Editorial: Understanding Molecular Mechanisms in Diabetic Cardiomyopathy (DCM)

Cardiovascular disease is the leading cause of death worldwide, and diabetes, the most common metabolic syndrome, causes a 2–5 times higher risk for heart disease (1). Specifically, cardiovascular complications in people with diabetes mellitus (DM) are 2-3-fold more elevated than in non-diabetic counterparts, leading to a higher chance of causing diabetic cardiomyopathy (DCM). DCM is a prominent disease in people with DM, and molecular mechanisms that drive DCM are not fully understood as the disease itself is multifactorial and challenging potential treatment options (2). Therefore, this Research Topic is focused on understanding the molecular mechanism(s) contributing to DCM. The Research Topic comprised review and research articles from different experts working on DCM. The Research Topic of original research and review topics highlights the multifactorial molecular mechanisms involved in the DCM and some recent therapeutic advances in preclinical approaches at various levels in the pipeline.VS laboratory is partially supported by the American Heart Association grants (20CDA35260096 and 20TPA3542000)

Hydrazine-1,2-diium bis­(3-carb­oxy-4-hy­droxy­benzene­sulfonate) tetra­hydrate

Reaction of 5-sulfosalicylic acid with hydrazine hydrate at pH = 1 results in the formation of the title hydrated salt, 0.5N2H6 2+·C7H5O6S−·2H2O. The hydrazinium dications lie on centres of inversion. They are located between 3-carb­oxy-4-hy­droxy­benzene­sulfonate anions, forming inter­molecular N—H⋯O hydrogen bonds with sulfonate ions and water mol­ecules of crystallisation. Further intra- and inter­molecular O—H⋯O hydrogen bonds are observed in the crystal structure

Acetylation and phosphorylation of human TFAM regulate TFAM-DNA interactions via contrasting mechanisms

Mitochondrial transcription factor A (TFAM) is essential for the maintenance, expression and transmission of mitochondrial DNA (mtDNA). However, mechanisms for the post-translational regulation of TFAM are poorly understood. Here, we show that TFAM is lysine acetylated within its high-mobility-group box 1, a domain that can also be serine phosphorylated. Using bulk and single-molecule methods, we demonstrate that site-specific phosphoserine and acetyllysine mimics of human TFAM regulate its interaction with non-specific DNA through distinct kinetic pathways. We show that higher protein concentrations of both TFAM mimics are required to compact DNA to a similar extent as the wild-type. Compaction is thought to be crucial for regulating mtDNA segregation and expression. Moreover, we reveal that the reduced DNA binding affinity of the acetyl-lysine mimic arises from a lower on-rate, whereas the phosphoserine mimic displays both a decreased on-rate and an increased off-rate. Strikingly, the increased off-rate of the phosphoserine mimic is coupled to a significantly faster diffusion of TFAM on DNA. These findings indicate that acetylation and phosphorylation of TFAM can fine-tune TFAM-DNA binding affinity, to permit the discrete regulation of mtDNA dynamics. Furthermore, our results suggest that phosphorylation could additionally regulate transcription by altering the ability of TFAM to locate promoter sites

Progress in fluidized bed assisted abrasive jet machining (FB-AJM): Internal polishing of aluminium tubes

This paper deals with the internal finishing of tubular components made from a high strength aluminium alloy (AA 6082 T6) using a fluidized bed assisted abrasive jet machining (FB-AJM) system. Firstly, a Taguchi's experimental plan was used to investigate the influence of abrasive jet speed, machining cycle, and abrasive mesh size on surface roughness and material removal trends. Secondly, the leading finishing mechanisms were studied using combined 3d profilometer-SEM analysis to monitor the evolution of the surface morphology of machined workpieces. Finally, the circumferential uniformity and precision machining of the inner surface of workpieces were tested by evaluating the values of the more significant roughness parameters in different circumferential locations. Consistent trends of surface roughness vs. operational parameters were measured, and significant material removal was found to affect the workpieces during machining. As a result, FB-AJM was found to preferentially machine the asperities and irregularities of the surface, thereby altering the overall surface morphology producing more regular and smoother finishing. Moreover, the good circumferential uniformity and machining accuracy FB-AJM guarantees even on ductile aluminium alloy workpieces ensure that this technology can be applied to a diverse set of industrial components. (C) 2006 Elsevier Ltd. All rights reserved

Исследовательская деятельность эколого-биологической направленности в НОУ "Эврика" - эффективное средство профессиональной ориентации учащихся

В статье научно-исследовательская деятельность эколого-биологической направленности старшеклассников НОУ "Эврика" г. Нижнего Новгорода рассматривается как одна из значимых инновационных форм профессионального самоопределения. Материалом исследования послужил анализ программ конференции городского научного общества учащихся "Эврика" и судьбы выпускников данного общества. Отмечена тенденция роста популярности эколого-биологических исследований среди старшеклассников г. Нижнего Новгорода и успешное вхождение в профессию выпускников научного общества учащихся.In the article, the research activity of the ecology and biology of senior pupils of the scientific society of the pupils "Eureka" in Nizhny Novgorod is considered as one of the significant innovative forms of professional self-determination. The material of the study was the analysis of the programs of the conference of the city scientific society of the students "Eureka" and the fate of the graduates of this society. The tendency of growth of popularity of ecological and biological researches among senior pupils of Nizhny Novgorod and successful entry into the profession of graduates of the scientific society of students is noted

Predicting Software Revision Outcomes on Github Using Structural Holes Theory

Many software repositories are hosted publicly online via social platforms. Online users contribute to the software projects not only by providing feedback and suggestions, but also by submitting revisions to improve the software quality. This study takes a close look at revisions and examines the impact of social media networks on the revision outcome. A novel approach with a mix of different research methods (e.g., ego-centric social network analysis, structural holes theory and survival analysis) is used to build a comprehensible model to predict the revision outcome. The predictive performance is validated using real life datasets obtained from GitHub, the social coding website, which contains 32,962 pull requests to submit revisions, 20,399 distinctive software project repositories, and a social network of 234,322 users. Good predictive performance has been achieved with an average AUC of 0.84. The results suggest that a repository host's position in the ego network plays an important role in determining the duration before a revision is accepted. Specifically, hosts that are positioned in between densely connected social groups are likely to respond more quickly to accept the revisions. The study demonstrates that online social networks are vital to software development and advances the understanding of collaboration in software development research. The proposed method can be applied to support decision making in software development to forecast revision duration. The result also has several implications for managing project collaboration using social media

The influence of powder particle velocity and microstructure on the properties of cold sprayed copper coatings

No literature exists on the influence of the velocity of Cu powder particles (during cold spraying) on the properties of the coatings like porosity, hardness, electrical conductivity, residual stress, and microstructure. Similarly, though the occurrence of dynamic recrystallization in the Cu powder particle during its deformation under the cold sprayed process has been well documented, its influence on the properties of the coating has not been studied. In this study, it is shown that while porosity of the coating is determined directly by the powder particle velocity, the other properties like hardness, electrical conductivity, and residual stress are determined not only by the particle velocity which depends on stagnation pressure and preheating temperature of the air (process gas) but also additionally on preheating temperature of air per se. The extent of powder particle fragmentation and dynamic recrystallization as a function of particle velocity has been quantified in terms of the grain boundary area fraction and the influence of the latter parameter on the coating properties has also been presented

Understanding diabetes-induced cardiomyopathy from the perspective of renin angiotensin aldosterone system

Experimental and clinical evidence suggests that diabetic subjects are predisposed to a distinct cardiovascular dysfunction, known as diabetic cardiomyopathy (DCM), which could be an autonomous disease independent of concomitant micro and macrovascular disorders. DCM is one of the prominent causes of global morbidity and mortality and is on a rising trend with the increase in the prevalence of diabetes mellitus (DM). DCM is characterized by an early left ventricle diastolic dysfunction associated with the slow progression of cardiomyocyte hypertrophy leading to heart failure, which still has no effective therapy. Although the well-known "Renin Angiotensin Aldosterone System (RAAS)" inhibition is considered a gold-standard treatment in heart failure, its role in DCM is still unclear. At the cellular level of DCM, RAAS induces various secondary mechanisms, adding complications to poor prognosis and treatment of DCM. This review highlights the importance of RAAS signaling and its major secondary mechanisms involving inflammation, oxidative stress, mitochondrial dysfunction, and autophagy, their role in establishing DCM. In addition, studies lacking in the specific area of DCM are also highlighted. Therefore, understanding the complex role of RAAS in DCM may lead to the identification of better prognosis and therapeutic strategies in treating DCM.Qatar National Research Fund - Rapid Response Cal