scholarly journals Protein abundance is key to distinguish promiscuous from functional phosphorylation based on evolutionary information

2012 ◽  
Vol 367 (1602) ◽  
pp. 2594-2606 ◽  
Author(s):  
Emmanuel D. Levy ◽  
Stephen W. Michnick ◽  
Christian R. Landry
Keyword(s):  
Protein Function ◽  
Evolutionary Conservation ◽  
Evolutionary Information ◽  
Key Factors ◽  
Evolutionary Patterns ◽  
Functional Sites ◽  
Saccharomyces Bayanus ◽  
Regulate Protein ◽  
Protein Conservation ◽  
The Impact

In eukaryotic cells, protein phosphorylation is an important and widespread mechanism used to regulate protein function. Yet, of the thousands of phosphosites identified to date, only a few hundred at best have a characterized function. It was recently shown that these functional sites are significantly more conserved than phosphosites of unknown function, stressing the importance of considering evolutionary conservation in assessing the global functional landscape of phosphosites. This leads us to review studies that examined the impact of phosphorylation on evolutionary conservation. While all these studies have shown that conservation is greater among phosphorylated sites compared with non-phosphorylated ones, the magnitude of this difference varies greatly. Further, not all studies have considered key factors that may influence the rate of phosphosite evolution. Such key factors are their localization in ordered or disordered regions, their stoichiometry or the abundance of their corresponding protein. Here we take into account all of these factors simultaneously, which reveals remarkable evolutionary patterns. First, while it is well established that protein conservation increases with abundance, we show that phosphosites partly follow an opposite trend. More precisely, Saccharomyces cerevisiae phosphosites present among abundant proteins are 1.5 times more likely to diverge in the closely related species Saccharomyces bayanus when compared with phosphosites present in the 5 per cent least abundant proteins. Second, we show that conservation is coupled to stoichiometry, whereby sites frequently phosphorylated are more conserved than those rarely phosphorylated. Finally, we provide a model of functional and noisy or ‘accidental’ phosphorylation that explains these observations.

scholarly journals Transient exposure of a buried phosphorylation site in an autoinhibited protein

2021 ◽  
Author(s):  
Simone Orioli ◽  
Kresten Lindorff-Larsen
Keyword(s):  
Protein Function ◽  
Molten Globule ◽  
Phosphorylation Site ◽  
Structural Disorder ◽  
Helical Structures ◽  
Post Translational Modifications ◽  
Cis Acting ◽  
Functional Sites ◽  
Inhibitory Domain ◽  
Regulate Protein

Autoinhibition is a mechanism used to regulate protein function, often by making functional sites inaccessible through the interaction with a cis-acting inhibitory domain. Such autoinhibitory domains often display a substantial degree of structural disorder when unbound, and only become structured in the inhibited state. This structural dynamics makes it difficult to study the structural origin of regulation, including effects of regulatory post-translational modifications. Here, we study the autoinhibition of the Dbl Homology domain in the protein Vav1 by the so-called acidic inhibitory domain. We use molecular simulations to study the process by which a mostly unstructured inhibitory domain folds upon binding and how transient exposure of a key buried tyrosine residue makes it accessible for phosphorylation. We show that the inhibitory domain, which forms a helix in the bound and inhibited stated, samples helical structures already before binding and that binding occurs via a molten-globule-like intermediate state. Together, our results shed light on key interactions that enable the inhibitory domain to sample a finely-tuned equilibrium between an inhibited and a kinase-accessible state.

Secular stagnation in the modern world

2018 ◽  
pp. 125-141 ◽  
Author(s):  
S. M. Drobyshevsky ◽  
P. V. Trunin ◽  
A. V. Bozhechkova
Keyword(s):  
Public Debt ◽  
Capital Accumulation ◽  
Technological Development ◽  
Japanese Economy ◽  
Modern World ◽  
Key Factors ◽  
Destruction Process ◽  
Secular Stagnation ◽  
The Impact

The paper studies the factors of secular stagnation. Key factors of long-term slowdown in economic growth include the slowdown of technological development, aging population, human capital accumulation limits, high public debt, creative destruction process violation etc. The authors analyze key theoretical aspects of long-term stagnation and study the impact of these factors on Japanies economy. The authors conclude that most of the factors have significant influence on the Japanese economy for recent decades, but they cannot explain all dynamics. For Russia, on the contrary, we do not see any grounds for considering the decline in the economy since 2013 as an episode of secular stagnation.

Implication of Medical Treatment for Surgical Strategies in IBD

2019 ◽  
Vol 20 (13) ◽  
pp. 1363-1368
Author(s):  
Krisztina B. Gecse ◽  
Christianne J. Buskens
Keyword(s):  
Nutritional Status ◽  
Medical Treatment ◽  
Significant Proportion ◽  
Timing Of Surgery ◽  
Multidisciplinary Management ◽  
Key Factors ◽  
Surgical Strategies ◽  
Immunosuppressive Medications ◽  
Medical Paradigm ◽  
The Impact

Despite changing medical paradigm, still a significant proportion of patients with IBD require surgery. The patient's general condition, including nutritional status and the use of immunosuppressive medications is of great importance with regard to surgical complications, as well as the choice of optimal surgical strategy. The indication and the timing of surgery are key factors for the multidisciplinary management of IBD patients. The purpose of this review is to provide an overview on the impact of medical treatment on surgical strategies in IBD.

Examining Organizational, Cultural, and Individual-Level Factors Related to Workplace Safety and Health Awareness and Risks: A Systematic Review and Metric Analysis (Preprint)

2018 ◽  
Author(s):  
Edmund W. J. Lee ◽  
Han Zheng ◽  
Htet Htet Aung ◽  
Megha Rani Aroor ◽  
Chen Li ◽  
...  
Keyword(s):  
Systematic Review ◽  
Citation Count ◽  
Workplace Safety ◽  
Key Factors ◽  
Health Awareness ◽  
Individual Level ◽  
Metric Analysis ◽  
Safety And Health ◽  
The Impact ◽  
The Relationship

BACKGROUND Promoting safety and health awareness and mitigating risks are of paramount importance to companies in high-risk industries. Yet, there are very few studies that have synthesized findings from existing online workplace safety and health literature to identify what are the key factors that are related to (a) safety awareness, (b) safety risks, (c) health awareness, and (d) health risks. OBJECTIVE As one of the first systematic reviews in the area of workplace health and safety, this study aims to identify the factors related to safety and health awareness as well as risks, and systematically map these factors within three levels: organizational, cultural, and individual level. Also, this review aims to assess the impact of these workplace safety and health publications in both academic (e.g., academic databases, Mendeley, and PlumX) and non-academic settings (e.g., social media platform). METHODS The systematic review was conducted in line with procedures recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). First, Proquest, ScienceDirect and Scopus were identified as suitable databases for the systematic review. Second, after inputting search queries related to safety and health awareness and risks, the articles were evaluated based on a set of inclusion and exclusion criteria. Third, the factors identified in the included articles were coded systematically. Fourth, the research team assessed the impact of the articles through a combination of traditional and new metric analysis methods: citation count, Altmetric Attention Score, Mendeley readers count, usage count, and capture count. RESULTS Out of a total of 4,831 articles retrieved from the three databases, 51 articles were included in the final sample and were systematically coded. The results revealed six categories of organizational (management commitment, management support, organizational safety communication, safety management systems, physical work environment, and organizational environment), two cultural (interpersonal support and organizational culture), and four individual (perception, motivation, attitude and behavior) level factors that relate to safety and health awareness and risk. In terms of impact, the relationship between citation count and the various metrics measuring academic activity (e.g., Mendeley readers, usage count, and capture count) were mostly significant while the relationship between citation count and Altmetric Attention Score was non-significant. CONCLUSIONS This study provides a macro view of the current state of workplace safety and health research and gives scholars an indication on some of the key factors of safety and health awareness and risks. Researchers should also be cognizant that while their work may receive attention from the scholarly community, it is important to tailor their communication messages for the respective industries they are studying to maximize the receptivity and impact of their findings. CLINICALTRIAL N.A.

Poland

2017 ◽  
Author(s):  
Detlef Pollack ◽  
Gergely Rosta
Keyword(s):  
Catholic Church ◽  
Agricultural Production ◽  
The State ◽  
Religious Culture ◽  
Key Factors ◽  
Pope John Paul Ii ◽  
National Values ◽  
The Impact ◽  
State Socialist ◽  
The Church

The chapter on Poland focuses on two questions. Why, in contrast to all other state-socialist countries, did the church’s capacity for integration actually increase rather than decrease despite persecution and discrimination during the communist period? And why has this capacity also remained more or less constant (albeit to a lesser extent) in the period since the end of communist rule? The authors have identified four key factors in the remarkable resistance of the Polish Catholic Church during the period of communist persecution: the fusion of religious and national values, the specific conflict dynamics of the church’s struggle with the state, the structural conservatism of agricultural production in Poland, and the actions of Pope John Paul II. Explanations for the surprising stability of religiosity in Poland after 1990 point to the behaviour of the Church itself, to the internal pluralization of Catholicism, and to the impact of a homogeneous religious culture.

scholarly journals Graphene-based 3D XNOR-VRRAM with ternary precision for neuromorphic computing

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Batyrbek Alimkhanuly ◽  
Joon Sohn ◽  
Ik-Joon Chang ◽  
Seunghyun Lee
Keyword(s):  
Neural Network ◽  
Energy Consumption ◽  
Recognition Accuracy ◽  
Material Selection ◽  
Weighted Sum ◽  
Device Design ◽  
Key Factors ◽  
Neuromorphic Computing ◽  
Device Scaling ◽  
The Impact

AbstractRecent studies on neural network quantization have demonstrated a beneficial compromise between accuracy, computation rate, and architecture size. Implementing a 3D Vertical RRAM (VRRAM) array accompanied by device scaling may further improve such networks’ density and energy consumption. Individual device design, optimized interconnects, and careful material selection are key factors determining the overall computation performance. In this work, the impact of replacing conventional devices with microfabricated, graphene-based VRRAM is investigated for circuit and algorithmic levels. By exploiting a sub-nm thin 2D material, the VRRAM array demonstrates an improved read/write margins and read inaccuracy level for the weighted-sum procedure. Moreover, energy consumption is significantly reduced in array programming operations. Finally, an XNOR logic-inspired architecture designed to integrate 1-bit ternary precision synaptic weights into graphene-based VRRAM is introduced. Simulations on VRRAM with metal and graphene word-planes demonstrate 83.5 and 94.1% recognition accuracy, respectively, denoting the importance of material innovation in neuromorphic computing.

scholarly journals Effective Demand Forecasting in Health Supply Chains: Emerging Trend, Enablers, and Blockers

Logistics ◽  
2021 ◽  
Vol 5 (1) ◽  
pp. 12
Author(s):  
Lakshmy Subramanian
Keyword(s):  
Supply Chains ◽  
Demand Forecasting ◽  
Weak Links ◽  
Key Factors ◽  
Scarce Resources ◽  
Weakest Link ◽  
Emerging Trends ◽  
A Chain ◽  
Health Commodities ◽  
The Impact

Health supply chains aim to improve access to healthcare, and this can be attained only when health commodities appropriate to the health needs of the global population are developed, manufactured, and made available when and where needed. The weak links in the health supply chains are hindering the access of essential healthcare resulting in inefficient use of scarce resources and loss of lives. A chain is only as strong as its weakest link, and demand forecasting is one of the weakest links of health supply chains. Also, many of the existing bottlenecks in supply chains and health systems impede the accurate forecasting of demand, and without the ability to forecast demand with certainty, the stakeholders cannot plan and make commitments for the future. Forecasts are an important feeder for budgeting and logistics planning. Under this backdrop, the study examines how improved forecasting can lead to better short-term and long-term access to health commodities and outlines market-related risks. It explores further how incentives are misaligned creating an uneven distribution of risks, leading to the inability to match demand and supply. For this purpose, a systematic literature review was performed, analyzing 71 articles from a descriptive and content approach. Findings indicate the emerging trends in global health and the consequences of inaccurate demand forecasting for health supply chains. The content analysis identifies key factors that can pose a varying degree of risks for the health supply chain stakeholders. The study highlights how the key factors emerge as enablers and blockers, depending on the impact on the overall health supply chains. The study also provides recommendations for actions for reducing these risks. Consequently, limitations of this work are presented, and opportunities are identified for future lines of research. Finally, the conclusion confirms that by adopting a combination of approaches, stakeholders can ensure better information sharing, identify avenues of diversifying risks, and understand the implications.

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