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991.
Cesarini S Spallarossa A Ranise A Fossa P La Colla P Sanna G Collu G Loddo R 《Bioorganic & medicinal chemistry》2008,16(7):4160-4172
992.
Perrone MG Santandrea E Bleve L Vitale P Colabufo NA Jockers R Milazzo FM Sciarroni AF Scilimati A 《Bioorganic & medicinal chemistry》2008,16(5):2473-2488
Since it is widely distributed into the body, beta(3)-adrenoceptor is becoming an attractive target for the treatment of several pathologies such as obesity, type 2 diabetes, metabolic syndrome, cachexia, overactive bladder, ulcero-inflammatory disorder of the gut, preterm labour, anxiety and depressive disorders, and heart failure. New compounds belonging to the class of arylethanolamines bearing one or two stereogenic centres were prepared in good yields as racemates and optically active forms. They were, then, evaluated for their intrinsic activity towards beta(3)-adrenoceptor and their affinity for beta(1)- and beta(2)-adrenergic receptors. Stereochemical features were found to play a crucial role in determining the behaviour of such compounds. In particular, alpha-racemic, (alphaR)- and (alphaS)-2-{4-[2-(2-hydroxy-2-phenylethylamino)ethyl]phenoxy}-2- methylpropanoic acid, (alpha-rac, beta-rac)-, (alphaR, betaS)- and (alphaR, betaR)- 2-{4-[2-(2-hydroxy-2-phenylethylamino)ethyl]phenoxy}propanoic acid were found to be endowed with beta(3)-adrenoceptor agonistic activity. Whereas, (alphaS, betaS)- and (alphaS, betaR)-2-{4-[2-(2-hydroxy-2-phenylethylamino)ethyl]phenoxy}propanoic acid behaved as beta(3)-adrenoceptor inverse agonists. Such compounds showed no affinity for beta(1)- and beta(2)-adrenergic receptor, respectively. Thus, resulting highly selective beta(3)-adrenoceptor ligands. 相似文献
993.
Novellino L De Filippo A Deho P Perrone F Pilotti S Parmiani G Castelli C 《Cellular signalling》2008,20(5):872-883
994.
Vincenzo Penteriani Maria Del Mar Delgado Paola Bartolommei Carlotta Maggio Carlos Alonso‐Alvarez Graham J. Holloway 《Journal of avian biology》2008,39(2):215-221
The interactions among the multiple factors regulating predator-prey relationships make predation a more complex process than previously thought. The degree to which substandard individuals are captured disproportionately seems to be better a function of the difficulty of prey capture than of the hunting techniques (coursing vs. ambushing predators). That is, when the capture and killing of a prey species is easy, substandard individuals will be predated in proportion to their occurrence in the prey population. In the present study, we made use of eagle owls Bubo bubo and their main prey, the rabbit Oryctolagus cuniculus : (a) the brightness of the white tails of rabbits seems to be correlated with the physical condition of individuals, (b) by using the tails of predated rabbits as an index of individual condition, we found that eagle owls seem to prefer substandard individuals (characterized by duller tails), and (c) by using information from continuous radiotracking of 14 individuals, we suggest that the difficulty of rabbit capture could be low. Although the relative benefits of preying on substandard individuals should considerably decrease when a predator is attacking an easy prey, we hypothesise that the eagle owl preference for substandard individuals could be due to the easy detection of poor individuals by a visual cue, the brightness of the rabbit tail. Several elements allow us to believe that this form of visual communication between a prey and one of its main predators could be more widespread than previously thought. In fact: (a) visual signalling plays a relevant role in intraspecific communication in eagle owls and, consequently, visual signals could also play a role in interspecific interactions, and (b) empirical studies showed that signals may inform the predator that it has been perceived, or that the prey is in a sufficiently healthy state to elude the predator. 相似文献
995.
Siracusano A Margutti P Delunardo F Profumo E Riganò R Buttari B Teggi A Ortona E 《International journal for parasitology》2008,38(12):1371-1376
Cystic echinococcosis (CE), a zoonosis caused by the development of Echinococcus granulosus tapeworm larvae in the internal organs of ungulates and humans, continues to pose a major public health burden in underdeveloped and industrialised areas worldwide. Research designed to improve parasitic disease control and find out more about parasite biology has already identified a number of E. granulosus antigenic molecules. The major E. granulosus immunomodulant antigen isolated from hydatid fluid is antigen B, a 120kDa polymeric lipoprotein consisting of various 8kDa subunits. By inhibiting elastase activity and neutrophil chemotaxis and eliciting a non-protective Th2 cell response, antigen B helps the parasite evade the human response. In this review, we briefly discuss current information on the molecular characteristics and immunomodulatory properties of E. granulosus antigen B. Besides focusing on findings that provide intriguing insights into the complex interplay between host and parasite, we suggest how this information could extend the current therapeutic options in inflammatory diseases. 相似文献
996.
Alessio Fortunati Silvia Piconese Paola Tassone Simone Ferrari Fernando Migliaccio 《Plant signaling & behavior》2008,3(11):989-990
A new Arabidopsis mutant is characterized (rha1) that shows, in the roots, reduced right-handed slanting, reduced gravitropism and resistance to 2,4-D, TIBA, NPA and ethylene. It also shows reduced length in the shoot and root, reduced number of lateral roots and shorter siliques. The gene was cloned through TAIL-PCR and resulted in a HSF. Because none of the known gravitropic and auxinic mutants result from damage in a HSF, rha1 seems to belong to a new class of this group of mutants. Quantitative PCR analysis showed that the expression of the gene is increased by heat and cold shock, and by presence of 2,4-D in the media. Study of the expression through the GUS reporter gene revealed increased expression in clinostated and gravistimulated plants, but only in adult tissues, and not in the apical meristems of shoots and roots.Key words: auxin, ethylene, slanting, gravitropism, HSFsArabidopsis primary roots, and especially those from some ecotypes (Ws, Landsberg), when grown on an agar dish, tilted on the vertical, show a wavy pattern, and a clear slanting towards a direction that has been considered the right-hand.1–4 In the case of the mutant rha1, the right-handed slanting is notably reduced, its primary roots growing partly to the right-hand, partly straight down and partly to the left-hand, even though a slight preference for the right-hand is apparent.In addition, its roots show resistance to the inhibitory action of the auxin 2,4-D, ethylene (ACC), and the auxin transport inhibitors TIBA and NPA. These characteristics qualify the mutant as an auxinic one, and therefore a connection between the reduced slanting and the auxinic disturbances could be imagined. It is not known, however, what controls the slanting process itself, even though it appears as the consequence of a chiral circumnutational process. As reported,4 it seems the result of a chiral circumnutation with preference for the right-hand, transformed in a lateral slanting movement, because of the impact of the helix with the hard agar surface. This process results in the formation of waves, when the circumnutation helix impactig the agar reverses direction at every half turn, or the formation of large loops and strict loops (coils) when there is no reversion. The latter case seems to be a consequence of the fact that gravity is no longer “felt”. This has been previously noted in some mutants, or sometimes in old roots.rha1 is not the only mutant known to show reduction or increase of slanting, because other mutants were reported by Rutherford and Masson,3 and subsequent publications from the same group. Almost all show an increase of slant, with the exception of rhd3 and its alleles that show a complete suppression of the process.5 The mutated gene in rha1 was cloned through TAIL-PCR and shown to be a HSF. No other auxinic mutant, among those for which the gene was cloned, is known to be mutated in a HSF.HSFs, that are characteristically involved in the activation of the HSPs (heat shock proteins), which protect the cells from damage arising from high temperature and other stresses, have been shown to be involved also in different processes.6,7 Hence, also in the case of rha1, we can well imagine other different functions, beside that of counteracting the heat shock. In particular, since the connection with auxin regulated processes is evident, we can suppose that the action could be on the PP2A phosphatase, as in the case of the rcn1 mutant, or of the human HSF2. The RCN1 protein corresponds to one unit of the PP2A,8 and the HSF29 has been shown to substitute itself for the C subunit and alter the function of the phosphatase (Fig. 1). Experiments directed to see if a heat shock can modify the slanting of the roots in the wild-type and rha1, gave negative results, even though these experiments will need to be repeated under more widely ranging conditions. These results seem to indicate that the mechanism which induces asymmetric growth in roots is complex, and it is not controlled by a single gene.Open in a separate windowFigure 1Model proposed for the regulation of the PP2A activity by the RHA1 protein. (modified after Hong and Sarge, 1999).On the other hand, another puzzling characteristic of rha1 is the fact that its roots are resistant only to the auxin 2,4-D, and not to NAA and IAA. Differences in the response of the primary roots to different auxins have already been reported, and it was suggested that the response to NAA should be different, because this substance can penetrate passively the cell membranes.10 In the case of rha1, however, it seems that IAA can also penetrate the cells passively. This is in line with the chemiosmotic hypothesis,11 but seems in contrast with the previous supposition. The resistance to ethylene, however, could indicate that the reduced inhibitory effect of 2,4-D is a consequence of the ethylene production induced by the synthetic auxin. On the other hand, the resistance to the auxin transport inhibitors TIBA and NPA, cannot be explained so easily. Possibly, in the mutant rha1, there is a reduced level of receptors for the considered substances.Using semiquantitative PCR analysis it was shown that rha1 retains the function of a HSF, the gene being clearly upregulated by heat and cold stress, and also by 2,4-D, but not by rotation on a clinostat or gravistimulation. The upregulation of the expression by 2,4-D was confirmed by a study of GUS expression in a transformed rha1, and with this technique the effects of gravity and simulated microgravity appeared clearly stimulatory too. No GUS expression however was apparent in the shoot and root meristems, and consequently we propose that the gene does not influence the first part of the graviresponse, but possibly the general transport of auxin through the plant.Thus, the mutant seems to be disturbed in root gravitropism, as well as in responses to the auxines and circumnutation. However not in the general circumnutation process, but in its chiral aspect, which is the cause of the slanting to the right-hand. Gravitropism, circumnutation and auxin physiology, thus, seem to be in some way connected in a complex integrated process, that, hopefully, will be gradually revealed in all its different aspects, through the future efforts of plant scientists. 相似文献
997.
Paola Spessotto Anna Gronkowska Rainer Deutzmann Roberto Perris Alfonso Colombatti 《Matrix biology》2003,22(4):351-361
To identify the laminin isoforms of the basement membranes that could be implicated in the extravasation process of neoplastic lymphocytes, a number of purified laminins and one native renal laminin complex were comparatively investigated for their ability to promote migration of neoplastic lymphocytes in vitro. The identity/composition of a human placental laminin complex was asserted by combining immunochemical assays, sequence determination of tryptic peptides, and ultrastructural analysis to be composed predominantly of laminin-10 in which the coiled-coil C-terminal regions and the G globular domain of the alpha5 chain were preserved intact despite the enzymatic treatment used for its isolation. Lymphoma and leukemic cell lines failed to migrate towards laminin-4, -9, -11, moved poorly in response to laminin-1, -2/4, -5 and the renal laminin complex, but markedly locomoted towards the subendothelial laminin-8 and -10. The motility-promoting interaction with these latter laminins was interchangeably mediated by the alpha3beta1 and alpha6beta1 integrins. Lymphocyte locomotion on laminins assayed in the presence of cytokines was either reduced or enhanced suggesting that local cytokine milieu could further influence motility response. 相似文献
998.
Saino Nicola; Ambrosini Roberto; Martinelli Roberta; Ninni Paola; Moller Anders Pape 《Behavioral ecology》2003,14(1):16-22
In some passerines, parents allocate more food to offspringwith the brightest red gapes, but the function of parental decisionsbased on offspring gape coloration is unknown. We hypothesizethat gape coloration is part of a communication system wherenestlings reveal their condition to attending parents, whichmay thus base their decisions on reliable signals of offspringreproductive value. We analyze the effects of brood size manipulation,injection with an immunogen and food deprivation, on gape coloration,morphology, and T-cellmediated immunocompetence of nestlingbarn swallows (Hirundo rustica). For each gape we measured threecomponents of coloration (hue, saturation, and brightness) andobtained an overall color score by principal component analysis.Enlargement of brood size and injection with an antigen resultedin less red and less saturated and brighter gape color. Nestlingsin enlarged broods had smaller body mass and T-cellmediatedimmunocompetence compared to those in reduced broods. A positivecovariation existed between redness and saturation of gape colorand T-cellmediated immunocompetence. Gape color siblingsraised in different nests did not depend on parentage. Thus,condition-dependent gape coloration can reveal different componentsof nestling state on which parents may base their adaptive decisionsabout allocation of care to the offspring. 相似文献
999.
Antonio Giordano Paola Cesari Lorena Capparuccia Mario Castellucci Saverio Cinti 《Brain Cell Biology》2003,32(4):345-352
Semaphorins are cell surface and/or soluble signals that exert an inhibitory control on axon guidance. Sema3A, the vertebrate-secreted semaphorin, binds to neuropilin-1, which together with plexins constitutes the functional receptor. To verify whether Sema3A is produced by white adipocytes and, in that case, to detect its targets in white adipose tissue, we studied the cell production and tissue distribution of Sema3A and neuropilin-1 in rat retroperitoneal and epididymal adipose depots. Sema3A and neuropilin-1 were detected in these depots by Western blotting. The immunohistochemical results showed that Sema3A is produced in, and possibly secreted by, smooth muscle cells of arteries and white adipocytes. Accordingly, neuropilin-1 was found on perivascular and parenchymal nerves. Such a pattern of distribution is in line with a role for secreted Sema3A in the growth and plasticity of white adipose tissue nerves. Indeed, after fasting, when white adipocytes are believed to be overstimulated by noradrenaline and rearrangement of the parenchymal nerve supply may occur, adipocytic expression of Sema3A is reduced. Finally, the presence of neuropilin-1 in some white adipocytes raises the interesting possibility that Sema3A also exerts an autocrine-paracrine role on these cells. 相似文献
1000.
Modified peptides in anti-cancer vaccines: are we eventually improving anti-tumour immunity? 总被引:1,自引:0,他引:1
Iero M Filipazzi P Castelli C Belli F Valdagni R Parmiani G Patuzzo R Santinami M Rivoltini L 《Cancer immunology, immunotherapy : CII》2009,58(7):1159-1167
The discovery of tumour antigens recognized by T cells and the features of immune responses directed against them has paved
the way to a multitude of clinical studies aimed at boosting anti-tumour T cell immunity as a therapeutic tool for cancer
patients. One of the different strategies explored to ameliorate the immunogenicity of tumour antigens in vaccine protocols
is represented by the use of optimized peptides or altered peptide ligands, whose amino acid sequence has been modified for
improving HLA binding or TCR interaction with respect to native epitopes. However, despite the promising results achieved
with preclinical studies, the clinical efficacy of this approach has not yet met the expectations. Although multiple reasons
could explain the relative failure of altered peptide ligands as more effective cancer vaccines, the possibility that T cells
primed by modified tumour peptides might may be unable to effectively cross-recognize tumour cells has not been sufficiently
addressed. Indeed, the introduction of conservative amino acid substitutions may still produce diverse and unpredictable changes
in the HLA/peptide interface, with consequent modifications of the TCR repertoire that can interact with the complex. This
could lead to the expansion of a broad array of T cells whose TCRs may not necessarily react with equivalent affinity with
the original antigenic epitope. Considering the results presently achieved with this vaccine approach, and the emerging availability
of alternative strategies for boosting anti-tumour immunity, the use of modified tumour peptides could be reconsidered.
This article is a symposium paper from the conference “Immunotherapy—From Basic Research to Clinical Applications”, Symposium
of the Collaborative Research Center (SFB) 685, held in Tübingen, Germany, 6–7 March 2008. 相似文献