides. In many developing communities, shortages often force households to depend on water tankers amongst other potential sources for the delivery of water for domestic and/or potable use. While water tankers have become an integral part of the water supply system in many countries, the sector is often unregulated and operates with little governmental supervision...
December 6, 2016: Journal of Environmental Management
https://www.readbyqxmd.com/read/27936427/an-observed-rise-in-%C3%AE-hydroxybutyrate-associated-deaths-in-london-evidence-to-suggest-a-possible-link-with-concomitant-rise-in-chemsex
#18
Joanna Hockenhull, Kevin G Murphy, Sue Paterson
BACKGROUND: Gamma-hydroxybutyrate (GHB) is the drug most linked to acute harm out of those used in chemsex, the incidence of which is reported to be increasing. However, there have been few systematic studies of the harms associated with GHB use. We investigated GHB-associated deaths from London coroners' jurisdictions between 2011 and 2015. METHODS: Blood and urine samples were collected by pathologists and submitted for toxicological analysis at the request of coroners...
December 2, 2016: Forensic Science International
https://www.readbyqxmd.com/read/27936426/statistical-comparison-of-mass-spectra-for-identification-of-amphetamine-type-stimulants
#19
Melissa A Bodnar Willard, Victoria L McGuffin, Ruth Waddell Smith
A method for the statistical comparison of mass spectral data is demonstrated for applications in controlled substance analysis. The method uses an unequal variance t-test at each mass-to-charge ratio in the scan range to determine if two spectra are statistically associated or discriminated. If the two spectra are associated, a random-match probability is calculated to estimate the likelihood that the mass spectral fragmentation pattern in question occurs by random chance alone. If the two spectra are discriminated, the fragment ions responsible for the discrimination are determined...
November 22, 2016: Forensic Science International
https://www.readbyqxmd.com/read/27936425/did-a-lucky-shot-sink-the-submarine-h-l-hunley
#20
Rachel M Lance, Henry Warder, Cameron R Dale Bass
The H.L. Hunley was the first submarine to be successful in combat, sinking the Union vessel Housatonic outside Charleston Harbor in 1864 during the Civil War. However, despite marking a milestone in military history, little is known about this vessel or why it sank. One popular theory is the "lucky shot" theory: the hypothesis that small arms fire from the crew of the Housatonic may have sufficiently damaged the submarine to sink it. However, ballistic experiments with cast iron samples, analysis of historical experiments firing Civil War-era projectiles at cast iron samples, and calculation of the tidal currents and sinking trajectory of the submarine indicate that this theory is not likely...
December 2, 2016: Forensic Science International
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