Calcium channel blockers modulate airway constriction in the canine lung periphery

We studied the effect of two voltage-sensitive calcium channel blockers on Na2EDTA-induced bronchoconstriction in the canine lung periphery. A wedged bronchoscope technique was used to measure collateral system resistance before and after challenges with aerosolized Na2EDTA, hypocapnia, aerosolized acetylcholine, and increased flow of dry air in anesthetized mongrel dogs. Nifedipine, a dihydropyridine calcium channel blocker, reduced hypocapnia-induced bronchoconstriction by 88 +/- 6% (SE) but did not alter Na2EDTA-induced constriction. Verapamil, a phenylalkylamine calcium channel blocker, attenuated hypocapnia- and Na2EDTA-induced bronchoconstriction by 69 +/- 6 and 44 +/- 7%, respectively, but did not significantly alter responses to either acetylcholine or dry air challenge. We conclude that calcium influx through voltage-sensitive calcium channels, perhaps of the T subtype, has a limited role in the initiation of Na2EDTA-induced bronchoconstriction in the canine lung periphery.     

Epitopic analysis by anti-I-Ak monoclonal antibodies of I-Ak-restricted presentation of lysozyme peptides

Anti-I-A mAb were used as probes of functional epitopes for both the presentation of hen egg lysozyme (HEL) peptides to I-Ak-restricted T cell hybridomas and the direct binding of the HEL (46-61) peptide. When mAb directed to polymorphic regions of I-Ak were used as inhibitors of Ag presentation, several different patterns of inhibition were observed among T cells specific for the same HEL peptide as well as among T cells specific for different fragments of HEL. Although there appears to be a conserved usage of some TCR V beta gene segments among the T cell hybrids specific for the same HEL peptide, no correlation is evident between a single V gene usage and susceptibility to blocking of Ag presentation by a particular anti-I-Ak mAb. Several of the mAb demonstrated T cell "clonotypic blocking" of Ag presentation, whereas others blocked presentation to every T cell hybrid tested, regardless of the peptide specificity. When mAb directed to nonpolymorphic regions of the I-A molecule were tested for their ability to block Ag presentation, little or no inhibition was observed. In addition, Fab' fragments of inhibitory mAb functioned identically to their intact homologous counterparts in their ability to block Ag presentation indicating that "nonspecific" steric hindrance was not playing a major role in the inhibitions observed. When the polymorphic region-directed anti-I-A mAb were tested for their ability to block the direct binding of the lysozyme peptide HEL(46-61) to I-Ak, those mAb that block HEL presentation to all T cell hybrids were found to block the binding of this peptide. However, anti-I-A mAb that demonstrate selective inhibition of T cell hybrid stimulation during Ag presentation, i.e., those directed to polymorphic serologic specificities Ia.15 and Ia.19, do not block the binding of HEL(46-61) to I-Ak. These data indicate that functionally independent epitopes exist on the I-Ak molecule for the binding of antigenic peptides and for interaction with the TCR.     

Increased Neural Cell Adhesion Molecule in the CSF of Patients with Mood Disorder

Abstract: Neural cell adhesion molecule (N-CAM) is involved in cell-cell interactions during synaptogenesis, morphogenesis, and plasticity of the nervous system. Disturbances in synaptic restructuring and neural plasticity may be related to the pathogenesis of several neuropsychiatric diseases, including mood disorders and schizophrenia. Disturbances in brain cellular function may alter concentrations of N-CAM in the CSF. Soluble human N-CAM proteins are detectable in the CSF but are minor constituents of serum. We have recently found an increase in N-CAM content in the CSF of patients with schizophrenia. Although the pathogenesis of both schizophrenia and mood disorders is unknown, ventriculomegaly, decreased temporal lobe volume, and subcortical structural abnormalities have been reported for both disorders. We have therefore measured N-CAM concentrations in the CSF of patients with mood disorder. There were significant increases in amounts of N-CAM immunoreactive proteins, primarily the 120-kDa band, in the CSF of psychiatric inpatients with bipolar mood disorder type I and recurrent unipolar major depression. There were no differences in bipolar mood disorder type II patients as compared with normals. There were no significant effects of medication treatment on N-CAM concentrations. It is possible that the 120-kDa N-CAM band present in the CSF is derived from CNS cells as a secreted soluble N-CAM isoform. Our results suggest the possibility of latent state-related disturbances in N-CAM cellular function, i.e., residue from a previous episode, or abnormal N-CAM turnover in the CNS of patients with mood disorder.     

INFLUENCE OF NATURAL ULTRAVIOLET RADIATION ON LOTIC PERIPHYTIC DIATOM COMMUNITY GROWTH,BIOMASS ACCRUAL,AND SPECIES COMPOSITION: SHORT-TERM VERSUS LONG-TERM EFFECTS1, 2

Growth rates, accumulation dynamics, and species succession of periphytic diatom communities were examined in the presence and absence of natural ultraviolet (UV) radiation using a series of outdoor, continuous-flow experimental flumes located on the South Thompson River, British Columbia. In a short-term experiment (2–3 wk), log-phase growth rates of naturally seeded diatom communities comprised of Tabellaria fenestrata (Lyngb.) Kütz., T. flocculosa (Roth) Kütz., Fragilaria crotonesis Kitton, and F. vaucheriae (Ehr.) Peter. exposed to 90% ambient photosynthetically active radiation (PAR) + UV were 30–40% lower than growth rates under 90% PAR alone. UV inhibition of growth rate was independent of the degree of P limitation within the range of relative specific growth rates (μ:μ_max-P) of 0.5–1.0. In a long-term trial, inhibition of attached diatom accumulation under 90% PAR + UV during the first 2–3 wk was corroborated. Reduction of full sunlight to 50% PAR + UV prevented the initial inhibition phase. The initial inihibitory effect of 90% PAR + UV on algal accumulation was reversed after 3–4 wk, and by 5 wk total diatom abundance (chlorophyll a, cell numbers and cell biovolumes) in communities exposed to PAR + UV were 2–4-old greater than in communities protected from UV. Under 90% PAR + UV and 50% PAR + UV, a succession to stalked diatom genera (Cymbella and Gomphoneis) occurred. Species succession under UV radiation doubled the mean cell size of the diatom communities. The shift from inhibition to a long-term increase in the autotrophic community under PAR + UV compared to PAR alone provides further evidence against the use of short-term incubation experiments to define the long-term implications of increases in UVB. These results suggest that the ecological effects of present-day levels of UVB and UVB:UVA ratios on autotrophic communities are not well understood and might be mediated through complex trophic level interactions.     

Juvenile proportion as a predictor of freshwater turtle population change

The extreme longevity of turtles and tortoises can make it difficult to determine the conservation status of their populations because high annual adult survival may mask gradual attrition due to low levels of recruitment. When long-term demographic trends are unknown and available data are insufficient for population modelling, it may be assumed that a scarcity of juveniles indicates low recruitment that will result in population ageing and numerical decline. However, the reliability with which the proportion of juveniles foreshadows demographic change is uncertain. We tested the hypothesis that a low proportion of juveniles in a turtle population presages its ageing by analysing over 20 years of survey data for five discrete populations of the Australian western saw-shelled turtle (Myuchelys bellii: Chelidae), a listed threatened species. The analysis tested whether the initial proportion of juvenile turtles in each population was related to its temporal trend in average body size. The five populations had varied structure and trends, with the initial proportion of juvenile turtles ranging from 10% to 39% and average body size increasing over time in some populations and decreasing in others. Contrary to expectation, the initial proportion of juveniles was unrelated to the trend in average body size and, by inference, average age, indicating that effective trend forecasting requires more detailed demographic information than merely population structure.     

Using ecological networks to answer questions in global biogeography and ecology

Ecological networks have classically been studied at site and landscape scales, yet recent efforts have been made to collate these data into global repositories. This offers an opportunity to integrate and upscale knowledge about ecological interactions from local to global scales to gain enhanced insights from the mechanistic information provided by these data. By drawing on existing research investigating patterns in ecological interactions at continental to global scales, we show how data on ecological networks, collected at appropriate scales, can be used to generate an improved understanding of many aspects of ecology and biogeography—for example, species distribution modelling, restoration ecology and conservation. We argue that by understanding the patterns in the structure and function of ecological networks across scales, it is possible to enhance our understanding of the natural world.     

Multiple molecular recognition properties of the lipocalin protein family

The lipocalins, a diverse family of small extracellular ligand proteins, display a remarkable range of different molecular properties. While their binding of small hydrophobic molecules, and to a lesser extent their binding to cell surface receptors, is well known, it is shown here that formation of macromolecular complexes is also a common feature of this family. Analysis of known crystallographic structures reveals that the lipocalins process a conserved common structure: an antiparallel β-barrel with a repeated +1 topology. Comparisons show that within this overall similarity the structure of individual proteins is specifically adapted to bind their particular ligands, forming a binding site from an internal cavity (within the barrel) and/or an external loop scaffold, which gives rise to different binding modes that reflects the need to accommodate ligands of different shape, size, and chemical structure. The architecture of the lipocalin fold suggests that the both the ends and sides of this barrel are topologically distinct, differences also apparent in analyses of structural and sequence variation within the family. These different can be linked to experimental evidence suggesting a possible functional dichotomy between the two ends of the lipocalin fold. The structurally invariant end of the molecule may be implicated in general binding small ligands and forming macromolecular complexes via an exposed binding surface.     

Synthesis and fungicidal activity of 2,2′-bipyridine derivatives

A series of substituted 2,2′-bipyridine derivatives was prepared using the Kröhnke reaction and alkylation of 4,4′-dimethyl-2,2′-bipyridine. These compounds were screened for fungicidal activity against 9 plant diseases. 5-Phenyl-2,2′-bipyridine exhibited strong preventative and curative fungicidal activity against wheat powdery mildew (Erisyphe graminis) and wheat leaf rust (Puccinia recondita).