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https://www.readbyqxmd.com/read/29144943/re-propensity-score-analysis-of-radical-cystectomy-versus-bladder-sparing-trimodal-therapy-in-the-setting-of-a-multidisciplinary-bladder-cancer-clinic
#1
https://www.readbyqxmd.com/read/29141559/new-histopathological-genetic-features-to-improve-active-surveillance-selection-for-low-risk-prostate-cancer
#2
Lih-Ming Wong, Kevin Chu, Niall Corcoran, Sam Norden
BACKGROUND: A recent surge in biomarkers to aid management of men with prostate cancer has occurred. Their applications are varied and not all tests are applicable to the active surveillance setting. OBJECTIVE: To review primary evidence on genetic and immunohistochemical biomarkers, and their role on patient selection and risk stratification for men on active surveillance for prostate cancer. EVIDENCE ACQUISITION: A PubMed electronic search using the terms (biomarker or genetic or histopathological) AND ("prostate cancer" AND "active surveillance") was performed from inception to April 2015...
November 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29115543/the-screening-and-analysis-of-protein-signatures-and-signaling-associated-with-chemoresistance-based-on-protein-pathway-array-technology-in-gastric-cancer
#3
Guodong Lian, Leping Li, Fei Ye, Daguang Wang, Jinglei Liu, Yulong Shi, Changqing Jing, Jian Suo, David Y Zhang, Man Chen
The present study was aimed to identify proteins associated with signaling pathways involved in chemoresistance, and establish a predictive model for chemoresistance in gastric cancer patients after radical surgery. A total of 140 clinically-staged III gastric cancer samples from patients after D2 radical gastrectomy were enrolled in the present study. Protein Pathway Array (PPA) and 286 antibodies were used to assess the protein expression in tumor tissues of patients. The Significance Analysis of Microarray (SAM) software and clustering and discriminant analysis were used to identify differentially expressed proteins between chemosensitive and chemoresistant subsets, and a predictive model for chemoresistance was established using the independent predictive factors...
November 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29091410/reaction-catalyzed-by-genk-a-cobalamin-dependent-radical-s-adenosyl-l-methionine-methyltransferase-in-the-biosynthetic-pathway-of-gentamicin-proceeds-with-retention-of-configuration
#4
Hak Joong Kim, Yung-Nan Liu, Reid M McCarty, Hung-Wen Liu
Many cobalamin (Cbl)-dependent radical S-adenosyl-l-methionine (SAM) methyltransferases have been identified through sequence alignment and/or genetic analysis; however, few have been studied in vitro. GenK is one such enzyme that catalyzes methylation of the 6'-carbon of gentamicin X2 (GenX2) to produce G418 during the biosynthesis of gentamicins. Reported herein, several alternative substrates and fluorinated substrate analogs were prepared to investigate the mechanism of methyl transfer from Cbl to the substrate as well as the substrate specificity of GenK...
November 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29076625/the-radical-sam-enzyme-nirj-catalyzes-the-removal-of-two-propionate-side-chains-during-heme-d1-biosynthesis
#5
Linda Boss, Ramona Oehme, Susan Billig, Claudia Birkemeyer, Gunhild Layer
Heme d1 is a modified tetrapyrrole playing an important role for denitrification by acting as the catalytically essential cofactor in the cytochrome cd1 nitrite reductase of many denitrifying bacteria. In the course of heme d1 biosynthesis, the two propionate side chains on pyrrole rings A and B of the intermediate 12,18-didecarboxysiroheme are removed from the tetrapyrrole macrocycle. In the final heme d1 molecule, the propionate groups are replaced by two keto functions. Although it was speculated that the Radical SAM enzyme NirJ might be responsible for the removal of the propionate groups and introduction of the keto functions, this has not been shown experimentally, so far...
October 27, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29072833/radical-breakthroughs-in-natural-product-and-cofactor-biosynthesis
#6
Kenichi Yokoyama
The radical SAM (S-adenosyl-l-methionine) superfamily is one of the largest group of enzymes with >113000 annotated sequences [Landgraf, B. J., et al. (2016) Annu. Rev. Biochem. 85, 485-514]. Members of this superfamily catalyze the reductive cleavage of SAM using an oxygen sensitive 4Fe-4S cluster to transiently generate 5'-deoxyadenosyl radical that is subsequently used to initiate diverse free radical-mediated reactions. Because of the unique reactivity of free radicals, radical SAM enzymes frequently catalyze chemically challenging reactions critical for the biosynthesis of unique structures of cofactors and natural products...
November 9, 2017: Biochemistry
https://www.readbyqxmd.com/read/29066399/molecular-characterization-and-expression-analyses-of-the-viperin-gene-in-larimichthys-crocea-family-sciaenidae
#7
Jianshe Zhang, Cheng Liu, Shujiang Zhao, Shaoyu Guo, Bin Shen
In this study, we sequenced and characterized an interferon-stimulated gene Viperin homologue, LcViperin, from large yellow croaker (Larimichthys crocea). The LcViperin encodes 354 amino acids and contains an N-terminal amphipathic α-helix domain, a radical S-adenosyl-l-methionine (SAM) domain and a highly conserved C-terminal domain. The analyses of LcViperin promoter region revealed nine kinds of putative transcriptional factor binding sites, including five putative ICSBP (IRF-8) binding sites and one putative IRF-1 binding site, indicating that the expression of LcViperin might be induced by the type I IFN response...
October 21, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29064664/nitrogenase-cofactor-assembly-an-elemental-inventory
#8
Nathaniel S Sickerman, Markus W Ribbe, Yilin Hu
Nitrogenase is known for its remarkable ability to catalyze the reduction of N2 to NH3, and C1 substrates to short-chain hydrocarbon products, under ambient conditions. The best-studied Mo-nitrogenase utilizes a complex metallocofactor as the site of substrate binding and reduction. Designated the M-cluster, this [MoFe7S9C(R-homocitrate)] cluster can be viewed as [MoFe3S3] and [Fe4S3] subclusters bridged by three μ2-sulfides and one μ6-interstitial carbide, with its Mo end further coordinated by an R-homocitrate moiety...
October 24, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29059773/re-clinical-and-therapeutic-factors-associated-with-adverse-pathological-outcomes-in-clinically-node-negative-patients-treated-with-neoadjuvant-cisplatin-based-chemotherapy-and-radical-cystectomy
#9
https://www.readbyqxmd.com/read/29058144/rectal-gastrointestinal-stromal-tumor-gist-in-the-era-of-imatinib-organ-preservation-and-improved-oncologic-outcome
#10
Michael J Cavnar, Lin Wang, Vinod P Balachandran, Cristina R Antonescu, William D Tap, Mary Keohan, Sam Singer, Larissa Temple, Garrett M Nash, Martin R Weiser, Jose G Guillem, Julio Garcia Aguilar, Ronald P DeMatteo, Philip B Paty
BACKGROUND: Approximately 5% of gastrointestinal stromal tumors (GISTs) originate in the rectum, and historically, radical resection was commonly performed. Little is known about the outcome for rectal GIST in the era of imatinib. METHODS: Using a prospectively maintained database, this study retrospectively analyzed 47 localized primary rectal GISTs treated at our center from 1982 to 2016, stratified by when imatinib became available in 2000. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were analyzed by the Kaplan-Meier method...
October 20, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29040833/a-novel-approach-for-uv-patterning-with-binary-polymer-brushes
#11
Lifu Li, Tadashi Nakaji-Hirabayashi, Hiromi Kitano, Kohji Ohno, Yoshiyuki Saruwatari, Kazuyoshi Matsuoka
A mixed self-assembled monolayer (SAM) of an initiator (3-(2-bromo-2-isobutyryloxy)propyl triethoxysilane) for atom transfer radical polymerization (ATRP) and an agent (6-(triethoxysilyl)hexyl 2-(((methylthio)carbonothioyl)thio)-2-phenylacetate) for reversible addition-fragmentation chain transfer (RAFT) polymerization was constructed on the surface of a silicon wafer or glass plate by a silane coupling reaction. When a UV light at 254nm was irradiated at the mixed SAM through a photomask, the surface density of the bromine atom at the end of BPE in the irradiated region was drastically reduced by UV-driven scission of the BrC bond, as observed by X-ray photoelectron spectroscopy...
October 7, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29039940/the-radical-s-adenosylmethionine-methylase-nosn-catalyzes-both-c1-transfer-and-formation-of-the-ester-linkage-of-the-side-ring-system-during-the-biosynthesis-of-nosiheptide
#12
Joseph W LaMattina, Bo Wang, Edward D Badding, Lauren K Gadsby, Tyler Grove, Squire J Booker
Nosiheptide, a member of the e series of macrocyclic thiopeptide natural products, contains a side-ring system composed of a 3,4-dimethylindolic acid (DMIA) moiety connected to Glu6 and Cys8 of the thiopeptide backbone via ester and thioester linkages, respectively. Herein, we show that NosN, a predicted class C radical S-adenosylmethionine (SAM) methylase, catalyzes both the transfer of a C1 unit from SAM to 3-methylindolic acid linked to Cys8 of a synthetic substrate surrogate as well as the formation of the ester linkage between Glu6 and the nascent C4 methylene moiety of DMIA...
October 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28955359/purification-and-in-vitro-activity-of-mitochondria-targeted-nitrogenase-cofactor-maturase-nifb
#13
Stefan Burén, Xi Jiang, Gema López-Torrejón, Carlos Echavarri-Erasun, Luis M Rubio
Active NifB is a milestone in the process of engineering nitrogen fixing plants. NifB is an extremely O2-sensitive S-adenosyl methionine (SAM)-radical enzyme that provides the key metal cluster intermediate (NifB-co) for the biosyntheses of the active-site cofactors of all three types of nitrogenases. NifB and NifB-co are unique to diazotrophic organisms. In this work, we have expressed synthetic codon-optimized versions of NifB from the γ-proteobacterium Azotobacter vinelandii and the thermophilic methanogen Methanocaldococcus infernus in Saccharomyces cerevisiae and in Nicotiana benthamiana...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28911781/theory-and-application-of-the-relationship-between-steady-state-isotope-effects-on-enzyme-intermediate-concentrations-and-net-rate-constants
#14
Mark W Ruszczycky, Hung-Wen Liu
Steady-state kinetic isotope effects on enzyme-catalyzed reactions are often interpreted in terms of the microscopic rate constants associated with the elementary reactions of interest. Unfortunately, this approach can lead to confusion, especially when more than one elementary reaction is isotopically sensitive, because it forces one to consider the full catalytic cycle one step at a time rather than as a complete whole. Herein we argue that shifting focus from intrinsic effects to net rate constants and enzyme intermediate concentrations provides a more natural and holistic interpretation by which the effects of partial rate limitation are more easily understood...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28895719/radical-s-adenosylmethionine-enzymes-involved-in-ripp-biosynthesis
#15
REVIEW
Nilkamal Mahanta, Graham A Hudson, Douglas A Mitchell
Ribosomally synthesized and post-translationally modified peptides (RiPPs) display a diverse range of structures and continue to expand as a natural product class. Accordingly, RiPPs exhibit a wide array of bioactivities, acting as broad and narrow spectrum growth suppressors, antidiabetics, and antinociception and anticancer agents. Because of these properties, and the complex repertoire of post-translational modifications (PTMs) that give rise to these molecules, RiPP biosynthesis has been intensely studied...
October 10, 2017: Biochemistry
https://www.readbyqxmd.com/read/28893989/structures-of-the-peptide-modifying-radical-sam-enzyme-suib-elucidate-the-basis-of-substrate-recognition
#16
Katherine M Davis, Kelsey R Schramma, William A Hansen, John P Bacik, Sagar D Khare, Mohammad R Seyedsayamdost, Nozomi Ando
Posttranslational modification of ribosomally synthesized peptides provides an elegant means for the production of biologically active molecules known as RiPPs (ribosomally synthesized and posttranslationally modified peptides). Although the leader sequence of the precursor peptide is often required for turnover, the exact mode of recognition by the modifying enzymes remains unclear for many members of this class of natural products. Here, we have used X-ray crystallography and computational modeling to examine the role of the leader peptide in the biosynthesis of a homolog of streptide, a recently identified peptide natural product with an intramolecular lysine-tryptophan cross-link, which is installed by the radical S-adenosylmethionine (SAM) enzyme, StrB...
September 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28882206/mechanism-based-strategies-for-structural-characterization-of-radical-sam-reaction-intermediates
#17
Katherine M Davis, Amie K Boal
X-ray crystallographic characterization of enzymes at different stages in their reaction cycles can provide unique insight into the reaction pathway, the number and type of intermediates formed, and their structural context. The known mechanistic diversity in the radical S-adenosylmethionine (SAM) superfamily of enzymes makes it an appealing target for such studies as more than 100,000 sequences have been identified to date with wide-ranging reactivities that share a pattern of complex radical-mediated chemistry...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28882204/tsrm-as-a-model-for-purifying-and-characterizing-cobalamin-dependent-radical-s-adenosylmethionine-methylases
#18
Anthony J Blaszczyk, Roy X Wang, Squire J Booker
Cobalamin-dependent radical S-adenosylmethionine (SAM) methylases play vital roles in the de novo biosynthesis of many antibiotics, cofactors, and other important natural products, yet remain an understudied subclass of radical SAM enzymes. In addition to a [4Fe-4S] cluster that is ligated by three cysteine residues, these enzymes also contain an N-terminal cobalamin-binding domain. In vitro studies of these enzymes have been severely limited because many are insoluble or sparingly soluble upon their overproduction in Escherichia coli...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28874373/hyperbaric-oxygen-sensitizes-anoxic-pseudomonas-aeruginosa-biofilm-to-ciprofloxacin
#19
Mette Kolpen, Christian J Lerche, Kasper N Kragh, Thomas Sams, Klaus Koren, Anna S Jensen, Laura Line, Thomas Bjarnsholt, Oana Ciofu, Claus Moser, Michael Kühl, Niels Høiby, Peter Ø Jensen
Chronic Pseudomonas aeruginosa lung infection is characterized by the presence of endobronchial antibiotic-tolerant biofilm, which is subject to strong oxygen (O2) depletion due to the activity of surrounding polymorphonuclear leukocytes. The exact mechanisms affecting the antibiotic susceptibility of biofilms remain unclear, but accumulating evidence suggests that the efficacy of several bactericidal antibiotics is enhanced by stimulation of aerobic respiration of pathogens, while lack of O2 increases their tolerance...
November 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28851582/long-term-psychological-and-quality-of-life-effects-of-active-surveillance-and-watchful-waiting-after-diagnosis-of-low-risk-localised-prostate-cancer
#20
Sam J Egger, Ross J Calopedos, Dianne L O'Connell, Suzanne K Chambers, Henry H Woo, David P Smith
BACKGROUND: Long-term psychological well-being and quality-of-life are important considerations when deciding whether to undergo active treatment for low-risk localised prostate cancer. OBJECTIVE: To assess the long-term effects of active surveillance (AS) and/or watchful waiting (WW) on psychological and quality-of-life outcomes for low-risk localised prostate cancer patients. DESIGN, SETTING, AND PARTICIPANTS: The Prostate Cancer Care and Outcome Study is a population-based prospective cohort study in New South Wales, Australia...
August 26, 2017: European Urology
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