Evolution of the progenitor binary of V1309 Scorpii before merger

It was recently demonstrated that the eruption of V1309 Sco was a result of a merger of the components of a cool contact binary. We computed a set of evolutionary models of the detached binaries with different initial parameters to compare it with pre-burst observations of V1309 Sco. The models are based on our recently developed evolutionary model of the formation of cool contact binaries. The best agreement with observations was obtained for binaries with initial masses of 1.8-2.0 solar masses and initial periods of 2.5-3.1 d. The evolution of these binaries consists of three phases: at first the binary is detached and both components lose mass and angular momentum through a magnetized wind. This takes almost two thirds of the total evolutionary lifetime. The remaining third is spent in a semi-detached configuration of the Algol-type, following the Roche-lobe overflow by the initially more massive component. When the other component leaves the main sequence and moves toward the giant branch, a contact configuration is formed for a short time, followed by the coalescence of both components.Comment: 5 pages, 1 figure, Astronomy and Astrophysics, in prin

A gp41 MPER-specific llama VHH requires a hydrophobic CDR3 for neutralization but not for antigen recognition

The membrane proximal external region (MPER) of the HIV-1 glycoprotein gp41 is targeted by the broadly neutralizing antibodies 2F5 and 4E10. To date, no immunization regimen in animals or humans has produced HIV-1 neutralizing MPER-specific antibodies. We immunized llamas with gp41-MPER proteoliposomes and selected a MPER-specific single chain antibody (VHH), 2H10, whose epitope overlaps with that of mAb 2F5. Bi-2H10, a bivalent form of 2H10, which displayed an approximately 20-fold increased affinity compared to the monovalent 2H10, neutralized various sensitive and resistant HIV-1 strains, as well as SHIV strains in TZM-bl cells. X-ray and NMR analyses combined with mutagenesis and modeling revealed that 2H10 recognizes its gp41 epitope in a helical conformation. Notably, tryptophan 100 at the tip of the long CDR3 is not required for gp41 interaction but essential for neutralization. Thus bi-2H10 is an anti-MPER antibody generated by immunization that requires hydrophobic CDR3 determinants in addition to epitope recognition for neutralization similar to the mode of neutralization employed by mAbs 2F5 and 4E10

Potent and Broad Neutralization of HIV-1 by a Llama Antibody Elicited by Immunization

Llamas (Lama glama) naturally produce heavy chain–only antibodies (Abs) in addition to conventional Abs. The variable regions (VHH) in these heavy chain–only Abs demonstrate comparable affinity and specificity for antigens to conventional immunoglobulins despite their much smaller size. To date, immunizations in humans and animal models have yielded only Abs with limited ability to neutralize HIV-1. In this study, a VHH phagemid library generated from a llama that was multiply immunized with recombinant trimeric HIV-1 envelope proteins (Envs) was screened directly for HIV-1 neutralization. One VHH, L8CJ3 (J3), neutralized 96 of 100 tested HIV-1 strains, encompassing subtypes A, B, C, D, BC, AE, AG, AC, ACD, CD, and G. J3 also potently neutralized chimeric simian-HIV strains with HIV subtypes B and C Env. The sequence of J3 is highly divergent from previous anti–HIV-1 VHH and its own germline sequence. J3 achieves broad and potent neutralization of HIV-1 via interaction with the CD4-binding site of HIV-1 Env. This study may represent a new benchmark for immunogens to be included in B cell–based vaccines and supports the development of VHH as anti–HIV-1 microbicides

Indirect imaging of an accretion disk rim in the long-period interacting binary W Crucis

Light curves of the long-period Algols are known for their complex shape (asymmetry in the eclipse, light variations outside eclipse, changes from cycle-to-cycle), and their interpretation is not possible in the standard model of binary stars. Complex structures present in these active Algol systems could be studied with the eclipse-mapping method which was successfully applied to the new 7-color photometric observations in the Geneva system of W Cru, belonging to the isolated group of these active Algols. Several cycles of this long-period (198.5 days) eclipsing binary have been covered by observations. We have used a modified Rutten's approach to the eclipse-mapping. The optimization of the system's parameters and the recovery of the disk intensity distribution are performed using a genetic algorithm (GA). It is found that a hot component is hidden in the thick accretion disk which confirms previous findings. The mass of the component, M1 = 8.2 Ms indicates that it is a mid-B type star. The mass-losing component is filling its critical lobe which means it is a G-type supergiant with a mass M2 = 1.6 Ms. The disk is geometrically very extended and its outer radius is about 80% of the primary's critical lobe. A reconstructed image reveals a rather clumpy and nonuniform brightness distribution of an accretion disk rim in this almost edge-on seen system. This clumpyness accounts for light curve distortions and asymmetries, as well as for secular changes.Comment: 10 pages, 5 figures, accepted for publication in A&

Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1

To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols

Two-Partner Secretion Systems of Neisseria meningitidis Associated with Invasive Clonal Complexes▿ †

The two-partner secretion (TPS) pathway is widespread among gram-negative bacteria and facilitates the secretion of very large and often virulence-related proteins. TPS systems consist of a secreted TpsA protein and a TpsB protein involved in TpsA transport across the outer membrane. Sequenced Neisseria meningitidis genomes contain up to five TpsA- and two TpsB-encoding genes. Here, we investigated the distribution of TPS-related open reading frames in a collection of disease isolates. Three distinct TPS systems were identified among meningococci. System 1 was ubiquitous, while systems 2 and 3 were significantly more prevalent among isolates of hyperinvasive clonal complexes than among isolates of poorly invasive clonal complexes. In laboratory cultures, systems 1 and 2 were expressed. However, several sera from patients recovering from disseminated meningococcal disease recognized the TpsAs of systems 2 and 3, indicating the expression of these systems during infection. Furthermore, we showed that the major secreted TpsAs of systems 1 and 2 depend on their cognate TpsBs for transport across the outer membrane and that the system 1 TpsAs undergo processing. Together, our data indicate that TPS systems may contribute to the virulence of N. meningitidis