The value of good Biozzi antibody-producing strains of mice for the production of monoclonal antibodies]

We report here that using Biozzi's high and low responder strains of Mice in the preparation of monoclonal antibodies against human T lymphocytes, we observed with the high responder strain 1) a higher number of hybrids; 2) a huge increase in the proportion of hybrids secreting on antibody directed against human lymphocytes.     

Suppressor effects and cyclic AMP accumulation by the CD29 molecule of CD4+ lymphocytes

Integrins are a superfamily of related molecules whose function, where known, is to mediate adhesion. The so-called very-late-activation antigen (VLA) family includes at least five distinct heterodimers, each composed of a unique alpha-subunit non-covalently associated with a common beta-subunit. Several members of the family have been shown to bind extracellular matrix proteins, but the function of VLA-4 is so far unknown. VLA-4 is the only member of the family detected on thymocytes and resting T cells. We show here that an antibody which recognizes the beta-subunit of VLA-4 (CD29) on T cells can inhibit CD4+ cell proliferation triggered by CD2 or CD3, and that binding of this antibody to activated T cells leads to an increase in cyclic AMP levels which is comparable to that elicited by forskolin. These negative signalling effects are unique to this antibody: other CD29 antibodies do not affect the growth of activated CD4 cells but enhance the proliferation of whole T cell populations and abrogate the suppressive effects of mitomycin-treated CD8 cells on CD4-cell growth. Taken together, our results indicate that VLA-4 functions in cell-cell interactions and that it is the target for the suppressive effects of CD8 cells on CD4 cells.     

Perpendicular switching of a single ferromagnetic layer induced by in-plane current injection

Modern computing technology is based on writing, storing and retrieving information encoded as magnetic bits. Although the giant magnetoresistance effect has improved the electrical read out of memory elements, magnetic writing remains the object of major research efforts. Despite several reports of methods to reverse the polarity of nanosized magnets by means of local electric fields and currents, the simple reversal of a high-coercivity, single-layer ferromagnet remains a challenge. Materials with large coercivity and perpendicular magnetic anisotropy represent the mainstay of data storage media, owing to their ability to retain a stable magnetization state over long periods of time and their amenability to miniaturization. However, the same anisotropy properties that make a material attractive for storage also make it hard to write to. Here we demonstrate switching of a perpendicularly magnetized cobalt dot driven by in-plane current injection at room temperature. Our device is composed of a thin cobalt layer with strong perpendicular anisotropy and Rashba interaction induced by asymmetric platinum and AlOx interface layers. The effective switching field is orthogonal to the direction of the magnetization and to the Rashba field. The symmetry of the switching field is consistent with the spin accumulation induced by the Rashba interaction and the spin-dependent mobility observed in non-magnetic semiconductors, as well as with the torque induced by the spin Hall effect in the platinum layer. Our measurements indicate that the switching efficiency increases with the magnetic anisotropy of the cobalt layer and the oxidation of the aluminium layer, which is uppermost, suggesting that the Rashba interaction has a key role in the reversal mechanism. To prove the potential of in-plane current switching for spintronic applications, we construct a reprogrammable magnetic switch that can be integrated into non-volatile memory and logic architectures. This device is simple, scalable and compatible with present-day magnetic recording technology.     

Inclusive fitness theory and eusociality

Arising from M. A. Nowak, C. E. Tarnita & E. O. Wilson 466, 1057-1062 (2010); Nowak et al. reply. Nowak et al. argue that inclusive fitness theory has been of little value in explaining the natural world, and that it has led to negligible progress in explaining the evolution of eusociality. However, we believe that their arguments are based upon a misunderstanding of evolutionary theory and a misrepresentation of the empirical literature. We will focus our comments on three general issues.     

Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B

Members of the killer cell immunoglobulin-like receptor (KIR) family, a large group of polymorphic receptors expressed on natural killer (NK) cells, recognize particular peptide-laden human leukocyte antigen (pHLA) class I molecules and have a pivotal role in innate immune responses. Allelic variation and extensive polymorphism within the three-domain KIR family (KIR3D, domains D0-D1-D2) affects pHLA binding specificity and is linked to the control of viral replication and the treatment outcome of certain haematological malignancies. Here we describe the structure of a human KIR3DL1 receptor bound to HLA-B*5701 complexed with a self-peptide. KIR3DL1 clamped around the carboxy-terminal end of the HLA-B*5701 antigen-binding cleft, resulting in two discontinuous footprints on the pHLA. First, the D0 domain, a distinguishing feature of the KIR3D family, extended towards β2-microglobulin and abutted a region of the HLA molecule with limited polymorphism, thereby acting as an 'innate HLA sensor' domain. Second, whereas the D2-HLA-B*5701 interface exhibited a high degree of complementarity, the D1-pHLA-B*5701 contacts were suboptimal and accommodated a degree of sequence variation both within the peptide and the polymorphic region of the HLA molecule. Although the two-domain KIR (KIR2D) and KIR3DL1 docked similarly onto HLA-C and HLA-B respectively, the corresponding D1-mediated interactions differed markedly, thereby providing insight into the specificity of KIR3DL1 for discrete HLA-A and HLA-B allotypes. Collectively, in association with extensive mutagenesis studies at the KIR3DL1-pHLA-B*5701 interface, we provide a framework for understanding the intricate interplay between peptide variability, KIR3D and HLA polymorphism in determining the specificity requirements of this essential innate interaction that is conserved across primate species.     

Attributing physical and biological impacts to anthropogenic climate change

Significant changes in physical and biological systems are occurring on all continents and in most oceans, with a concentration of available data in Europe and North America. Most of these changes are in the direction expected with warming temperature. Here we show that these changes in natural systems since at least 1970 are occurring in regions of observed temperature increases, and that these temperature increases at continental scales cannot be explained by natural climate variations alone. Given the conclusions from the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report that most of the observed increase in global average temperatures since the mid-twentieth century is very likely to be due to the observed increase in anthropogenic greenhouse gas concentrations, and furthermore that it is likely that there has been significant anthropogenic warming over the past 50 years averaged over each continent except Antarctica, we conclude that anthropogenic climate change is having a significant impact on physical and biological systems globally and in some continents.     

The Polycomb group protein EZH2 directly controls DNA methylation

The establishment and maintenance of epigenetic gene silencing is fundamental to cell determination and function. The essential epigenetic systems involved in heritable repression of gene activity are the Polycomb group (PcG) proteins and the DNA methylation systems. Here we show that the corresponding silencing pathways are mechanistically linked. We find that the PcG protein EZH2 (Enhancer of Zeste homolog 2) interacts-within the context of the Polycomb repressive complexes 2 and 3 (PRC2/3)-with DNA methyltransferases (DNMTs) and associates with DNMT activity in vivo. Chromatin immunoprecipitations indicate that binding of DNMTs to several EZH2-repressed genes depends on the presence of EZH2. Furthermore, we show by bisulphite genomic sequencing that EZH2 is required for DNA methylation of EZH2-target promoters. Our results suggest that EZH2 serves as a recruitment platform for DNA methyltransferases, thus highlighting a previously unrecognized direct connection between two key epigenetic repression systems.