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the role of the 3' terminus of the sindbis virus genome in minus-strand initiation site selection.genome replication of plus-strand rna viruses begins with the generation of a minus-strand copy of the genome. minus-strand synthesis must initiate at or close to the 3' end of the genome and progress to processive elongation to yield the appropriate template for genomic rna synthesis. the sindbis virus genome possesses a 3' polyadenylate tail preceded by a 19 nucleotide conserved sequence element (3' cse). analyses of in vitro and in vivo synthesized minus-strand rna presented in this manuscrip ...200616297426
kinetic evaluation of photosensitivity in genetically engineered neurons expressing green algae light-gated channels.neurons become photosensitive by genetically introducing one of green algae-derived protein, channelrhodopsin-2 (chr2). here, we quantitatively investigated the rapidness of the light-gated current of chr2 expressed in pc12 cells using blue light-emitting diode (led) light. the light-gated current consists of two components, inactivating and non-inactivating. the magnitude of inactivating component was almost linearly related to the light intensity. the non-inactivating component showed a tenden ...200616298005
translation of sindbis virus 26s mrna does not require intact eukariotic initiation factor 4g.the infection of baby hamster kidney (bhk) cells by sindbis virus gives rise to a drastic inhibition of cellular translation, while under these conditions the synthesis of viral structural proteins directed by the subgenomic 26s mrna takes place efficiently. here, the requirement for intact initiation factor eif4g for the translation of this subgenomic mrna has been examined. to this end, sv replicons that contain the protease of human immunodeficiency virus type 1 (hiv-1) or the poliovirus 2a(p ...200616343528
cd8+ t cells require perforin to clear west nile virus from infected neurons.injury to neurons after west nile virus (wnv) infection is believed to occur because of viral and host immune-mediated effects. previously, we demonstrated that cd8+ t cells are required for the resolution of wnv infection in the central nervous system (cns). cd8+ t cells can control infection by producing antiviral cytokines (e.g., gamma interferon or tumor necrosis factor alpha) or by triggering death of infected cells through perforin- or fas ligand-dependent pathways. here, we directly evalu ...200616352536
identification and characterization of a penaeus monodon lymphoid cell-expressed receptor for the yellow head virus.the yellow head virus is a positive-sense, single-stranded rna virus that causes significant mortality in farmed penaeid shrimp. this study sought to isolate and characterize the receptor protein used by the virus to gain entry into penaeus monodon oka (lymphoid) organ cells, a primary target of yellow head virus infections. virus overlay protein binding assay on oka organ membrane preparations identified a 65-kda protein, and antibodies raised against this protein inhibited virus entry in prima ...200616352551
viral transgenesis of embryonic cell cultures from the freshwater microcrustacean daphnia.the aim of this study was to determine whether a recombinant vesicular stomatitis virus (vsv) vector encoding a transgene could be used to infect and express a foreign gene in embryonic primary cell cultures derived from the freshwater microcrustacean daphnia, the most widely used ecotoxicological model organism. to facilitate the evaluation of gene transfer, a reproducible method for establishing primary cultures from daphnia embryonic tissues was developed. within 24 hr after infection, transg ...200616358270
evaluation of cis-acting elements in the rubella virus subgenomic rna that play a role in its translation.the subgenomic (sg) mrna of rubella virus (rub) contains the structural protein open reading frame (sp-orf) that is translated to produce the three virion structural proteins: capsid (c) and glycoproteins e2 and e1. rub expression vectors have been developed that express heterologous genes from the sg rna, including replicons which replace the sp-orf with a heterologous gene, and these expression vectors are candidate vaccine vectors. in the related alphaviruses, translational enhancing elements ...200616172842
the efficient packaging of venezuelan equine encephalitis virus-specific rnas into viral particles is determined by nsp1-3 synthesis.alphaviruses are regarded as attractive systems for expression of heterologous genes and development of recombinant vaccines. venezuelan equine encephalitis virus (vee)-based vectors are particularly promising because of their specificity to lymphoid tissues and strong resistance to interferon. to improve understanding of the vee genome packaging and optimize application of this virus as a vector, we analyzed in more detail the mechanism of packaging of the vee-specific rnas. the presence of the ...200616239019
novel putative targets of n-ethylmaleimide sensitive fusion protein (nsf) and alpha/beta soluble nsf attachment proteins (snaps) include the pak-binding nucleotide exchange factor betapix.n-ethylmaleimide sensitive fusion protein (nsf) is a chaperone that plays a crucial role in the fusion of vesicles with target membranes. nsf mediates the atp-consuming dissociation of a core protein complex that assembles during vesicle fusion and it thereby recharges the fusion machinery to perform multiple rounds of fusion. the binding of nsf to the core complex is mediated by co-chaperones named soluble nsf attachment proteins (snaps), for which three isoforms (alpha, beta and gamma) are kno ...200616795052
hepatitis c virus entry depends on clathrin-mediated endocytosis.due to difficulties in cell culture propagation, the mechanisms of hepatitis c virus (hcv) entry are poorly understood. here, postbinding cellular mechanisms of hcv entry were studied using both retroviral particles pseudotyped with hcv envelope glycoproteins (hcvpp) and the hcv clone jfh-1 propagated in cell culture (hcvcc). hcvpp entry was measured by quantitative real-time pcr after 3 h of contact with target cells, and hcvcc infection was quantified by immunoblot analysis and immunofluoresce ...200616809302
pkr and rnase l contribute to protection against lethal west nile virus infection by controlling early viral spread in the periphery and replication in neurons.west nile virus (wnv) is a neurotropic, mosquito-borne flavivirus that can cause lethal meningoencephalitis. type i interferon (ifn) plays a critical role in controlling wnv replication, spread, and tropism. in this study, we begin to examine the effector mechanisms by which type i ifn inhibits wnv infection. mice lacking both the interferon-induced, double-stranded-rna-activated protein kinase (pkr) and the endoribonuclease of the 2',5'-oligoadenylate synthetase-rnase l system (pkr(-/-) x rl(-/ ...200616809306
prime-boost immunization using dna vaccine and recombinant orf virus protects pigs against pseudorabies virus (herpes suid 1).the present study demonstrates the protective potential of a novel prime-boost vaccination strategy of pigs against lethal pseudorabies virus (prv; herpes suid 1) infection. animals were primed with sindbis virus-derived plasmids that express viral glycoproteins gc and gd (gc- and gd-psin) and subsequently booster immunized with orf virus (orfv; parapoxvirus) recombinants expressing gc and gd (d1701-vrvgc and -vrvgd). the prime-boost vaccination induced strong humoral and cellular-like prv-speci ...200616814432
tumor-specific in vivo transfection with hsv-1 thymidine kinase gene using a sindbis viral vector as a basis for prodrug ganciclovir activation and pet.one type of gene therapy of tumors, gene-directed enzyme-prodrug therapy (gdept), holds considerable promise, although practical considerations limit its clinical applicability. these include the lack of acceptable noninvasive methods that are adaptable to humans for selective tumor targeting of the therapeutic genetic material. sindbis virus is an oncolytic, alpha-virus that selectively targets tumors through the 67-kda laminin receptor (lamr). in this report we describe a novel approach that p ...200616818948
maintenance of cd8 effector t cells by cd4 helper t cells eradicates growing tumors and promotes long-term tumor immunity.human papillomavirus, particularly type 16 (hpv-16), is present in more than 99% of cervical cancers, and oncogenic hpv infection is one of the most important etiologies. it is now clear that cd4(+) t cells play an important role in controlling hpv-associated lesions because immunocompromised patients have a higher frequency of hpv-associated lesions. in the current study, we characterized the significance of cd4(+) t cells in the generation of e7-specific cd8(+) t cell immune responses in mice ...200616824651
epitope-blocking enzyme-linked immunosorbent assay for detection of antibodies to ross river virus in vertebrate sera.we describe the development of an epitope-blocking enzyme-linked immunosorbent assay (elisa) for the sensitive and rapid detection of antibodies to ross river virus (rrv) in human sera and known vertebrate host species. this elisa provides an alternative method for the serodiagnosis of rrv infections.200616829622
carrageenan is a potent inhibitor of papillomavirus infection.certain sexually transmitted human papillomavirus (hpv) types are causally associated with the development of cervical cancer. our recent development of high-titer hpv pseudoviruses has made it possible to perform high-throughput in vitro screens to identify hpv infection inhibitors. comparison of a variety of compounds revealed that carrageenan, a type of sulfated polysaccharide extracted from red algae, is an extremely potent infection inhibitor for a broad range of sexually transmitted hpvs. ...200616839203
entry of feline calicivirus is dependent on clathrin-mediated endocytosis and acidification in endosomes.feline calicivirus is a major causative agent of respiratory disease in cats. it is also one of the few cultivatable members of caliciviridae. we have examined the entry process of feline calicivirus (fcv). an earlier study demonstrated that acidification in endosomes may be required. we have confirmed this observation and expanded upon it, demonstrating, using drugs to inhibit the various endocytic pathways and dominant-negative mutants, that fcv infects cells via clathrin-mediated endocytosis. ...200616840330
newcastle disease virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death.newcastle disease virus (ndv), an avian paramyxovirus, is tumor selective and intrinsically oncolytic. here, we present evidence that genetically modified, recombinant ndv strains are cytotoxic to human tumor cell lines of ecto-, endo-, and mesodermal origin. we show that cytotoxicity against tumor cells is due to multiple caspase-dependent pathways of apoptosis independent of interferon signaling competence. the signaling pathways of ndv-induced, cancer cell-selective apoptosis are not well und ...200616840332
ribosomal protein s6 associates with alphavirus nonstructural protein 2 and mediates expression from alphavirus messages.although alphaviruses dramatically alter cellular function within hours of infection, interactions between alphaviruses and specific host cellular proteins are poorly understood. although the alphavirus nonstructural protein 2 (nsp2) is an essential component of the viral replication complex, it also has critical auxiliary functions that determine the outcome of infection in the host. to gain a better understanding of nsp2 function, we sought to identify cellular proteins with which venezuelan e ...200616840351
utilization of host sr protein kinases and rna-splicing machinery during viral replication.although the viral genome is often quite small, it encodes a broad series of proteins. the virus takes advantage of the host-rna-processing machinery to provide the alternative splicing capability necessary for the expression of this proteomic diversity. serine-arginine-rich (sr) proteins and the kinases that activate them are central to this alternative splicing machinery. in studies reported here, we use the hiv genome as a model. we show that hiv expression decreases overall sr protein/activi ...200616840555
bats: important reservoir hosts of emerging viruses.bats (order chiroptera, suborders megachiroptera ["flying foxes"] and microchiroptera) are abundant, diverse, and geographically widespread. these mammals provide us with resources, but their importance is minimized and many of their populations and species are at risk, even threatened or endangered. some of their characteristics (food choices, colonial or solitary nature, population structure, ability to fly, seasonal migration and daily movement patterns, torpor and hibernation, life span, roo ...200616847084
cryptosporidium parvum infects human cholangiocytes via sphingolipid-enriched membrane microdomains.cryptosporidium parvum attaches to intestinal and biliary epithelial cells via specific molecules on host-cell surface membranes including gal/galnac-associated glycoproteins. subsequent cellular entry of this parasite depends on host-cell membrane alterations to form a parasitophorous vacuole via activation of phosphatidylinositol 3-kinase (pi-3k)/cdc42-associated actin remodelling. how c. parvum hijacks these host-cell processes to facilitate its infection of target epithelia is unclear. using ...200616848787
sindbis virus infection of two model insect cell systems--a comparative study.sindbis, the prototype of the alphaviruses causes mosquito-borne diseases in mammals and replicates in a wide variety of vertebrate and invertebrate cell cultures. this characteristic can be exploited to use the vast array of drosophila genetic information available for investigations of the interaction of sindbis virus with an alternate invertebrate host. for this purpose, a comparative study of sindbis virus infection of schnieder-2 drosophila (s2) cells to cells of the mosquito aedes albopict ...200616854488
a 5' rna element promotes dengue virus rna synthesis on a circular genome.the mechanisms of rna replication of plus-strand rna viruses are still unclear. here, we identified the first promoter element for rna synthesis described in a flavivirus. using dengue virus as a model, we found that the viral rdrp discriminates the viral rna by specific recognition of a 5' element named sla. we demonstrated that rna-rna interactions between 5' and 3' end sequences of the viral genome enhance dengue virus rna synthesis only in the presence of an intact sla. we propose a novel me ...200616882970
hiv and cxcr4 in a kiss of autophagic death.aids is characterized by cd4+ t lymphocyte depletion, yet the mechanisms underlying this central aspect of hiv pathogenesis are still poorly understood. in this issue of the jci, espert et al. identify a mechanism by which the hiv envelope glycoprotein can induce death in uninfected cd4+ t cells (see the related article beginning on page 2161). the hiv envelope glycoprotein interacts with cxc chemokine receptor 4 to activate the lysosomal degradation pathway of autophagy, which is necessary for ...200616886053
autophagy is involved in t cell death after binding of hiv-1 envelope proteins to cxcr4.hiv-1 envelope glycoproteins (env), expressed at the cell surface, induce apoptosis of uninfected cd4+ t cells, contributing to the development of aids. here we demonstrate that, independently of hiv replication, transfected or hiv-infected cells that express env induced autophagy and accumulation of beclin 1 in uninfected cd4+ t lymphocytes via cxcr4. the same phenomena occurred in a t cell line and in transfected hek.293 cells that expressed both wild-type cxcr4 and a truncated form of cd4 tha ...200616886061
tracking and elucidating alphavirus-host protein interactions.viral infections cause profound alterations in host cells. here, we explore the interactions between proteins of the alphavirus sindbis and host factors during the course of mammalian cell infection. using a mutant virus expressing the viral nsp3 protein tagged with green fluorescent protein (gfp) we directly observed nsp3 localization and isolated nsp3-interacting proteins at various times after infection. these results revealed that host factor recruitment to nsp3-containing complexes was time ...200616895903
actin-associated neurabin-protein phosphatase-1 complex regulates hippocampal plasticity.protein phosphatase-1 (pp1) has been implicated in the control of long-term potentiation (ltp) and depression (ltd) in rat hippocampal ca1 neurons. pp1 catalytic subunits associate with multiple postsynaptic regulatory subunits, but the pp1 complexes that control hippocampal ltp and ltd in the rat hippocampus remain unidentified. the neuron-specific actin-binding protein, neurabin-i, is enriched in dendritic spines, and tethers pp1 to actin-rich postsynaptic density to regulate morphology and ma ...200616899074
transient low ph treatment enhances infection of lentiviral vector pseudotypes with a targeting sindbis envelope.efficient transduction of primary hematopoietic cell types by oncoretroviral vectors and lentiviral vectors with a variety of different envelope pseudotypes has proven to be difficult. we recently developed a lentiviral vector based upon a modified sindbis virus envelope that allows targeted transduction via antibody recognition to specific cells in unfractionated cell populations. however, similar to other envelope pseudotypes, the utility of this vector for some primary hematopoietic cells was ...200616905172
structural and functional basis for adp-ribose and poly(adp-ribose) binding by viral macro domains.macro domains constitute a protein module family found associated with specific histones and proteins involved in chromatin metabolism. in addition, a small number of animal rna viruses, such as corona- and toroviruses, alphaviruses, and hepatitis e virus, encode macro domains for which, however, structural and functional information is extremely limited. here, we characterized the macro domains from hepatitis e virus, semliki forest virus, and severe acute respiratory syndrome coronavirus (sars ...200616912299
rapid adaptation of a recombinant vesicular stomatitis virus to a targeted cell line.vesicular stomatitis virus (vsv) is being developed for cancer therapy. we created a recombinant replicating vsv (rrvsv) that preferentially infected her2/neu-expressing breast cancer cells. this rrvsv did not express the native vsv-g glycoprotein (gp). instead, it expressed a chimeric sindbis gp which included a single-chain antibody (sca) directed to the human her2/neu receptor. the virus infected mouse mammary carcinoma cells (d2f2/e2) expressing her2/neu 23-fold better than the parent cells ...200616912309
role of the low-density lipoprotein receptor in entry of bovine viral diarrhea virus.among several proposed cellular receptors for bovine viral diarrhea virus (bvdv), the low-density lipoprotein (ldl) receptor is of special interest because it is also considered a receptor for the related hepatitis c virus. it has been reported that an anti-ldl receptor monoclonal antibody blocked the infection of bovine cells by bvdv and that the resistance of bovine crib cells (cells resistant to infection with bvdv) (e. f. flores and r. o. donis, virology 208:565-575, 1995) to bvdv infection ...200616928760
rotavirus activates jnk and p38 signaling pathways in intestinal cells, leading to ap-1-driven transcriptional responses and enhanced virus replication.rotavirus infection is known to regulate transcriptional changes in many cellular genes. the transcription factors nf-kappab and ap-1 are activated by rotavirus infection, but the upstream processes leading to these events are largely unidentified. we therefore studied the activation state during rotavirus infection of c-jun nh2-terminal kinase (jnk) and p38, which are kinases known to activate ap-1. as assessed by western blotting using phospho-specific antibodies, infection with rhesus rotavir ...200616928761
phylogenetic analysis of buggy creek virus: evidence for multiple clades in the western great plains, united states of america.we present the first detailed phylogenetic analysis of buggy creek virus (bcrv), a poorly known alphavirus with transmission cycles involving a cimicid swallow bug (oeciacus vicarius) vector and cliff swallows (petrochelidon pyrrhonota) and house sparrows (passer domesticus) as the principal avian hosts. nucleotide sequences of a 2,075-bp viral envelope glycoprotein-coding region, covering the entire pe2 gene, were determined for 33 bcrv isolates taken from swallow bugs at cliff swallow colonies ...200616936062
c-e1 fusion protein synthesized by rubella virus di rnas maintained during serial passage.rubella virus (rub) replicons are derivatives of the rub infectious cdna clone that retain the nonstructural open reading frame (ns-orf) that encodes the replicase proteins but not the structural protein orf (sp-orf) that encodes the virion proteins. rub defective interfering (di) rnas contain deletions within the sp-orf and thus resemble replicons. di rnas often retain the 5' end of the capsid protein (c) gene that has been shown to modulate virus-specific rna synthesis. however, when replicons ...200616938325
alphavirus capsid protein helix i controls a checkpoint in nucleocapsid core assembly.the assembly of the alphavirus nucleocapsid core has been investigated using an in vitro assembly system. the c-terminal two-thirds of capsid protein (cp), residues 81 to 264 in sindbis virus (sinv), have been previously shown to have all the rna-cp and cp-cp contacts required for core assembly in vitro. helix i, which is located in the n-terminal dispensable region of the cp, has been proposed to stabilize the core by forming a coiled coil in the cp dimer formed by the interaction of residues 8 ...200616940497
altered central nervous system gene expression caused by congenitally acquired persistent infection with lymphocytic choriomeningitis virus.neonatal infection of most mouse strains with lymphocytic choriomeningitis virus (lcmv) leads to a life-long persistent infection characterized by high virus loads in the central nervous system (cns) in the absence of inflammation and tissue destruction. these mice, however, exhibit impaired learning and memory. the occurrence of cognitive defects in the absence of overt cns pathology led us to the hypothesis that chronic virus infection may contribute to neuronal dysfunction by altering the hos ...200616940520
modulation of the unfolded protein response by the severe acute respiratory syndrome coronavirus spike protein.perturbation of the function of endoplasmic reticulum (er) causes stress leading to the activation of cell signaling pathways known as the unfolded protein response (upr). severe acute respiratory syndrome (sars) coronavirus (sars-cov) uses er as a site for synthesis and processing of viral proteins. in this report, we demonstrate that infection with sars-cov induces the upr in cultured cells. a comparison with m, e, and nsp6 proteins indicates that sars-cov spike (s) protein sufficiently induce ...200616940539
acid sphingomyelinase deficiency increases susceptibility to fatal alphavirus encephalomyelitis.sindbis virus (sv), an enveloped virus with a single-stranded, plus-sense rna genome, is the prototype alphavirus in the togaviridae family. in mice, sv infects neurons and can cause apoptosis of immature neurons. sphingomyelin (sm) is the most prevalent cellular sphingolipid, is particularly abundant in the nervous systems of mammals, and is required for alphavirus fusion and entry. the level of sm is tightly regulated by sphingomyelinases. a defect in acid sphingomyelinase (asmase) results in ...200616943298
the effects of n-terminal insertion into vsv-g of an scfv peptide.recombinant retroviruses, including lentiviruses, are the most widely used vectors for both in vitro and in vivo stable gene transfer. however, the inability to selectively deliver transgenes into cells of interest limits the use of this technology. due to its wide tropism, stability and ability to pseudotype a range of viral vectors, vesicular stomatitis virus g protein (vsv-g) is the most commonly used pseudotyping protein. here, we attempted to engineer this protein for targeting purposes. ch ...200616948856
immunization with a low-dose replicon dna vaccine encoding phl p 5 effectively prevents allergic sensitization.replicase-based dna vaccines stimulate t(h)1-biased immune responses at ultralow doses and induce self-removal of transfected cells through apoptosis. both aspects are important requirements for efficient and safe dna-based immunotherapy of type i allergies.200616950295
detection of seroconversion to west nile virus, usutu virus and sindbis virus in uk sentinel chickens.we previously reported evidence of west nile virus (wnv) circulation in uk birds, probably introduced by migratory birds from overseas. we now demonstrate wnv-specific seroconversion in sentinel chickens raised on an english farm. maternal neutralizing antibodies to wnv in hatchlings declined within three weeks. during the following months, healthy chickens developed wnv neutralizing antibodies that were confirmed by immunoblotting and indirect immunofluorescence tests using wnv antigens. the pr ...200616952307
recombination and selection in the evolution of picornaviruses and other mammalian positive-stranded rna viruses.picornaviridae are a large virus family causing widespread, often pathogenic infections in humans and other mammals. picornaviruses are genetically and antigenically highly diverse, with evidence for complex evolutionary histories in which recombination plays a major part. to investigate the nature of recombination and selection processes underlying the evolution of serotypes within different picornavirus genera, large-scale analysis of recombination frequencies and sites, segregation by serotyp ...200616956935
reverse transcription-pcr-enzyme-linked immunosorbent assay for rapid detection and differentiation of alphavirus infections.due to the lack of a rapid, simple, and inexpensive assay for detecting alphavirus infections, we combined a reverse transcription-pcr with an enzyme-linked immunosorbent assay (rt-pcr-elisa) to identify human pathogenic alphaviruses that are endemic in the new world. by combining the sensitivity of pcr, the detection simplicity of elisa, and the specificities of dna probes, this method rapidly detected and differentiated closely related species and subtypes of several medically important alphav ...200616957044
antiviral action of the tumor suppressor arf.oncogenic viruses frequently target the pathways controlled by tumor suppressor genes, suggesting an extra function for these proteins as antiviral factors. the control exerted by the tumor suppressor arf on cellular proliferation is crucial to restrict tumor development; however, a potential contribution of arf to prevent viral infectivity has remained unexplored. in the present study, we investigated the consequences of loss or increased expression of arf on viral infection. our results reveal ...200616957780
venezuelan equine encephalitis virus transmission and effect on pathogenesis.quantifying the dose of an arbovirus transmitted by mosquitoes is essential for designing pathogenesis studies simulating natural infection of vertebrates. titration of saliva collected in vitro from infected mosquitoes may not accurately estimate titers transmitted during blood feeding, and infection by needle injection may affect vertebrate pathogenesis. we compared the amount of venezuelan equine encephalitis virus collected from the saliva of aedes taeniorhynchus to the amount injected into ...200616965696
o'nyong-nyong virus, chad.we report the first laboratory-confirmed human infection with o'nyong-nyong virus in chad. this virus was isolated from peripheral blood mononuclear cells of a patient with evidence of a seroconversion to a virus related to chikungunya virus. genome sequence was partly determined, and phylogenetic studies were conducted.200616965706
oligomerization of hepatitis c virus core protein is crucial for interaction with the cytoplasmic domain of e1 envelope protein.hepatitis c virus (hcv) contains two membrane-associated envelope glycoproteins, e1 and e2, which assemble as a heterodimer in the endoplasmic reticulum (er). in this study, predictive algorithms and genetic analyses of deletion mutants and glycosylation site variants of the e1 glycoprotein were used to suggest that the glycoprotein can adopt two topologies in the er membrane: the conventional type i membrane topology and a polytopic topology in which the protein spans the er membrane twice with ...200616971440
translation of the flavivirus kunjin ns3 gene in cis but not its rna sequence or secondary structure is essential for efficient rna packaging.our previous studies using trans-complementation analysis of kunjin virus (kun) full-length cdna clones harboring in-frame deletions in the ns3 gene demonstrated the inability of these defective complemented rnas to be packaged into virus particles (w. j. liu, p. l. sedlak, n. kondratieva, and a. a. khromykh, j. virol. 76:10766-10775). in this study we aimed to establish whether this requirement for ns3 in rna packaging is determined by the secondary rna structure of the ns3 gene or by the essen ...200616971441
functions of the stem region of the semliki forest virus fusion protein during virus fusion and assembly.membrane fusion of the alphaviruses is mediated by the e1 protein, a class ii virus membrane fusion protein. during fusion, e1 dissociates from its heterodimer interaction with the e2 protein and forms a target membrane-inserted e1 homotrimer. the structure of the homotrimer is that of a trimeric hairpin in which e1 domain iii and the stem region fold back toward the target membrane-inserted fusion peptide loop. the e1 stem region has a strictly conserved length and several highly conserved resi ...200616971447
site-directed antibodies against the stem region reveal low ph-induced conformational changes of the semliki forest virus fusion protein.the e1 envelope protein of the alphavirus semliki forest virus (sfv) is a class ii fusion protein that mediates low ph-triggered membrane fusion during virus infection. like other class i and class ii fusion proteins, during fusion e1 inserts into the target membrane and rearranges to form a trimeric hairpin structure. the postfusion structures of the alphavirus and flavivirus fusion proteins suggest that the "stem" region connecting the fusion protein domain iii to the transmembrane domain inte ...200616973563
the 37/67-kilodalton laminin receptor is a receptor for adeno-associated virus serotypes 8, 2, 3, and 9.adeno-associated virus serotype 8 (aav8) is currently emerging as a powerful gene transfer vector, owing to its capability to efficiently transduce many different tissues in vivo. while this is believed to be in part due to its ability to uncoat more readily than other aav serotypes such as aav2, understanding all the processes behind aav8 transduction is important for its application and optimal use in human gene therapy. here, we provide the first report of a cellular receptor for aav8, the 37 ...200616973587
testosterone correlates with venezuelan equine encephalitis virus infection in macaques.here we briefly report testosterone and cytokine responses to venezuelan equine encephalitis virus (veev) in macaques which were used as part of a larger study conducted by the department of defense to better characterize pathological responses to aerosolized veev in non-human primates. serial samples were collected and analyzed for testosterone and cytokines prior to and during infection in 8 captive male macaques. infected animals exhibited a febrile response with few significant changes in cy ...200616571136
hippocampal long-term potentiation is supported by presynaptic and postsynaptic tyrosine receptor kinase b-mediated phospholipase cgamma signaling.neurotrophins have been shown to play a critical role in activity-dependent synaptic plasticity such as long-term potentiation (ltp) in the hippocampus. although the role of brain-derived neurotrophic factor (bdnf) and its tyrosine kinase receptor [tyrosine receptor kinase b (trkb)] is well documented, it still remains unresolved whether presynaptic or postsynaptic activation of trkb is involved in the induction of ltp. to address this question, we locally and specifically interfered with a down ...200616571757
recovery of a recombinant salmonid alphavirus fully attenuated and protective for rainbow trout.sleeping disease virus (sdv) is a member of the new salmonid alphavirus genus within the togaviridae family. the single-stranded rna genome of sdv is 11,894 nucleotides long, excluding the 3' poly(a) tail. a full-length cdna has been generated; the cdna was fused to a hammerhead ribozyme sequence at the 5' end and inserted into a transcription plasmid (pcdna3) backbone, yielding psdv. by transfection of psdv into fish cells, recombinant sdv (rsdv) was successfully recovered. demonstration of the ...200616571825
formation of nsp3-specific protein complexes during sindbis virus replication.alphaviruses are arthropod-borne viruses (arboviruses) that include a number of important human and animal pathogens. their replication proceeds in the cytoplasm of infected cells and does not directly depend on nuclei. alphaviruses encode only four nonstructural proteins that are required for the replication of viral genome and transcription of the subgenomic rna. however, the replicative enzyme complexes (rcs) appear to include cellular proteins and assemble on cellular organelles. we have dev ...200616571828
hiv protease cleaves poly(a)-binding protein.the pabp [poly(a)-binding protein] is able to interact with the 3' poly(a) tail of eukaryotic mrna, promoting its translation. cleavage of pabp by viral proteases encoded by several picornaviruses and caliciviruses plays a role in the abrogation of cellular protein synthesis. we report that infection of mt-2 cells with hiv-1 leads to efficient proteolysis of pabp. analysis of pabp integrity was carried out in bhk-21 (baby-hamster kidney) and cos-7 cells upon individual expression of the protease ...200616594896
combining caspase and mitochondrial dysfunction inhibitors of apoptosis to limit cell death in mammalian cell cultures.apoptosis is now recognized as a significant problem in mammalian cell culture. therefore, in this study, a single gene and multigene approach to inhibit apoptosis has been examined. stable chinese hamster ovary (cho) cell lines were generated to overexpress different single, dual, and triple combinations of three apoptosis inhibitor genes. two upstream inhibitors involved in the mitochondrial pathway, bcl-x(l) and aven, were expressed in addition to a downstream inhibitor of caspases. the caspa ...200616598795
antiviral effect of the mammalian translation initiation factor 2alpha kinase gcn2 against rna viruses.in mammals, four different protein kinases, heme-regulated inhibitor, double-stranded rna-dependent protein kinase (pkr), general control non-derepressible-2 (gcn2) and pkr-like endoplasmic reticulum kinase, regulate protein synthesis in response to environmental stresses by phosphorylating the alpha-subunit of the initiation factor 2 (eif2alpha). we now report that mammalian gcn2 is specifically activated in vitro upon binding of two nonadjacent regions of the sindbis virus (sv) genomic rna to ...200616601681
dual role of the exocyst in ampa receptor targeting and insertion into the postsynaptic membrane.intracellular membrane trafficking of glutamate receptors at excitatory synapses is critical for synaptic function. however, little is known about the specialized trafficking events occurring at the postsynaptic membrane. we have found that two components of the exocyst complex, sec8 and exo70, separately control synaptic targeting and insertion of ampa-type glutamate receptors. sec8 controls the directional movement of receptors towards synapses through pdz-dependent interactions. in contrast, ...200616601687
gene therapy that safely targets and kills tumor cells throughout the body.the authors studied the therapeutic value of sindbis vectors for advanced metastatic cancer by using a variety of clinically accurate mouse models and demonstrated through imaging, histological, and molecular data that sindbis vectors systemically and specifically infect/detect and kill metastasized tumors in vivo, leading to significant suppression of tumor growth and enhanced survival. use of two different bioluminescent genetic markers for the ivis imaging system (xenogen corp., alameda, ca) ...200616608394
repair and polyadenylation of a naturally occurring hepatitis c virus 3' nontranslated region-shorter variant in selectable replicon cell lines.the 3' nontranslated region (ntr) of the hepatitis c virus (hcv) genome is highly conserved and contains specific cis-acting rna motifs that are essential in directing the viral replication machinery to initiate at the correct 3' end of the viral genome. since the ends of viral genomes may be damaged by cellular rnases, preventing the initiation of viral rna replication, stable rna hairpin structures in the 3' ntr may also be essential in host defense against exoribonucleases. during 3'-terminal ...200616611892
mutations in the endodomain of sindbis virus glycoprotein e2 define sequences critical for virus assembly.envelopment of sindbis virus at the plasma membrane is a multistep process in which an initial step is the association of the e2 protein via a cytoplasmic endodomain with the preassembled nucleocapsid. sindbis virus is vectored in nature by blood-sucking insects and grows efficiently in a number of avian and mammalian vertebrate hosts. the assembly of sindbis virus, therefore, must occur in two very different host cell environments. mammalian cells contain cholesterol which insect membranes lack ...200616611906
time- and temperature-dependent activation of hepatitis c virus for low-ph-triggered entry.hepatitis c virus (hcv) is an important human pathogen associated with chronic liver disease. recently, based on a genotype 2a isolate, tissue culture systems supporting complete replication and infectious virus production have been developed. in this study, we used cell culture-produced infectious hcv to analyze the viral entry pathway into huh-7.5 cells. bafilomycin a1 and concanamycin a, inhibitors of vacuolar atpases, prevented hcv entry when they were present prior to infection and had mini ...200616439530
neonatal immunization with a sindbis virus-dna measles vaccine induces adult-like neutralizing antibodies and cell-mediated immunity in the presence of maternal antibodies.infants younger than age 9 mo do not respond reliably to the live attenuated measles vaccine due the immaturity of their immune system and the presence of maternal abs that interfere with successful immunization. we evaluated the immune responses elicited by sindbis virus replicon-based dna vaccines encoding measles virus (mv) hemagglutinin (h, pmsin-h) or both hemagglutinin and fusion (f, pmsinh-fdu) glycoproteins in neonatal mice born to naive and measles-immune mothers. despite the presence o ...200616622037
partial reconstitution of the cd4+-t-cell compartment in cd4 gene knockout mice restores responses to tuberculosis dna vaccines.reactivation tuberculosis (tb) is a serious problem in immunocompromised individuals, especially those with human immunodeficiency virus (hiv) coinfection. the adaptive immune response mediated by cd4+ and cd8+ t cells is known to confer protection against tb. hence, vaccines against tb are designed to activate these two components of the immune system. anti-tb dna vaccines encoding the immunodominant proteins ag85a, ag85b, and psts-3 from mycobacterium tuberculosis are ineffective in mice lacki ...200616622212
[detection of banna virus-specific nucleic acid with taqman rt-pcr assay].to develop a rapid and more sensitive taqman rt-pcr assay specific for banna virus.200616642219
sindbis virus replicon particles encoding calreticulin linked to a tumor antigen generate long-term tumor-specific immunity.alphavirus vectors have emerged as a promising strategy for the development of cancer vaccines and gene therapy applications. in this study, we used the replication-defective vaccine vector sin replicon particles from a new packaging cell line (pcl) to develop sin replicon particles encoding calreticulin (crt) linked to a model tumor antigen, human papillomavirus type 16 (hpv16) e7 protein. the linkage of crt to e7 in sin replicon particles resulted in a significant increase in e7-specific cd8(+ ...200616645621
bioportfolio: lifelong persistence of variant and prototypic erythrovirus dna genomes in human tissue.human erythrovirus is a minute, single-stranded dna virus causing many diseases, including erythema infectiosum, arthropathy, and fetal death. after primary infection, the viral genomes persist in solid tissues. besides the prototype, virus type 1, two major variants (virus types 2 and 3) have been identified recently, the clinical significance and epidemiology of which are mostly unknown. we examined 523 samples of skin, synovium, tonsil, or liver (birth year range, 1913-2000), and 1,640 sera, ...200616651522
induction of apoptosis limits cytomegalovirus cross-species infection.cross-species infections are responsible for the majority of emerging and re-emerging viral diseases. however, little is known about the mechanisms that restrict viruses to a certain host species, and the factors viruses need to cross the species barrier and replicate in a different host. cytomegaloviruses (cmvs) are representatives of the beta-herpesviruses that are highly species specific. they replicate only in cells of their own or a closely related species. in this study, the molecular mech ...200616688216
altered immune response to cns viral infection in mice with a conditional knock-down of macrophage-lineage cells.neuroadapted sindbis virus (nsv) is a neuronotropic virus that causes hindlimb paralysis in susceptible mice and rats. the authors and others have demonstrated that though death of infected motor neurons occurs, bystander death of uninfected neurons also occurs and both contribute to the paralysis that ensues following infection. the authors have previously shown that the treatment of nsv-infected mice with minocycline, an inhibitor that has many functions within the central nervous system (cns) ...200616691560
gamma interferon plays a crucial early antiviral role in protection against west nile virus infection.west nile virus (wnv) causes a severe central nervous system (cns) infection in humans, primarily in the elderly and immunocompromised. prior studies have established an essential protective role of several innate immune response elements, including alpha/beta interferon (ifn-alpha/beta), immunoglobulin m, gammadelta t cells, and complement against wnv infection. in this study, we demonstrate that a lack of ifn-gamma production or signaling results in increased vulnerability to lethal wnv infect ...200616699014
molecular determinants of substrate specificity for semliki forest virus nonstructural protease.the c-terminal cysteine protease domain of semliki forest virus nonstructural protein 2 (nsp2) regulates the virus life cycle by sequentially cleaving at three specific sites within the virus-encoded replicase polyprotein p1234. the site between nsp3 and nsp4 (the 3/4 site) is cleaved most efficiently. analysis of semliki forest virus-specific cleavage sites with shuffled n-terminal and c-terminal half-sites showed that the main determinants of cleavage efficiency are located in the region prece ...200616699022
a herpes simplex virus recombinant that exhibits a single-chain antibody to her2/neu enters cells through the mammary tumor receptor, independently of the gd receptors.the human epidermal growth factor receptor 2/neuregulin (her2/neu) receptor is overexpressed in highly malignant mammary and ovarian tumors and correlates with a poor prognosis. it is a target for therapy; humanized monoclonal antibodies to her2 have led to increased survival of patients with her2/neu-positive breast cancer. as a first step in the design of an oncolytic herpes simplex virus able to selectively infect her2/neu-positive cells, we constructed two recombinants, r-lm11 and r-lm11l, t ...200616699034
genome microevolution of chikungunya viruses causing the indian ocean outbreak.a chikungunya virus outbreak of unprecedented magnitude is currently ongoing in indian ocean territories. in réunion island, this alphavirus has already infected about one-third of the human population. the main clinical symptom of the disease is a painful and invalidating poly-arthralgia. besides the arthralgic form, 123 patients with a confirmed chikungunya infection have developed severe clinical signs, i.e., neurological signs or fulminant hepatitis.200616700631
phosphatidylserine is involved in gene expression from sindbis virus subgenomic promoter.sindbis virus replication is mediated by an rna replicase translated from viral rna genome. the replicase synthesizes progeny genomic rna and shorter rna (subgenomic rna) carrying viral structural genes in association with cytoplasmic membranes. here we examined the involvement of a membrane lipid, phosphatidylserine (ps), in sindbis virus gene expression using chinese hamster ovary cell mutants. when the mutant cells were transfected with viral replicon rna, in which the structural genes downst ...200616701551
potential arbovirus emergence and implications for the united kingdom.arboviruses have evolved a number of strategies to survive environmental challenges. this review examines the factors that may determine arbovirus emergence, provides examples of arboviruses that have emerged into new habitats, reviews the arbovirus situation in western europe in detail, discusses potential arthropod vectors, and attempts to predict the risk for arbovirus emergence in the united kingdom. we conclude that climate change is probably the most important requirement for the emergence ...200616704800
ubp43 is a novel regulator of interferon signaling independent of its isg15 isopeptidase activity.interferons (ifns) regulate diverse cellular functions through activation of the janus kinase-signal transducer and activator of transcription (jak-stat) pathway. lack of ubp43, an ifn-inducible isg15 deconjugating enzyme, leads to ifn hypersensitivity in ubp43-/- mice, suggesting an important function of ubp43 in downregulation of ifn responses. here, we show that ubp43 negatively regulates ifn signaling independent of its isopeptidase activity towards isg15. ubp43 functions specifically for ty ...200616710296
production and characterization of vaccines based on flaviviruses defective in replication.to develop new vaccine candidates for flavivirus infections, we have engineered two flaviviruses, yellow fever virus (yfv) and west nile virus (wnv), that are deficient in replication. these defective pseudoinfectious viruses (pivs) lack a functional copy of the capsid (c) gene in their genomes and are incapable of causing spreading infection upon infection of cells both in vivo and in vitro. however, they produce extracellular e protein in form of secreted subviral particles (svps) that are kno ...200616712897
partial beclin 1 silencing aggravates doxorubicin- and fas-induced apoptosis in hepg2 cells.to investigate the role of beclin 1 on the susceptibility of hepg2 cells to undergo apoptosis after anti-fas antibody or doxorubicin treatment.200616718815
type i interferons are essential for the efficacy of replicase-based dna vaccines.the immunogenicity and efficacy of nucleic acid vaccines can be greatly enhanced when antigen production is under the control of an alphaviral replicase enzyme. however, replicase-mediated mrna overproduction does not necessarily result in enhanced antigen level. instead, the strong adaptive immune response of alphavirus replicon-based vectors is due to their production of double-stranded rna (dsrna) intermediates, which trigger innate immunity. because viral infections are known to trigger inna ...200616725231
sindbis virus nonstructural protein nsp2 is cytotoxic and inhibits cellular transcription.replication of alphaviruses in vertebrate cells strongly affects cell physiology and ultimately leads to development of a cytopathic effect (cpe) and cell death. sindbis virus (sin) replication causes major changes in cellular macromolecular synthesis, in which the strong downregulation of transcription of cellular mrnas and rrnas plays a critical role. sin nonstructural protein nsp2 was previously proposed as one of the main regulators of virus-host cell interactions, because point mutations in ...200616731907
blocking of interferon-induced jak-stat signaling by japanese encephalitis virus ns5 through a protein tyrosine phosphatase-mediated mechanism.japanese encephalitis virus (jev), a mosquito-borne flavivirus that causes severe human disease, has been shown to block the interferon (ifn)-induced janus kinase signal transducer and activation of transcription (jak-stat) signaling cascade by preventing tyk2 tyrosine phosphorylation and stat activation. in this study, we demonstrate that expression of the jev nonstructural protein ns5 readily blocked ifn-stimulated jak-stat signaling events such as stat1 nuclear translocation and tyrosine phos ...200616731929
polyadenylation of genomic rna and initiation of antigenomic rna in a positive-strand rna virus are controlled by the same cis-element.genomes and antigenomes of many positive-strand rna viruses contain 3'-poly(a) and 5'-poly(u) tracts, respectively, serving as mutual templates. mechanism(s) controlling the length of these homopolymeric stretches are not well understood. here, we show that in coxsackievirus b3 (cvb3) and three other enteroviruses the poly(a) tract is approximately 80-90 and the poly(u) tract is approximately 20 nt-long. mutagenesis analysis indicate that the length of the cvb3 3'-poly(a) is determined by the or ...200616738134
tau aggregation and progressive neuronal degeneration in the absence of changes in spine density and morphology after targeted expression of alzheimer's disease-relevant tau constructs in organotypic hippocampal slices.alzheimer's disease (ad) is characterized by progressive loss of neurons in selected brain regions, extracellular accumulations of amyloid beta, and intracellular fibrils containing hyperphosphorylated tau. tau mutations in familial tauopathies confirmed a central role of tau pathology; however, the role of tau alteration and the sequence of tau-dependent neurodegeneration in ad remain elusive. using sindbis virus-mediated expression of ad-relevant tau constructs in hippocampal slices, we show t ...200616738255
regulation of inducible nitric oxide synthase gene in glial cells.elevated levels of no produced within the central nervous system (cns) are associated with the pathogenesis of neuroinflammatory and neurodegenerative human diseases such as multiple sclerosis, hiv dementia, brain ischemia, trauma, parkinson's disease, and alzheimer's disease. resident glial cells in the cns (astroglia and microglia) express inducible nitric oxide synthase (inos) and produce high levels of no in response to a wide variety of proinflammatory and degenerative stimuli. although pat ...200616771683
suppression of the interferon-mediated innate immune response by pseudorabies virus.pseudorabies virus (prv) is an alphaherpesvirus related to the human pathogens herpes simplex virus type 1 (hsv-1) and varicella-zoster virus. prv is capable of infecting and killing a wide variety of mammals. how it avoids innate immune defenses in so many hosts is not understood. while the anti-interferon (ifn) strategies of hsv-1 have been studied, little is known about how prv evades the ifn-mediated immune response. in this study, we determined if wild-type prv infection can overcome the es ...200616775323
x-ray structures of the n- and c-terminal domains of a coronavirus nucleocapsid protein: implications for nucleocapsid formation.coronaviruses cause a variety of respiratory and enteric diseases in animals and humans including severe acute respiratory syndrome. in these enveloped viruses, the filamentous nucleocapsid is formed by the association of nucleocapsid (n) protein with single-stranded viral rna. the n protein is a highly immunogenic phosphoprotein also implicated in viral genome replication and in modulating cell signaling pathways. we describe the structure of the two proteolytically resistant domains of the n p ...200616775348
pkcdelta-mediated regulation of flip expression in human colon cancer cells.flice-like inhibitory protein (flip), a naturally occurring caspase-inhibitory protein that lacks the critical cysteine domain necessary for catalytic activity, is a negative regulator of fas-induced apoptosis. decreased flip levels sensitize tumor cells to fas- and trail-mediated apoptosis; however, the cellular mechanisms regulating flip expression have not been defined. here, we examined the roles of the pkc and nf-kappab pathway in the regulation of flip in human colon cancers. flip mrna lev ...200616052516
template requirements for recognition and copying by sindbis virus rna-dependent rna polymerase.the sindbis virus (sin) nonstructural protein nsp4 possesses the rna-dependent rna polymerase activity required for the replication of the sin genome and transcription of a subgenomic mrna during infection. isolation of this protein from other viral components of the rna synthetic complex allowed the characterization of template requirements for nsp4-mediated genome replication. the major findings of this study are: (i) in the absence of other viral proteins nsp4 is capable of copying sin plus- ...200716979682
ab initio random model method facilitates 3d reconstruction of icosahedral particles.model-based, three-dimensional (3d) image reconstruction procedures require a starting model to initiate data analysis. we have designed an ab initio method, which we call the random model (rm) method, that automatically generates models to initiate structural analysis of icosahedral viruses imaged by cryo-electron microscopy. the robustness of the rm procedure was demonstrated on experimental sets of images for five representative viruses. the rm method also provides a straightforward way to ge ...200716979906
possible ecology and epidemiology of medically important mosquito-borne arboviruses in great britain.nine different arboviruses are known to be transmitted by, or associated with, mosquitoes in europe, and several (west nile, sindbis and tahyna viruses) are reported to cause outbreaks of human disease. although there have been no reported human cases in great britain (gb), there have been no published in-depth serological surveys for evidence of human infection. this paper investigates the ecological and entomological factors that could influence or restrict transmission of these viruses in gb, ...200716893487
the inhibitors of protein acylation, cerulenin and tunicamycin, increase voltage-dependent ca(2+) currents in the insulin-secreting ins 832/13 cell.as it has been suggested that protein acylation plays a role in nutrient stimulus-secretion coupling in the pancreatic beta-cell, we examined the insulin-secreting ins 832/13 beta-cell line for evidence that protein acylation was involved. the perforated whole-cell configuration was employed to voltage-clamp ins 832/13 cells. voltage pulses were applied and ca(2+) currents measured in the presence and absence of the protein acylation inhibitors cerulenin and tunicamycin. both inhibitors enhanced ...200717548064
tyrosine phosphorylation regulates nuclear translocation of pkcdelta.pkcdelta is essential for apoptosis, but regulation of the proapoptotic function of this ubiquitous kinase is not well understood. nuclear translocation of pkcdelta is necessary and sufficient to induce apoptosis and is mediated via a c-terminal bipartite nuclear localization sequence. however, pkcdelta is found predominantly in the cytoplasm of nonapoptotic cells, and the apoptotic signal that activates its nuclear translocation is not known. we show that in salivary epithelial cells, phosphory ...200718059334
rapidly inducible, genetically targeted inactivation of neural and synaptic activity in vivo.inducible and reversible perturbation of the activity of selected neurons in vivo is critical to understanding the dynamics of brain circuits. several genetically encoded systems for rapid inducible neuronal silencing have been developed in the past few years offering an arsenal of tools for in vivo experiments. some systems are based on ion-channels or pumps, others on g protein coupled receptors, and yet others on modified presynaptic proteins. inducers range from light to small molecules to p ...200718054219
flock house virus induces apoptosis by depletion of drosophila inhibitor-of-apoptosis protein diap1.the molecular mechanisms by which rna viruses induce apoptosis and apoptosis-associated pathology are not fully understood. here we show that flock house virus (fhv), one of the simplest rna viruses (family, nodaviridae), induces robust apoptosis of permissive drosophila line-1 (dl-1) cells. to define the pathway by which fhv triggers apoptosis in this model invertebrate system, we investigated the potential role of drosophila apoptotic effectors during infection. suggesting the involvement of h ...200717989181
krüppel homolog 1 (kr-h1) mediates juvenile hormone action during metamorphosis of drosophila melanogaster.juvenile hormone (jh) given at pupariation inhibits bristle formation and causes pupal cuticle formation in the abdomen of drosophila melanogaster due to its prolongation of expression of the transcription factor broad (br). in a microarray analysis of jh-induced gene expression in abdominal integument, we found that krüppel homolog 1 (kr-h1) was up-regulated during most of adult development. quantitative real-time pcr analyses showed that kr-h1 up-regulation began at 10h after puparium formatio ...200718036785
characterization and expression patterns of let-7 microrna in the silkworm (bombyx mori).lin-4 and let-7, the two founding members of heterochronic microrna genes, are firstly confirmed in caenorhabditis elegans to control the proper timing of developmental programs in a heterochronic pathway. let-7 has been thought to trigger the onset of adulthood across animal phyla. ecdysone and broad-complex are required for the temporal expression of let-7 in drosophila melanogaster. for a better understanding of the conservation and functions of let-7, we seek to explore how it is expressed i ...200717651473
pd-catalyzed c-c bond-forming reactions of thymidine mesitylene sulfonate.facile synthesis of c-4 aryl pyrimidinone nucleoside analogues from an easily prepared o4-arylsulfonate derivative of thymidine is reported. two o4-arylsulfonylthymidine precursors, (4-methylphenyl)sulfonyl and (2,4,6-trimethylphenyl)sulfonyl, were prepared and analyzed for their stabilities. of the two, the latter possessed suitable stability as well as reactivity for pd-catalyzed c-c bond-forming reactions with a variety of arylboronic acids. these reactions at the c-4 position are nontrivial ...200717595142
effect of ceramide n-acyl chain and polar headgroup structure on the properties of ordered lipid domains (lipid rafts).ceramides are sphingolipids that greatly stabilize ordered membrane domains (lipid rafts), and displace cholesterol from them. ceramide-rich rafts have been implicated in diverse biological processes. because ceramide analogues have been useful for probing the biological function of ceramide, and may have biomedical applications, it is important to characterize how ceramide structure affects membrane properties, including lipid raft stability and composition. in this report, fluorescence quenchi ...200717574203
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