Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells

B cell responses are critical for antiviral immunity. However, a comprehensive picture of antigen-specific B cell differentiation, clonal proliferation, and dynamics in different organs after infection is lacking. Here, by combining single-cell RNA and B cell receptor (BCR) sequencing of antigen-specific cells in lymph nodes, spleen, and lungs after influenza infection in mice, we identify several germinal center (GC) B cell subpopulations and organ-specific differences that persist over the course of the response. We discover transcriptional differences between memory cells in lungs and lymphoid organs and organ-restricted clonal expansion. Remarkably, we find significant clonal overlap between GC-derived memory and plasma cells. By combining BCR-mutational analyses with monoclonal antibody (mAb) expression and affinity measurements, we find that memory B cells are highly diverse and can be selected from both low- and high-affinity precursors. By linking antigen recognition with transcriptional programming, clonal proliferation, and differentiation, these finding provide important advances in our understanding of antiviral immunity

9-(trans-2',trans-3'-Dihydroxycyclopent-4'-Enyl)-Adenine and -3-Deazaadenine: Analogs of Neplanocin A Which Retain Potent Antiviral Activity but Exhibit Reduced Cytotoxicity

Two synthetic analogs of neplanocin A, which were shown in a separate study to be inhibitors of S-adenosylhomocysteine hydrolase and devoid of substrate activity with adenosine kinase, were found in this study to inhibit vaccinia virus replication in murine L929 cells but to have reduced cytotoxicity compared with that of the parent compound. These results confirm that S-adenosylhomocysteine hydrolase is the molecular target which mediates the antiviral effects of neplanocin A and that transformation by cellular adenosine kinase mediates its cytotoxic properties.This work was supported by Public Health Service research grant GM-29332 from the National Institutes of Health

Summary of the Very Large Hadron Collider Physics and Detector Workshop

One of the options for an accelerator beyond the LHC is a hadron collider with higher energy. Work is going on to explore accelerator technologies that would make such a machine feasible. This workshop concentrated on the physics and detector issues associated with a hadron collider with an energy in the center of mass of the order of 100 to 200 TeV

Using modern software tools to design, simulate and test a Level 1 trigger sub-system for the D Zero Detector

This paper describes a system which uses a commercial spreadsheet program and commercial hardware on an IBM PC to develop and test a track finding system for the D Zero Level 1 scintillating Fiber Trigger. The trigger system resides in a VME crate. This system allows the user to generate test input, write the pattern to the hardware simulate the results in software, read the hardware result: compare the results and inform the user of any differences

Broad-Spectrum Antiviral Activities of Neplanocin A, 3-Deazaneplanocin A, and Their 5'-Nor Derivatives

The neplanocin A analogs, 3-deazaneplanocin A, 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)adenine (DHCA), and 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)-3-deazaadenine (DHCDA), all potent inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase, were studied for their broad-spectrum antiviral potential. 3-Deazaneplanocin A, DHCA, and DHCDA proved specifically effective against vesicular stomatitis virus, vaccinia virus, parainfluenza virus, reovirus, and rotavirus. Their selectivity was greater than that of neplanocin A, particularly against vesicular stomatitis virus and rotavirus. As could be expected from adenosine analogs that are directly targeted at AdoHcy hydrolase, 3-deazaneplanocin A, DHCA, and DHCDA were fully active in adenosine kinase-deficient cells, implying that their activity did not depend on phosphorylation by adenosine kinase. None of the AdoHcy hydrolase inhibitors showed selective activity against human immunodeficiency virus (type 1). 3-Deazaneplanocin A at a dose of 0.5 mg/kg per day conferred marked protection against a lethal infection of newborn mice with vesicular stomatitis virus.This work was supported by the Belgian Fonds voor Geneeskundig Wetenschappelijk Onderzoek (project no. 3.0040.83) and the Belgian Geconcerteerde Onderzoeksacties (project no. 85/90-79). We thank Anita Van Lierde, Frieda De Meyer, Ria Van Berwaer, Ann Absillis, Etsuko Nitanai, and Willy Zeegers for excellent technical assistance and Christiane Callebaut for fine editorial help

Determination of the Strange Quark Content of the Nucleon from a Next-to-Leading-Order QCD Analysis of Neutrino Charm Production

We present the first next-to-leading-order QCD analysis of neutrino charm production, using a sample of 6090 $\nu_\mu$- and $\bar\nu_\mu$-induced opposite-sign dimuon events observed in the CCFR detector at the Fermilab Tevatron. We find that the nucleon strange quark content is suppressed with respect to the non-strange sea quarks by a factor \kappa = 0.477 \: ^{+\:0.063}_{-\:0.053}, where the error includes statistical, systematic and QCD scale uncertainties. In contrast to previous leading order analyses, we find that the strange sea $x$-dependence is similar to that of the non-strange sea, and that the measured charm quark mass, $m_c = 1.70 \pm 0.19 \:{\rm GeV/c}^2$, is larger and consistent with that determined in other processes. Further analysis finds that the difference in $x$-distributions between $xs(x)$ and $x\bar s(x)$ is small. A measurement of the Cabibbo-Kobayashi-Maskawa matrix element $|V_{cd}|=0.232 ^{+\:0.018}_{-\:0.020}$ is also presented. uufile containing compressed postscript files of five Figures is appended at the end of the LaTeX source.Comment: Nevis R#150

A Precise Measurement of the Weak Mixing Angle in Neutrino-Nucleon Scattering

We report a precise measurement of the weak mixing angle from the ratio of neutral current to charged current inclusive cross-sections in deep-inelastic neutrino-nucleon scattering. The data were gathered at the CCFR neutrino detector in the Fermilab quadrupole-triplet neutrino beam, with neutrino energies up to 600 GeV. Using the on-shell definition, ${\rm sin ^2\theta_W} \equiv 1 - \frac{{\rm M_W} ^2}{{\rm M_Z} ^2}$, we obtain ${\rm sin ^2\theta_W} = 0.2218 \pm 0.0025 ({\rm stat.}) \pm 0.0036 ({\rm exp.\: syst.}) \pm 0.0040 ({\rm model})$.Comment: 10 pages, Nevis Preprint #1498 (Submitted to Phys. Rev. Lett.