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91.
The C‐terminal tails of heterotrimeric kinesin‐2 motor subunits directly bind to α‐tubulin1: Possible implications for cilia‐specific tubulin entry 下载免费PDF全文
Mukul Girotra Shalini Srivastava Anuttama Kulkarni Ayan Barbora Kratika Bobra Debnath Ghosal Pavithra Devan Amol Aher Akanksha Jain Dulal Panda Krishanu Ray 《Traffic (Copenhagen, Denmark)》2017,18(2):123-133
The assembly of microtubule‐based cytoskeleton propels the cilia and flagella growth. Previous studies have indicated that the kinesin‐2 family motors transport tubulin into the cilia through intraflagellar transport. Here, we report a direct interaction between the C‐terminal tail fragments of heterotrimeric kinesin‐2 and α‐tubulin1 isoforms in vitro. Blot overlay screen, affinity purification from tissue extracts, cosedimentation with subtilisin‐treated microtubule and LC‐ESI‐MS/MS characterization of the tail‐fragment‐associated tubulin identified an association between the tail domains and α‐tubulin1A/D isotype. The interaction was confirmed by Forster's resonance energy transfer assay in tissue‐cultured cells. The overexpression of the recombinant tails in NIH3T3 cells affected the primary cilia growth, which was rescued by coexpression of a α‐tubulin1 transgene. Furthermore, fluorescent recovery after photobleach analysis in the olfactory cilia of Drosophila indicated that tubulin is transported in a non‐particulate form requiring kinesin‐2. These results provide additional new insight into the mechanisms underlying selective tubulin isoform enrichment in the cilia. 相似文献
92.
Teppo Hiltunen G?k?e B. Ayan Lutz Becks 《Proceedings. Biological sciences / The Royal Society》2015,282(1808)
Environmental fluctuations, species interactions and rapid evolution are all predicted to affect community structure and their temporal dynamics. Although the effects of the abiotic environment and prey evolution on ecological community dynamics have been studied separately, these factors can also have interactive effects. Here we used bacteria–ciliate microcosm experiments to test for eco-evolutionary dynamics in fluctuating environments. Specifically, we followed population dynamics and a prey defence trait over time when populations were exposed to regular changes of bottom-up or top-down stressors, or combinations of these. We found that the rate of evolution of a defence trait was significantly lower in fluctuating compared with stable environments, and that the defence trait evolved to lower levels when two environmental stressors changed recurrently. The latter suggests that top-down and bottom-up changes can have additive effects constraining evolutionary response within populations. The differences in evolutionary trajectories are explained by fluctuations in population sizes of the prey and the predator, which continuously alter the supply of mutations in the prey and strength of selection through predation. Thus, it may be necessary to adopt an eco-evolutionary perspective on studies concerning the evolution of traits mediating species interactions. 相似文献
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Ovarian and pancreatic cancers are two of the most aggressive and lethal cancers, whose management faces only limited therapeutic options. Typically, these tumors spread insidiously accompanied first with atypical symptoms, and usually shift to a drug resistance phenotype with the current pharmaceutical armamentarium. Thus, the development of new drugs acting via a different mechanism of action represents a clear priority. Herein, we are reporting for the first time that the aminosteroid derivative RM-133, developed in our laboratory, displays promising activity on two models of aggressive cancers, namely ovarian (OVCAR-3) and pancreatic (PANC-1) cancers. The IC50 value of RM-133 was 0.8 μM and 0.3 μM for OVCAR-3 and PANC-1 cell lines in culture, respectively. Based on pharmacokinetic studies on RM-133 using 11 different vehicles, we selected two main vehicles: aqueous 0.4% methylcellulose:ethanol (92:8) and sunflower oil:ethanol (92:8) for in vivo studies. Using subcutaneous injection of RM-133 with the methylcellulose-based vehicle, growth of PANC-1 tumors xenografted to nude mice was inhibited by 63%. Quite interestingly, RM-133 injected subcutaneously with the methylcellulose-based or sunflower-based vehicles reduced OVCAR-3 xenograft growth by 122% and 100%, respectively. After the end of RM-133 treatment using the methylcellulose-based vehicle, OVCAR-3 tumor growth inhibition was maintained for ≥ 1 week. RM-133 was also well tolerated in the whole animal, no apparent sign of toxicity having been detected in the xenograft studies. 相似文献
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The fungal genus Puccinia, comprising of several menacing pathogens, has been a persistent peril to global agriculture. Genome sequencing of various members of Puccinia offers a scope to excavate their genomic riddles. The present study has been addressed at exploring the complex niceties of codon and amino acid usage patterns and subsequent elucidation of the determinants that drive such behavior. Multivariate statistical analysis revealed a complex interplay of natural selection for translation and compositional bias to be operational on the codon usage patterns. Gene expression level was observed to be the most competent factor governing codon usage behavior of the genus. In spite of subtle AT richness of the genus, potential highly expressed gene sets were found to preferentially employ GC rich optimal codons. Estimation of relative dinucleotide abundance revealed preference toward the employment of GpA, CpA, TpC, and TpG dinucleotides and restraint from using TpA dinucleotide among the members of the genus. Extensive codon context analysis revealed that codon pairs with GpA, CpA, TpC, and TpG dinucleotides were over-represented and codon pairs with TpA dinucleotide were extensively avoided at the codon–codon (cP3–cA1) junctions. Amino acid usage signatures of the genus were found to be influenced considerably by several imperative factors like aromatic and hydrophobic character of the encoded gene products, genomic compositional constraint, and gene expressivity. Detailed know-how of the potential highly expressed gene sets and associated optimal codons in the genus promise to be informative for the scientific community engaged in combating Puccinia pathogenesis. 相似文献
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Zhicheng Jin Jessica M. Berthiaume Qingling Li Fabrice Henry Zhong Huang Sushabhan Sadhukhan Peng Gao Gregory P. Tochtrop Michelle A. Puchowicz Guo-Fang Zhang 《The Journal of biological chemistry》2014,289(46):32327-32338
Oxidative stress triggers the peroxidation of ω-6-polyunsaturated fatty acids to reactive lipid fragments, including (2E)-4-hydroxy-2-nonenal (HNE). We previously reported two parallel catabolic pathways of HNE. In this study, we report a novel metabolite that accumulates in rat liver perfused with HNE or 4-hydroxynonanoic acid (HNA), identified as 3-(5-oxotetrahydro-2-furanyl)propanoyl-CoA. In experiments using a combination of isotopic analysis and metabolomics studies, three catabolic pathways of HNE were delineated following HNE conversion to HNA. (i) HNA is ω-hydroxylated to 4,9-dihydroxynonanoic acid, which is subsequently oxidized to 4-hydroxynonanedioic acid. This is followed by the degradation of 4-hydroxynonanedioic acid via β-oxidation originating from C-9 of HNA breaking down to 4-hydroxynonanedioyl-CoA, 4-hydroxyheptanedioyl-CoA, or its lactone, 2-hydroxyglutaryl-CoA, and 2-ketoglutaric acid entering the citric acid cycle. (ii) ω-1-hydroxylation of HNA leads to 4,8-dihydroxynonanoic acid (4,8-DHNA), which is subsequently catabolized via two parallel pathways we previously reported. In catabolic pathway A, 4,8-DHNA is catabolized to 4-phospho-8-hydroxynonanoyl-CoA, 3,8-dihydroxynonanoyl-CoA, 6-hydroxyheptanoyl-CoA, 4-hydroxypentanoyl-CoA, propionyl-CoA, and acetyl-CoA. (iii) The catabolic pathway B of 4,8-DHNA leads to 2,6-dihydroxyheptanoyl-CoA, 5-hydroxyhexanoyl-CoA, 3-hydroxybutyryl-CoA, and acetyl-CoA. Both in vivo and in vitro experiments showed that HNE can be catabolically disposed via ω- and ω-1-oxidation in rat liver and kidney, with little activity in brain and heart. Dietary experiments showed that ω- and ω-1-hydroxylation of HNA in rat liver were dramatically up-regulated by a ketogenic diet, which lowered HNE basal level. HET0016 inhibition and mRNA expression level suggested that the cytochrome P450 4A are main enzymes responsible for the NADPH-dependent ω- and ω-1-hydroxylation of HNA/HNE. 相似文献
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Amit Lahiri Ayan Lahiri Namrata Iyer Priyanka Das Dipshikha Chakravortty 《Microbes and infection / Institut Pasteur》2010,12(11):809-818
Salmonella, a Gram-negative facultative intracellular pathogen is capable of infecting vast array of hosts. The striking ability of Salmonella to overcome every hurdle encountered in the host proves that they are true survivors. In the host, Salmonella infects various cell types and needs to survive and replicate by countering the defense mechanism of the specific cell. In this review, we will summarize the recent insights into the cell biology of Salmonella infection. Here, we will focus on the findings that deal with the specific mechanism of various cell types to control Salmonella infection. Further, the survival strategies of the pathogen in response to the host immunity will also be discussed in detail. Better understanding of the mechanisms by which Salmonella evade the host defense system and establish pathogenesis will be critical in disease management. 相似文献
100.
Hanafy M. Ismail Vijay Kumar Rudra P. Singh Christopher Williams Pushkar Shivam Ayan Ghosh Rinki Deb Geraldine M. Foster Janet Hemingway Michael Coleman Marlize Coleman Pradeep Das Mark J. I. Paine 《PLoS neglected tropical diseases》2016,10(1)