CATNAP: a tool to compile, analyze and tally neutralizing antibody panels

CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. It is a comprehensive platform focusing on neutralizing antibody potencies in conjunction with viral sequences. CATNAP integrates neutralization and sequence data from published studies, and allows users to analyze that data for each HIV Envelope protein sequence position and each antibody. The tool has multiple data retrieval and analysis options. As input, the user can pick specific antibodies and viruses, choose a panel from a published study, or supply their own data. The output superimposes neutralization panel data, virus epidemiological data, and viral protein sequence alignments on one page, and provides further information and analyses. The user can highlight alignment positions, or select antibody contact residues and view position-specific information from the HIV databases. The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. Website name: CATNAP (Compile, Analyze and Tally NAb Panels). Website address: http://hiv.lanl.gov/catnap

Ruler elements in chromatin remodelers set nucleosome array spacing and phasing

Arrays of regularly spaced nucleosomes dominate chromatin and are often phased by alignment to reference sites like active promoters. How the distances between nucleosomes (spacing), and between phasing sites and nucleosomes are determined remains unclear, and specifically, how ATP-dependent chromatin remodelers impact these features. Here, we used genome-wide reconstitution to probe how Saccharomyces cerevisiae ATP-dependent remodelers generate phased arrays of regularly spaced nucleosomes. We find that remodelers bear a functional element named the ‘ruler’ that determines spacing and phasing in a remodeler-specific way. We use structure-based mutagenesis to identify and tune the ruler element residing in the Nhp10 and Arp8 modules of the INO80 remodeler complex. Generally, we propose that a remodeler ruler regulates nucleosome sliding direction bias in response to (epi)genetic information. This finally conceptualizes how remodeler-mediated nucleosome dynamics determine stable steady-state nucleosome positioning relative to other nucleosomes, DNA bound factors, DNA ends and DNA sequence elements

Extreme N-emitters at high-redshift: signatures of supermassive stars and globular cluster or black hole formation in action?

[Abridged] Using the JWST/NIRSpec observations from CEERS we found an extreme N-emitter, CEERS-1019 at z=8.6782 showing intense NIV and NIII emission. From the observed rest-UV and optical lines we conclude that it is compatible with photoionization from stars and we determine accurate abundances for C, N, O, and Ne, relative to H, finding a highly supersolar ratio log(N/O) = -0.18+/-0.11, and normal log(C/O) = -0.75+/-0.11 and log(Ne/O) = -0.63+/-0.07, for its low metallicity, 12+log(O/H)= 7.70+/-0.18. We also analyze other N-emitters from the literature. All show strongly enhanced N/O ratios and two of them normal C/O. Massive star ejecta from WR stars are needed to explain the galaxies with enhanced C/O (Lynx arc and Mrk 996). On the other hand, supermassive stars (>1000 Msun, SMS) in the ``conveyer-belt model'' put forward to explain globular clusters (GCs), predict a high N/O and small changes in C/O, compatible with CEERS-1019, the Sunburst cluster, SMACS2031, and GN-z11. Based on the chemical abundances, possible enrichment scenarios, compactness, and high ISM density, we suggest that CEERS-1019, SMACS2031, and the Sunburst cluster could contain proto-GCs. Finally, we propose that some N-emitters enriched by SMS could also have formed intermediate-mass black holes, and we suggest that this might be the case for GN-z11. Our observations and analysis reinforce the suggested link between some N-emitters and proto-GC formation, which is supported both by empirical evidence and quantitative models. Furthermore, the observations provide possible evidence for the presence of supermassive stars in the early Universe (z>8) and at z~2-3. Our analysis also suggests that the origin and nature of the N-emitters is diverse, including also objects like GN-z11 which possibly host an AGN.Comment: Submitted to A&A, 19 pages, 8 figures, 4 table

HIV Types, Groups, Subtypes and Recombinant Forms: Errors in Replication, Selection Pressure and Quasispecies

HIV-1 is a chimpanzee virus which was transmitted to humans by several zoonotic events resulting in infection with HIV-1 groups M P, and in parallel transmission events from sooty mangabey monkey viruses leading to infections with HIV-2 groups A H. Both viruses have circulated in the human population for about 80 years. In the infected patient, HIV mutates, and by elimination of some of the viruses by the action of the immune system individual quasispecies are formed. Along with the selection of the fittest viruses, mutation and recombination after superinfection with HIV from different groups or subtypes have resulted in the diversity of their patterns of geographic distribution. Despite the high variability observed, some essential parts of the HIV genome are highly conserved. Viral diversity is further facilitated in some parts of the HIV genome by drug selection pressure and may also be enhanced by different genetic factors, including HLA in patients from different regions of the world. Viral and human genetic factors influence pathogenesis. Viral genetic factors are proteins such as Tat, Vif and Rev. Human genetic factors associated with a better clinical outcome are proteins such as APOBEC, langerin, tetherin and chemokine receptor 5 (CCR5) and HLA B27, B57, DRB1{*}1303, KIR and PARD3B. Copyright (C) 2012 S. Karger AG, Base

Elucidation of Hepatitis C Virus Transmission and Early Diversification by Single Genome Sequencing

A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma viral RNA to identify transmitted/founder (T/F) viruses in 17 subjects with acute community-acquired HCV infection. Sequences from 13 of 17 acute subjects, but none of 14 chronic controls, exhibited one or more discrete low diversity viral lineages. Sequences within each lineage generally revealed a star-like phylogeny of mutations that coalesced to unambiguous T/F viral genomes. Numbers of transmitted viruses leading to productive clinical infection were estimated to range from 1 to 37 or more (median = 4). Four acutely infected subjects showed a distinctly different pattern of virus diversity that deviated from a star-like phylogeny. In these cases, empirical analysis and mathematical modeling suggested high multiplicity virus transmission from individuals who themselves were acutely infected or had experienced a virus population bottleneck due to antiviral drug therapy. These results provide new quantitative and qualitative insights into HCV transmission, revealing for the first time virus-host interactions that successful vaccines or treatment interventions will need to overcome. Our findings further suggest a novel experimental strategy for identifying full-length T/F genomes for proteome-wide analyses of HCV biology and adaptation to antiviral drug or immune pressures