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Cadmium (Cd) is highly toxic to the environment and humans. Plants are capable of absorbing Cd from the soil and of transporting part of this Cd to their shoot tissues. In Arabidopsis, the plasma membrane Heavy Metal ATPase 4 (HMA4) transporter mediates Cd xylem loading for export to shoots, in addition to zinc (Zn). A recent study showed that di-Cys motifs present in the HMA4 C-terminal extension (AtHMA4c) are essential for high-affinity Zn binding and transport in planta. In this study, we have characterized the role of the AtHMA4c di-Cys motifs in Cd transport in planta and in Cd-binding in vitro. In contrast to the case for Zn, the di-Cys motifs seem to be partly dispensable for Cd transport as evidenced by limited variation in Cd accumulation in shoot tissues of hma2hma4 double mutant plants expressing native or di-Cys mutated variants of AtHMA4. Expression analysis of metal homeostasis marker genes, such as AtIRT1, excluded that maintained Cd accumulation in shoot tissues was the result of increased Cd uptake by roots. In vitro Cd-binding assays further revealed that mutating di-Cys motifs in AtHMA4c had a more limited impact on Cd-binding than it has on Zn-binding. The contributions of the AtHMA4 C-terminal domain to metal transport and binding therefore differ for Zn and Cd. Our data suggest that it is possible to identify HMA4 variants that discriminate Zn and Cd for transport.

The discovery that the non-protein coding part of human genome, dismissed as “junk DNA,” is actively transcripted and carries out crucial functions is probably one of the most important discoveries of the past decades. These transcripts are becoming the rising stars of modern biology. In this review, we have casted a new light on RNAs. We have placed these molecules in the context of life origins, evolution with a big emphasize on the “RNA networks” concept. We discuss how this view can help us to understand the global role of RNA networks in modern cells, and can change our perception of the cell biology and therapy. Finally, although high-throughput methods as well as traditional case-to-case studies have laid the groundwork for our current knowledge of transcriptomes, we would like to discuss new strategies that are better suited to uncover and tackle these integrated and complex RNA networks.

Monoclonal antibodies are playing an increasing role in both human and animal health. Different strategies of protein and chemical engineering, including humanization techniques of non-human antibodies were applied successfully to optimize clinical performances of antibodies. Despite the emergence of techniques allowing the development of fully human antibodies such as transgenic Xeno-mice, antibody humanization remains a standard procedure for therapeutic antibodies. An important prerequisite for antibody humanization requires standardized numbering methods to define precisely complementary determining regions (CDR), frameworks and residues from the light and heavy chains that affect the binding affinity and/or specificity of the antibody-antigen interaction. The recently generated deep-sequencing data and the increasing number of solved three-dimensional structures of antibodies from human and non-human origins have led to the emergence of numerous databases. However, these different databases use different numbering conventions and CDR definitions. In addition, the large fluctuation of the variable chain lengths, especially in CDR3 of heavy chains (CDRH3), hardly complicates the comparison and analysis of antibody sequences and the identification of the antigen binding residues. This review compares and discusses the different numbering schemes and “CDR” definition that were established up to date. Furthermore, it summarizes concepts and strategies used for numbering residues of antibodies and CDR residues identification. Finally, it discusses the importance of specific sets of residues in the binding affinity and/or specificity of immunoglobulins.