CEP152 is a genome maintenance protein disrupted in Seckel syndrome

Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation.     

A coat subunit of Golgi-derived non-clathrin-coated vesicles with homology to the clathrin-coated vesicle coat protein beta-adaptin

Four high-molecular-weight proteins form the main subunits of the coat of Golgi-derived (non-clathrin) coated vesicles. One of these coat proteins, beta-COP, is identical to a Golgi-associated protein of relative mass 110,000 (110K) that shares homology with the adaptin proteins of clathrin-coated vesicles. This connection, and the comparable molecular weights of the coat proteins of Golgi-derived and clathrin-coated vesicles, indicates that they may be structurally related. The identification of beta-COP as the 110K protein explains the blocking of secretion by the drug brefeldin A.     

Conformation and toxicity of amanitins

Zusammenfassung Die Cottoneffekte der Amanitine konnten dem Indolteil bzw. den Amidgruppen des Molekühls zugeordnet werden. Das untoxische Amanullin besitzt die gleiche Konformation wie die toxischen Peptide, das untoxische Aldoamanitin dagegen eine andere. Die absolute Konfiguration der Sulfoxidgruppe der Amatoxine ist identisch mit der des toxischen Phalloidinsulfoxids.

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Part 43 of the series: Components of the green deathcap toadstoolAmanita phalloides. Part 42:F. Fahrenholz, H. Faulstich andTh. Wieland, Liebigs Annln Chem.743, 83 (1971).

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Acknowledgment. The authors wish to express their gratitude toDr. A. Buku for preparation of methyl--aldoamanitin.     

Umlagerung von Azulen in Naphthalin

Summary Azulene (I) is converted into Naphthalene (II) by heating for 48 hours to 330° C.

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74. Mitt. zur Kenntnis der Sesquiterpene.     

A study on the pharmacokinetics in mouse of adenine-9-beta-D-arabinofuranoside 5-monophosphate conjugated with lactosaminated albumin

In plasma of mice injected with adenine-9-beta-D-arabinofuranoside monophosphate (ara-AMP) coupled to human lactosaminated serum albumin (L-HSA) some of the ara-AMP molecules are enzymatically released, whereas others remain linked to L-HSA. Evidence has been obtained that ara-AMP is not deaminated when it is conjugated to L-HSA, in contrast to the free drug which is rapidly metabolized to its hypoxanthine derivative.     

Variation in FTO contributes to childhood obesity and severe adult obesity

We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses.     

Conjugates of adenine 9-α-D-arabinofuranoside monophosphate (ara-AMP) with lactosaminated homologous albumin are not immunogenic in the mouse

Summary Conjugates of adenine-9--D-arabinofuranoside (ara-A) or of ara-A monophosphate (ara-AMP) with asialofetuin or with heterologous lactosaminated serum albumin (L-SA) are strong antibody inducers. But ara-AMP conjugates prepared with homologous L-SA are not immunogenic, at least in mice.Acknowledgments. This work was supported by Consiglio Nazionale delle Ricerche, Progetto finalizzato, Controllo crescita neoplasica, grant 800154596. Ara-AMP was a gift from Dr M. L. Black, Warner-Lambert Co (Ann Arbor, MI). The excellent technical assistance of Mr Goffredo Nanetti is gratefully acknowledged.     

Ein neues Verfahren zur Herstellung von 19-Norsteroiden

Summary The new methods for the production of 19-norsteroids described involve the conversion of 5-halogen-6-hydroxy-steroids into the corresponding 5-halogen-6:19-ethers either with lead tetraacetate or by the hypoiodite reaction^8,10. The 6:19-oxygen bridge is then opened reductively either directly or after oxidation of the 6:19-ethers to lactones or preferably after introduction of a ^4,6-3-oxo grouping. Acylolytic cleavage of the ⁴-3-oxo-6:19-ethers followed by alkaline hydrolysis gives ^4,6-3-oxo-19-hydroxy-steroids. The 19-hydroxycompounds formed are easily converted into 19-norsteroids by known methods.

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Über Steroide, 189. (vorläufige) Mitteilung; 188. Mitt. vgl.J. Kalvoda, J. Schmidlin, G. Anner undA. Wettstein, Exper.18, 398 (1962).     

Legionella pneumophila down-regulates MHC class I expression of human monocytic host cells and thereby inhibits T cell activation

Legionella (L.) pneumophila, the causative agent of Legionnaires disease, is an intracellular pathogen of alveolar macrophages that resides in a compartment displaying features of endoplasmatic reticulum (ER). In this study, we show that intracellular multiplication of L. pneumophila results in a remarkable decrease in MHC class I expression by the infected monocytes. During intracellular multiplication, L. pneumophila absorbs ER-resident chaperons such as calnexin and BiP, molecules that are required for the correct formation of the MHC class I complex. Due to reduced MHC class I expression, stimulation of allogeneic blood mononuclear cells was severely inhibited by infected host cells but cytotoxicity of autologous natural killer cells against Legionella-infected monocytes was not enhanced. Thus, reduced expression of MHC class I in infected monocytes may resemble a new immune escape mechanism induced by L. pneumophila.Received 22 November 2004; received after revision 27 December 2004; accepted 5 January 2005