The Binding of a Glycoprotein 120 V3 Loop Peptide to HIV-1 Neutralizing Antibodies STRUCTURAL IMPLICATIONS

Abstract The structural and antigenic properties of a peptide ("CRK") derived from the V3 loop of HIV-1 gp120 protein were studied using NMR and SPR techniques. The sequence of CRK corresponds to the central portion of the V3 loop containing the highly conserved "GPGR" residue sequence. Although the biological significance of this conserved sequence is unknown, the adoption of conserved secondary structure (type II β-turn) in this region has been proposed. The tendency of CRK (while free or conjugated to protein), to adopt such structure and the influence of such structure upon CRK antigenicity were investigated by NMR and SPR, respectively. Regardless of conjugation, CRK is conformationally averaged in solution but a weak tendency of the CRK "GPGR" residues to adopt a β-turn conformation was observed after conjugation. The influence of GPGR structure upon CRK antigenicity was investigated by measuring the affinities of two cognate antibodies: "5023A" and "5025A," for CRK, protein-conjugated CRK and gp120 protein. Each antibody bound to all the antigens with nearly the same affinity. From these data, it appears that: (a) antibody binding most likely involves an induced fit of the peptide and (b) the gp120 V3 loop is probably conformationally heterogeneous. Since 5023A and 5025A are HIV-1 neutralizing antibodies, neutralization in these cases appears to be independent of adopted GPGR β-turn structure

The Deep Water Abundance on Jupiter: New Constraints from Thermochemical Kinetics and Diffusion Modeling

We have developed a one-dimensional thermochemical kinetics and diffusion model for Jupiter's atmosphere that accurately describes the transition from the thermochemical regime in the deep troposphere (where chemical equilibrium is established) to the quenched regime in the upper troposphere (where chemical equilibrium is disrupted). The model is used to calculate chemical abundances of tropospheric constituents and to identify important chemical pathways for CO-CH4 interconversion in hydrogen-dominated atmospheres. In particular, the observed mole fraction and chemical behavior of CO is used to indirectly constrain the Jovian water inventory. Our model can reproduce the observed tropospheric CO abundance provided that the water mole fraction lies in the range (0.25-6.0) x 10^-3 in Jupiter's deep troposphere, corresponding to an enrichment of 0.3 to 7.3 times the protosolar abundance (assumed to be H2O/H2 = 9.61 x 10^-4). Our results suggest that Jupiter's oxygen enrichment is roughly similar to that for carbon, nitrogen, and other heavy elements, and we conclude that formation scenarios that require very large (>8 times solar) enrichments in water can be ruled out. We also evaluate and refine the simple time-constant arguments currently used to predict the quenched CO abundance on Jupiter, other giant planets, and brown dwarfs.Comment: 42 pages, 7 figures, 4 tables, with note added in proof. Accepted for publication in Icarus [in press

Identification of competing ultrafast all-optical switching mechanisms in Si woodpile photonic crystals

We present a systematic study of ultrafast all-optical switching of Si photonic band gap woodpile crystals using broadband tunable nondegenerate pump-probe spectroscopy. At pump-probe coincidence, we investigate the behavior the differential reflectivity at the blue edge of the stopband for a wide range of pump- and probe frequencies. Both dispersive and absorptive features are observed from the probe spectra at coincidence. As the pump frequency is tuned through half the electronic bandgap of Si, the magnitude of both these features increases. For the first time we unambiguously identify this dispersive effect with the electronic Kerr effect in photonic crystals, and attribute the the absorptive features to nondegenerate two photon absorption. The dispersive and absorptive nonlinear coefficients are extracted, and are found to agree well with literature. Finally, we propose a nondegenerate figure of merit (NFOM), which defines the quality of switching for all nondegenerate optical switching processes.Comment: Accepted by JOSA

The integrity and organization of the human AIPL1 functional domains is critical for its role as a HSP90-dependent co-chaperone for rod PDE6

Biallelic mutations in the photoreceptor-expressed aryl hydrocarbon receptor interacting protein-like 1 (AIPL1) are associated with autosomal recessive Leber congenital amaurosis (LCA), the most severe form of inherited retinopathy in early childhood. AIPL1 functions as a photoreceptor-specific co-chaperone that interacts with the molecular chaperone HSP90 to facilitate the stable assembly of the retinal cyclic GMP (cGMP) phosphodiesterase (PDE6) holoenzyme. In this study, we characterized the functional deficits of AIPL1 variations, some of which induce aberrant pre-mRNA AIPL1 splicing leading to the production of al- ternative AIPL1 isoforms. We investigated the ability of the AIPL1 variants to mediate an interaction with HSP90 and modulate the rod cGMP PDE6 stability and activity. Our data revealed that both the FK506 binding protein (FKBP)-like domain and the tetra- tricopeptide repeat (TPR) domain of AIPL1 are required for interaction with HSP90. We further demonstrate that AIPL1 signifi- cantly modulates the catalytic activity of heterologously expressed rod PDE6. Although the N-terminal FKBP-like domain of AIPL1 binds the farnesylated PDE6a subunit through direct interaction with the farnesyl moiety, mutations compromising the integrity of the C-terminal TPR domain of AIPL1 also failed to modulate PDE6 activity efficiently. These AIPL1 variants moreover failed to promote the HSP90-dependent stabilization of the PDE6a subunit in the cytosol. In summary, we have successfully vali- dated the disease-causing status of the AIPL1 variations in vitro. Our findings provide insight into the mechanism underlying the co-chaperone role of AIPL1 and will be critical for ensuring an early and effective diagnosis of AIPL1 LCA patients

Building a Systematic Online Living Evidence Summary of COVID-19 Research

Throughout the global coronavirus pandemic, we have seen an unprecedented volume of COVID-19 researchpublications. This vast body of evidence continues to grow, making it difficult for research users to keep up with the pace of evolving research findings. To enable the synthesis of this evidence for timely use by researchers, policymakers, and other stakeholders, we developed an automated workflow to collect, categorise, and visualise the evidence from primary COVID-19 research studies. We trained a crowd of volunteer reviewers to annotate studies by relevance to COVID-19, study objectives, and methodological approaches. Using these human decisions, we are training machine learning classifiers and applying text-mining tools to continually categorise the findings and evaluate the quality of COVID-19 evidence

The collapse of Io's primary atmosphere in Jupiter eclipse

International audienceVolcanic outgassing due to tidal heating is the ultimate source of a tenuous SO2 atmosphere around Jupiter's moon Io. The question of whether SO2 frost on the surface plays a part, and to what degree, in maintaining Io's atmosphere with the constant volcanic outgassing is still debated. It is believed that for a sublimation-supported atmosphere, the primary atmosphere should collapse during eclipses by Jupiter, as the SO2 vapor pressure is strongly coupled to the temperature of the ice on the surface. No direct observations of Io's atmosphere in eclipse have previously been possible, due to the simultaneous need for high spectral and time sensitivity, as well as a high signal-to-noise ratio. Here we present the first ever high-resolution spectra at 19 µm of Io's SO2 atmosphere in Jupiter eclipse from the Gemini telescope. The strongest atmospheric band depth is seen to dramatically decay from 2.5 ± (0.08)% before the eclipse to 0.18 ± (0.16)% after 40 min in eclipse. Further modeling indicates that the atmosphere has collapsed shortly after eclipse ingress, implying that the atmosphere of Io has a strong sublimation-controlled component. The atmospheric column density—from pre-eclipse to in-eclipse—drops by a factor of 5 ± 2