Soluble CD40 ligand can replace the normal T cell-derived CD40 ligand signal to B cells in T cell-dependent activation

We have constructed a soluble chimeric fusion protein between the mouse CD8 alpha chain and the mouse CD40 T cell ligand. This protein binds to both human and mouse B cells. By itself it induced a modest degree of B cell proliferation, but together with anti-immunoglobulin (anti-Ig) antibody it greatly stimulated B cell proliferation, as determined by both [3H]thymidine uptake and increase in cell numbers. These data are evidence that the CD40 ligand on T cells provides a signal that drives B cell proliferation. This signal is synergistic with that delivered by anti-Ig antibody

Factors Responsible for the Stability and the Existence of a Clean Energy Gap of a Silicon Nanocluster

We present a critical theoretical study of electronic properties of silicon nanoclusters, in particular the roles played by symmetry, relaxation, and hydrogen passivation on the the stability, the gap states and the energy gap of the system using the order-N [O(N)] non-orthogonal tight-binding molecular dynamics and the local analysis of electronic structure.Comment: 26 pages including figure

Thermally stimulated H emission and diffusion in hydrogenated amorphous silicon

We report first principles ab initio density functional calculations of hydrogen dynam- ics in hydrogenated amorphous silicon. Thermal motion of the host Si atoms drives H diffusion, as we demonstrate by direct simulation and explain with simple models. Si-Si bond centers and Si ring centers are local energy minima as expected. We also describe a new mechanism for break- ing Si-H bonds to release free atomic H into the network: a fluctuation bond center detachment (FBCD) assisted diffusion. H dynamics in a-Si:H is dominated by structural fluctuations intrinsic to the amorphous phase not present in the crystal.Comment: 4 pages, 5 figures, In press EPL (Jun. 2007

Escape from Human Monoclonal Antibody Neutralization Affects In Vitro and In Vivo Fitness of Severe Acute Respiratory Syndrome Coronavirus

Severe Acute Respiratory Syndrome (SARS) emerged as a human disease in 2002 and detailed phylogenetic analysis and epidemiological studies have suggested that the SARS-Coronavirus (SARS-CoV) originated from animals. The Spike (S) glycoprotein has been identified as a major target of protective immunity and contains at least three regions that are targeted by neutralizing antibodies in the S1 and S2 domains. We previously characterized a panel of neutralizing human monoclonal antibodies (MAbs) but the majority of epitopes recognized by the MAbs remained unknown

Therapeutic efficacy of antibodies lacking FcgammaR against lethal Dengue virus infection Is due to neutralizing potency and blocking of enhancing antibodies

<div><p>Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) are life-threatening complications following infection with one of the four serotypes of dengue virus (DENV). At present, no vaccine or antiviral therapies are available against dengue. Here, we characterized a panel of eight human or mouse-human chimeric monoclonal antibodies (MAbs) and their modified variants lacking effector function and dissected the mechanism by which some protect against antibody-enhanced lethal DENV infection. We found that neutralizing modified MAbs that recognize the fusion loop or the A strand epitopes on domains II and III of the envelope protein, respectively, act therapeutically by competing with and/or displacing enhancing antibodies. By analyzing these relationships, we developed a novel <em>in vitro</em> suppression-of-enhancement assay that predicts the ability of modified MAbs to act therapeutically against antibody-enhanced disease <em>in vivo</em>. These studies provide new insight into the biology of DENV pathogenesis and the requirements for antibodies to treat lethal DENV disease.</p> </div

[De beatitudine, gratia sanctificante et scientia Dei]

La fecha no consta sino en el segundo tratado, 1618 (fol. 1r). Cada tratado tiene foliación distintaContenido:1.-[De beatitudine]-. 2.-Disputationes selectissimae in compendium redactae ex materia de gratia sanctificante reverendissimi P. M. Ioannis Baptistae Lanzabeche, anno 1618-. 3.-Breve compendium commentariorum in materiam de scientia Dei, de ideis et aliis quae pertinent ad eius perfectionem intellectualem, a quaestione 14 S. Thomae usqiie ad 18-Encuadernación: Perg. Rotulata:.: Lanzavecchia. De scientia Dei. El angulo superior derecho deteriorado por tintas corrosivas, sin afectar al texto. | Marcas procedencia: Biblioteca Provincial y de la Universidad de Sevilla / Est. 1 de Ms. Tab. C. La signatura antigua parece ser la del Colegio de San Hermenegildo de SevillaA 332/04

Immunogenetic Mechanisms Driving Norovirus GII.4 Antigenic Variation

Noroviruses are the principal cause of epidemic gastroenteritis worldwide with GII.4 strains accounting for 80% of infections. The major capsid protein of GII.4 strains is evolving rapidly, resulting in new epidemic strains with altered antigenic potentials. To test if antigenic drift may contribute to GII.4 persistence, human memory B cells were immortalized and the resulting human monoclonal antibodies (mAbs) characterized for reactivity to a panel of time-ordered GII.4 virus-like particles (VLPs). Reflecting the complex exposure history of the volunteer, human anti-GII.4 mAbs grouped into three VLP reactivity patterns; ancestral (1987–1997), contemporary (2004–2009), and broad (1987–2009). NVB 114 reacted exclusively to the earliest GII.4 VLPs by EIA and blockade. NVB 97 specifically bound and blocked only contemporary GII.4 VLPs, while NBV 111 and 43.9 exclusively reacted with and blocked variants of the GII.4.2006 Minerva strain. Three mAbs had broad GII.4 reactivity. Two, NVB 37.10 and 61.3, also detected other genogroup II VLPs by EIA but did not block any VLP interactions with carbohydrate ligands. NVB 71.4 cross-neutralized the panel of time-ordered GII.4 VLPs, as measured by VLP-carbohydrate blockade assays. Using mutant VLPs designed to alter predicted antigenic epitopes, two evolving, GII.4-specific, blockade epitopes were mapped. Amino acids 294–298 and 368–372 were required for binding NVB 114, 111 and 43.9 mAbs. Amino acids 393–395 were essential for binding NVB 97, supporting earlier correlations between antibody blockade escape and carbohydrate binding variation. These data inform VLP vaccine design, provide a strategy for expanding the cross-blockade potential of chimeric VLP vaccines, and identify an antibody with broadly neutralizing therapeutic potential for the treatment of human disease. Moreover, these data support the hypothesis that GII.4 norovirus evolution is heavily influenced by antigenic variation of neutralizing epitopes and consequently, antibody-driven receptor switching; thus, protective herd immunity is a driving force in norovirus molecular evolution

Emergence of New Pandemic GII.4 Sydney Norovirus Strain Correlates With Escape From Herd Immunity

Background. GII.4 noroviruses are a significant source of acute gastroenteritis worldwide, causing the majority of human norovirus outbreaks. Evolution of the GII.4 major capsid protein occurs rapidly, resulting in the emergence of new strains that produce successive waves of pandemic disease. A new pandemic isolate, GII.4 2012 Sydney, largely replaced previously circulating strains in late 2012. We compare the antigenic properties of GII.4 2012 Sydney with previously circulating strains. Methods. To determine whether GII.4-2012 Sydney is antigenically different from recently circulating strains GII.4-2006 Minerva and GII.4-2009 New Orleans in previously identified blockade epitopes, we compared reactivity and blockade profiles of GII.4-2006, GII.4-2009, and GII.4-2012 virus-like particles in surrogate neutralization/blockade assays using monoclonal antibodies and human polyclonal sera. Results. Using monoclonal antibodies that map to known blockade epitopes in GII.4-2006 and GII.4-2009 and human outbreak polyclonal sera, we demonstrate either complete loss or significantly reduced reactivity and blockade of GII.4.2012 compared to GII.4-2006 and GII.4-2009. Conclusions. GII.4-2012 Sydney is antigenically different from GII.4-2006 Minerva and GII.4-2009 New Orleans in at least 2 key blockade epitopes. Viral evolution in key potential neutralization epitopes likely allowed GII.4-2012 to escape from human herd immunity and emerge as the new predominant strai

Understanding the differential hygienic behavior towards drone brood in Apis mellifera colonies from Argentina

Brood diseases of Apis mellifera colonies constitute a main problem of beekeeping worldwide. Worker bees display a social health mechanism that consists in detecting, uncapping and removing dead or diseased brood from the hive: the hygienic behavior (CH). These activities are induced by olfactory cues and have been described as associated to hygiene of brood parasitized by Varroa destructor. This mite have preference for drone brood, but the efficiency of CH towards their cells is significantly lower compared with cells of worker brood, being left uninspected by workers. Some authors suggest that a possible cause of the CH differences is due to the cell wax cap of drone brood (thicker than worker cells) acting as a barrier to volatile compounds and obstructing disease detection. The aims of this research were to study the differential CH towards worker and drone brood belonging to highly hygienic colonies from Argentina, and to explore the importance of drone cell wax cap as an interfering factor in the transmission of chemical signals. To this end, removal percentages of pin-killed worker and drone brood were recorded and an innovative cell wax cap exchange was implemented in three different treatments: pin-killed worker pupa with a healthy drone cell wax cap; a healthy worker pupa with a pin-killed drone cell wax cap; and a healthy worker pupa covered with a healthy drone cell wax cap (control). Results showed a greater removal towards worker cells than drone cells. For the cell wax cap exchange experiment, we found that the removal of pin-killed worker pupae covered with healthy drone cell wax cap was significantly high, while the removal of healthy worker pupae covered with pin-killed drone opercula was low. These preliminary results confirms a differential behavior between both type of brood cells and suggests that the cell wax cap of drone brood is not interfering the detection of chemical compounds from the diseased brood by worker bees, regardless the thickness. This work contributes to a better understanding of the detection activity of different types of diseased brood and provides information useful to control strategies of varroosis and other brood diseases.Fil: Dowd, D. Duggan. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Genética; ArgentinaFil: Muntaabski, Irina. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigacion En Ciencias Veterinarias y Agronomicas. Instituto de Agrobiotecnologia y Biologia Molecular. Grupo Vinculado Instituto de Genetica "ewald A. Favret" Al Iabimo | Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Pque. Centenario. Instituto de Agrobiotecnologia y Biologia Molecular. Grupo Vinculado Instituto de Genetica "ewald A. Favret" Al Iabimo.; ArgentinaFil: Russo, R. M.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Genética; ArgentinaFil: Landi, L.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Recursos Naturales. Instituto de Recursos Biológicos; ArgentinaFil: Lanzavecchia, S. B.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Genética; ArgentinaFil: Cladera, J. L.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Genética; ArgentinaFil: Palacio, M. A.. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Bedascarrabure, E.. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigacion de Agroindustria. Instituto de Ingeniería Rural.; ArgentinaFil: Scannapieco, Alejandra Carla. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigacion En Ciencias Veterinarias y Agronomicas. Instituto de Agrobiotecnologia y Biologia Molecular. Grupo Vinculado Instituto de Genetica "ewald A. Favret" Al Iabimo | Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Pque. Centenario. Instituto de Agrobiotecnologia y Biologia Molecular. Grupo Vinculado Instituto de Genetica "ewald A. Favret" Al Iabimo.; ArgentinaFil: Liendo, María Clara. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigacion En Ciencias Veterinarias y Agronomicas. Instituto de Agrobiotecnologia y Biologia Molecular. Grupo Vinculado Instituto de Genetica "ewald A. Favret" Al Iabimo | Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Pque. Centenario. Instituto de Agrobiotecnologia y Biologia Molecular. Grupo Vinculado Instituto de Genetica "ewald A. Favret" Al Iabimo.; Argentina46th Apimondia International Apicultural Congress: Beekeeping together within agricultureQuébecCanadáInternational Federation of Beekeepers' AssociationsCanadian Honey Counci

Exceptionally potent human monoclonal antibodies are effective for prophylaxis and therapy of tetanus in mice

Human monoclonal antibodies were used here to study the mechanism of neuron intoxication by tetanus neurotoxin and to evaluate them as a safe preventive and therapeutic substitute of hyperimmune sera for tetanus in mice. By screening memory B cells of immune donors, we selected two monoclonal antibodies specific for tetanus neurotoxin with exceptionally high neutralizing activities, which were extensively characterized both structurally and functionally. We found that these antibodies interfere with the binding and translocation of the neurotoxin into neurons by interacting with two epitopes, whose definition pinpoints crucial events in the cellular pathogenesis of tetanus. This information explains the unprecedented neutralization ability of these antibodies, which were found to be exceptionally potent in preventing experimental tetanus when injected in mice long before the neurotoxin. Moreover, their Fab derivatives neutralized tetanus neurotoxin in post-exposure experiments, suggesting their potential therapeutic use via intrathecal injection. As such, these human monoclonal antibodies, as well as their Fab derivatives, meet all requirements for being considered for prophylaxis and therapy of human tetanus and are ready for clinical trials