Development of portable NMR polarimeter system for polarized HD target

A portable NMR polarimeter system has been developed to measure the polarization of a polarized Hydrogen-Deuteride (HD) target for hadron photoproduction experiments at SPring-8. The polarized HD target is produced at the Research Center for Nuclear Physics (RCNP), Osaka university and is transported to SPring-8. The HD polarization should be monitored at both places. We have constructed the portable NMR polarimeter system by replacing the devices in the conventional system with the software system with PCI eXtensions for Instrumentation (PXI). The weight of the NMR system is downsized from 80 kg to 7 kg, and the cost is reduced to 25%. We check the performance of the portable NMR polarimeter system. The signal-to-noise (S/N) ratio of the NMR signal for the portable system is about 50% of that for the conventional NMR system. This performance of the portable NMR system is proved to be compatible with the conventional NMR system for the polarization measurement.Comment: 6 page, 8 figures, 2011/Mar/9 Replace Author

Distillation of hydrogen isotopes for polarized HD target

We have developed a cryogenic distillation system to purify Hydrogen-Deuteride (HD) gas for a polarized HD target in LEPS experiments at SPring-8. A small amount of ortho-H$_2$ ($\sim$0.01%) in the HD gas plays an important role in efficiently polarizing the HD target. Since there are 1$\sim$5% impurities of H$_2$ and D$_2$ in commercially available HD gases, it is inevitable that the HD gas is purified up to $\sim$99.99%. The distillation system has a cryogenic pot (17$\sim$21 K) containing many small stainless steel cells called Heli-pack. Commercial HD gas with an amount of 5.2 mol is fed into the pot. We carried out three distillation runs by changing temperatures (17.5 K and 20.5 K) and gas extraction speeds (1.3 ml/min and 5.2 ml/min). The extracted gas was analyzed by using a gas analyzer system combining a quadrupole mass spectrometer with a gas chromatograph. The HD gas of 1 mol with a purity better than 99.99% has been successfully obtained. The effective NTS (Number of Theoretical Stages), which is an indicator of the distillator performances, is obtained as 37.2$\pm$0.6. This value is in reasonable agreement with a designed value of 37.9. The HD target is expected to be efficiently polarized under a well-controlled condition by doping an optimal amount of ortho-H$_2$ to the purified HD gas.Comment: 7 pages, 8 figures, 2 tables, updated 2011-12-1

DOC2B: A Novel Syntaxin-4 Binding Protein Mediating Insulin-Regulated GLUT4 Vesicle Fusion in Adipocytes

OBJECTIVE— Insulin stimulates glucose uptake in skeletal muscle and adipose tissues primarily by stimulating the translocation of vesicles containing a facilitative glucose transporter, GLUT4, from intracellular compartments to the plasma membrane. The formation of stable soluble N-ethyl-maleimide–sensitive fusion protein [NSF] attachment protein receptor (SNARE) complexes between vesicle-associated membrane protein-2 (VAMP-2) and syntaxin-4 initiates GLUT4 vesicle docking and fusion processes. Additional factors such as munc18c and tomosyn were reported to be negative regulators of the SNARE complex assembly involved in GLUT4 vesicle fusion. However, despite numerous investigations, the positive regulators have not been adequately clarified

Accumulation of human-adapting mutations during circulation of A(H1N1)pdm09 influenza virus in humans in the United Kingdom

The influenza pandemic that emerged in 2009 provided an unprecedented opportunity to study adaptation of a virus recently acquired from an animal source during human transmission. In the United Kingdom, the novel virus spread in three temporally distinct waves between 2009 and 2011. Phylogenetic analysis of complete viral genomes showed that mutations accumulated over time. Second- and third-wave viruses replicated more rapidly in human airway epithelial (HAE) cells than did the first-wave virus. In infected mice, weight loss varied between viral isolates from the same wave but showed no distinct pattern with wave and did not correlate with viral load in the mouse lungs or severity of disease in the human donor. However, second- and third-wave viruses induced less alpha interferon in the infected mouse lungs. NS1 protein, an interferon antagonist, had accumulated several mutations in second- and third-wave viruses. Recombinant viruses with the third-wave NS gene induced less interferon in human cells, but this alone did not account for increased virus fitness in HAE cells. Mutations in HA and NA genes in third-wave viruses caused increased binding to alpha-2,6-sialic acid and enhanced infectivity in human mucus. A recombinant virus with these two segments replicated more efficiently in HAE cells. A mutation in PA (N321K) enhanced polymerase activity of third-wave viruses and also provided a replicative advantage in HAE cells. Therefore, multiple mutations allowed incremental changes in viral fitness, which together may have contributed to the apparent increase in severity of A(H1N1)pdm09 influenza virus during successive waves. IMPORTANCE: Although most people infected with the 2009 pandemic influenza virus had mild or unapparent symptoms, some suffered severe and devastating disease. The reasons for this variability were unknown, but the numbers of severe cases increased during successive waves of human infection in the United Kingdom. To determine the causes of this variation, we studied genetic changes in virus isolates from individual hospitalized patients. There were no consistent differences between these viruses and those circulating in the community, but we found multiple evolutionary changes that in combination over time increased the virus's ability to infect human cells. These adaptations may explain the remarkable ability of A(H1N1)pdm09 virus to continue to circulate despite widespread immunity and the apparent increase in severity of influenza over successive waves of infection

Airway surveillance and lung viral control by memory T cells induced by COVID-19 mRNA vaccine

Although SARS-CoV-2 evolution seeds a continuous stream of antibody-evasive viral variants, COVID-19 mRNA vaccines provide robust protection against severe disease and hospitalization. Here, we asked whether mRNA vaccine-induced memory T cells limits lung SARS-CoV-2 replication and severe disease. We show that mice and humans receiving booster BioNTech mRNA vaccine developed potent CD8 T-cell responses and show similar kinetics of expansion and contraction of granzyme B/perforin-expressing effector CD8 T cells. Both monovalent and bivalent mRNA vaccines elicited strong expansion of a heterogeneous pool of terminal effectors and memory precursor effector CD8 T cells in spleen, inguinal and mediastinal lymph nodes, pulmonary vasculature, and most surprisingly in the airways, suggestive of systemic and regional surveillance. Further, we document that: (1) CD8 T-cell memory persists in multiple tissues for >200 days; (2) following challenge with pathogenic SARS-CoV-2, circulating memory CD8 T cells rapidly extravasate to the lungs and promote expeditious viral clearance, by mechanisms that require CD4 T cell help; (3) adoptively transferred splenic memory CD8 T cells traffic to the airways, and promote lung SARS-CoV-2 clearance. These findings provide new insights into the critical role of memory T cells in preventing severe lung disease following breakthrough infections with antibody-evasive SARS-CoV-2 variants

Penetration of infectious prion protein in the intestine during the lactation period.

Prion diseases are fatal neurodegenerative zoonotic foodborne disorders, which are caused by an abnormal isoform of prion protein (PrPSc) derived from the cellular isoform of prion protein (PrPC). According to epidemiological surveillance and in vivo experiments, exposure to the PrPSc during the weaning period is fraught with risk, suggesting that, during development, the intestinal defenses and the immune system are involved in PrPSc infection susceptibility. Although it remains unclear how PrPSc passes through the natural biological barriers during its invasion of intestinal cells, the 37 kDa/67 kDa laminin receptor is suspected to be one of the receptors involved in PrPSc-incorporation. In addition, we have recently shown that the neonatal Fc receptor (nFcR), which contributes to the uptake of maternal antibodies into the intestine, may play an important role in PrPSc incorporation. In this review, recent studies on PrPSc uptake and models of PrPSc incorporation into the intestine via the laminin and Fc receptors are described