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N-end rule

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https://www.readbyqxmd.com/read/28431231/sequestration-from-protease-adaptor-confers-differential-stability-to-protease-substrate
#1
Jinki Yeom, Kyle J Wayne, Eduardo A Groisman
According to the N-end rule, the N-terminal residue of a protein determines its stability. In bacteria, the adaptor ClpS mediates proteolysis by delivering substrates bearing specific N-terminal residues to the protease ClpAP. We now report that the Salmonella adaptor ClpS binds to the N terminus of the regulatory protein PhoP, resulting in PhoP degradation by ClpAP. We establish that the PhoP-activated protein MgtC protects PhoP from degradation by outcompeting ClpS for binding to PhoP. MgtC appears to act exclusively on PhoP, as it did not alter the stability of a different ClpS-dependent ClpAP substrate...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28426839/medical-history-in-the-hellenic-journal-of-nuclear-medicine
#2
EDITORIAL
Andreas Otte, Byeong Cheol Ahn
The Hellenic Journal of Nuclear Medicine is about to celebrate its 20th anniversary end of 2017. On board of the editorial team since 2003, this journal has influenced me like a good friend over the many past years. From time to time, the journal has published interesting and valuable historical notes. They show that nuclear medicine has a history and that medicine is its basis. They also teach us today, and some of the ancient perspectives and approaches are still valid. The reader of HJNM may be interested in these historical contributions, as they are timeless...
January 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28401622/predicting-mortality-in-the-emergency-department-external-validation-and-derivation-of-a-clinical-prediction-tool
#3
Rajat N Moman, Caitlin Loprinzi Brauer, Katherine M Kelsey, Rachel D Havyer, Christine M Lohse, M Fernanda Bellolio
BACKGROUND: he Choosing Wisely campaign has called for better engagement of palliative and hospice care services for patients in the emergency department (ED). PREDICT is a clinical prediction tool that was derived in an Australian ED cohort. It assesses a patient's risk of mortality at one year to select those who would benefit from advanced care planning. Such goals of care discussion can improve patients' ability to communicate what they want out of their healthcare and, in cases of end-of-life, potentially reduce the number of futile interventions...
April 12, 2017: Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine
https://www.readbyqxmd.com/read/28392261/bound-waters-mediate-binding-of-diverse-substrates-to-a-ubiquitin-ligase
#4
Juliana Muñoz-Escobar, Edna Matta-Camacho, Cordelia Cho, Guennadi Kozlov, Kalle Gehring
The N-end rule pathway controls the half-life of proteins based on their N-terminal residue. Positively charged type 1 N-degrons are recognized by a negatively charged pocket on the Zn finger named the UBR box. Here, we show that the UBR box is rigid, but bound water molecules in the pocket provide the structural plasticity required to bind different positively charged amino acids. Ultra-high-resolution crystal structures of arginine, histidine, and methylated arginine reveal that water molecules mediate the binding of N-degron peptides...
March 27, 2017: Structure
https://www.readbyqxmd.com/read/28389126/pro-moting-the-turnover-of-gluconeogenic-enzymes-by-a-new-branch-of-the-n-end-rule-pathway
#5
David A Dougan
The N-end rule pathway is a set of protein degradation systems that link the in vivo stability of a protein to its N-terminal residue. A recent paper from Alexander Varshavsky's laboratory [1] identifies a new branch of the N-end rule pathway that specifically recognizes the N-terminal Pro residue of key gluconeogenesis enzymes.
April 4, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28356211/pkd2-related-autosomal-dominant-polycystic-kidney-disease-prevalence-clinical-presentation-mutation-spectrum-and%C3%A2-prognosis
#6
Emilie Cornec-Le Gall, Marie-Pierre Audrézet, Eric Renaudineau, Maryvonne Hourmant, Christophe Charasse, Eric Michez, Thierry Frouget, Cécile Vigneau, Jacques Dantal, Pascale Siohan, Hélène Longuet, Philippe Gatault, Laure Ecotière, Frank Bridoux, Lise Mandart, Catherine Hanrotel-Saliou, Corina Stanescu, Pascale Depraetre, Sophie Gie, Michiel Massad, Aude Kersalé, Guillaume Séret, Jean-François Augusto, Philippe Saliou, Sandrine Maestri, Jian-Min Chen, Peter C Harris, Claude Férec, Yannick Le Meur
BACKGROUND: PKD2-related autosomal dominant polycystic kidney disease (ADPKD) is widely acknowledged to be of milder severity than PKD1-related disease, but population-based studies depicting the exact burden of the disease are lacking. We aimed to revisit PKD2 prevalence, clinical presentation, mutation spectrum, and prognosis through the Genkyst cohort. STUDY DESIGN: Case series, January 2010 to March 2016. SETTINGS & PARTICIPANTS: Genkyst study participants are individuals older than 18 years from 22 nephrology centers from western France with a diagnosis of ADPKD based on Pei criteria or at least 10 bilateral kidney cysts in the absence of a familial history...
March 26, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28338551/standardizing-robotic-lobectomy-feasibility-and-safety-in-128-consecutive-lobectomies-within-a-single-healthcare-system
#7
John F Lazar, Laurence N Spier, Alan R Hartman, Richard S Lazzaro
OBJECTIVE: Single-surgeon cohorts assessing robotically assisted video-assisted thoracic (RA-VATS) lobectomy have reported good outcomes, but there are little data regarding multiple surgeons applying a standard technique in separate hospitals. The purpose of this study was to show how a standardized robotic technique is both safe and reproducible between surgeons and institutions. METHODS: From July 1, 2012, to October 1, 2013, patients undergoing RA-VATS lobectomy for both benign and malignant disease were identified from a prospectively collected database of two thoracic surgeons from different hospitals within the same healthcare system and retrospectively analyzed...
March 23, 2017: Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery
https://www.readbyqxmd.com/read/28335006/a-platform-for-functional-assessment-of-large-variant-libraries-in-mammalian-cells
#8
Kenneth A Matreyek, Jason J Stephany, Douglas M Fowler
Sequencing-based, massively parallel genetic assays have revolutionized our ability to quantify the relationship between many genotypes and a phenotype of interest. Unfortunately, variant library expression platforms in mammalian cells are far from ideal, hindering the study of human gene variants in their physiologically relevant cellular contexts. Here, we describe a platform for phenotyping variant libraries in transfectable mammalian cell lines in two steps. First, a landing pad cell line with a genomically integrated, Tet-inducible cassette containing a Bxb1 recombination site is created...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28332493/plant-cysteine-oxidases-are-dioxygenases-that-directly-enable-arginyl-transferase-catalysed-arginylation-of-n-end-rule-targets
#9
Mark D White, Maria Klecker, Richard J Hopkinson, Daan A Weits, Carolin Mueller, Christin Naumann, Rebecca O'Neill, James Wickens, Jiayu Yang, Jonathan C Brooks-Bartlett, Elspeth F Garman, Tom N Grossmann, Nico Dissmeyer, Emily Flashman
Crop yield loss due to flooding is a threat to food security. Submergence-induced hypoxia in plants results in stabilization of group VII ETHYLENE RESPONSE FACTORs (ERF-VIIs), which aid survival under these adverse conditions. ERF-VII stability is controlled by the N-end rule pathway, which proposes that ERF-VII N-terminal cysteine oxidation in normoxia enables arginylation followed by proteasomal degradation. The PLANT CYSTEINE OXIDASEs (PCOs) have been identified as catalysts of this oxidation. ERF-VII stabilization in hypoxia presumably arises from reduced PCO activity...
March 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28317149/association-between-variants-in-genes-involved-in-the-immune-response-and-prostate-cancer-risk-in-men-randomized-to-the-finasteride-arm-in-the-prostate-cancer-prevention-trial
#10
Danyelle A Winchester, Cathee Till, Phyllis J Goodman, Catherine M Tangen, Regina M Santella, Teresa L Johnson-Pais, Robin J Leach, Jianfeng Xu, S Lilly Zheng, Ian M Thompson, M Scott Lucia, Scott M Lippman, Howard L Parnes, William B Isaacs, Angelo M De Marzo, Charles G Drake, Elizabeth A Platz
BACKGROUND: We reported that some, but not all single nucleotide polymorphisms (SNPs) in select immune response genes are associated with prostate cancer, but not individually with the prevalence of intraprostatic inflammation in the Prostate Cancer Prevention Trial (PCPT) placebo arm. Here, we investigated whether these same SNPs are associated with risk of lower- and higher-grade prostate cancer in men randomized to finasteride, and with prevalence of intraprostatic inflammation among controls...
June 2017: Prostate
https://www.readbyqxmd.com/read/28287060/end-to-end-anastomosis-in-the-management-of-laryngotracheal-defects
#11
E D Gozen, M Yener, Z B Erdur, E Karaman
OBJECTIVE: To present clinical experience and surgical outcomes of end-to-end anastomosis in the management of laryngotracheal stenosis and tracheal defects following invasive thyroid malignancy resection. METHODS: A retrospective analysis was performed of 14 patients with laryngotracheal stenosis and tracheal invasive thyroid malignancy. All patients underwent tracheal or cricotracheal resection and primary end-to-end anastomosis. RESULTS: Length of stenosis was 1...
May 2017: Journal of Laryngology and Otology
https://www.readbyqxmd.com/read/28277608/real-time-detection-of-proteolysis1-prt1-mediated-ubiquitination-via-fluorescently-labeled-substrate-probes
#12
Augustin C Mot, Erik Prell, Maria Klecker, Christin Naumann, Frederik Faden, Bernhard Westermann, Nico Dissmeyer
The N-end rule pathway has emerged as a major system for regulating protein functions by controlling their turnover in medical, animal and plant sciences as well as agriculture. Although novel functions and enzymes of the pathway have been discovered, the ubiquitination mechanism and substrate specificity of N-end rule pathway E3 ubiquitin ligases have remained elusive. Taking the first discovered bona fide plant N-end rule E3 ligase PROTEOLYSIS1 (PRT1) as a model, we used a novel tool to molecularly characterize polyubiquitination live, in real time...
March 9, 2017: New Phytologist
https://www.readbyqxmd.com/read/28258616/focal-salvage-hifu-in-radiorecurrent-prostate-cancer
#13
A Kanthabalan, M Peters, M Van Vulpen, N McCartan, R G Hindley, A Emara, M C Moore, M Arya, M Emberton, H U Ahmed
OBJECTIVE: To assess short to medium term cancer control rates and side effects of focal salvage High Intensity Focused Ultrasound (HIFU). MATERIALS AND METHODS: A retrospective registry analysis identified 150 men who underwent focal salvage HIFU (Sonablate 500) (November 2006-August 2015). Metastatic disease was excluded using the nodal assessment on the pelvic MRI, a radioisotope bone scan and PET imaging (choline-FDG-PET or Choline PET-CT). In our current clinical practice, metastatic disease must be ruled out by both Choline PET and bone scan...
March 4, 2017: BJU International
https://www.readbyqxmd.com/read/28224424/dynamic-characteristic-mechanism-of-atrial-septal-defect-using-real-time-three-dimensional-echocardiography-and-evaluation-of-right-ventricular-functions
#14
Gao-Wa Sharen, Jun Zhang, Chuan Qin, Qing Lv
The dynamic characteristics of the area of the atrial septal defect (ASD) were evaluated using the technique of real-time three-dimensional echocardiography (RT 3DE), the potential factors responsible for the dynamic characteristics of the area of ASD were observed, and the overall and local volume and functions of the patients with ASD were measured. RT 3DE was performed on the 27 normal controls and 28 patients with ASD. Based on the three-dimensional data workstations, the area of ASD was measured at P wave vertex, R wave vertex, T wave starting point, and T wave terminal point and in the T-P section...
February 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28209776/distance-dependent-gradient-in-nmdar-driven-spine-calcium-signals-along-tapering-dendrites
#15
Alison S Walker, Guilherme Neves, Federico Grillo, Rachel E Jackson, Mark Rigby, Cian O'Donnell, Andrew S Lowe, Gema Vizcay-Barrena, Roland A Fleck, Juan Burrone
Neurons receive a multitude of synaptic inputs along their dendritic arbor, but how this highly heterogeneous population of synaptic compartments is spatially organized remains unclear. By measuring N-methyl-d-aspartic acid receptor (NMDAR)-driven calcium responses in single spines, we provide a spatial map of synaptic calcium signals along dendritic arbors of hippocampal neurons and relate this to measures of synapse structure. We find that quantal NMDAR calcium signals increase in amplitude as they approach a thinning dendritic tip end...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28199445/plant-arginyltransferases-ates
#16
Tatiana Domitrovic, Anna K Fausto, Tatiane da F Silva, Elisson Romanel, Maite F S Vaslin
Regulation of protein stability and/or degradation of misfolded and damaged proteins are essential cellular processes. A part of this regulation is mediated by the so-called N-end rule proteolytic pathway, which, in concert with the ubiquitin proteasome system (UPS), drives protein degradation depending on the N-terminal amino acid sequence. One important enzyme involved in this process is arginyl-t-RNA transferase, known as ATE. This enzyme acts post-translationally by introducing an arginine residue at the N-terminus of specific protein targets to signal degradation via the UPS...
February 13, 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28191571/a-computer-based-prediction-platform-for-the-reaction-of-ozone-with-organic-compounds-in-aqueous-solution-kinetics-and-mechanisms
#17
Minju Lee, Lorenz C Blum, Emanuel Schmid, Kathrin Fenner, Urs von Gunten
Ozonation of secondary wastewater effluents can reduce the discharge of micropollutants by transforming their chemical structures. Therefore, a better understanding of the formation of transformation products during ozonation is important. In this study, a computer-based prediction platform for the kinetics and mechanisms of the reactions of ozone with organic compounds was developed to enable in silico predictions of transformation products. With the developed prediction platform, reaction kinetics expressed as second-order rate constants for the reactions of ozone with selected organic compounds (kO3, M(-1) s(-1)) can be predicted based on an adapted kO3 prediction model from a previous study (Lee et al...
February 13, 2017: Environmental Science. Processes & Impacts
https://www.readbyqxmd.com/read/28183314/dpp-4-inhibition-has-no-acute-effect-on-bnp-and-its-n-terminal-pro-hormone-measured-by-commercial-immune-assays-a-randomized-cross-over-trial-in-patients-with-type-2-diabetes
#18
Gian Paolo Fadini, Benedetta Maria Bonora, Mattia Albiero, Martina Zaninotto, Mario Plebani, Angelo Avogaro
BACKGROUND: Use of dipeptidyl peptidase-4 inhibitors (DPP4-i) for the treatment of type 2 diabetes (T2D) has been associated with a possible increase in the risk for heart failure (HF). B-type natriuretic peptide (BNP), which is both a biomarker of HF and a hemodynamically active hormone, is a substrate of DPP-4. We herein tested the acute effects of the DPP-4i linagliptin on BNP and NT-proBNP in a cross-over placebo-controlled trial in patients with T2D with and without chronic kidney disease (CKD)...
February 10, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28167503/ubiquitylation-activates-a-peptidase-that-promotes-cleavage-and-destabilization-of-its-activating-e3-ligases-and-diverse-growth-regulatory-proteins-to-limit-cell-proliferation-in-arabidopsis
#19
Hui Dong, Jack Dumenil, Fu-Hao Lu, Li Na, Hannes Vanhaeren, Christin Naumann, Maria Klecker, Rachel Prior, Caroline Smith, Neil McKenzie, Gerhard Saalbach, Liangliang Chen, Tian Xia, Nathalie Gonzalez, Mathilde Seguela, Dirk Inze, Nico Dissmeyer, Yunhai Li, Michael W Bevan
The characteristic shapes and sizes of organs are established by cell proliferation patterns and final cell sizes, but the underlying molecular mechanisms coordinating these are poorly understood. Here we characterize a ubiquitin-activated peptidase called DA1 that limits the duration of cell proliferation during organ growth in Arabidopsis thaliana The peptidase is activated by two RING E3 ligases, Big Brother (BB) and DA2, which are subsequently cleaved by the activated peptidase and destabilized. In the case of BB, cleavage leads to destabilization by the RING E3 ligase PROTEOLYSIS 1 (PRT1) of the N-end rule pathway...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28162984/eltrombopag-versus-placebo-for-low-risk-myelodysplastic-syndromes-with-thrombocytopenia-eqol-mds-phase-1-results-of-a-single-blind-randomised-controlled-phase-2-superiority-trial
#20
Esther N Oliva, Caterina Alati, Valeria Santini, Antonella Poloni, Alfredo Molteni, Pasquale Niscola, Flavia Salvi, Grazia Sanpaolo, Enrico Balleari, Ulrich Germing, Pierre Fenaux, Aspasia Stamatoullas, Giuseppe A Palumbo, Prassede Salutari, Stefana Impera, Paolo Avanzini, Agostino Cortelezzi, Anna Marina Liberati, Paola Carluccio, Francesco Buccisano, Maria Teresa Voso, Stefano Mancini, Austin Kulasekararaj, Fortunato Morabito, Monica Bocchia, Patrizia Cufari, Maria Antonietta Aloe Spiriti, Irene Santacaterina, Maria Grazia D'Errigo, Irene Bova, Gina Zini, Roberto Latagliata
BACKGROUND: In myelodysplastic syndromes, thrombocytopenia is associated with mortality, but treatments in this setting are scarce. We tested whether eltrombopag, a thrombopoietin receptor agonist, might be effective in improving thrombocytopenia in lower-risk myelodysplastic syndromes and severe thrombocytopenia. METHODS: EQoL-MDS was a single-blind, randomised, controlled, phase 2 superiority trial of adult patients with low-risk or International Prognostic Scoring System intermediate-1-risk myelodysplastic syndromes and severe thrombocytopenia...
March 2017: Lancet Haematology
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