VENTRICULAR REPOLARIZATION MEASURES IN PROFESSIONAL AND AMATEUR ATHLETES WITH HIGH NORMAL ARTERIAL PRESSURE.

There is merely little data regarding changes in repolarization among professional athletes with prehypertension, especially in comparison with amateur athletes. It was previously shown that disturbances of repolarization may have an important role in the development of cardiac changes in athletes and be observed in a number of conditions, such as ventricular hypertrophy, channelopathies, and aortic aneurysm. Therefore, in this study, it has been aimed to compare the ventricular repolarization measures in professional and amateur athletes with high normal arterial pressure.Thirty professional and thirty amateur all-around track and field athletes were enrolled in this project. According to the level of sport activities and the presence of HNBP, all athletes were divided into 4 groups. The first group consisted of professional athletes with normal and optimal blood pressure (NOBP) values (<130/80 mmHg, total of 21 persons), the second group was formed by 9 professional athletes with HNBP (≥130/85 mmHg), the following 3rd (17 persons) and 4th (13 persons) groups were composed by amateur athletes with the level of arterial blood pressure up to 130/85 mmHg and higher respectively. We have indicated that professional athletes with upper normal values of blood pressure have an extension of the TpTe interval compared to other groups of athletes, the average value of this indicator comprised 86 ± 10.94 ms, which, however, was below the dangerous level of >100 ms. This group of people also showed an increase in the ratio of TpTe/QT values (p=0.001) in the absence of a significant difference in S-Tpc intervals (p=0.605). These changes indicate an increase in transmural dispersion of repolarization with the development of left ventricular remodeling of professional athletes with upper normal values of blood pressure. In order to establish a connection between the revealed features of repolarization and non-functional overreaching/overtraining and altered autonomic cardiovascular activity with sympathetic activation syndrome, other pathogenesis features, their clinical and prognostic value, further examinations are required.

Transfer of trace elements in the ocean-atmosphere-continent system as a factor in the formation of the elemental composition of the Earth's soil cover.

The dynamics of global flows of matter in the biosphere has been studied. The general law of redistribution of average elemental compositions in the biosphere between the solid and liquid phases (lithosphere-hydrosphere) is established. In these processes, the main role is played by "living matter." The most active processes of redistribution of mean elemental compositions in the biosphere take place in the places of "life thickening" (biogeochemical barriers) such as ocean-atmosphere, river-sea and hydrosphere-lithosphere. The result of these processes is a general relative increase in the concentrations of trace elements in the environment of living organisms. A new methodological approach is proposed to study the role of the transfer of trace elements in the ocean-atmosphere-continent system as a factor in the formation of the elemental composition of the Earth's soil cover.

[Neurulation continues: the parade commander is...apical constriction].

Neurulation is traditionally defined as the process of closure of the neural tube. New data have shown that the major driving forces ofneurulation continue to operate with the closure of the neural tube, at least until the central canal of the neural tube has formed. Owing to this, the paper proposes to distinguish two periods of neurulation. According to these notions, early neurulation corresponds to the period of closure of the neural tube, and late neurulation corresponds to the period of formation of the central canal. Examples of neural tube defects that affect late neurulation are discussed.

Camptothecin-induced downregulation of MLL5 contributes to the activation of tumor suppressor p53.

Mixed lineage leukemia 5 (MLL5) has been implicated in multiple aspects of cell physiology, such as hematopoiesis, cell cycle control and chromatin regulatory network. In this study, we present evidence that MLL5 is involved in the camptothecin (CPT)-induced p53 activation. CPT promoted the degradation of MLL5 protein in a time- and dose-dependent manner in actively replicating cells. The downregulation of MLL5 led to phosphorylation of p53 at Ser392, which was abrogated by exogenous overexpression of MLL5. In MLL5-knockdown cells, p53 protein was stabilized and bound to DNA with higher affinity, leading to activation of downstream genes. Co-immunoprecipitation showed that MLL5 preferentially interacted with the tetramerized form of p53, and knockdown of MLL5 promoted chromatin accumulation of p53 tetramers, suggesting that the association of MLL5 with p53 may prevent the p53 tetramers from binding to the chromatin target sites. The role of MLL5 in CPT-induced p53 activation was conserved in developing zebrafish, where CPT downregulated zebrafish Mll5 protein, and the microinjection of zebrafish mll5 mRNA substantially blocked the CPT-induced apoptosis. In summary, our study proposed MLL5 as a novel component in the regulation of p53 homeostasis and a new cellular determinant of CPT.

Myogenesis and molecules - insights from zebrafish Danio rerio.

Myogenesis is a fundamental process governing the formation of muscle in multicellular organisms. Recent studies in zebrafish Danio rerio have described the molecular events occurring during embryonic morphogenesis and have thus greatly clarified this process, helping to distinguish between the events that give rise to fast v. slow muscle. Coupled with the well-known Hedgehog signalling cascade and a wide variety of cellular processes during early development, the continual research on D. rerio slow muscle precursors has provided novel insights into their cellular behaviours in this organism. Similarly, analyses on fast muscle precursors have provided knowledge of the behaviour of a sub-set of epitheloid cells residing in the anterior domain of somites. Additionally, the findings by various groups on the roles of several molecules in somitic myogenesis have been clarified in the past year. In this study, the authors briefly review the current trends in the field of research of D. rerio trunk myogenesis.

[Search for tissue-specific regulatory elements using Tol2 transposon as an example of evolutionary synthesis of genomics and developmental biology].

The GFP gene controlled by a mini-promoter of the gene was cloned into a modified nonautonomous transposon Tol2 from the medaka genome. Such transposon cannot itself transpose, but external transposase allows it to integrate into the germ cell genome, where it remains after transposase is depleted. This gives rise to a transgenic zebrafish line stably maintained for many generations. This approach was used to obtain several tens of transgenic zebrafish lines, each of which demonstrates stably inherited pattern of GFP expression. This pattern depends on the enhancer activity in the vicinity of the transposon integration site. These lines can be used for the analysis of DNA sequences of enhancers, in vivo studies of complex cell morphogenesis, description of organs whose development has not been described in zebrafish, and analysis of activity of genes controlled by the identified promoters during development. Current data on the transgenic lines were integrated into the dedicated ZETRAP database. At the second stage of this project, the transposon was mobilized by a short-term exposure of two transgenic lines to transposase and left the initial chromosomal location. This allowed us to isolate about 20 transgenic lines with new expression patterns. This approach can be successfully used to study the zebrafish biology and anatomy, activity of the regulatory part of the genome, and development of new promising techniques in developmental biology and, in the foreseeable future, gene therapy.

[Influence of alimentary microelementosis on superoxide dismutase and glutathione peroxidase activities].

Studies of K(m) for glutathione peroxidase (GPx) and activities of superoxide dismutase and GPx were carried out in liver and erythrocytes of rats kept on either the normal semisynthetic diet or a high-fat diet with increased content of Cu, Zn, Mn, and Se. The diet containing microelement additions caused the increase in TBH affinity of liver and erythrocite GPx, as well as the decrease of liver SOD observed on the 14th day of the treatment of rats with the high-fat diet with additional increase of Cu, Zn, Mn, and Se.

RhoA prevents apoptosis during zebrafish embryogenesis through activation of Mek/Erk pathway.

RhoA small GTPase, as a key regulator for actin cytoskeletal rearrangement, plays pivotal roles during morphogenesis, cytokinesis, phagocytosis and cell migration, but little is known about its signaling mechanism that controls cell survival in vivo. Using zebrafish as a model, we show that non-overlapping antisense morpholinos that block either translation or splicing of rhoA lead to extensive apoptosis during embryogenesis, resulting in overall reduction of body size and body length. These defects are associated with reduced activation of growth-promoting Erk and decreased expression of anti-apoptotic bcl-2. Moreover, ectopic expression of rhoA, Mek or BCL-2 mRNA rescues such phenotypes. Consistently, combined suppression of RhoA and Mek/Erk or Bcl-2 pathways by sub-optimal dose of rhoA morpholino and pharmacological inhibitors for either Mek (U0126) or Bcl-2 (HA 14-1) can induce developmental abnormalities and enhanced apoptosis, similar to those caused by effective RhoA knockdown. Furthermore, U0126 abrogates the rescue by RhoA and MEK but not BCL-2. In contrast, HA 14-1 effectively abolishes all functional rescues by RhoA, MEK or BCL-2, supporting that RhoA prevents apoptosis by activation of Mek/Erk pathway and requiring Bcl-2. These findings reveal an important genetic and functional relationship between RhoA with Mek/Erk and Bcl-2 for cell survival control during embryogenesis.

White spot syndrome virus (WSSV) infects specific hemocytes of the shrimp Penaeus merguiensis.

White spot syndrome virus (WSSV) was specifically detected by PCR in Penaeus merguiensis hemocytes, hemolymph and plasma. This suggested a close association between the shrimp hemolymph and the virus. Three types of hemocyte from shrimp were isolated using flow cytometry. Dynamic changes of the hemocyte subpopulations in P. merguiensis at different times after infection were observed, indicating that the WSSV infection selectively affected specific subpopulations. Immunofluorescence assay (IFA) and a Wright-Giemsa double staining study of hemocyte types further confirmed the cellular localization of the virus in the infected hemocytes. Electron microscopy revealed virus particles in both vacuoles and the nucleus of the semigranular cells (SGC), as well as in the vacuoles of the granular cells (GC). However, no virus could be detected in the hyaline cells (HC). Our results suggest that the virus infects 2 types of shrimp hemocytes--GCs and SGCs. The SGC type contains higher virus loads and exhibits faster infection rates, and is apparently more susceptible to WSSV infection.

Expression pattern of two zebrafish genes, cxcr4a and cxcr4b.

We cloned and mapped two novel zebrafish genes, cxcr4a and cxcr4b, which are closely related to mammalian CXCR4. Expression analysis by reverse transcription-polymerase chain reaction and in situ hybridization demonstrated that these two genes are expressed in most cell lineages known to express Cxcr4 in mammals. These genes are co-expressed in lateral mesoderm and posterior midbrain. The transcripts of cxcr4a were detected in interneurons and endoderm, whereas cxcr4b was specifically expressed in sensory neurons, motoneurons and cerebellum. In the lateral mesoderm, cxcr4b transcripts appeared earlier than those of cxcr4a. Thus, the function of mammalian CXCR4 could be split between the two zebrafish genes. These genes probably derived from the genome duplication event, which occurred during the evolution of teleosts. Similar pairs of Cxcr4 may exist in other species, where genome duplication has occurred.

Expression of brain subtype creatine kinase in the zebrafish embryo.

Creatine kinases (CK) play crucial roles in intracellular energy transfer. We have isolated a cDNA from zebrafish embryos, which encodes a CK highly related to the mammalian brain subtype creatine kinase (BCK). The bck mRNA is expressed maternally in the zebrafish embryo and transcripts are distributed uniformly in blastula and gastrula stages. Expression becomes restricted to the prechordal plate and the nervous system during subsequent somitogenesis stages. bck transcripts are abundant in primary neurons in the developing central nervous system of the 1-day-old embryo. While some bck expression persists in the hindbrain, expression vanishes in the spinal cord of the 2-day-old embryo. In summary, the expression pattern of bck is highly dynamic and suggests a role for bck during gastrulation and neuronal differentiation.

A novel zebrafish bHLH gene, neurogenin3, is expressed in the hypothalamus.

Many basic helix-loop-helix transcriptional factors play important roles in vertebrate neurogenesis. Among them, Neurogenins act as determination factors and initiate the expression of differentiation genes such as neuroD and other neurogenic genes. Here we describe a zebrafish cDNA (neurogenin3 or ngn3) encoding a novel member of the Neurogenin family closest to mouse Ngn3 and human NGN3. Using a zebrafish radiation hybrid panel, ngn3 was mapped to zebrafish linkage group 13 and the region displayed a conserved synteny with the region of human chromosome 10 containing NGN3. As judged by RT-PCR and whole-mount in situ hybridization, ngn3 expression in zebrafish started much later than other neurogenin genes, at only around 24 h post-fertilization (hpf) and with a higher level of expression on the left side of the anterio-ventral diencephalon. Later at 48 hpf, ngn3 expression was detected in a small number of cells in the tuberal hypothalamus. Unlike Ngn3 in the mouse, zebrafish ngn3 mRNAs were not detected in developing pancreas and spinal cord. Genomic Southern blot hybridization suggested that a closely related sequence is present in the zebrafish genome and the hypothetical gene might result from the recent genome duplication in certain teleost lineage and share the function of the common ancestor with the currently characterized ngn3.

[T-Box genes and developmental decisions that cells make]. / T-boks-geny i vybor kletkami putei razvitia.

During gastrulation in vertebrate embryos, three definitive germ layers (ectoderm, mesoderm, and endoderm) are formed by organized and coordinated cell movements. In zebrafish, further subdivision of the mesoderm gives rise to the axial, adaxial and paraxial mesoderm. The axial mesoderm contributes to the prechordal plate and notochord whereas the adaxial and paraxial cells give rise to slow and fast muscles, respectively (Devoto et al., 1996; Blagden et al., 1997; Currie and Ingham, 1998). An inductive interaction in which the notochord plays an essential role will also provide an input in forming other specialized types of tissue contributing to the axial structures: the floor plate located dorsally to the notochord in the ventral spinal cord and the hypochord located ventrally of the notochord and deriving probably from the endoerm. It is known that despite the difference in developmental roles (Strähle et al., 1993; Krauss et al., 1993), the floor plate and hypochord co-express a number of common molecular markers (Jan et al., 1995; our unpublished results) that may illustrate a certain similarity of their origin. Their close proximity to the notochord determines specialized features of these structures that differ substantially from the rest of the neural tube and endoderm, correspondingly. Once formed under the influence of the notochordal signaling, the floor plate will acquire an ability, similar to the notochord, to express genes of the Hedgehog family and several other groups of genes and to induce specification of ventral cell types in the neural tube during later development (for review, see Korzh, 1998). The biology of the hypochord is much less understood. It seems that the hypochord develops slightly later than the floor plate. It may be required for proper positioning of the dorsal aorta as well as induction of some other endoderm derivatives.

[N.A. Dobrovolskaya-Zavadskaya and the discovery of the T gene]. / N.A. Dobrovolsakya-Zavadskaya i otkrytie T-gena.

Nadezhda Alexandrovna Dobrovolskaya-Zavadskaya was born in Kiev on September 13, 1878. She studied medicine in Saint Petersburg where in the early 1900s, Dobrovolskaya became one of the best known women surgeons. After the First World War started in 1914, she joined the Russian army and worked in military hospitals until 1917, when the revolution dramatically changed the fate of Russia and all Russians. At the end of civil war she was working in the hospital in the army of General Wrangel. After the defeat of Wrangel in 1920, Dobrovolskaya left Russia and went into exile. Like many other Russian emigr[symbol: see text]s, she came to Paris after fleeing Crimea via Turkey and Egypt. (Unfortunately, this period of the life of Nadezhda Dobrovolskaya is completely unknown to me.)

Expression of two novel zebrafish iroquois homologues (ziro1 and ziro5) during early development of axial structures and central nervous system.

Previously, we reported a zebrafish iroquois gene, ziro3, and its expression during early embryogenesis (Mech. Dev. 87 (1999) 165). In the present study, we have isolated two novel zebrafish iroquois genes, ziro1 and ziro5, homologs of mouse Irx1 and mouse Irx5, respectively. The expression of both genes is initiated in dorsal neuroectoderm and mesoderm during gastrulation. Later, their expression appears in the central nervous system (CNS), excluding the telencephalon and most of the diencephalon. ziro1 expression is complementary to that of ziro3 in the notochord and later in the gut. In contrast, ziro5 expression mostly overlaps with that of ziro3. Interestingly, all three iroquois zebrafish genes are expressed in the notochord while only Irx3 is active in the mouse notochord. Their expression in later stages of embryogenesis was also compared.

Developmental analysis of ceruloplasmin gene and liver formation in zebrafish.

Formation of the liver in zebrafish has been analyzed during normal embryogenesis using ceruloplasmin (Cp) as a specific marker. The asymmetric expression of Cp has been detected in dorsal endoderm at 16 hpf and later in the early hepatic cells in the yolk sac. The liver primordium can be detected after 32 hpf. In oep-/- mutant, which lacks dorsal endoderm, the liver fails to form. In the notochordless flh-/- mutant, the asymmetry of the liver has been lost. Therefore the notochord, dorsal endoderm and endoderm of the yolk sac play a role in liver formation in zebrafish.