The institute for damage prevention in the civil law of the member states of the Commonwealth of Independent States

The authors considered the development and the current state of the damage prevention institute in the civil legislation of the member states of the Commonwealth of Independent States. They singled out and substantiated the key features of damage prevention claim. They noted the shortcomings of legal regulation in this area and made some offers to improve the legislatio

Whole exome sequencing links dental tumor to an autosomal-dominant mutation in ANO5 gene associated with gnathodiaphyseal dysplasia and muscle dystrophies

Tumors of the jaws may represent different human disorders and frequently associate with pathologic bone fractures. In this report, we analyzed two affected siblings from a family of Russian origin, with a history of dental tumors of the jaws, in correspondence to original clinical diagnosis of cementoma consistent with gigantiform cementoma (GC, OMIM: 137575). Whole exome sequencing revealed the heterozygous missense mutation c.1067G \u3e A (p.Cys356Tyr) in ANO5 gene in these patients. To date, autosomal-dominant mutations have been described in the ANO5 gene for gnathodiaphyseal dysplasia (GDD, OMIM: 166260), and multiple recessive mutations have been described in the gene for muscle dystrophies (OMIM: 613319, 611307); the same amino acid (Cys) at the position 356 is mutated in GDD. These genetic data and similar clinical phenotypes demonstrate that the GC and GDD likely represent the same type of bone pathology. Our data illustrate the significance of mutations in single amino-acid position for particular bone tissue pathology. Modifying role of genetic variations in another gene on the severity of the monogenic trait pathology is also suggested. Finally, we propose the model explaining the tissue-specific manifestation of clinically distant bone and muscle diseases linked to mutations in one gene

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability

DBSolve Optimum: a software package for kinetic modeling which allows dynamic visualization of simulation results

<p>Abstract</p> <p>Background</p> <p>Systems biology research and applications require creation, validation, extensive usage of mathematical models and visualization of simulation results by end-users. Our goal is to develop novel method for visualization of simulation results and implement it in simulation software package equipped with the sophisticated mathematical and computational techniques for model development, verification and parameter fitting.</p> <p>Results</p> <p>We present mathematical simulation workbench DBSolve Optimum which is significantly improved and extended successor of well known simulation software DBSolve5. Concept of "dynamic visualization" of simulation results has been developed and implemented in DBSolve Optimum. In framework of the concept graphical objects representing metabolite concentrations and reactions change their volume and shape in accordance to simulation results. This technique is applied to visualize both kinetic response of the model and dependence of its steady state on parameter. The use of the dynamic visualization is illustrated with kinetic model of the Krebs cycle.</p> <p>Conclusion</p> <p>DBSolve Optimum is a user friendly simulation software package that enables to simplify the construction, verification, analysis and visualization of kinetic models. Dynamic visualization tool implemented in the software allows user to animate simulation results and, thereby, present them in more comprehensible mode. DBSolve Optimum and built-in dynamic visualization module is free for both academic and commercial use. It can be downloaded directly from <url>http://www.insysbio.ru</url>.</p

Clinical Guidelines of the Russian Society of Surgeons, the Russian Gastroenterological Association, the Association of Surgeons-Hepatologists and the Endoscopic Society “REndO” on Diagnostics and Treatment of Chronic Pancreatitis

Aim: to present modern methods of diagnosis and treatment of chronic pancreatitis for gastroenterologists, general practitioners and physicians.Chronic pancreatitis (CP) is a long-term inflammatory disease of the pancreas, manifested by irreversible morphological changes in the parenchyma and pancreatic ducts, which cause pain and/or persistent impairment of function. Current concept on the etiology of CP is reflected by the TIGAR-O classification. The criteria for establishing the diagnosis of CP include typical attacks of abdominal pain and/or clinical and laboratory signs of exocrine, endocrine insufficiency with the mandatory detection of characteristic morphological changes (calcifications in the parenchyma and pancreatic ductal stones, dilatation of the main pancreatic duct and its branches). CT, MRCP, and pancreatobiliary endosonography are recommended as the methods of choice to verify the diagnosis of CP. Conservative treatment of patients with CP is provided for symptom relief and prevention of complications. Individual cases with severe non-interactable abdominal pain, as well as a complicated course of the disease (development of ductal hypertension due to main pancreatic duct stones or strictures, obstructive jaundice caused by compression of the common bile duct, symptomatic postnecrotic cysts, portal hypertension due to compression of the portal vein or thrombosis of the splenic vein, persistent duodenal obstruction, pseudoaneurysm of the celiac trunk basin and the superior mesenteric artery) serve as an indication for endoscopic or surgical treatment. The Guidelines set out modern approaches to the diagnosis, conservative, endoscopic and surgical treatment of CP, and the prevention of its complications.Conclusion. The implementation of clinical guidelines can contribute to the timely diagnosis and improve the quality of medical care for patients with chronic pancreatitis

An MCDA Approach for Evaluating Hydrogen Storage Systems for Future Vehicles

International audienceHydrogen, a non carbonated energy carrier, is often considered as one possible solution to reduce greenhouse gas emissions from human activity. The use of hydrogen as a possible alternative fuel for automotive applications is envisaged by car manufacturers. However, before a large scale commercialization of hydrogen vehicles, numerous challenges have to be faced, among which the on-board storage of hydrogen. This paper provides a description of the implementation of an MCDA approach for evaluating various competing hydrogen storage technologies for future vehicles. This implementation has been conducted within the STORHY European research project. The MACBETH method has been identified as an appropriate approach for the evaluation and comparison of the technologies from a technical point of view. The evaluation process has been entirely implemented on one hand with several experts from CEA and on the other hand with one of the STORHY car manufacturers. The implementation within the project confirmed that this evaluation method could be used for “application-oriented” multicriteria evaluations. The advantages and drawbacks of the method are finally discussed

The institute for damage prevention in the civil law of the member states of the Commonwealth of Independent States

The authors considered the development and the current state of the damage prevention institute in the civil legislation of the member states of the Commonwealth of Independent States. They singled out and substantiated the key features of damage prevention claim. They noted the shortcomings of legal regulation in this area and made some offers to improve the legislatio

RFLP discordance in a PKU family due to a deletion in the PAH gene

: We have previously reported preliminary data on a PKU family showing a discordant segregation of Pvu II (b) alleles at the PAH locus. A combination of several restriction enzymes and probe C2.6 (Intron 2) as well as STR typing were used to dissect the molecular structure of the PAH gene around exon 3. In this family, the results of this analysis and a re-examination of the physical map of the 5'-end of the gene provided strong evidence for the occurrence of a deletion removing exon 3. The "Sicilian" (approximately 2.5 kb) and "Yemenite Jew" (6.7 kb) deletions, the latter one also deleting exon 3, are different in terms of both the 5'-end breakpoint and apparent length. This study, besides adding a new member to the long and increasing list of nearly 200 PAH gene mutations, also proposes to undertake a careful evaluation of RFLP discordances incidentally detected at the PAH locus