bluuebunny/crossref_metadata_2025_split huggingface dataset:
Purification and characterization of endocan (endothelial cell‐specific molecule‐1), a circulating proteoglycan involved in tumour progression and inflammatory diseases
Authors: Sarrazin Stéphane , Bechard David , Lassalle Philippe , Lyon Malcolm , Scherpereel Arnaud , Lortat‐Jacob Hugues , Ouatas Taoufik , Delehedde Maryse 
Published: August 2004

Introduction  By virtue of the multiplicity of their protein‐binding partners (e.g. growth factors, cytokines/chemokines), proteoglycans have been shown to be involved in the regulation of a large number of pathophysiological processes including cancer and inflammatory diseases. We have studied and characterized endocan, also called endothelial cell‐specific molecule‐1 (ESM‐1), which represents a new group of circulating proteoglycans. Endocan is mainly expressed by endothelial cells but also by epithelial cells from lung, gut and kidney. Structurally, endocan is constituted of a mature polypeptide of 165 amino acids with a single glycosaminoglycan chain covalently linked to the serine at position 137 (Béchard et al. 2001).Methods and results  We showed that human umbilical vein endothelial cells expressed endocan specifically with a single chain of dermatan sulfate (DS) as glycosaminoglycan moiety. As shown by surface plasmon resonance, the DS chain directly interacts with cytokines and growth factors including hepatocyte growth factor/scatter factor and could be responsible for endocan's biological activities. Human embryonic kidney 293 cells, which have been genetically engineered to overexpress endocan, induce tumour growth when injected subcutaneously in SCID mice. Moreover, inflammatory cytokines such as TNF‐a and IL‐1 have been shown to increase the synthesis and the secretion of endocan from human umbilical vein endothelial cells.Conclusion  These results suggest that circulating levels of endocan may represent a novel marker for cancer and inflammatory diseases. Further studies on its GAG structure could help us to better understand the biological activities of endocan and to design future glycomic‐based therapies.
Anti‐inflammatory actions of green tea catechins and ligands of peroxisome proliferator‐activated receptors
Authors: Trekli M. , Buttle D. , Guesdon F. 
Published: August 2004

Introduction  Green tea catechins and peroxisome proliferator‐activated receptor (PPAR) agonists have been shown to reduce inflammation associated with collagen‐induced arthritis in mice (Haqqi et al. 1999; Cuzzocrea et al. 2003) and to inhibit other markers of inflammation (Vankemmelbeke et al. 2003; Sabatini et al. 2002; Singh et al. 2003; Jiang et al. 1998). We are investigating the mechanisms by which catechins and PPAR agonists interfere with the signalling pathways of the pro‐inflammatory cytokines, IL‐1 and TNF.Materials and methods  Epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC), epicatechin (EC) and fenofibrate were from Sigma Aldrich, Poole, UK. Rosiglitazone was from Cayman Chemical, Ann Arbor, MI, USA. Cytokines and IL‐8 ELISA were from NIBSC. IL‐6 ELISA from eBiosciences (San Diego, CA, USA). Cells used were primary fibroblasts from inflamed periodontal tissue or osteoarthritic chondrocytes from discarded tissue following surgery.Results  We show the significant suppression of cytokine‐induced IL‐6 and IL‐8 release by EGCG, which is dose‐ and cell‐type dependent. The other three catechins have a much lesser effect. Preliminary results show that PPAR agonists also interfere with TNF‐induced IL‐8 production.Discussion  Green tea has a long history of human consumption, and epidemiological studies have shown that it can reduce inflammatory diseases (Greenwald et al. 2002). Our results confirm that EGCG has the strongest anti‐inflammatory effect, compared with the other three catechins. They also indicate that the mechanism of action of EGCG is cell‐type dependent. This could be because the compound targets components of pro‐inflammatory signalling pathways whose expression is restricted to certain differentiated cell types. Alternatively, the different sensitivities of cells to EGCG could reflect differences in their ability to metabolize the compound. Further experiments are needed to discriminate between these hypotheses.
Analysis of CD44 hyaluronan‐binding domain mutants by NMR
Authors: Wright A.J. , Banerji S. , Noble M. , Jackson D.G. , Campbell I.D. , Day A.J. 
Published: August 2004

Introduction  Hyaluronan (HA) is a ubiquitous high molecular mass glycosaminoglycan composed of a repeating disaccharide. CD44, the major cell surface receptor for HA, has a HA‐binding domain (CD44_HABD) at the N‐terminus of the protein, the 3D structure of which has been determined by both NMR and X‐ray crystallography (Teriete et al. 2004); NMR spectra collected on the protein in complex with HA oligosaccharides has allowed us to predict how they may thread across the interaction surface. Amino acids previously implicated in HA binding include R41, Y42, R78 and Y79 (Peach et al. 1993; Bajorath et al. 1998), which form a cluster on the surface of the Link module‐like region (Teriete et al. 2004), as well as residues in the C‐terminal extension (R150, R154, K158 and R162) (Peach et al. 1993). The position of the putative‐binding residues in the C‐terminal segment, and NMR data, led to the hypothesis of two modes of HA binding (Teriete et al. 2004). Here, this hypothesis is tested by NMR studies of single‐site mutants in the context of the CD44_HABD construct.Materials and methods  Four mutants of CD44_HABD were made, each with a single residue substitution (R150A, R154A, K158A and R162A). These constructs were expressed as 15N‐labelled proteins in Escherichia coli, refolded and purified to homogeneity. 1H–15N HSQC spectra were acquired on the mutants in the presence of varying concentrations of HA hexasaccharide (HA6) and compared to the wild‐type construct to determine changes of protein fold and ligand binding.Results  The mutants R150A, R154A and K158A have similar HSQC spectra to wild‐type CD44_HABD except for local chemical shift perturbations around the altered residue. Conversely, the R162A mutant has widespread chemical shift differences compared to wild‐type indicating that this mutation disrupts the fold. On binding HA6, the R150A, R154A and K158A mutants all experience shift perturbations similar to that seen with the wild‐type protein.Discussion  The interaction of HA6 with wild‐type CD44_HABD has been found to cause a significant conformational change in the protein (Teriete et al. 2004). The results here indicate that this ligand‐induced rearrangement can also occur in the R150A, R154A and R158A mutants. Therefore, these mutations do not seem to affect the binding of CD44 to HA6. It has been shown previously that the R162A mutation has reduced affinity for HA compared to wild‐type protein (Peach et al. 1993). This loss of function may be due to the perturbation of the protein fold, and it is possible therefore that R162 does not participate directly in binding. Work is in progress to test the functional activity of these CD44_HABD mutants using ELISA‐like assays and to investigate their chemical shift perturbation in the presence of longer oligosaccharides.
Maintenance of anaesthesia with sevoflurane or isoflurane effects on adverse airway events in smokers
Authors: Wild M. R. , Gornall C. B. , Griffiths D. E. , Curran J. 
Published: August 2004

SummaryPatients who smoke are at risk of coughing and other adverse airway events during induction of anaesthesia. We have studied the incidence of adverse airway events in smokers under isoflurane or sevoflurane anaesthesia after induction with propofol. Smokers inhaling isoflurane had a 45% incidence of adverse airway events compared to 10% in those inhaling sevoflurane (p = 0.013).
Potential immaturity of the T‐cell and antigen‐presenting cell interaction in cord blood with particular emphasis on the CD40‐CD40 ligand costimulatory pathway
Authors: Han P. , Mcdonald T. , Hodge G. 
Published: August 2004

SummaryThere are reports of immaturity of the neonatal immune system, which may explain the low incidence of graft‐versus‐host‐disease (GVHD) after cord blood transplantation. The CD40 ligand (CD40L)–CD40 interaction is important in regulating the cellular immune response. We hypothesized that the neonatal immune system may show immaturity in this interaction. We studied the function of the CD40L–CD40 interaction in the T‐cell interaction with B cells and monocytes in cord blood compared with adult blood in vitro. Consistent with previous reports, CD4+ T cells do not express CD40L after T‐cell activation. In whole blood, adult monocytes, but not neonatal monocytes, were activated following T‐cell activation. However, the activation of adult monocytes was not dependent on the CD40L–CD40 interaction. Using the CD40L trimer (Lt), we showed that cord B cells have comparable responses to CD40 ligation to those of the adult B cells. Both cord and adult monocytes do not respond as well as B cells and this is probably related to low density of expression of CD40. However, interferon‐γ up‐regulated CD40 on adult monocytes but not on cord monocytes. This potentiated the adult monocyte response to CD40 ligation by CD40Lt. Our findings suggest that the neonatal CD40L–CD40 pair is immature in the cellular immune response involving monocytes and that interferon‐γ fails to activate neonatal monocytes for a response to CD40L. These findings suggest that in the inflammatory microenvironment of cord blood transplantation neonatal monocytes may play a minor role in the effector arm of the immune response. This finding may be one of several mechanisms for the low incidence of GVHD that is observed following cord blood transplantation. Also the ligand‐receptor immaturity may contribute to the increased susceptibility of newborns to certain infections.
Monocytosis and accelerated activation of lymphocytes in C1q‐deficient autoimmune‐prone mice
Authors: Trendelenburg Marten , Manderson Anthony P. , Fossati‐Jimack Liliane , Walport Mark J. , Botto Marina 
Published: August 2004

SummaryC1q deficiency has been shown to accelerate spontaneous autoimmunity in mice. We studied the time course of activation of monocytes and lymphocytes in autoimmune and non‐autoimmune mice in the presence or absence of C1q as a disease accelerator. Autoimmune MRL\Mp.C1qa−\− and non‐autoimmune C57BL\6.C1qa−\− mice were analysed at various time points between 6 and 33 weeks of age and compared to strain‐ and age‐matched C1q‐sufficient controls. Splenic and peritoneal leucocytes were analysed by flow cytometry and plasma levels of immunoglobulin M (IgM), total IgG, IgG subclasses and IgM autoantibodies were measured. Both C1q‐deficient strains had significantly more splenic monocytes than their controls at all time points analysed. In addition, MRL\Mp.C1qa−\− but not C57BL/6.C1qa−\− mice developed splenic hypercellularity starting at about 12–17 weeks old, had signs of accelerated CD4+ T‐cell activation and showed a marked increase in splenic plasma cells and total serum IgM levels from about 22 weeks of age. The accelerated CD4+ T‐cell activation was not due to a direct inhibitory effect of C1q on T cells. These data show that C1q deficiency causes splenic monocytosis together with accelerated T‐cell activation in an autoimmune‐prone mouse strain.
Improving M cell mediated transport across mucosal barriers: do certain bacteria hold the keys?
Authors: Man Angela L. , Prieto‐Garcia Maria Elena , Nicoletti Claudio 
Published: August 2004

SummarySpecialized microfold (M) cells of the follicle‐associated epithelium (FAE) of the mucosal‐associated lymphoid tissue (MALT) in gut and the respiratory system play an important role in the genesis of both mucosal and systemic immune responses by delivering antigenic substrate to the underlying lymphoid tissue where immune responses start. Although it has been shown that dendritic cells (DC) also have the ability to sample antigens directly from the gut lumen, M cells certainly remain the most important antigen‐sampling cell to be investigated in order to devise novel methods to improve mucosal delivery of biologically active compounds. Recently, novel information on the interactions between bacteria and FAE have come to light that unveil further the complex cross‐talk taking place at mucosal interfaces between bacteria, epithelial cells and the immune system and which are central to the formation and function of M cells. In particular, it has been shown that M cell mediated transport of antigen across the FAE is improved rapidly by exposure to certain bacteria, thus opening the way to identify new means to achieve a more effective mucosal delivery. Here, these novel findings and their potential in mucosal immunity are analysed and discussed, and new approaches to improve antigen delivery to the mucosal immune system are also proposed.
Phenotypic selection and regulation of reproduction in different environments in wild barley
Authors: Volis S. , Verhoeven K. J. F. , Mendlinger S. , Ward D. 
Published: August 2004

Abstract
Plasticity of the phenotypic architecture of wild barley, Hordeum spontaneum, was studied in response to water and nutrient stress. Direct and indirect selection on several vegetative and reproductive traits was estimated and path analysis used to reveal how regulating pathways via maternal investment differed between environments. Vegetative traits displayed differential regulating effect on fitness across experimental environments: (1) increase in size was selected for under optimal conditions and under water stress, but not under nutrient stress; (2) allocation to root biomass was selected for under optimal conditions, but it had no effect under nutrient stress and was strongly selected against when water was limiting; (3) delayed onset of reproduction was selected under nutrient limitation whereas earlier onset was selected under water stress. The regulating effect of reproductive traits on final reproductive output also differed across treatments, operating either at the ‘early’ stage of plant development through varying the number of initiated spikelets per spike (no stress and water stress treatment) or at the ‘late’ developmental stage adjusting the fertile spikelet weight (no stress and nutrient stress treatment). Reproductive output was regulated via seed abortion under no stress and water stress treatments. Although the underlying mechanism of the regulation through abortion has yet to be discovered, the specific mechanism of abortion under water stress appears to be different from that under optimal conditions. Our results demonstrate that not only is the character architecture in wild barley plastic and sensitive to changing availability of water and nutrients, but the regulating mechanism of maternal investment is also environmentally sensitive.
Sperm competition and diversity in rodent copulatory behaviour
Authors: Stockley P. , Preston B. T. 
Published: August 2004

Abstract
The copulatory behaviour of male mammals is characterized by striking diversity in patterns of copulatory stimulation and ejaculation frequency. We conducted comparative analyses of rodents to investigate the potential influence of sperm competition in the evolution of copulatory behaviour. We found that increasing sperm competition is associated with faster rates of stimulation and earlier ejaculation among species in which males perform multiple intromissions prior to ejaculation, but with no overall change in the number of intromissions per ejaculation. Increasing sperm competition is also associated with a higher frequency of repeated ejaculations with the same female, and with shorter refractory periods between repeated copulations. Increasing sperm competition level thus appears to select for male ability to ejaculate more rapidly and more frequently with each female mated. As prolonged copulations are known to reduce female remating rates, these findings indicate that males may experience opposing selection pressures on copulatory behaviour with respect to offensive and defensive aspects of sperm competition. We conclude that sperm competition is likely to be an important selection pressure explaining diversity in mammalian copulatory behaviour.
Variation in the degree and costs of adaptive phenotypic plasticity among Rana temporaria populations
Authors: Merilä J. , Laurila A. , Lindgren B. 
Published: August 2004

Abstract
Adaptive phenotypic plasticity in the form of capacity to accelerate development as a response to pond drying risk is known from many amphibian species. However, very little is known about factors that might constrain the evolution of this type of plasticity, and few studies have explored to what degree plasticity might be constrained by trade-offs dictated by adaptation to different environmental conditions. We compared the ability of southern and northern Scandinavian common frog (Rana temporaria) larvae originating from 10 different populations to accelerate their development in response to simulated pond drying risk and the resulting costs in metamorphic size in a factorial laboratory experiment. We found that (i) northern larvae developed faster than the southern larvae in all treatments, (ii) a capacity to accelerate the response was present in all five southern and all five northern populations tested, but that the magnitude of the response was much larger (and less variable) in the southern than in the northern populations, and that (iii) significant plasticity costs in metamorphic size were present in the southern populations, the plastic genotypes having smaller metamorphic size in the absence of desiccation risk, but no evidence for plasticity costs was found in the northern populations. We suggest that the weaker response to pond drying risk in the northern populations is due to stronger selection on large metamorphic size as compared with southern populations. In other words, seasonal time constraints that have selected the northern larvae to be fast growing and developing, may also constrain their innate ability for adaptive phenotypic plasticity.
Recombination and loss of complementation: a more than two-fold cost for parthenogenesis
Authors: Archetti M. 
Published: August 2004

Abstract
Certain types of asexual reproduction lead to loss of complementation, that is unmasking of recessive deleterious alleles. A theoretical measure of this loss is calculated for apomixis, automixis and endomitosis in the cases of diploidy and polyploidy. The effect of the consequent unmasking of deleterious recessive mutations on fitness is also calculated. Results show that, depending on the number of lethal equivalents and on the frequency of recombination, the cost produced by loss of complementation after few generations of asexual reproduction may be greater than the two-fold cost of meiosis. Maintaining complementation may, therefore, provide a general short-term advantage for sexual reproduction. Apomixis can replace sexual reproduction under a wide range of parameters only if it is associated with triploidy or tetraploidy, which is consistent with our knowledge of the distribution of apomixis.
When mutualists are pathogens: an experimental study of the symbioses between Steinernema (entomopathogenic nematodes) and Xenorhabdus (bacteria)
Authors: Sicard M. , Ferdy J.-B. , Pagès S. , Le Brun N. , Godelle B. , Boemare N. , Moulia C. 
Published: August 2004

Abstract
In this paper, we investigate the level of specialization of the symbiotic association between an entomopathogenic nematode (Steinernema carpocapsae) and its mutualistic native bacterium (Xenorhabdus nematophila). We made experimental combinations on an insect host where nematodes were associated with non-native symbionts belonging to the same species as the native symbiont, to the same genus or even to a different genus of bacteria. All non-native strains are mutualistically associated with congeneric entomopathogenic nematode species in nature. We show that some of the non-native bacterial strains are pathogenic for S. carpocapsae. When the phylogenetic relationships between the bacterial strains was evaluated, we found a clear negative correlation between the effect a bacterium has on nematode fitness and its phylogenetic distance to the native bacteria of this nematode. Moreover, only symbionts that were phylogenetically closely related to the native bacterial strain were transmitted. These results suggest that co-evolution between the partners has led to a high level of specialization in this mutualism, which effectively prevents horizontal transmission. The pathogenicity of some non-native bacterial strains against S. carpocapsae could result from the incapacity of the nematode to resist specific virulence factors produced by these bacteria.
Complex genetic architecture of population differences in adult lifespan of a beetle: nonadditive inheritance, gender differences, body size and a large maternal effect
Authors: Fox C. W. , Czesak M. E. , Wallin W. G. 
Published: August 2004

Abstract
Evolutionary responses to selection can be complicated when there is substantial nonadditivity, which limits our ability to extrapolate from simple models of selection to population differentiation and speciation. Studies of Drosophila melanogaster indicate that lifespan and the rate of senescence are influenced by many genes that have environment- and sex-specific effects. These studies also demonstrate that interactions among alleles (dominance) and loci (epistasis) are common, with the degree of interaction differing between the sexes and among environments. However, little is known about the genetic architecture of lifespan or mortality rates for organisms other than D. melanogaster. We studied genetic architecture of differences in lifespan and shapes of mortality curves between two populations of the seed beetle, Callosobruchus maculatus (South India and Burkina Faso populations). These two populations differ in various traits (such as body size and adult lifespan) that have likely evolved via host-specific selection. We found that the genetic architecture of lifespan differences between populations differs substantially between males and females; there was a large maternal effect on male lifespan (but not on female lifespan), and substantial dominance of long-life alleles in females (but not males). The large maternal effect in males was genetically based (there was no significant cytoplasmic effect) likely due to population differences in maternal effects genes that influence lifespan of progeny. Rearing host did not affect the genetic architecture of lifespan, and there was no evidence that genes on the Y-chromosome influence the population differences in lifespan. Epistatic interactions among loci were detectable for the mortality rate of both males and females, but were detectable for lifespan only after controlling for body size variation among lines. The detection of epistasis, dominance, and sex-specific genetic effects on C. maculatus lifespan is consistent with results from line cross and quantitative trait locus studies of D. melanogaster.