Clearance-inducing antibodies are responsible for protection against the acute phase of Trypanosoma cruzi infection in mice

Light chain deposition disease is a severe complication of certain immunoproliferative disorders, due to the secretion of a monoclonal light chain which precipitates close to basement membranes of several tissues. A kappa isotype restriction and an unusual frequency of a variable region subgroup (VkappaIV) suggest that precise structural features govern the propensity of pathogenic light chains to precipitate in extracellular spaces. We studied primary structures of light chains from six patients with light chain deposition disease in comparison with light chains from other pathological conditions. Sequence alignment revealed the presence of certain amino acids only in light chain deposition disease, in particular non-polar replacing hydrophilic residues. To determine the role of these residues, structures of the variable domain from four kappa chains belonging to VkappaI and VkappaIV subgroups responsible for deposition disease were modeled using known immunoglobulins as templates. The most evident structural features shared by all pathogenic light chains were hydrophobic residues exposed to the solvent in complementarity determining regions 1 or 3. In contrast to immunoglobulin light chain-related amyloidosis, where deposition of organized material might be due to electrostatic interactions between light chain dimers, hydrophobic interactions could enhance amorphous precipitation in non-amyloid light chain deposition disease.     

Phenytoin blocks the reversal of a classically conditioned discriminative eyeblink response in rabbits

The aim of the present study was to assess the role of vascular alpha 1D-adrenoceptors in the sympathetic vasopressor response in vivo. Specifically, we evaluated the effect of a selective alpha 1D-adrenoceptor antagonist, BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4,5)dec ane-7,9- dione 2HCl), on the vasopressor response induced by preganglionic (T7-T9) sympathetic stimulation in the pithed rat. The vasopressor response was dose-dependently sensitive to inhibition by intravenous BMY 7378 (0.1, 0.31, 1 and 3.1 mg/kg), doses of 1 and 3.1 mg/kg being equally effective. Like BMY 7378, 5-methylurapidil (0.1, 0.31, 1 and 3.1 mg/kg) antagonized the vasopressor response to spinal stimulation; doses of 1 and 3.1 mg/kg were also equally effective. In combination experiments, BMY 7378 (1 mg/kg, i.v.) and the alpha 1A-adrenoceptor antagonist, 5-methylurapidil (1 mg/kg, i.v.), showed an additive effect. The present results demonstrate that the alpha 1D-adrenoceptor subtype plays an important role in the pressor response to sympathetic nerve stimulation in the pithed rat, and confirm the participation of the alpha 1A-adrenoceptor subtype in the same response.     

Aggregation-linked kinetic heterogeneity in bovine cardiac myosin subfragment 1

Studies of the cardiac myosin fragment 1 concentration dependence of the rate constants for adenosine 5'-triphosphate (ATP) binding and steady-state hydrolysis reveal that the observed rate constants are remarkably dependent on the protein concentration. The kinetics for ATP binding are biphasic, and both the fast- and slow-phase rate constants and the respective fractions of fast and slow material vary as a function of protein concentration. Two different types of kinetic experiments were conducted, one in which the ATP concentration was fixed but the subfragment 1 concentration was varied and another for which the ATP/subfragment 1 ratio was fixed but both concentrations were varied. The results of these two experiments on cardiac subfragment 1 are consistent with an ATP-dependent reversible aggregation. Light-scattering experiments confirm the presence of this aggregation and the ATP dependence. Similar studies on rabbit skeletal subfragment 1 give monophasic, protein-independent kinetics consistent with a monomeric species in solution. a simple monomer--dimer mechanism can account for the cardiac subfragment 1 kinetic results when changes in tryptophan fluorescence are used. However, the light-scattering results show that cardiac myosin subfragment 1 undergoes multiple reversible molecular weight changes in solution and may be tetrameric at high concentrations.     

A study of the interaction between a propagating crack and an uncoated/coated elastic inclusion using the BE technique

The purpose of the present work is a parametrical study of the interaction between a propagating edge-crack and an embedded elastic fibre using the Boundary Element (BE) technique. Uniaxial fibre reinforced composites generally have very good properties in the direction of the fibres, but in conventional multi-layer crossply laminates it is cracking in the transverse direction which effectively limits the strength of a stressed body. Therefore, in this study the propagation of a crack in the transverse direction is considered, i.e., in a plane containing the fibre axes, rather than perpendicular to the fibres. Crack deflection/attraction mechanisms and their associated energy release rate variations are investigated for a range of Young's moduli and Poisson's ratio mismatches, and crack offsets with respect to the inclusion centreline. Furthermore, the effects of a third-phase, i.e., coating, applied to the fibre's surface are analysed, and results have been obtained for different coating thicknesses and elastic moduli ratios. From this investigation it was found that the Poisson's ratio of the different phases could have a significant effect on the crack trajectory, and hence the energetics involved in the process of crack deflection are also dramatically altered. This opens up the possibility of enhancing the fracture toughness of fibre reinforced composite materials by considering the Poisson's ratio of the individual phases when selecting the particular material combination.     

Compatible cell connections for multifamily dynamic logic gates

Dynamic logic is an alternative way of making logic circuit cells and numerous techniques have been developed to take advantage of its unique characteristics. Particularly, techniques such as the true-single-phase-clock (TSPC) have been used very successfully for fast and low-power applications. However one cannot synthesize dynamic logic gates with the same ease as static gates. One reason is there are no simple rules to connect the many circuit types of dynamic gates to static gates. This paper addresses the problem of finding connection rules for a given set of gate types. The fundamental cell circuit types for dynamic logic gates are analyzed first together with static logic gates. A common set of principles of operation and connections is then identified and later applied to discover which are the feasible connections between cell circuit types identified.     

Role of acoustic striae in hearing: discrimination of sound-source elevation

After years of systematic experimentation, we finally uncovered one thing the dorsal system contributes to hearing which the ventral system may not -- the mechanism for orienting to an elevated sound source [Sutherland, D.P., Masterton, R.B., Glendenning, K.K. (1998) Behav. Brain Res. in press]. This paper follows up this one positive result on a historical background of uniformly negative results. The focus of this report is on the fusiform cells of the dorsal cochlear nucleus whose axons course through the dorsal acoustic stria (DAS). Because electrophysiological studies have shown that the cues for sensing the elevation of a sound source would seem to be best analyzed by the dorsal cochlear nucleus, we tested, behaviorally, normal cats and cats deprived of their DAS or intermediate acoustic stria, bilaterally or ipsilaterally (with or without their contralateral ear deafened), for their ability to orient to elevated sources of broad-band noise. For behavioral testing, we made use of a conventional shock-avoidance procedure. The results lead to the conclusion that DCN and DAS may play no role in learned elevation discriminations. This result builds on that of another of our papers which suggests that a deficit in reflexive discrimination of elevation is strictly auditory in nature [Sutherland, D.P., Masterton, R.B., Glendenning, K.K. (1998) Behav. Brain Res. in press].     

Following sustainable development in relation to the north-south dialogue: ecosystem health and sustainability indicators

The necessity for policy makers to follow the processes in relation to sustainability demands new tools for management, a major aspect of which is integrated attention to economic and sociocultural influences together with environmental issues. North and South have specific positions and responsibilities with regard to sustainable development, and management tools--such as indicators--should reflect them. Because the North-South dialogue is changing, different approaches to deal with the relationships are needed (e.g., introduction of reciprocity, equity, and participation), while at the same time doing justice to the individual social, economic, and cultural characteristics of a country. Ecosystem health can be defined by requirements such as resilience, vigor, organization, and relations, which may be used for totally different systems as well. Because integration is a crucial aspect of the new tools, it is argued that integrating conceptual tools such as the environment-economy-society triangle, the PSIR-causality chain, and the Daly triangle in addition to other described integration tools is fundamental for decision makers. Crucial issues when dealing with indicators for sustainable development are integration and balance, attention to users, use of system characteristics, and understanding southern perspectives in this context.