Phosphorylation controls autoinhibition of cytoplasmic linker protein-170

Author Posting. © American Society for Cell Biology, 2010. This article is posted here by permission of American Society for Cell Biology for personal use, not for redistribution. The definitive version was published in Molecular Biology of the Cell 21 (2010): 2661-2673, doi:10.1091/mbc.E09-12-1036.Cytoplasmic linker protein (CLIP)-170 is a microtubule (MT) plus-end-tracking protein that regulates MT dynamics and links MT plus ends to different intracellular structures. We have shown previously that intramolecular association between the N and C termini results in autoinhibition of CLIP-170, thus altering its binding to MTs and the dynactin subunit p150Glued (J. Cell Biol. 2004: 166, 1003–1014). In this study, we demonstrate that conformational changes in CLIP-170 are regulated by phosphorylation that enhances the affinity between the N- and C-terminal domains. By using site-directed mutagenesis and phosphoproteomic analysis, we mapped the phosphorylation sites in the third serine-rich region of CLIP-170. A phosphorylation-deficient mutant of CLIP-170 displays an "open" conformation and a higher binding affinity for growing MT ends and p150Glued as compared with nonmutated protein, whereas a phosphomimetic mutant confined to the "folded back" conformation shows decreased MT association and does not interact with p150Glued. We conclude that phosphorylation regulates CLIP-170 conformational changes resulting in its autoinhibition.This work was supported by National Institutes of Health grant GM-25062 (to G.G.B.); Netherlands Organization for Scientific Research grants (to A. A. and N. G.); a Cancer Genomics Centre grant (to J.v.H.); and Presidential Program of Russian Academy of Sciences and RFBP grant 05-04-4915 (to E.S.N.)

The Power of VPL: Validation of Prior Learning as a Multi-targeted Approach For Access to Learning Opportunities For All

Preface from Ruud Duvekot: Learning is more than ever important and valuable, people are encouraged to invest in their potential throughout their lives, taking into account their prior learning. According to policy papers all across the globe, this should concern all citizens, including the underrepresented groups and non-traditional learners with regard to higher education because everywhere the knowledge-economy needs more higher-educated participation from all..

Phosphorylation controls autoinhibition of cytoplasmic linker protein-170

Author Posting. © American Society for Cell Biology, 2010. This article is posted here by permission of American Society for Cell Biology for personal use, not for redistribution. The definitive version was published in Molecular Biology of the Cell 21 (2010): 2661-2673, doi:10.1091/mbc.E09-12-1036.Cytoplasmic linker protein (CLIP)-170 is a microtubule (MT) plus-end-tracking protein that regulates MT dynamics and links MT plus ends to different intracellular structures. We have shown previously that intramolecular association between the N and C termini results in autoinhibition of CLIP-170, thus altering its binding to MTs and the dynactin subunit p150Glued (J. Cell Biol. 2004: 166, 1003–1014). In this study, we demonstrate that conformational changes in CLIP-170 are regulated by phosphorylation that enhances the affinity between the N- and C-terminal domains. By using site-directed mutagenesis and phosphoproteomic analysis, we mapped the phosphorylation sites in the third serine-rich region of CLIP-170. A phosphorylation-deficient mutant of CLIP-170 displays an "open" conformation and a higher binding affinity for growing MT ends and p150Glued as compared with nonmutated protein, whereas a phosphomimetic mutant confined to the "folded back" conformation shows decreased MT association and does not interact with p150Glued. We conclude that phosphorylation regulates CLIP-170 conformational changes resulting in its autoinhibition.This work was supported by National Institutes of Health grant GM-25062 (to G.G.B.); Netherlands Organization for Scientific Research grants (to A. A. and N. G.); a Cancer Genomics Centre grant (to J.v.H.); and Presidential Program of Russian Academy of Sciences and RFBP grant 05-04-4915 (to E.S.N.)

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Louis BEGIONI, Sophie SAFFI, Ştefan GENCĂRĂU, Marco CASTAGNA (coord), Sistemi linguistici – Sisteme lingvistice – Sistèmes linguistiques, Editura Cirrmi, Paris, Presa Universitară Clujeană, Cluj-Napoca, 2012, 278 p.

Revista Sisteme lingvistice, de o valoare însemnată pentru domeniul vast al studiului limbilor romanice, are ca obiectiv ilustrarea principalelor teme şi dezbateri care se formează în jurul lingvisticii. Această revistă îşi propune să evidenţieze domeniile pe care lingvistica le presupune. Barierele lingvistice sunt eliminate, întrucât orice limbă poate fi obiect de analiză în interiorul acestei reviste şi, mai mult, toate abordările teoretice sunt acceptate, ceea ce nu poate fi decât un beneficiu pentru disciplinele ştiinţei limbajului. Această deschidere este cuprinsă şi în titlul publicaţiei, tradus în trei limbi romanice, tocmai pentru a sublinia similitudinea şi legăturile dintre acestea. Comitetul ştiinţific al revistei reuneşte nume cunoscute ariei limbilor romanice, aspect care îi conferă un statut aparte

Ways of intervention in the education and recovery of children with multiple visual disabilities

AbstractThe inexistence of a totally coherent way of intervening in the case of multiple pathologies in children was also felt in the case of visual disabilities which incited to the finding of some efficient solutions that fit optimally on the casuistry, socio-material conditions, etc. The project “Luminita”, initiated in 1997 as a result of the cooperation of the Ability Foundation “Speranta” and the Perkins School for the Blind in Boston through the Hilton/Perkins Program represented an adequate response to the existent situation. The research followed the implementation, performance and the perfection of education – rehabilitation programs, improvement and extension of the education and rehabilitation services but also the formation and perfection of specialists, guidance for parents, etc. The specificity of the methodological alternatives used, of the individual rehabilitation programs and material resources provided, the partnership levels and the results obtained, the problems and difficulties met, represent the subject of this paper

Methods of developing children's emotional intelligence

AbstractAlmost a century ago, Thorndike had the foresight to announce to the world that IQ is not the only type of intelligence. And he was right. What he was referring to is emotional intelligence, the product of two main factors – personal and social competency – without which one cannot envisage the human personality of the 21st century. Emotions have taught humanity how to think, Luc de Vauvenargues said. Those emotions that are not dealt with disrupt the mind and body while those emotions that are transformed in abilities ensure a better productivity, more satisfactions derived from everyday activities and positive interpersonal relationships, they drive us to assume accountability as well as bolster up our self-control, among many other things. Our attempt to develop and optimize the involvement of emotions in achieving individual success was aimed at the following objectives. Discovering the four unique areas of EQ: self-awareness, self-management, social awareness, relationship management. Developing EQ through the use of specific techniques. Using EQ for: cognitive and interrelational advantages, lowering stress level, the increase of individual productivity, comprehending emotions, positively interacting with others, etc. This paper deals exactly with the most efficient methods of developing emotional intelligence in children