Functional outcomes of structural peculiarities of striated muscle tropomyosin

Tropomyosin is a dimer coiled-coil actin-binding protein. Adjacent tropomyosin molecules connect each other ‘head-to-tail’ via an overlap junction and form a continuous strand that winds around an actin filament and controls the actin–myosin interaction. High cooperativity of muscle contraction largely depends on tropomyosin characteristics. Here we summarise experimental evidence that local peculiarities of tropomyosin structure have long-range effects and determine functional properties of the strand, including changes in its bending stiffness and interaction with actin and myosin. Point mutations and posttranslational modifications help to probe the roles of the conserved ‘non-canonical’ residues, clusters of stabilising and destabilising core residues, and core gap in tropomyosin function. The data suggest that tropomyosin structural lability including a diversity of homo- and heterodimers of different isoforms provide a balance of stiffness, flexibility, and strength of interaction with partner sarcomere proteins necessary for fine-tuning of Ca²⁺ regulation in various types of striated muscles.

     

Understanding neurobehavioral genetics of zebrafish

Abstract

Due to its fully sequenced genome, high genetic homology to humans, external fertilization, fast development, transparency of embryos, low cost and active reproduction, the zebrafish (Danio rerio) has become a novel promising model organism in biomedicine. Zebrafish are a useful tool in genetic and neuroscience research, including linking various genetic mutations to brain mechanisms using forward and reverse genetics. These approaches have produced novel models of rare genetic CNS disorders and common brain illnesses, such as addiction, aggression, anxiety and depression. Genetically modified zebrafish also foster neuroanatomical studies, manipulating neural circuits and linking them to different behaviors. Here, we discuss recent advances in neurogenetics of zebrafish, and evaluate their unique strengths, inherent limitations and the rapidly growing potential for elucidating the conserved roles of genes in neuropsychiatric disorders.     

Discussions and decisions of the 2012–2014 International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group,January 2012–June 2013

The International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group prepares proposals on the classification and nomenclature of filoviruses to reflect current knowledge or to correct disagreements with the International Code of Virus Classification and Nomenclature (ICVCN). In recent years, filovirus taxonomy has been corrected and updated, but parts of it remain controversial, and several topics remain to be debated. This article summarizes the decisions and discussion of the currently acting ICTV Filoviridae Study Group since its inauguration in January 2012.     

Electrophilically activated nitroalkanes in reaction with aliphatic diamines en route to imidazolines

A novel synthetic methodology for the assembly of imidazolines via an unusual reaction between nitroalkanes and aliphatic 1,2-diamines in the presence of phosphorous acid is described. In contrast to the related highly efficient preparation of benzimidazoles from aromatic amines, this process represents a major synthetic challenge and for a long time was elusive. Analysis of the method limitations is provided.

Imidazolines were assembled via an unusual reaction between nitroalkanes and aliphatic 1,2-diamines in the presence of phosphorous acid.     

Stimulation of Innate Immunity by In Vivo Cyclic di-GMP Synthesis Using Adenovirus

The bacterial second messenger cyclic di-GMP (c-di-GMP) stimulates inflammation by initiating innate immune cell recruitment and triggering the release of proinflammatory cytokines and chemokines. These properties make c-di-GMP a promising candidate for use as a vaccine adjuvant, and numerous studies have demonstrated that administration of purified c-di-GMP with different antigens increases protection against infection in animal models. Here, we have developed a novel approach to produce c-di-GMP inside host cells as an adjuvant to exploit a host-pathogen interaction and initiate an innate immune response. We have demonstrated that c-di-GMP can be synthesized in vivo by transducing a diguanylate cyclase (DGC) gene into mammalian cells using an adenovirus serotype 5 (Ad5) vector. Expression of DGC led to the production of c-di-GMP in vitro and in vivo, and this was able to alter proinflammatory gene expression in murine tissues and increase the secretion of numerous cytokines and chemokines when administered to animals. Furthermore, coexpression of DGC modestly increased T-cell responses to a Clostridium difficile antigen expressed from an adenovirus vaccine, although no significant differences in antibody titers were observed. This adenovirus c-di-GMP delivery system offers a novel method to administer c-di-GMP as an adjuvant to stimulate innate immunity during vaccination.     

Predictors of Mortality Following Aortic Valve Replacement in Aortic Stenosis Patients

Background: Understanding of the risk factors for the development of adverse outcomes after aortic valve replacement is necessary to develop timely preventive measures and to improve the results of surgical treatment. Methods: We analyzed patients with aortic stenosis (n = 742) who underwent surgical treatment in the period 2014–2020. The average age was 63 (57;69) years—men 58%, women 42%. Results: The hospital mortality rate was 3% (22 patients). The following statistically significant threshold values (cut-off points) were obtained in the ROC analysis: aortic cross-clamp time > 93 min AUC (CI) 0.676 (0.640–0.710), p = 0.010; cardiopulmonary bypass time > 144 min AUC (CI) 0.809 (0.778–0.837), p < 0.0001, hemoglobin before op <120 g/L. AUC (CI) 0.762 (0.728–0.793), p < 0.0001, hematocrit before op <39% AUC (CI) 0.755 (0.721–0.786), p < 0.001, end-diastolic dimension index >2.39 AUC (CI) 0.647 (0.607–0.686), p = 0.014, end-systolic dimension index > 1.68 AUC (CI) 0.657 (0.617–0.695), p = 0.009. Statistically significant independent predictors of hospital mortality were identified: BMI > 30 kg/m² (OR 2.84; CI 1.15–7.01), ischemic heart disease (OR 3.65; CI 1.01–13.2), diabetes (OR 3.88; CI 1.38–10.9), frequent ventricular ectopy before operation (OR 9.78; CI 1.91–50.2), mitral valve repair (OR 4.47; CI 1.76–11.3), tricuspid valve repair (OR 3.06; CI 1.09–8.58), 3 and more procedures (OR 4.44; CI 1.67–11.8). Conclusions: The hospital mortality rate was 3%. The main indicators associated with the risk of death were: diabetes, overweight (body mass index more than 30 kg/m²), frequent ventricular ectopy before surgery, hemoglobin level below 120 g/L, hematocrit level below 39%, longer cardiopulmonary bypass time and aortic cross-clamp time, additional mitral and tricuspid valve interventions.     

Leukocytospermia: relationship to sperm deoxyribonucleic acid integrity in patients evaluated for male factor infertility

The purpose of our study was to analyze the relationship of leukocytospermia to sperm DNA damage as assessed by the DNA integrity assay. Results indicate that leukocytospermia has a significant negative effect on the standard semen parameters of concentration, motility, and morphology but at most a very weak effect on DNA integrity as measured by the DNA fragmentation assay.