Alloxan and streptozotocin are widely used to induce experimental diabetes in animals. The mechanism of their action in B cells of the pancreas has been intensively investigated and now is quite well understood. The cytotoxic action of both these diabetogenic agents is mediated by reactive oxygen species, however, the source of their generation is different in the case of alloxan and streptozotocin. Alloxan and the product of its reduction, dialuric acid, establish a redox cycle with the formation of superoxide radicals. These radicals undergo dismutation to hydrogen peroxide. Thereafter highly reactive hydroxyl radicals are formed by the Fenton reaction. The action of reactive oxygen species with a simultaneous massive increase in cytosolic calcium concentration causes rapid destruction of B cells. Streptozotocin enters the B cell via a glucose transporter (GLUT2) and causes alkylation of DNA. DNA damage induces activation of poly ADP-ribosylation, a process that is more important for the diabetogenicity of streptozotocin than DNA damage itself. Poly ADP-ribosylation leads to depletion of cellular NAD+ and ATP. Enhanced ATP dephosphorylation after streptozotocin treatment supplies a substrate for xanthine oxidase resulting in the formation of superoxide radicals. Consequently, hydrogen peroxide and hydroxyl radicals are also generated. Furthermore, streptozotocin liberates toxic amounts of nitric oxide that inhibits aconitase activity and participates in DNA damage. As a result of the streptozotocin action, B cells undergo the destruction by necrosis., T. Szkudelski., and Obsahuje bibliografii
The fundamental biochemical processes of 5-methylcytosine (5-mC) synthesis, maintenance, conversion and removal determine the time and spatial pattern of DNA methylation. This has a strong effect on a plethora of physiological aspects of cellular metabolism. While the presence of 5-mC within the promoter region can silence gene expression, its derivative - 5-hydroxymethylcytosine exerts an opposite effect. Dysregulations in the metabolism of 5-mC lead to an altered DNA methylation pattern which is linked with a disrupted epigenome, and are considered to play a significant part in the etiology of several human diseases. A summary of recent knowledge about the molecular processes participating in DNA methylation pattern shaping is provided here., R. Murín, M. Abdalla, N. Murínová, J. Hatok, D. Dobrota., and Obsahuje bibliografii
Recent studies have demonstrated that some microRNAs (miRNAs) inhibit bone formation by inhibiting the translation of specific genes. Several in vitro studies have suggested that miR - 23a inhibits osteogenic differentiation by suppressing the translation of Runx2, a transcription factor essential for osteoblastogenesis, and of Sa tb2, a member of the special AT-rich binding protein family. In the pr esent study, we used a gain -of-function approach to determine the roles of miR -23a in bone formation and homeostasis in vivo . The miR -23a transgenic (Tg) mice grew normally and their body size and weight were similar to those of wild -type (WT) littermates. Bone structure and morphology were similar in Tg and WT mice. Furthermore, the numbers of osteoblasts and osteoclasts, as well as their activities in bone were similar between Tg and WT mice. Our results indicate that miR -23 has limited roles in bone form ation and maintenance in vivo in mice., J. Park, S. Wada, T. Ushida, T. Akimoto., and Obsahuje bibliografii
A mineralogical study of the weathering crusts rich in P and Mn from the locality Hodušín - Božetice at Milevsko is presented. The locality belongs to the central part of the variegated group of Sušice and Votice in the Moldanubian Unit. From the analytical methods used, the IR-spectroscopy yielded satisfactory results. The main crust components subjected to weathering are apatite (of a CarHap B - dahllite type) and Mn-minerals (massive black psilomelane, the needle-aggregates probably comprise a poorly recrystallized psilomelane). Disintegrated rocks consist of a mixture of clay minerals, calcite and relicts of primary minerals (quartz, K-feldspars, albite, pyroxene and rutile). The origin and the source material of these crusts rich in P and Mn can not be unambiguously determined. Apatites without CL-effects indicate that the weathering crusts have originated in a strongly oxidative environment. Well documented neighbouring occurrences of phosphate minerals in the variegated group of Sušice and Votice are associated with graphitic rocks. Optical and quantitative chemical analyses of the rocks suggest that the source of apatite could possible be calc-silicate rocks (erlans) close to the graphitic rocks. Hypothetically, the metaphosphorite layers in the variegated Moldanubian Unit can also be considered a possible source of phosphorus., M. Brož, M. Kovářová, Z. Losos, M. Linhartová and V. Vávra., and Obsahuje bibliografii
The Mediterranean flour moth, Ephestia kuehniella is a widespread pest of stored products and a classical object in experimental biology. In the present study, we determined its complete mitochondrial genome sequence. The genome is circular, consists of 15,327 bp and comprises 13 protein-coding, 2 rRNA- and 22 tRNA-coding genes in an order typical for the Ditrysia clade of the order Lepidoptera. A phylogenetic study of the Lepidoptera based on complete mitochondrial genomes places E. kuehniella correctly in the family Pyralidae and supports major lepidopteran taxa as phylogenetic clades. The W chromosome of E. kuehniella is an exceptionally rich reservoir of originally mitochondrial sequences (numts). Around 0.7% of the W DNA was found to be of mitochondrial origin, 83% of the mitogenome sequence was represented between 1-11 × in the W chromosome. Phylogenetic analysis further revealed that these numts are an evolutionary recent acquisition of the W chromosome., Katrin Lämmermann, Heiko Vogel, Walther Traut., and Obsahuje bibliografii
Familial hypercholesterolemia (FH) is most frequently caused by LDLR or APOB mutations. Therefore, the aim of our study was to examine the genetic background of Slovak patients suspected of FH. Patients with clinical suspicion of FH (235 unrelated probands and 124 family relatives) were recruited throughout Slovakia during the years 2011-2015. The order of DNA analyses in probands was as follows: 1. APOB mutation p.Arg3527Gln by real-time PCR method, 2. direct sequencing of the LDLR gene 3. MLPA analysis of the LDLR gene. We have identified 14 probands and 2 relatives with an APOB mutation p.Arg3527Gln, and 89 probands and 75 relatives with 54 different LDLR mutations. Nine of LDLR mutations were novel (i.e. p .Asp90Glu, c.314-2A>G, p.Asp136Tyr, p.Ser177Pro, p.Lys225_Glu228delinsCysLys, p.Gly478Glu, p.Gly675Trpfs*42, p.Leu680Pro, p.Thr832Argfs*3). This is the first study on molecular genetics of FH in Slovakia encompassing the analysis of whole LDLR gene. Geneti c etiology of FH was confirmed in 103 probands (43.8 %). Out of them, 86.4 % of probands carried the LDLR gene mutation and remaining 13.6 % probands carried the p.Arg3527Gln APOB mutation., D. Gabčová, B. Vohnout, D. Staníková, M. Hučkova, M. Kadurová, M. Debreová, M. Kozárová, Ľ. Fábryová, Slovak FH Study Group, J. Staník, I. Klimeš, K. Rašlová, D. Gašperiková., and Obsahuje bibliografii
Large and small rDNA sequences of 41 species of the family Opecoelidae are utilised to produce phylogenetic inference trees, using brachycladioids and lepocreadioids as outgroups. Sequences were newly generated for 13 species. The resulting Bayesian trees show a monophyletic Opecoelidae. The earliest divergent group is the Stenakrinae, based on two species which are not of the type-genus. The next well-supported clade to diverge is constituted of three species of Helicometra Odhner, 1902. Based on this tree and the characters of the egg and uterus, a new subfamily, the Helicometrinae, is erected and defined to include the genera Helicometra, Helicometrina Linton, 1910 and Neohelicometra Siddiqi et Cable, 1960. The subfamily Opecoelinae is found to be monophyletic, but the Plagioporinae is paraphyletic. The single representative of the Opecoelininae (not of the type genus) is nested within a group of deep-sea 'plagioporines'. The two representatives of the Opistholebetidae are embedded within a group of shallow-water 'plagioporine' species. The Opistholebetidae is reduced to subfamily status pro tem as its morphological and biological characteristics are distinctive. This implies that as opecoelid systematics develops with more molecular evidence, several further subfamilies will be recognised. Many of the morphological characters were found to be homoplasious, but the characters defining the Helicometrinae and Opecoelinae, such as filamented eggs, reduced cirrus-sac and uterine seminal receptacle, are closely correlated with the inferred phylogeny., Rodney A. Bray, Thomas H. Cribb, D. Timothy J. Littlewood, Andrea Waeschenbach., and Obsahuje bibliografii
Arthrospira maxima is unique among cyanobacteria, growing at alkaline pH (<11) in concentrated (bi)carbonate (1.2 M saturated) and lacking carbonic anhydrases. We investigated dissolved inorganic carbon (DIC) roles within PSII of A. maxima cells oximetrically and fluorometrically, monitoring the light reactions on the donor and acceptor sides of PSII. We developed new methods for removing DIC based on a (bi)carbonate chelator and magnesium for (bi)carbonate ionpairing. We established relative affinities of three sites: the water-oxidizing complex (WOC), non-heme iron/QA-, and solvent-accessible arginines throughout PSII. Full reversibility is achieved but (bi)carbonate uptake requires light. DIC depletion at the non-heme iron site and solvent-accessible arginines greatly reduces the yield of O2 due to O2 uptake, but accelerates the PSII-WOC cycle, specifically the S2-S3 and S3-S0 transitions. DIC removal from the WOC site abolishes water oxidation and appears to influence free energy stabilization of the WOC from a site between CP43-R357 and Ca2+., G. Ananyev, C. Gates, G. C. Dismukes., and Obsahuje bibliografické odkazy
This article argues that understanding any space or site relies on a knowledge of its fourth dimension - the timescape. It will explore this by situating the investigation in the museum - a place of heightened contrivance which could easily be shallowly interpreted as "mere style". It will defend a new method of investigating museum temporality which combines both phenomenology and literary theory, and will replace the idea of geo-epistemology with geochronic epistemology: an understanding of context and situation which takes on time as well as spatial location. In so doing, it moves on from notions of the museum as a place out of time, situating it in the networks of meaning, power and politics in which we have lived and are living. Thus, "the whole space of the exhibition" as Lyotard said, "becomes the remains of all time": the Museum on the Edge of Forever., Tento článek pracuje s argumentem, že porozumění jakémukoliv prostoru či místu se odvíjí od znalosti jeho čtvrtého rozměru – krajiny času. Toto tvrzení probádává tak, že zasazuje výzkum do muzea – místa se zvýšenou mírou machinace, již by bylo snadno povrchně interpretovat jako "pouhý styl“. Článek obhajuje novou metodu zkoumání temporality muzea, jež v sobě kombinuje fenomenologii i literární teorii a nahrazuje myšlenku geoepistemologie geochronickou epistemologií: porozuměním kontextu a situaci, jež je umístěno jak v čase, tak v prostoru. Tím, že tak činí, se článek posunuje od pojetí muzea jakožto místa mimo čas a zasazuje jej do sítí významů, moci a politiky, v nichž jsme žili a stále žijeme. Takto se "veškerý prostor výstavy“, jak poznamenal Lyotard, "stává pozůstatkem všeho času: muzeem na okraji věčnosti., and Jennifer Walklate.