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N-end rule

Stephen M Hadlow, Ross A Pinder, Mark G L Sayers
In Australian rules football structured increases in ball size during development end with the transition to the Size 5 (adult) ball at the Under-15 age group. This study assessed changes in kick technique and performance in experienced junior performers when using Size 4 and 5 Australian rules footballs. Participants (n = 22, 13.77 ± 0.61 years) performed drop punt kicks in 2 representative tasks; a Decision-Making Test (DMT) (n = 14) and Set-Shot Test (SST) (n = 14 + 8). Results indicate participants sustained their level of kick performance (accuracy and quality of ball spin) in both tests when using a Size 5 football...
October 6, 2016: Journal of Sports Sciences
Anne E Holland, Ajay Mahal, Catherine J Hill, Annemarie L Lee, Angela T Burge, Narelle S Cox, Rosemary Moore, Caroline Nicolson, Paul O'Halloran, Aroub Lahham, Rebecca Gillies, Christine F McDonald
BACKGROUND: Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor. We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation. METHODS: A randomised controlled equivalence trial with 12 months follow-up. Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist...
September 26, 2016: Thorax
Bogdan S Melnik, Galina S Nagibina, Anatoly S Glukhov, Tatiana N Melnik, Vladimir N Uversky
Various effects of amino acid substitutions on properties of globular proteins have been described in a large number of research papers. Nevertheless, no definite "rule" has been formulated as of yet that could be used by experimentalists to introduce desirable changes in the properties of proteins. Herein we attempt to establish such a "rule". To this end, a hypothesis is proposed on the effects of substitutions of hydrophobic residues with large number of contacts on free energies of different states of a globular protein...
September 14, 2016: Biochimica et Biophysica Acta
Daniela Justa-Schuch, Maria Silva-Garcia, Esther Pilla, Michael Engelke, Markus Kilisch, Christof Lenz, Ulrike Möller, Fumihiko Nakamura, Henning Urlaub, Ruth Geiss-Friedlander
The aminopeptidase DPP9 removes dipeptides from N-termini of substrates having a proline or alanine in second position. Although linked to several pathways including cell survival and metabolism, the molecular mechanisms underlying these outcomes are poorly understood. We identified a novel interaction of DPP9 with Filamin A, which recruits DPP9 to Syk, a central kinase in B-cell signalling. Syk signalling can be terminated by degradation, requiring the ubiquitin E3 ligase Cbl. We show that DPP9 cleaves Syk to produce a neo N-terminus with serine in position 1...
September 10, 2016: ELife
Mohamed A Eldeeb, Richard P Fahlman
Cellular signalling leading to the initiation of apoptosis typically results in the activation of caspases which in turn leads to the proteolytic generation of protein fragments with new or altered cellular functions. Increasing numbers of reports are demonstrating that the activity of many of these proteolytically activated protein fragments can be attenuated by their selective degradation by the N-End Rule pathway. Here we report the first evidence that selective degradation of a caspase product by the N-End Rule pathway can be modulated by phosphorylation...
September 6, 2016: Journal of Biological Chemistry
Sophie Dupuis-Girod, Alexis Ambrun, Evelyne Decullier, Anne-Emmanuelle Fargeton, Adeline Roux, Valentine Bréant, Bettina Colombet, Sophie Rivière, César Cartier, Pascal Lacombe, Thierry Chinet, Sandra Blivet, Jean-Hugues Blondel, Brigitte Gilbert-Dussardier, Xavier Dufour, Justin Michel, Jean-Robert Harle, Patrick Dessi, Frédéric Faure
BACKGROUND: Epistaxis is the most frequent and disabling manifestation of hereditary hemorrhagic telangiectasia (HHT). The efficacy of intravenous bevacizumab (an anti-vascular endothelial growth factor monoclonal antibody) for epistaxis has been shown. However, the efficacy of intranasal bevacizumab has yet to be evaluated. OBJECTIVE: To evaluate the efficacy of 3 different doses of bevacizumab administered as a nasal spray in a repeated manner for the duration of nosebleeds in patients with HHT...
September 6, 2016: JAMA: the Journal of the American Medical Association
Huan-Bin Shi, Guo-Qing Chen, Ya-Ping Chen, Bo Dong, Jian-Ping Lu, Xiao-Hong Liu, Fu-Cheng Lin
The ubiquitin system modulates protein functions through targeting substrates for ubiquitination. Here, E2 conjugating enzyme MoRad6-related ubiquitination pathways are identified and analyzed in Magnaporthe oryzae, the causal agent of rice blast disease. Disruption of MoRad6 leads to severe defects in growth, sporulation, conidial germination, appressorium formation, and plant infection. To depict the functions of MoRad6, three putative ubiquitin ligases, MoRad18, MoBre1 and MoUbr1, are also characterized...
August 31, 2016: Environmental Microbiology
Yanxialei Jiang, Jeeyoung Lee, Jung Hoon Lee, Joon Won Lee, Ji Hyeon Kim, Won Hoon Choi, Young Dong Yoo, Hyunjoo Cha-Molstad, Bo Yeon Kim, Yong Tae Kwon, Sue Ah Noh, Kwang Pyo Kim, Min Jae Lee
The N-terminal amino acid of a protein is an essential determinant of ubiquitination and subsequent proteasomal degradation in the N-end rule pathway. Using para-chloroamphetamine (PCA), a specific inhibitor of the arginylation branch of the pathway (Arg/N-end rule pathway), we identified that blocking the Arg/N-end rule pathway significantly impaired the fusion of autophagosomes with lysosomes. Under ER stress, ATE1-encoded Arg-tRNA-protein transferases carry out the N-terminal arginylation of the ER heat shock protein HSPA5 that initially targets cargo proteins, along with SQSTM1, to the autophagosome...
August 25, 2016: Autophagy
Pritha Agarwalla, Rajkumar Banerjee
Recent study has shown that N-end rule pathway, an ubiquitin dependent proteolytic system, counteracts cell death by degrading many antisurvival protein fragments like BCLxL, BRCA1, RIPK1, etc. Inhibition of the N-end rule pathway can lead to metabolic stabilization of proapoptotic protein fragments like RIPK1, thereby sensitizing cells to programmed cell death. Receptor interacting serine-threonine protein kinase-1 (RIPK1) is one of the upstream regulators of programmed necrosis known as necroptosis. Necroptosis is particularly gaining attention of cancer biologists as it provides an alternate therapeutic modality to kill cancer cells, which often evolve multiple strategies to circumvent growth inhibition by apoptosis...
2016: Molecular Therapy Oncolytics
Dariel Ashton-Beaucage, Caroline Lemieux, Christian M Udell, Malha Sahmi, Samuel Rochette, Marc Therrien
RAS-induced MAPK signaling is a central driver of the cell proliferation apparatus. Disruption of this pathway is widely observed in cancer and other pathologies. Consequently, considerable effort has been devoted to understanding the mechanistic aspects of RAS-MAPK signal transmission and regulation. While much information has been garnered on the steps leading up to the activation and inactivation of core pathway components, comparatively little is known on the mechanisms controlling their expression and turnover...
August 2016: PLoS Biology
Lauren E Graniero, Ethan L Grossman, Aaron O'Dea
To examine N-isotope ratios ((15)N/(14)N) in tissues and shell organic matrix of bivalves as a proxy for natural and anthropogenic nutrient fluxes in coastal environments, Pinctada imbricata, Isognomon alatus, and Brachidontes exustusbivalves were live-collected and analyzed from eight sites in Bocas del Toro, Panama. Sites represent a variety of coastal environments, including more urbanized, uninhabited, riverine, and oceanic sites. Growth under differing environmental conditions is confirmed by δ (18)O values, with open ocean Escudo de Veraguas shells yielding the highest average δ (18)O (-1...
2016: PeerJ
Brandon Wadas, Konstantin I Piatkov, Christopher S Brower, Alexander Varshavsky
N(α)-terminal arginylation (Nt-arginylation) of proteins is mediated by the Ate1 arginyltransferase (R-transferase), a component of the Arg/N-end rule pathway. This proteolytic system recognizes proteins containing N-terminal degradation signals called N-degrons, polyubiquitylates these proteins, and thereby causes their degradation by the proteasome. The definitively identified ("canonical") residues that are Nt-arginylated by R-transferase are N-terminal Asp, Glu, and (oxidized) Cys. Over the last decade, several publications have suggested (i) that Ate1 can also arginylate non-canonical N-terminal residues; (ii) that Ate1 is capable of arginylating not only α-amino groups of N-terminal residues but also γ-carboxyl groups of internal (non-N-terminal) Asp and Glu; and (iii) that some isoforms of Ate1 are specific for substrates bearing N-terminal Cys residues...
September 30, 2016: Journal of Biological Chemistry
Henriette Aksnes, Adrian Drazic, Michaël Marie, Thomas Arnesen
N-terminal (Nt) acetylation is known to be a highly abundant co-translational protein modification, but the recent discovery of Golgi- and chloroplast-resident N-terminal acetyltransferases (NATs) revealed that it can also be added post-translationally. Nt-acetylation may act as a degradation signal in a novel branch of the N-end rule pathway, whose functions include the regulation of human blood pressure. Nt-acetylation also modulates protein interactions, targeting, and folding. In plants, Nt-acetylation plays a role in the control of resistance to drought and in regulation of immune responses...
September 2016: Trends in Biochemical Sciences
Yujiao Liu, Chao Liu, Wen Dong, Wei Li
The N-end rule pathway is a unique branch of the ubiquitin-proteasome system in which the determination of a protein's half-life is dependent on its N-terminal residue. The N-terminal residue serves as the degradation signal of a protein and thus called N-degron. N-degron can be recognized and modifed by several steps of post-translational modifications, such as oxidation, deamination, arginylation or acetylation, it then polyubiquitinated by the N-recognin for degradation. The molecular basis of the N-end rule pathway has been elucidated and its physiological functions have been revealed in the past 30 years...
September 2016: Frontiers of Medicine
Tonino Bombardini, Louis A Mulieri, Stefano Salvadori, Marco Fabio Costantino, Maria Chiara Scali, Mario Marzilli, Eugenio Picano
INTRODUCTION AND OBJECTIVES: The variation between rest and peak stress end-systolic pressure-volume relation is an afterload-independent index of left ventricular contractility. Whether and to what extent it depends on end-diastolic volume remains unclear. The aim of this study was to assess the dependence of the delta rest-stress end-systolic pressure-volume relation on end-diastolic volume in patients with negative stress echo and all ranges of resting left ventricular function. METHODS: We analyzed interpretable data obtained in 891 patients (593 men, age 63 ± 12 years) with ejection fraction 47% ± 12%: 338 were normal or near-normal or hypertensive; 229 patients had coronary artery disease; and 324 patients had ischemic or nonischemic dilated cardiomyopathy...
July 27, 2016: Revista Española de Cardiología
Lorena Simón-Gracia, Hedi Hunt, Pablo Scodeller, Jens Gaitzsch, Venkata Ramana Kotamraju, Kazuki N Sugahara, Olav Tammik, Erkki Ruoslahti, Giuseppe Battaglia, Tambet Teesalu
Polymersomes are versatile nanoscale vesicles that can be used for cytoplasmic delivery of payloads. Recently, we demonstrated that pH-sensitive polymersomes exhibit an intrinsic selectivity towards intraperitoneal tumor lesions. A tumor homing peptide, iRGD, harbors a cryptic C-end Rule (CendR) motif that is responsible for neuropilin-1 (NRP-1) binding and for triggering extravasation and tumor penetration of the peptide. iRGD functionalization increases tumor selectivity and therapeutic efficacy of systemic drug-loaded nanoparticles in many tumor models...
October 2016: Biomaterials
M M Hofmann, L G Cheke, N S Clayton
String-pulling is a widely used paradigm in animal cognition research to assess what animals understand about the functionality of strings as a means to obtain an out-of-reach reward. This study aimed to systematically investigate what rules Western scrub-jays (Aphelocoma californica) use to solve different patterned string tasks, i.e. tasks in which subjects have to choose between two or more strings of which only one is connected to the reward, or where one is more efficient. Arranging strings in a parallel configuration showed that the jays were generally capable of solving multiple-string tasks and acted in a goal-directed manner...
November 2016: Animal Cognition
Daniel J Gibbs, Mark Bailey, Hannah M Tedds, Michael J Holdsworth
Contents 1188 I. 1188 II. 1189 III. 1190 IV. 1191 V. 1192 1192 References 1192 SUMMARY: The amino- (N-) terminus (Nt) of a protein can undergo a diverse array of co- and posttranslational modifications. Many of these create degradation signals (N-degrons) that mediate protein destruction via the N-end rule pathway of ubiquitin-mediated proteolysis. In plants, the N-end rule pathway has emerged as a major system for regulated control of protein stability. Nt-arginylation-dependent degradation regulates multiple growth, development and stress responses, and recently identified functions of Nt-acetylation can also be linked to effects on the in vivo half-lives of Nt-acetylated proteins...
September 2016: New Phytologist
R Mathew, N Davies, J Manthorpe, S Iliffe
OBJECTIVE: Decision-making, when providing care and treatment for a person with dementia at the end of life, can be complex and challenging. There is a lack of guidance available to support practitioners and family carers, and even those experienced in end of life dementia care report a lack of confidence in decision-making. It is thought that the use of heuristics (rules of thumb) may aid decision-making. The aim of this study is to identify whether heuristics are used in end of life dementia care, and if so, to identify the context in which they are being used...
2016: BMJ Open
Maria Klecker, Nico Dissmeyer
The automated SPOT (synthetic peptide arrays on membrane support technique) synthesis technology has entrenched as a rapid and robust method to generate peptide libraries on cellulose membrane supports. The synthesis method is based on conventional Fmoc chemistry building up peptides with free N-terminal amino acids starting at their cellulose-coupled C-termini. Several hundreds of peptide sequences can be assembled with this technique on one membrane comprising a strong binding potential due to high local peptide concentrations...
2016: Methods in Molecular Biology
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