anal Crystallographic and kinetic analyses of the FdsBG subcomplex of the cytosolic formate dehydrogenase FdsABG from Cupriavidus necator [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Formate oxidation to carbon dioxide is a key reaction in one-carbon compound metabolism, and its reverse reaction represents the first step in carbon assimilation in the acetogenic and methanogenic branches of many anaerobic organisms. The molybdenum-containing dehydrogenase FdsABG is a soluble NAD+-dependent formate dehydrogenase and a member of the NADH dehydrogenase superfamily. Here, we present the first structure of the FdsBG subcomplex of the cytosolic FdsABG formate dehydrogenase from the hydrogen-oxidizing bacterium Cupriavidus necator H16 both with and without bound NADH. The structures revealed that the two iron-sulfur clusters, Fe4S4 in FdsB and Fe2S2 in FdsG, are closer to the FMN than they are in other NADH dehydrogenases. Rapid kinetic studies and EPR measurements of rapid freeze-quenched samples of the NADH reduction of FdsBG identified a neutral flavin semiquinone, FMNH•, not previously observed to participate in NADH-mediated reduction of the FdsABG holoenzyme. We found that this semiquinone forms through the transfer of one electron from the fully reduced FMNH−, initially formed via NADH-mediated reduction, to the Fe2S2 cluster. This Fe2S2 cluster is not part of the on-path chain of iron-sulfur clusters connecting the FMN of FdsB with the active-site molybdenum center of FdsA. According to the NADH-bound structure, the nicotinamide ring stacks onto the re-face of the FMN. However, NADH binding significantly reduced the electron density for the isoalloxazine ring of FMN and induced a conformational change in residues of the FMN-binding pocket that display peptide-bond flipping upon NAD+ binding in proper NADH dehydrogenases. Full Article
anal Tariffs on Germany a card Trump seems willing to play, analyst says By feedproxy.google.com Published On :: Tue, 21 Jan 2020 14:34:30 +0000 Source CNBC URL https://www.cnbc.com/video/2019/12/03/tariffs-on-germany-a-card-trump-seems-will... Release date 03 December 2019 Expert Dr Lindsay Newman In the news type Op-ed Hide date on homepage Full Article
anal Spectral analysis and representation of solutions of integro-differential equations with fractional exponential kernels By www.ams.org Published On :: Fri, 10 Apr 2020 08:09 EDT V. V. Vlasov and N. A. Rautian Trans. Moscow Math. Soc. 80 (2020), 169-188. Abstract, references and article information Full Article
anal Tool for the analysis of Second National Reports on the Implementation of the Cartagena Protocol on Biosafety now available on the BCH By bch.cbd.int Published On :: Thu, 01 Dec 2011 00:00:00 GMT Full Article
anal CBD News: 15e École d'été en évaluation environnementale Évaluation de la durabilité du développement urbain et industriel: outils d'analyse de l'empreinte écologique et des impacts sociaux et sanitaires By www.cbd.int Published On :: Tue, 01 Feb 2011 00:00:00 GMT Full Article
anal CBD News: Statement by Mr. Braulio F. de Souza Dias , CBD Executive Secretary, at the opening of the Regional Workshop for South, East and Southeast Asia on the Preparation of the Fifth National Report and Regional Scenario Analysis, Incheon City, Republi By www.cbd.int Published On :: Mon, 20 May 2013 00:00:00 GMT Full Article
anal New analytical tools for HDG in elasticity, with applications to elastodynamics By www.ams.org Published On :: Tue, 07 Apr 2020 14:09 EDT Shukai Du and Francisco-Javier Sayas Math. Comp. 89 (2019), 1745-1782. Abstract, references and article information Full Article
anal Stability, analyticity, and maximal regularity for parabolic finite element problems on smooth domains By www.ams.org Published On :: Tue, 07 Apr 2020 14:09 EDT Takahito Kashiwabara and Tomoya Kemmochi Math. Comp. 89 (2020), 1647-1679. Abstract, references and article information Full Article
anal Analytic Methods in Arithmetic Geometry By www.ams.org Published On :: Thu, 26 Dec 2019 09:58 EST Alina Bucur and David Zureick-Brown, editors. American Mathematical Society | Centre de Recherches Mathematiques, 2019, CONM, volume 740, approx. 256 pp. ISBN: 978-1-4704-3784-8 (print), 978-1-4704-5629-0 (online). This volume contains the proceedings of the Arizona Winter School 2016, which was held from March 12–16, 2016, at The University of Arizona,... Full Article
anal Analytic Trends in Mathematical Physics By www.ams.org Published On :: Tue, 07 Jan 2020 09:23 EST Houssam Abdul-Rahman, Robert Sims and Amanda Young, editors. American Mathematical Society, 2020, CONM, volume 741, approx. 208 pp. ISBN: 978-1-4704-4841-7 (print), 978-1-4704-5388-6 (online). This volume contains the proceedings of the Arizona School of Analysis and Mathematical Physics, held from March 5–9, 2018, at the University of... Full Article
anal Complex Analysis and Spectral Theory By www.ams.org Published On :: Mon, 10 Feb 2020 06:20 EST H. Garth Dales, Dmitry Khavinson and Javad Mashreghi, editors. American Mathematical Society | Centre de Recherches Mathematiques, 2020, CONM, volume 743, approx. 296 pp. ISBN: 978-1-4704-4692-5 (print), 978-1-4704-5453-1 (online). This volume contains the proceedings of the Conference on Complex Analysis and Spectral Theory, in celebration of Thomas Ransford's 60th birthday, held... Full Article
anal Advances in Harmonic Analysis and Partial Differential Equations By www.ams.org Published On :: Fri, 10 Apr 2020 05:23 EDT Donatella Danielli and Irina Mitrea, editors. American Mathematical Society, 2020, CONM, volume 748, approx. 210 pp. ISBN: 978-1-4704-4896-7 (print), 978-1-4704-5516-3 (online). This volume contains the proceedings of the AMS Special Session on Harmonic Analysis and Partial Differential Equations, held from April 21–22,... Full Article
anal ????-theory in Algebra, Analysis and Topology By www.ams.org Published On :: Tue, 21 Apr 2020 07:58 EDT Guillermo Cortiñas and Charles A. Weibel, editors. American Mathematical Society, 2020, CONM, volume 749, approx. 398 pp. ISBN: 978-1-4704-5026-7 (print), 978-1-4704-5594-1 (online). This volume contains the proceedings of the ICM 2018 satellite school and workshop K-theory conference in Argentina. The school was held... Full Article
anal Analyticity up to the boundary for the Stokes and the Navier-Stokes systems By www.ams.org Published On :: Wed, 08 Apr 2020 11:21 EDT Guher Camliyurt, Igor Kukavica and Vlad Vicol Trans. Amer. Math. Soc. 373 (2020), 3375-3422. Abstract, references and article information Full Article
anal Corrigendum to “The Łojasiewicz exponent of a continuous subanalytic function at an isolated zero” By www.ams.org Published On :: Thu, 02 Apr 2020 13:59 EDT Phạm Tiến Sơn Proc. Amer. Math. Soc. 148 (2020), 2739-2741. Abstract, references and article information Full Article
anal ????-analogues of several ????-formulas By www.ams.org Published On :: Thu, 02 Apr 2020 13:59 EDT Chuanan Wei Proc. Amer. Math. Soc. 148 (2020), 2287-2296. Abstract, references and article information Full Article
anal Top Google Analytics tips By www.techworld.com Published On :: Fri, 12 Jul 2019 12:30:00 GMT Full Article
anal Math in the Media - May 2020:John Conway, "magical mathematician", Topological analysis of zebrafish, teaching online... By www.ams.org Published On :: Mon, 04 May 2020 00:00:00 EST Full Article
anal Microlocalization of Subanalytic Sheaves By www.ams.org Published On :: Luca Prelli, Universita degli Studi di Padova - A publication of the Societe Mathematique de France, 2013, 101 pp., Softcover, ISBN-13: 978-2-85629-768-1, List: US$45, All AMS Members: US$36, SMFMEM/135 The author defines the specialization and microlocalization functors for subanalytic sheaves. Applying these tools to the sheaves of tempered and... Full Article
anal Harmonic Analysis and Partial Differential Equations By www.ams.org Published On :: Patricio Cifuentes and Jose Garcia-Cuerva, Universidad Autonoma de Madrid, Gustavo Garrigos, Universidad de Murcia, Eugenio Hernandez, Universidad Autonoma de Madrid, Jose Maria Martell, Javier Parcet, and Keith M. Rogers, Consejo Superior de Investigaciones Cientificas, and Alberto Ruiz, Fernando Soria, and Ana Vargas, Universidad Autonoma de Madrid, Editors - AMS, 2014, 178 pp., Softcover, ISBN-13: 978-0-8218-9433-0, List: US$78, All AMS Members: US$62.40, CONM/612 This volume contains the Proceedings of the 9th International Conference on Harmonic Analysis and Partial Differential Equations, held June 11-15,... Full Article
anal Structural and mutational analyses of the bifunctional arginine dihydrolase and ornithine cyclodeaminase AgrE from the cyanobacterium Anabaena [Enzymology] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 In cyanobacteria, metabolic pathways that use the nitrogen-rich amino acid arginine play a pivotal role in nitrogen storage and mobilization. The N-terminal domains of two recently identified bacterial enzymes: ArgZ from Synechocystis and AgrE from Anabaena, have been found to contain an arginine dihydrolase. This enzyme provides catabolic activity that converts arginine to ornithine, resulting in concomitant release of CO2 and ammonia. In Synechocystis, the ArgZ-mediated ornithine–ammonia cycle plays a central role in nitrogen storage and remobilization. The C-terminal domain of AgrE contains an ornithine cyclodeaminase responsible for the formation of proline from ornithine and ammonia production, indicating that AgrE is a bifunctional enzyme catalyzing two sequential reactions in arginine catabolism. Here, the crystal structures of AgrE in three different ligation states revealed that it has a tetrameric conformation, possesses a binding site for the arginine dihydrolase substrate l-arginine and product l-ornithine, and contains a binding site for the coenzyme NAD(H) required for ornithine cyclodeaminase activity. Structure–function analyses indicated that the structure and catalytic mechanism of arginine dihydrolase in AgrE are highly homologous with those of a known bacterial arginine hydrolase. We found that in addition to other active-site residues, Asn-71 is essential for AgrE's dihydrolase activity. Further analysis suggested the presence of a passage for substrate channeling between the two distinct AgrE active sites, which are situated ∼45 Å apart. These results provide structural and functional insights into the bifunctional arginine dihydrolase–ornithine cyclodeaminase enzyme AgrE required for arginine catabolism in Anabaena. Full Article
anal Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation [Enzymology] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 Numerous zinc ectoenzymes are metalated by zinc and activated in the compartments of the early secretory pathway before reaching their destination. Zn transporter (ZNT) proteins located in these compartments are essential for ectoenzyme activation. We have previously reported that ZNT proteins, specifically ZNT5–ZNT6 heterodimers and ZNT7 homodimers, play critical roles in the activation of zinc ectoenzymes, such as alkaline phosphatases (ALPs), by mobilizing cytosolic zinc into these compartments. However, this process remains incompletely understood. Here, using genetically-engineered chicken DT40 cells, we first determined that Zrt/Irt-like protein (ZIP) transporters that are localized to the compartments of the early secretory pathway play only a minor role in the ALP activation process. These transporters included ZIP7, ZIP9, and ZIP13, performing pivotal functions in maintaining cellular homeostasis by effluxing zinc out of the compartments. Next, using purified ALP proteins, we showed that zinc metalation on ALP produced in DT40 cells lacking ZNT5–ZNT6 heterodimers and ZNT7 homodimers is impaired. Finally, by genetically disrupting both ZNT5 and ZNT7 in human HAP1 cells, we directly demonstrated that the tissue-nonspecific ALP-activating functions of both ZNT complexes are conserved in human cells. Furthermore, using mutant HAP1 cells, we uncovered a previously-unrecognized and unique spatial regulation of ZNT5–ZNT6 heterodimer formation, wherein ZNT5 recruits ZNT6 to the Golgi apparatus to form the heterodimeric complex. These findings fill in major gaps in our understanding of the molecular mechanisms underlying zinc ectoenzyme activation in the compartments of the early secretory pathway. Full Article
anal Determination of globotriaosylceramide analogs in the organs of a mouse model of Fabry disease [Lipids] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 Fabry disease is a heritable lipid disorder caused by the low activity of α-galactosidase A and characterized by the systemic accumulation of globotriaosylceramide (Gb3). Recent studies have reported a structural heterogeneity of Gb3 in Fabry disease, including Gb3 isoforms with different fatty acids and Gb3 analogs with modifications on the sphingosine moiety. However, Gb3 assays are often performed only on the selected Gb3 isoforms. To precisely determine the total Gb3 concentration, here we established two methods for determining both Gb3 isoforms and analogs. One was the deacylation method, involving Gb3 treatment with sphingolipid ceramide N-deacylase, followed by an assay of the deacylated products, globotriaosylsphingosine (lyso-Gb3) and its analogs, by ultra-performance LC coupled to tandem MS (UPLC-MS/MS). The other method was a direct assay established in the present study for 37 Gb3 isoforms and analogs/isoforms by UPLC-MS/MS. Gb3s from the organs of symptomatic animals of a Fabry disease mouse model were mainly Gb3 isoforms and two Gb3 analogs, such as Gb3(+18) containing the lyso-Gb3(+18) moiety and Gb3(−2) containing the lyso-Gb3(−2) moiety. The total concentrations and Gb3 analog distributions determined by the two methods were comparable. Gb3(+18) levels were high in the kidneys (24% of total Gb3) and the liver (13%), and we observed Gb3(−2) in the heart (10%) and the kidneys (5%). These results indicate organ-specific expression of Gb3 analogs, insights that may lead to a deeper understanding of the pathophysiology of Fabry disease. Full Article
anal Correction: Comparative structure-function analysis of bromodomain and extraterminal motif (BET) proteins in a gene-complementation system. [Additions and Corrections] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 VOLUME 295 (2020) PAGES 1898–1914Yichen Zhong's name was misspelled. The correct spelling is shown above. Full Article
anal SAS Notes for SAS®9 - 53757: Frequently asked questions about report alerts in SAS Visual Analytics in 7.5 and earlier By feedproxy.google.com Published On :: Tue, 5 May 2020 12:39:04 EST SAS Visual Analytics can be configured to send a notification to specific users when report objects contain data that meets certain criteria. This SAS note contains frequently asked questions about setting up alerts. Full Article VISANLYTBNDL+SAS+Visual+Analytics
anal X-ray analysis sheds light on construction and conservation of artefacts from Henry VIII's warship By www.eurekalert.org Published On :: Tue, 28 Apr 2020 00:00:00 EDT (University of Warwick) 21st century X-ray technology has allowed University of Warwick scientists to peer back through time at the production of the armour worn by the crew of Henry VIII's favoured warship, the Mary Rose. Full Article
anal Ancient Andes, analyzed By www.eurekalert.org Published On :: Thu, 07 May 2020 00:00:00 EDT (Harvard Medical School) An international research team has conducted the first in-depth, wide-scale study of the genomic history of ancient civilizations in the central Andes mountains and coast before European contact. The findings reveal early genetic distinctions between groups in nearby regions, population mixing within and beyond the Andes, surprising genetic continuity amid cultural upheaval, and ancestral cosmopolitanism among some of the region's most well-known ancient civilizations. Full Article
anal Iatrogenic Inpatient Hypoglycemia: Risk Factors, Treatment, and Prevention: Analysis of Current Practice at an Academic Medical Center With Implications for Improvement Efforts By spectrum.diabetesjournals.org Published On :: 2008-10-01 Gregory A. MaynardOct 1, 2008; 21:241-247Articles Full Article
anal What Next After the Facebook and Cambridge Analytica Revelations? By feedproxy.google.com Published On :: Wed, 23 May 2018 11:00:00 +0000 Research Event 2 July 2018 - 6:00pm to 7:30pm Chatham House, London Event participants Silkie Carlo, Director, Big Brother WatchProfessor David Kaye, UN Special Rapporteur on the Promotion and Protection of the Right to Freedom of Opinion and Expression, University of California, Irvine, School of Law Professor Lorna McGregor, Principal Investigator and Co-Director of the ESRC, Human Rights, Big Data and Technology ProjectJames Williams, Oxford Internet InstituteChair: Harriet Moynihan, Associate Fellow, International Law Programme, Chatham House Please note this event was originally scheduled on 13 June 2018 and has been postponed to 2 July 2018.Technology companies, social media platforms and other internet intermediaries dominate the digital age, and harnessing data in algorithmic and artificial intelligence systems is widespread, from political campaigns to judicial sentencing.The recent Facebook and Cambridge Analytica revelations provide a sharp illustration of the risks to human rights and democracy posed by data-mining and "platform capital".These revelations have focused public and policy debate on two key issues. First, they raise questions of how accountability and remedies can be effectively achieved, particularly where companies close in the wake of such revelations. Second, key questions arise on what regulation should look like.Facebook has pledged to respect privacy of its users better, but how effective is self-regulation? There has been heavy emphasis on the role that the EU General Data Protection Regulation (GDPR) can play to improve the protection of privacy and data protection, but will it be enough? What are the implications for international law - how can the established standards in human rights and data protection respond to these challenges?This event, co-hosted with the ESRC, Human Rights, Big Data and Technology Project, will be followed by a drinks reception.Read the meeting summary on the Human Rights, Big Data and Technology Project website. Department/project International Law Programme, International Law Discussion Group Full Article
anal Determination of globotriaosylceramide analogs in the organs of a mouse model of Fabry disease [Lipids] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Fabry disease is a heritable lipid disorder caused by the low activity of α-galactosidase A and characterized by the systemic accumulation of globotriaosylceramide (Gb3). Recent studies have reported a structural heterogeneity of Gb3 in Fabry disease, including Gb3 isoforms with different fatty acids and Gb3 analogs with modifications on the sphingosine moiety. However, Gb3 assays are often performed only on the selected Gb3 isoforms. To precisely determine the total Gb3 concentration, here we established two methods for determining both Gb3 isoforms and analogs. One was the deacylation method, involving Gb3 treatment with sphingolipid ceramide N-deacylase, followed by an assay of the deacylated products, globotriaosylsphingosine (lyso-Gb3) and its analogs, by ultra-performance LC coupled to tandem MS (UPLC-MS/MS). The other method was a direct assay established in the present study for 37 Gb3 isoforms and analogs/isoforms by UPLC-MS/MS. Gb3s from the organs of symptomatic animals of a Fabry disease mouse model were mainly Gb3 isoforms and two Gb3 analogs, such as Gb3(+18) containing the lyso-Gb3(+18) moiety and Gb3(−2) containing the lyso-Gb3(−2) moiety. The total concentrations and Gb3 analog distributions determined by the two methods were comparable. Gb3(+18) levels were high in the kidneys (24% of total Gb3) and the liver (13%), and we observed Gb3(−2) in the heart (10%) and the kidneys (5%). These results indicate organ-specific expression of Gb3 analogs, insights that may lead to a deeper understanding of the pathophysiology of Fabry disease. Full Article
anal Genetic Profile and Functional Proteomics of Anal Squamous Cell Carcinoma: Proposal for a Molecular Classification By feedproxy.google.com Published On :: 2020-04-01 Lucía Trilla-FuertesApr 1, 2020; 19:690-700Research Full Article
anal Integrative Metabolic Pathway Analysis Reveals Novel Therapeutic Targets in Osteoarthritis By feedproxy.google.com Published On :: 2020-04-01 Beatriz RochaApr 1, 2020; 19:574-588Research Full Article
anal Dysregulation of Exosome Cargo by Mutant Tau Expressed in Human-Induced Pluripotent Stem Cell (iPSC) Neurons Revealed by Proteomics Analyses By feedproxy.google.com Published On :: 2020-04-15 Sonia PodvinApr 15, 2020; 0:RA120.002079v1-mcp.RA120.002079Research Full Article
anal Immediate adaptation analysis implicates BCL6 as an EGFR-TKI combination therapy target in NSCLC By feedproxy.google.com Published On :: 2020-03-31 Yan Zhou TranMar 31, 2020; 0:RA120.002036v1-mcp.RA120.002036Research Full Article
anal Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling By feedproxy.google.com Published On :: 2020-04-06 Samuel W EntwisleApr 6, 2020; 0:RA120.001946v2-mcp.RA120.001946Research Full Article
anal DEqMS: a method for accurate variance estimation in differential protein expression analysis By feedproxy.google.com Published On :: 2020-03-23 Yafeng ZhuMar 23, 2020; 0:TIR119.001646v1-mcp.TIR119.001646Technological Innovation and Resources Full Article
anal Acquiring and Analyzing Data Independent Acquisition Proteomics Experiments without Spectrum Libraries By feedproxy.google.com Published On :: 2020-04-20 Lindsay K PinoApr 20, 2020; 0:P119.001913v1-mcp.P119.001913Perspective Full Article
anal 11C-choline PET/CT in recurrent prostate cancer: retrospective analysis in a large US patient series By jnm.snmjournals.org Published On :: 2019-12-20T13:25:42-08:00 Purpose: To evaluate 11C-choline PET/CT detection performance for biochemically recurrent prostate cancer (PCa) in a large non-European cohort in the context of emerging evidence for PSMA PET in this setting, and to map patterns of PCa recurrence. Methods: We retrospectively analyzed 11C-choline PET/CT scans from 287 patients who were enrolled onto an imaging protocol based on rising prostate-specific antigen (PSA) levels (mean:3.43 ng/mL, median:0.94 ng/mL, range:0.15–89.91) and suspected recurrent PCa. A total of 187 patients had undergone primary radical prostatectomy (RP; 79/187 had secondary radiotherapy), 30 had undergone primary radiotherapy (RT), and 70 had persistent PSA elevation after receiving initial treatment (69 post-RP, 1 post-RT). The level of suspicion for recurrence on 11C-choline PET/CT was scored (0:negative, 1:equivocal, 2:positive) by two readers. The correlation between 11C-choline PET/CT positivity and initial treatment, Gleason score, NCCN stage, PSA level, PSA doubling time, PSA velocity, and time between initial treatment and PET imaging was evaluated. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria were used to map 11C-choline recurrence patterns. Results: Considering scores 1 and 2 as positives, consensus between the two readers deemed 66% of the 11C-choline PET/CT scans as positive. When sorted by PSA level, 45% of patients with PSA<0.5 ng/mL, 56% of patients with PSA 0.5–0.99 ng/mL, 70% of patients with PSA 1.0–1.99 ng/mL, and 90% of patients with PSA ≥2.0 ng/mL scored either 1 or 2 on 11C-choline PET/CT scans. When considering scores of 2 only, 11C-choline PET/CT positivity was 54% (28%, 46%, 62%, and 81%, respectively, for patients with PSA <0.5 ng/mL, 0.5–0.99 ng/mL, 1.0–1.99 ng/mL, and ≥2.0 ng/mL). In multivariate analysis, only the PSA level was significantly associated with scan positivity. Pattern analysis showed that pelvic lymph nodes were the most common site of recurrence, and 28% of patients had 11C-choline-positive suspected recurrences outside the initial treatment field. Conclusion: 11C-choline PET/CT can detect PCa recurrence even among patients with low PSA levels when interpretation accounts for the clinical context, providing a certain pre-test probability. Until PSMA agents are fully approved for PCa, choline PET/CT may provide clinical utility. Full Article
anal Radioiodine Ablation of Remaining Thyroid Lobe in Patients with Differentiated Thyroid Cancer Treated by Lobectomy. A systematic review and meta-analysis. By jnm.snmjournals.org Published On :: 2020-04-24T14:33:41-07:00 Purpose: We aimed to conduct a systematic review and meta-analysis of studies reporting the performance of radioactive iodine therapy (131-I therapy) in differentiating thyroid cancer (DTC) patients requiring a completion treatment following lobectomy. We also evaluated the response to 131-I therapy according to 2015ATA guidelines and the adverse events. Methods: A specific search strategy was designed to find articles evaluating the use of I-131 in patients with evidence of DTC after lobectomy. PubMed, CENTRAL, Scopus and Web of Science were searched. The search was updated until January 2020, without language restriction. Data were cross-checked and any discrepancy discussed. A proportion meta-analysis (with 95%CI) was performed using the random-effects model. Meta-regressions on I-131 success were attempted. Results: The pooled success ablation rate was 69% with better results in patients receiving a single administration of about 3.7 GBq; high heterogeneity was found (I2 85%), and publication bias was absent (Egger test: P = 0.57). Incomplete structural responses were recorded in only 14 of 695 (2%) patients enrolled in our analysis. Incomplete biochemical responses were observed in 8 to 24% of patients, with higher rates (24%) in patients receiving low radioiodine activities (~1.1 GBq) and lower rates (from 8 to 18%) in patients receiving higher activities of radioiodine (~3.7 Gbq). Neck pain due to thyroiditis was reported in up to 18% of patients but, in most cases, symptoms resolved after oral paracetamol or a short course of prednisone. Conclusion: Lobar ablation with 131-I is effective especially when high 131I activities are used. However, the rate of incomplete biochemical response to initial treatment appears to be slightly higher than the classical scheme of initial treatment of DTC. "Radioisotopic lobectomy" should be considered for patients with low-to-intermediate risk DTC requiring completion treatment after lobectomy due to specific individual risk factors and/or patient’s preferences. Full Article
anal NEMESIS: Non-inferiority, Individual Patient Meta-analysis of Selective Internal Radiation Therapy with Yttrium-90 Resin Microspheres versus Sorafenib in Advanced Hepatocellular Carcinoma By jnm.snmjournals.org Published On :: 2020-05-01T11:16:57-07:00 In randomized clinical trials (RCTs), no survival benefit has been observed for selective internal radiotherapy (SIRT) over sorafenib in patients with advanced hepatocellular carcinoma (aHCC). This study aimed to assess by means of a meta-analysis whether overall survival (OS) with SIRT, as monotherapy or followed by sorafenib, is non-inferior to sorafenib, and compare safety profiles for patients with aHCC. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library up to February 2019 to identify RCTs comparing SIRT as monotherapy, or followed by sorafenib, to sorafenib monotherapy among patients with aHCC. The main outcomes were OS and frequency of treatment-related severe adverse events (AEs grade ≥3). The per-protocol population was the primary analysis population. A non-inferiority margin of 1.08 in terms of hazard ratio (HR) was pre-specified for the upper boundary of 95% confidence interval (CI) for OS. Pre-specified subgroup analyses were performed. Results: Three RCTs, involving 1,243 patients, comparing sorafenib with SIRT (SIRveNIB and SARAH) or SIRT followed by sorafenib (SORAMIC), were included. After randomization, 411/635 (64.7%) patients allocated to SIRT and 522/608 (85.8%) allocated to sorafenib completed the studies without major protocol deviations. Median OS with SIRT, whether or not followed by sorafenib, was non-inferior to sorafenib (10.2 and 9.2 months, [HR 0.91, 95% CI 0.78–1.05]). Treatment-related severe adverse events were reported in 149/515 patients (28.9%) who received SIRT and 249/575 (43.3%) who received sorafenib only (p<0.01). Conclusion: SIRT as initial therapy for aHCC is non-inferior to sorafenib in terms of OS, and offers a better safety profile. Full Article
anal Reported differences between Digital and Analog PET/CT studies By jnm.snmjournals.org Published On :: 2020-05-01T11:16:57-07:00 Full Article
anal Correction: Graph Algorithms for Condensing and Consolidating Gene Set Analysis Results. [Additions and Corrections] By feedproxy.google.com Published On :: 2020-02-01T00:05:30-08:00 Full Article
anal Site-specific N-glycan Analysis of Antibody-binding Fc {gamma} Receptors from Primary Human Monocytes [Research] By feedproxy.google.com Published On :: 2020-02-01T00:05:30-08:00 FcRIIIa (CD16a) and FcRIIa (CD32a) on monocytes are essential for proper effector functions including antibody dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). Indeed, therapeutic monoclonal antibodies (mAbs) that bind FcRs with greater affinity exhibit greater efficacy. Furthermore, post-translational modification impacts antibody binding affinity, most notably the composition of the asparagine(N)-linked glycan at N162 of CD16a. CD16a is widely recognized as the key receptor for the monocyte response, however the post-translational modifications of CD16a from endogenous monocytes are not described. Here we isolated monocytes from individual donors and characterized the composition of CD16a and CD32a N-glycans from all modified sites. The composition of CD16a N-glycans varied by glycosylation site and donor. CD16a displayed primarily complex-type biantennary N-glycans at N162, however some individuals expressed CD16a V158 with ~20% hybrid and oligomannose types which increased affinity for IgG1 Fc according to surface plasmon resonance binding analyses. The CD16a N45-glycans contain markedly less processing than other sites with >75% hybrid and oligomannose forms. N38 and N74 of CD16a both contain highly processed complex-type N-glycans with N-acetyllactosamine repeats and complex-type biantennary N-glycans dominate at N169. The composition of CD16a N-glycans isolated from monocytes included a higher proportion of oligomannose-type N-glycans at N45 and less sialylation plus greater branch fucosylation than we observed in a recent analysis of NK cell CD16a. The additional analysis of CD32a from monocytes revealed different features than observed for CD16a including the presence of a predominantly biantennary complex-type N-glycans with two sialic acids at both sites (N64 and N145). Full Article
anal N-glycosylation Site Analysis Reveals Sex-related Differences in Protein N-glycosylation in the Rice Brown Planthopper (Nilaparvata lugens) [Research] By feedproxy.google.com Published On :: 2020-03-01T00:05:26-08:00 Glycosylation is a common modification of proteins and critical for a wide range of biological processes. Differences in protein glycosylation between sexes have already been observed in humans, nematodes and trematodes, and have recently also been reported in the rice pest insect Nilaparvata lugens. Although protein N-glycosylation in insects is nowadays of high interest because of its potential for exploitation in pest control strategies, the functionality of differential N-glycosylation between sexes is yet unknown. In this study, therefore, the occurrence and role of sex-related protein N-glycosylation in insects were examined. A comprehensive investigation of the N-glycosylation sites from the adult stages of N. lugens was conducted, allowing a qualitative and quantitative comparison between sexes at the glycopeptide level. N-glycopeptide enrichment via lectin capturing using the high mannose/paucimannose-binding lectin Concanavalin A, or the Rhizoctonia solani agglutinin which interacts with complex N-glycans, resulted in the identification of over 1300 N-glycosylation sites derived from over 600 glycoproteins. Comparison of these N-glycopeptides revealed striking differences in protein N-glycosylation between sexes. Male- and female-specific N-glycosylation sites were identified, and some of these sex-specific N-glycosylation sites were shown to be derived from proteins with a putative role in insect reproduction. In addition, differential glycan composition between males and females was observed for proteins shared across sexes. Both lectin blotting experiments as well as transcript expression analyses with complete insects and insect tissues confirmed the observed differences in N-glycosylation of proteins between sexes. In conclusion, this study provides further evidence for protein N-glycosylation to be sex-related in insects. Furthermore, original data on N-glycosylation sites of N. lugens adults are presented, providing novel insights into planthopper's biology and information for future biological pest control strategies. Full Article
anal Peptidomic Analysis of Urine from Youths with Early Type 1 Diabetes Reveals Novel Bioactivity of Uromodulin Peptides In Vitro [Research] By feedproxy.google.com Published On :: 2020-03-01T00:05:26-08:00 Chronic hyperglycemia is known to disrupt the proteolytic milieu, initiating compensatory and maladaptive pathways in the diabetic kidney. Such changes in intrarenal proteolysis are captured by the urinary peptidome. To elucidate the early kidney response to chronic hyperglycemia, we conducted a peptidomic investigation into urines from otherwise healthy youths with type 1 diabetes and their non-diabetic peers using unbiased and targeted mass spectrometry-based techniques. This cross-sectional study included two separate cohorts for the discovery (n = 30) and internal validation (n = 30) of differential peptide excretion. Peptide bioactivity was predicted using PeptideRanker and subsequently verified in vitro. Proteasix and the Nephroseq database were used to identify putative proteases responsible for peptide generation and examine their expression in diabetic nephropathy. A total of 6550 urinary peptides were identified in the discovery analysis. We further examined the subset of 162 peptides, which were quantified across all thirty samples. Of the 15 differentially excreted peptides (p < 0.05), seven derived from a C-terminal region (589SGSVIDQSRVLNLGPITRK607) of uromodulin, a kidney-specific protein. Increased excretion of five uromodulin peptides was replicated in the validation cohort using parallel reaction monitoring (p < 0.05). One of the validated peptides (SGSVIDQSRVLNLGPI) activated NFB and AP-1 signaling, stimulated cytokine release, and enhanced neutrophil migration in vitro. In silico analyses highlighted several potential proteases such as hepsin, meprin A, and cathepsin B to be responsible for generating these peptides. In summary, we identified a urinary signature of uromodulin peptides associated with early type 1 diabetes before clinical manifestations of kidney disease and discovered novel bioactivity of uromodulin peptides in vitro. Our present findings lay the groundwork for future studies to validate peptide excretion in larger and broader populations, to investigate the role of bioactive uromodulin peptides in high glucose conditions, and to examine proteases that cleave uromodulin. Full Article
anal Proteomic Analysis Reveals that Topoisomerase 2A is Associated with Defective Sperm Head Morphology [Research] By feedproxy.google.com Published On :: 2020-03-01T00:05:26-08:00 Male infertility is widespread and estimated to affect 1 in 20 men. Although in some cases the etiology of the condition is well understood, for at least 50% of men, the underlying cause is yet to be classified. Male infertility, or subfertility, is often diagnosed by looking at total sperm produced, motility of the cells and overall morphology. Although counting spermatozoa and their associated motility is routine, morphology assessment is highly subjective, mainly because of the procedure being based on microscopic examination. A failure to diagnose male-infertility or sub-fertility has led to a situation where assisted conception is often used unnecessarily. As such, biomarkers of male infertility are needed to help establish a more consistent diagnosis. In the present study, we compared nuclear extracts from both high- and low-quality spermatozoa by LC-MS/MS based proteomic analysis. Our data shows that nuclear retention of specific proteins is a common facet among low-quality sperm cells. We demonstrate that the presence of Topoisomerase 2A in the sperm head is highly correlated to poor head morphology. Topoisomerase 2A is therefore a potential new biomarker for confirming male infertility in clinical practice. Full Article
anal Genetic Profile and Functional Proteomics of Anal Squamous Cell Carcinoma: Proposal for a Molecular Classification [Research] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 Anal squamous cell carcinoma is a rare tumor. Chemo-radiotherapy yields a 50% 3-year relapse-free survival rate in advanced anal cancer, so improved predictive markers and therapeutic options are needed. High-throughput proteomics and whole-exome sequencing were performed in 46 paraffin samples from anal squamous cell carcinoma patients. Hierarchical clustering was used to establish groups de novo. Then, probabilistic graphical models were used to study the differences between groups of patients at the biological process level. A molecular classification into two groups of patients was established, one group with increased expression of proteins related to adhesion, T lymphocytes and glycolysis; and the other group with increased expression of proteins related to translation and ribosomes. The functional analysis by the probabilistic graphical model showed that these two groups presented differences in metabolism, mitochondria, translation, splicing and adhesion processes. Additionally, these groups showed different frequencies of genetic variants in some genes, such as ATM, SLFN11 and DST. Finally, genetic and proteomic characteristics of these groups suggested the use of some possible targeted therapies, such as PARP inhibitors or immunotherapy. Full Article
anal Integrative Metabolic Pathway Analysis Reveals Novel Therapeutic Targets in Osteoarthritis [Research] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 In osteoarthritis (OA), impairment of cartilage regeneration can be related to a defective chondrogenic differentiation of mesenchymal stromal cells (MSCs). Therefore, understanding the proteomic- and metabolomic-associated molecular events during the chondrogenesis of MSCs could provide alternative targets for therapeutic intervention. Here, a SILAC-based proteomic analysis identified 43 proteins related with metabolic pathways whose abundance was significantly altered during the chondrogenesis of OA human bone marrow MSCs (hBMSCs). Then, the level and distribution of metabolites was analyzed in these cells and healthy controls by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), leading to the recognition of characteristic metabolomic profiles at the early stages of differentiation. Finally, integrative pathway analysis showed that UDP-glucuronic acid synthesis and amino sugar metabolism were downregulated in OA hBMSCs during chondrogenesis compared with healthy cells. Alterations in these metabolic pathways may disturb the production of hyaluronic acid (HA) and other relevant cartilage extracellular matrix (ECM) components. This work provides a novel integrative insight into the molecular alterations of osteoarthritic MSCs and potential therapeutic targets for OA drug development through the enhancement of chondrogenesis. Full Article
anal Proteomic Analysis of Salmonella-modified Membranes Reveals Adaptations to Macrophage Hosts [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Systemic infection and proliferation of intracellular pathogens require the biogenesis of a growth-stimulating compartment. The gastrointestinal pathogen Salmonella enterica commonly forms highly dynamic and extensive tubular membrane compartments built from Salmonella-modified membranes (SMMs) in diverse host cells. Although the general mechanism involved in the formation of replication-permissive compartments of S. enterica is well researched, much less is known regarding specific adaptations to different host cell types. Using an affinity-based proteome approach, we explored the composition of SMMs in murine macrophages. The systematic characterization provides a broader landscape of host players to the maturation of Salmonella-containing compartments and reveals core host elements targeted by Salmonella in macrophages as well as epithelial cells. However, we also identified subtle host specific adaptations. Some of these observations, such as the differential involvement of the COPII system, Rab GTPases 2A, 8B, 11 and ER transport proteins Sec61 and Sec22B may explain cell line-dependent variations in the pathophysiology of Salmonella infections. In summary, our system-wide approach demonstrates a hitherto underappreciated impact of the host cell type in the formation of intracellular compartments by Salmonella. Full Article
anal Lithium ion adduction enables UPLC-MS/MS-based analysis of multi-class 3-hydroxyl group-containing keto-steroids By feedproxy.google.com Published On :: 2020-04-01 Qiuyi WangApr 1, 2020; 61:570-579Methods Full Article