L1 (LINE-1) retrotransposable elements provide a "fossil" record of the phylogenetic history of murid rodents

The single most difficult problem in phylogenetic analysis is deciding whether a shared taxonomic character is due to common ancestry or one that appeared independently due to convergence, parallelism, or reversion to an ancestral state. Mammalian L1 retrotransposons undergo periodic amplifications in which multiple copies of the elements are interspersed in the genome. Because these elements apparently are transmitted only by inheritance and are retained in the genome, a shared L1 amplification event can only be an inherited ancestral character. We propose that L1 amplification events can be an excellent tool for analyzing mammalian evolution and demonstrate here how we addressed several refractory problems in rodent systematics using L1 DNA as a taxonomic character.      

Hormonal regulation of anabolic processes and of protein utilization efficiency in the early postnatal period

The levels of thyroid, pituitary and steroid hormones-thyroxine, triiodothyronine and 11-hydroxycorticosteroids in the blood serum, somatotropin in the pituitary, and processes of protein assimilation were studied in rats in the early postnatal period. The highest endogenous production of thyroxine, triiodothyronine and somatotropin was detected in 15-day-old rats. The highest level of protein utilization was detected in 7 to 15-day-old rats, followed by the lowering of the utilization on changing over to definitive nutrition. Endogenous production of the anabolic hormones thyroxine, triiodothyronine and somatotropin was found to correlate with a high level of protein utilization in rats within the first days of life after birth.     

New principles in determining the biological value of proteins

Some new principles are suggested in determination of the protein biological values that take into account the amino acid composition and the processes occurring in the course of protein assimilation. Food proteins have a significant effect on the protein-amino acid metabolism of the organism by reducing oxidative catabolism of essential amino acids which are deficient in the utilized protein, i.e. they have a compensating effect on the deficiency of exogenous essential amino acids. The understanding of the process allowed the author to approach the solution of the problem of the replacement of the amino acid score with the biological value. For this purpose two new parameters which determine the quality and the second phase of protein assimilation have been introduced, i.e. potential biological value (BVp) and compensation coefficient (C), respectively. The experimental biological value (BV) is determined as the sum of the two parameters: BV = BVp + C.     

Influence of clinorotation on embryoid body morphology

The compensatory effects of gravitation at early stages of embryonic development have been investigated using the slow clinorotation of embryoid bodies generated from R1 mouse embryonic stem cells. An analysis of semithin sections (1–2μm) and an electron microscopy study of embryoid bodies revealed cells at different stages of maturation. A significant decrease (compared to the control) in embryonic stem cells undergoing apoptosis, as well as in noticeably reduced hollow areas, were found in clinorotated embryonic bodies. We propose that the lack of large cysts may be caused by the delay in initial differentiation and morphogenesis stages associated with autophagy processes in embryonic bodies.     

Interaction of Lipophilic Conjugates of Modified siRNAs with Hematopoietic Cells In Vitro and In Vivo

Russian Journal of Bioorganic Chemistry - Delivery of siRNAs to blood cells is one of the most difficult tasks since there are no efficient and nontoxic methods of delivering nucleic acids to these...     

Plant virus infection development as affected by heavy metal stress

The work was focused on the investigation of possible dependencies between the development of viral infection in plants and the presence of high heavy metal concentrations in soil. Field experiments have been conducted in order to study the development of systemic tobacco mosaic virus (TMV) infection in Lycopersicon esculentum L. cv. Miliana plants under effect of separate salts of heavy metals Cu, Zn and Pb deposited in soil. As it is shown, simultaneous effect of viral infection and heavy metals in tenfold maximum permissible concentration leads to decrease of total chlorophyll content in experiment plants mainly due to the degradation of chlorophyll a. The reduction of chlorophyll concentration under the combined influence of both stress factors was more serious comparing to the separate effect of every single factor. Plants' treatment with toxic concentrations of lead and zinc leaded to slight delay in the development of systemic TMV infection together with more than twofold increase of virus content in plants that may be an evidence of synergism between these heavy metal's and virus' effects. Contrary, copper although decreased total chlorophyll content but showed protective properties and significantly reduced amount of virus in plants.     

Lectins of marine hydrobionts

Data from the literature and results of our research on lectins isolated from some kinds of marine hydrobionts such as clams, ascidians, sea worms, sponges, and algae are presented in this review. Results of comparative analysis of the basic physicochemical properties and biological activity of lectins isolated from various sources are discussed.     

Role of oxidative stress and mitochondria in onset of urinary bladder dysfunction under acute urine retention

Acute urine retention is a frequent complication in patients with benign hyperplasia of the prostate gland. According to studies made on experimental animals and people, it is accompanied by the deterioration of the bladder blood supply. This study attempts to explore the relationship of intramural blood flow, production of reactive oxygen species, and functional state of the bladder detrusor in modeling of acute urine retention in rats, as well as the impact of mitochondria-targeted antioxidants (which are supposed to alleviate the effects of oxidative stress induced by experimental ischemia) on these parameters. The study showed beneficial effects of mitochondria-targeted antioxidant SkQR1 in preventing damage of the bladder caused by acute urinary retention, which suggests the therapeutic use of this type of compounds for the treatment of ischemic abnormalities of the urinary bladder.     

Molecular targets in the search for endothelium-protecting compounds

Impairment of endothelial function forms basis for many cardiovascular diseases, therefore today it becomes an independent target for therapeutic action, and the search for new compounds possessing endothelium-protective properties is one of the prospective goals of the pharmacotherapy and medicinal chemistry. An efficient instrument to solve the problem is the use of methods of molecular modeling. Application of the methods is possible only if detailed information on three-dimensional structure and function of molecular targets—receptors and enzymes responsible for signal transduction both inside and outside endothelial cells—is available. In the review we collected the data on the structure and functions of various macromolecules involved in the process of regulation of vascular tone. The structure of endothelial NO-synthase (EC 1.14.13.39) (eNOS) responsible for synthesis of nitrogen oxide and involved in the process of vascular tone regulation is described. The importance of its substrate, L-arginine, from the point of view of eNOS activity regulation is emphasized; the data on structure and functions of L-arginine transport system are presented. Also, various pathways of eNOS activity regulation are described, including activation and competitive inhibition through binding of exogenous substances in its active center and inhibition through caveolin binding at eNOS oxygenase domain among them, as well as regulation by means of phosphorylation of individual eNOS amino acid residues by protein kinases and their dephosphorylation by phosphatases. The importance of membrane receptors of endotheliocytes as targets for substances possessing endothelium-protective activity is emphasized. Receptors of endothelin, thrombocyte activation factor, prostaglandins, bradykinin, histamine, serotonin, and protein kinase-activated receptors are among them. The importance of calcium and potassium ion channels in vessel cells for endothelium protection is emphasized. Finally, the macromolecules discussed in the review are considered as targets in the search for endothelium-protective therapeutic agents by the proposed approaches and methods of molecular modeling.     

DNA methylation-associated colonic mucosal immune and defense responses in treatment-na?ve pediatric ulcerative colitis

Inflammatory bowel diseases (IBD) are emerging globally, indicating that environmental factors may be important in their pathogenesis. Colonic mucosal epigenetic changes, such as DNA methylation, can occur in response to the environment and have been implicated in IBD pathology. However, mucosal DNA methylation has not been examined in treatment-naïve patients. We studied DNA methylation in untreated, left sided colonic biopsy specimens using the Infinium HumanMethylation450 BeadChip array. We analyzed 22 control (C) patients, 15 untreated Crohn’s disease (CD) patients, and 9 untreated ulcerative colitis (UC) patients from two cohorts. Samples obtained at the time of clinical remission from two of the treatment-naïve UC patients were also included into the analysis. UC-specific gene expression was interrogated in a subset of adjacent samples (5 C and 5 UC) using the Affymetrix GeneChip PrimeView Human Gene Expression Arrays. Only treatment-naïve UC separated from control. One-hundred-and-twenty genes with significant expression change in UC (> 2-fold, P < 0.05) were associated with differentially methylated regions (DMRs). Epigenetically associated gene expression changes (including gene expression changes in the IFITM1, ITGB2, S100A9, SLPI, SAA1, and STAT3 genes) were linked to colonic mucosal immune and defense responses. These findings underscore the relationship between epigenetic changes and inflammation in pediatric treatment-naïve UC and may have potential etiologic, diagnostic, and therapeutic relevance for IBD.