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321.
IL‐23 drives differentiation of peripheral γδ17 T cells from adult bone marrow‐derived precursors 下载免费PDF全文
Pedro H Papotto Natacha Gonçalves‐Sousa Nina Schmolka Andrea Iseppon Sofia Mensurado Brigitta Stockinger Julie C Ribot Bruno Silva‐Santos 《EMBO reports》2017,18(11):1957-1967
Pro‐inflammatory interleukin (IL)‐17‐producing γδ (γδ17) T cells are thought to develop exclusively in the thymus during fetal/perinatal life, as adult bone marrow precursors fail to generate γδ17 T cells under homeostatic conditions. Here, we employ a model of experimental autoimmune encephalomyelitis (EAE) in which hematopoiesis is reset by bone marrow transplantation and demonstrate unequivocally that Vγ4+ γδ17 T cells can develop de novo in draining lymph nodes in response to innate stimuli. In vitro, γδ T cells from IL‐17 fate‐mapping reporter mice that had never activated the Il17 locus acquire IL‐17 expression upon stimulation with IL‐1β and IL‐23. Furthermore, IL‐23R (but not IL‐1R1) deficiency severely compromises the induction of γδ17 T cells in EAE, demonstrating the key role of IL‐23 in the process. Finally, we show, in a composite model involving transfers of both adult bone marrow and neonatal thymocytes, that induced γδ17 T cells make up a substantial fraction of the total IL‐17‐producing Vγ4+ T‐cell pool upon inflammation, which attests the relevance of this novel pathway of peripheral γδ17 T‐cell differentiation. 相似文献
322.
Rui F. Oliveira Natacha Carvalho† Jason Miranda†‡ Emanuel J. Gonçalves Matthew Grober‡ & Ricardo Serrão Santos† 《Ethology : formerly Zeitschrift fur Tierpsychologie》2002,108(3):223-235
In the Azorean rock-pool blenny, sexually active males may adopt alternative reproductive tactics. In the present paper the relationship between the presence of satellite males and the reproductive success of nest-holders was investigated by comparing nests with and without an associated satellite male. Males with an associated satellite male suffered more conspecific intrusions but they did not display a higher frequency of attacks towards conspecifics. Nest-holder males were more aggressive towards other conspecifics than towards satellites and the tolerance of nest-holders towards satellites was inversely correlated with the time spent by the satellites in the breeding territory, which suggests control by the nest-holder male of the satellite investment in shared territorial defence. Nest-holders with an associated satellite male had higher condition factors and received more female visits and more spawnings. These results bear two possible interpretations. (1) Nest-holders benefit from the presence of a satellite male by increased attractiveness of their nests to females; satellite males are mutualists helping to defend the nest-owner's territory and to attract females, which is why they are tolerated. (2) Satellite males associate preferentially with more successful nest-holder males which have higher condition factors, and by doing so have more opportunities to achieve parasitic fertilizations. Only experiments will allow these two hypotheses to be distinguished. 相似文献
323.
Ramon R. P. P. B. de Menezes Clarissa P. Mello Danya B. Lima Louise D. Tessarolo Tiago Lima Sampaio Lívia C. F. Paes Natacha T. Q. Alves Eudmar M. Assis Junior Roberto C. P. Lima Junior Marcos H. Toyama Alice M. C. Martins 《PloS one》2016,11(3)
Viperidae venom has several local and systemic effects, such as pain, edema, inflammation, kidney failure and coagulopathy. Additionally, bothropic venom and its isolated components directly interfere on cellular metabolism, causing alterations such as cell death and proliferation. Inflammatory cells are particularly involved in pathological envenomation mechanisms due to their capacity of releasing many mediators, such as nitric oxide (NO). NO has many effects on cell viability and it is associated to the development of inflammation and tissue damage caused by Bothrops and Bothropoides venom. Bothropoides insularis is a snake found only in Queimada Grande Island, which has markedly toxic venom. Thus, the aim of this work was to evaluate the biological effects of Bothropoides insularis venom (BiV) on RAW 264.7 cells and assess NO involvement. The venom was submitted to colorimetric assays to identify the presence of some enzymatic components. We observed that BiV induced H2O2 production and showed proteolytic and phospholipasic activities. RAW 264.7 murine macrophages were incubated with different concentrations of BiV and then cell viability was assessed by MTT reduction assay after 2, 6, 12 and 24 hours of incubation. A time- and concentration-dependent effect was observed, with a tendency to cell proliferation at lower BiV concentrations and cell death at higher concentrations. The cytotoxic effect was confirmed after lactate dehydrogenase (LDH) measurement in the supernatant from the experimental groups. Flow cytometry analyses revealed that necrosis is the main cell death pathway caused by BiV. Also, BiV induced NO release. The inhibition of both proliferative and cytotoxic effects with L-NAME were demonstrated, indicating that NO is important for these effects. Finally, BiV induced an increase in iNOS expression. Altogether, these results demonstrate that B. insularis venom have proliferative and cytotoxic effects on macrophages, with necrosis participation. We also suggest that BiV acts by inducing iNOS expression and causing NO release. 相似文献
324.
Natacha Coelho María Elena González-Benito Anabela Romano 《Acta Physiologiae Plantarum》2014,36(12):3333-3336
Tuberaria major is an endangered endemic species from the Algarve, in the south of Portugal. We investigated two techniques for the cryopreservation of T. major shoot tips, namely vitrification and encapsulation-dehydration. Before the cryopreservation trials, shoot tips were precultured for 1 day on liquid Murashige and Skoog (MS) medium containing 0.3 M sucrose. For the vitrification method, shoots tips were exposed for 0, 30, 60, 90 and 120 min to plant vitrification solution 2 (PVS2). As for the encapsulation-dehydration method, shoot tips were dried inside a laminar air flow cabinet for 0, 1, 2, 3, 4, 5 and 6 h at room temperature. The highest regrowth percentages were approximately 60 and 67 % for vitrification and encapsulation-dehydration, respectively. The best times were 60 min exposure to PVS2 for vitrification and 3 h desiccation for encapsulation-dehydration. Though these are preliminary results, the use of the cryopreservation techniques tested here proved to be an important asset in the conservation of this endangered species and will complement the conservation strategies previously developed. 相似文献
325.
Genevieve Paulissen Natacha Rocks Maud M Gueders Celine Crahay Florence Quesada-Calvo Sandrine Bekaert Jonathan Hacha Mehdi El Hour Jean-Michel Foidart Agnes Noel Didier D Cataldo 《Respiratory research》2009,10(1):127
Lungs are exposed to the outside environment and therefore to toxic and infectious agents or allergens. This may lead to permanent activation of innate immune response elements. A Disintegrin And Metalloproteinases (ADAMs) and ADAMs with Thrombospondin motifs (ADAMTS) are proteinases closely related to Matrix Metalloproteinases (MMPs). These multifaceted molecules bear metalloproteinase and disintegrin domains endowing them with features of both proteinases and adhesion molecules. Proteinases of the ADAM family are associated to various physiological and pathological processes and display a wide spectrum of biological effects encompassing cell fusion, cell adhesion, "shedding process", cleavage of various substrates from the extracellular matrix, growth factors or cytokines... This review will focus on the putative roles of ADAM/ADAMTS proteinases in airway diseases such as asthma and COPD. 相似文献
326.
Veerapen N Reddington F Salio M Cerundolo V Besra GS 《Bioorganic & medicinal chemistry》2011,19(1):221-228
Stimulation of iNKT cells by ??-galactosyl ceramide (??-GalCer), also known as KRN7000, and its truncated analogue OCH induces both Th1- and Th2-cytokines, with OCH inducing a Th2-cytokine bias. Skewing of the iNKT cells’ response towards either a Th1- or Th2-cytokine profile offers potential therapeutic benefits. The length of both the acyl and the sphingosine chains in ??-galactosyl ceramides is known to influence the cytokine release profile. We have synthesized analogues of ??-GalCer with truncated sphingosine chains for biological evaluation, with particular emphasis on the Th1/Th2 distribution. Starting from a common precursor, d-lyxose, the sphingosine derivatives were synthesised via a straightforward Wittig condensation. 相似文献
327.
Background
Used as contrast agents for brain magnetic resonance imaging (MRI), markers for beta-amyloid deposits might allow early diagnosis of Alzheimer''s disease (AD). We evaluated the cost-effectiveness of such a diagnostic test, MRI+CLP (contrastophore-linker-pharmacophore), should it become clinically available.Methodology/Principal Findings
We compared the cost-effectiveness of MRI+CLP to that of standard diagnosis using currently available cognition tests and of standard MRI, and investigated the impact of a hypothetical treatment efficient in early AD. The primary analysis was based on the current French context for 70-year-old patients with Mild Cognitive Impairment (MCI). In alternative “screen and treat” scenarios, we analyzed the consequences of systematic screenings of over-60 individuals (either population-wide or restricted to the ApoE4 genotype population). We used a Markov model of AD progression; model parameters, as well as incurred costs and quality-of-life weights in France were taken from the literature. We performed univariate and probabilistic multivariate sensitivity analyses.The base-case preferred strategy was the standard MRI diagnosis strategy. In the primary analysis however, MRI+CLP could become the preferred strategy under a wide array of scenarios involving lower cost and/or higher sensitivity or specificity. By contrast, in the “screen and treat” analyses, the probability of MRI+CLP becoming the preferred strategy remained lower than 5%.Conclusions/Significance
It is thought that anti-beta-amyloid compounds might halt the development of dementia in early stage patients. This study suggests that, even should such treatments become available, systematically screening the over-60 population for AD would only become cost-effective with highly specific tests able to diagnose early stages of the disease. However, offering a new diagnostic test based on beta-amyloid markers to elderly patients with MCI might prove cost-effective. 相似文献328.
Different modes of acoustic communication in deep‐diving short‐finned pilot whales (Globicephala macrorhynchus) 下载免费PDF全文
Jacobo Marrero Pérez Frants H. Jensen Laia Rojano‐Doñate Natacha Aguilar de Soto 《Marine Mammal Science》2017,33(1):59-79
Toothed whales use a pneumatic sound generator to produce echolocation and communication sounds. Increasing hydrostatic pressure at depth influences the amplitude and duration of calls but not of echolocation clicks. Here we test the hypothesis that information transfer at depth might be facilitated by click‐based communication signals. Wild short‐finned pilot whales (27) instrumented with multisensor DTAGs produced four main types of communication signals: low‐ and medium‐frequency calls (median fundamental frequency: 1.7 and 2.9 kHz), two‐component calls (median frequency of the low and high frequency components: 2 and 9 kHz), and rasps (burst‐pulses with median interclick interval of 21 ms). Rasps can be confused with foraging buzzes, but rasps are shorter and slower, and are not associated with fast changes in body acceleration nor reduced acoustic output of buzzes, characteristic of prey capture attempts. Contrary to calls, the energy flux density of rasps was not significantly affected by depth. This, and a different information content, may explain the observed increase in the relative occurrence of rasps with respect to calls at depth, and supports the hypothesis that click‐based communication signals may facilitate communication under high hydrostatic pressure. However, calls are produced at depth also, indicating that they may carry additional information relevant for deep‐diving animals, including potential communication among whales diving at the same time in this highly social deep‐diving species. 相似文献
329.
Tye H Mueller SG Prestle J Scheuerer S Schindler M Nosse B Prevost N Brown CJ Heifetz A Moeller C Pedret-Dunn A Whittaker M 《Bioorganic & medicinal chemistry letters》2011,21(1):34-37
The discovery of a novel series of 5-HT2C agonists based on a tricyclic pyrazolopyrimidine scaffold is described. Compounds with good levels of in vitro potency and moderate to good levels of selectivity with respect to the 5-HT2A and 5-HT2B receptors were identified. One of the analogues (7g) was found to be efficacious in a sub-chronic weight loss model. A key limitation of the series of compounds was that they were found to be potent inhibitors of the hERG ion channel. Some compounds, bearing polar side chains were identified which showed a much reduced hERG liability however these compounds were sub-optimal in terms of their in vitro potency or selectivity. 相似文献
330.
Luísa Gigante Carvalheiro Jacobus Christiaan Biesmeijer Gita Benadi Jochen Fründ Martina Stang Ignasi Bartomeus Christopher N. Kaiser‐Bunbury Mathilde Baude Sofia I. F. Gomes Vincent Merckx Katherine C. R. Baldock Andrew T. D. Bennett Ruth Boada Riccardo Bommarco Ralph Cartar Natacha Chacoff Juliana Dänhardt Lynn V. Dicks Carsten F. Dormann Johan Ekroos Kate S.E. Henson Andrea Holzschuh Robert R. Junker Martha Lopezaraiza‐Mikel Jane Memmott Ana Montero‐Castaño Isabel L. Nelson Theodora Petanidou Eileen F. Power Maj Rundlöf Henrik G. Smith Jane C. Stout Kehinde Temitope Teja Tscharntke Thomas Tscheulin Montserrat Vilà William E. Kunin 《Ecology letters》2014,17(11):1389-1399
Co‐flowering plant species commonly share flower visitors, and thus have the potential to influence each other's pollination. In this study we analysed 750 quantitative plant–pollinator networks from 28 studies representing diverse biomes worldwide. We show that the potential for one plant species to influence another indirectly via shared pollinators was greater for plants whose resources were more abundant (higher floral unit number and nectar sugar content) and more accessible. The potential indirect influence was also stronger between phylogenetically closer plant species and was independent of plant geographic origin (native vs. non‐native). The positive effect of nectar sugar content and phylogenetic proximity was much more accentuated for bees than for other groups. Consequently, the impact of these factors depends on the pollination mode of plants, e.g. bee or fly pollinated. Our findings may help predict which plant species have the greatest importance in the functioning of plant–pollination networks. 相似文献