Biophysical Properties of the Alternative Ion Permeation Pore in TRPM3

Innate immune responses to pathogens are driven by co-presentation of multiple pathogen-associated molecular patterns (PAMPs). Combinations of PAMPs can trigger synergistic immune responses, but the underlying molecular mechanisms of synergy are poorly understood. Here, we used synthetic particulate carriers co-loaded with monophosphoryl lipid A (MPLA) and CpG as pathogen-like particles (PLPs) to dissect the signaling pathways responsible for dual adjuvant immune responses. PLP-based co-delivery of MPLA and CpG to GM-CSF–driven mouse bone marrow–derived antigen-presenting cells (BM-APCs) elicited synergistic interferon-β (IFN-β) and interleukin-12p70 (IL-12p70) responses, which were strongly influenced by the biophysical properties of PLPs. Mechanistically, we found that MyD88 and interferon regulatory factor 5 (IRF5) were necessary for IFN-β and IL-12p70 production, while TRIF signaling was required for the synergistic response. Both the kinetics and magnitude of downstream TRAF6 and IRF5 signaling drove the synergy. These results identify the key mechanisms of synergistic Toll-like receptor 4 (TLR4)–TLR9 co-signaling in mouse BM-APCs and underscore the critical role of signaling kinetics and biophysical properties on the integrated response to combination adjuvants.

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Shifts in soil and plant functional diversity along an altitudinal gradient in the French Alps

BMC Research Notes ◽

10.1186/s13104-021-05468-0 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Alexia Stokes ◽

Guillermo Angeles ◽

Fabien Anthelme ◽

Eduardo Aranda-Delgado ◽

Isabelle Barois ◽

...

Keyword(s):

Plant Community ◽

Functional Diversity ◽

Plant Communities ◽

Species Abundance ◽

Chemical Properties ◽

Water Infiltration ◽

Temperate Climate ◽

Biophysical Properties ◽

Tropical Zone ◽

Soil Microbial

Abstract Objectives Altitude integrates changes in environmental conditions that determine shifts in vegetation, including temperature, precipitation, solar radiation and edaphogenetic processes. In turn, vegetation alters soil biophysical properties through litter input, root growth, microbial and macrofaunal interactions. The belowground traits of plant communities modify soil processes in different ways, but it is not known how root traits influence soil biota at the community level. We collected data to investigate how elevation affects belowground community traits and soil microbial and faunal communities. This dataset comprises data from a temperate climate in France and a twin study was performed in a tropical zone in Mexico. Data description The paper describes soil physical and chemical properties, climatic variables, plant community composition and species abundance, plant community traits, soil microbial functional diversity and macrofaunal abundance and diversity. Data are provided for six elevations (1400–2400 m) ranging from montane forest to alpine prairie. We focused on soil biophysical properties beneath three dominant plant species that structure local vegetation. These data are useful for understanding how shifts in vegetation communities affect belowground processes, such as water infiltration, soil aggregation and carbon storage. Data will also help researchers understand how plant communities adjust to a changing climate/environment.

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Improvement of Biophysical Properties and Affinity of a Human Anti-L1CAM Therapeutic Antibody through Antibody Engineering Based on Computational Methods

International Journal of Molecular Sciences ◽

10.3390/ijms22136696 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6696

Author(s):

Heesu Chae ◽

Seulki Cho ◽

Munsik Jeong ◽

Kiyoung Kwon ◽

Dongwook Choi ◽

...

Keyword(s):

Computational Methods ◽

Human Monoclonal Antibody ◽

Antibody Engineering ◽

Antigen Binding ◽

Post Translational Modification ◽

Biophysical Properties ◽

Preclinical Development ◽

Cell Bank ◽

Aggregation Propensity

The biophysical properties of therapeutic antibodies influence their manufacturability, efficacy, and safety. To develop an anti-cancer antibody, we previously generated a human monoclonal antibody (Ab417) that specifically binds to L1 cell adhesion molecule with a high affinity, and we validated its anti-tumor activity and mechanism of action in human cholangiocarcinoma xenograft models. In the present study, we aimed to improve the biophysical properties of Ab417. We designed 20 variants of Ab417 with reduced aggregation propensity, less potential post-translational modification (PTM) motifs, and the lowest predicted immunogenicity using computational methods. Next, we constructed these variants to analyze their expression levels and antigen-binding activities. One variant (Ab612)—which contains six substitutions for reduced surface hydrophobicity, removal of PTM, and change to the germline residue—exhibited an increased expression level and antigen-binding activity compared to Ab417. In further studies, compared to Ab417, Ab612 showed improved biophysical properties, including reduced aggregation propensity, increased stability, higher purification yield, lower pI, higher affinity, and greater in vivo anti-tumor efficacy. Additionally, we generated a highly productive and stable research cell bank (RCB) and scaled up the production process to 50 L, yielding 6.6 g/L of Ab612. The RCB will be used for preclinical development of Ab612.

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