Chemie von α-Aminonitrilen. XVII. Oligo(nukleodipeptamidinium)-Salze

Experiments directed towards a chemical etiology of nucleic acids aim at uncovering facts that may help us to rationalize Nature\u27s choice of the RNA structure in the evolution of a genetic system. A strategy towards finding such facts is to synthesize potential nucleic acid alternatives and to systematically compare their functional properties (base pairing, nonenzymic replication, sequence- specific catalysis) on the chemical level with those of RNA. Nucleic acid alternatives are chosen by the criterion of whether their potential for constitutional self-assembly without enzymes is judged by chemical reasoning to be comparable to, or greater than, that of RNA. Alternatives which turn out to be functional could have (but have not or may have only temporarily) been chosen as a genetic system. Alternatives that are found to be non-functional can be dropped from the list of hypothetical RNA-competitors. Parallel to our work on nucleic acid alternatives based on hexopyranose sugars, we have studied potential pairing systems that contain dipeptide derivatives instead of sugar phosphates as building blocks of their backbones. Oligo-nucleodipeptamidinium salts of the constitutional type shown in Figure 3 can be interpreted as representing oligomers of corresponding nucleodipeptide nitriles which, in turn, can be derived from dipeptidic serine nitriles. This paper summarizes our observations on the synthesis and properties of thyminyl- and adenyl-derivatives of (L)-oligo-nucleodipeptamidinium salts (up to decamers) belonging to the constitutional type shown in Figures 9 and 10. Such oligomers are soluble in aqueous medium but turn out to be sensitive to hydrolysis at pH-values above 4 (half life of dimers at pH = 6, 1-3 h at room temperature, ca. 30 h at 0 °C). Neither in UV-spectroscopically determined mixing curves (c » 11 pM, pH = 4, 4 °C, 1 M NaCl) of mixtures of hexamers that contain complementary bases, nor in CD- spectra of (1 : 1) mixtures of the corresponding decamers (similar conditions) could we observe signs of adenine-thymine base pairing. Although these observations must be considered as preliminary since they are rather limited with regard to structural variations, conditions and observation methods, the properties observed for these materials discourage the view that such oligo-nucleodipeptamidinium salts might have been competitors to RNA. EINLEITUNG »Sie (die Naturstoffe) sind das Ergebnis einer drei Milliarden Jahre dauernden Entwicklung der lebendigen Welt und haben wáhrend einer langen Zeit die Auslese der Evolution überstanden. Ich bin überzeugt, dass sie immer eine Botschaft enthalten, und dass es unsere Aufgabe ist, diese zu entziffern.« (V. Prelog

High genetic diversity among Mycobacterium tuberculosis complex strains from Sierra Leone

<p>Abstract</p> <p>Background</p> <p>Among tuberculosis (TB) high incidence regions, Sub-Saharan Africa is particularly affected with approx. 1.6 million new cases every year. Besides this dramatic situation, data on the diversity of <it>Mycobacterium tuberculosis </it>complex (MTBC) strains causing this epidemic in this area are only sparsely available. Here we analyzed the population structure of strains from Sierra Leone with a special focus on the prevalence of <it>M. africanum</it>.</p> <p>Results</p> <p>A total of 97 strains isolated from smear positive cases registered for re-treatment in the Western Area and Kenema districts in years 2003/2004 were investigated by susceptibility testing (first line drugs) and molecular typing (IS<it>6110 </it>fingerprinting, spoligotyping, and MIRU-VNTR typing).</p> <p>Among the strains analyzed, 32 were resistant to isoniazid, and 11 were multidrug resistant (at least resistant to isoniazid and rifampin). The population diversity was high with two previously described <it>M. africanum </it>lineages (West African-1, n = 6; West African-2, n = 17) and seven <it>M. tuberculosis </it>lineages (Haarlem, n = 14; LAM, n = 15; EAI, n = 4; Beijing, n = 4; S-type, n = 4, X-type, n = 1; Cameroon, n = 4). Furthermore, two new <it>M. tuberculosis </it>genotypes Sierra Leone-1 (n = 7) and -2 (n = 10) were found. Strain classification according to a 7 bp deletion in pks1/15 revealed that the majority of <it>M. tuberculosis </it>strains belonged to the Euro American lineage (66 out of 74).</p> <p>Conclusion</p> <p>Resistance rates in Sierra Leone have reached an alarming level. The population structure of MTBC strains shows an intriguing diversity raising the question of possible consequences for TB epidemic and for the introduction of new diagnostic tests or treatment strategies in West Africa.</p

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Neues von The Missing Lin

SRP-35, a newly identified protein of the skeletal muscle sarcoplasmic reticulum, is a retinol dehydrogenase

In the present study we provide evidence that SRP-35, a protein we identified in rabbit skeletal muscle sarcoplasmic reticulum, is an all-trans-retinol dehydrogenase. Analysis of the primary structure and tryptic digestion revealed that its N-terminus encompasses a short hydrophobic sequence bound to the sarcoplasmic reticulum membrane, whereas its C-terminal catalytic domain faces the myoplasm. SRP-35 is also expressed in liver and adipocytes, where it appears in the post-microsomal supernatant; however, in skeletal muscle, SRP-35 is enriched in the longitudinal sarcoplasmic reticulum. Sequence comparison predicts that SRP-35 is a short-chain dehydrogenase/reductase belonging to the DHRS7C [dehydrogenase/reductase (short-chain dehydrogenase/reductase family) member 7C] subfamily. Retinol is the substrate of SRP-35, since its transient overexpression leads to an increased production of all-trans-retinaldehyde. Transfection of C2C12 myotubes with a fusion protein encoding SRP-35-EYFP (enhanced yellow fluorescent protein) causes a decrease of the maximal Ca²? released via RyR (ryanodine receptor) activation induced by KCl or 4-chloro-m-chresol. The latter result could be mimicked by the addition of retinoic acid to the C2C12 cell tissue culture medium, a treatment which caused a significant reduction of RyR1 expression. We propose that in skeletal muscle SRP-35 is involved in the generation of all-trans-retinaldehyde and may play an important role in the generation of intracellular signals linking Ca2+ release (i.e. muscle activity) to metabolism

Побожій С.І. Мистецтвознавчі нариси: монографія. - Суми, 2013. - 416 с.: 112 арк. іл.

Рецензія Сергія Дегтярьова на книжку "Побожій С.І. Мистецтвознавчі нариси: монографія. - Суми, 2013. - 416 с.: 112 арк. іл.".Рецензия Сергея Дегтярёва на книгу "Побожій С.І. Мистецтвознавчі нариси: монографія. - Суми, 2013. - 416 с.: 112 арк. іл.".Review of the book "Побожій С.І. Мистецтвознавчі нариси: монографія. - Суми, 2013. - 416 с.: 112 арк. іл." by Sergiy Degtyaryov

Les compétences des sages-femmes selon la loi

Deutsch: Seit Anfang Jahr ist das Gesundheitsberufegesetz in Kraft und definiert die Kom­petenzen von Hebammen und sechs weiteren Berufsgruppen. Ein Gesetz regelt nicht nur Pflichten, es beinhaltet auch Rechte und bietet Schutz. Entstanden ist es in mehrjähriger, intensiver Zusammenarbeit von Behörden und Vertreterinnen aus der Berufskonferenz sowie unter Einbezug von Hebammen aus verschiedenen Bereichen der Praxis und der Lehre. Sie haben mit grosser Umsicht und Sorgfalt die grund­legenden Formulierungen erarbeitet und in den Vernehmlassungen verteidigt Français: La loi sur les professions de la santé est en vigueur depuis le début de l’année et définit les compétences des sages-femmes et de six autres professions. Une telle loi règle non seulement les devoirs mais aussi les droits et offre une protection. Elle a été créée après plusieurs années de coopération intensive entre les autorités et les représentants de la Conférence professionnelle ainsi qu'avec la participation de sages-femmes de divers domaines de la pratique et de l'enseignement. Celles-ci ont élaboré les formulations de base avec grand soin et diligence et les ont défendues lors des consultations

Neues von The Missing Link

Neues von The Missing Lin

First microwave-assisted synthesis of an electron-rich phosphane and its coordination chemistry with platinum(II) and palladium(II)

The P–O ligand 3-(di(2-methoxyphenyl)phosphanyl)propionic acid (HL) was synthesized by a microwave-assisted reaction of a secondary phosphane. The coordination of HL to PtII yielded the neutral mononuclear complex trans-[PtCl(κ2-P,O-L)(κ-P-HL)] (1), while the reaction of PdClMe(η4-COD) (COD = 1,4-cyclooctadiene) with HL in the presence of NEt3 gave the anionic PdII compound of the formula (HNEt3)[PdClMe(κ2-P,O-L)] (2). Upon crystallization of the latter compound the neutral chloride-bridged dimetallic compound cis-[Pd(μ-Cl)Me(HL)]2 (3) was obtained. HL, 1 and 3·CH2Cl2 have been characterized by single crystal X-ray structure analyses