Mechanisms underlying celiac disease and its neurologic manifestations

The extra-intestinal manifestations of celiac disease (CD), including ataxia and peripheral neuropathy, are increasingly being recognized as the presenting symptoms of this autoimmune disease. Although there is a greater understanding of the pathogenesis of the intestinal lesions in CD the mechanisms behind the neurologic manifestations of CD have not been elucidated. In this article, the authors review the cellular and molecular mechanisms behind the histopathologic changes in the intestine, discuss the presentation and characteristics of neurologic manifestations of CD, review the data on the mechanisms behind these manifestations, and discuss the diagnosis and treatment of CD. Molecular mimicry and intermolecular help may play a role in the development of neurologic complications.Received 11 March 2004; received after revision 29 October 2004; accepted 12 November 2004     

A novel pattern of fast calcium oscillations points to calcium and electrical activity cross-talk in rat chromaffin cells

Slow oscillations of cytosolic calcium ion concentration – – typically originate from release by intracellular stores, but in some cell types can be triggered and sustained by Ca²⁺ influx as well. In this study we simultaneously monitored changes in and in the electrical activity of the cell membrane by combining indo-1 and patch-clamp measurements in single rat chromaffin cells. By this approach we observed a novel type of spontaneous oscillations, much faster than those previously described in these cells. These oscillations are triggered and sustained by complex electrical activity (slow action potentials and spike bursts), require Ca²⁺ influx and do not involve release from intracellular stores. The possible physiological implications of this new pathway of intracellular signalling are discussed.Received 30 July 2004; received after revision 14 October 2004; accepted 1 November 2004     

The PREPL A protein, a new member of the prolyl oligopeptidase family, lacking catalytic activity

The PREPL (previously called KIAA0436) gene encodes a putative serine peptidase from the prolyl oligopeptidase family. A chromosomal deletion involving the PREPL gene leads to a severe syndrome with multiple symptoms. Homology with oligopeptidase B suggested that the enzyme cleaves after an arginine or lysine residue. Several PREPL splice variants have been identified, and a 638-residue variant (PREPL A) was expressed in Escherichia coli and purified. Its secondary structure was similar to that of oligopeptidase B, but differential-scanning calorimetry indicated a higher conformational stability. Dimerization may account for the enhanced stability. Unexpectedly, the PREPL A protein did not cleave peptide substrates containing a P1 basic residue, but did slowly hydrolyse an activated ester substrate, and reacted with diisopropyl fluorophosphate. These results indicated that the catalytic serine is a reactive residue. However, the negligible hydrolytic activity suggests that the function of PREPL A is different from that of the other members of the prolyl oligopeptidase family.     

Why the Afshar experiment does not refute complementarity

A modified version of Young's experiment by Shahriar Afshar demonstrates that, prior to what appears to be a “which-way” measurement, an interference pattern exists. Afshar has claimed that this result constitutes a violation of the Principle of Complementarity. This paper discusses the implications of this experiment and considers how Cramer's Transactional Interpretation easily accommodates the result. It is also shown that the Afshar experiment is analogous in key respects to a spin one-half particle prepared as “spin up along x”, subjected to a nondestructive confirmation of that preparation, and post-selected in a specific state of spin along z. The terminology “which-way” or “which-slit” is critiqued; it is argued that this usage by both Afshar and his critics is misleading and has contributed to confusion surrounding the interpretation of the experiment. Nevertheless, it is concluded that Bohr would have had no more problem accounting for the Afshar result than he would in accounting for the aforementioned pre- and post-selection spin experiment, in which the particle's preparation state is confirmed by a nondestructive measurement prior to post-selection. In addition, some new inferences about the interpretation of delayed choice experiments are drawn from the analysis.     

Statistical tests on two characteristics of the shapes of cluster diagrams

A cluster diagram is a rooted planar tree that depicts the hierarchical agglomeration of objects into groups of increasing size. On the null hypothesis that at each stage of the clustering procedure all possible joins are equally probable, we derive the probability distributions for two properties of these diagrams: (1)S, the number of single objects previously ungrouped that are joined in the final stages of clustering, and (2)m _k, the number of groups ofk+1 objects that are formed during the process. Ecological applications of statistical tests for these properties are described and illustrated with data from weed communities of Saskatchewan fields.This work was supported by the Natural Sciences and Engineering Research Council of Canada.     

Programmable and autonomous computing machine made of biomolecules.

Devices that convert information from one form into another according to a definite procedure are known as automata. One such hypothetical device is the universal Turing machine, which stimulated work leading to the development of modern computers. The Turing machine and its special cases, including finite automata, operate by scanning a data tape, whose striking analogy to information-encoding biopolymers inspired several designs for molecular DNA computers. Laboratory-scale computing using DNA and human-assisted protocols has been demonstrated, but the realization of computing devices operating autonomously on the molecular scale remains rare. Here we describe a programmable finite automaton comprising DNA and DNA-manipulating enzymes that solves computational problems autonomously. The automaton's hardware consists of a restriction nuclease and ligase, the software and input are encoded by double-stranded DNA, and programming amounts to choosing appropriate software molecules. Upon mixing solutions containing these components, the automaton processes the input molecule via a cascade of restriction, hybridization and ligation cycles, producing a detectable output molecule that encodes the automaton's final state, and thus the computational result. In our implementation 1012 automata sharing the same software run independently and in parallel on inputs (which could, in principle, be distinct) in 120 microl solution at room temperature at a combined rate of 109 transitions per second with a transition fidelity greater than 99.8%, consuming less than 10-10 W.     

How 'spin ice' freezes.

The large degeneracy of states resulting from the geometrical frustration of competing interactions is an essential ingredient of important problems in fields as diverse as magnetism, protein folding and neural networks. As first explained by Pauling, geometrical frustration of proton positions is also responsible for the unusual low-temperature thermodynamics of ice and its measured 'ground state' entropy. Recent work has shown that the geometrical frustration of ice is mimicked by Dy2Ti2O7, a site-ordered magnetic material in which the spins reside on a lattice of corner-sharing tetrahedra where they form an unusual magnetic ground state known as 'spin ice'. Here we identify a cooperative spin-freezing transition leading to the spin-ice ground state in Dy2Ti2O7. This transition is associated with a very narrow range of relaxation times, and represents a new form of spin-freezing. The dynamics are analogous to those associated with the freezing of protons in ice, and they provide a means through which to study glass-like behaviour and the consequences of frustration in the limit of low disorder.