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https://www.readbyqxmd.com/read/28209776/distance-dependent-gradient-in-nmdar-driven-spine-calcium-signals-along-tapering-dendrites
#1
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...
February 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28199445/plant-arginyltransferases-ates
#2
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
#3
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
#4
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
#5
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...
February 6, 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
#6
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...
February 2, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28143909/papers-of-note-in-science-355-6323
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28011903/safety-and-efficacy-of-obinutuzumab-with-chop-or-bendamustine-in-previously-untreated-follicular-lymphoma
#16
Andrew Grigg, Martin J S Dyer, Marcos González Díaz, Martin Dreyling, Simon Rule, Guiyuan Lei, Andrea Knapp, Elisabeth Wassner-Fritsch, Paula Marlton
The GAUDI study assessed safety and preliminary efficacy of induction therapy with obinutuzumab plus chemotherapy, followed by maintenance with obinutuzumab alone, in previously untreated patients with follicular lymphoma. Assignment to chemotherapy was decided on a per center basis before patient enrollment. Patients (n=81) received 4-6 cycles of obinutuzumab plus bendamustine every 4 weeks or 6-8 cycles of obinutuzumab plus CHOP every 3 weeks. Patients with an end-of-treatment response were eligible for obinutuzumab maintenance therapy every 3 months for 2 years or until disease progression...
December 23, 2016: Haematologica
https://www.readbyqxmd.com/read/27936067/deletion-at-the-gcnt2-locus-causes-autosomal-recessive-congenital-cataracts
#17
Bushra Irum, Shahid Y Khan, Muhammad Ali, Muhammad Daud, Firoz Kabir, Bushra Rauf, Fareeha Fatima, Hira Iqbal, Arif O Khan, Saif Al Obaisi, Muhammad Asif Naeem, Idrees A Nasir, Shaheen N Khan, Tayyab Husnain, Sheikh Riazuddin, Javed Akram, Allen O Eghrari, S Amer Riazuddin
PURPOSE: The aim of this study is to identify the molecular basis of autosomal recessive congenital cataracts (arCC) in a large consanguineous pedigree. METHODS: All participating individuals underwent a detailed ophthalmic examination. Each patient's medical history, particularly of cataracts and other ocular abnormalities, was compiled from available medical records and interviews with family elders. Blood samples were donated by all participating family members and used to extract genomic DNA...
2016: PloS One
https://www.readbyqxmd.com/read/27908704/on-the-relationship-between-cell-cycle-analysis-with-ergodic-principles-and-age-structured-cell-population-models
#18
K Kuritz, D Stöhr, N Pollak, F Allgöwer
Cyclic processes, in particular the cell cycle, are of great importance in cell biology. Continued improvement in cell population analysis methods like fluorescence microscopy, flow cytometry, CyTOF or single-cell omics made mathematical methods based on ergodic principles a powerful tool in studying these processes. In this paper, we establish the relationship between cell cycle analysis with ergodic principles and age structured population models. To this end, we describe the progression of a single cell through the cell cycle by a stochastic differential equation on a one dimensional manifold in the high dimensional dataspace of cell cycle markers...
November 28, 2016: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/27846997/safety-compliance-and-safety-climate-a-repeated-cross-sectional-study-in-the-oil-and-gas-industry
#19
Sverre A Kvalheim, Øyvind Dahl
INTRODUCTION: Violations of safety rules and procedures are commonly identified as a causal factor in accidents in the oil and gas industry. Extensive knowledge on effective management practices related to improved compliance with safety procedures is therefore needed. Previous studies of the causal relationship between safety climate and safety compliance demonstrate that the propensity to act in accordance with prevailing rules and procedures is influenced to a large degree by workers' safety climate...
December 2016: Journal of Safety Research
https://www.readbyqxmd.com/read/27845678/deep-logic-networks-inserting-and-extracting-knowledge-from-deep-belief-networks
#20
Son N Tran, Artur S d'Avila Garcez
Developments in deep learning have seen the use of layerwise unsupervised learning combined with supervised learning for fine-tuning. With this layerwise approach, a deep network can be seen as a more modular system that lends itself well to learning representations. In this paper, we investigate whether such modularity can be useful to the insertion of background knowledge into deep networks, whether it can improve learning performance when it is available, and to the extraction of knowledge from trained deep networks, and whether it can offer a better understanding of the representations learned by such networks...
November 8, 2016: IEEE Transactions on Neural Networks and Learning Systems
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