bluuebunny/crossref_metadata_2025_split huggingface dataset:
Desensitisation of mast cell β2‐adrenoceptor‐mediated responses by salmeterol and formoterol
Authors: Scola Anne‐Marie , Chong Lee K , Suvarna S Kim , Chess‐Williams Russell , Peachell Peter T 
Published: January 2004

The long‐acting β2‐adrenoceptor agonist formoterol (10−10–10−6 M) inhibited the IgE‐dependent release of histamine from human lung mast cells in a concentration‐dependent manner. Formoterol was more potent and a full agonist relative to the nonselective β‐adrenoceptor agonist isoprenaline. By contrast, the long‐acting β2‐adrenoceptor agonist salmeterol (10−10–10−6 M) was about two‐thirds less efficacious than either formoterol or isoprenaline as an inhibitor of histamine release.
Isoprenaline, formoterol and salmeterol (all at 10−5 M) increased total cell cAMP levels in mast cells over basal by 361±90 (P<0.05), 321±89 (P<0.05) and 64±24% (P>0.05), respectively.
Long‐term (24 h) incubation of mast cells with formoterol (10−6 M) or salmeterol (10−6 M) essentially abolished the subsequent ability of isoprenaline to inhibit histamine release. Both formoterol and salmeterol were more effective at inducing the functional desensitisation than isoprenaline (10−6 M) or the short‐acting β2‐adrenoceptor agonist salbutamol (10−6 M).
The desensitisation induced by long‐term treatments with salmeterol and formoterol was specific for β2‐adrenoceptor‐mediated inhibition of histamine release as the inhibitory effects of alternative cAMP‐elevating compounds, prostaglandin E2, a receptor‐mediated activator of adenylate cyclase, and forskolin, a direct activator of adenylate cyclase, were unaffected by desensitising treatments.
Radioligand binding studies were performed to determine β2‐adrenoceptor density in cell membranes after pretreatment (24 h) of cells with agonists. Isoprenaline, formoterol and salmeterol (all at 10−6 M) reduced β2‐adrenoceptor density by 13±5 (P>0.05), 49±13 (P<0.05) and 35±17% (P>0.05), respectively.
These data indicate that long‐term exposure of mast cells to both salmeterol and formoterol can cause substantial levels of desensitisation to β2‐adrenoceptor‐mediated responses in mast cells.

British Journal of Pharmacology (2004) 141, 163–171. doi:10.1038/sj.bjp.0705599
Reactive nitrogen species scavenging, rather than nitric oxide inhibition, protects from articular cartilage damage in rat zymosan‐induced arthritis
Authors: Bezerra Mirna Marques , Brain Susan D , Greenacre Stan , Jerônimo Selma Maria Bezerra , De Melo Liana Batista , Keeble Julie , Da Rocha Francisco Airton Castro 
Published: January 2004

The contribution of nitric oxide (NO) and peroxynitrite (PN) to inflammation in a zymosan‐induced (1 mg, intra‐articular, i.art.) rat model of arthritis was assessed by histopathology and by measuring the glycosaminoglycan (GAG) content of the articular cartilage.
Progression of the chronic synovitis in zymosan‐induced arthritis (ZYA) was associated with increased nitrite and nitrotyrosine (3‐NT) levels in the joint exudates that paralleled a progressive loss of the GAG content. An increase in 3‐NT was also observed after i.art. PN.
The nonselective nitric oxide synthase (NOS) inhibitor L‐NG‐nitroarginine methyl ester (25–75 mg kg−1day−1) or the selective inducible NOS inhibitor aminoguanidine (50–100 mg kg−1day−1) given 1 h before (prophylactic) or 3 days after (therapeutic) injection of the zymosan ameliorated the synovitis, but worsened the GAG loss, as measured at the end of the experiment (day 7).
The PN scavenger uric acid (100–250 mg kg−1 i.p. four times daily) given prophylactically until the end of the experiment (day 14), in a dose compatible with its PN scavenging activity, significantly decreased both the synovitis and the GAG loss.
In conclusion, PN formation is associated with cartilage damage in addition to proinflammatory activity in ZYA. NOS inhibitors and a PN scavenger were able to reduce the cellular infiltration, while displaying opposite effects on cartilage homeostasis either by enhancing or ameliorating the damage, respectively.

British Journal of Pharmacology (2004) 141, 172–182. doi:10.1038/sj.bjp.0705600
Correlation between spontaneous electrical, calcium and mechanical activity in detrusor smooth muscle of the guinea‐pig bladder
Authors: Hashitani Hikaru , Brading Alison F , Suzuki Hikaru 
Published: January 2004

To investigate the cellular mechanisms underlying spontaneous excitation of smooth muscle of the guinea‐pig urinary bladder, isometric tension was measured in muscle bundles while recording the membrane potential from a cell in the bundle with a microeletrode. Changes in the intracellular calcium concentration ([Ca2+]i; calcium transients) were recorded in strips loaded with the fluorescent dye, fura‐PE3.
In 40% of preparations, individual action potentials and contractions, which were abolished by nifedipine (1 μM), were generated. In the remaining preparations, bursting action potentials and contractions were generated. Contractions were again abolished by nifedipine (1 μM), while higher concentrations of nifedipine (10–30 μM) were required to prevent the electrical activity.
Carbachol (0.1 μM) increased the frequency of action potentials and corresponding contractions. Apamin (0.1 μM) potentiated bursting activity and enhanced phasic contraction. Charybdotoxin (CTX, 50 nM) induced prolonged action potentials that generated enlarged contractions. In contrast, levcromakalim (0.1 μM) reduced the frequency of action potentials, action potential bursts and the size of the contractions.
Forskolin (0.1 μM), 8‐bromoguanosin 3′, 5′ cyclic monophosphate (8Br‐cGMP, 0.1 mM) and Y‐26763 (10 μM) suppressed contractions without reducing the amplitude of either action potentials or Ca transients.
This paper confirms that action potentials and associated calcium transients are fundamental mechanisms in generating spontaneous contractions in smooth muscles of the guinea‐pig bladder. However, in parallel with the excitation–contraction coupling, the sensitivity of the contractile proteins for Ca2+ may play an important role in regulating spontaneous excitation and can be modulated by cyclic nucleotides and Rho kinase.

British Journal of Pharmacology (2004) 141, 183–193. doi:10.1038/sj.bjp.0705602
Genetic diversity and structure of urban populations ofPierisbutterflies assessed using amplified fragment length polymorphism
Authors: Takami Yasuoki , Koshio Chiharu , Ishii Minoru , Fujii Hisashi , Hidaka Toshitaka , Shimizu Isamu 
Published: January 2004

AbstractConservation programs in urban ecosystems need to determine the genetic background in populations of urban dwellers. We examined the genetic diversity and structure ofPieris rapaeandP.meleteusing AFLP markers, and compared them between species and between urban and rural environments. As a result: (i) in both species, there was no reduction in genetic diversity within urban populations by direct comparison of diversity measurements, although the analysis of molecular variance suggested significant reductions in the variance within seasonal subpopulations in urban populations; (ii)P.rapaeretained greater genetic diversity within species and populations; (iii) populations of both species showed significant genetic differentiation, andP.meletewas more strongly subdivided; (iv) in both species, geographically close populations did not cluster with one another in theupgmaanalysis; (v) there was no genetic isolation due to geographical distance in either species; (vi) the genetic composition of seasonal subpopulations differed in urban populations of both species, and the genetic distances among subpopulations were correlated with seasonal differences inP.rapaeand with temporal differences inP.melete. These results indicate that the genetic diversity in urban populations of both species was reduced at times, but was maintained by dispersal from genetically differentiated populations. Differences in the ability and mode of dispersal in the two species may be reflected in the degree of population subdivision and patterns of seasonal change in the genetic composition.
Effective size of two feral domestic cat populations (Felis catusL.): effect of the mating system
Authors: Kaeuffer R. , Pontier D. , Devillard S. , Perrin N. 
Published: January 2004

AbstractA variety of behavioural traits have substantial effects on the gene dynamics and genetic structure of local populations. The mating system is a plastic trait that varies with environmental conditions in the domestic cat (Felis catus) allowing an intraspecific comparison of the impact of this feature on genetic characteristics of the population. To assess the potential effect of the heterogenity of males’ contribution to the next generation on variance effective size, we applied the ecological approach of Nunney & Elam (1994) based upon a demographic and behavioural study, and the genetic ‘temporal methods’ of Waples (1989) and Berthieret al. (2002) using microsatellite markers. The two cat populations studied were nearly closed, similar in size and survival parameters, but differed in their mating system. Immigration appeared extremely restricted in both cases due to environmental and social constraints. As expected, the ratio of effective size to census number (Ne/N) was higher in the promiscuous cat population (harmonic mean = 42%) than in the polygynous one (33%), whenNewas calculated from the ecological method. Only the genetic results based on Waples’ estimator were consistent with the ecological results, but failed to evidence an effect of the mating system. Results based on the estimation of Berthieret al. (2002) were extremely variable, withNesometimes exceeding census size. Such low reliability in the genetic results should retain attention for conservation purposes.
Limited effect of anthropogenic habitat fragmentation on molecular diversity in a rain forest skink, Gnypetoscincus queenslandiae
Authors: Sumner Joanna , Jessop Tim , Paetkau David , Moritz Craig 
Published: January 2004

AbstractTo examine the effects of recent habitat fragmentation, we assayed genetic diversity in a rain forest endemic lizard, the prickly forest skink (Gnypetoscincus queenslandiae), from seven forest fragments and five sites in continuous forest on the Atherton tableland of northeastern Queensland, Australia. The rain forest in this region was fragmented by logging and clearing for dairy farms in the early 1900s and most forest fragments studied have been isolated for 50–80 years or nine to 12 skink generations. We genotyped 411 individuals at nine microsatellite DNA loci and found fewer alleles per locus in prickly forest skinks from small rain forest fragments and a lower ratio of allele number to allele size range in forest fragments than in continuous forest, indicative of a decrease in effective population size. In contrast, and as expected for populations with small neighbourhood sizes, neither heterozygosity nor variance in allele size differed between fragments and sites in continuous forests. Considering measures of among population differentiation, there was no increase in FST among fragments and a significant isolation by distance pattern was identified across all 12 sites. However, the relationship between genetic (FST) and geographical distance was significantly stronger for continuous forest sites than for fragments, consistent with disruption of gene flow among the latter. The observed changes in genetic diversity within and among populations are small, but in the direction predicted by the theory of genetic erosion in recently fragmented populations. The results also illustrate the inherent difficulty in detecting genetic consequences of recent habitat fragmentation, even in genetically variable species, and especially when effective population size and dispersal rates are low.
Historical data refute recent range contraction as cause of low genetic diversity in isolated frog populations
Authors: Hoffman Eric A. , Blouin Michael S. 
Published: January 2004

AbstractThis study tested whether low genetic diversity in remnant populations of a declining amphibian is best explained by recent bottlenecks or by a history of being peripheral. We compared diversity from eight microsatellite loci in historical and extant populations from the interior and former periphery of the species’ range. We found that historic peripheral populations already had reduced levels of genetic variation before the range contraction. Therefore, low diversity in remnants could not be ascribed to recent range contractions. This study shows that a common conservation strategy for rescuing genetically depauperate populations, artificial gene flow, may often be unwarranted and detrimental to evolutionarily important peripheral populations.
Fine‐scale diversity and specificity in the most prevalent lineage of symbiotic dinoflagellates (Symbiodinium, Dinophyceae) of the Caribbean
Authors: Santos S. R. , Shearer T. L. , Hannes A. R. , Coffroth M. A. 
Published: January 2004

AbstractThe success of coral reefs is due to obligate mutualistic symbioses involving invertebrates and photosynthetic dinoflagellate symbionts belonging to the genus Symbiodinium. In the Caribbean, the vast majority of octocorals and other invertebrate hosts associate with Symbiodinium clade B, and more selectively, with a single lineage of this clade, Symbiodinium B1/B184. Although B1/B184 represents the most prevalent Symbiodinium in the Caribbean, there is little evidence supporting fine‐scale diversity and host–alga specificity within this lineage. We explored simultaneously the questions of diversity and specificity in Symbiodinium B1/B184 by sequencing the flanking regions of two polymorphic microsatellites from a series of Symbiodinium clade B cultures along with Symbiodinium B1/B184 populations of the octocorals Pseudopterogorgia elisabethae, P. bipinnata and Gorgonia ventalina. Seven unique sequence variants were identified based on concatenation of the two loci. Phylogenetic analyses of these variants, which we refer to as phylotypes, recognized five as belonging to B1/B184, thus providing the first evidence of distinct taxa within this Symbiodinium lineage. Furthermore, sympatric P. elisabethae and P. bipinnata at San Salvador in the Bahamas were found to harbour distinct Symbiodinium B1/B184 phylotypes, demonstrating unequivocally the existence of fine‐scale specificity between Caribbean octocorals and these algae. Taken together, this study exemplifies the complex nature of Symbiodinium biodiversity and specificity.
Inbreeding avoidance in Cunningham's skinks (Egernia cunninghami) in natural and fragmented habitat
Authors: Stow A. J. , Sunnucks P. 
Published: January 2004

AbstractHabitat fragmentation/alteration has been proposed as a distinct process threatening the viability of populations of many organisms. One expression of its impact may be the disruption of core population processes such as inbreeding avoidance. Using the experimental design outlined in our companion paper, we report on the impact of habitat alteration (deforestation) on inbreeding in the rock‐dwelling Australian lizard Egernia cunninghami. Ten microsatellite loci were used to calculate relatedness coefficients of potential and actual breeding pairs, and to examine mate‐choice and heterozygosity. Despite significantly less dispersal and higher within‐group relatedness between potential mates in deforested than in natural habitats, this did not result in significantly more inbred matings. Average relatedness amongst breeding pairs was low, with no significant difference between natural and fragmented populations in relatedness between breeding pairs, or individual heterozygosity. Active avoidance of close kin as mates was indicated by the substantially and significantly lower relatedness in actual breeding pairs than potential ones. These facts, and heterozygote excesses in all groups of immature lizards from both habitats, show that E. cunninghami maintained outbreeding in the face of increased accumulation of relatives.
High mate and site fidelity in Cunningham's skinks (Egernia cunninghami) in natural and fragmented habitat
Authors: Stow A. J. , Sunnucks P. 
Published: January 2004

AbstractWhile habitat alteration has considerable potential to disrupt important within‐population processes, such as mating and kin structure, via changed patterns of dispersal, this has rarely been tested. We are investigating the impact of anthropogenic habitat alteration on the population biology of the rock‐dwelling Australian lizard Egernia cunninghami on the Central Tablelands of New South Wales, Australia, by comparing deforested and adjacent naturally vegetated areas. The novel analyses in this paper, and its companion, build on previous work by adding a new replicate site, more loci and more individuals. The additional microsatellite loci yield sufficient power for parentage analysis and the sociobiological inferences that flow from it. Genetic and capture–mark–recapture techniques were used to investigate mate and site fidelity and associated kin structure. Analyses of the mating system and philopatry using 10 microsatellite loci showed high levels of site fidelity by parents and their offspring in natural and deforested habitats. Parentage assignment revealed few individuals with multiple breeding partners within seasons and fidelity of pairs across two or more breeding seasons was typical. Despite reduced dispersal, increased group sizes and significant, dramatic increases in relatedness among individuals within rock outcrops in deforested areas, no significant differences between deforested and natural areas were evident in the degree of multiple mating or philopatry of breeding partners within and across seasons. With the exception that there was a significantly higher proportion of unmated males in the deforested area, the social and mating structure of this species has so far been surprisingly robust to substantial perturbation of dispersal and relatedness structure. Nonetheless, approximately 10‐fold elevation of mean pairwise relatedness in the deforested areas has great potential to increase inbred matings, which is investigated in the companion paper.
Extensive chloroplast haplotype variation indicates Pleistocene hybridization and radiation of North American Arabis drummondii, A. × divaricarpa, and A. holboellii (Brassicaceae)
Authors: Dobeš C. H. , Mitchell‐Olds T. , Koch M. A. 
Published: January 2004

Abstract Arabis drummondii, A. holboellii and their hybrid A. × divaricarpa are widespread perennials of open habitats in North America. A phylogenetic analysis based on noncoding chloroplast DNA sequences (trnL intron and trnL/F intergenic spacer) resolved A. drummondii as a monophyletic taxon, but found A. holboellii to bear chloroplast haplotypes from highly diverged evolutionary lineages. This raised the question of a possible polyphyletic origin of A. holboellii. Arabis × divaricarpa was found to be of recent and polytopic origin, a result consistent with its presumed hybrid origin. One hundred and three chloroplast haplotypes were detected within 719 Arabis accessions investigated. The majority of chloroplast‐types were estimated to have arisen prior to the Wisconsin glaciation. Phylogeographical analysis using nested clade analysis, suggested for A. holboellii (i) past fragmentation events, partitioning genetic variation in several instances between the Sierra Nevada, the Southern Rocky Mountains and the Colorado Plateau on the one hand and the Central to Northern Rockies of the United States and adjacent Cascades on the other; and for both parental species (ii) recolonization of major areas formerly covered by the Wisconsin glaciation by three haplotypes; and (iii) restricted gene flow indicating isolation by distance in areas south of the last glacial maximum. Arabis × divaricarpa is closely codistributed with its parental species and resampled their haplotypes. The highest genetic diversity was found in the Rocky Mountains from Idaho and Montana south to Utah and Colorado. This area was further hypothesized to have played a major role in the origin of both parental species and probably represented an important glacial refugium. However, evidence for glacial refugia was also found in arctic and boreal regions of Alaska and near the Great Lakes. In comparison to nuclear ribosomal internal transcribed spacer data, chloroplast DNA divergence was very high and evidently predated the origin of A. drummondii and possibly A. holboellii. Divergence of major chloroplast lineages dates back to the middle of the Pleistocene at least. Extensive hybridization is the most likely evolutionary factor working on A. holboellii to explain the revealed discrepancy in nuclear DNA and chloroplast DNA diversification.
Genetic structure among closely spaced leks in a peripheral population of lesser prairie‐chickens
Authors: Bouzat Juan L. , Johnson Kristine 
Published: January 2004

AbstractWe evaluated the genetic structure of birds from four closely spaced leks in a peripheral population of lesser prairie‐chickens (Tympanuchus pallidicinctus). Analyses of molecular variance revealed significant genetic structuring among birds from different leks for six microsatellite loci (FST = 0.036; P = 0.002), but we found no genetic differentiation at the mtDNA control region. Significant deviations from Hardy–Weinberg revealed an excess of homozygote genotypes within each of the leks studied (FIS = 0.190–0.307), indicative of increased inbreeding. Estimates of relatedness using microsatellite data suggest that the genetic structuring among lesser prairie‐chicken leks occurs in part because of a lek mating system in which males at some leks are related. Structuring may also be caused by stochastic effects associated with a historical decline in population size leading to small, semi‐isolated leks and high site fidelity by reproductive males. Results from this study suggest that microspatial genetic structuring may occur in lek‐mating bird species with low levels of dispersal.
Unreliable mtDNA data due to nuclear insertions: a cautionary tale from analysis of humans and other great apes
Authors: Thalmann O. , Hebler J. , Poinar H. N. , Pääbo S. , Vigilant L. 
Published: January 2004

AbstractAnalysis of mitochondrial DNA sequence variation has been used extensively to study the evolutionary relationships of individuals and populations, both within and across species. So ubiquitous and easily acquired are mtDNA data that it has been suggested that such data could serve as a taxonomic ‘barcode’ for an objective species classification scheme. However, there are technical pitfalls associated with the acquisition of mtDNA data. One problem is the presence of translocated pieces of mtDNA in the nuclear genome of many taxa that may be mistaken for authentic organellar mtDNA. We assessed the extent to which such ‘numt’ sequences may pose an overlooked problem in analyses of mtDNA from humans and apes. Using long‐range polymerase chain reaction (PCR), we generated necessarily authentic mtDNA sequences for comparison with sequences obtained using typical methods for a segment of the mtDNA control region in humans, chimpanzees, bonobos, gorillas and orangutans. Results revealed that gorillas are notable for having such a variety of numt sequences bearing high similarity to authentic mtDNA that any analysis of mtDNA using standard approaches is rendered impossible. Studies on humans, chimpanzees, bonobos or orangutans are apparently less problematic. One implication is that explicit measures need to be taken to authenticate mtDNA sequences in newly studied taxa or when any irregularities arise. Furthermore, some taxa may not be amenable to analysis of mtDNA variation at all.