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101.
Lipids revert inert Abeta amyloid fibrils to neurotoxic protofibrils that affect learning in mice 总被引:1,自引:0,他引:1 下载免费PDF全文
Martins IC Kuperstein I Wilkinson H Maes E Vanbrabant M Jonckheere W Van Gelder P Hartmann D D'Hooge R De Strooper B Schymkowitz J Rousseau F 《The EMBO journal》2008,27(1):224-233
Although soluble oligomeric and protofibrillar assemblies of Abeta-amyloid peptide cause synaptotoxicity and potentially contribute to Alzheimer's disease (AD), the role of mature Abeta-fibrils in the amyloid plaques remains controversial. A widely held view in the field suggests that the fibrillization reaction proceeds 'forward' in a near-irreversible manner from the monomeric Abeta peptide through toxic protofibrillar intermediates, which subsequently mature into biologically inert amyloid fibrils that are found in plaques. Here, we show that natural lipids destabilize and rapidly resolubilize mature Abeta amyloid fibers. Interestingly, the equilibrium is not reversed toward monomeric Abeta but rather toward soluble amyloid protofibrils. We characterized these 'backward' Abeta protofibrils generated from mature Abeta fibers and compared them with previously identified 'forward' Abeta protofibrils obtained from the aggregation of fresh Abeta monomers. We find that backward protofibrils are biochemically and biophysically very similar to forward protofibrils: they consist of a wide range of molecular masses, are toxic to primary neurons and cause memory impairment and tau phosphorylation in mouse. In addition, they diffuse rapidly through the brain into areas relevant to AD. Our findings imply that amyloid plaques are potentially major sources of soluble toxic Abeta-aggregates that could readily be activated by exposure to biological lipids. 相似文献
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104.
Fernanda P. Werneck Cristiano Nogueira Guarino R. Colli Jack W. Sites Jr Gabriel C. Costa 《Journal of Biogeography》2012,39(9):1695-1706
Aim To investigate the historical distribution of the Cerrado across Quaternary climatic fluctuations and to generate historical stability maps to test: (1) whether the ‘historical climate’ stability hypothesis explains squamate reptile richness in the Cerrado; and (2) the hypothesis of Pleistocene connections between savannas located north and south of Amazonia. Location The Cerrado, a savanna biome and a global biodiversity hotspot distributed mainly in central Brazil. Methods We generated occurrence datasets from 1000 presence points randomly selected from the entire distribution of the Cerrado, as determined by two spatial definitions. We modelled the potential Cerrado distribution by implementing a maximum‐entropy machine‐learning algorithm across four time projections: current, mid‐Holocene (6 ka), Last Glacial Maximum (LGM, 21 ka) and Last Interglacial (LIG, 120 ka). We generated historical stability maps (refugial areas) by overlapping presence/absence projections of all scenarios, and checked consistencies with qualitative comparisons with available fossil pollen records. We built a spatially explicit simultaneous autoregressive model to explore the relationship between current climate, climatic stability, and squamate species richness. Results Models predicted the LGM and LIG as the periods of narrowest and widest Cerrado distributions, respectively, and were largely corroborated by palynological evidence. We found evidence for two savanna corridors (eastern coastal during the LIG, and Andean during the LGM) and predicted a large refugial area in the north‐eastern Cerrado (Serra Geral de Goiás refugium). Variables related to climatic stability predicted squamate richness better than present climatic variables did. Main conclusions Our results indicate that Bolivian savannas should be included within the Cerrado range and that the Cerrado’s biogeographical counterparts are not Chaco and Caatinga but rather the disjunct savannas of the Guyana shield plateaus. Climatic stability is a good predictor of Cerrado squamate richness, and our stability maps could be used in future studies to test diversity patterns and genetic signatures of different taxonomic groups and as a higher‐order landscape biodiversity surrogate for conservation planning. 相似文献
105.
Rhynchocyon udzungwensis is a recently described and poorly understood sengi (giant elephant-shrew) endemic to two small montane forests in Southern Tanzania, and surrounded in lower forests by R. cirnei reichardi. In this study, we investigate the molecular genetic relationship between R. udzungwensis and R. c. reichardi, and the possible role that shifting species distributions in response to climate fluctuations may have played in shaping their evolutionary history. Rhynchocyon udzungwensis and R. c. reichardi individuals were sampled from five localities for genetic analyses. Three mitochondrial and two nuclear loci were used to construct species trees for delimitation and to determine whether introgression was detectable either from ancient or ongoing hybridization. All species-tree results show R. udzungwensis and R. c. reichardi as distinct lineages, though mtDNA shows evidence of introgression in some populations. Nuclear loci of each species were monophyletic, implying introgression is exclusively historical. Because we found evidence of introgression, we used distribution data and species distribution modelling for present, glacial, and interglacial climate cycles to predict how shifting species distributions may have facilitated hybridization in some populations. Though interpretations are affected by the limited range of these species, a likely scenario is that the mtDNA introgression found in eastern mid-elevation populations was facilitated by low numbers of R. udzungwensis that expanded into lowland heavily occupied R. c. reichardi areas during interglacial climate cycles. These results imply that relationships within the genus Rhynchocyon may be confounded by porous species boundaries and introgression, even if species are not currently sympatric. 相似文献
106.
Francesca Pennacchietti Stefania Abbruzzetti Aba Losi Carmen Mandalari Roberta Bedotti Cristiano Viappiani Francesca Cella Zanacchi Alberto Diaspro Wolfgang G?rtner 《PloS one》2014,9(9)
We report thermal recovery kinetics of the lit state into the parental dark state, measured for the blue light-sensing photoreceptor YtvA inside overexpressing E. coli and B. subtilis bacterial cells, performed for the wild type and several mutated proteins. Recovery was followed as a recovery of the fluorescence, as this property is only found for the parental but not for the photochemically generated lit state. When cells were deposited onto a microscope glass plate, the observed thermal recovery rate in the photocycle was found ca. ten times faster in comparison to purified YtvA in solution. When the E. coli or B. subtilis colonies were soaked in an isotonic buffer, the dark relaxation became again much slower and was very similar to that observed for YtvA in solution. The observed effects show that rate constants can be tuned by the cellular environment through factors such as hydration. 相似文献
107.
Margherita Maranesi Cesare Castellini Cecilia Dall’Aglio Linda Petrucci Simona Mattioli Cristiano Boiti Massimo Zerani 《Phytochemistry Reviews》2018,17(4):801-814
Adequate fat diet supplementation shows variable positive effects in farm animal breeding. Omega-3 and n-6 PUFAs are able to modulate several reproductive effectors: the luteolytic PGF2α, the luteotropic PGE2, the nuclear receptor PPARG, and steroids such as E2 and P4. PUFA supplementation favours fertility, onset of estrus, embryo survival, and also parturition by reducing preterm labour risk. These effects are likely mediated by the balance modulation of PGF2α and PGE2 productions, the syntheses of E2 and P4, and the activation of PPARG. As regards to male fertility, the effects of n-3 or n-6 PUFA supplementation at high concentrations in the diet are relatively unknown. PUFAs confer to the spermatozoa plasma membrane the fluidity it needs to achieve fertilization and seem to stimulate the Leydig cell production of testosterone through the regulation of the steroidogenic acute regulatory protein, a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones. As regards to female fertility, PUFA supplementation mediates a broad range of actions in reproductive processes involving pregnancy establishment, uterine endocrinology, and preterm birth. The perfectly composed follicular environment shapes oocyte quality and thus female fertility. Since both oocytes and embryos are vulnerable to microenvironment changes, nutritional alterations and FA unavailability can lead to their defects. The aim of the present review is to examine the effects of n-3 and n-6 PUFAs on male and female reproductive performances and the correlated endocrine mechanisms. 相似文献
108.
A stereodynamic fluorescent probe for amino acids. Circular dichroism and circularly polarized luminescence analysis 下载免费PDF全文
Nadia Alessandra Carmo dos Santos Elena Badetti Giulia Licini Sergio Abbate Giovanna Longhi Cristiano Zonta 《Chirality》2018,30(1):65-73
The use of stereodynamic probes is becoming one of the leading strategies for the fast and effective determination of enantiomeric excess. Recently, we reported a series of novel molecular architectures based on a modified tris(2‐pyridylmethyl)amine complex (TPMA), which are able to amplify the electronic CD, in the case of Zn(II) assemblies and vibrational CD, in the case of Co(II) assemblies. Herein, we report a structural modification of the ligand with the purpose to obtain a fluorescent chiral probe. The study deals with the synthesis of the novel ligand, the formation of the self‐assembly system with amino acids, and the study of the electronic CD and circularly polarized luminescence. 相似文献
109.
Michelle Klautau Claudia A. M. Russo Cristiano Lazoski Nicole Boury-Esnault John P. Thorpe Antonio M. Sol-Cava 《Evolution; international journal of organic evolution》1999,53(5):1414-1422
The sponge species Chondrilla nucula has a simple morphology and a very wide geographical distribution. To verify whether the latter might be an artifact of the former, samples of this species were collected across 10,000 km of its range, in the Mediterranean, the Caribbean, and the southwestern atlantic. The classical (spicule morphology) and molecular (allozymes) systematic approaches were compared, to try to define the geographic limits between populations and detect possible cryptic species. We found five distinct genetic forms within C. nucula that sometimes showed morphological homogeneity and other times plasticity. The difference in size of spicules could not be related to the clear-cut genetic differences, suggesting that the use of spicule sizes for sponge systematics should be reappraised. The population of one of the genetic forms along 3000 km of the Brazilian coast was highly structured (FST = 0.21; Nem = 0.96). Our results reject the null hypothesis of cosmopolitanism of C. nucula and indicate that the putative worldwide distribution of some marine sponges, and possibly many other benthic invertebrates, may be the result of overly conservative systematics. Cryptic species appear to be particularly prevalent when genera are well defined but species are characterized by only a few morphological characters. 相似文献
110.
Stressful housing conditions like social isolation have been shown to profoundly affect the physiology and health of various organisms which is rarely addressed in fish species. In the present study, we used a shoaling species, zebrafish, to investigate the stress reactivity of grouped and individually housed fish. We also hypothesized if isolation is a stressful condition may disrupt growth performance and innate immune response of individuals. To this end, fish were housed individually (social isolated treatment) or in groups of five fish (control treatment) for 60 days. Growth indices of fish were not affected by social isolation. Sixty-day social isolation did insignificant effect on baseline cortisol levels of specimens; however, individually housed zebrafish showed lower plasma cortisol to chasing stress than the control grouped fish. On the contrary, exposure to predator caused higher cortisol levels in social isolated fish. Serum lysozyme activity of isolated individuals was significantly lower than control fish, but activity of serum complement remained unchanged. Our results represent evidences that zebrafish experienced social isolation showed broad changes in physiological and immunological functions which may affect the quality of life. 相似文献