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21.
Diego Sbardella Grazia R. Tundo Andrea Coletta Julien Marcoux Efthymia Ioanna Koufogeorgou Chiara Ciaccio Anna M. Santoro Danilo Milardi Giuseppe Grasso Paola Cozza Marie-Pierre Bousquet-Dubouch Stefano Marini Massimo Coletta 《Cellular and molecular life sciences : CMLS》2018,75(18):3441-3456
The interaction of insulin-degrading enzyme (IDE) with the main intracellular proteasome assemblies (i.e, 30S, 26S and 20S) was analyzed by enzymatic activity, mass spectrometry and native gel electrophoresis. IDE was mainly detected in association with assemblies with at least one free 20S end and biochemical investigations suggest that IDE competes with the 19S in vitro. IDE directly binds the 20S and affects its proteolytic activities in a bimodal fashion, very similar in human and yeast 20S, inhibiting at (IDE)?≤?30 nM and activating at (IDE)?≥?30 nM. Only an activating effect is observed in a yeast mutant locked in the “open” conformation (i.e., the α-3ΔN 20S), envisaging a possible role of IDE as modulator of the 20S “open”–”closed” allosteric equilibrium. Protein–protein docking in silico proposes that the interaction between IDE and the 20S could involve the C-term helix of the 20S α-3 subunit which regulates the gate opening of the 20S. 相似文献
22.
Nair KS Hmani-Aifa M Ali Z Kearney AL Ben Salem S Macalinao DG Cosma IM Bouassida W Hakim B Benzina Z Soto I Söderkvist P Howell GR Smith RS Ayadi H John SW 《Nature genetics》2011,43(6):579-584
Angle-closure glaucoma (ACG) is a subset of glaucoma affecting 16 million people. Although 4 million people are bilaterally blind from ACG, the causative molecular mechanisms of ACG remain to be defined. High intraocular pressure induces glaucoma in ACG. High intraocular pressure traditionally was suggested to result from the iris blocking or closing the angle of the eye, thereby limiting aqueous humor drainage. Eyes from individuals with ACG often have a modestly decreased axial length, shallow anterior chamber and relatively large lens, features that predispose to angle closure. Here we show that genetic alteration of a previously unidentified serine protease (PRSS56) alters axial length and causes a mouse phenotype resembling ACG. Mutations affecting this protease also cause a severe decrease of axial length in individuals with posterior microphthalmia. Together, these data suggest that alterations of this serine protease may contribute to a spectrum of human ocular conditions including reduced ocular size and ACG. 相似文献
23.
Dalila Cisco Collatto Aline Dresch Daniel Pacheco Lacerda Ione Ghislene Bentz 《Systemic Practice and Action Research》2018,31(3):239-267
Action research is one of the research methods that seeks to develop scientific knowledge while simultaneously acting to solve real problems. Design science and design science research are approaches that address problem-solving oriented researches, converging in this aspect with the objectives of action research. A significant part of the literature discusses action research and design science research separately. However, there are some early discussions regarding the similarities and the differences between these research methods. The objective of this study is to deepen an analysis that distinguishes action research, design science and design science research as research methods considering their convergences and divergences. This leads to the discussion of the need for a third method: action design research. This study was conducted based on a configurative systematic literature review. The analysis and the synthesis of literature took into account themes and content analyses. Some results could be observed. First, there is a significant number of similarities among these research methods; second, there are complementary and positive synergies in their use; and third, the concepts of artifact and classes of problems seem to contribute both to the proposition and to the evaluation of the results obtained by action research. Finally, it was possible to establish a set of possibilities for the use of action research and design science research in a combined manner. The limitations of this study have a theoretical nature. There is a need for a comparative analysis of the use of action research and design science research and the use of action research under the paradigm of design science. 相似文献
24.
Renato Cordeiro de Amorim 《Journal of Classification》2016,33(2):210-242
In a real-world data set, there is always the possibility, rather high in our opinion, that different features may have different degrees of relevance. Most machine learning algorithms deal with this fact by either selecting or deselecting features in the data preprocessing phase. However, we maintain that even among relevant features there may be different degrees of relevance, and this should be taken into account during the clustering process.With over 50 years of history, K-Means is arguably the most popular partitional clustering algorithm there is. The first K-Means based clustering algorithm to compute feature weights was designed just over 30 years ago. Various such algorithms have been designed since but there has not been, to our knowledge, a survey integrating empirical evidence of cluster recovery ability, common flaws, and possible directions for future research. This paper elaborates on the concept of feature weighting and addresses these issues by critically analyzing some of the most popular, or innovative, feature weighting mechanisms based in K-Means. 相似文献
25.
Cornelius F Boerkoel Hiroshi Takashima Joy John Jiong Yan Pawel Stankiewicz Lisa Rosenbarker Jean-Luc André Radovan Bogdanovic Antoine Burguet Sandra Cockfield Isabel Cordeiro Stefan Fründ Friederike Illies Mark Joseph Ilkka Kaitila Giuliana Lama Chantal Loirat D Ross McLeod David V Milford Elizabeth M Petty Francisco Rodrigo Jorge M Saraiva Beate Schmidt Graham C Smith Jürgen Spranger Anja Stein Hannelore Thiele Jane Tizard Rosanna Weksberg James R Lupski David W Stockton 《Nature genetics》2002,30(2):215-220
Schimke immuno-osseous dysplasia (SIOD, MIM 242900) is an autosomal-recessive pleiotropic disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction and T-cell immunodeficiency. Using genome-wide linkage mapping and a positional candidate approach, we determined that mutations in SMARCAL1 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), are responsible for SIOD. Through analysis of data from persons with SIOD in 26 unrelated families, we observed that affected individuals from 13 of 23 families with severe disease had two alleles with nonsense, frameshift or splicing mutations, whereas affected individuals from 3 of 3 families with milder disease had a missense mutation on each allele. These observations indicate that some missense mutations allow retention of partial SMARCAL1 function and thus cause milder disease. 相似文献
26.
27.
R S Cordeiro J Assreuy Filho C A Flores F Q Cunha M A Martins H N Vasconcelos 《Experientia》1984,40(3):301-302
Mice inoculated with Plasmodium berghei developed a drastic and significant pulmonary edema. Treatment of animals with phenoxybenzamine rendered mice hyporeactive to this physiopathological alteration. 相似文献
28.
Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes 总被引:25,自引:0,他引:25
Kondo S Schutte BC Richardson RJ Bjork BC Knight AS Watanabe Y Howard E de Lima RL Daack-Hirsch S Sander A McDonald-McGinn DM Zackai EH Lammer EJ Aylsworth AS Ardinger HH Lidral AC Pober BR Moreno L Arcos-Burgos M Valencia C Houdayer C Bahuau M Moretti-Ferreira D Richieri-Costa A Dixon MJ Murray JC 《Nature genetics》2002,32(2):285-289
29.
S-Adenosyl-L-homocysteine is able to bind to brain membranes. We used this characteristic to measure the level of S-adenosyl-L-homocysteine in rat brain tissue. The method is rapid, at the same time very sensitive (down to 10(-7) M) and specific. 相似文献
30.
P. Fonlupt M. Roche L. Cronenberger H. Pacheco 《Cellular and molecular life sciences : CMLS》1979,35(8):1089-1090
Summary S-Adenosylhomocysteine (10–7–10–5 M) activated norepinephrine (NE) and serotonin (5HT) in vitro uptake in synaptosomal preparations from rat brain, but did not affect dopamine (DA) uptake. When administered to rats (7 mg/kg i.p.), it had the same effect on in vitro NE and 5HT uptake. It did not affect NE and 5HT release.Work achieved within the frame of the research contract institut Mérieux., Institut National des Sciences Appliquées. 相似文献