Alternative synthetic route for the heterometallic CO-releasing [Sb@Rh12(CO)27]3− icosahedral carbonyl cluster and synthesis of its new unsaturated [Sb@Rh12(CO)24]4− and dimeric [{Sb@Rh12Sb(CO)25}2Rh(CO)2PPh3]7− derivatives

The hetero-metallic [Sb@Rh12(CO)27]3? cluster has been known as for over three decades thanks to Vidal and co-workers, and represents the first example of an E-centered (E=heteroatom) icosahedral rhodium carbonyl cluster. However, its synthesis required high temperature (140–160 °C) and elevated CO pressure (400 atm). Applying the redox condensation method for cluster preparation, we herein report a new synthetic, high-yield route for preparing [Sb@Rh12(CO)27]3? under much milder conditions of temperature and pressure. Notably, when the same synthesis was carried out under N2 instead of CO atmosphere, the new isostructural but unsaturated derivative [Sb@Rh12(CO)24]4? was obtained, for which we report the full X-ray structural characterization. This species represents one of the few examples of an icosahedral cluster disobeying the electron-counting Wade-Mingos rules, possessing less than the expected 170 cluster valence electrons (CVEs). Judging from IR monitoring, the two species can be obtained one from the other by switching between N2 and CO atmosphere, making [Sb@Rh12(CO)27]3? a spontaneous CO-releasing molecule. Finally, the study of the chemical reactivity of [Sb@Rh12(CO)27]3? with PPh3 allowed us to obtain the new [{Sb@Rh12Sb(CO)25}2Rh(CO)2PPh3]7? dimeric compound, for which we herein report the full X-ray structural and 31P NMR analyses.     

Structure of the 30S translation initiation complex

Translation initiation, the rate-limiting step of the universal process of protein synthesis, proceeds through sequential, tightly regulated steps. In bacteria, the correct messenger RNA start site and the reading frame are selected when, with the help of initiation factors IF1, IF2 and IF3, the initiation codon is decoded in the peptidyl site of the 30S ribosomal subunit by the fMet-tRNA(fMet) anticodon. This yields a 30S initiation complex (30SIC) that is an intermediate in the formation of the 70S initiation complex (70SIC) that occurs on joining of the 50S ribosomal subunit to the 30SIC and release of the initiation factors. The localization of IF2 in the 30SIC has proved to be difficult so far using biochemical approaches, but could now be addressed using cryo-electron microscopy and advanced particle separation techniques on the basis of three-dimensional statistical analysis. Here we report the direct visualization of a 30SIC containing mRNA, fMet-tRNA(fMet) and initiation factors IF1 and GTP-bound IF2. We demonstrate that the fMet-tRNA(fMet) is held in a characteristic and precise position and conformation by two interactions that contribute to the formation of a stable complex: one involves the transfer RNA decoding stem which is buried in the 30S peptidyl site, and the other occurs between the carboxy-terminal domain of IF2 and the tRNA acceptor end. The structure provides insights into the mechanism of 70SIC assembly and rationalizes the rapid activation of GTP hydrolysis triggered on 30SIC-50S joining by showing that the GTP-binding domain of IF2 would directly face the GTPase-activated centre of the 50S subunit.     

Depression and antidepressants: molecular and cellular aspects

Clinical depression is viewed as a physical and psychic disease process having a neuropathological basis, although a clear understanding of its ethiopathology is still missing. The observation that depressive symptoms are influenced by pharmacological manipulation of monoamines led to the hypothesis that depression results from reduced availability or functional deficiency of monoaminergic transmitters in some cerebral regions. However, there are limitations to current monoamine theories related to mood disorders. Recently, a growing body of experimental data has showed that other classes of endogenous compounds, such as neuropeptides and amino acids, may play a significant role in the pathophysiology of affective disorders. With the development of neuroscience, neuronal networks and intracellular pathways have been identified and characterized, describing the existence of the interaction between monoamines and receptors in turn able to modulate the expression of intracellular proteins and neurotrophic factors, suggesting that depression/antidepressants may be intermingled with neurogenesis/neurodegenerative processes.     

RACK1 depletion in a mouse model causes lethality, pigmentation deficits and reduction in protein synthesis efficiency

The receptor for activated C-kinase 1 (RACK1) is a conserved structural protein of 40S ribosomes. Strikingly, deletion of RACK1 in yeast homolog Asc1 is not lethal. Mammalian RACK1 also interacts with many nonribosomal proteins, hinting at several extraribosomal functions. A knockout mouse for RACK1 has not previously been described. We produced the first RACK1 mutant mouse, in which both alleles of RACK1 gene are defective in RACK1 expression (ΔF/ΔF), in a pure C57 Black/6 background. In a sample of 287 pups, we observed no ΔF/ΔF mice (72 expected). Dissection and genotyping of embryos at various stages showed that lethality occurs at gastrulation. Heterozygotes (ΔF/+) have skin pigmentation defects with a white belly spot and hypopigmented tail and paws. ΔF/+ have a transient growth deficit (shown by measuring pup size at P11). The pigmentation deficit is partly reverted by p53 deletion, whereas the lethality is not. ΔF/+ livers have mild accumulation of inactive 80S ribosomal subunits by polysomal profile analysis. In ΔF/+ fibroblasts, protein synthesis response to extracellular and pharmacological stimuli is reduced. These results highlight the role of RACK1 as a ribosomal protein converging signaling to the translational apparatus.     

First dairying in green Saharan Africa in the fifth millennium BC

In the prehistoric green Sahara of Holocene North Africa-in contrast to the Neolithic of Europe and Eurasia-a reliance on cattle, sheep and goats emerged as a stable and widespread way of life, long before the first evidence for domesticated plants or settled village farming communities. The remarkable rock art found widely across the region depicts cattle herding among early Saharan pastoral groups, and includes rare scenes of milking; however, these images can rarely be reliably dated. Although the faunal evidence provides further confirmation of the importance of cattle and other domesticates, the scarcity of cattle bones makes it impossible to ascertain herd structures via kill-off patterns, thereby precluding interpretations of whether dairying was practiced. Because pottery production begins early in northern Africa the potential exists to investigate diet and subsistence practices using molecular and isotopic analyses of absorbed food residues. This approach has been successful in determining the chronology of dairying beginning in the 'Fertile Crescent' of the Near East and its spread across Europe. Here we report the first unequivocal chemical evidence, based on the δ(13)C and Δ(13)C values of the major alkanoic acids of milk fat, for the adoption of dairying practices by prehistoric Saharan African people in the fifth millennium bc. Interpretations are supported by a new database of modern ruminant animal fats collected from Africa. These findings confirm the importance of 'lifetime products', such as milk, in early Saharan pastoralism, and provide an evolutionary context for the emergence of lactase persistence in Africa.     

Sex hormones and concentration of noradrenalin and dopamine in the anterior hypothalamus of castrated rats

Zusammenfassung Die Autoren stellen fest, dass bei Ratten durch Kastration der Gehalt an Noradrenalin und Dopamin im vordern Teil des Hypothalamus ansteigt. Erst hohe Dosen von Östradiol und Progesteron können den Kastrationseffekt wieder zum Verschwinden bringen.

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A previous communication was presented at the XI Meeting of the Sociedad Argentina de Investigacion Clinica, Buenos Aires, 30th October — 2nd November, 1966.

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Fellow of the Consejo Nacional de Investigaciones Cientificas y Tecnicas de la Argentina.     

C-18 hydroxy steroids from the Mediterranean gorgonianLeptogorgia sarmentosa

Summary Five new polyoxygenated steroids, 24-methylcholesta-1,4,22E-trien-16, 18,20-triol-3-one (1), cholest-1,4,22E-trien-16, 18,20-triol-3-one (2), 24-methylcholesta-4,22E-dien-16, 18, 20-triol-3-one (3), cholesta-4,22E-dien-16, 18,20-triol-3-one (4) and 27-nor-24-methylcholesta-4,22E-dien-16,18,20-triol-3-one (5), have been found in a marine organism, the gorgonianLeptogorgia sarmentosa.This work has been done with the financial support of Progetto Finalizzato der la Chimica Fine e Secondaria, C.N.R., Roma. The authors are grateful to Zoological Station of Naples for collecting the gorgonian. Thanks are also due to Mr A. Crispino and Mr G. Scognamiglio for their technical assistance.     

Further sesterterpenes from the spongeSpongia nitens: 12-epi-scalaradial and 12,18-diepi-scalaradial

Summary 2 new tetracarbocyclic sesterterpenes, isomers of the previously² described scalaradial (1), have been isolated from the marine spongeSpongia nitens and their structures have been established to be2 and3; during the structural work, evidence on the stereochemistry of1,2 and3 has been obtained.This work is part of the Progetto Finalizzato per l'Oceanografia e i Fondi Marini, C.N.R., Roma. We thank the Zoological Station (Naples) for the collection of the sponge, A. Crispino, C. Di Pinto and A. Milone for their technical assistance and Prof. C. Santacroce for generous gifts of scalaradial.