The light chain but not the heavy chain of botulinum A toxin inhibits exocytosis from permeabilized adrenal chromaffin cells

The heavy and light chains of botulinum A toxin were separated by anion exchange chromatography. Their intracellular actions were studied using bovine adrenal chromaffin cells permeabilized with streptolysin O. Purified light chain inhibited the Ca2+-stimulated [3H]noradrenaline release with a half-maximal effect at about 1.8 nM. The inhibition was incomplete. Heavy chain up to 28 nM was neither effective by itself nor did it enhance the inhibitory effect of light chain. It is concluded that the light chain of botulinum A toxin contains the functional domain responsible for the inhibition of exocytosis

Amylase release from streptolysin O-permeabilized pancreatic acinar cells. Effects of Ca2+, guanosine 5'-[gamma-thio]triphosphate, cyclic AMP, tetanus toxin and botulinum A toxin

The molecular requirements for amylase release and the intracellular effects of botulinum A toxin and tetanus toxin on amylase release were investigated using rat pancreatic acinar cells permeabilized with streptolysin O. Micromolar concentrations of free Ca2+ evoked amylase release from these cells. Maximal release was observed in the presence of 30 microM free Ca2+. Ca(2+)-stimulated, but not basal, amylase release was enhanced by guanosine 5'-[gamma-thio]triphosphate (GTP[S]) (3-4 fold) or cyclic AMP (1.5-2 fold). Neither the two-chain forms of botulinum A toxin and tetanus toxin, under reducing conditions, nor the light chains of tetanus toxin, inhibited amylase release triggered by Ca2+, or combinations of Ca2+ + GTP[S] or Ca2+ + cAMP. The lack of inhibition was not due to inactivation of botulinum A toxin or tetanus toxin by pancreatic acinar cell proteolytic enzymes, as toxins previously incubated with permeabilized pancreatic acinar cells inhibited Ca(2+)-stimulated [3H]noradrenaline release from streptolysin O-permeabilized adrenal chromaffin cells. These data imply that clostridial neurotoxins inhibit a Ca(2+)-dependent mechanism which promotes exocytosis in neural and endocrine cells, but not in exocrine cells

The role of expertise in dynamic risk assessment: a reflection of the problem-solving strategies used by experienced fireground commanders

Although the concept of dynamic risk assessment has in recent times become more topical in the training manuals of most high risk domains, only a few empirical studies have reported how experts actually carry out this crucial task. The knowledge gap between research and practice in this area therefore calls for more empirical investigation within the naturalistic environment. In this paper, we present and discuss the problem solving strategies employed by sixteen experienced operational firefighters using a qualitative knowledge elicitation tool — the critical decision method. Findings revealed that dynamic risk assessment is not merely a process of weighing the risks of a proposed course of action against its benefits, but rather an experiential and pattern recognition process. The paper concludes by discussing the implications of designing training curriculum for the less experienced officers using the elicited expert knowledge

Exploring the functional domain and the target of the tetanus toxin light chain in neurohypophysial terminals

The tetanus toxin light chain blocks calcium induced vasopressin release from neurohypophysial nerve terminals. Here we show that histidine residue 233 within the putative zinc binding motif of the tetanus toxin light chain is essential for the inhibition of exocytosis, in the rat. The zinc chelating agent dipicolinic acid as well as captopril, an inhibitor of zinc-dependent peptidases, counteract the effect of the neurotoxin. Synthetic peptides, the sequences of which correspond to motifs present in the cytoplasmic domain of the synaptic vesicle membrane protein synaptobrevin 1 and 2, prevent the effect of the tetanus toxin light chain. Our results indicate that zinc bound to the zinc binding motif constitutes the active site of the tetanus toxin light chain. Moreover they suggest that cleavage of synaptobrevin by the neurotoxin causes the inhibition of exocytotic release of vasopressin from secretory granules

Proton spin polarizabilities from polarized Compton scattering

Polarized Compton scattering off the proton is studied within the framework of subtracted dispersion relations for photon energies up to 300 MeV. As a guideline for forthcoming experiments, we focus the attention on the role of the proton's spin polarizabilities and investigate the most favorable conditions to extract them with a minimum of model dependence. We conclude that a complete separation of the four spin polarizabilities is possible, at photon energies between threshold and the $\Delta(1232)$ region, provided one can achieve polarization measurements with an accuracy of a few percent.Comment: 26 pages, 7 figures

Next Generation Cosmology: Constraints from the Euclid Galaxy Cluster Survey

We study the characteristics of the galaxy cluster samples expected from the European Space Agency's Euclid satellite and forecast constraints on cosmological parameters describing a variety of cosmological models. The method used in this paper, based on the Fisher Matrix approach, is the same one used to provide the constraints presented in the Euclid Red Book (Laureijs et al.2011). We describe the analytical approach to compute the selection function of the photometric and spectroscopic cluster surveys. Based on the photometric selection function, we forecast the constraints on a number of cosmological parameter sets corresponding to different extensions of the standard LambdaCDM model. The dynamical evolution of dark energy will be constrained to Delta w_0=0.03 and Delta w_a=0.2 with free curvature Omega_k, resulting in a (w_0,w_a) Figure of Merit (FoM) of 291. Including the Planck CMB covariance matrix improves the constraints to Delta w_0=0.02, Delta w_a=0.07 and a FoM=802. The amplitude of primordial non-Gaussianity, parametrised by f_NL, will be constrained to \Delta f_NL ~ 6.6 for the local shape scenario, from Euclid clusters alone. Using only Euclid clusters, the growth factor parameter \gamma, which signals deviations from GR, will be constrained to Delta \gamma=0.02, and the neutrino density parameter to Delta Omega_\nu=0.0013 (or Delta \sum m_\nu=0.01). We emphasise that knowledge of the observable--mass scaling relation will be crucial to constrain cosmological parameters from a cluster catalogue. The Euclid mission will have a clear advantage in this respect, thanks to its imaging and spectroscopic capabilities that will enable internal mass calibration from weak lensing and the dynamics of cluster galaxies. This information will be further complemented by wide-area multi-wavelength external cluster surveys that will already be available when Euclid flies. [Abridged]Comment: submitted to MNRA

Dispersive magnetic excitations in the S=1 antiferromagnet Ba3_3Mn2_2O8_8

We present powder inelastic neutron scattering measurements of the S=1 dimerized antiferromagnet Ba$_3$Mn$_2$O$_8$. The $T=1.4$ K magnetic spectrum exhibits a spin-gap of $\Delta \approx 1.0$ meV and a dispersive spectrum with a bandwidth of approximately 1.5 meV. Comparison to coupled dimer models describe the dispersion and scattering intensity accurately and determine the exchange constants in Ba$_3$Mn$_2$O$_8$. The wave vector dependent scattering intensity confirms the proposed S=1 dimer bond. Temperature dependent measurements of the magnetic excitations indicate the presence of both singlet-triplet and thermally activated triplet-quintet excitations.Comment: 8 pages, 8 figures, Submitted to Physical Review B, Resubmited versio

Stable ultrahigh-density magneto-optical recordings using introduced linear defects

The stability of data bits in magnetic recording media at ultrahigh densities is compromised by thermal `flips' -- magnetic spin reversals -- of nano-sized spin domains, which erase the stored information. Media that are magnetized perpendicular to the plane of the film, such as ultrathin cobalt films or multilayered structures, are more stable against thermal self-erasure than conventional memory devices. In this context, magneto-optical memories seem particularly promising for ultrahigh-density recording on portable disks, and bit densities of $\sim$100 Gbit inch$^{-2}$ have been demonstrated using recent advances in the bit writing and reading techniques. But the roughness and mobility of the magnetic domain walls prevents closer packing of the magnetic bits, and therefore presents a challenge to reaching even higher bit densities. Here we report that the strain imposed by a linear defect in a magnetic thin film can smooth rough domain walls over regions hundreds of micrometers in size, and halt their motion. A scaling analysis of this process, based on the generic physics of disorder-controlled elastic lines, points to a simple way by which magnetic media might be prepared that can store data at densities in excess of 1 Tbit inch$^{-2}$.Comment: 5 pages, 4 figures, see also an article in TRN News at http://www.trnmag.com/Stories/041801/Defects_boost_disc_capacity_041801.htm

Melting of the Na layers in solid Na0.8CoO2

Data of 23Na NMR spectra- and relaxation measurements are interpreted as suggesting that, upon increasing temperature the Na layers in Na0.8CoO2 adopt a 2D liquid state at T=291 K. The corresponding first order phase transition is preceded by a rapidly increasing mobility and diffusion of Na ions above 200K. Above 291 K the 23Na NMR response is similar to that previously observed in superionic conductors with planar Na layers.Comment: 4 pages, 4 figure