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31.
Myriam M. Ouberai Juan Wang Marcus J. Swann Celine Galvagnion Tim Guilliams Christopher M. Dobson Mark E. Welland 《The Journal of biological chemistry》2013,288(29):20883-20895
There is increasing evidence for the involvement of lipid membranes in both the functional and pathological properties of α-synuclein (α-Syn). Despite many investigations to characterize the binding of α-Syn to membranes, there is still a lack of understanding of the binding mode linking the properties of lipid membranes to α-Syn insertion into these dynamic structures. Using a combination of an optical biosensing technique and in situ atomic force microscopy, we show that the binding strength of α-Syn is related to the specificity of the lipid environment (the lipid chemistry and steric properties within a bilayer structure) and to the ability of the membranes to accommodate and remodel upon the interaction of α-Syn with lipid membranes. We show that this interaction results in the insertion of α-Syn into the region of the headgroups, inducing a lateral expansion of lipid molecules that can progress to further bilayer remodeling, such as membrane thinning and expansion of lipids out of the membrane plane. We provide new insights into the affinity of α-Syn for lipid packing defects found in vesicles of high curvature and in planar membranes with cone-shaped lipids and suggest a comprehensive model of the interaction between α-Syn and lipid bilayers. The ability of α-Syn to sense lipid packing defects and to remodel membrane structure supports its proposed role in vesicle trafficking. 相似文献
32.
Anne-Christine Hick Anne-Sophie Delmarcelle Mahé Bouquet Sabrina Klotz Tamara Copetti Celine Forez Patrick Van Der Smissen Pierre Sonveaux Jean-François Collet Olivier Feron Pierre J. Courtoy Christophe E. Pierreux 《Developmental biology》2013
The thyroid is a highly vascularized endocrine gland, displaying a characteristic epithelial organization in closed spheres, called follicles. Here we investigate how endothelial cells are recruited into the developing thyroid and if they control glandular organization as well as thyrocytes and C-cells differentiation. We show that endothelial cells closely surround, and then invade the expanding thyroid epithelial cell mass to become closely associated with nascent polarized follicles. This close and sustained endothelial:epithelial interaction depends on epithelial production of the angiogenic factor, Vascular Endothelial Growth Factor-A (VEGF-A), as its thyroid-specific genetic inactivation reduced the endothelial cell pool of the thyroid by >90%. Vegfa KO also displayed decreased C-cells differentiation and impaired organization of the epithelial cell mass into follicles. We developed an ex vivo model of thyroid explants that faithfully mimicks bilobation of the thyroid anlagen, endothelial and C-cells invasion, folliculogenesis and differentiation. Treatment of thyroid explants at e12.5 with a VEGFR2 inhibitor ablated the endothelial pool and reproduced ex vivo folliculogenesis defects observed in conditional Vegfa KO. In the absence of any blood supply, rescue by embryonic endothelial progenitor cells restored folliculogenesis, accelerated lumen expansion and stimulated calcitonin expression by C-cells. In conclusion, our data demonstrate that, in developing mouse thyroid, epithelial production of VEGF-A is necessary for endothelial cells recruitment and expansion. In turn, endothelial cells control epithelial reorganization in follicles and C-cells differentiation. 相似文献
33.
Guillaume Emaresi Anne‐Lyse Ducrest Pierre Bize Hannes Richter Celine Simon Alexandre Roulin 《Molecular ecology》2013,22(19):4915-4930
The adaptive function of melanin‐based coloration is a long‐standing debate. A recent genetic model suggested that pleiotropy could account for covariations between pigmentation, behaviour, morphology, physiology and life history traits. We explored whether the expression levels of genes belonging to the melanocortin system (MC1R, POMC, PC1/3, PC2 and the antagonist ASIP), which have many pleiotropic effects, are associated with melanogenesis (through variation in the expression of the genes MITF, SLC7A11, TYR, TYRP1) and in turn melanin‐based coloration. We considered the tawny owl (Strix aluco) because individuals vary continuously from light to dark reddish, and thus, colour variation is likely to stem from differences in the levels of gene expression. We measured gene expression in feather bases collected in nestlings at the time of melanin production. As expected, the melanocortin system was associated with the expression of melanogenic genes and pigmentation. Offspring of darker reddish fathers expressed PC1/3 to lower levels but tended to express PC2 to higher levels. The convertase enzyme PC1/3 cleaves the POMC prohormone to obtain ACTH, while the convertase enzyme PC2 cleaves ACTH to produce α‐melanin‐stimulating hormone (α‐MSH). ACTH regulates glucocorticoids, hormones that modulate stress responses, while α‐MSH induces eumelanogenesis. We therefore conclude that the melanocortin system, through the convertase enzymes PC1/3 and PC2, may account for part of the interindividual variation in melanin‐based coloration in nestling tawny owls. Pleiotropy may thus account for the covariation between phenotypic traits involved in social interactions (here pigmentation) and life history, morphology, behaviour and physiology. 相似文献
34.
Ryan T Jones Sara M Vetter John Montenieiri Jennifer Holmes Scott A Bernhardt Kenneth L Gage 《The ISME journal》2013,7(1):224-228
We collected Oropsylla montana from rock squirrels, Spermophilus varigatus, and infected a subset of collected fleas with Yersinia pestis, the etiological agent of plague. We used bar-tagged DNA pyrosequencing to characterize bacterial communities of wild, uninfected controls and infected fleas. Bacterial communities within Y. pestis-infected fleas were substantially more similar to one another than communities within wild or control fleas, suggesting that infection alters the bacterial community in a directed manner such that specific bacterial lineages are severely reduced in abundance or entirely eliminated from the community. Laboratory conditions also significantly altered flea-associated bacterial communities relative to wild communities, but much less so than Y. pestis infection. The abundance of Firmicutes decreased considerably in infected fleas, and Bacteroidetes were almost completely eliminated from both the control and infected fleas. Bartonella and Wolbachia were unaffected or responded positively to Y. pestis infection. 相似文献
35.
36.
Jacques Amar Céline Lange Ga?lle Payros Celine Garret Chantal Chabo Olivier Lantieri Michael Courtney Michel Marre Marie Aline Charles Beverley Balkau Rémy Burcelin D.E.S.I.R. Study Group 《PloS one》2013,8(1)
Aim
We recently described a human blood microbiome and a connection between this microbiome and the onset of diabetes. The aim of the current study was to assess the association between blood microbiota and incident cardiovascular disease.Methods and Results
D.E.S.I.R. is a longitudinal study with the primary aim of describing the natural history of the metabolic syndrome and its complications. Participants were evaluated at inclusion and at 3-, 6-, and 9-yearly follow-up visits. The 16S ribosomal DNA bacterial gene sequence, that is common to the vast majority of bacteria (Eubac) and a sequence that mostly represents Proteobacteria (Pbac), were measured in blood collected at baseline from 3936 participants. 73 incident cases of acute cardiovascular events, including 30 myocardial infarctions were recorded. Eubac was positively correlated with Pbac (r = 0.59; P<0.0001). In those destined to have cardiovascular complications, Eubac was lower (0.14±0.26 vs 0.12±0.29 ng/µl; P = 0.02) whereas a non significant increase in Pbac was observed. In multivariate Cox analysis, Eubac was inversely correlated with the onset of cardiovascular complications, (hazards ratio 0.50 95% CI 0.35–0.70) whereas Pbac (1.56, 95%CI 1.12–2.15) was directly correlated.Conclusion
Pbac and Eubac were shown to be independent markers of the risk of cardiovascular disease. This finding is evidence for the new concept of the role played by blood microbiota dysbiosis on atherothrombotic disease. This concept may help to elucidate the relation between bacteria and cardiovascular disease. 相似文献37.
Alice Matone Marie-Pier Scott-Boyer Jerome Carayol Parastoo Fazelzadeh Gregory Lefebvre Armand Valsesia Celine Charon Jacques Vervoort Arne Astrup Wim H. M. Saris Melissa Morine J?rg Hager 《PloS one》2016,11(3)
Background and Scope
Weight loss success is dependent on the ability to refrain from regaining the lost weight in time. This feature was shown to be largely variable among individuals, and these differences, with their underlying molecular processes, are diverse and not completely elucidated. Altered plasma metabolites concentration could partly explain weight loss maintenance mechanisms. In the present work, a systems biology approach has been applied to investigate the potential mechanisms involved in weight loss maintenance within the Diogenes weight-loss intervention study.Methods and Results
A genome wide association study identified SNPs associated with plasma glycine levels within the CPS1 (Carbamoyl-Phosphate Synthase 1) gene (rs10206976, p-value = 4.709e-11 and rs12613336, p-value = 1.368e-08). Furthermore, gene expression in the adipose tissue showed that CPS1 expression levels were associated with successful weight maintenance and with several SNPs within CPS1 (cis-eQTL). In order to contextualize these results, a gene-metabolite interaction network of CPS1 and glycine has been built and analyzed, showing functional enrichment in genes involved in lipid metabolism and one carbon pool by folate pathways.Conclusions
CPS1 is the rate-limiting enzyme for the urea cycle, catalyzing carbamoyl phosphate from ammonia and bicarbonate in the mitochondria. Glycine and CPS1 are connected through the one-carbon pool by the folate pathway and the urea cycle. Furthermore, glycine could be linked to metabolic health and insulin sensitivity through the betaine osmolyte. These considerations, and the results from the present study, highlight a possible role of CPS1 and related pathways in weight loss maintenance, suggesting that it might be partly genetically determined in humans. 相似文献38.
Ewelina Krzywinska Amelie Cornillon Nerea Allende-Vega Dang-Nghiem Vo Celine Rene Zhao-Yang Lu Christine Pasero Daniel Olive Nathalie Fegueux Patrick Ceballos Yosr Hicheri Michal Sobecki Jean-Fran?ois Rossi Guillaume Cartron Martin Villalba 《PloS one》2016,11(4)
The leucocyte-specific phosphatase CD45 is present in two main isoforms: the large CD45RA and the short CD45RO. We have recently shown that distinctive expression of these isoforms distinguishes natural killer (NK) populations. For example, co-expression of both isoforms identifies in vivo the anti tumor NK cells in hematological cancer patients. Here we show that low CD45 expression associates with less mature, CD56bright, NK cells. Most NK cells in healthy human donors are CD45RA+CD45RO-. The CD45RA-RO+ phenotype, CD45RO cells, is extremely uncommon in B or NK cells, in contrast to T cells. However, healthy donors possess CD45RAdimRO- (CD45RAdim cells), which show immature markers and are largely expanded in hematopoietic stem cell transplant patients. Blood borne cancer patients also have more CD45RAdim cells that carry several features of immature NK cells. However, and in opposition to their association to NK cell progenitors, they do not proliferate and show low expression of the transferrin receptor protein 1/CD71, suggesting low metabolic activity. Moreover, CD45RAdim cells properly respond to in vitro encounter with target cells by degranulating or gaining CD69 expression. In summary, they are quiescent NK cells, with low metabolic status that can, however, respond after encounter with target cells. 相似文献
39.
40.
Steven P. Govek Celine Bonnefous Jackaline D. Julien Johnny Y. Nagasawa Mehmet Kahraman Andiliy G. Lai Karensa L. Douglas Anna M. Aparicio Beatrice D. Darimont Katherine L. Grillot James D. Joseph Joshua A. Kaufman Kyoung-Jin Lee Nhin Lu Michael J. Moon Rene Y. Prudente John Sensintaffar Peter J. Rix Nicholas D. Smith 《Bioorganic & medicinal chemistry letters》2019,29(3):367-372
Potent estrogen receptor ligands typically contain a phenolic hydrogen-bond donor. The indazole of the selective estrogen receptor degrader (SERD) ARN-810 is believed to mimic this. Disclosed herein is the discovery of ARN-810 analogs which lack this hydrogen-bond donor. These SERDs induced tumor regression in a tamoxifen-resistant breast cancer xenograft, demonstrating that the indazole NH is not necessary for robust ER-modulation and anti-tumor activity. 相似文献