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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
#1
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...
March 20, 2017: Prostate
https://www.readbyqxmd.com/read/28287060/end-to-end-anastomosis-in-the-management-of-laryngotracheal-defects
#2
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...
March 13, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28143909/papers-of-note-in-science-355-6323
#12
Annalisa M VanHook
This week's articles include new research about how dengue virus can deplete platelets; a distinct N-end rule pathway for turnover of gluconeogenic enzymes in yeast; and the involvement of SUMO, ubiquitin, and the proteasome in meiotic recombination.
January 31, 2017: Science Signaling
https://www.readbyqxmd.com/read/28134412/-guide-document-for-assistance-the-end-of-the-life
#13
Gian Piero Sancipriano
There are not any laws in Italy that rule the path of the end of life. Therefore, the doctor has to take as a reference the Supreme Judgment of the Court of Cassation 16/10/2007 n 21748. The author is proposing a different, realistic and convenient form that could be used by the patient and both his tutor and doctor to walk through the path that brings to the end of life. This document shows respect for the sanctity of life and safeguards willingness and dignity of the patient. Its purpose is to register the treatment for symptoms that leads to death, basing the relationship between a patient and his doctor on trust and confidence...
November 2016: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28130986/recognition-of-substrate-degrons-by-e3-ubiquitin-ligases-and-modulation-by-small-molecule-mimicry-strategies
#14
REVIEW
Xavier Lucas, Alessio Ciulli
The ubiquitin-proteasome system is a master regulator of protein homeostasis, by which proteins are initially targeted for poly-ubiquitination by E3 ligases and then degraded into short peptides by the proteasome. Nature evolved diverse peptidic motifs, termed degrons, to signal substrates for degradation. We discuss degrons of the N-end rule pathway and also degrons characterized by post-translational modifications, including phosphorylation and hydroxylation. In each case we detail the structural basis of E3 ligase:degron recognition and small-molecule mimicry approaches that disrupt those protein-protein interactions...
January 25, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28126757/an-n-end-rule-pathway-that-recognizes-proline-and-destroys-gluconeogenic-enzymes
#15
Shun-Jia Chen, Xia Wu, Brandon Wadas, Jang-Hyun Oh, Alexander Varshavsky
Cells synthesize glucose if deprived of it, and destroy gluconeogenic enzymes upon return to glucose-replete conditions. We found that the Gid4 subunit of the ubiquitin ligase GID in the yeast Saccharomyces cerevisiae targeted the gluconeogenic enzymes Fbp1, Icl1, and Mdh2 for degradation. Gid4 recognized the N-terminal proline (Pro) residue and the ~5-residue-long adjacent sequence motifs. Pck1, the fourth gluconeogenic enzyme, contains Pro at position 2; Gid4 directly or indirectly recognized Pro at position 2 of Pck1, contributing to its targeting...
January 27, 2017: Science
https://www.readbyqxmd.com/read/28122942/comparative-analysis-of-mitochondrial-n-termini-from-mouse-human-and-yeast
#16
Sarah E Calvo, Olivier Julien, Karl R Clauser, Hongying Shen, Kimberli J Kamer, James A Wells, Vamsi K Mootha
The majority of mitochondrial proteins are encoded in the nuclear genome, translated in the cytoplasm, and directed to the mitochondria by a N-terminal presequence that is cleaved upon import. Recently, N-proteome catalogs have been generated for mitochondria from yeast and from human U937 cells. Here we applied the subtiligase method to determine N-termini for 327 proteins in mitochondria isolated from mouse liver and kidney. Comparative analysis between mitochondrial N-termini from mouse, human, and yeast proteins shows that while presequences are poorly conserved at the sequence level, other presequence properties are extremely conserved including a length of ~20-60aa, a net charge between +3 to +6, and the presence of stabilizing amino acids at the N-termini of mature proteins that follows the N-end rule from bacteria...
January 25, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28111955/opposite-electron-transfer-dissociation-and-higher-energy-collisional-dissociation-fragmentation-characteristics-of-proteolytic-k-r-x-n-and-x-nk-r-peptides-provide-benefits-for-peptide-sequencing-in-proteomics-and-phosphoproteomics
#17
Liana Tsiatsiani, Piero Giansanti, Richard A Scheltema, Henk van den Toorn, Christopher M Overall, A F Maarten Altelaar, Albert J R Heck
A key step in shotgun proteomics is the digestion of proteins into peptides amenable for mass spectrometry. Tryptic peptides can be readily sequenced and identified by collision-induced dissociation (CID) or higher-energy collisional dissociation (HCD) because the fragmentation rules are well-understood. Here, we investigate LysargiNase, a perfect trypsin mirror protease, because it cleaves equally specific at arginine and lysine residues, albeit at the N-terminal end. LysargiNase peptides are therefore practically tryptic-like in length and sequence except that following ESI, the two protons are now both positioned at the N-terminus...
December 2, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/28108038/the-effect-of-endotracheal-tubes-versus-laryngeal-mask-airways-on-perioperative-respiratory-adverse-events-in-infants-a-randomised-controlled-trial
#18
Thomas F E Drake-Brockman, Anoop Ramgolam, Guicheng Zhang, Graham L Hall, Britta S von Ungern-Sternberg
BACKGROUND: Perioperative respiratory adverse events (PRAE) are the most common critical incidents in paediatric anaesthesia and occur more often in infants. Use of laryngeal mask airways (LMAs) is associated with reduced PRAE compared with endotracheal tubes in older children (>1 year). We aimed to evaluate the effect of these devices on the incidence of PRAE in infants. METHODS: We did a randomised controlled trial at the Princess Margaret Hospital for Children in Perth (WA, Australia) by recruiting infants (aged 0-12 months) undergoing general (with or without regional or local) anaesthesia with anticipated fentanyl dose 1 μg/kg or lower for minor elective surgery...
January 17, 2017: Lancet
https://www.readbyqxmd.com/read/28079768/interpregnancy-interval-after-termination-of-pregnancy-and-the-risks-of-adverse-outcomes-in-subsequent-birth
#19
Jaana Männistö, Aini Bloigu, Maarit Mentula, Mika Gissler, Oskari Heikinheimo, Maarit Niinimäki
OBJECTIVE: To assess whether the length of the interpregnancy interval after termination of pregnancy influences the risk of preterm birth, low birth weight, and small-for-gestational-age neonates in a subsequent pregnancy. METHODS: In this register-based study, we included all women (N=19,894) who underwent termination of pregnancy between 2000 and 2009 and whose subsequent pregnancy ended in live singleton delivery. The women were divided into five groups depending on the interpregnancy interval between termination of pregnancy and subsequent conception: interpregnancy interval less than 6 months (n=2,956), 6 to less than 12 months (n=3,203), 12 to less than 18 months (n=2,623), 18 to less than 24 months (n=2,076), and 24 months or greater (n=9,036)...
February 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28057878/pseudoautosomal-abnormalities-in-terminal-azfb-c-deletions-are-associated-with-isochromosomes-yp-and-may-lead-to-abnormal-growth-and-neuropsychiatric-function
#20
A Castro, F Rodríguez, M Flórez, P López, B Curotto, D Martínez, A Maturana, M C Lardone, C Palma, V Mericq, M Ebensperger, F Cassorla
STUDY QUESTION: Are copy number variations (CNVs) in the pseudoautosomal regions (PARs) frequent in subjects with Y-chromosome microdeletions and can they lead to abnormal stature and/or neuropsychiatric disorders? SUMMARY ANSWER: Only subjects diagnosed with azoospermia factor (AZF)b+c deletions spanning to the end of the Y chromosome (i.e. terminal deletions) harbor Y isochromosomes and/or cells 45,X that lead to pseudoautosomal gene CNVs, which were associated with abnormal stature and/or neuropsychiatric disorders...
January 5, 2017: Human Reproduction
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