Experimental approaches for the identi®cation of functionally important regions on the surface of a protein involve mutagenesis, in which exposed residues are replaced one after another while the change in binding to other proteins or changes in activity are recorded. However, practical considerations limit the use of these methods to small-scale studies, precluding a full mapping of all the functionally important residues on the surface of a protein. We present here an alternative approach involving the use of evolutionary data in the form of multiple-sequence alignment for a protein family to identify hot spots and surface patches that are likely to be in contact with other proteins, domains, peptides, DNA, RNA or ligands. The underlying assumption in this approach is that key residues that are important for binding should be conserved throughout evolution, just like residues that are crucial for maintaining the protein fold, i.e. buried residues. A main limitation in the implementation of this approach is that the sequence space of a protein family may be unevenly sampled, e.g. mammals may be overly represented. Thus, a seemingly conserved position in the alignment may re¯ect a taxonomically uneven sampling, rather than being indicative of structural or functional importance. To avoid this problem, we present here a novel methodology based on evolutionary relations among proteins as revealed by inferred phylogenetic trees, and demonstrate its capabilities for mapping binding sites in SH2 and PTB signaling domains. A computer program that implements these ideas is available freely at: http://ashtoret.tau.ac.il/ $ rony

Abstract:The public communication of science and technology largely depends on its framing in the news media but scientists' role in this process has only been explored indirectly. This study focuses on storied accounts told by scientists when asked to present their research or provide expert advice in the course of a news interview. 150 items from a current affairs talk show broadcast in the Israeli media were explored through a methodology combining narrative and conversation analysis. Using the concept of framing as originally proposed by Goffman (1974) we show that researchers use personal accounts as a way of reframing news stories introduced by the program hosts. Elements of method and rationale, which are usually considered technical and are shunned in journalistic reports, emerged as a crucial element in the accounts that experts themselves provide. The implications for framing research and science communication training are discussed.http://mc.manuscriptcentral.com/PSCIENCE The public communication of science and technology largely depends on its framing in the news media but scientists' role in this process has only been explored indirectly. This study focuses on storied accounts told by scientists when asked to present their research or provide expert advice in the course of a news interview. 150 items from a current affairs talk show broadcast in the Israeli media were explored through a methodology combining narrative and conversation analysis. Using the concept of framing as originally proposed by Goffman (1974) we show that researchers use personal accounts as a way of reframing news stories introduced by the program hosts. Elements of method and rationale, which are usually considered technical and are shunned in journalistic reports, emerged as a crucial element in the accounts that experts themselves provide. The implications for framing research and science communication training are discussed.

Metaphor use is shown to respond to the interactional context and participants' roles in communicating the topic reported.

The news media form major sources of information to the general public in matters of science and health. And yet journalists and experts differ in what they consider as newsworthy and relevant. This article analyses in detail a current affair interview with a health expert reporting on a new research on attention deficit hyperactivity disorder (ADHD). Applying Bamberg’s three-level model for positioning analysis, the interview is searched for the stories that speakers introduce, attend to their embedding in the design of questions and answers and examine how their tellers are positioned therein as knowledgeable regarding ADHD. The narratives identified are shown to enable the adopting and shifting between various expert positions including that of the scientific researcher, the advice-giving expert and the more specific identity of the public health clinician. Shifts between these positions are shown to reflect the claims and counter-claims that the interviewee and interviewers are making and backing. These findings are discussed for their implications regarding the use of narratives in presenting science to media audiences.

The discovery by Hans Spemann of the "organizer" tissue and its ability to induce the formation of the amphibian embryo's neural tube inspired leading embryologists to attempt to elucidate embryonic inductions' underlying mechanism. Joseph Needham, who during the 1930s conducted research in biochemical embryology, proposed that embryonic induction is mediated by a specific chemical entity embedded in the inducing tissue, surmising that chemical to be a hormone of sterol-like structure. Along with embryologist Conrad H. Waddington, they conducted research aimed at the isolation and functional characterization of the underlying agent. As historians clearly pointed out, embryologists came to question Needham's biochemical approach; he failed to locate the hormone he sought and eventually abandoned his quest. Yet, this study finds that the difficulties he ran into resulted primarily from the limited conditions for conducting his experiments at his institute. In addition, Needham's research reflected the interests of leading biochemists in hormone and cancer research, because it offered novel theoretical models and experimental methods for engaging with the function of the hormones and carcinogens they isolated. Needham and Waddington were deterred neither by the mounting challenges nor by the limited experimental infrastructure. Like their colleagues in hormone and cancer research, they anticipated difficulties in attempting to establish causal links between complex biological phenomena and simple chemical triggering.

During the 1920s, concerns over occupational cancers in the tar, coal-gas and synthetic dye industries stimulated investigations into the responsible carcinogenic agents. Chemical pathologist Ernest L. Kennaway and organic chemist James W. Cook at London's Cancer Hospital Research Institute were the first to identify pure carcinogenic coal-tar polyaromatic hydrocarbons. Cook, who joined Kennaway in 1929, synthesised and tested hundreds of compounds, seeking to identify the exact relationship between chemical constitution and cancer. This paper reviews Cook's research programme until the early 1940s, and the attempt of his collaborator, Cambridge biochemist Joseph Needham, to identify the biological basis of carcinogenesis. In this, they drew upon structural and functional analogies between recently discovered hormones and carcinogens. Cook established novel ways of studying chemical carcinogenesis, although conflicting empirical results and understandings of cancerous growth militated against the development of a coherent mechanistic theory.

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