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71.
A membrane leucine heptad contributes to trafficking, signaling, and transformation by latent membrane protein 1
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Latent membrane protein 1 (LMP1) of Epstein Barr virus (EBV) is important for maintaining proliferation of EBV-infected B cells. LMP1, unlike its cellular counterpart, CD40, signals without a ligand and is largely internal to the plasma membrane. In order to understand how LMP1 initiates its ligand-independent signaling, we focused on a leucine heptad in LMP1's first membrane-spanning domain that was shown to be necessary for LMP1's signaling through NF-kappaB. LZ1EBV, a recombinant EBV genetically altered to express LZ1, a derivative of LMP1 in which a leucine heptad was replaced with alanines, transformed B cells with 56% of wild-type (wt) EBV's efficiency, demonstrating the importance of this heptad. To elucidate the mechanism by which this domain contributes to the functions of LMP1, the properties of the wt and LZ1 were compared in transfected cells. LZ1 failed to home to lipid rafts as efficiently as did wt LMP1. The distribution of tagged derivatives of LZ1 also differed from that of wt LMP1 in transfected cells. LZ1's defect in homing to lipid rafts and altered trafficking likely underlie the defect in transformation of LZ1EBV. While the third and fourth membrane-spanning domains of LMP1 foster its trafficking to the Golgi, the leucine heptad within the first membrane-spanning domain contributes to its trafficking, particularly to internal rafts. B cells that are successfully transformed by LZ1EBV have the same average number of viral genomes and the same fraction of cells with capped LZ1 at the cell surface but express 50% more of the LZ1 allele than wt infected cells. 相似文献
72.
Antitumor agents. 258. Syntheses and evaluation of dietary antioxidant--taxoid conjugates as novel cytotoxic agents 总被引:1,自引:0,他引:1
Nakagawa-Goto K Yamada K Nakamura S Chen TH Chiang PC Bastow KF Wang SC Spohn B Hung MC Lee FY Lee FC Lee KH 《Bioorganic & medicinal chemistry letters》2007,17(18):5204-5209
Various dietary antioxidants, including vitamins, flavonoids, curcumin, and a coumarin, were conjugated with paclitaxel (1) through an ester linkage. The newly synthesized compounds were evaluated for cytotoxic activity against several human tumor cell lines as well as the corresponding normal cell lines. Interestingly, most tested conjugates selectively inhibited the growth of 1A9 (ovarian) and KB (nasopharyngeal) tumor cells without activity against other cell lines. Particularly, conjugates 16 and 20 were highly active against 1A9 (ED(50) value of 0.005 microg/mL) as well as KB (ED(50) values of 0.005 and 0.14 microg/mL, respectively) cells. Compound 22b, the glycinate ester salt of vitamin E conjugated with 1, appears to be a promising lead for further development as a clinical trial candidate as it exhibited strong inhibitory activity against Panc-1 (pancreatic cancer) with less effect on the related E6E7 (normal) cell line. 相似文献
73.
Increased behavioral and neuronal sensitivity to sex pheromone after brief odor experience in a moth
Plasticity in the response to stimuli related to food and oviposition cues is well documented in insects. However, responses to cues related to reproduction, for example, sex pheromones, are considered to be innate and thus not affected by experience. Here we show that brief preexposure to sex pheromones, without ensuing reward, lowers the threshold for behavioral response and augments the sensitivity in antennal lobe interneurons to pheromone compared with naive male moths. Thus, the sex pheromone system in insects can be modulated by experience. In addition, we show that the behavioral attraction to sex pheromone increases after preexposure in a time-dependent manner: a short-term effect, possibly a form of sensitization, and a long-term effect after more than 24 h. The behavioral long-term effect is paralleled by an increase in sensitivity of interneurons in the primary olfactory center, whereas the peripheral olfactory system does not change its sensitivity. We hypothesize that short-term sensitization to sex pheromone serves as a kind of alert system, whereas the long-term effect improves male performance when reproductively active females are present. 相似文献
74.
Wang SW Parhar K Chiu KJ Tran A Gangoiti P Kong J Gonzalez M Salh B Duronio V Steinbrecher UP Gómez-Muñoz A 《Cellular signalling》2007,19(8):1772-1783
75.
Dyneins across eukaryotes: a comparative genomic analysis 总被引:1,自引:0,他引:1
Dyneins are large minus-end-directed microtubule motors. Each dynein contains at least one dynein heavy chain (DHC) and a variable number of intermediate chains (IC), light intermediate chains (LIC) and light chains (LC). Here, we used genome sequence data from 24 diverse eukaryotes to assess the distribution of DHCs, ICs, LICs and LCs across Eukaryota. Phylogenetic inference identified nine DHC families (two cytoplasmic and seven axonemal) and six IC families (one cytoplasmic). We confirm that dyneins have been lost from higher plants and show that this is most likely because of a single loss of cytoplasmic dynein 1 from the ancestor of Rhodophyta and Viridiplantae, followed by lineage-specific losses of other families. Independent losses in Entamoeba mean that at least three extant eukaryotic lineages are entirely devoid of dyneins. Cytoplasmic dynein 2 is associated with intraflagellar transport (IFT), but in two chromalveolate organisms, we find an IFT footprint without the retrograde motor. The distribution of one family of outer-arm dyneins accounts for 2-headed or 3-headed outer-arm ultrastructures observed in different organisms. One diatom species builds motile axonemes without any inner-arm dyneins (IAD), and the unexpected conservation of IAD I1 in non-flagellate algae and LC8 (DYNLL1/2) in all lineages reveals a surprising fluidity to dynein function. 相似文献
76.
Hydrobiologia - Efficient management of invasive species benefits from understanding patterns of persistence and change over time. In this study, we compare distribution and abundance of the... 相似文献
77.
Mohammed Jamshad Jack Charlton Yu-Pin Lin Sarah?J. Routledge Zharain Bawa Timothy?J. Knowles Michael Overduin Niek Dekker Tim?R. Dafforn Roslyn?M. Bill David?R. Poyner Mark Wheatley 《Bioscience reports》2015,35(2)
G-protein coupled receptors (GPCRs) constitute the largest class of membrane proteins and are a major drug target. A serious obstacle to studying GPCR structure/function characteristics is the requirement to extract the receptors from their native environment in the plasma membrane, coupled with the inherent instability of GPCRs in the detergents required for their solubilization. In the present study, we report the first solubilization and purification of a functional GPCR [human adenosine A2A receptor (A2AR)], in the total absence of detergent at any stage, by exploiting spontaneous encapsulation by styrene maleic acid (SMA) co-polymer direct from the membrane into a nanoscale SMA lipid particle (SMALP). Furthermore, the A2AR–SMALP, generated from yeast (Pichia pastoris) or mammalian cells, exhibited increased thermostability (∼5°C) compared with detergent [DDM (n-dodecyl-β-D-maltopyranoside)]-solubilized A2AR controls. The A2AR–SMALP was also stable when stored for prolonged periods at 4°C and was resistant to multiple freeze-thaw cycles, in marked contrast with the detergent-solubilized receptor. These properties establish the potential for using GPCR–SMALP in receptor-based drug discovery assays. Moreover, in contrast with nanodiscs stabilized by scaffold proteins, the non-proteinaceous nature of the SMA polymer allowed unobscured biophysical characterization of the embedded receptor. Consequently, CD spectroscopy was used to relate changes in secondary structure to loss of ligand binding ([3H]ZM241385) capability. SMALP-solubilization of GPCRs, retaining the annular lipid environment, will enable a wide range of therapeutic targets to be prepared in native-like state to aid drug discovery and understanding of GPCR molecular mechanisms. 相似文献
78.
Tadpoles risk attack from both aquatic and aerial predators. We investigated how body size and group size influenced the behaviour of tadpoles before and during a predatory attack from above to test the predictions of the theoretical economic escape model. We examined escape (swimming) response of small and large Cuban tree frog (Osteopilus septentrionalis) tadpoles kept under three density treatments and predicted that increased group size, body size and depth in the water column would all reduce perceived risk and, therefore, escape responses to simulated predation. Compared with the lower density groups, tadpoles in higher density groups moved shorter distances, and many individuals did not even move away in response to being touched. Contrary to our predictions based on the economic escape model, smaller tadpoles (which should be more vulnerable to a greater suite of predators) were less reactive than larger tadpoles, and this result may reflect different costs of escape. Finally, although tadpoles might be exposed to a wider range of predator species (aerial as well as aquatic predators), we found no effect of initial depth on escape responses. In conclusion, it appears that the main benefit of increased group density in O. septentrionalis tadpoles is likely to be predator dilution, and that variation in densities of tadpoles influences the escape behaviour of individual tadpoles, regardless of tadpole size. 相似文献
79.
Samit Kumar Dutta Pedro Serrano Andrew Proudfoot Michael Geralt Bill Pedrini Kurt Wüthrich 《Journal of biomolecular NMR》2015,61(1):47-53
A standard set of three APSY-NMR experiments has been used in daily practice to obtain polypeptide backbone NMR assignments in globular proteins with sizes up to about 150 residues, which had been identified as targets for structure determination by the Joint Center for Structural Genomics (JCSG) under the auspices of the Protein Structure Initiative (PSI). In a representative sample of 30 proteins, initial fully automated data analysis with the software UNIO-MATCH-2014 yielded complete or partial assignments for over 90 % of the residues. For most proteins the APSY data acquisition was completed in less than 30 h. The results of the automated procedure provided a basis for efficient interactive validation and extension to near-completion of the assignments by reference to the same 3D heteronuclear-resolved [1H,1H]-NOESY spectra that were subsequently used for the collection of conformational constraints. High-quality structures were obtained for all 30 proteins, using the J-UNIO protocol, which includes extensive automation of NMR structure determination. 相似文献
80.
Sophie H. Kromann Ahmed M. Saveer Muhammad Binyameen Marie Bengtsson G?ran Birgersson Bill S. Hansson Fredrik Schlyter Peter Witzgall Rickard Ignell Paul G. Becher 《Proceedings. Biological sciences / The Royal Society》2015,282(1799)
Mating has profound effects on animal physiology and behaviour, not only in females but also in males, which we show here for olfactory responses. In cotton leafworm moths, Spodoptera littoralis, odour-mediated attraction to sex pheromone and plant volatiles are modulated after mating, producing a behavioural response that matches the physiological condition of the male insect. Unmated males are attracted by upwind flight to sex pheromone released by calling females, as well as to volatiles of lilac flowers and green leaves of the host plant cotton, signalling adult food and mating sites, respectively. Mating temporarily abolishes male attraction to females and host plant odour, but does not diminish attraction to flowers. This behavioural modulation is correlated with a response modulation in the olfactory system, as shown by electro-physiological recordings from antennae and by functional imaging of the antennal lobe, using natural odours and synthetic compounds. An effect of mating on the olfactory responses to pheromone and cotton plant volatiles but not to lilac flowers indicates the presence of functionally independent neural circuits within the olfactory system. Our results indicate that these circuits interconnect and weigh perception of social and habitat odour signals to generate appropriate behavioural responses according to mating state. 相似文献