Do ELF magnetic fields affect human reaction time?

Two double-blind studies were run in an attempt to confirm the finding that a 0.2 Hz magnetic field affects simple reaction time (RT) in humans, whereas a 0.1 Hz field does not. In the first experiment, 12 volunteer subjects were exposed to a continuous 0.2 Hz, 0.1 Hz, or sham field in a fully counter-balanced, within-subjects design. Subjects were run singly for one condition each day over 3 consecutive days with a field strength of 1.1 mT and a daily exposure duration of 5 min. Neither magnetic field had any effect on RT at any time during the exposure. One condition of a second study, using a new group of 24 volunteer subjects, also failed to find any field effects at 0.2 Hz. Additionally, the second study failed to show any effects when the frequency, flux density, and field orientation were set according to parametric resonance theory. It is suggested that, although ELF magnetic field effects on human behaviour may be elusive, future research can improve detection rates by paying greater attention to reducing error variance and increasing statistical power. © 1995 Wiley-Liss, Inc.     

A Redescription of Calicotyle australis Johnston, 1934 (Monogenea: Monocotylidae) from the Type-host Trygonorrhina Fasciata (Rhinobatidae) off Adelaide, South Australia, Including Descriptions of Live and Silver Stained Larvae

Calicotyle australis Johnston, 1934 (Monogenea Monxocotylidae) is redescribed from the cloaca of the type-host, the southern fiddler ray Trygonorrhina fasciata (Rhinobatidae) off Adelaide, South Australia. Lobed glands joining the oötype are reported for the first time and may be characteristic of the genus. The presence of an appendix associated with the seminal vesicle in C. australis, previously reported as absent, is confirmed. The anatomy of the oncomiracidium of C. australis is described from observations of live larvae, and the number and distribution of ciliated epidermal cells and sensilla, revealed by silver staining larvae, is also described. Use of larval characters to distinguish between species of Calicotyle Diesing, 1850 and other closely related monocotylids is discussed.     

High-frequency network oscillations in cerebellar cortex

Both cerebellum and neocortex receive input from the somatosensory system. Interaction between these regions has been proposed to underpin the correct selection and execution of motor commands, but it is not clear how such interactions occur. In neocortex, inputs give rise to population rhythms, providing a spatiotemporal coding strategy for inputs and consequent outputs. Here, we show that similar patterns of rhythm generation occur in cerebellum during nicotinic receptor subtype activation. Both gamma oscillations (30-80 Hz) and very fast oscillations (VFOs, 80-160 Hz) were generated by intrinsic cerebellar cortical circuitry in the absence of functional glutamatergic connections. As in neocortex, gamma rhythms were dependent on GABA(A) receptor-mediated inhibition, whereas VFOs required only nonsynaptically connected intercellular networks. The ability of cerebellar cortex to generate population rhythms within the same frequency bands as neocortex suggests that they act as a common spatiotemporal code within which corticocerebellar dialog may occur.     

Substrate binding and C-H bond activation in the soluble methane monooxygenase hydroxylase

 The selective oxidation of CH₄ to CH₃OH is a conceptually simple, yet functionally difficult, chemical transformation. In nature, this reaction is performed by methane monooxygenases, the soluble class of which employ carboxylate-bridged dinuclear iron centers to activate dioxygen. The process by which small molecules access the active site of the sMMO hydroxylase, the structures of intermediates in the catalytic reaction cycle, and mechanistic details about the attack on the C–H bond are subjects of intense investigation. In this commentary, we present our current views on exogenous ligand binding and dioxygen activation at the active site and the mechanism of alkane hydroxylation. Received: 20 October 1997 / Accepted: 26 February 1998     

Specific amino acid residues in the second hypervariable region of HLA-DQA1 and DQB1 chain genes promote the Ro (SS-A)/La (SS-B) autoantibody responses

In order to define the HLA-DR and DQ alleles, as well as the specific DQA1 and DQB1 chain genes involved in the anti-Ro/La autoantibody responses, RFLP analysis and sequence-specific oligonucleotide typing was carried out on 58 Caucasians and 48 American blacks with SLE or Sj?gren's syndrome and anti-Ro antibodies. Among both Caucasian and black patients, the highest relative risk for the anti-Ro response (both with and without accompanying anti-La) was conferred by heterozygosity for the DQw2.1 (in linkage disequilibrium with HLA-DR3) and DQw6 (a subtype of DQw1) alleles compared with either 269 normal race-matched controls or 80 anti-Ro negative SLE/Sj?gren's syndrome patients. Analysis of individual DQA1 and DQB1 chain alleles revealed that DQA1*0501 and DQB1*0201 were most frequent, followed by DQA1 and DQB1 alleles comprising DQw6. In patients not possessing DQw2.1 and/or DQw6 alleles, HLA-DQB1*0302 and HLA-DQA1*0401 (especially in blacks) were significantly increased. Nucleotide sequence analysis of these associated alleles showed that 100% of patients with anti-Ro had a glutamine residue at position 34 of the outermost domain of the DQA1 chain and/or a leucine at position 26 of the outermost domain of the DQB1 chain. Patients with anti-Ro plus La were more likely to have all four of their DQA1/DQB1 chains containing these amino acid residues than either anti-Ro-negative SLE patients or controls. These data implicate specific amino acid residues on both DQA1 and DQB1 chains located in the floor of the Ag binding cleft of the HLA-DQA1:B1 heterodimer and further suggest a role for "gene dosage" in the anti-Ro (+/- La) autoantibody response.     

Mechanistic inferences from the binding of ligands to LpxC, a metal-dependent deacetylase

The metal-dependent deacetylase LpxC catalyzes the first committed step of lipid A biosynthesis in Gram-negative bacteria. Accordingly, LpxC is an attractive target for the development of inhibitors that may serve as potential new antibiotics for the treatment of Gram-negative bacterial infections. Here, we report the 2.7 A resolution X-ray crystal structure of LpxC complexed with the substrate analogue inhibitor TU-514 and the 2.0 A resolution structure of LpxC complexed with imidazole. The X-ray crystal structure of LpxC complexed with TU-514 allows for a detailed examination of the coordination geometry of the catalytic zinc ion and other enzyme-inhibitor interactions in the active site. The hydroxamate group of TU-514 forms a bidentate chelate complex with the zinc ion and makes hydrogen bond interactions with conserved active site residues E78, H265, and T191. The inhibitor C-4 hydroxyl group makes direct hydrogen bond interactions with E197 and H58. Finally, the C-3 myristate moiety of the inhibitor binds in the hydrophobic tunnel of the active site. These intermolecular interactions provide a foundation for understanding structural aspects of enzyme-substrate and enzyme-inhibitor affinity. Comparison of the TU-514 complex with cacodylate and imidazole complexes suggests a possible substrate diphosphate binding site and highlights residues that may stabilize the tetrahedral intermediate and its flanking transition states in catalysis. Evidence of a catalytic zinc ion in the native zinc enzyme coordinated by H79, H238, D242, and two water molecules with square pyramidal geometry is also presented. These results suggest that the native state of this metallohydrolase may contain a pentacoordinate zinc ion, which contrasts with the native states of archetypical zinc hydrolases such as thermolysin and carboxypeptidase A.     

Twitching motility is essential for virulence in Dichelobacter nodosus

Type IV fimbriae are essential virulence factors of Dichelobacter nodosus, the principal causative agent of ovine foot rot. The fimA fimbrial subunit gene is required for virulence, but fimA mutants exhibit several phenotypic changes and it is not certain if the effects on virulence result from the loss of type IV fimbria-mediated twitching motility, cell adherence, or reduced protease secretion. We showed that mutation of either the pilT or pilU gene eliminated the ability to carry out twitching motility. However, the pilT mutants displayed decreased adhesion to epithelial cells and reduced protease secretion, whereas the pilU mutants had wild-type levels of extracellular protease secretion and adherence. These data provided evidence that PilT is required for the type IV fimbria-dependent protease secretion pathway in D. nodosus. It was postulated that sufficient fimbrial retraction must occur in the pilU mutants to allow protease secretion, but not twitching motility, to take place. Although no cell movement was detected in a pilU mutant of D. nodosus, aberrant motion was detected in an equivalent mutant of Pseudomonas aeruginosa. These observations explain how in D. nodosus protease secretion can occur in a pilU mutant but not in a pilT mutant. In addition, virulence studies with sheep showed that both the pilT and pilU mutants were avirulent, providing evidence that mutation of the type IV fimbrial system affects virulence by eliminating twitching motility, not by altering cell adherence or protease secretion.