3,574 research outputs found

    Epistasis and Entropy

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    Epistasis is a key concept in the theory of adaptation. Indicators of epistasis are of interest for large system where systematic fitness measurements may not be possible. Some recent approaches depend on information theory. We show that considering shared entropy for pairs of loci can be misleading. The reason is that shared entropy does not imply epistasis for the pair. This observation holds true also in the absence of higher order epistasis. We discuss a refined approach for identifying pairwise interactions using entropy

    Epistasis and Shapes of Fitness Landscapes

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    The relationship between the shape of a fitness landscape and the underlying gene interactions, or epistasis, has been extensively studied in the two-locus case. Gene interactions among multiple loci are usually reduced to two-way interactions. We present a geometric theory of shapes of fitness landscapes for multiple loci. A central concept is the genotope, which is the convex hull of all possible allele frequencies in populations. Triangulations of the genotope correspond to different shapes of fitness landscapes and reveal all the gene interactions. The theory is applied to fitness data from HIV and Drosophila melanogaster. In both cases, our findings refine earlier analyses and reveal previously undetected gene interactions.Comment: 31 pages, 7 figures; typos removed, Example 3.10 adde

    The W100 pocket on HIV-1 gp120 penetrated by b12 is not a target for other CD4bs monoclonal antibodies

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    <p>Abstract</p> <p>Background</p> <p>The conserved CD4 binding site (CD4bs) on HIV-1 gp120 is a major target for vaccines. It is a priority to determine sites and structures within the CD4bs that are important for inclusion in vaccines. We studied a gp120 pocket penetrated by W100 of the potent CD4bs monoclonal antibody (mab), b12. We compared HIV-1 envelopes and corresponding mutants that carried blocked W100 pockets to evaluate whether other CD4bs mabs target this site.</p> <p>Findings</p> <p>All CD4bs mabs tested blocked soluble CD4 binding to gp120 consistent with their designation as CD4bs directed antibodies. All CD4bs mabs tested neutralized pseudovirions carrying NL4.3 wild type (wt) envelope. However, only b12 failed to neutralize pseudoviruses carrying mutant envelopes with a blocked W100 pocket. In addition, for CD4bs mabs that neutralized pseudovirions carrying primary envelopes, mutation of the W100 pocket had little or no effect on neutralization sensitivity.</p> <p>Conclusions</p> <p>Our data indicate that the b12 W100 pocket on gp120 is infrequently targeted by CD4bs mabs. This site is therefore not a priority for preservation in vaccines aiming to elicit antibodies targeting the CD4bs.</p

    On preparation of the W-states from atomic ensembles

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    A scheme, where three atomic ensembles can be prepared in the states of the W-class via Raman type interaction of strong classical field and a projection measurement involved three single-photon detectors and two beamsplitters, are considered. The obtained atomic entanglement consists of the Dicke or W-states of each of the ensembles.Comment: 4 pages, 1 figure, minor correction

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

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    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

    Producing organic wheat with high grain protein content: the significance of intercropping and the need for diagnostic tools

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    Grain quality of wheat is one of the major concerns of organic farming production. Cereal-legume intercropping may be of significance in this regard as it enhances the yield productivity and the grain protein content (GPC) of the intercropped wheat. However, fitted tools are needed for the diagnosis and management of such interspecific canopies. Our main objectives were i) to analyse the effect of intercropping and N-management on organic farming performances and ii) to analyse the relationships between N-status indicators and GPC of intercropped wheat. These objectives were assessed in winter pea–wheat intercrops in 2007 and 2009 in western France. Our study confirmed the significance of intercropping in the production of wheat with high GPC. We showed that tools for diagnosis, fitted for sole crops to manage grain yield and GPC (N nutrition index, chlorophyll meter), can be used on intercropped wheat