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.     

Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences

We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.     

Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression

Reactive oxygen species are involved in many cellular metabolic and signalling processes and are thought to have a role in disease, particularly in carcinogenesis and ageing. We have generated mice with targeted inactivation of Prdx1, a member of the peroxiredoxin family of antioxidant enzymes. Here we show that mice lacking Prdx1 are viable and fertile but have a shortened lifespan owing to the development beginning at about 9 months of severe haemolytic anaemia and several malignant cancers, both of which are also observed at increased frequency in heterozygotes. The haemolytic anaemia is characterized by an increase in erythrocyte reactive oxygen species, leading to protein oxidation, haemoglobin instability, Heinz body formation and decreased erythrocyte lifespan. The malignancies include lymphomas, sarcomas and carcinomas, and are frequently associated with loss of Prdx1 expression in heterozygotes, which suggests that this protein functions as a tumour suppressor. Prdx1-deficient fibroblasts show decreased proliferation and increased sensitivity to oxidative DNA damage, whereas Prdx1-null mice have abnormalities in numbers, phenotype and function of natural killer cells. Our results implicate Prdx1 as an important defence against oxidants in ageing mice.     

Relationship between the microstructure and properties of thermomechanically processed Fe-17Mn and Fe-17Mn-3Al steels

Two austenitic Mn steels(Fe-17 Mn and Fe-17 Mn-3 Al(wt%, so as the follows)) were subjected to thermomechanical processing(TMP) consisting of forging followed by solutionization and hot rolling. The rolled samples were annealed at 650 and 800°C to relieve the internal stress and to induce recrystallization. The application of TMP and heat treatment to the Fe-17 Mn/Fe-17 Mn-3 Al steels refined the austenite grain size from 169 μm in the as-solutionized state to 9–13 μm, resulting in a substantial increase in hardness from HV 213 to HV 410 for the Fe-17 Mn steel and from HV 210 to HV 387 for the Fe-17 Mn-3 Al steel. The elastic modulus values, as evaluated by the nanoindentation technique, increased from(175 ± 11) to(220 ± 12) GPa and from(163 ± 15) to(205 ± 13) GPa for the Fe-17 Mn and Fe-17 Mn-3 Al steels, respectively. The impact energy of the thermomechanically processed austenitic Mn steels was lower than that of the steels in their as-solutionized state. The addition of Al to the Fe-17 Mn steel decreased the hardness and elastic modulus but increased the impact energy.     

Isocardenolides

Zusammenfassung Ein einfacher Weg zur Synthese eines von zwei möglichen isomeren Cardenoliden wurde entwickelt und die Reaktionsfolge an Hand der Überführung von Pregnenolon in Isocardenolide V gezeigt.

---

---

Steroids and Related Natural Products XXI. For the previous contribution refer to:G. R. Pettit andP. Hofer, Helv. chim. Acta46, 2142 (1963).

---

A preliminary account of this study was presented (December 1963) at the VI. Pan-American Congress of Pharmacy and Biochemistry, Mexico City (Mexico).

---

This investigation was supported by PHS Research Grants CY-4074 (C3) to CA-04074-06 from the National Cancer Institute, Public Health Service.     

Ion-solvent interaction from viscosity,apparent molar volume and conductivity data of bromates,iodates and sulphates of potassium and sodium in dioxane-water mixtures at different temperatures

Summary The viscosity, apparent molar volume and conductivity of KBrO₃, NaBrO₃, KIO₃, NaIO₃, K₂SO₄ and Na₂SO₄ at mass fraction of dioxane (10, 20 and 30%) — water mixtures at 30–45°C±0.01°C have been measured. The ions appear to interact and the ion-solvent interaction is of the order BrO ₃ ^– >IO ₃ ^– >SO ₄ ^2– .     

Constituants amers deBrucea amarissima structures des brucéines A,B et C

Summary Evidence is presented for the structures (II a), (II b) and (II c) for the bruceines A, B and C, the bitter principles isolated from the seeds ofBrucea amarissima.

---

---

18ème Communication sur les constituants amers des Simarubacées; 17ème Communication, voir².