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https://www.readbyqxmd.com/read/28212251/serum-mast-cell-tryptase-as-a-marker-of-posttraumatic-joint-contracture-in-a-rabbit-model
#1
Michaela Kopka, Michael J Monument, A Dean Befus, Mei Zhang, David A Hart, Paul T Salo, Prism S Schneider, Cun-Yi Fan, Xiangdang Liang, Alexandra Garven, Kevin A Hildebrand
OBJECTIVES: Mast cells have been identified as key mediators of posttraumatic joint contracture, and stabilizing medications (ketotifen) have been shown to decrease contracture severity. Serum mast cell tryptase (SMCT) levels are used clinically to monitor mast cell-mediated conditions. The goals of this study were to determine if SMCT levels are elevated in the setting of joint contracture, if they can be decreased in association with ketotifen therapy, and if they correlate with contracture severity...
March 2017: Journal of Orthopaedic Trauma
https://www.readbyqxmd.com/read/28191894/open-ringed-structure-of-the-cdt1-mcm2-7-complex-as-a-precursor-of-the-mcm-double-hexamer
#2
Yuanliang Zhai, Erchao Cheng, Hao Wu, Ningning Li, Philip Yuk Kwong Yung, Ning Gao, Bik-Kwoon Tye
The minichromosome maintenance complex (MCM) hexameric complex (Mcm2-7) forms the core of the eukaryotic replicative helicase. During G1 phase, two Cdt1-Mcm2-7 heptamers are loaded onto each replication origin by the origin-recognition complex (ORC) and Cdc6 to form an inactive MCM double hexamer (DH), but the detailed loading mechanism remains unclear. Here we examine the structures of the yeast MCM hexamer and Cdt1-MCM heptamer from Saccharomyces cerevisiae. Both complexes form left-handed coil structures with a 10-15-Å gap between Mcm5 and Mcm2, and a central channel that is occluded by the C-terminal domain winged-helix motif of Mcm5...
February 13, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28191893/structural-basis-of-mcm2-7-replicative-helicase-loading-by-orc-cdc6-and-cdt1
#3
Zuanning Yuan, Alberto Riera, Lin Bai, Jingchuan Sun, Saikat Nandi, Christos Spanos, Zhuo Angel Chen, Marta Barbon, Juri Rappsilber, Bruce Stillman, Christian Speck, Huilin Li
To initiate DNA replication, the origin recognition complex (ORC) and Cdc6 load an Mcm2-7 double hexamer onto DNA. Without ATP hydrolysis, ORC-Cdc6 recruits one Cdt1-bound Mcm2-7 hexamer, thus forming an ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) helicase-loading intermediate. Here we report a 3.9-Å structure of Saccharomyces cerevisiae OCCM on DNA. Flexible Mcm2-7 winged-helix domains (WHDs) engage ORC-Cdc6. A three-domain Cdt1 configuration embraces Mcm2, Mcm4, and Mcm6, thus comprising nearly half of the hexamer. The Cdt1 C-terminal domain extends to the Mcm6 WHD, which binds the Orc4 WHD...
February 13, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28191892/mechanism-and-timing-of-mcm2-7-ring-closure-during-dna-replication-origin-licensing
#4
Simina Ticau, Larry J Friedman, Kanokwan Champasa, Ivan R Corrêa, Jeff Gelles, Stephen P Bell
The opening and closing of two ring-shaped Mcm2-7 DNA helicases is necessary to license eukaryotic origins of replication, although the mechanisms controlling these events are unclear. The origin-recognition complex (ORC), Cdc6 and Cdt1 facilitate this process by establishing a topological link between each Mcm2-7 hexamer and origin DNA. Using colocalization single-molecule spectroscopy and single-molecule Förster resonance energy transfer (FRET), we monitored ring opening and closing of Saccharomyces cerevisiae Mcm2-7 during origin licensing...
February 13, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28166228/rapid-turnover-of-dnaa-at-replication-origin-regions-contributes-to-initiation-control-of-dna-replication
#5
Katrin Schenk, Ana B Hervás, Thomas C Rösch, Marc Eisemann, Bernhard A Schmitt, Stephan Dahlke, Luise Kleine-Borgmann, Seán M Murray, Peter L Graumann
DnaA is a conserved key regulator of replication initiation in bacteria, and is homologous to ORC proteins in archaea and in eukaryotic cells. The ATPase binds to several high affinity binding sites at the origin region and upon an unknown molecular trigger, spreads to several adjacent sites, inducing the formation of a helical super structure leading to initiation of replication. Using FRAP analysis of a functional YFP-DnaA allele in Bacillus subtilis, we show that DnaA is bound to oriC with a half-time of 2...
February 6, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28155188/inducible-expression-of-bs2-r-gene-from-capsicum-chacoense-in-sweet-orange-citrus-sinensis-l-osbeck-confers-enhanced-resistance-to-citrus-canker-disease
#6
Lorena Noelia Sendín, Ingrid Georgina Orce, Rocío Liliana Gómez, Ramón Enrique, Carlos Froilán Grellet Bournonville, Aldo Sergio Noguera, Adrián Alberto Vojnov, María Rosa Marano, Atilio Pedro Castagnaro, María Paula Filippone
Transgenic expression of the pepper Bs2 gene confers resistance to Xanthomonas campestris pv. vesicatoria (Xcv) pathogenic strains which contain the avrBs2 avirulence gene in susceptible pepper and tomato varieties. The avrBs2 gene is highly conserved among members of the Xanthomonas genus, and the avrBs2 of Xcv shares 96% homology with the avrBs2 of Xanthomonas citri subsp. citri (Xcc), the causal agent of citrus canker disease. A previous study showed that the transient expression of pepper Bs2 in lemon leaves reduced canker formation and induced plant defence mechanisms...
February 2, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/28143590/the-most-important-questions-in-cancer-research-and-clinical-oncology-question-2-5-obesity-related-cancers-more-questions-than-answers
#7
EDITORIAL
Ajit Venniyoor
Obesity is recognized as the second highest risk factor for cancer. The pathogenic mechanisms underlying tobacco-related cancers are well characterized and effective programs have led to a decline in smoking and related cancers, but there is a global epidemic of obesity without a clear understanding of how obesity causes cancer. Obesity is heterogeneous, and approximately 25% of obese individuals remain healthy (metabolically healthy obese, MHO), so which fat deposition (subcutaneous versus visceral, adipose versus ectopic) is "malignant"? What is the mechanism of carcinogenesis? Is it by metabolic dysregulation or chronic inflammation? Through which chemokines/genes/signaling pathways does adipose tissue influence carcinogenesis? Can selective inhibition of these pathways uncouple obesity from cancers? Do all obesity related cancers (ORCs) share a molecular signature? Are there common (over-lapping) genetic loci that make individuals susceptible to obesity, metabolic syndrome, and cancers? Can we identify precursor lesions of ORCs and will early intervention of high risk individuals alter the natural history? It appears unlikely that the obesity epidemic will be controlled anytime soon; answers to these questions will help to reduce the adverse effect of obesity on human condition...
January 31, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28112645/structure-of-the-active-form-of-human-origin-recognition-complex-and-its-atpase-motor-module
#8
Ante Tocilj, Kin Fan On, Zuanning Yuan, Jingchuan Sun, Elad Elkayam, Huilin Li, Bruce Stillman, Leemor Joshua-Tor
Binding of the Origin Recognition Complex (ORC) to origins of replication marks the first step in the initiation of replication of the genome in all eukaryotic cells. Here, we report the structure of the active form of human ORC determined by X-ray crystallography and cryo-electron microscopy. The complex is composed of an ORC1/4/5 motor module lobe in an organization reminiscent of the DNA polymerase clamp loader complexes. A second lobe contains the ORC2/3 subunits. The complex is organized as a double-layered shallow corkscrew, with the AAA+ and AAA+-like domains forming one layer, and the winged-helix domains (WHDs) forming a top layer...
January 23, 2017: ELife
https://www.readbyqxmd.com/read/28094588/mechanisms-and-regulation-of-dna-replication-initiation-in-eukaryotes
#9
Matthew W Parker, Michael R Botchan, James M Berger
Cellular DNA replication is initiated through the action of multiprotein complexes that recognize replication start sites in the chromosome (termed origins) and facilitate duplex DNA melting within these regions. In a typical cell cycle, initiation occurs only once per origin and each round of replication is tightly coupled to cell division. To avoid aberrant origin firing and re-replication, eukaryotes tightly regulate two events in the initiation process: loading of the replicative helicase, MCM2-7, onto chromatin by the origin recognition complex (ORC), and subsequent activation of the helicase by its incorporation into a complex known as the CMG...
January 17, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28009613/serum-mast-cell-tryptase-as-a-marker-of-post-traumatic-joint-contracture-in-a-rabbit-model
#10
Michaela Kopka, Michael J Monument, A Dean Befus, Mei Zhang, David A Hart, Paul T Salo, Prism S Schneider, Cun-Yi Fan, Xiangdang Liang, Alexandra Garven, Kevin A Hildebrand
OBJECTIVES: Mast cells have been identified as key mediators of post-traumatic joint contracture, and stabilizing medications (Ketotifen) have been shown to decrease contracture severity. Serum mast cell tryptase (SMCT) levels are used clinically to monitor mast cell-mediated conditions. The goals of this study were to determine if SMCT levels are elevated in the setting of joint contracture, if they can be decreased in association with Ketotifen therapy, and if they correlate with contracture severity...
November 7, 2016: Journal of Orthopaedic Trauma
https://www.readbyqxmd.com/read/27974008/a-novel-native-collagen-dressing-with-advantageous-properties-to-promote-physiological-wound-healing
#11
C Wiegand, B A Buhren, E Bünemann, H Schrumpf, B Homey, R G Frykberg, F Lurie, P A Gerber
OBJECTIVE: Chronic hard-to-heal wounds generate high costs and resource use in western health systems and are the focus of intense efforts to improve healing outcomes. Here, we introduce a novel native collagen (90 %):alginate (10 %) wound dressing and compare it with the established oxidised dressings Method: Matrices were analysed by atomic force microscopy (AMF), scanning electron microscopy (SEM), and immunoelectron microscopy for collagen types I, III and V. Viability assays were performed with NIH-3T3 fibroblasts...
December 2, 2016: Journal of Wound Care
https://www.readbyqxmd.com/read/27943081/disambiguation-and-integration-in-korean-relative-clause-processing
#12
Michael Mansbridge, Sunju Park, Katsuo Tamaoka
Previous studies on Korean relative clauses (RC) show that, with respect to processing, object-extracted relative clauses (ORC) are more difficult to process at the head noun than subject-extracted relative clauses within temporarily ambiguous contexts. ORCs, however, are predicted by experience-based processing models to incur a greater processing cost during early processing stages at the RC verb, since it is a likely locus of disambiguation for RCs in Korean, and because ORCs are a less frequent structure...
December 10, 2016: Journal of Psycholinguistic Research
https://www.readbyqxmd.com/read/27941259/direct-determination-of-cadmium-in-seawater-by-standard-addition-icp-qms-qms-with-an-orc
#13
Yanbei Zhu, Akihide Itoh
A method for direct and precise determination of Cd in seawater by ICP-QMS/QMS was developed, where a high matrix introducing unit permitted the direct introduction of seawater without clogging the cones while the matrix effect of seawater was canceled by standard addition. NH3 gas was selected as the reaction gas for removing the MoO interferences with the measurement of Cd isotopes, effectively improving the signal to background ratio. The lower limit of detection obtained at (114)Cd was 0.0002 ng mL(-1), which is enough for the determination of Cd in natural seawater...
2016: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
https://www.readbyqxmd.com/read/27924004/temporal-association-of-orca-lrwd1-to-late-firing-origins-during-g1-dictates-heterochromatin-replication-and-organization
#14
Yating Wang, Abid Khan, Anna B Marks, Owen K Smith, Sumanprava Giri, Yo-Chuen Lin, Rachel Creager, David M MacAlpine, Kannanganattu V Prasanth, Mirit I Aladjem, Supriya G Prasanth
DNA replication requires the recruitment of a pre-replication complex facilitated by Origin Recognition Complex (ORC) onto the chromatin during G1 phase of the cell cycle. The ORC-associated protein (ORCA/LRWD1) stabilizes ORC on chromatin. Here, we evaluated the genome-wide distribution of ORCA using ChIP-seq during specific time points of G1. ORCA binding sites on the G1 chromatin are dynamic and temporally regulated. ORCA association to specific genomic sites decreases as the cells progressed towards S-phase...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27914447/acoustical-gas-leak-detection-in-the-presence-of-multiple-reflections-dispersion-and-uncorrelated-noise-using-optimized-residual-complexity
#15
A M Ahmadi, A Amjadi, A R Bahrampour, H Ravanbod, S Tofighi
Precise acoustical leak detection calls for robust time-delay estimates, which minimize the probability of false alarms in the face of dispersive propagation, multiple reflections, and uncorrelated background noise. Providing evidence that higher order modes and multi-reflected signals behave like sets of correlated noise, this work uses a regression model to optimize residual complexity in the presence of both correlated and uncorrelated noise. This optimized residual complexity (ORC) is highly robust since it takes into account both the level and complexity of noise...
September 2016: Journal of the Acoustical Society of America
https://www.readbyqxmd.com/read/27906128/two-subunits-of-human-orc-are-dispensable-for-dna-replication-and-proliferation
#16
Etsuko Shibata, Manjari Kiran, Yoshiyuki Shibata, Samarendra Singh, Shashi Kiran, Anindya Dutta
The six-subunit Origin Recognition Complex (ORC) is believed to be an essential eukaryotic ATPase that binds to origins of replication as a ring-shaped heterohexamer to load MCM2-7 and initiate DNA replication. We have discovered that human cell lines in culture proliferate with intact chromosomal origins of replication after disruption of both alleles of ORC2 or of the ATPase subunit, ORC1. The ORC1 or ORC2-depleted cells replicate with decreased chromatin loading of MCM2-7 and become critically dependent on another ATPase, CDC6, for survival and DNA replication...
December 1, 2016: ELife
https://www.readbyqxmd.com/read/27900466/overview-of-the-impact-of-depression-and-anxiety-in-chronic-obstructive-pulmonary-disease
#17
Josep Montserrat-Capdevila, Pere Godoy, Josep Ramon Marsal, Ferran Barbé, Josep Pifarré, Miquel Alsedà, Marta Ortega
BACKGROUND: Anxiety and depression are common entities in patients diagnosed with COPD. However, the impact that they have on the exacerbation of illness is scarcely studied. OBJECTIVE: To determine if the presence of anxiety and depression is associated with a greater risk of frequent exacerbation (≥2 per year) in patients diagnosed with COPD. PATIENTS AND METHODS: A cohort study that analysed frequent exacerbation and associated factors in 512 patients monitored during 2 years...
November 29, 2016: Lung
https://www.readbyqxmd.com/read/27864185/the-pediatric-international-knee-documentation-committee-pedi-ikdc-subjective-knee-evaluation-form-normative-data
#18
Adam Y Nasreddine, Patricia L Connell, Leslie A Kalish, Susan Nelson, Maura D Iversen, Allen F Anderson, Mininder S Kocher
BACKGROUND: Children are participating in sports at an increasingly younger age, which has contributed to an increased incidence of knee injuries among this population. Because of increased interest in the application of patient-reported outcome measures in orthopaedic surgery to evaluate treatment results, numerous knee outcome scores, including the International Knee Documentation Committee Subjective Form (IKDC), have been used to evaluate the knee. Although the IKDC has been validated only in adults, it is also being used for children because of a lack of appropriate outcome scores in the pediatric population...
November 18, 2016: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/27862828/introduction-of-robot-assisted-radical-cystectomy-within-an-established-enhanced-recovery-programme
#19
Catherine Miller, Nicholas J Campain, Rachel Dbeis, Mark Daugherty, Nicholas Batchelor, Elizabeth Waine, John S McGrath
OBJECTIVES: To describe the implementation phase of a robot-assisted radical cystectomy (RARC) programme including side-effect profiles and impact on length of stay (LOS). PATIENTS AND METHODS: In all, 114 consecutive patients (82% male) underwent RARC and urinary diversion between April 2013 and December 2015 [ileal conduit (97 patients) and orthotopic neobladder (17)]. Surgery was performed by two surgeons within a designated regional cancer centre. No exclusion criteria were applied...
November 15, 2016: BJU International
https://www.readbyqxmd.com/read/27836746/trf2-recruits-orc-through-trfh-domain-dimerization
#20
Mitsunori Higa, Tatsunori Kushiyama, Seiichiro Kurashige, Daisuke Kohmon, Kouki Enokitani, Satoko Iwahori, Nozomi Sugimoto, Kazumasa Yoshida, Masatoshi Fujita
Telomeres are specialized chromatin structures that prevent the degradation and instability of the ends of linear chromosomes. While telomerase maintains long stretches of the telomeric repeat, the majority of telomeric DNA is duplicated by conventional DNA replication. A fundamental step in eukaryotic DNA replication involves chromatin binding of the origin recognition complex (ORC). In human cells, telomeric repeat binding factor 2 (TRF2) is thought to play a role in the recruitment of ORC onto telomeres...
January 2017: Biochimica et Biophysica Acta
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