Peculiar effects of muscarinic M1, M2, and M 3 receptor blockers on cardiac chronotropic function in neonatal rats

Department of Anatomy, Physiology, and Human Health Protection, Kazan (Volga Region) Federal University, Russia The effects of muscarinic M 1, M2, and M3 cholinergic receptor blockade on the regulation of chronotropic function of the heart were studied in vivo in 7-day-old rat pups. Intravenous injection of M2 receptor blocker gallamine produced no changes in cardiac chronotropy. In contrast, M1 receptor blocker pirenzepine and M3 receptor blocker 4DAMP provoked bradycardia. These data attest to the involvement of M1 and especially M3 cholinergic receptors in the regulation of cardiac chronotropy in rat pups, which confirms the view on pronounced species-specific and age-related peculiarities in the heart control mechanisms. © 2012 Springer Science+Business Media New York

Blockade of different subtypes of α1-adrenoceptors produces opposite effect on heart chronotropy in newborn rats

We compared the effects of blockade of α1A-, α1-, and α1D-subtypes of α1- adrenoceptors on the cardiac rhythm in newborn rats. Different responses of the heart were observed after blockade of several subtypes of α1- adrenoceptors. Administration of WB 4101, a selective blocker of α1A-adrenoceptors, increased heart rate, while blockade of α1AD-adrenoceptors with BMY 7378 decelerated of heart rhythm. Blockade of α1-adrenoceptors with chloroethylclonidine produced no significant effects on heart chronotropy. © 2012 Springer Science+Business Media New York

Peculiar effects of muscarinic M1, M2, and M3 receptor blockers on cardiac chronotropic function in neonatal rats.

The effects of muscarinic M(1), M(2), and M(3) cholinergic receptor blockade on the regulation of chronotropic function of the heart were studied in vivo in 7-day-old rat pups. Intravenous injection of M(2) receptor blocker gallamine produced no changes in cardiac chronotropy. In contrast, M(1) receptor blocker pirenzepine and M(3) receptor blocker 4DAMP provoked bradycardia. These data attest to the involvement of M(1) and especially M(3) cholinergic receptors in the regulation of cardiac chronotropy in rat pups, which confirms the view on pronounced species-specific and age-related peculiarities in the heart control mechanisms

Speech development of preschool children with mental retardation in the classroom to familiarize with the environment on the basis of fairy tales

В статье представлены результаты исследования эффективности использования сказок как средства развития речи детей дошкольного возраста с задержкой психического развития. Исследование проводилось на базе дошкольной образовательной организации, реализующей в том числе инклюзивные формы обучения.The article presents the results of research on the effectiveness of using fairy tales as a means of development of speech of preschool children with mental retardation. The study was conducted on the basis of preschool educational institution, implements,including the inclusive form of education

Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation

Extensive studies of the structure–function relationship of antibodies have established that conventional immunoglobulins contain two copies of the antigen-binding fragment (Fab), each of which serves as an autonomous and complete unit for recognizing an antigen. In this paper, we report a previously unidentified mode of antibody–antigen recognition, dubbed “antigen clasping,” where two antigen-binding sites cooperatively clasp one antigen, and the design of a long-neck antibody format that facilitates antigen clasping. Antigen clasping led to recombinant antibodies for histone posttranslational modifications with extraordinarily high specificity, valuable tools for epigenetic research. This study substantially broadens the long-standing paradigm for antibody–antigen recognition

Comparative analysis of molecular RFLP and SNP markers in assessing and understanding the genetic diversity of various chicken breeds

Monitoring the genetic diversity of small populations is important with respect to conserving rare and valuable chicken breeds, as well as discovery and innovation in germplasm research and application. Restriction fragment length polymorphisms (RFLPs), the molecular markers that underlie multilocus DNA fingerprinting (MLDF), have historically been employed for this purpose, but over the past two decades, there has been an irreversible shift toward high-throughput single-nucleotide polymorphisms (SNPs). In this study, we conducted a comparative analysis of archived MLDF results and new data from whole-genome SNP genotyping (SNPg) among 18 divergently selected breeds representing a large sample of the world gene pool. As a result, we obtained data that fit the general concept of the phylogenetic distribution of the studied breeds and compared them with RFLP and SNP markers. RFLPs were found to be useful markers for retrospective assessment of changes in the genetic architecture and variability underlying the phenotypic variation in chicken populations, especially when samples from previous generations used for MLDF are unavailable for SNPg. These results can facilitate further research necessary to assess the possibility of extrapolating previous MLDF results to study the long-term dynamics of genetic diversity in various small chicken germplasm populations over time. In general, the whole-genome characterization of populations and breeds by multiple SNP loci will further form the basis for the development and implementation of genomic selection with the aim of effective use of the genetic potential of the domestic gene pool in the poultry industry

A Pilot Study of Abnormal Growth in Autism Spectrum Disorders and Other Childhood Psychiatric Disorders

The aims of the current study were to examine whether early growth abnormalities are (a) comparable in autism spectrum disorders (ASD) and other childhood psychiatric disorders, and (b) specific to the brain or generalized to the whole body. Head circumference, height, and weight were measured during the first 19 months of life in 129 children with ASD and 59 children with non-ASD psychiatric disorders. Both groups showed comparable abnormal patterns of growth compared to population norms, especially regarding height and head circumference in relation to height. Thus abnormal growth appears to be related to psychiatric disorders in general and is mainly expressed as an accelerated growth of height not matched by an increase in weight or head circumference

Identification and Structural Characterization of a New Three-Finger Toxin Hemachatoxin from Hemachatus haemachatus Venom

10.1371/journal.pone.0048112PLoS ONE710

Snake Cytotoxins Bind to Membranes via Interactions with Phosphatidylserine Head Groups of Lipids

The major representatives of Elapidae snake venom, cytotoxins (CTs), share similar three-fingered fold and exert diverse range of biological activities against various cell types. CT-induced cell death starts from the membrane recognition process, whose molecular details remain unclear. It is known, however, that the presence of anionic lipids in cell membranes is one of the important factors determining CT-membrane binding. In this work, we therefore investigated specific interactions between one of the most abundant of such lipids, phosphatidylserine (PS), and CT 4 of Naja kaouthia using a combined, experimental and modeling, approach. It was shown that incorporation of PS into zwitterionic liposomes greatly increased the membrane-damaging activity of CT 4 measured by the release of the liposome-entrapped calcein fluorescent dye. The CT-induced leakage rate depends on the PS concentration with a maximum at approximately 20% PS. Interestingly, the effects observed for PS were much more pronounced than those measured for another anionic lipid, sulfatide. To delineate the potential PS binding sites on CT 4 and estimate their relative affinities, a series of computer simulations was performed for the systems containing the head group of PS and different spatial models of CT 4 in aqueous solution and in an implicit membrane. This was done using an original hybrid computational protocol implementing docking, Monte Carlo and molecular dynamics simulations. As a result, at least three putative PS-binding sites with different affinities to PS molecule were delineated. Being located in different parts of the CT molecule, these anion-binding sites can potentially facilitate and modulate the multi-step process of the toxin insertion into lipid bilayers. This feature together with the diverse binding affinities of the sites to a wide variety of anionic targets on the membrane surface appears to be functionally meaningful and may adjust CT action against different types of cells