Effect of cyproheptadine on the octopamine-induced responses in the mammalian central nervous system

Summary Extracellular recordings have been made from rat thalamic neurones anaesthetized with urethane, 1.5–2 g/kg i.p. Iontophoretically applied octopamine excited certain thalamic neurones in the ventral basal complex while inhibiting others. Both effects were reversibly antagonized by iontophoretically applied cyproheptadine without affecting responses to noradrenaline and dopamine.Acknowledgment. We are grateful to Merck, Sharp and Dohme for a gift of cyproheptadine HCl.     

De novo mutations revealed by whole-exome sequencing are strongly associated with autism

Multiple studies have confirmed the contribution of rare de novo copy number variations to the risk for autism spectrum disorders. But whereas de novo single nucleotide variants have been identified in affected individuals, their contribution to risk has yet to be clarified. Specifically, the frequency and distribution of these mutations have not been well characterized in matched unaffected controls, and such data are vital to the interpretation of de novo coding mutations observed in probands. Here we show, using whole-exome sequencing of 928 individuals, including 200 phenotypically discordant sibling pairs, that highly disruptive (nonsense and splice-site) de novo mutations in brain-expressed genes are associated with autism spectrum disorders and carry large effects. On the basis of mutation rates in unaffected individuals, we demonstrate that multiple independent de novo single nucleotide variants in the same gene among unrelated probands reliably identifies risk alleles, providing a clear path forward for gene discovery. Among a total of 279 identified de novo coding mutations, there is a single instance in probands, and none in siblings, in which two independent nonsense variants disrupt the same gene, SCN2A (sodium channel, voltage-gated, type II, α subunit), a result that is highly unlikely by chance.     

The age of the Milky Way inner halo

The Milky Way galaxy has several components, such as the bulge, disk and halo. Unravelling the assembly history of these stellar populations is often restricted because of difficulties in measuring accurate ages for low-mass, hydrogen-burning stars. Unlike these progenitors, white dwarf stars, the 'cinders' of stellar evolution, are remarkably simple objects and their fundamental properties can be measured with little ambiguity. Here I report observations of newly formed white dwarf stars in the halo of the Milky Way, and a separate analysis of archival data in the well studied 12.5-billion-year-old globular cluster Messier 4. I measure the mass distribution of the remnant stars and invert the stellar evolution process to develop a mathematical relation that links this final stellar mass to the mass of their immediate progenitors, and therefore to the age of the parent population. By applying this technique to a small sample of four nearby and kinematically confirmed halo white dwarf stars, I calculate the age of local field halo stars to be 11.4?±?0.7 billion years. The oldest globular clusters formed 13.5?billion years ago. Future observations of newly formed white dwarf stars in the halo could be used to reduce the uncertainty, and to probe relative differences between the formation times of the youngest globular clusters and the inner halo.     

Lamprey-like gills in a gnathostome-related Devonian jawless vertebrate

So far, the Palaeozoic fossil jawless vertebrates have not provided any direct evidence for the organization of the gills, apart from vague impressions--supposedly left by gill filaments--on the bony surface of the gill chamber in certain armoured forms or 'ostracoderms' (for example, osteostracans and heterostracans). The latter are currently regarded as more closely related to the living jawed vertebrates (crown gnathostomes) than to the living jawless vertebrates (hagfish and lampreys, or cyclostomes). Here we report the first direct evidence for the position of the gill filaments--possibly supported by gill rays--enclosed by gill pouches in a 370-million year (Myr)-old jawless vertebrate, Endeiolepis, from the Late Devonian fossil fish site of Miguasha, Quebec, Canada. This extinct jawless fish has much the same gill organization as living lampreys, although it possesses an unusually large number of gill pouches--a condition unlike that in any extant vertebrates and that raises questions about gill development. Endeiolepis is currently regarded as a close relative of anaspids, a group of 410-430-Myr-old 'ostracoderms'. Assuming that current vertebrate phylogeny is correct, this discovery demonstrates that pouches enclosing the gills are primitive for vertebrates, but have been subsequently lost in jawed vertebrates.     

A low density of 0.8 g cm(-3) for the Trojan binary asteroid 617 Patroclus

The Trojan population consists of two swarms of asteroids following the same orbit as Jupiter and located at the L4 and L5 stable Lagrange points of the Jupiter-Sun system (leading and following Jupiter by 60 degrees ). The asteroid 617 Patroclus is the only known binary Trojan. The orbit of this double system was hitherto unknown. Here we report that the components, separated by 680 km, move around the system's centre of mass, describing a roughly circular orbit. Using this orbital information, combined with thermal measurements to estimate the size of the components, we derive a very low density of 0.8(- 0.1)+0.2 g cm(-3). The components of 617 Patroclus are therefore very porous or composed mostly of water ice, suggesting that they could have been formed in the outer part of the Solar System.