689 research outputs found
A comparison of attitudes to IPv6 in three countries
Internet Protocol (IP), the underlying protocol upon which the Internet is based, has a number of serious flaws, including limited address space, security and performance limitations. Since the early 1990s a new version of IP (IPv6) has been developed in which these problems are addressed. Yet despite years of “hype”, adoption of IPv6 has been minimal or non-existent. Many efforts have been made to encourage IPv6 adoption around the world but none have been widely successful. The decision to adopt is influenced by the information available to the decision maker. This paper reports the results of studies of attitudes and perceptions to IPv6 in three countries and determines that the prevalent information about the standard in each country is often scarce and inaccurate. This contributes to reluctance to adopt IPv6 and further exacerbates the problem. The paper concludes with recommendations to improve available information so as to increase IPv6 acceptance and adoption
Biogeographical comparison of the emergent macrophyte, Sagittaria platyphylla in its native and introduced ranges
Understanding why some plant species become invasive is important to predict and prevent future weed threats and identify appropriate management strategies. Many hypotheses have been proposed to explain why plants become invasive, yet few studies have quantitatively compared plant and population parameters between native and introduced range populations to gain an objective perspective on the causes of plant invasion. The present study uses a biogeographical field survey to compare morphological and reproductive traits and abundance between the native range (USA) and two introduced ranges (Australia and South Africa) of Sagittaria platyphylla (Engelm.) J.G. Sm (Alismataceae), a highly invasive freshwater macrophyte. Introduced and native populations differed in sexual reproductive output with the number of achenes per fruiting head and individual achene weight found to be 40% and 50% greater in introduced populations respectively. However, no other morphological traits were found to be consistently different between the native and both introduced ranges, especially after taking into account differences in environmental conditions between the three ranges. Although populations in introduced regions were larger and occupied greater percentage cover, no differences in plant density were evident. Our results suggest that, apart from sexual reproduction, many of the trait patterns observed in S. platyphylla are influenced by environmental and habitat conditions within the native and invaded ranges. We conclude that the enemy release hypothesis best explains the results observed for sexual reproduction. In particular, we hypothesise that a release from natural enemies, specifically a pre-dispersal seed predator, may induce reproductive plasticity in S. platyphylla
Identification of human monoclonal antibodies specific for CCR5 from an antibody library derived from HIV-infected long-term non-progressors
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Stapled HIV-1 Peptides Recapitulate Antigenic Structures and Engage Broadly Neutralizing Antibodies
Hydrocarbon stapling can restore bioactive, α-helical structure to natural peptides, yielding research tools and prototype therapeutics to dissect and target protein interactions. Here, we explore the capacity of peptide stapling to generate high fidelity, protease-resistant mimics of antigenic structures for vaccine development. HIV-1 has been refractory to vaccine technologies thus far, although select human antibodies can broadly neutralize HIV-1 by targeting sequences of the gp41 juxtamembrane fusion apparatus. To develop candidate HIV-1 immunogens, we generated and characterized stabilized α-helices of the membrane proximal external region (SAH-MPER) of gp41. SAH-MPER peptides were remarkably protease-resistant and bound to the broadly neutralizing 4E10 and 10E8 antibodies with high affinity, recapitulating the structure of the MPER epitope when differentially engaged by the two anti-HIV Fabs. Thus, stapled peptides may provide a new opportunity to develop chemically-stabilized antigens for vaccination
Gluon fragmentation to quarkonia
Gluon fragmentation to heavy quarkonia is studied herein. We
compute these D-wave states' polarized fragmentation functions and find that
they are enhanced by large numerical prefactors. The prospects for detecting
the lowest lying charmonium state at the Tevatron are discussed.Comment: 10 pages with 4 uuencoded figures, CALT-68-195
Gene-Specific Substitution Profiles Describe the Types and Frequencies of Amino Acid Changes during Antibody Somatic Hypermutation
Somatic hypermutation (SHM) plays a critical role in the maturation of antibodies, optimizing recognition initiated by recombination of V(D)J genes. Previous studies have shown that the propensity to mutate is modulated by the context of surrounding nucleotides and that SHM machinery generates biased substitutions. To investigate the intrinsic mutation frequency and substitution bias of SHMs at the amino acid level, we analyzed functional human antibody repertoires and developed mGSSP (method for gene-specific substitution profile), a method to construct amino acid substitution profiles from next-generation sequencing-determined B cell transcripts. We demonstrated that these gene-specific substitution profiles (GSSPs) are unique to each V gene and highly consistent between donors. We also showed that the GSSPs constructed from functional antibody repertoires are highly similar to those constructed from antibody sequences amplified from non-productively rearranged passenger alleles, which do not undergo functional selection. This suggests the types and frequencies, or mutational space, of a majority of amino acid changes sampled by the SHM machinery to be well captured by GSSPs. We further observed the rates of mutational exchange between some amino acids to be both asymmetric and context dependent and to correlate weakly with their biochemical properties. GSSPs provide an improved, position-dependent alternative to standard substitution matrices, and can be utilized to developing software for accurately modeling the SHM process. GSSPs can also be used for predicting the amino acid mutational space available for antigen-driven selection and for understanding factors modulating the maturation pathways of antibody lineages in a gene-specific context. The mGSSP method can be used to build, compare, and plot GSSPs1; we report the GSSPs constructed for 69 common human V genes (DOI: 10.6084/m9.figshare.3511083) and provide high-resolution logo plots for each (DOI: 10.6084/m9.figshare.3511085)
Structures of the CCR5 N Terminus and of a Tyrosine-Sulfated Antibody with HIV-1 gp120 and CD4
The CCR5 co-receptor binds to the HIV-l gp120 envelope glycoprotein and facilitates HIV-l entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (α-helix) and 412d (extendedloop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-l interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system
Could enemy release explain invasion success of Sagittaria platyphylla in Australia and South Africa?.
Sagittaria platyphylla (delta arrowhead) is an emergent aquatic macrophyte native to southeastern United States of America that has been introduced into Australia and South Africa as an ornamental pond and aquarium plant. Compared to plants in the native range, S. platyphylla in the introduced range have greater reproductive capacity and form extensive infestations that dominate shallow waterbodies. One explanation for the invasive success of S. platyphylla in introduced countries is that plants are devoid of biotic pressures that would regulate population abundance in their native range (the enemy release hypothesis). We previously reported on field surveys that documented the number of pathogens and insect herbivores associated with S. platyphylla in native and introduced ranges. Here, we quantify the damage caused by these natural enemies to S. platyphylla in the two ranges. As predicted, damage to plants caused by pathogens and insect herbivores was much greater in the native than the introduced range at both the plant and population level. In introduced regions herbivory was low (less than 10%) in every plant part, while in North America insect damage to fruiting heads was 46% (of fruiting heads attacked), damage to leaves was between 33 to 57%, and internal herbivore damage to petioles and the inflorescence scapes was 56% and 43% respectively. Pathogen damage to leaves was between 39 to 57% of leaves per plant affected, compared to 9% in Australia and 8% in South Africa. This lack of biotic resistance from herbivores and disease may have facilitated S. platyphylla invasion in Australia and South Africa
Adaptation of HIV-1 Envelope Glycoprotein gp120 to Humoral Immunity over the Course of the Epidemic
Since 2009, a large panel of broad and potent monoclonal neutralizing antibodies (MoNAbs) against HIV-1 have been isolated. These MoNAbs can protect from lllV-1 infection and suppress established infection in animal models. Because their efficacy should be evaluated in human clinical
trials, it is of importance to define the sensitivity of the most contemporary transmitted variants to these MoNAbs. We, and others previously, reported that HIV-1 has become more resistant to neutralization over the course of the epidemic (Bunnik et al., Nature Med 2010, Bouvin-Pley et al., PloS Pathog 2013).
Methods: Here we extended the analyses to the most potent
MoNAbs described since then, either more recently isolated or improved by structure-based gene modifications.
Results: We fully confirmed the first observations showing an increasing resistance of HIV-1 clade B over time to MoNAbs targeting the major gp l20 epitopes but not to MoNAbs targeting the gp41 MPER. Despite this evolution, some MoNAbs still were able to neutralize efficiently the most recently transmitted HIV-1 variants (2006-2010). The most potent MoNAbs were the bi-specific PG9- and PG16-iMab that alone were able to neutralize an variants at less than 0.4 mg/mL. The sensitivity to iMAb remained similar over time, suggesting that the trend of increasing resistance to PG9-/PG16-iMAb may be attributed only to die antigen binding domain of PG9/PG16. NIH45-46m2 (and -m7), 10-1074 and 10E8 were also highly potent and, if combined, reached the potency of PG9-/PG16-iMAb. We also observed that 3BNC 117 was almost as potent as the modified NIH45-46 antibodies, and that the lama-derived JM4IgG2b was the most potent Ab among those that do not target the major gp 120 neutralizing epitopes.
Conclusions: These data clearly suggest a continuous drift of the env gene of HIV-1 elude B over the epidemic, and that not a single epitope is concerned but the entire gp120 as a whole. The consequences of this adaptation on the envelope functionality are being explored
Mapping monoclonal anti-SARS-CoV-2 antibody repertoires against diverse coronavirus antigens
Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged continuously, challenging the effectiveness of vaccines, diagnostics, and treatments. Moreover, the possibility of the appearance of a new betacoronavirus with high transmissibility and high fatality is reason for concern. In this study, we used a natively paired yeast display technology, combined with next-generation sequencing (NGS) and massive bioinformatic analysis to perform a comprehensive study of subdomain specificity of natural human antibodies from two convalescent donors. Using this screening technology, we mapped the cross-reactive responses of antibodies generated by the two donors against SARS-CoV-2 variants and other betacoronaviruses. We tested the neutralization potency of a set of the cross-reactive antibodies generated in this study and observed that most of the antibodies produced by these patients were non-neutralizing. We performed a comparison of the specific and non-specific antibodies by somatic hypermutation in a repertoire-scale for the two individuals and observed that the degree of somatic hypermutation was unique for each patient. The data from this study provide functional insights into cross-reactive antibodies that can assist in the development of strategies against emerging SARS-CoV-2 variants and divergent betacoronaviruses
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