The contribution of organizational culture,structure, and leadership factors in the digital transformation of SMEs: a mixed-methods approach

Cognition, Technology & Work - Contributing to the scarce literature on how companies can deal with their business model of digital transition, this work explores the digital transformation...     

Exposing bugs in JavaScript engines through test transplantation and differential testing

Software Quality Journal - JavaScript is a popular programming language today with several implementations competing for market dominance. Although a specification document and a conformance test...     

Zinc use efficiency of maize-wheat cropping after inoculation with Azospirillum brasilense

Nutrient Cycling in Agroecosystems - Sustainable zinc (Zn) management strategies are needed to improve cereal yield production, particularly under tropical savannah conditions. Inoculation with...     

A Germline-Encoded Structural Arginine Trap Underlies the Anti-DNA Reactivity of a Murine V Gene Segment

Autoimmunity may have its origins of early repertoire selection in developmental B cells. Such a primary repertoire is probably shaped by selecting B cells that can efficiently perform productive signaling, stimulated by self-antigens in the bone marrow, such as DNA. In support of that idea, we previously found a V segment from V_H10 family that can form antibodies that bind to DNA independent of CDR3 usage. In this paper we designed four antibody fragments in a novel single-chain pre-BCR (scpre-BCR) format containing germinal V gene segments from families known to bind DNA (V_H10) or not (V_H4) connected to a murine surrogate light chain (SLC), lacking the highly charged unique region (UR), by a hydrophilic peptide linker. We also tested the influence of CDR2 on DNA reactivity by shuffling the CDR2 loop. The scpre-BCRs were expressed in bacteria. V_H10 bearing scpre-BCR could bind DNA, while scpre-BCR carrying the V_H4 segment did not. The CDR2 loop shuffling hampered V_H10 reactivity while displaying a gain-of-function in the nonbinding V_H4 germline. We modeled the binding sites demonstrating the conservation of a positivity charged pocket in the V_H10 CDR2 as the possible cross-reactive structural element. We presented evidence of DNA reactivity hardwired in a V gene, suggesting a structural mechanism for innate autoreactivity. Therefore, while autoreactivity to DNA can lead to autoimmunity, efficiently signaling for B cell development is likely a trade-off mechanism leading to the selection of potentially autoreactive repertoires.