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In einer Sandgrube östlich des Ortes Buer fand sich eine knapp 2 m mächtige Schichtfolge aus Torf, Mudde und humosem Schluff, unterlagert von Beckenschluff, Geschiebelehm und kieshaitigen Schmelzwassersanden aus dem Orenthe-Stadium der Saale-Kaltzeit. Überlagert werden die organischen Schichten von Beckenschluff und Lößlehm der Weichsel- Kaltzeit. Die pollenanalytischen Ergebnisse zeigen, daß die 30 cm mächtige Torfschicht im Hangenden des Beckenschluffs mit Sicherheit in das frühe Eem-Interglazial zu stellen ist. Die typischen Pollenabschnitte liegen in sehr komprimierter Form vor, lassen aber gleichwohl die kontinuierliche Abfolge der charakteristischen Waldzeiten erkennen. Besonders bemerkenswert sind die im Vergleich zu anderen Eem-Vorkommen des norddeutschen Flachlandes hohen Ulmen-Werte. Wegen seiner vegetationsgeschichtlichen Besonderheiten und da das Profil das einzige in einem Tagesaufschluß zugängliche Eem-Interglazial-Vorkommen Niedersachsens ist, wurde beantragt, es als geologisches Naturdenkmal unter Naturschutz zu stellen.
Die kutane Larva migrans ist eine in ihrem klinischen Bild typische Hautinfektion, die durch aktives Eindringen und anschließende epidermale Wanderung von Nematodenlarven hervorgerufen wird. Dieses typische klinische Bild wird durch Larven von Hakenwürmern, meist Ancylostoma braziliense, selten andere bei Kaniden und Feliden vorkommende Hakenwurmarten, verursacht.
Ziele der Leitlinie sind die Verbesserung der Versorgung der Patienten durch Optimierung von Diagnostik und Therapie bei Infektionen mit Larva migrans cutanea sowie die Verbesserung der Kenntnisse von Ärztinnen und Ärzte über aktuelle Therapieoptionen.
Ribosome biogenesis in eukaryotes requires the participation of a large number of ribosome assembly factors. The highly conserved eukaryotic nucleolar protein Nep1 has an essential but unknown function in 18S rRNA processing and ribosome biogenesis. In Saccharomyces cerevisiae the malfunction of a temperature-sensitive Nep1 protein (nep1-1ts) was suppressed by the addition of S-adenosylmethionine (SAM). This suggests the participation of Nep1 in a methyltransferase reaction during ribosome biogenesis. In addition, yeast Nep1 binds to a 6-nt RNA-binding motif also found in 18S rRNA and facilitates the incorporation of ribosomal protein Rps19 during the formation of pre-ribosomes. Here, we present the X-ray structure of the Nep1 homolog from the archaebacterium Methanocaldococcus jannaschii in its free form (2.2 Å resolution) and bound to the S-adenosylmethionine analog S-adenosylhomocysteine (SAH, 2.15 Å resolution) and the antibiotic and general methyltransferase inhibitor sinefungin (2.25 Å resolution). The structure reveals a fold which is very similar to the conserved core fold of the SPOUT-class methyltransferases but contains a novel extension of this common core fold. SAH and sinefungin bind to Nep1 at a preformed binding site that is topologically equivalent to the cofactor-binding site in other SPOUT-class methyltransferases. Therefore, our structures together with previous genetic data suggest that Nep1 is a genuine rRNA methyltransferase.
A new artificial regulatory system for essential genes in yeast is described. It prevents translation of target mRNAs upon tetracycline (tc) binding to aptamers introduced into their 5'UTRs. Exploiting direct RNA–ligand interaction renders auxiliary protein factors unnecessary. Therefore, our approach is strain independent and not susceptible to interferences by heterologous expressed regulatory proteins. We use a simple PCR-based strategy, which allows easy tagging of any target gene and the level of gene expression can be adjusted due to various tc aptamer-regulated promoters. As proof of concept, five differently expressed genes were targeted, two of which could not be regulated previously. In all cases, adding tc completely prevented growth and, as shown for Nop14p, rapidly abolished de novo protein synthesis providing a powerful tool for conditional regulation of yeast gene expression.
Nach einer kurzen schweren Krankheit verstarb unerwartet am 30.07.2000 im Alter von 77 Jahren Karl Kiesewetter, langjähriger Leiter der Fachgruppe Ornithologie und Naturschutz Weißenfels. Mehr als 50 Jahre hat sich Karl Kiesewetter unermüdlich für den Erhalt unserer heimischen Natur mit ihrer Tier- und Pflanzenwelt eingesetzt. Seit 1963 bis zu seinem Tode leitete er die Weißenfelser Fachgruppe Ornithologie und Naturschutz und leistete hier eine gründliche und systematische Erfassungsarbeit, vor allem zu Brutvögeln im Landkreis Weißenfels.
Bei der zusammenfassenden Analyse unterschiedlicher empirischer Qualifikations- und Forschungsprojekte mit ganz unterschiedlichen Fragestellungen und Erkenntnisinteressen (vgl. Nittel, Schütz, Tippelt 2014; Burkart, Meyer, Stemmer 2016; Meyer 2017; Nittel, Tippelt 2018) zeigt sich sehr deutlich immer wieder ein und dasselbe Phänomen: In den beruflichen Selbstbeschreibungen von pädagogisch Tätigen aus der Elementar- wie der Primarbildung, der Sekundarstufe I und II, der Sozialpädagogik, der Erwachsenenbildung und den Hochschulen nehmen die Begriffe Begleiten und Begleitung eine zentrale Stellung ein. ...
Sphingosine-1-phosphate (S1P) lyase irreversibly cleaves S1P, thereby catalysing the ultimate step of sphingolipid degradation. We show here that embryonic fibroblasts from S1P lyase-deficient mice (Sgpl1−/−-MEFs), in which S1P and sphingosine accumulate, have features of Niemann-Pick disease type C (NPC) cells. In the presence of serum, overall cholesterol content was elevated in Sgpl1−/−-MEFs, due to upregulation of the LDL receptor and enhanced cholesterol uptake. Despite this, activation of sterol regulatory element-binding protein-2 was increased in Sgpl1−/−-MEFs, indicating a local lack of cholesterol at the ER. Indeed, free cholesterol was retained in NPC1-containing vesicles, which is a hallmark of NPC. Furthermore, upregulation of amyloid precursor protein in Sgpl1−/−-MEFs was mimicked by an NPC1 inhibitor in Sgpl1+/+-MEFs and reduced by overexpression of NPC1. Lysosomal pH was not altered by S1P lyase deficiency, similar to NPC. Interestingly, lysosomal Ca2+ content and bafilomycin A1-induced [Ca2+]i increases were enhanced in Sgpl1−/−-MEFs, contrary to NPC. These results show that both a primary defect in cholesterol trafficking and S1P lyase deficiency cause overlapping phenotypic alterations, and challenge the present view on the role of sphingosine in lysosomal Ca2+ homeostasis.
Nep1 (Emg1) is a highly conserved nucleolar protein with an essential function in ribosome biogenesis. A mutation in the human Nep1 homolog causes Bowen–Conradi syndrome—a severe developmental disorder. Structures of Nep1 revealed a dimer with a fold similar to the SPOUT-class of RNA-methyltransferases suggesting that Nep1 acts as a methyltransferase in ribosome biogenesis. The target for this putative methyltransferase activity has not been identified yet. We characterized the RNA-binding specificity of Methanocaldococcus jannaschii Nep1 by fluorescence- and NMR-spectroscopy as well as by yeast three-hybrid screening. Nep1 binds with high affinity to short RNA oligonucleotides corresponding to nt 910–921 of M. jannaschii 16S rRNA through a highly conserved basic surface cleft along the dimer interface. Nep1 only methylates RNAs containing a pseudouridine at a position corresponding to a previously identified hypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine (m1acp3-Psi) in eukaryotic 18S rRNAs. Analysis of the methylated nucleoside by MALDI-mass spectrometry, HPLC and NMR shows that the methyl group is transferred to the N1 of the pseudouridine. Thus, Nep1 is the first identified example of an N1-specific pseudouridine methyltransferase. This enzymatic activity is also conserved in human Nep1 suggesting that Nep1 is the methyltransferase in the biosynthesis of m1acp3-Psi in eukaryotic 18S rRNAs.
Sphingosine 1 phosphate (S1P) lyase (Sgpl1) catalyses the irreversible cleavage of S1P and thereby the last step of sphingolipid degradation. Loss of Sgpl1 in humans and mice leads to accumulation of sphingolipids and multiple organ injuries. Here, we addressed the role of hepatocyte Sgpl1 for regulation of sphingolipid homoeostasis by generating mice with hepatocyte-specific deletion of Sgpl1 (Sgpl1HepKO mice). Sgpl1HepKO mice had normal body weight, liver weight, liver structure and liver enzymes both at the age of 8 weeks and 8 months. S1P, sphingosine and ceramides, but not glucosylceramides or sphingomyelin, were elevated by ~1.5–2-fold in liver, and this phenotype did not progress with age. Several ceramides were elevated in plasma, while plasma S1P was normal. Interestingly, S1P and glucosylceramides, but not ceramides, were elevated in bile of Sgpl1HepKO mice. Furthermore, liver cholesterol was elevated, while LDL cholesterol decreased in 8-month-old mice. In agreement, the LDL receptor was upregulated, suggesting enhanced uptake of LDL cholesterol. Expression of peroxisome proliferator-activated receptor-γ, liver X receptor and fatty acid synthase was unaltered. These data show that mouse hepatocytes largely compensate the loss of Sgpl1 by secretion of accumulating sphingolipids in a specific manner into blood and bile, so that they can be excreted or degraded elsewhere.
(NBu4)2[Co4(SPh)6Cl4] (1) and [Co4(SPh)6CU(PPh3)2] (2) are prepared by the reaction of (NBu4)[CoCl3(PPh3)] and [CoCl2(PPh3)2] with PhSSiMe3 in toluene solution. The overall description of the Co4S6Cl4 core is that o f a nearly regular Co4-tetrahedron inscribed in an irregular octahedron of the bridging S atoms resulting in an “adamantane” type cage. 1 reacts with Na[Mn(CO)5] to form the dinuclear complex (NBu4)[Mn2(SPh)3(CO)6] (4). Each Mn atom is bound to three CO and three μ2-SPh ligands. The Mn-Mn contact (318.5 pm) does not indicate metal-metal bonding.
