Pathophysiological Role of Mitochondrial Potassium Channels and their Modulation by Drugs

2018 ◽  
Vol 25 (23) ◽  
pp. 2661-2674 ◽  
Author(s):  
Valentina Citi ◽  
Vincenzo Calderone ◽  
Alma Martelli ◽  
Maria C. Breschi ◽  
Lara Testai
Keyword(s):  
Mitochondrial Function ◽  
Critical Role ◽  
Decisive Role ◽  
Point Of View ◽  
Pharmacological Intervention ◽  
Mammalian Tissues ◽  
Pathophysiological Role ◽  
Multiple Drugs ◽  
Neuro Protection

Background: Mitochondria play a central role in ATP-generating processes. Indeed, in mammalian tissues, up to 90% of ATP is generated by mitochondria through the process of oxidative phosphorylation; furthermore, mitochondria are involved in multiple signal transduction pathways. A rapidly expanding body of literature has confirmed that mitochondria play a pivotal role in apoptosis, cardio- and neuro-protection, and various neurodegenerative disorders, ranging from Parkinson’s to Alzheimer’s disease. Mitochondria are also the targets of multiple drugs, some of these are specifically designed to affect mitochondrial function, while others have primary targets in other cellular locations but may interact with mitochondria because of the presence of numerous targets on this organelle. In this regard, mitochondrial potassium (mitoK) channels play a critical role in mitochondrial function and, consequently, in the metabolism of the whole cell. <p> Objective: To describe mitoK channels from a structural point of view and investigate their pathophysiological roles, focusing on possible specific modulators that might be useful as pharmacological tools in the treatment of various pathologies characterized by mitoK involvement. <p> Results: mitoK channels play a decisive role in several pathologies, including cardiovascular diseases, particularly in myocardial infarction and neurodegenerative diseases, and they are emerging as promising oncological targets. <p> Conclusions: mitoK channels represent novel targets, and mitoK channel modulators represent an exciting tool for pharmacological intervention against such pathological conditions.

Critical Role of Supply Chain Decoupling Point in Mass Customisation from Its Upstream and Downstream Information Systems Point of View

2011 ◽  
pp. 185-196
Author(s):  
S. Saghiri
Keyword(s):  
Supply Chain ◽  
Information Systems ◽  
Critical Role ◽  
Point Of View ◽  
Information Flows ◽  
Mass Customisation ◽  
Different Types ◽  
Type Information ◽  
Different Levels

Concentrating on the role of supply chain decoupling point, this chapter introduces different levels of customisation and mass operations and three types of mass customisation. It argues that in each mass customisation type, information systems which are upstream and downstream of the decoupling point can be varied. Consequently, information flows in different types of mass customisation have been examined. This analysis is an endeavour to organise mass customisation information systems across the supply chain, while it can be a useful structure for future researches in this area as well.

The Role of Criminalistic Classification and Defendants’ Typification in the Formation of Forensic Recommendations for Prosecuting in Court

Lex Russica ◽  
2020 ◽  
pp. 69-83
Author(s):  
S. L. Kislenko
Keyword(s):  
Decisive Role ◽  
Criminal Activity ◽  
Point Of View ◽  
Practical Significance ◽  
Public Prosecutor ◽  
Criminal Prosecution ◽  
Criminal Proceedings ◽  
First Case ◽  
Court Proceedings

Systemic characteristics of the doctrine dealing with the person committing a crime predetermine the complexity of the use of information about him or her in the process of criminal prosecution. Systemic information on the behavioral aspects of the person in the process of genesis of criminal and post-criminal activity, as well as its procedural status, will be of great importance in the work of law enforcement agencies as a systematic structure. Criminalistically significant aspects of criminal activity (and behavior) as a systemic holistic structure should be discussed when the decisive role of personal features is determined not only in the mechanism of the criminal act, but also beyond it. The activity of the person that takes place both before the criminal prosecution (criminal aspect) and during the proceedings (post-criminal aspect) should be investigated. Therefore, the identity of the defendant should be considered in the context of such categories as the identity of an offender and the identity of an accused (a suspect). The typification of defendants is necessary In order to improve the effectiveness of the prosecution of offenders in court proceedings. The classification approach allows us to develop targeted recommendations (methods, tactical complexes) to maintain the prosecution. Obtaining and using information about the identity of the defendant implies the need for the public prosecutor to interact with other authorities involved in prosecution process. The author comes to the conclusion that the study of personal and behavioral characteristics of the defendant has important theoretical and practical significance. In the first case, the generalization of such knowledge contributes to the development of criminalistic theory in general and its certain sections in particular. From a practical point of view, accumulation of such knowledge contributes to the formation of targeted criminalistic recommendations used to improve the effectiveness of criminal prosecution of persons who committed crimes within the framework of criminal proceedings.

scholarly journals Embedded Philanthropic CSR in Digital China: Unified View of Prosocial and Pro-environmental Practices

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Ye ◽  
Zain Rafique ◽  
Rongting Zhou ◽  
Fahad Asmi ◽  
Muhammad Azfar Anwar ◽  
...  
Keyword(s):  
Mobile Application ◽  
Critical Role ◽  
Point Of View ◽  
Activation Model ◽  
Environmental Practices ◽  
Public Benefits ◽  
Unified View ◽  
Corporate Social ◽  
Digital China

In recent decades, China has transformed from a conventional society into a digitally competitive nation. From an economic perspective, embedded corporate social responsibility (CSR) is gaining a new height where gamified charity is a trendy approach. By adopting the norm activation model from the point of view of the stimulus–organism–response framework, this research theoretically conceptualized the role of the mobile application environment (including telepresence, functional transparency, and accessibility) to map the cognition and philanthropic behavioral intentions of consumers in the gamified setting. The quantified survey comprised 669 respondents. The findings highlighted the critical role of functional transparency and telepresence of a mobile application in driving consumers’ warm glow and ascribed responsibility. The research underlined the presence of the unique DNA of Internet Plus Charity (Public Benefits) for prosocial and pro-environmental purposes in China under the umbrella of philanthropic CSR.

scholarly journals Inhibiting adenine synthesis attenuates glioblastoma cell stemness and temozolomide resistance

2021 ◽  
Author(s):  
Simranjit X. Singh ◽  
Rui Yang ◽  
Kristen Roso ◽  
Landon J. Hansen ◽  
Changzheng Du ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mitochondrial Function ◽  
Brain Cancer ◽  
De Novo ◽  
Critical Role ◽  
Glioblastoma Cell ◽  
Respiratory Capacity ◽  
Complementary Approach

Glioblastoma (GBM) is a lethal brain cancer exhibiting high levels of drug resistance, a feature partially imparted by tumor cell stemness. Recent work shows that homozygous MTAP deletion, a genetic alteration occurring in about half of all GBMs, promotes stemness in GBM cells. Exploiting MTAP loss-conferred deficiency in adenine salvage, we demonstrate that transient adenine blockade via treatment with L-Alanosine (ALA), an inhibitor of de novo adenine synthesis, attenuates stemness of MTAP-deficient GBM cells. This ALA-induced reduction in stemness is accompanied by compromised mitochondrial function, highlighted by diminished spare respiratory capacity. Direct pharmacological inhibition of mitochondrial respiration recapitulates the effect of ALA on GBM cell stemness, suggesting ALA targets stemness partially via affecting mitochondrial function. Finally, in agreement with diminished stemness and compromised mitochondrial function, we show that ALA sensitizes GBM cells to temozolomide (TMZ) in vitro and in an orthotopic GBM model. Collectively, these results identify critical roles of adenine supply in maintaining mitochondrial function and stemness of GBM cells, highlight a critical role of mitochondrial function in sustaining GBM stemness, and implicate adenine synthesis inhibition as a complementary approach for treating MTAP-deleted GBMs.

Restoration of Barrier Function in Injured Intestinal Mucosa

2007 ◽  
Vol 87 (2) ◽  
pp. 545-564 ◽  
Author(s):  
Anthony T. Blikslager ◽  
Adam J. Moeser ◽  
Jody L. Gookin ◽  
Samuel L. Jones ◽  
Jack Odle
Keyword(s):  
Small Intestine ◽  
Basement Membrane ◽  
Barrier Function ◽  
Ex Vivo ◽  
Critical Role ◽  
Acute Injury ◽  
Epithelial Basement Membrane ◽  
Mammalian Tissues ◽  
Epithelial Basement

Mucosal repair is a complex event that immediately follows acute injury induced by ischemia and noxious luminal contents such as bile. In the small intestine, villous contraction is the initial phase of repair and is initiated by myofibroblasts that reside immediately beneath the epithelial basement membrane. Subsequent events include crawling of healthy epithelium adjacent to the wound, referred to as restitution. This is a highly regulated event involving signaling via basement membrane integrins by molecules such as focal adhesion kinase and growth factors. Interestingly, however, ex vivo studies of mammalian small intestine have revealed the importance of closure of the interepithelial tight junctions and the paracellular space. The critical role of tight junction closure is underscored by the prominent contribution of the paracellular space to measures of barrier function such as transepithelial electrical resistance. Additional roles are played by subepithelial cell populations, including neutrophils, related to their role in innate immunity. The net result of reparative mechanisms is remarkably rapid closure of mucosal wounds in mammalian tissues to prevent the onset of sepsis.

Diagnostic Parameters

1992 ◽  
Vol 59 (1) ◽  
pp. 21-25 ◽  
Author(s):  
W. Artibani
Keyword(s):  
Critical Role ◽  
Benign Prostatic Hypertrophy ◽  
Point Of View ◽  
Pressure Flow ◽  
Homogeneous Groups ◽  
Detrusor Contractility ◽  
Pressure Flow Study ◽  
Voided Volume ◽  
Flow Study

Many parameters are available for evaluating patients with benign prostatic hypertrophy (BPH) in order to assess the necessity for treatment and to evaluate results. At present there is no real agreement on their order of importance. This paper tries to define from a theoretical and practical point of view the role of the following parameters: symptoms; symptom scores; visual scores; time/voided volume chart; prostate size; uroflowmetry, nomograms for flow; residual urine; pressure/flow study; mathematical and computer processing of pressure/flow study. The Author underlines the critical role of invasive urodynamics (pressure/flow study) in categorizing patients as obstructed or non-obstructed, in grading the severity of outflow obstruction and in evaluating the pattern of detrusor contractility. Present studies to evaluate the results of old and recent treatments should include invasive urodynamics in order to obtain homogeneous groups of patients and to overcome the prevailing empiricism.

scholarly journals Specific aspects of globalization

2008 ◽  
Vol 53 (No. 2) ◽  
pp. 65-68 ◽  
Author(s):  
M. Svatoš
Keyword(s):  
Sustainable Development ◽  
Decisive Role ◽  
Adaptation Strategy ◽  
Point Of View ◽  
Human Society ◽  
Human Adaptation ◽  
Negative Effects ◽  
The Earth ◽  
Global Problems

The decisive role of globalization processes and development tendencies has many positive and negative effects in economic (foreign-trade), environmental, and (bio) technological areas. From the evolution point of view still very successful human adaptation strategy hit the basic limit given by the capacity of the Earth biosphere. The evolution determinants of human society and their economic or technological activities manifesting themselves by global problems can find way out of sustainable development. The application of the so-called preventive principle represents a great dilemma.

Action Research and Epistemology

1996 ◽  
Vol 1 (2-3) ◽  
pp. 281-297
Author(s):  
Kjell S. Johannessen
Keyword(s):  
Action Research ◽  
Decisive Role ◽  
Point Of View ◽  
Rule Following ◽  
Human Practices

It is argued that more attention should be paid to the epistemological foundations of action research. Doing this from a pragmatic point of view, the author points to the decisive role of human practices regarding such fundamental issues as the constitution of meaningful signs, the application of concepts as rule-following, the contextuality of knowledge, and the marginal relevance of theory. The concept of practice not only points to the ways in which our concepts are established, it also comprises the skills involved in handling the conceptualized phenomena, our pre-reflective familiarity with them, expressed in the sureness of our behavior towards them, and the discernment exercised in applying or withholding a given concept on a particular occasion. These factors are all relevant to the establishment of knowledge, but they cannot themselves be fully and straightforwardly articulated by verbal means. Nevertheless, they represent what we go by when we apply concepts and other types of rules.

scholarly journals Mitochondrial Dysfunction, Insulin Resistance, and Potential Genetic Implications

Endocrinology ◽  
2020 ◽  
Vol 161 (4) ◽  
Author(s):  
Panjamaporn Sangwung ◽  
Kitt Falk Petersen ◽  
Gerald I Shulman ◽  
Joshua W Knowles
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Function ◽  
Ex Vivo ◽  
Critical Role ◽  
Whole Body ◽  
Genetic Studies ◽  
Cellular Energy

Abstract Insulin resistance (IR) is fundamental to the development of type 2 diabetes (T2D) and is present in most prediabetic (preDM) individuals. Insulin resistance has both heritable and environmental determinants centered on energy storage and metabolism. Recent insights from human genetic studies, coupled with comprehensive in vivo and ex vivo metabolic studies in humans and rodents, have highlighted the critical role of reduced mitochondrial function as a predisposing condition for ectopic lipid deposition and IR. These studies support the hypothesis that reduced mitochondrial function, particularly in insulin-responsive tissues such as skeletal muscle, white adipose tissue, and the liver, is inextricably linked to tissue and whole body IR through the effects on cellular energy balance. Here we discuss these findings as well as address potential mechanisms that serve as the nexus between mitochondrial malfunction and IR.

scholarly journals The Environmental Strategy of Businesses as an Option under Recession in Greece

2018 ◽  
Vol 10 (12) ◽  
pp. 4399 ◽  
Author(s):  
Andreas Fousteris ◽  
Eleni Didaskalou ◽  
Markos-Marios Tsogas ◽  
Dimitrios Georgakellos
Keyword(s):  
Financial Performance ◽  
Competitive Advantage ◽  
Economic Crisis ◽  
Critical Role ◽  
Economic Recession ◽  
Decisive Role ◽  
Business Environment ◽  
Environmental Strategy ◽  
The Impact

In recent years and mostly during the last two decades, the decisive role of the environment in the business administration field and business life in general has emerged. In the modern, fast changing, and highly competitive business environment, and even more so in the context of the recent economic crisis, businesses constantly struggle to survive, trying to resolve problems and improve their performance and competitive advantage. Therefore, they must save and invest substantial sums of money to build strong infrastructure, to change procedures, and to produce environmentally friendly products. In view of the above, the current study attempted to examine the impact of environmental strategy on the growth of medium and large enterprises in all sectors in Greece, in a period of economic crisis. The study, carried out in February and March 2018, confirmed the positive correlation and the critical role of environmental strategy in the financial performance of Greek enterprises during this period of economic recession. Both eco-efficient practices and innovative practices lead to the creation of competitive advantage and, thus, to the improvement of the financial performance of a firm.

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