The three-dimensional structure of foot-and-mouth disease virus at 2.9 A resolution

The structure of foot-and-mouth disease virus has been determined at close to atomic resolution by X-ray diffraction without experimental phase information. The virus shows similarities with other picornaviruses but also several unique features. The canyon or pit found in other picornaviruses is absent; this has important implications for cell attachment. The most immunogenic portion of the capsid, which acts as a potent peptide vaccine, forms a disordered protrusion on the virus surface.     

The CD2 antigen associates with the T-cell antigen receptor CD3 antigen complex on the surface of human T lymphocytes

T lymphocytes can be activated by various stimuli directed either against the T-cell antigen receptor-CD3 antigen complex (Ti-CD3) or the CD2 molecule; see ref. 1 for a review. Activation signals generated by antigen binding to the antigen-specific alpha/beta heterodimer (Ti) are thought to be transduced via the invariant CD3 gamma, epsilon and delta chains, and the associated zeta and eta subunits. The physiological role of the interaction of CD2 with its homologous cell-surface associated ligand LFA-3 remains to be fully elucidated. It has been suggested that CD2 regulates an antigen-independent pathway of activation or that signals delivered via CD2 are an integral part of the antigen-specific pathway. Several recent studies have indicated a requirement for the Ti-CD3 complex in CD2 signalling. Thus, mutant T-cell lines expressing CD2, but not Ti-CD3, on the cell surface cannot be activated via the CD2 molecules. Functional interaction between the Ti-CD3 complex and the CD2 antigen suggests that these T-lymphocyte cell-surface structures are physically associated. Here we use a digitonin-based solubilization procedure to explore this possibility and show that 40% of the cell-surface CD2 molecules can be specifically co-precipitated in association with the Ti-CD3 complex.     

Identification of ϱ-antigenic determinants on the surface,of mouse T-lymphocytes

Summary A monospecific antiserum has been prepared in rabbits against purified -antigen, a 100,000 mol.wt glycoprotein found on the surface of mouse L-cells. This antiserum has been employed to demonstrate the presence of -antigenic determinants selectively on the surface of mouse T-, but not B-lymphocytes.We thank Drs A. Christopher and R. Hunt for advice during the course of these studies. This work was supported by grants from the U.S. Public Health Service and the American Cancer Society.     

Chromosome 3-linked frontotemporal dementia

Frontotemporal dementia accounts for a significant minority of all cases of presenile dementia. Many pedigrees have been described in which frontotemporal dementia is inherited as an autosomal dominant trait. Frontotemporal dementia is genetically heterogeneous with loci identified on chromosome 17 and chromosome 3. Clinical, pathological and genetic findings are described in a large Danish family in which the disease gene lies in the pericentromeric region of chromosome 3.     

Phylogenetic analyses do not support horizontal gene transfers from bacteria to vertebrates.

Horizontal gene transfer (HGT) has long been recognized as a principal force in the evolution of genomes. Genome sequences of Archaea and Bacteria have revealed the existence of genes whose similarity to loci in distantly related organisms is explained most parsimoniously by HGT events. In most multicellular organisms, such genetic fixation can occur only in the germ line. Therefore, it is notable that the publication of the human genome reports 113 incidents of direct HGT between bacteria and vertebrates, without any apparent occurrence in evolutionary intermediates, that is, non-vertebrate eukaryotes. Phylogenetic analysis arguably provides the most objective approach for determining the occurrence and directionality of HGT. Here we report a phylogenetic analysis of 28 proposed HGT genes, whose presence in the human genome had been confirmed by polymerase chain reaction (PCR). The results indicate that most putative HGT genes are present in more anciently derived eukaryotes (many such sequences available in non-vertebrate EST databases) and can be explained in terms of descent through common ancestry. They are, therefore, unlikely to be examples of direct HGT from bacteria to vertebrates.     

Polycystin-L is a calcium-regulated cation channel permeable to calcium ions.

Polycystic kidney diseases are genetic disorders in which the renal parenchyma is progressively replaced by fluid-filled cysts. Two members of the polycystin family (polycystin-1 and -2) are mutated in autosomal dominant polycystic kidney disease (ADPKD), and polycystin-L is deleted in mice with renal and retinal defects. Polycystins are membrane proteins that share significant sequence homology, especially polycystin-2 and -L (50% identity and 71% similarity). The functions of the polycystins remain unknown. Here we show that polycystin-L is a calcium-modulated nonselective cation channel that is permeable to sodium, potassium and calcium ions. Patch-clamp experiments revealed single-channel activity with a unitary conductance of 137 pS. Channel activity was substantially increased when either the extracellular or intracellular calcium-ion concentration was raised, indicating that polycystin-L may act as a transducer of calcium-mediated signalling in vivo. Its large single-channel conductance and regulation by calcium ions distinguish it from other structurally related cation channels.     

Synaptosomal adenosine triphosphatase (ATPase) inhibition by organophosphates.

Chicken spinal cord adenosine triphosphatases (both Na+, K+ stimulated and ouabain insensitive) were inhibited by tri-o-tolyl phosphate (TOTP, a neurotoxic organophosphate which is not a cholinesterase inhibitor) and mevinphos (a non-neurotoxic compound but inhibitor of cholinesterases). The inhibition was concentration and time dependent, with an initial rapid drop in activity followed by a gradual exponential decline.     

Models and perspectives on stage: remarks on Giere’s Scientific perspectivism

Ron Giere’s recent book Scientific perspectivism sets out an account of science that attempts to forge a via media between two popular extremes: absolutist, objectivist realism on the one hand, and social constructivism or skeptical anti-realism on the other. The key for Giere is to treat both scientific observation and scientific theories as perspectives, which are limited, partial, contingent, context-, agent- and purpose-dependent, and pluralism-friendly, while nonetheless world-oriented and modestly realist. Giere’s perspectivism bears significant similarity to earlier ideas of Paul Feyerabend and John Dewey. Comparing these to Giere’s work not only uncovers a consilience of ideas, but also can help to fill out Giere’s account in places where it is not fully developed, as well as helping us understand the work of these earlier authors and their continuing relevance to contemporary concerns in philosophy of science.     

What is a Definition?

According to the standard view of definition, all defined terms are mere stipulations, based on a small set of primitive terms. After a brief review of the Hilbert-Frege debate, this paper goes on to challenge the standard view in a number of ways. Examples from graph theory, for example, suggest that some key definitions stem from the way graphs are presented diagramatically and do not fit the standard view. Lakatos's account is also discussed, since he provides further examples that suggest many definitions are much more than mere convenient abbreviations. This revised version was published online in July 2006 with corrections to the Cover Date.