Synthetic peptides related to eledoisin. Physalaemin-like peptides

Riassunto Vengono riportate le proprietà di una serie di peptidi sintetici affini per struttura alla fisalemina.     

Rauwolfia alkaloids XXXV. potent,fast-acting sedatives derived from methyl reserpate

Zusammenfassung Durch Umsetzung des Methyl-Reserpates (Ic) mit Diazomethan in Gegenwart von Fluoborsäure wird 18-O-Methylreserpsäure-methylester (Id) gewonnen. Reaktion des 18-O-p-Brombenzolsulfonylreserpsäure-methylesters (Ie) mit Methanol und Triäthylamin führt dagegen zum isomeren 18-epi-Methyläther (IIa). Diese Produkte, und besonders ihre wasserlöslichen Hydrochloride, besitzen ausgeprägte sedative Eigenschaften mit schnellem Wirkungseintritt; sie sind aber nicht hypotensiv wirksam.     

Amino acids from ultraviolet irradiation of interstellar ice analogues

Amino acids are the essential molecular components of living organisms on Earth, but the proposed mechanisms for their spontaneous generation have been unable to account for their presence in Earth's early history. The delivery of extraterrestrial organic compounds has been proposed as an alternative to generation on Earth, and some amino acids have been found in several meteorites. Here we report the detection of amino acids in the room-temperature residue of an interstellar ice analogue that was ultraviolet-irradiated in a high vacuum at 12 K. We identified 16 amino acids; the chiral ones showed enantiomeric separation. Some of the identified amino acids are also found in meteorites. Our results demonstrate that the spontaneous generation of amino acids in the interstellar medium is possible, supporting the suggestion that prebiotic molecules could have been delivered to the early Earth by cometary dust, meteorites or interplanetary dust particles.     

The gene encoding proline dehydrogenase modulates sensorimotor gating in mice

Hemizygous cryptic deletions of the q11 band of human chromosome 22 have been associated with a number of psychiatric and behavioural phenotypes, including schizophrenia. Here we report the isolation and characterization of PRODH, a human homologue of Drosophila melanogaster sluggish-A (slgA), which encodes proline dehydrogenase responsible for the behavioural phenotype of the slgA mutant. PRODH is localized at chromosome 22q11 in a region deleted in some psychiatric patients. We also isolated the mouse homologue of slgA (Prodh), identified a mutation in this gene in the Pro/Re hyperprolinaemic mouse strain and found that these mice have a deficit in sensorimotor gating accompanied by regional neurochemical alterations in the brain. Sensorimotor gating is a neural filtering process that allows attention to be focused on a given stimulus, and is affected in patients with neuropsychiatric disorders. Furthermore, several lines of evidence suggest that proline may serve as a modulator of synaptic transmission in the mammalian brain. Our observations, in conjunction with the chromosomal location of PRODH, suggest a potential involvement of this gene in the 22q11-associated psychiatric and behavioural phenotypes.     

Occurrence of a physalaemin-like polypeptide (Uperolein) and other active polypeptides in the skin ofUperoleia rugosa

Riassunto Gli estratti metanolici della pelle diUperoleia rugosa, piccolo anfibio australiano, contengono, oltre ad eventuali costituenti attivi minori, due polipeptidi altamente attivi. Il primo è caratterizzato da una intensa azione stimolante sul colon e sull'utero di ratto; il secondo, per il quale viene proposto il nome diuperoleina, è dotato di potente azione ipotensiva nel cane e nel coniglio, di potente azione stimolante sul colon di coniglio e di potente azione scialagoga nel ratto. L'uperoleina è strettamente vicina da un punto di vista biologico, e presumibilmente anche chimico, alla eledoisina e alla fisalemina.     

Metabolic effects of neopyrithiamine and the aneurin contents in the tissues of the rat

Riassunto Ratti trattati con neopiritiamina presentano un contenuto particolarmente basso di aneurina nel tessuto nervoso (cervello) e non rispondono alla somministrazione di glucoso (per os) con aumento di Q.R. e di produzione calorica come, invece, fanno i controlli e i ratti carenzati mediante la dieta (3–4 settimane).     

Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice

In the mammalian retina, besides the conventional rod-cone system, a melanopsin-associated photoreceptive system exists that conveys photic information for accessory visual functions such as pupillary light reflex and circadian photo-entrainment. On ablation of the melanopsin gene, retinal ganglion cells that normally express melanopsin are no longer intrinsically photosensitive. Furthermore, pupil reflex, light-induced phase delays of the circadian clock and period lengthening of the circadian rhythm in constant light are all partially impaired. Here, we investigated whether additional photoreceptive systems participate in these responses. Using mice lacking rods and cones, we measured the action spectrum for phase-shifting the circadian rhythm of locomotor behaviour. This spectrum matches that for the pupillary light reflex in mice of the same genotype, and that for the intrinsic photosensitivity of the melanopsin-expressing retinal ganglion cells. We have also generated mice lacking melanopsin coupled with disabled rod and cone phototransduction mechanisms. These animals have an intact retina but fail to show any significant pupil reflex, to entrain to light/dark cycles, and to show any masking response to light. Thus, the rod-cone and melanopsin systems together seem to provide all of the photic input for these accessory visual functions.     

Non-destructive determination of local strain with 100-nanometre spatial resolution

Structure sizes of approximately 180 nm are now standard in microelectronics, and state-of-the-art fabrication techniques can reduce these to just a few tens of nanometres. But at these length scales, the strain induced at interfaces can locally distort the crystal lattice, which may in turn affect device performance in an unpredictable way. A means of non-destructively characterizing such strain fields with high spatial resolution and sensitivity is therefore highly desirable. One approach is to use Raman spectroscopy, but this is limited by the intrinsic approximately 0.5-microm resolution limit of visible light probes. Techniques based on electron-beam diffraction can achieve the desired nanometre-scale resolution. But either they require complex sample preparation procedures (which may alter the original strain field) or they are sensitive to distortional (but not dilational) strain within only the top few tens of nanometres of the sample surface. X-rays, on the other hand, have a much greater penetration depth, but have not hitherto achieved strain analysis with sub-micrometre resolution. Here we describe a magnifying diffraction imaging procedure for X-rays which achieves a spatial resolution of 100nm in one dimension and a sensitivity of 10(-4) for relative lattice variations. We demonstrate the suitability of this procedure for strain analysis by measuring the strain depth profiles beneath oxidized lines on silicon crystals.     

A 15.65-solar-mass black hole in an eclipsing binary in the nearby spiral galaxy M 33

Stellar-mass black holes are found in X-ray-emitting binary systems, where their mass can be determined from the dynamics of their companion stars. Models of stellar evolution have difficulty producing black holes in close binaries with masses more than ten times that of the Sun (>10; ref. 4), which is consistent with the fact that the most massive stellar black holes known so far all have masses within one standard deviation of 10. Here we report a mass of (15.65 +/- 1.45) for the black hole in the recently discovered system M 33 X-7, which is located in the nearby galaxy Messier 33 (M 33) and is the only known black hole that is in an eclipsing binary. To produce such a massive black hole, the progenitor star must have retained much of its outer envelope until after helium fusion in the core was completed. On the other hand, in order for the black hole to be in its present 3.45-day orbit about its (70.0 +/- 6.9) companion, there must have been a 'common envelope' phase of evolution in which a significant amount of mass was lost from the system. We find that the common envelope phase could not have occurred in M 33 X-7 unless the amount of mass lost from the progenitor during its evolution was an order of magnitude less than what is usually assumed in evolutionary models of massive stars.     

Genome-wide analysis of human kinases in clathrin- and caveolae/raft-mediated endocytosis

Endocytosis is a key cellular process, encompassing different entry routes and endocytic compartments. To what extent endocytosis is subjected to high-order regulation by the cellular signalling machinery remains unclear. Using high-throughput RNA interference and automated image analysis, we explored the function of human kinases in two principal types of endocytosis: clathrin- and caveolae/raft-mediated endocytosis. We monitored this through infection of vesicular stomatitis virus, simian virus 40 and transferrin trafficking, and also through cell proliferation and apoptosis assays. Here we show that a high number of kinases are involved in endocytosis, and that each endocytic route is regulated by a specific kinase subset. Notably, one group of kinases exerted opposite effects on the two endocytic routes, suggesting coordinate regulation. Our analysis demonstrates that signalling functions such as those controlling cell adhesion, growth and proliferation, are built into the machinery of endocytosis to a much higher degree than previously recognized.