A method for sequencing peptides: A co-operation of diphenyl phosphorazidate and 2-mercapto- or 2-hydroxypyridine for N-acyldiketopiperazine formation

Summary A new method for sequencing peptides is proposed. As a model experiment for this, Bz-Gly-Pro-OH and Bz-Gly-Sar-OH were conveniently converted to their diketopiperazine derivatives by a co-operation of diphenyl phosphorazidate and 2-mercapto- or 2-hydroxypyridine.     

Northern Hemisphere forcing of climatic cycles in Antarctica over the past 360,000 years

The Milankovitch theory of climate change proposes that glacial-interglacial cycles are driven by changes in summer insolation at high northern latitudes. The timing of climate change in the Southern Hemisphere at glacial-interglacial transitions (which are known as terminations) relative to variations in summer insolation in the Northern Hemisphere is an important test of this hypothesis. So far, it has only been possible to apply this test to the most recent termination, because the dating uncertainty associated with older terminations is too large to allow phase relationships to be determined. Here we present a new chronology of Antarctic climate change over the past 360,000 years that is based on the ratio of oxygen to nitrogen molecules in air trapped in the Dome Fuji and Vostok ice cores. This ratio is a proxy for local summer insolation, and thus allows the chronology to be constructed by orbital tuning without the need to assume a lag between a climate record and an orbital parameter. The accuracy of the chronology allows us to examine the phase relationships between climate records from the ice cores and changes in insolation. Our results indicate that orbital-scale Antarctic climate change lags Northern Hemisphere insolation by a few millennia, and that the increases in Antarctic temperature and atmospheric carbon dioxide concentration during the last four terminations occurred within the rising phase of Northern Hemisphere summer insolation. These results support the Milankovitch theory that Northern Hemisphere summer insolation triggered the last four deglaciations.     

CD38 is critical for social behaviour by regulating oxytocin secretion

CD38, a transmembrane glycoprotein with ADP-ribosyl cyclase activity, catalyses the formation of Ca2+ signalling molecules, but its role in the neuroendocrine system is unknown. Here we show that adult CD38 knockout (CD38-/-) female and male mice show marked defects in maternal nurturing and social behaviour, respectively, with higher locomotor activity. Consistently, the plasma level of oxytocin (OT), but not vasopressin, was strongly decreased in CD38-/- mice. Replacement of OT by subcutaneous injection or lentiviral-vector-mediated delivery of human CD38 in the hypothalamus rescued social memory and maternal care in CD38-/- mice. Depolarization-induced OT secretion and Ca2+ elevation in oxytocinergic neurohypophysial axon terminals were disrupted in CD38-/- mice; this was mimicked by CD38 metabolite antagonists in CD38+/+ mice. These results reveal that CD38 has a key role in neuropeptide release, thereby critically regulating maternal and social behaviours, and may be an element in neurodevelopmental disorders.     

Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets

Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host-range determinant as it mediates virus binding to host-specific cellular receptors. Here we assess the molecular changes in HA that would allow a virus possessing subtype H5 HA to be transmissible among mammals. We identified a reassortant H5 HA/H1N1 virus-comprising H5 HA (from an H5N1 virus) with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus-that was capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but was not highly pathogenic and did not cause mortality. These results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals; however, we do not know whether the four mutations in the H5 HA identified here would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral gene segments may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian-human reassortant viruses as tested here, may emerge. Our findings emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolates, which will inform the development, production and distribution of effective countermeasures.     

High secretory activity in the pancreatic B cells of a diabetic strain of the Japanese mouse

Zusammenfassung Elektronenmikroskopische Untersuchung von B-Zellen der Pankreas eines diabetischen Stammes japanischer Mäuse erbrachte den Hinweis gesteigerter Insulin-Synthese, bzw. gesteigerten Insulin-Ausflusses.     

Travel at low energetic cost by swimming and wave-riding bottlenose dolphins.

Over the past 50 years there has been much speculation about the energetic cost of swimming and wave-riding by dolphins. When aligned properly in front of the bow of moving ships in the stern wake of small boats, on wind waves, and even in the wake of larger cetaceans, the animals appear to move effortlessly through the water without the benefit of propulsive strokes by the flukes. Theoretically, body streamlining as well as other anatomical and behavioural adaptations contribute to low transport costs in these animals. The economy of movement permitted by wave-riding has been perceived as an energetic advantage for the swimming dolphin, but has been hard to prove in the absence of physiological data for exercising cetaceans. Here we determine the aerobic and anaerobic costs of swimming and wave-riding in bottlenose dolphins and find that the minimum cost of transport for swimming dolphins is 1.29 +/- 0.05 J kg-1 m-1 at a cruising speed of 2.1 m s-1. Aerobic costs are nearly twice as high for swimming seals and sea lions, and 8-12 times higher for human swimmers. Wave-riding by dolphins provides additional benefits in terms of speed. The results indicate that behavioural, physiological and morphological factors make swimming an economical form of high-speed travel for dolphins.