Hubble Space Telescope Imaging of Lyman Alpha Emission at z=4.4

We present the highest redshift detections of resolved Lyman alpha emission, using Hubble Space Telescope/ACS F658N narrowband-imaging data taken in parallel with the Wide Field Camera 3 Early Release Science program in the GOODS CDF-S. We detect Lyman alpha emission from three spectroscopically confirmed z = 4.4 Lyman alpha emitting galaxies (LAEs), more than doubling the sample of LAEs with resolved Lyman alpha emission. Comparing the light distribution between the rest-frame ultraviolet continuum and narrowband images, we investigate the escape of Lyman alpha photons at high redshift. While our data do not support a positional offset between the Lyman alpha and rest-frame ultraviolet (UV) continuum emission, the half-light radii in two out of the three galaxies are significantly larger in Lyman alpha than in the rest-frame UV continuum. This result is confirmed when comparing object sizes in a stack of all objects in both bands. Additionally, the narrowband flux detected with HST is significantly less than observed in similar filters from the ground. These results together imply that the Lyman alpha emission is not strictly confined to its indigenous star-forming regions. Rather, the Lyman alpha emission is more extended, with the missing HST flux likely existing in a diffuse outer halo. This suggests that the radiative transfer of Lyman alpha photons in high-redshift LAEs is complicated, with the interstellar-medium geometry and/or outflows playing a significant role in galaxies at these redshifts.Comment: Submitted to the Astrophysical Journal. 11 pages, 10 figure

Distribution, variability and sources of tropospheric ozone over south China in spring: intensive ozonesonde measurements at five locations and modeling analysis

We examine the characteristics of the spatial distribution and variability of tropospheric ozone (O3) by analysis of 93 ozonesonde profiles obtained at five stations over south China (18–30 N) during a field campaign in April–May 2004. We use a global 3-D chemical transport model (GEOS-Chem) to interpret these characteristics and to quantify the sources of tropospheric O3 over south China during this period. The observed tropospheric O3 mixing ratios showed strong spatiotemporal variability due to a complex interplay of various dynamical and chemical processes. A prominent feature in the upper and middle troposphere (UT/MT) was the frequent occurrence of high O3 mixing ratios shown as tongues extending down from the lower stratosphere or as isolated layers at all stations. The model largely captured the observed pattern of day-to-day variability in tropospheric O3 mixing ratios at all stations, but often underestimated those tongues or isolated layers of O3 enhancements observed in the UT/MT, especially at low-latitude stations. We found that tropospheric O3 along the southeast China coast was mainly produced within Asia. Lightning NOx emissions (over South Asia and equatorial Africa) and/or stratospheric influences were responsible for major events of high O3 observed in the UT/MT at all stations. Underestimated contributions of these sources likely led to the model’s underestimate in the low-latitude UT/MT O3. This study emphasizes the need for improved understanding of lightning NOx emissions and stratospheric influences over the Eurasian and African continents and for better representation of these processes in current global models

Characterization of a Peptide Domain within the GB Virus C NS5A Phosphoprotein that Inhibits HIV Replication

BACKGROUND:GBV-C infection is associated with prolonged survival in HIV-infected people and GBV-C inhibits HIV replication in co-infection models. Expression of the GBV-C nonstructural phosphoprotein 5A (NS5A) decreases surface levels of the HIV co-receptor CXCR4, induces the release of SDF-1 and inhibits HIV replication in Jurkat CD4+ T cell lines. METHODOLOGY/PRINCIPAL FINDINGS:Jurkat cell lines stably expressing NS5A protein and peptides were generated and HIV replication in these cell lines assessed. HIV replication was significantly inhibited in all cell lines expressing NS5A amino acids 152-165. Substitution of an either alanine or glycine for the serine at position 158 (S158A or S158G) resulted in a significant decrease in the HIV inhibitory effect. In contrast, substituting a phosphomimetic amino acid (glutamic acid; S158E) inhibited HIV as well as the parent peptide. HIV inhibition was associated with lower levels of surface expression of the HIV co-receptor CXCR4 and increased release of the CXCR4 ligand, SDF-1 compared to control cells. Incubation of CD4+ T cell lines with synthetic peptides containing amino acids 152-167 or the S158E mutant peptide prior to HIV infection resulted in HIV replication inhibition compared to control peptides. CONCLUSIONS/SIGNIFICANCE:Expression of GBV-C NS5A amino acids 152-165 are sufficient to inhibit HIV replication in vitro, and the serine at position 158 appears important for this effect through either phosphorylation or structural changes in this peptide. The addition of synthetic peptides containing 152-167 or the S158E substitution to Jurkat cells resulted in HIV replication inhibition in vitro. These data suggest that GBV-C peptides or a peptide mimetic may offer a novel, cellular-based approach to antiretroviral therapy

Validation of ozone measurements from the Atmospheric Chemistry Experiment (ACE)

This paper presents extensive bias determination analyses of ozone observations from the Atmospheric Chemistry Experiment (ACE) satellite instruments: the ACE Fourier Transform Spectrometer (ACE-FTS) and the Measurement of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation (ACE-MAESTRO) instrument. Here we compare the latest ozone data products from ACE-FTS and ACE-MAESTRO with coincident observations from nearly 20 satellite-borne, airborne, balloon-borne and ground-based instruments, by analysing volume mixing ratio profiles and partial column densities. The ACE-FTS version 2.2 Ozone Update product reports more ozone than most correlative measurements from the upper troposphere to the lower mesosphere. At altitude levels from 16 to 44 km, the average values of the mean relative differences are nearly all within +1 to +8%. At higher altitudes (45 60 km), the ACE-FTS ozone amounts are significantly larger than those of the comparison instruments, with mean relative differences of up to +40% (about + 20% on average). For the ACE-MAESTRO version 1.2 ozone data product, mean relative differences are within +/- 10% (average values within +/- 6%) between 18 and 40 km for both the sunrise and sunset measurements. At higher altitudes (similar to 35-55 km), systematic biases of opposite sign are found between the ACE-MAESTRO sunrise and sunset observations. While ozone amounts derived from the ACE-MAESTRO sunrise occultation data are often smaller than the coincident observations (with mean relative differences down to -10%), the sunset occultation profiles for ACE-MAESTRO show results that are qualitatively similar to ACE-FTS, indicating a large positive bias (mean relative differences within +10 to +30%) in the 45-55 km altitude range. In contrast, there is no significant systematic difference in bias found for the ACE-FTS sunrise and sunset measurements

Conserved Motifs within Hepatitis C Virus Envelope (E2) RNA and Protein Independently Inhibit T Cell Activation

<div><p>T cell receptor (TCR) signaling is required for T-cell activation, proliferation, differentiation, and effector function. Hepatitis C virus (HCV) infection is associated with impaired T-cell function leading to persistent viremia, delayed and inconsistent antibody responses, and mild immune dysfunction. Although multiple factors appear to contribute to T-cell dysfunction, a role for HCV particles in this process has not been identified. Here, we show that incubation of primary human CD4+ and CD8+ T-cells with HCV RNA-containing serum, HCV-RNA containing extracellular vesicles (EVs), cell culture derived HCV particles (HCVcc) and HCV envelope pseudotyped retrovirus particles (HCVpp) inhibited TCR-mediated signaling. Since HCVpp’s contain only E1 and E2, we examined the effect of HCV E2 on TCR signaling pathways. HCV E2 expression recapitulated HCV particle-induced TCR inhibition. A highly conserved, 51 nucleotide (nt) RNA sequence was sufficient to inhibit TCR signaling. Cells expressing the HCV E2 coding RNA contained a short, virus-derived RNA predicted to be a Dicer substrate, which targeted a phosphatase involved in Src-kinase signaling (PTPRE). T-cells and hepatocytes containing HCV E2 RNA had reduced PTPRE protein levels. Mutation of 6 nts abolished the predicted Dicer interactions and restored PTPRE expression and proximal TCR signaling. HCV RNA did not inhibit distal TCR signaling induced by PMA and Ionomycin; however, HCV E2 protein inhibited distal TCR signaling. This inhibition required lymphocyte-specific tyrosine kinase (Lck). Lck phosphorylated HCV E2 at a conserved tyrosine (Y613), and phospho-E2 inhibited nuclear translocation of NFAT. Mutation of Y613 restored distal TCR signaling, even in the context of HCVpps. Thus, HCV particles delivered viral RNA and E2 protein to T-cells, and these inhibited proximal and distal TCR signaling respectively. These effects of HCV particles likely aid in establishing infection and contribute to viral persistence.</p></div

HCV envelope (E2) coding RNA is sufficient to inhibit proximal T cell receptor (TCR) signaling.

<p>Jurkat cells were generated that stably expressed HCV envelope (E2) RNA (coding aa 384–703) with a frame-shift mutation to abolish protein expression from isolates belonging to genotype (GT) 2a and GT3, or the GT 2a sequence in which four cytidine residues were changed to alanine residues. TCR induced IL-2 release from these Jurkat cells were measured after 24 hour stimulation with anti-CD3/CD28 (A). Activation of lymphocyte specific tyrosine kinase (Lck) was measured by immunoblotting for phosphoY394 following anti-CD3 stimulation (B). Total Lck served as the loading control. The RNA sequence of the HCV E2 (aa 603–619) coding region from the different HCV genotypes (GT) and mutants are shown in panel (C). Conserved sequences are underlined and mutations introduced into the GT 2a sequence noted by * (C). Small RNAs were amplified following 3’linker ligation and specific cDNA synthesis. Small RNAs were cloned and sequenced, and the HCV E2 region encoding (aa 590–621) was detected in Jurkat cells expressing HCV E2 protein. Panel (D) demonstrates the partial sequence of the plasmid (pCR2.1) and HCV E2 RNA amplification product, followed by the oligonucleotide linker sequence. *<i>P</i>< 0.01; ns = not significant.</p