Src Binds Cortactin Through An Sh2 Domain Cystine-Mediated Linkage

Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions

Application of Hansch’s Model to Capsaicinoids and Capsinoids: A Study Using the Quantitative Structure−Activity Relationship. A Novel Method for the Synthesis of Capsinoids

We describe a synthetic approach for two families of compounds, the capsaicinoids and capsinoids, as part of a study of the quantitative relationship between structure and activity

Chemical Properties of Element 105 in Aqueous Solution: Halide Complex Formation and Anion Exchange into Triisoctyl Amine

Studies of the halide complexation of element 105 in aqueous solution were performed on 34-s 262Ha produced in the 249Bk(18-O,5n) reaction. The 262Ha was detected by measuring the fission and alpha activities associated with its decay and the alpha decays of its daughter, 4.3-s 258Lr. Time-correlated pairs of parent and daughter alpha particles provided a unique identification of the presence of 262Ha. About 1600 anion exchange separations of 262Ha from HCl and mixed HC1/HF solutions were performed on a one-minute time scale. Reversed-phase micro-chromatographic columns incorporating triisooctyl amine (TIOA) on an inert support were used in the computer-controlled liquid chromatography apparatus, ARCA II. 262Ha was shown to be adsorbed on the column from either 12 M HCl/0.02 M HF or 10 M HCl solutions like its homologs Nb and Ta, and like Pa. In elutions with 4 M HCl/0.02 M HF (Pa-Nb fraction), and with 6 M HNO3/O.OI5 M HF (Ta fraction), the 262Ha activity was found in the Pa-Nb fraction showing that the anionic halide complexes are different from those of Ta, and are more like those of Nb and Pa. In separate elutions with 10 M HCl/0.025 M HF (Pa fraction) and 6 M HN03/0.015 M HF (stripping of Nb) the 262Ha was found to be equally divided between the Pa and Nb fractions. The non-tantalum like halide complexation of Ha is indicative of the formation of oxohalide or hydroxohalide complexes, like [NbOCU]" and [PaOCl4] or [Pa(OH)2Cl4]", at least for intermediate HCl concentrations, in contrast to the pure halide complexes in Ta, like [TaCl6]-

Have we seen the geneticisation of society? Expectations and evidence

Abby Lippman’s geneticization thesis, of the early 1990s, argued and anticipated that with the rise of genetics, increasing areas of social and health related activities would come to be understood and defined in genetic terms leading to major changes in society, medicine and health care. We review the considerable literature on geneticization and consider how the concept stands both theoretically and empirically across scientific, clinical, popular and lay discourse and practice. Social science scholarship indicates that relatively little of the original claim of the geneticization thesis has been realised, highlighting the development of more complex and dynamic accounts of disease in scientific discourse and the complexity of relationships between bioscientific, clinical and lay understandings. This scholarship represents a shift in social science understandings of the processes of sociotechnical change, which have moved from rather simplistic linear models to an appreciation of disease categories as multiply understood. Despite these shifts, we argue that a genetic imaginary persists, which plays a performative role in driving investments in new gene-based developments. Understanding the enduring power of this genetic imaginary and its consequences remains a key task for the social sciences, one which treats ongoing genetic expectations and predictions in a sceptical yet open way

Electrochemical half-reaction-assisted sub-bandgap photon sensing in a graphene hybrid phsotodetector

The photogating effect has been previously utilized to realize ultra-high photoresponsivity in a semiconductor-graphene hybrid photodetector. However, the spectral response of the graphene hybrid photodetector was limited by the bandgap of the incorporated semiconductor, which partially compromised the broadband absorption of graphene. Here, we show that this limitation can be overcome in principle by harnessing the electron-accepting ability of the electrochemical half-reaction. In our new graphene phototransistor, the electrochemical half-reaction serves as an effective reversible electron reservoir to accept the photoexcited hot electron from graphene, which promotes the sub-bandgap photosensitivity in a silver chloride (AgCl)-graphene photodetector. The photoconductive gain of ~ 3 × 109 electrons per photon in the AgCl-graphene hybrid is favored by the long lifetime of photoexcited carriers in the chemically reversible redox couple of AgCl/Ag0, enabling a significant visible light (400–600 nm) responsivity that is far beyond the band-edge absorption of AgCl. This work not only presents a new strategy to achieve an electrically tunable sub-bandgap photoresponse in semiconductor-graphene heterostructures but also provides opportunities for utilizing the electrochemical half reaction in other two-dimensional systems and optoelectronic devices.published_or_final_versio