Optical frequency metrology

Extremely narrow optical resonances in cold atoms or single trapped ions can be measured with high resolution. A laser locked to such a narrow optical resonance could serve as a highly stable oscillator for an all-optical atomic clock. However, until recently there was no reliable clockwork mechanism that could count optical frequencies of hundreds of terahertz. Techniques using femtosecond-laser frequency combs, developed within the past few years, have solved this problem. The ability to count optical oscillations of more than 1015 cycles per second facilitates high-precision optical spectroscopy, and has led to the construction of an all-optical atomic clock that is expected eventually to outperform today's state-of-the-art caesium clocks.     

No supernovae associated with two long-duration gamma-ray bursts

It is now accepted that long-duration gamma-ray bursts (GRBs) are produced during the collapse of a massive star. The standard 'collapsar' model predicts that a broad-lined and luminous type Ic core-collapse supernova accompanies every long-duration GRB. This association has been confirmed in observations of several nearby GRBs. Here we report that GRB 060505 (ref. 10) and GRB 060614 (ref. 11) were not accompanied by supernova emission down to limits hundreds of times fainter than the archetypal supernova SN 1998bw that accompanied GRB 980425, and fainter than any type Ic supernova ever observed. Multi-band observations of the early afterglows, as well as spectroscopy of the host galaxies, exclude the possibility of significant dust obscuration and show that the bursts originated in actively star-forming regions. The absence of a supernova to such deep limits is qualitatively different from all previous nearby long-duration GRBs and suggests a new phenomenological type of massive stellar death.     

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.     

Functional mechanisms of the cellular prion protein (PrPC) associated anti-HIV-1 properties

The cellular prion protein PrP(C)/CD230 is a GPI-anchor protein highly expressed in cells from the nervous and immune systems and well conserved among vertebrates. In the last decade, several studies suggested that PrP(C) displays antiviral properties by restricting the replication of different viruses, and in particular retroviruses such as murine leukemia virus (MuLV) and the human immunodeficiency virus type 1 (HIV-1). In this context, we previously showed that PrP(C) displays important similarities with the HIV-1 nucleocapsid protein and found that PrP(C) expression in a human cell line strongly reduced HIV-1 expression and virus production. Using different PrP(C) mutants, we report here that the anti-HIV-1 properties are mostly associated with the amino-terminal 24-KRPKP-28 basic domain. In agreement with its reported RNA chaperone activity, we found that PrP(C) binds to the viral genomic RNA of HIV-1 and negatively affects its translation. Using a combination of biochemical and cell imaging strategies, we found that PrP(C) colocalizes with the virus assembly machinery at the plasma membrane and at the virological synapse in infected T cells. Depletion of PrP(C) in infected T cells and microglial cells favors HIV-1 replication, confirming its negative impact on the HIV-1 life cycle.     

A rare variant in MYH6 is associated with high risk of sick sinus syndrome

Through complementary application of SNP genotyping, whole-genome sequencing and imputation in 38,384 Icelanders, we have discovered a previously unidentified sick sinus syndrome susceptibility gene, MYH6, encoding the alpha heavy chain subunit of cardiac myosin. A missense variant in this gene, c.2161C>T, results in the conceptual amino acid substitution p.Arg721Trp, has an allelic frequency of 0.38% in Icelanders and associates with sick sinus syndrome with an odds ratio = 12.53 and P = 1.5 × 10?2?. We show that the lifetime risk of being diagnosed with sick sinus syndrome is around 6% for non-carriers of c.2161C>T but is approximately 50% for carriers of the c.2161C>T variant.     

In vitro inactivation of gonadotropin receptors,a membrane-associated action?

Summary Under in vitro conditions the time-dependent inactivation process of LH/HCG receptors is nearly identical in ovarian and testicular homogenates but different in gonadal membrane preparations. In the ovarian membranes the loss of binding sites during the first preincubation time is faster than in testicular membranes, especially in membranes of luteinized rat ovaries. Compared with the homogenates, however, the receptor-inactivation in the membranes is generally delayed. The inhibitory effect of metabolic agents on receptor inactivation indicates that membrane-associated actions are involved in this process.This work was supported in part by the Deutsche Forschungsgemeinschaft (Si 185/2). We thank Mrs Rita Rudolph for skilful technical assistance.     

The structure of gephyrotoxin (GTX) 223AB

Summary The structure 3-butyl-5-propylindolizidine (2), tentatively assigned to a minor alkaloid in skin extracts from a number of poison frogs of the Neotropical genusDendrobates, has been confirmed and its stereochemistry determined as 5E, 9E (2d) by comparison on GC and GC-MS with the four synthetic diastereomers2a-2d.     

A new view on an old drug: Pilocarpine

Zusammenfassung Pilocarpin ist ein geeignetes Beispiel einer parasympathischen Substanz mit dualistischer Wirkung. Auf Grund der Variationen in der Eigenaktivität (intrinsic activity) des Pilocarpins an verschiedenen Organen und Arten tritt entweder die parasympathomimetische oder die parasympatholytische Wirkung in den Vordergrund.     

Uranvererzungen in Gesteinen des Bernhardkristallins (Kt. Wallis,Schweiz)

Résumé Des roches radioactives ont été découvertes dans les galeries de la Grande Dixence S.A. (voir loc.A etB de la Fig. 1). Les analyses aux rayons X, les analyses chimiques et chalcographiques ont montré la présence de l'uranium sous forme de pechblende. La minéralisation se manifeste, dans les micaschistes gréseux et chloriteux, par des niveaux noirâtres. La pechblende est associée à la pyrite, la chalcopyrite, la galène, la covelline et l'hématite (loc.A). A Sarreyer (loc. B) la minéralisation n'est pas apparente. La roche radioactive est un quartzite sériciteux carbonaté, contenant de l'uranium.     

Die nomographische Bestimmung des logarithmischen Durchschnittes von Versuchsdaten und die graphische Ermittlung von Regressionswerten

Summary A nomogram has been constructed for the estimation of the logarithmic mean of four measurements. This nomogram makes it possible to transform the empirical data without tables and without computing.