High Affinity Antigen Recognition of the Dual Specific Variants of Herceptin Is Entropy-Driven in Spite of Structural Plasticity

The antigen-binding site of Herceptin, an anti-human Epidermal Growth Factor Receptor 2 (HER2) antibody, was engineered to add a second specificity toward Vascular Endothelial Growth Factor (VEGF) to create a high affinity two-in-one antibody bH1. Crystal structures of bH1 in complex with either antigen showed that, in comparison to Herceptin, this antibody exhibited greater conformational variability, also called “structural plasticity”. Here, we analyzed the biophysical and thermodynamic properties of the dual specific variants of Herceptin to understand how a single antibody binds two unrelated protein antigens. We showed that while bH1 and the affinity-improved bH1-44, in particular, maintained many properties of Herceptin including binding affinity, kinetics and the use of residues for antigen recognition, they differed in the binding thermodynamics. The interactions of bH1 and its variants with both antigens were characterized by large favorable entropy changes whereas the Herceptin/HER2 interaction involved a large favorable enthalpy change. By dissecting the total entropy change and the energy barrier for dual interaction, we determined that the significant structural plasticity of the bH1 antibodies demanded by the dual specificity did not translate into the expected increase of entropic penalty relative to Herceptin. Clearly, dual antigen recognition of the Herceptin variants involves divergent antibody conformations of nearly equivalent energetic states. Hence, increasing the structural plasticity of an antigen-binding site without increasing the entropic cost may play a role for antibodies to evolve multi-specificity. Our report represents the first comprehensive biophysical analysis of a high affinity dual specific antibody binding two unrelated protein antigens, furthering our understanding of the thermodynamics that drive the vast antigen recognition capacity of the antibody repertoire

Robustness of common hemodynamic indicators with respect to numerical resolution in 38 middle cerebral artery aneurysms

Background: Using computational fluid dynamics (CFD) to compute the hemodynamics in cerebral aneurysms has received much attention in the last decade. The usability of these methods depends on the quality of the computations, highlighted in recent discussions. The purpose of this study is to investigate the convergence of common hemodynamic indicators with respect to numerical resolution. Methods: 38 middle cerebral artery bifurcation aneurysms were studied at two different resolutions (one comparable to most studies, and one finer). Relevant hemodynamic indicators were collected from two of the most cited studies, and were compared at the two refinements. In addition, correlation to rupture was investigated. Results: Most of the hemodynamic indicators were very well resolved at the coarser resolutions, correlating with the finest resolution with a correlation coefficient >0.95. The oscillatory shear index (OSI) had the lowest correlation coefficient of 0.83. A logarithmic Bland-Altman plot revealed noticeable variations in the proportion of the aneurysm under low shear, as well as in spatial and temporal gradients not captured by the correlation alone. Conclusion: Statistically, hemodynamic indicators agree well across the different resolutions studied here. However, there are clear outliers visible in several of the hemodynamic indicators, which suggests that special care should be taken when considering individual assessment

Evaluación del efecto de la intersiembra primaveral de pasto llorón (Eragrostis curvula) sobre pasturas degradadas de pasto llorón en el Sudoeste Bonaerense = Evaluation of the effect of spring interplanting of weeping grass (Eragrostis curvula) on degraded weeping grass pastures in the Southwest of Buenos Aires

El objetivo de este trabajo fue evaluar el efecto de la intersiembra en primavera de dos densidades de semilla de pasto llorón sobre la Densidad de matas y la Producción de Materia Seca (PMS) en una pastura degradada de pasto llorón sudoeste bonaerense.EEA BordenaveFil: Torres Carbonell, Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bordenave. Agencia de Extensión Rural Bahía Blanca; Argentina.Fil: Torres Carbonell, Carlos. Universidad Nacional del Sur. Departamento de Agronomía; Argentina.Fil: Marinissen Angel Néstor. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bordenave. Agencia de Extensión Rural Bahía Blanca; Argentina.Fil: Lauric, Miriam Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bordenave. Agencia de Extensión Rural Bahía Blanca; Argentina.Fil: De Leo, Gerónimo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bordenave. Agencia de Extensión Rural Bahía Blanca; Argentina.Fil: Baioni, S. Universidad Nacional del Sur. Departamento de Agronomía; Argentina.Fil: Armando, L. Universidad Nacional del Sur. Departamento de Agronomía; Argentina.Fil: Carrera, A. Universidad Nacional del Sur. Departamento de Agronomía; Argentina.Fil: Fioretti, M. Universidad Nacional del Sur. Departamento de Agronomía; Argentina

Peatland vascular plant functional types affect methane dynamics by altering microbial community structure

Peatlands are natural sources of atmospheric methane (CH4), an important greenhouse gas. It is established that peatland methane dynamics are controlled by both biotic and abiotic conditions, yet the interactive effect of these drivers is less studied and consequently poorly understood. Climate change affects the distribution of vascular plant functional types (PFTs) in peatlands. By removing specific PFTs, we assessed their effects on peat organic matter chemistry, microbial community composition and on potential methane production (PMP) and oxidation (PMO) in two microhabitats (lawns and hummocks). Whilst PFT removal only marginally altered the peat organic matter chemistry, we observed considerable changes in microbial community structure. This resulted in altered PMP and PMO. PMP was slightly lower when graminoids were removed, whilst PMO was highest in the absence of both vascular PFTs (graminoids and ericoids), but only in the hummocks. Path analyses demonstrate that different plant-soil interactions drive PMP and PMO in peatlands and that changes in biotic and abiotic factors can have auto-amplifying effects on current CH4 dynamics.Synthesis. Changing environmental conditions will, both directly and indirectly, affect peatland processes, causing unforeseen changes in CH4 dynamics. The resilience of peatland CH4 dynamics to environmental change therefore depends on the interaction between plant community composition and microbial communities

Data from: Peatland vascular plant functional types affect methane dynamics by altering microbial community structure

1. Peatlands are natural sources of atmospheric methane (CH4), an important greenhouse gas. It is established that peatland methane dynamics are controlled by both biotic and abiotic conditions, yet the interactive effect of these drivers is less studied and consequently poorly understood. 2. Climate change affects the distribution of vascular plant functional types (PFTs) in peatlands. By removing specific PFTs, we assessed their effects on peat organic matter chemistry, microbial community composition and on potential methane production (PMP) and oxidation (PMO) in two microhabitats (lawns and hummocks). 3. Whilst PFT removal only marginally altered the peat organic matter chemistry, we observed considerable changes in microbial community structure. This resulted in altered PMP and PMO. PMP was slightly lower when graminoids were removed, whilst PMO was highest in the absence of both vascular PFTs (graminoids and ericoids), but only in the hummocks. 4. Path analyses demonstrate that different plant–soil interactions drive PMP and PMO in peatlands and that changes in biotic and abiotic factors can have auto-amplifying effects on current CH4 dynamics. 5. Synthesis. Changing environmental conditions will, both directly and indirectly, affect peatland processes, causing unforeseen changes in CH4 dynamics. The resilience of peatland CH4 dynamics to environmental change therefore depends on the interaction between plant community composition and microbial communities

Ecosystem respiration

To asses the effect of vascular plant removal in aforementioned experiment, one year after the start of the experiment, we measured carbon dioxide respiration rates on 10 cm diameter collars using an automated soil CO2 flux system (LI-8100, LI-COR Biosciences, USA). We compare the fluxes from the vascular plant removal plots with respiration rates from comparable areas in the control plots with little or no vascular plant cover, and assessed the relationship with the amount of removed biomass