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911.
Vitamin C modulates glutamate transport and NMDA receptor function in the retina 总被引:1,自引:0,他引:1
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Ivan Domith Renato Socodato Camila C. Portugal Andressa F. Munis Aline T. Duarte‐Silva Roberto Paes‐de‐Carvalho 《Journal of neurochemistry》2018,144(4):408-420
912.
Binding screen for cystic fibrosis transmembrane conductance regulator correctors finds new chemical matter and yields insights into cystic fibrosis therapeutic strategy
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Justin D. Hall Hong Wang Laura J. Byrnes Suman Shanker Kelong Wang Ivan V. Efremov P. Andrew Chong Julie D. Forman‐Kay Ann E. Aulabaugh 《Protein science : a publication of the Protein Society》2016,25(2):360-373
The most common mutation in cystic fibrosis (CF) patients is deletion of F508 (ΔF508) in the first nucleotide binding domain (NBD1) of the CF transmembrane conductance regulator (CFTR). ΔF508 causes a decrease in the trafficking of CFTR to the cell surface and reduces the thermal stability of isolated NBD1; it is well established that both of these effects can be rescued by additional revertant mutations in NBD1. The current paradigm in CF small molecule drug discovery is that, like revertant mutations, a path may exist to ΔF508 CFTR correction through a small molecule chaperone binding to NBD1. We, therefore, set out to find small molecule binders of NBD1 and test whether it is possible to develop these molecules into potent binders that increase CFTR trafficking in CF‐patient‐derived human bronchial epithelial cells. Several fragments were identified that bind NBD1 at either the CFFT‐001 site or the BIA site. However, repeated attempts to improve the affinity of these fragments resulted in only modest gains. Although these results cannot prove that there is no possibility of finding a high‐affinity small molecule binder of NBD1, they are discouraging and lead us to hypothesize that the nature of these two binding sites, and isolated NBD1 itself, may not contain the features needed to build high‐affinity interactions. Future work in this area may, therefore, require constructs including other domains of CFTR in addition to NBD1, if high‐affinity small molecule binding is to be achieved. 相似文献
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Pablo?Ramon?Gualberto?Cardoso Emerson?Vasconcelos?de?Andrade Lima Mariana?Modesto?de?Andrade Lima Moacyr?Jesus?Barreto?de?Melo Rêgo Claudia?Diniz?Lopes?Marques Ivan?da?Rocha Pitta Angela?Luzia?Branco?Pinto?Duarte Maira?Galdino?da?Rocha PittaEmail author 《European cytokine network》2016,27(1):1-5
Objective and Design
Psoriasis is a common, enigmatic, and recurrent disease. The precise etiology and pathogenesis of psoriasis are still unclear. Psoriasis has been treated as an inflammatory disorder related to an underlying Th1/Th17-dominated immune response. Interleukins are involved in the development of psoriasis lesions through Th-17-associated inflammation. Th1 and Th17 cytokines are found in skin lesions and in the peripheral blood of psoriasis patients.We sought to analyze serum levels of IL-1-β, IL-8, IL-9, IL-27, IL-29, IL-35, IFN-γ, TNF and TGF-β in patients with psoriasis and healthy control volunteers.Material
Blood samples were collected from fifty-three patients with psoriasis and thirty-five healthy controls.Methods
Serum cytokines concentrations were determined using an enzyme-linked immunosorbent assay.Results
Serum IL-8, IL-9, IL-27, IL-29 and TNF levels were statistically significant in psoriasis patients. Detectable serum IL-9 levels were found in 47 patients of the 53 in the psoriasis group.Conclusions
Interleukins-8, 27, 29 and TNF levels measured in the serum of psoriasis patients were slightly elevated as compared to healthy controls in a weakly significant way. On the other hand, there were highly significant differences in IL-9 levels between the two groups.914.
Animal behaviour shapes the ecological effects of ocean acidification and warming: moving from individual to community‐level responses
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Biological communities are shaped by complex interactions between organisms and their environment as well as interactions with other species. Humans are rapidly changing the marine environment through increasing greenhouse gas emissions, resulting in ocean warming and acidification. The first response by animals to environmental change is predominantly through modification of their behaviour, which in turn affects species interactions and ecological processes. Yet, many climate change studies ignore animal behaviour. Furthermore, our current knowledge of how global change alters animal behaviour is mostly restricted to single species, life phases and stressors, leading to an incomplete view of how coinciding climate stressors can affect the ecological interactions that structure biological communities. Here, we first review studies on the effects of warming and acidification on the behaviour of marine animals. We demonstrate how pervasive the effects of global change are on a wide range of critical behaviours that determine the persistence of species and their success in ecological communities. We then evaluate several approaches to studying the ecological effects of warming and acidification, and identify knowledge gaps that need to be filled, to better understand how global change will affect marine populations and communities through altered animal behaviours. Our review provides a synthesis of the far‐reaching consequences that behavioural changes could have for marine ecosystems in a rapidly changing environment. Without considering the pervasive effects of climate change on animal behaviour we will limit our ability to forecast the impacts of ocean change and provide insights that can aid management strategies. 相似文献
915.
Few multiyear precipitation–reduction experiments find a shift in the productivity–precipitation relationship
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Marc Estiarte Sara Vicca Josep Peñuelas Michael Bahn Claus Beier Bridget A. Emmett Philip A. Fay Paul J. Hanson Roland Hasibeder Jaime Kigel Gyorgy Kröel‐Dulay Klaus Steenberg Larsen Eszter Lellei‐Kovács Jean‐Marc Limousin Romà Ogaya Jean‐Marc Ourcival Sabine Reinsch Osvaldo E. Sala Inger Kappel Schmidt Marcelo Sternberg Katja Tielbörger Albert Tietema Ivan A. Janssens 《Global Change Biology》2016,22(7):2570-2581
Well‐defined productivity–precipitation relationships of ecosystems are needed as benchmarks for the validation of land models used for future projections. The productivity–precipitation relationship may be studied in two ways: the spatial approach relates differences in productivity to those in precipitation among sites along a precipitation gradient (the spatial fit, with a steeper slope); the temporal approach relates interannual productivity changes to variation in precipitation within sites (the temporal fits, with flatter slopes). Precipitation–reduction experiments in natural ecosystems represent a complement to the fits, because they can reduce precipitation below the natural range and are thus well suited to study potential effects of climate drying. Here, we analyse the effects of dry treatments in eleven multiyear precipitation–manipulation experiments, focusing on changes in the temporal fit. We expected that structural changes in the dry treatments would occur in some experiments, thereby reducing the intercept of the temporal fit and displacing the productivity–precipitation relationship downward the spatial fit. The majority of experiments (72%) showed that dry treatments did not alter the temporal fit. This implies that current temporal fits are to be preferred over the spatial fit to benchmark land‐model projections of productivity under future climate within the precipitation ranges covered by the experiments. Moreover, in two experiments, the intercept of the temporal fit unexpectedly increased due to mechanisms that reduced either water loss or nutrient loss. The expected decrease of the intercept was observed in only one experiment, and only when distinguishing between the late and the early phases of the experiment. This implies that we currently do not know at which precipitation–reduction level or at which experimental duration structural changes will start to alter ecosystem productivity. Our study highlights the need for experiments with multiple, including more extreme, dry treatments, to identify the precipitation boundaries within which the current temporal fits remain valid. 相似文献
916.
Responses of riparian plant communities and water quality after 8 years of passive ecological restoration using a BACI design 总被引:1,自引:0,他引:1
Isabelle?MullerEmail author Marion?Delisle Martine?Ollitrault Ivan?Bernez 《Hydrobiologia》2016,769(1):67-78
This study investigated the consequences of passive ecological restoration on a riparian habitat and on water quality. The restoration plan consists of excluding livestock by constructing fences along an entire stream 1 m from the stream bed, with the assumption that recovering riparian habitat will restore their ecological processes (e.g., filtration, soil stabilization). We measured responses of riparian plant communities and physico-chemical water quality. We presented data from an 8-year before-after control-impact design across a reference stream and a restored stream in a rural landscape in Normandy, France. Restoration appeared to modify plant communities. After 8 years of restoration, the restored stream had a complex riparian bank, similar to that of the reference stream, with an increase in the number of trees, a decrease in bare soil, and an increase in habitat heterogeneity. Despite this modification, water quality did not improve. The same low water quality in the reference stream demonstrated the need for a watershed-scale approach and for actions to improve agricultural practices before implementing restoration practices at a smaller scale. Nonetheless, the lack of improved water quality does not necessarily mean that the restoration failed. Other functions and services can be provided by excluding livestock. 相似文献
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