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191.
Mark F. Santos Germana Rappa Jana Karbanov Cheryl Vanier Chikao Morimoto Denis Corbeil Aurelio Lorico 《Journal of cellular and molecular medicine》2019,23(6):4408-4421
The intercellular communication mediated by extracellular vesicles (EVs) has gained international interest during the last decade. Interfering with the mechanisms regulating this cellular process might find application particularly in oncology where cancer cell‐derived EVs play a role in tumour microenvironment transformation. Although several mechanisms were ascribed to explain the internalization of EVs, little is our knowledge about the fate of their cargos, which are crucial to mediate their function. We recently demonstrated a new intracellular pathway in which a fraction of endocytosed EV‐associated proteins is transported into the nucleoplasm of the host cell via a subpopulation of late endosomes penetrating into the nucleoplasmic reticulum. Silencing tetraspanin CD9 both in EVs and recipient cells strongly decreased the endocytosis of EVs and abolished the nuclear transfer of their cargos. Here, we investigated whether monovalent Fab fragments derived from 5H9 anti‐CD9 monoclonal antibody (referred hereafter as CD9 Fab) interfered with these cellular processes. To monitor the intracellular transport of proteins, we used fluorescent EVs containing CD9‐green fluorescent protein fusion protein and various melanoma cell lines and bone marrow‐derived mesenchymal stromal cells as recipient cells. Interestingly, CD9 Fab considerably reduced EV uptake and the nuclear transfer of their proteins in all examined cells. In contrast, the divalent CD9 antibody stimulated both events. By impeding intercellular communication in the tumour microenvironment, CD9 Fab‐mediated inhibition of EV uptake, combined with direct targeting of cancerous cells could lead to the development of novel anti‐melanoma therapeutic strategies. 相似文献
192.
Denis V. Sudarikov Yulia V. Krymskaya Oksana G. Shevchenko Pavel A. Slepukhin Svetlana A. Rubtsova Aleksandr V. Kutchin 《化学与生物多样性》2019,16(11)
The synthesis of sulfenimines and sulfinimines has been carried out with 10‐hydroxyisocamphylthiol. The configuration of the compounds has been deduced by methods of NMR, DFT calculations and X‐ray diffraction analysis. The cytotoxic, antioxidant and membrane‐protective activity of the synthesized compounds as well as of the previously obtained sulfenimines and sulfinimines based on 4‐caranethiol have been determined. 相似文献
193.
Denis Copila‐Ciocianu Alina‐Andreea Zima Adam Petrusek 《Journal of Zoological Systematics and Evolutionary Research》2019,57(2):272-297
The multidisciplinarity of integrative taxonomy is particularly useful for clarifying the systematics of speciose groups that are poorly differentiated morphologically, and this approach can also illuminate their evolutionary history and biogeography. Here, we utilize it to examine the systematics and taxonomy of a newly recognized amphipod species, Gammarus hamaticornis n. sp., which belongs to a highly diverse genus of endemic freshwater crustaceans that show very limited morphological differentiation. Since this species is endemic to northern Dobrogea, a region at the northwestern Black Sea coast devoid of permafrost during the Last Glacial Maximum, we hypothesized that it survived in situ during the Quaternary climatic oscillations. We first examined the phylogenetic position of Gammarus hamaticornis n. sp. within the genus and then compared its morphology, phylogeography, distribution, and climatic niche with that of its sister species. Results indicate that G. hamaticornis n. sp. is most closely related to its widely distributed northern neighbor, G. kischineffensis, and a remarkable agreement was observed among morphological, multilocus coalescent and climatic analyses which supported the distinctiveness of both taxa. These apparently diverged during the Pliocene from a common ancestor that likely colonized freshwaters from the adjacent brackish basins of the shrinking Paratethys. The results indicate that G. hamaticornis n. sp. has persisted throughout the Pleistocene in northern Dobrogea, a hitherto hypothesized refugium confirmed for the first time with molecular genetic data. Due to its narrow geographical range, rarity in the local communities and highly fluctuating nature of the streams it inhabits, this species should be in the focus of future conservation priorities. 相似文献
194.
Justin O'Connor Andrew Pickworth Ben Fanson Denis Lovric 《Ecological Management & Restoration》2019,20(2):151-155
In the Barwon River, Australia, a tidal barrage formed a major impediment to fish movement so in 2013 a vertical slot fishway was installed. The assessment of fishways on tidal barriers is rare in Australia so to ensure the fishway was achieving its ecological objective (i.e. successfully passing the target size range of fish of 20–400 mm total length), fish were trapped at the entrance and exit on 12 occasions and the species composition, abundance and length of fish at the two locations were compared. Additionally, a section of the river downstream of the fishway was sampled to ensure fishway trapping accurately reflected the species composition wanting to use the fishway to move upstream. Eighteen species and 69,246 individual fish were caught in the fishway traps. Catch rates between locations did not differ for Common Galaxias (Galaxias maculatus) or Australian Smelt (Retropinna semoni), although species‐specific catch rates were lower at the exit for Flat‐headed Gudgeon (Philypnodon grandiceps), Tupong (Pseudaphritis urvillii) and Yellow‐eye Mullet (Aldrichetta forsteri). Length distribution between locations only differed for Australian Smelt with small fish under‐represented at the exit location (<25 mm total length). Eight species of fish were collected downstream of the fishway that were not collected in it; however, all of these were estuarine dependent except the non‐native Common Carp (Cyprinus carpio). Our results indicate that vertical slot fishways are a suitable design for improving river connectivity at a low head, tidal barrages in south‐eastern Australia. The study reiterates the importance of reinstating connectivity for species with obligate marine/freshwater migratory life history traits, and the indirect benefits of increased productivity made available to upstream areas. 相似文献
195.
Marine Schoeffler Anne-Laure Gaudin Fanny Ramel Odile Valette Yann Denis Wagdi Ben Hania Agnès Hirschler-Réa Alain Dolla 《Environmental microbiology》2019,21(1):360-373
Desulfovibrio species are representatives of microorganisms at the boundary between anaerobic and aerobic lifestyles, since they contain the enzymatic systems required for both sulfate and oxygen reduction. However, the latter has been shown to be solely a protective mechanism. By implementing the oxygen-driven experimental evolution of Desulfovibrio vulgaris Hildenborough, we have obtained strains that have evolved to grow with energy derived from oxidative phosphorylation linked to oxygen reduction. We show that a few mutations are sufficient for the emergence of this phenotype and reveal two routes of evolution primarily involving either inactivation or overexpression of the gene encoding heterodisulfide reductase. We propose that the oxygen respiration for energy conservation that sustains the growth of the O2-evolved strains is associated with a rearrangement of metabolite fluxes, especially NAD+/NADH, leading to an optimized O2 reduction. These evolved strains are the first sulfate-reducing bacteria that exhibit a demonstrated oxygen respiratory process that enables growth. 相似文献
196.
Beaulieu L Tolkatchev D Jetté JF Groleau D Subirade M 《Canadian journal of microbiology》2007,53(11):1246-1258
Antimicrobial peptides possess cationic and amphipathic properties that allow for interactions with the membrane of living cells. Bacteriocins from lactic acid bacteria, in particular, are currently being studied for their potential use as food preservatives and for applications in health care. However, bacteriocin exploitation is often limited owing to low production yields. Gene cloning and heterologous protein or peptide production is one way to possibly achieve overexpression of bacteriocins to support biochemical studies. In this work, production of recombinant active pediocin PA-1 (PedA) was accomplished in Escherichia coli using a thioredoxin (trx) gene fusion (trx-pedA) expression approach. Trx-PedA itself did not show any biological activity, but upon cleavage by an enterokinase, biologically active pediocin PA-1 was obtained. Recombinant pediocin PA-1 characteristics (molecular mass, biological activity, physicochemical properties) were very similar to those of native pediocin PA-1. In addition, a 4- to 5-fold increase in production yield was obtained, by comparison with the PA-1 produced naturally by Pediococcus acidilactici PAC 1.0. The new production method, although not optimized, offers great potential for supporting further investigations on pediocin PA-1 and as a first-generation process for the production of pediocin PA-1 for high-value applications. 相似文献
197.
The apical domain of epithelial cells is composed of distinct subdomains such as microvilli, primary cilia and a non-protruding region. Using the cholesterol-binding protein prominin-1 as a specific marker of plasma membrane protrusions we have previously proposed the co-existence of different cholesterol-based lipid microdomains (lipid rafts) within the apical domain [R?per, K., Corbeil, D. and Huttner, W.B. (2000), Retention of prominin in microvilli reveals distinct cholesterol-based lipid microdomains in the apical plasma membrane. Nat. Cell Biol. 2, 582-592]. To substantiate the hypothesis that the microvillar plasma membrane subdomains contain a distinct set of lipids compared to the planar portion we have investigated the distribution of prominin-1 and two raft-associated gangliosides GM(1) and GM(3) by fluorescence microscopy. GM(1) was found to co-localize with prominin-1 on microvilli whereas GM(3) was segregated from there suggesting its localization in the planar region. Regarding the primary cilium, overlapping fluorescent signals of GM(1) or GM(3) and prominin-1 were observed. Thus, our data demonstrate that specific ganglioside-enriched rafts are found in different apical subdomains and reveal that two plasma membrane protrusions with different structural bases (actin for the microvillus and tubulin for the cilium) are composed of distinct types of lipid. 相似文献
198.
Genetic load in sexual and asexual diploids: segregation, dominance and genetic drift 总被引:1,自引:0,他引:1
In diploid organisms, sexual reproduction rearranges allelic combinations between loci (recombination) as well as within loci (segregation). Several studies have analyzed the effect of segregation on the genetic load due to recurrent deleterious mutations, but considered infinite populations, thus neglecting the effects of genetic drift. Here, we use single-locus models to explore the combined effects of segregation, selection, and drift. We find that, for partly recessive deleterious alleles, segregation affects both the deterministic component of the change in allele frequencies and the stochastic component due to drift. As a result, we find that the mutation load may be far greater in asexuals than in sexuals in finite and/or subdivided populations. In finite populations, this effect arises primarily because, in the absence of segregation, heterozygotes may reach high frequencies due to drift, while homozygotes are still efficiently selected against; this is not possible with segregation, as matings between heterozygotes constantly produce new homozygotes. If deleterious alleles are partly, but not fully recessive, this causes an excess load in asexuals at intermediate population sizes. In subdivided populations without extinction, drift mostly occurs locally, which reduces the efficiency of selection in both sexuals and asexuals, but does not lead to global fixation. Yet, local drift is stronger in asexuals than in sexuals, leading to a higher mutation load in asexuals. In metapopulations with turnover, global drift becomes again important, leading to similar results as in finite, unstructured populations. Overall, the mutation load that arises through the absence of segregation in asexuals may greatly exceed previous predictions that ignored genetic drift. 相似文献
199.
200.
Mochel F Charles P Seguin F Barritault J Coussieu C Perin L Le Bouc Y Gervais C Carcelain G Vassault A Feingold J Rabier D Durr A 《PloS one》2007,2(7):e647
Huntington disease (HD) is a fatal neurodegenerative disorder, with no effective treatment. The pathogenic mechanisms underlying HD has not been elucidated, but weight loss, associated with chorea and cognitive decline, is a characteristic feature of the disease that is accessible to investigation. We, therefore, performed a multiparametric study exploring body weight and the mechanisms of its loss in 32 presymptomatic carriers and HD patients in the early stages of the disease, compared to 21 controls. We combined this study with a multivariate statistical analysis of plasma components quantified by proton nuclear magnetic resonance ((1)H NMR) spectroscopy. We report evidence of an early hypermetabolic state in HD. Weight loss was observed in the HD group even in presymptomatic carriers, although their caloric intake was higher than that of controls. Inflammatory processes and primary hormonal dysfunction were excluded. (1)H NMR spectroscopy on plasma did, however, distinguish HD patients at different stages of the disease and presymptomatic carriers from controls. This distinction was attributable to low levels of the branched chain amino acids (BCAA), valine, leucine and isoleucine. BCAA levels were correlated with weight loss and, importantly, with disease progression and abnormal triplet repeat expansion size in the HD1 gene. Levels of IGF1, which is regulated by BCAA, were also significantly lower in the HD group. Therefore, early weight loss in HD is associated with a systemic metabolic defect, and BCAA levels may be used as a biomarker, indicative of disease onset and early progression. The decreased plasma levels of BCAA may correspond to a critical need for Krebs cycle energy substrates in the brain that increased metabolism in the periphery is trying to provide. 相似文献