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71.
Fiona C. Lewis‐McDougall Prashant J. Ruchaya Eva Domenjo‐Vila Tze Shin Teoh Larissa Prata Beverley J. Cottle James E. Clark Prakash P. Punjabi Wael Awad Daniele Torella Tamara Tchkonia James L. Kirkland Georgina M. Ellison‐Hughes 《Aging cell》2019,18(3)
Aging leads to increased cellular senescence and is associated with decreased potency of tissue‐specific stem/progenitor cells. Here, we have done an extensive analysis of cardiac progenitor cells (CPCs) isolated from human subjects with cardiovascular disease, aged 32–86 years. In aged subjects (>70 years old), over half of CPCs are senescent (p16INK4A, SA‐β‐gal, DNA damage γH2AX, telomere length, senescence‐associated secretory phenotype [SASP]), unable to replicate, differentiate, regenerate or restore cardiac function following transplantation into the infarcted heart. SASP factors secreted by senescent CPCs renders otherwise healthy CPCs to senescence. Elimination of senescent CPCs using senolytics abrogates the SASP and its debilitative effect in vitro. Global elimination of senescent cells in aged mice (INK‐ATTAC or wild‐type mice treated with D + Q senolytics) in vivo activates resident CPCs and increased the number of small Ki67‐, EdU‐positive cardiomyocytes. Therapeutic approaches that eliminate senescent cells may alleviate cardiac deterioration with aging and restore the regenerative capacity of the heart. 相似文献
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73.
Manon Bonneau Beniamino Caputo Aude Ligier Rudy Caparros Sandra Unal Marco Perriat‐Sanguinet Daniele Arnoldi Mathieu Sicard Mylne Weill 《Molecular ecology》2019,28(21):4725-4736
Endosymbiotic Wolbachia bacteria are, to date, considered the most widespread symbionts in arthropods and are the cornerstone of major biological control strategies. Such a high prevalence is based on the ability of Wolbachia to manipulate their hosts' reproduction. One manipulation called cytoplasmic incompatibility (CI) is based on the death of the embryos generated by crosses between infected males and uninfected females or between individuals infected with incompatible Wolbachia strains. CI can be seen as a modification‐rescue system (or mod‐resc) in which paternal Wolbachia produce mod factors, inducing embryonic defects, unless the maternal Wolbachia produce compatible resc factors. Transgenic experiments in Drosophila melanogaster and Saccharomyces cerevisiae converged towards a model where the cidB Wolbachia gene is involved in the mod function while cidA is involved in the resc function. However, as cidA expression in Drosophila males was required to observe CI, it has been proposed that cidA could be involved in both resc and mod functions. A recent correlative study in natural Culex pipiens mosquito populations has revealed an association between specific cidA and cidB variations and changes in mod phenotype, also suggesting a role for both these genes in mod diversity. Here, by studying cidA and cidB genomic repertoires of individuals from newly sampled natural C. pipiens populations harbouring wPipIV strains from North Italy, we reinforce the link between cidB variation and mod phenotype variation fostering the involvement of cidB in the mod phenotype diversity. However, no association between any cidA variants or combination of cidA variants and mod phenotype variation was observed. Taken together our results in natural C. pipiens populations do not support the involvement of cidA in mod phenotype variation. 相似文献
74.
75.
Matteo Gentili Xavier Lahaye Francesca Nadalin Guilherme P.F. Nader Emilia Puig Lombardi Solène Herve Nilushi S. De Silva Derek C. Rookhuizen Elina Zueva Christel Goudot Mathieu Maurin Aurore Bochnakian Sebastian Amigorena Matthieu Piel Daniele Fachinetti Arturo Londoño-Vallejo Nicolas Manel 《Cell reports》2019,26(13):3798
76.
Diversity of Frankia microsymbionts of non-native Elaeagnus angustifolia L. plants spontaneously growing in a Tunisian desertic retreat area, the date-palm oasis of Tozeur, was investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR-sequencing techniques targeting the nifD-K intergenic spacer. Three PCR-RFLP haplotypes (I, II, and III) were detected among collected nodules. Haplotype I was detected at all five sampling sites and dominated the other haplotypes present at these sites. This haplotype was also exhibited by strain BMG5.10, which was isolated by a plant-capturing assay in 1998 from soil collected in the same locality, qualifying it to be the most competitive haplotype in the edapho-climatic condition of the studied desertic date-palm oasis. nifD-K sequences of the three haplotypes formed a closely related phylogenetic subgroup. These results suggest that Frankia variability is constrained by severe edapho-climatic conditions of retreated desert in Tunisian area. 相似文献
77.
The heart is the first organ to form and function in the vertebrate embryo. Furthermore, differences between the left and right sides of the embryo become first detectable during cardiac development. We observed strong cardiac laterality phenotypes in medaka embryos by manipulating Groucho protein activity. The phenotypes produced by misexpressing Tle4 and the dominant-negative Aes reveal a general effect of these corepressor proteins on left-right (LR) development. With the help of an inducible expression system, we were able to define temporally different phases for these effects. In an early phase during gastrulation, Groucho proteins regulate Brachyury expression in the dorsal forerunner cells, which later gives rise to the Kupffer's vesicle (KV). The interference of endogenous Groucho proteins by misexpression of Aes leads to KVs of reduced size, whereas overexpression of Tle4 results in enlarged KVs. The expression level of the cilia marker Lrd was also affected both positively and negatively from these treatments. In the late phase during somitogenesis, Groucho proteins regulate the asymmetric activities of Nodal and Lefty genes. Altering canonical Wnt signaling produced similar results in late embryos, however, this did not affect KV morphogenesis or Lrd expression in early embryos. Therefore, changes in Kupffer's vesicle morphogenesis and the laterality of visceral organs following alterations in Groucho corepressor levels demonstrate two distinct phases in which Groucho proteins help establish LR asymmetry in medaka fish. 相似文献
78.
Fu J Astarita G Gaetani S Kim J Cravatt BF Mackie K Piomelli D 《The Journal of biological chemistry》2007,282(2):1518-1528
Oleoylethanolamide (OEA) is a lipid mediator that inhibits food intake by activating the nuclear receptor peroxisome proliferator-activated receptor-alpha. In the rodent small intestine OEA levels decrease during food deprivation and increase upon refeeding, suggesting that endogenous OEA may participate in the regulation of satiety. Here we show that feeding stimulates OEA mobilization in the mucosal layer of rat duodenum and jejunum but not in the serosal layer from the same intestinal segments in other sections of the gastrointestinal tract (stomach, ileum, colon) or in a broad series of internal organs and tissues (e.g. liver, brain, heart, plasma). Feeding also increases the levels of other unsaturated fatty acid ethanolamides (FAEs) (e.g. linoleoylethanolamide) without affecting those of saturated FAEs (e.g. palmitoylethanolamide). Feeding-induced OEA mobilization is accompanied by enhanced accumulation of OEA-generating N-acylphosphatidylethanolamines (NAPEs) increased activity and expression of the OEA-synthesizing enzyme NAPE-phospholipase D, and decreased activity and expression of the OEAdegrading enzyme fatty acid amide hydrolase. Immunostaining studies revealed that NAPE-phospholipase D and fatty acid amide hydrolase are expressed in intestinal enterocytes and lamina propria cells. Collectively, these results indicate that nutrient availability controls OEA mobilization in the mucosa of the proximal intestine through a concerted regulation of OEA biosynthesis and degradation. 相似文献
79.
Ellison GM Torella D Karakikes I Purushothaman S Curcio A Gasparri C Indolfi C Cable NT Goldspink DF Nadal-Ginard B 《The Journal of biological chemistry》2007,282(15):11397-11409
A hyperadrenergic state is a seminal aspect of chronic heart failure. Also, "Takotsubo stress cardiomyopathy," is associated with increased plasma catecholamine levels. The mechanisms of myocyte damage secondary to excess catecholamine exposure as well as the consequence of this neurohumoral burst on cardiac stem cells (CSCs) are unknown. Cardiomyocytes and CSCs were exposed to high doses of isoproterenol (ISO), in vivo and in vitro. Male Wistar rats received a single injection of ISO (5 mg kg-1) and were sacrificed 1, 3, and 6 days later. In comparison with controls, LV function was impaired in rats 1 day after ISO and started to improve at 3 days. The fraction of dead myocytes peaked 1 day after ISO and decreased thereafter. ISO administration resulted in significant ryanodine receptor 2 (RyR2) hyperphosphorylation and RyR2-calstabin dissociation. JTV519, a RyR2 stabilizer, prevented the ISO-induced death of adult myocytes in vitro. In contrast, CSCs were resistant to the acute neurohumoral overload. Indeed, CSCs expressed a decreased and inverted complement of beta1/beta2-adrenoreceptors and absence of RyR2, which may explain their survival to ISO insult. Thus, a single injection of ISO causes diffuse myocyte death through Ca2+ leakage secondary to the acutely dysfunctional RyR2. CSCs are resistant to the noxious effects of an acute hyperadrenergic state and through their activation participate in the response to the ISO-induced myocardial injury. The latter could contribute to the ability of the myocardium to rapidly recover from acute hyperadrenergic damage. 相似文献
80.
Rigamonti D Bolognini D Mutti C Zuccato C Tartari M Sola F Valenza M Kazantsev AG Cattaneo E 《The Journal of biological chemistry》2007,282(34):24554-24562