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apoptosis in murine norovirus-infected raw264.7 cells is associated with downregulation of survivin.noroviruses (nvs) are recognized as a major cause of nonbacterial gastroenteritis in humans. studies of the human nvs continue to be hampered by the inability to propagate them in any cell culture system. until recently, most data concerning nv replication were derived from studies of feline calicivirus and rabbit hemorrhagic disease virus, which are cultivable members of the family caliciviridae. from such studies, it was proposed that caliciviruses induce apoptosis to facilitate the disseminat ...200919211757
dengue virus type 2 infections of aedes aegypti are modulated by the mosquito's rna interference pathway.a number of studies have shown that both innate and adaptive immune defense mechanisms greatly influence the course of human dengue virus (denv) infections, but little is known about the innate immune response of the mosquito vector aedes aegypti to arbovirus infection. we present evidence here that a major component of the mosquito innate immune response, rna interference (rnai), is an important modulator of mosquito infections. the rnai response is triggered by double-stranded rna (dsrna), whi ...200919214215
caspase inhibitor p35 is required for the production of robust baculovirus virions in trichoplusia ni tn-368 cells.apoptosis can protect lepidopteran insects against baculovirus infection by limiting viral replication. baculoviruses counter this response by expressing anti-apoptotic proteins such as the caspase inhibitor p35, which is expressed by several baculoviruses including autographa californica mutiple nucleopolyhedrovirus (acmnpv). mutants of acmnpv that lack the p35 gene induce apoptosis in spodoptera frugiperda cells, and replication of these mutants is severely curtailed in s. frugiperda cell line ...200919218211
characterization of a mimivirus rna cap guanine-n2 methyltransferase.a 2,2,7-trimethylguanosine (tmg) cap is a signature feature of eukaryal snrnas, telomerase rnas, and trans-spliced nematode mrnas. tmg and 2,7-dimethylguanosine (dmg) caps are also present on mrnas of two species of alphaviruses (positive strand rna viruses of the togaviridae family). it is presently not known how viral mrnas might acquire a hypermethylated cap. mimivirus, a giant dna virus that infects amoeba, encodes many putative enzymes and proteins implicated in rna transactions, including ...200919218551
low-density macroarray for rapid detection and identification of crimean-congo hemorrhagic fever virus.crimean-congo hemorrhagic fever (cchf) is a tick-borne viral zoonosis which occurs throughout africa, eastern europe, and asia and results in an approximately 30% fatality rate. a reverse transcription-pcr assay including a competitive internal control was developed on the basis of the most up-to-date genome information. biotinylated amplification products were hybridized to dna macroarrays on the surfaces of polymer supports, and hybridization events were visualized by incubation with a strepta ...200919225100
the regulation of disassembly of alphavirus cores.alphaviruses are used as model viruses for structure determination and for analysis of virus entry. they are used also as vectors for protein expression and gene therapy. virus particles are assembled by budding, using preformed cores and a modified cellular membrane. during entry, alphaviruses release the viral core into the cytoplasm. cores are disassembled during virus entry and accumulate in the cytoplasm during virus multiplication. the regulation of core disassembly is the subject of this ...200919225713
role of bnip3 and nix in cell death, autophagy, and mitophagy.bnip3 and nix are proteins related to the bh3-only family, which induce both cell death and autophagy. consistent with their ability to induce cell death, bnip3 and nix are implicated in the pathogenesis of cancer and heart disease. in tumor cells, bnip3 and nix are regulated by hypoxia, and the deregulation of bnip3 or nix expression is associated with tumor growth. in heart muscle, bnip3 and nix are regulated by hypoxia and galphaq-dependent signaling, respectively, and their expression is ass ...200919229244
role of conserved cysteines in the alphavirus e3 protein.alphavirus particles are covered by 80 glycoprotein spikes that are essential for viral entry. spikes consist of the e2 receptor binding protein and the e1 fusion protein. spike assembly occurs in the endoplasmic reticulum, where e1 associates with pe2, a precursor containing e3 and e2 proteins. e3 is a small, cysteine-rich, extracellular glycoprotein that mediates proper folding of pe2 and its subsequent association with e1. in addition, cleavage of e3 from the assembled spike is required to ma ...200919109378
host responses to wild-type and attenuated herpes simplex virus infection in the absence of stat1.humans and mice lacking the interferon signaling molecule stat1 are sensitive to a variety of pathogens due to their presumed inability to mount a strong innate immune response. the herpes simplex virus type 1 (hsv-1) virion host shutoff (vhs) protein is a multifunctional immunomodulator that counteracts the innate immune response and viruses lacking vhs are attenuated and effective live vaccines in animal models. to investigate the interplay of viruses with an immunocompromised host, we perform ...200919109391
transgenesis approaches for functional analysis of peptidergic cells in the silkworm bombyx mori.the domestic silkworm, bombyx mori represents an insect model of great scientific and economic importance. besides the establishment of a stable germline transformation using the piggybac vector, technically feasible methods for in vivo gene delivery and transient gene expression were developed using viral based vectors, especially sindbis viruses and baculoviruses. the recombinant baculovirus, autographa californica multiple nucleopolyhedrovirus (acmnpv), commonly used for large-scale protein p ...200919111552
axonal elongation triggered by stimulus-induced local translation of a polarity complex protein.during development, axon growth rates are precisely regulated to provide temporal control over pathfinding. the precise temporal regulation of axonal growth is a key step in the formation of functional synapses and the proper patterning of the nervous system. the rate of axonal elongation is increased by factors such as netrin-1 and nerve growth factor (ngf), which stimulate axon outgrowth using incompletely defined pathways. to clarify the mechanism of netrin-1- and ngf-stimulated axon growth, ...200919620967
performance of the realstar chikungunya virus real-time reverse transcription-pcr kit.a novel commercial chikungunya virus real-time reverse transcription-pcr (rt-pcr) kit was evaluated on a comprehensive panel of original patient samples. the assay was 100% sensitive and specific in comparison to a published real-time rt-pcr. viral loads from both assays were highly correlated. the kit proved to be suitable for routine use in patient care.200919625474
ars2 regulates both mirna- and sirna- dependent silencing and suppresses rna virus infection in drosophila.intrinsic immune responses autonomously inhibit viral replication and spread. one pathway that restricts viral infection in plants and insects is rna interference (rnai), which targets and degrades viral rna to limit infection. to identify additional genes involved in intrinsic antiviral immunity, we screened drosophila cells for modulators of viral infection using an rnai library. we identified ars2 as a key component of drosophila antiviral immunity. loss of ars2 in cells, or in flies, increas ...200919632183
west nile virus infection alters midgut gene expression in culex pipiens quinquefasciatus say (diptera: culicidae).alterations in gene expression in the midgut of female culex pipiens quinquefasciatus exposed to blood meals containing 6.8 logs plaque-forming units/ml of west nile virus (wnv) were studied by fluorescent differential display. twenty-six different cdnas exhibited reproducible differences after feeding on infected blood. of these, 21 cdnas showed an increase in expression, and 5 showed a decrease in expression as a result of wnv presence in the blood meal. genbank database searches showed that o ...200919635880
regulation of the proteasome by neuronal activity and calcium/calmodulin-dependent protein kinase ii.protein degradation via the ubiquitin proteasome system has been shown to regulate changes in synaptic strength that underlie multiple forms of synaptic plasticity. it is plausible, therefore, that the ubiquitin proteasome system is itself regulated by synaptic activity. by utilizing live-cell imaging strategies we report the rapid and dynamic regulation of the proteasome in hippocampal neurons by synaptic activity. we find that the blockade of action potentials (aps) with tetrodotoxin inhibited ...200919638347
oncolytic activity of sindbis virus in human oral squamous carcinoma cells.sindbis virus (sin) infection causes no or only mild symptoms (fever, rash, and arthralgia) in humans. however, sin has a strong cytopathic effect (cpe) on various cancer cells. this study focuses on the oncolytic activity of sin ar399 on oral cancer cells compared with reovirus, a well-known oncolytic virus that targets cancer cells.200919638980
similarities and differences in antagonism of neuron alpha/beta interferon responses by venezuelan equine encephalitis and sindbis alphaviruses.venezuelan equine encephalitis virus (veev) is highly virulent in adult laboratory mice, while sindbis virus (sinv) is avirulent regardless of dose or inoculation route, dependent upon functioning alpha/beta interferon (ifn-alpha/beta) responses. we have examined each virus' resistance to and/or antagonism of ifn-alpha/beta responses in neurons, a cell type targeted by both viruses in mice, by infecting ifn-alpha/beta-treated or untreated primary cultures with viruses or virus-derived replicons ...200919641001
exclusion of west nile virus superinfection through rna replication.superinfection exclusion is the ability of an established viral infection to interfere with a second viral infection. using west nile virus (wnv) as a model, we show that replicating replicons in bhk-21 cells suppress subsequent wnv infection. the wnv replicon also suppresses superinfections of other flaviviruses but not nonflaviviruses. mode-of-action analysis indicates that the exclusion of wnv superinfection occurs at the step of rna synthesis. the continuous culturing of wnv in the replicon- ...200919726510
a novel function of heparan sulfate in the regulation of cell-cell fusion.despite the important contribution of cell-cell fusion in the development and physiology of eukaryotes, little is known about the mechanisms that regulate this process. our study shows that glycosaminoglycans and more specifically heparan sulfate (hs) expressed on the cell surface and extracellular matrix may act as negative regulator of cell-cell fusion. using herpes simplex virus type-1 as a tool to enhance cell-cell fusion, we demonstrate that the absence of hs expression on the cell surface ...200919726670
replication cycle of chikungunya: a re-emerging arbovirus.arboviruses (or arthropod-borne viruses), represent a threat for the new century. the 2005-2006 year unprecedented epidemics of chikungunya virus (chikv) in the french reunion island in the indian ocean, followed by several outbreaks in other parts of the world such as india, have attracted the attention of clinicians, scientists, and state authorities about the risks linked to this re-emerging mosquito-borne virus. chikv, which belongs to the alphaviruses genus, was not previously regarded as a ...200919732931
complement modulates pathogenesis and antibody-dependent neutralization of west nile virus infection through a c5-independent mechanism.although the interactions of complement and viruses have been widely studied, the function of c5 and the membrane attack complex in the context of viral infection or antibody-mediated neutralization remains controversial. using c5-depleted or -deficient human or mouse sera, we show that c5 does not contribute to the antibody-dependent or -independent neutralization of west nile virus (wnv) in cell culture. consistent with this, c5 neither contributed to protection against wnv pathogenesis nor au ...200919744691
homing endonucleases catalyze double-stranded dna breaks and somatic transgene excision in aedes aegypti.aedes aegypti is a major vector of arthropod-borne viruses such as yellow fever virus and dengue viruses. efforts to discern the function of genes involved in important behaviours, such as vector competence and host seeking through reverse genetics, would greatly benefit from the ability to generate targeted gene disruptions. homing endonucleases are selfish elements which catalyze double-stranded dna (dsdna) breaks in a sequence-specific manner. in this report we demonstrate that the homing end ...200919754740
recombinant sindbis virus vectors designed to express protective antigen of bacillus anthracis protect animals from anthrax and display synergy with ciprofloxacin.recombinant sindbis viruses were engineered to express alternative forms of the protective antigen (pa) of bacillus anthracis. the recombinant viruses induced pa-specific immunoglobulin g and neutralizing antibodies in swiss webster mice. vaccination with the recombinant viruses induced immunity that offered some protection from a lethal ames strain spore challenge and synergized the protective effects of ciprofloxacin.200919759250
a novel system for the launch of alphavirus rna synthesis reveals a role for the imd pathway in arthropod antiviral response.alphaviruses are rna viruses transmitted between vertebrate hosts by arthropod vectors, primarily mosquitoes. how arthropods counteract alphaviruses or viruses per se is not very well understood. drosophila melanogaster is a powerful model system for studying innate immunity against bacterial and fungal infections. in this study we report the use of a novel system to analyze replication of sindbis virus (type species of the alphavirus genus) rna following expression of a sindbis virus replicon r ...200919763182
[using real-time pcr to evaluate the effect of viral inactivation by methylene blue with visible light].to investigate the feasibility of using real-time pcr to evaluate the effectiveness of sindbis virus inactivation by methylene blue with visible light. sindbis virus was treated by methylene blue with different intensity of visible light and the transcribed cdna was quantified by real-time pcr. residual infectivity of treated virus was tested by cell infection method as parallel control at the same time. the residual infectivity of virus decreased from 6.50 lgtcid50/ml to under the limit of dete ...200919769162
glycoprotein-dependent acidification of vesicular stomatitis virus enhances release of matrix protein.to study vesicular stomatitis virus (vsv) entry and uncoating, we generated a recombinant vsv encoding a matrix (m) protein containing a c-terminal tetracysteine lumio tag (rvsv-ml) that could be fluorescently labeled using biarsenical compounds. quantitative confocal microscopy showed that there is a transient loss of fluorescence at early times after the initiation of endocytosis of rvsv-ml-green (rvsv-mlg) virions, which did not occur when cells were treated with bafilomycin a1. the reduction ...200919776119
cis-acting rna elements in human and animal plus-strand rna viruses.the rna genomes of plus-strand rna viruses have the ability to form secondary and higher-order structures that contribute to their stability and to their participation in inter- and intramolecular interactions. those structures that are functionally important are called cis-acting rna elements because their functions cannot be complemented in trans. they can be involved not only in rna/rna interactions but also in binding of viral and cellular proteins during the complex processes of translation ...200919781674
gene gun administration of therapeutic hpv dna vaccination restores the efficacy of prolonged defrosted viral based vaccine.freshly defrosted vaccines generate promising antitumor immunity by raising both robust cd8 and cd4 responses with a tc1/th1-dominant cytokine profile. however, prolonged (overnight) defrosted sindbis virus-e7/hsp70 priming and vaccinia-e7/hsp70 booster in mouse model only elicited 20% long-term tumor-free survival in comparison with the fresh vaccines. the present study is to search the possible cause of its potency loss, and to evaluate the ability of pcdna-e7/hsp70 dna vaccination via gene gu ...200919781679
characteristics of alpha/beta interferon induction after infection of murine fibroblasts with wild-type and mutant alphaviruses.we examined the characteristics of interferon alpha/beta (ifn-alpha/beta) induction after alphavirus or control sendai virus (sev) infection of murine fibroblasts (mefs). as expected, sev infection of wild-type (wt) mefs resulted in strong dimerization of irf3 and the production of high levels of ifn-alpha/beta. in contrast, infection of mefs with multiple alphaviruses failed to elicit detectable ifn-alpha/beta. in more detailed studies, sindbis virus (sinv) infection caused dimerization and nuc ...200919782381
novel vaccines to human rabies.rabies, the most fatal of all infectious diseases, remains a major public health problem in developing countries, claiming the lives of an estimated 55,000 people each year. most fatal rabies cases, with more than half of them in children, result from dog bites and occur among low-income families in southeast asia and africa. safe and efficacious vaccines are available to prevent rabies. however, they have to be given repeatedly, three times for pre-exposure vaccination and four to five times fo ...200919787033
targeted transduction via cd4 by a lentiviral vector uses a clathrin-mediated entry pathway.we recently developed a novel targeting sindbis virus envelope pseudotyped lentiviral vector, 2.2zz, which acquires specific transduction capacity by antibody conjugation and binding with specific antigens on the surface of targeted cells. here we characterize the virological properties of this vector by examining its targeting to cd4 antigen. our results show that entry is dependent on cd4 cell surface density and occurs via the clathrin-mediated endocytic pathway. these findings provide insigh ...200919793825
heavily isotype-dependent protective activities of human antibodies against vaccinia virus extracellular virion antigen b5.antibodies against the extracellular virion (ev or eev) form of vaccinia virus are an important component of protective immunity in animal models and likely contribute to the protection of immunized humans against poxviruses. using fully human monoclonal antibodies (mabs), we now have shown that the protective attributes of the human anti-b5 antibody response to the smallpox vaccine (vaccinia virus) are heavily dependent on effector functions. by switching fc domains of a single mab, we have def ...200919793826
oncolytic virotherapy for oral squamous cell carcinoma using replication-competent viruses.oncolytic virotherapy utilizes viruses that can selectively destroy cancer cells without harming normal tissues. clinical trials of oncolytic viruses show that most oncolytic agents are well tolerated and safe. the virotherapeutic agents currently in use have limited potency when administered alone; however, combination therapy using virotherapeutic agents and conventional anticancer agents, such as chemotherapeutics, radiation, and gene therapy, exhibits encouraging levels of efficacy. advances ...200919833547
induction of membrane ceramides: a novel strategy to interfere with t lymphocyte cytoskeletal reorganisation in viral immunosuppression.silencing of t cell activation and function is a highly efficient strategy of immunosuppression induced by pathogens. by promoting formation of membrane microdomains essential for clustering of receptors and signalling platforms in the plasma membrane, ceramides accumulating as a result of membrane sphingomyelin breakdown are not only essential for assembly of signalling complexes and pathogen entry, but also act as signalling modulators, e. g. by regulating relay of phosphatidyl-inositol-3-kina ...200919834551
rift valley fever vaccines.rift valley fever virus (rvfv), which belongs to the genus phlebovirus, family bunyaviridae, is a negative-stranded rna virus carrying a tripartite rna genome. rvfv is transmitted by mosquitoes and causes large outbreaks among ruminants and humans in africa and the arabian peninsula. human patients develop an acute febrile illness, followed by a fatal hemorrhagic fever, encephalitis or ocular diseases, whereas ruminants experience abortions during outbreak. effective vaccination of both humans a ...200919837291
vaccines for venezuelan equine encephalitis.arboviruses are capable of causing encephalitis in animals and human population when transmitted by the vector or potentially via infectious aerosol. recent re-emergence of venezuelan equine encephalitis virus (veev) in south america emphasizes the importance of this pathogen to public health and veterinary medicine. despite its importance no antivirals or vaccines against veev are currently available in the usa. here we review some of the older and newer approaches aimed at generating a safe an ...200919837294
matrix protein 2 of influenza a virus blocks autophagosome fusion with lysosomes.influenza a virus is an important human pathogen causing significant morbidity and mortality every year and threatening the human population with epidemics and pandemics. therefore, it is important to understand the biology of this virus to develop strategies to control its pathogenicity. here, we demonstrate that influenza a virus inhibits macroautophagy, a cellular process known to be manipulated by diverse pathogens. influenza a virus infection causes accumulation of autophagosomes by blockin ...200919837376
betulin-derived compounds as inhibitors of alphavirus replication.this paper describes inhibition of semliki forest virus (sfv) replication by synthetic derivatives of naturally occurring triterpenoid betulin (1). chemical modifications were made to oh groups at c-3 and c-28 and to the c-20-c-29 double bond. a set of heterocyclic betulin derivatives was also assayed. a free or acetylated oh group at c-3 was identified as an important structural contributor for anti-sfv activity, 3,28-di-o-acetylbetulin (4) being the most potent derivative (ic50 value 9.1 micro ...200919839605
pathogenesis of aerosolized eastern equine encephalitis virus infection in guinea pigs.mice and guinea pigs were experimentally exposed to aerosols containing regionally-distinct strains (nj1959 or argm) of eastern equine encephalitis virus (eeev) at two exclusive particle size distributions. mice were more susceptible to either strain of aerosolized eeev than were guinea pigs; however, clinical signs indicating encephalitis were more readily observed in the guinea pigs. lower lethality was observed in both species when eeev was presented at the larger aerosol distribution (> 6 mu ...200919852817
characterization of untranslated regions of the salmonid alphavirus 3 (sav3) genome and construction of a sav3 based replicon.salmonid alphavirus (sav) causes disease in farmed salmonid fish and is divided into different genetic subtypes (sav1-6). here we report the cloning and characterization of the 5'- and 3'- untranslated regions (utr) of a sav3 isolated from atlantic salmon in norway. the sequences of the utrs are very similar to those of sav1 and sav2, but single nucleotide polymorphisms are present, also in the 3' - conserved sequence element (3'-cse). prediction of the rna secondary structure suggested putative ...200919860871
effect of xiap overexpression on sodium butyrate-induced apoptosis in recombinant chinese hamster ovary cells producing erythropoietin.previously, overexpression of x-linked inhibitor of apoptosis (xiap), which is known to inhibit activities of caspase-3, -7, and -9 in cho-k1 cells offered protection against sindbis virus-induced apoptosis. in this study, the potential role of xiap overexpression in recombinant cho (rcho) cells treated with sodium butyrate (nabu), which can increase the specific productivity, was investigated by establishing erythropoietin (epo)-producing rcho cells with regulated xiap overexpression (epo-off-x ...200919799944
autophagy in immunity against mycobacterium tuberculosis: a model system to dissect immunological roles of autophagy.the recognition of autophagy as an immune mechanism has been affirmed in recent years. one of the model systems that has helped in the development of our current understanding of how autophagy and more traditional immunity systems cooperate in defense against intracellular pathogens is macrophage infection with mycobacterium tuberculosis. m. tuberculosis is a highly significant human pathogen that latently infects billions of people and causes active disease in millions of patients worldwide. th ...200919802565
autophagy in mammalian antiviral immunity.autophagy plays diverse roles in cellular adaptation to stress and promotes vital housekeeping functions by recycling unused or damaged organelles and proteins. as an innate immune defense pathway, autophagy also protects against infection with diverse pathogens, including viruses. autophagy combats infections with both rna and dna viruses, and may function by degrading viral components, by promoting the survival of virally infected cells, and/or by activating innate and adaptive immunity. virus ...200919802570
heparan sulfate proteoglycans are required for cellular binding of the hepatitis e virus orf2 capsid protein and for viral infection.the hepatitis e virus (hev), a nonenveloped rna virus, is the causative agent of hepatitis e. the mode by which hev attaches to and enters into target cells for productive infection remains unidentified. open reading frame 2 (orf2) of hev encodes its major capsid protein, porf2, which is likely to have the determinants for virus attachment and entry. using an approximately 56-kda recombinant porf2 that can self-assemble as virus-like particles, we demonstrated that cell surface heparan sulfate p ...200919812150
viral bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68.gamma-herpesviruses (gammahvs) have developed an interaction with their hosts wherein they establish a life-long persistent infection and are associated with the onset of various malignancies. one critical virulence factor involved in the persistency of murine gamma-herpesvirus 68 (gammahv68) is the viral homolog of the bcl-2 protein (vbcl-2), which has been implicated to counteract both host apoptotic responses and autophagy pathway. however, the relative significance of the two activities of v ...200919816569
transgenic expression of glud1 (glutamate dehydrogenase 1) in neurons: in vivo model of enhanced glutamate release, altered synaptic plasticity, and selective neuronal vulnerability.the effects of lifelong, moderate excess release of glutamate (glu) in the cns have not been previously characterized. we created a transgenic (tg) mouse model of lifelong excess synaptic glu release in the cns by introducing the gene for glutamate dehydrogenase 1 (glud1) under the control of the neuron-specific enolase promoter. glud1 is, potentially, an important enzyme in the pathway of glu synthesis in nerve terminals. increased levels of glud protein and activity in cns neurons of hemizygou ...200919890003
therapeutic vaccines against human papillomavirus and cervical cancer.cervical cancer and its precursor intra-epithelial lesions are linked to infection by a subset of so-called "highrisk" human papillomavirus types, which are estimated to infect nearly four hundred million women worldwide. two prophylactic vaccines have been commercialized recently targeting hpv16 and 18, the most prevalent viral types found in cervical cancer, which operate through induction of capsid-specific neutralizing antibodies. however, in patients with persistent infection these vaccines ...200919915722
hiv-1 gag-specific immunity induced by a lentivector-based vaccine directed to dendritic cells.lentivectors (lvs) have attracted considerable interest for their potential as a vaccine delivery vehicle. in this study, we evaluate in mice a dendritic cell (dc)-directed lv system encoding the gag protein of human immunodeficiency virus (hiv) (lv-gag) as a potential vaccine for inducing an anti-hiv immune response. the dc-directed specificity is achieved through pseudotyping the vector with an engineered sindbis virus glycoprotein capable of selectively binding to the dc-sign protein. a singl ...200919918062
disrupted glutamate transporter expression in the spinal cord with acute flaccid paralysis caused by west nile virus infection.neuroinvasive west nile virus (wnv) infections may cause acute flaccid paralysis (afp); in fatal cases, anterior horn cell loss is presumed to be caused by direct viral infection. in related animal models, however, glutamate excitotoxicity mediates bystander injury of uninfected anterior horn cells, suggesting additional pathogenic mechanisms. we examined expression of the principal excitatory amino acid transporter (eaat) of astrocytes (i.e. eaat-2 in humans, glutamate transporter 1 in hamsters ...200919918118
beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of parkinson's and lewy body diseases.accumulation of the synaptic protein alpha-synuclein (alpha-syn) is a hallmark of parkinson's disease (pd) and lewy body disease (lbd), a heterogeneous group of disorders with dementia and parkinsonism, where alzheimer's disease and pd interact. accumulation of alpha-syn in these patients might be associated with alterations in the autophagy pathway. therefore, we postulate that delivery of beclin 1, a regulator of the autophagy pathway, might constitute a strategy toward developing a therapy fo ...200919864570
experimental passage of st. louis encephalitis virus in vivo in mosquitoes and chickens reveals evolutionarily significant virus characteristics.st. louis encephalitis virus (slev; flaviviridae, flavivirus) was the major cause of epidemic flaviviral encephalitis in the u.s. prior to the introduction of west nile virus (wnv) in 1999. however, outbreaks of slev have been significantly more limited then wnv in terms of levels of activity and geographic dispersal. one possible explanation for these variable levels of activity is that differences in the potential for each virus to adapt to its host cycle exist. the need for arboviruses to rep ...200919924238
prophylactic and therapeutic activity of fully human monoclonal antibodies directed against influenza a m2 protein.influenza virus infection is a prevalent disease in humans. antibodies against hemagglutinin have been shown to prevent infection and hence hemagglutinin is the major constituent of current vaccines. antibodies directed against the highly conserved extracellular domain of m2 have also been shown to mediate protection against influenza a infection in various animal models. active vaccination is generally considered the best approach to combat viral diseases. however, passive immunization is an at ...200920025741
identification of thieno[3,2-b]pyrrole derivatives as novel small molecule inhibitors of neurotropic alphaviruses.neurotropic alphaviruses such as western, eastern, and venezuelan equine encephalitis viruses cause serious and potentially fatal central nervous system infections in humans and are high-priority potential bioterrorism agents. there are currently no widely available vaccines or licensed therapies for these virulent pathogens. to identify potential novel antiviral drugs, we developed a cell-based assay with a western equine encephalitis virus replicon that expresses a luciferase reporter gene and ...200919239364
development of hepatitis c virus vaccines: challenges and progress.development of an effective vaccine against the hepatitis c virus (hcv) has long been defined as a difficult challenge due to the considerable variability of this rna virus and the observation that convalescent humans and chimpanzees could be re-infected after re-exposure. on the other hand, progress in the understanding of antiviral immune responses in patients with viral clearance has elucidated key mechanisms playing a role in the control of viral infection. studies investigating prophylactic ...200919249975
anti-apoptotic effects of protein kinase c-delta and c-fos in cisplatin-treated thyroid cells.we showed previously that cisplatin inititates a signalling pathway mediated by pkc-delta/extracellular signal-regulated kinase (erk), important for maintaining viability in pc cl3 thyroid cells. the studies described herein examined whether c-fos was associated with cisplatin resistance and the signalling link between c-fos and pkc-delta/erk.200919254279
cell type-specific targeting with surface-engineered lentiviral vectors co-displaying okt3 antibody and fusogenic molecule.the purpose of this study was to investigate the potential of a t-cell-related targeting method using a lentiviral vector-based gene delivery system.200919259792
pkr acts early in infection to suppress semliki forest virus production and strongly enhances the type i interferon response.the double-stranded rna-activated protein kinase (pkr) is a key regulator of protein translation, interferon (ifn) expression and cell survival. upon infection of vertebrate cells in continuous culture, the alphavirus semliki forest virus (sfv) initiates apoptosis and ifn synthesis. to determine the effect of pkr on sfv infection, we studied the course of infection in wild-type (wt) mice, mice with a genetic deletion of pkr (pkr-/-) and mouse embryo fibroblasts (mefs) derived from these mice. in ...200919264662
suppression of host gene expression by nsp1 proteins of group 2 bat coronaviruses.nsp1 protein of severe acute respiratory syndrome coronavirus (sars-cov), a group 2b cov, suppresses host gene expression by promoting host mrna degradation and translation inhibition. the present study analyzed the activities of nsp1 proteins from the group 2 bat cov strains rm1, 133, and hku9-1, belonging to groups 2b, 2c, and 2d, respectively. the host mrna degradation and translational suppression activities of nsp1 of sars-cov and rm1 nsp1 were similar and stronger than the activities of th ...200919264783
suppression of rna interference increases alphavirus replication and virus-associated mortality in aedes aegypti mosquitoes.arthropod-borne viruses (arboviruses) can persistently infect and cause limited damage to mosquito vectors. rna interference (rnai) is a mosquito antiviral response important in restricting rna virus replication and has been shown to be active against some arboviruses. the goal of this study was to use a recombinant sindbis virus (sinv; family togaviridae; genus alphavirus) that expresses b2 protein of flock house virus (fhv; family nodaviridae; genus alphanodavirus), a protein that inhibits rna ...200919265532
dynamin-dependent membrane drift recruits ampa receptors to dendritic spines.the surface expression and localization of ampa receptors (ampars) at dendritic spines are tightly controlled to regulate synaptic transmission. here we show that de novo exocytosis of the glur2 ampar subunit occurs at the dendritic shaft and that new ampars diffuse into spines by lateral diffusion in the membrane. however, membrane topology restricts this lateral diffusion. we therefore investigated which mechanisms recruit ampars to spines from the shaft and demonstrated that inhibition of dyn ...200919269965
distinct regulation of autophagic activity by atg14l and rubicon associated with beclin 1-phosphatidylinositol-3-kinase complex.beclin 1, a mammalian autophagy protein that has been implicated in development, tumour suppression, neurodegeneration and cell death, exists in a complex with vps34, the class iii phosphatidylinositol-3-kinase (pi(3)k) that mediates multiple vesicle-trafficking processes including endocytosis and autophagy. however, the precise role of the beclin 1-vps34 complex in autophagy regulation remains to be elucidated. combining mouse genetics and biochemistry, we have identified a large in vivo beclin ...200919270693
post-epidemic chikungunya disease on reunion island: course of rheumatic manifestations and associated factors over a 15-month period.although the acute manifestations of chikungunya virus (chikv) illness are well-documented, few data exist about the long-term rheumatic outcomes of chikv-infected patients. we undertook between june and september 2006 a retrospective cohort study aimed at assessing the course of late rheumatic manifestations and investigating potential risk factors associated with the persistence of these rheumatic manifestations over 15 months. 147 participants (>16 yrs) with laboratory-confirmed chikv disease ...200919274071
dual mechanism for the translation of subgenomic mrna from sindbis virus in infected and uninfected cells.infection of bhk cells by sindbis virus (sv) gives rise to a profound inhibition of cellular protein synthesis, whereas translation of viral subgenomic mrna that encodes viral structural proteins, continues for hours. to gain further knowledge on the mechanism by which this subgenomic mrna is translated, the requirements for some initiation factors (eifs) and for the presence of the initiator aug were examined both in infected and in uninfected cells. to this end, bhk cells were transfected with ...200919274090
adoptive transfer of human papillomavirus e7-specific ctl enhances tumor chemoresponse through the perforin/granzyme-mediated pathway.adoptive cytotoxic t lymphocyte (ctl) therapy has an important implication in treating cancer patients. here, we investigate whether adoptive transfer of human papillomavirus (hpv) e7-specific ctl can enhance tumor chemoresponse using an established cervical cancer animal model. cisplatin-based chemotherapy plus ctl therapy showed an improved therapeutic effectiveness, along with antitumor protective responses to a parental tumor cell rechallenge. cisplatin treatment dose-dependently increased t ...200919277009
the 5'utr-specific mutation in veev tc-83 genome has a strong effect on rna replication and subgenomic rna synthesis, but not on translation of the encoded proteins.venezuelan equine encephalitis virus (veev) is one of the most pathogenic members of the alphavirus genus in the togaviridae family. viruses in the veev serocomplex continuously circulate in the central and south america. the only currently available attenuated strain veev tc-83 is being used only for vaccination of at-risk laboratory workers and military personnel. its attenuated phenotype was shown to rely only on two point mutations, one of which, g3a, was found in the 5' untranslated region ...200919278709
reovirus activates transforming growth factor beta and bone morphogenetic protein signaling pathways in the central nervous system that contribute to neuronal survival following infection.viral infections of the central nervous system (cns) are important causes of worldwide morbidity and mortality, and understanding how viruses perturb host cell signaling pathways will facilitate identification of novel antiviral therapies. we now show that reovirus infection activates transforming growth factor beta (tgf-beta) and bone morphogenetic protein (bmp) signaling in a murine model of encephalitis in vivo. tgf-beta receptor i (tgf-beta ri) expression is increased and its downstream sign ...200919279118
hepatitis c virus ns2 is a protease stimulated by cofactor domains in ns3.chronic infection with hepatitis c virus (hcv) affects 130 million people worldwide and is a major cause of liver cirrhosis and liver cancer. after translation of the hcv rna genome into a polyprotein, 2 viral proteases process its non-structural protein (ns) region. while the essential chymotrypsin-like serine protease ns3-4a mediates all cleavages downstream of ns3, the ns2-3 cysteine protease catalyzes a vital cleavage at the ns2/3 site. protease activity of ns2-3 has been described to requir ...200919282477
how b cells shape the immune response against mycobacterium tuberculosis.extensive work illustrating the importance of cellular immune mechanisms for protection against mycobacterium tuberculosis has largely relegated b-cell biology to an afterthought within the tuberculosis (tb) field. however, recent studies have illustrated that b lymphocytes, through a variety of interactions with the cellular immune response, play previously underappreciated roles in shaping host defense against non-viral intracellular pathogens, including m. tuberculosis. work in our laboratory ...200919283721
role of n-linked glycosylation for sindbis virus infection and replication in vertebrate and invertebrate systems.each sindbis virus (sinv) surface glycoprotein has two sites for n-linked glycosylation (e1 positions 139 and 245 [e1-139 and e1-245] and e2 positions 196 and 318 [e2-196 and e2-318]). studies of sinv strain te12 mutants with each site eliminated identified the locations of carbohydrates by cryo-electron microscopy (s. v. pletnev et al., cell 105:127-136, 2001). in the current study, the effects of altered glycosylation on virion infectivity, growth in cells of vertebrates and invertebrates, hep ...200919297464
type i and type ii interferons inhibit the translation of murine norovirus proteins.human noroviruses are responsible for more than 95% of nonbacterial epidemic gastroenteritis worldwide. both onset and resolution of disease symptoms are rapid, suggesting that components of the innate immune response are critical in norovirus control. while the study of the human noroviruses has been hampered by the lack of small animal and tissue culture systems, our recent discovery of a murine norovirus (mnv) and its in vitro propagation have allowed us to begin addressing norovirus replicat ...200919297466
varicella-zoster virus infection induces autophagy in both cultured cells and human skin vesicles.when grown in cultured cells, varicella-zoster virus (vzv) forms many aberrant light particles and produces low titers. various studies have explored the reasons for such a phenotype and have pointed to impaired expression of specific late genes and at lysosomal targeting of egressing virions as possible causes. in the studies presented here, we report that the autophagic degradation pathway was induced at late time points after vzv infection of cultured cells, as documented by immunoblot analys ...200919297471
cell-to-cell spread of the rna interference response suppresses semliki forest virus (sfv) infection of mosquito cell cultures and cannot be antagonized by sfv.in their vertebrate hosts, arboviruses such as semliki forest virus (sfv) (togaviridae) generally counteract innate defenses and trigger cell death. in contrast, in mosquito cells, following an early phase of efficient virus production, a persistent infection with low levels of virus production is established. whether arboviruses counteract rna interference (rnai), which provides an important antiviral defense system in mosquitoes, is an important question. here we show that in aedes albopictus- ...200919297476
interferon-gamma coordinates ccl3-mediated neutrophil recruitment in vivo.we have shown previously that acute infection with the respiratory pathogen, pneumonia virus of mice (pvm), results in local production of the proinflammatory chemokine, ccl3, and that neutrophil recruitment in response to pvm infection is reduced dramatically in ccl3 -/- mice.200919298652
15-deoxy-delta12,14-prostaglandin j2 inhibits hiv-1 transactivating protein, tat, through covalent modification.controlling the hiv/aids epidemic remains a major challenge, with approximately 5 million new hiv infections annually. cyclopentenone prostaglandins (cypg), such as 15-deoxy-delta(12,14)-pgj(2) (15d-pgj(2)), are arachidonic acid-derived endogenous electrophiles that possess anti-hiv activity by an unknown mechanism. given that the reactive alpha,beta-unsaturated ketone in the cyclopentenone ring of 15d-pgj(2) covalently modifies key cys thiols in select proteins, we hypothesized that 15d-pgj(2) ...200919299483
filamin b: a scaffold for interferon signalling. 200919305389
corticosterone alters ampar mobility and facilitates bidirectional synaptic plasticity.the stress hormone corticosterone has the ability both to enhance and suppress synaptic plasticity and learning and memory processes. however, until today there is very little known about the molecular mechanism that underlies the bidirectional effects of stress and corticosteroid hormones on synaptic efficacy and learning and memory processes. in this study we investigate the relationship between corticosterone and ampa receptors which play a critical role in activity-dependent plasticity and h ...200919305644
properties and use of novel replication-competent vectors based on semliki forest virus.semliki forest virus (sfv) has a positive strand rna genome and infects different cells of vertebrates and invertebrates. the 5' two-thirds of the genome encodes non-structural proteins that are required for virus replication and synthesis of subgenomic (sg) mrna for structural proteins. sg-mrna is generated by internal initiation at the sg-promoter that is located at the complementary minus-strand template. different types of expression systems including replication-competent vectors, which rep ...200919317912
pick1-mediated glutamate receptor subunit 2 (glur2) trafficking contributes to cell death in oxygen/glucose-deprived hippocampal neurons.oxygen and glucose deprivation (ogd) induces delayed cell death in hippocampal ca1 neurons via ca(2+)/zn(2+)-permeable, glur2-lacking ampa receptors (ampars). following ogd, synaptic ampar currents in hippocampal neurons show marked inward rectification and increased sensitivity to channel blockers selective for glur2-lacking ampars. this occurs via two mechanisms: a delayed down-regulation of glur2 mrna expression and a rapid internalization of glur2-containing ampars during the ogd insult, whi ...200919321442
fas-mediated apoptotic signaling in the mouse brain following reovirus infection.type 3 (t3) reovirus strains induce apoptotic neuronal cell death and lethal encephalitis in infected mice. t3 strain dearing (t3d)-induced apoptosis in primary neuronal cultures occurs by a fas-mediated mechanism and requires the activation of caspase 8. we now show that fas mrna is upregulated in the brains of mice infected with encephalitic reovirus t3d and t3 strain abney (t3a) but not following infection with nonencephalitic reovirus type 1 strain lang. fas is upregulated in regions of the ...200919321603
major histocompatibility complex haplotype determines hsp70-dependent protection against measles virus neurovirulence.in vitro studies show that hsp70 promotes gene expression for multiple viral families, although there are few reports on the in vivo significance of virus-hsp70 interaction. previously we showed that hsp70-dependent stimulation of edmonston measles virus (ed mev) transcription caused an increased cytopathic effect and mortality in transgenic hsp70-overexpressing c57bl/6 mice (h-2(b)). the response to mev infection is influenced by the major histocompatibility complex haplotype; h-2(d) mice are r ...200919321604
synthesis, antiviral and anticancer activity of some novel thioureas derived from n-(4-nitro-2-phenoxyphenyl)-methanesulfonamide.due to a continuing effort to develop new antiviral agents, a series of 1-[4-(methanesulfonamido)-3-phenoxyphenyl]-3-alkyl/aryl thioureas 3a-i have been synthesized by the reaction of alkyl/aryl isothiocyanates with 4-amino-2-phenoxymethanesulfonanilide. these derivatives were structurally characterized by the use of spectral techniques and evaluated for their anticancer and antiviral activities. none of the tested compounds showed significant anticancer properties on a549 and l929 cell lines. a ...200919324473
hnrnp a1 interacts with the 5' untranslated regions of enterovirus 71 and sindbis virus rna and is required for viral replication.heterogeneous nuclear ribonucleoprotein (hnrnp) a1 is involved in pre-mrna splicing in the nucleus and translational regulation in the cytoplasm. the cytoplasmic redistribution of hnrnp a1 is a regulated process during viral infection and cellular stress. here we demonstrate that hnrnp a1 not only is an internal ribosome entry site (ires) trans-acting factor that binds specifically to the 5' untranslated region (utr) of enterovirus 71 (ev71) and regulates ires-dependent translation but also bind ...200919339352
jnk and p38 mitogen-activated protein kinase pathways contribute to porcine circovirus type 2 infection.infection with a wide variety of viruses often perturbs host cell signaling pathways including the jun nh(2)-terminal kinase/stress-activated kinase (jnk/sapk) and the p38 mitogen-activated protein kinase (p38/mapk), which are important components of cellular signal transduction pathways. the present study demonstrated for the first time that porcine circovirus type 2 (pcv2), which is the primary causative agent of an emerging swine disease, postweaning multisystemic wasting syndrome, can activa ...200919339353
lentiviral delivery of short hairpin rnas.in less than a decade after discovery, rna interference-mediated gene silencing is already being tested as potential therapy in clinical trials for a number of diseases. lentiviral vectors provide a means to express short hairpin rna (shrna) to induce stable and long-term gene silencing in both dividing and non-dividing cells and thus, are being intensively investigated for this purpose. however, induction of long-term shrna expression can also cause toxicities by inducing off-target effects and ...200919341774
attachment and entry of chlamydia have distinct requirements for host protein disulfide isomerase.chlamydia is an obligate intracellular pathogen that causes a wide range of diseases in humans. attachment and entry are key processes in infectivity and subsequent pathogenesis of chlamydia, yet the mechanisms governing these interactions are unknown. it was recently shown that a cell line, cho6, that is resistant to attachment, and thus infectivity, of multiple chlamydia species has a defect in protein disulfide isomerase (pdi) n-terminal signal sequence processing. ectopic expression of pdi i ...200919343202
clathrin-independent entry of baculovirus triggers uptake of e. coli in non-phagocytic human cells.the prototype baculovirus, autographa californica multiple nucleopolyhedrovirus, an insect pathogen, holds great potential as a gene therapy vector. to develop transductional targeting and gene delivery by baculovirus, we focused on characterizing the nature and regulation of its uptake in human cancer cells. baculovirus entered the cells along fluid-phase markers from the raft areas into smooth-surfaced vesicles devoid of clathrin. notably, regulators associated with macropinocytosis, namely ei ...200919352496
interferon-induced isg15 conjugation inhibits influenza a virus gene expression and replication in human cells.the ubiquitin-like isg15 protein, as well as its conjugating enzymes, is induced by type i interferons (ifns). experiments using isg15 knockout (isg15(-/-)) mice established that isg15 and/or its conjugation inhibits the replication of influenza a virus. however, in contrast to the virus inhibition results for mice, the rates of virus replication in isg15(+/+) and isg15(-/-) mouse embryo fibroblasts in tissue culture were similar. here we focus on human tissue culture cells and on the effect of ...200919357168
interferon-gamma prevents death of bystander neurons during cd8 t cell responses in the brain.t cells restricted to neurotropic viruses are potentially harmful as their activity may result in the destruction of neurons. in the borna disease virus (bdv) model, antiviral cd8 t cells entering the brain of infected mice cause neurological disease but no substantial loss of neurons unless the animals lack interferon-gamma (ifn-gamma). we show here that glutamate receptor antagonists failed to prevent bdv-induced neuronal loss in ifn-gamma-deficient mice, suggesting that excitotoxicity resulti ...200919359516
autophagy is an essential component of drosophila immunity against vesicular stomatitis virus.intrinsic innate immune mechanisms are the first line of defense against pathogens and exist to control infection autonomously in infected cells. here, we showed that autophagy, an intrinsic mechanism that can degrade cytoplasmic components, played a direct antiviral role against the mammalian viral pathogen vesicular stomatitis virus (vsv) in the model organism drosophila. we found that the surface glycoprotein, vsv-g, was likely the pathogen-associated molecular pattern (pamp) that initiated t ...200919362021
tumor necrosis factor-alpha modulates glutamate transport in the cns and is a critical determinant of outcome from viral encephalomyelitis.neuroadapted sindbis virus (nsv) is a neuronotropic virus that causes a fulminant encephalomyelitis in susceptible mice due to death of motor neurons in the brain and spinal cord. we and others have found that uninfected motor neurons die in response to nsv infection, at least in part due to disrupted astrocytic glutamate transport, resulting in excitotoxic motor neuron death. here, we examined the mechanisms of astrocyte dysregulation associated with nsv infection. treatment of organotypic slic ...200919368827
regulation of beclin 1 in autophagy.class iii phosphatidylinositol 3-kinase (pi3kc3) plays a pleiotropic role in autophagy and protein sorting pathways. the human core complex of pi3kc3 consists of three major components including pi3kc3/hvps34, p150 and beclin 1. how the specificity of pi3kc3 complex is derived towards autophagy is not clear. utilizing a sequential affinity purification coupled with mass spectrometry approach, we have successfully purified a human beclin 1 complex and cloned a novel protein we called barkor (becl ...200919372752
guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes.cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. it is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/ ...200919373242
lipids and membrane microdomains in hiv-1 replication.several critical steps in the replication cycle of human immunodeficiency virus type 1 (hiv-1) - entry, assembly and budding - are complex processes that take place at the plasma membrane of the host cell. a growing body of data indicates that these early and late steps in hiv-1 replication take place in specialized plasma membrane microdomains, and that many of the viral and cellular components required for entry, assembly, and budding are concentrated in these microdomains. in particular, a nu ...200919383519
the crystal structures of chikungunya and venezuelan equine encephalitis virus nsp3 macro domains define a conserved adenosine binding pocket.macro domains (also called "x domains") constitute a protein module family present in all kingdoms of life, including viruses of the coronaviridae and togaviridae families. crystal structures of the macro domain from the chikungunya virus (an "old world" alphavirus) and the venezuelan equine encephalitis virus (a "new world" alphavirus) were determined at resolutions of 1.65 and 2.30 a, respectively. these domains are active as adenosine di-phosphoribose 1''-phosphate phosphatases. both the chik ...200919386706
coordinated changes in dendritic arborization and synaptic strength during neural circuit development.neural circuit development requires concurrent morphological and functional changes. here, we identify coordinated and inversely correlated changes in dendritic morphology and mepsc amplitude following increased neural activity. we show that overexpression of beta-catenin, a molecule that increases total dendritic length, mimics the effects of increased neuronal activity by scaling down mepsc amplitudes, while postsynaptic expression of a protein that sequesters beta-catenin reverses the effects ...200919146814
apoptosis in animal models of virus-induced disease.apoptosis is associated with virus-induced human diseases of the central nervous system, heart and liver, and causes substantial morbidity and mortality. although virus-induced apoptosis is well characterized in individual cells in cell culture, virus-induced apoptosis in vivo and the role of apoptosis in virus-induced disease is not well established. this review focuses on animal models of virus-induced diseases of the central nervous system, heart and liver that provide insights into the role ...200919148180
targeted transduction of cd34+ hematopoietic progenitor cells in nonpurified human mobilized peripheral blood mononuclear cells.conventional gene-therapy applications of hematopoietic stem cells (hscs) involve purification of cd34+ progenitor cells from the mobilized peripheral blood, ex vivo transduction of the gene of interest into them, and reinfusion of the transduced cd34+ progenitor cells into patients. eliminating the process of purification would save labor, time and money, while enhancing hscs viability, transplantability and pluripotency. lentiviral vectors have been widely used in gene therapy because they inf ...200919152374
an alphavirus replicon-derived candidate vaccine against rift valley fever virus.rift valley fever virus (rvfv) is a mosquito-transmitted bunyavirus (genus phlebovirus) associated with severe disease in livestock and fatal encephalitis or haemorrhagic fever in a proportion of infected humans. although live attenuated and inactivated vaccines have been used in livestock, and on a limited scale in humans, there is a need for improved anti-rvfv vaccines. towards this goal, sindbis virus replicon vectors expressing the rvfv gn and gc glycoproteins, as well as the non-structural ...200919171081
in vitro activity and preclinical profile of tmc435350, a potent hepatitis c virus protease inhibitor.the hepatitis c virus (hcv) ns3/4a serine protease has been explored as a target for the inhibition of viral replication in preclinical models and in hcv-infected patients. tmc435350 is a highly specific and potent inhibitor of ns3/4a protease selected from a series of novel macrocyclic inhibitors. in biochemical assays using ns3/4a proteases of genotypes 1a and 1b, inhibition constants of 0.5 and 0.4 nm, respectively, were determined. tmc435350 inhibited hcv replication in a cellular assay (sub ...200919171797
two types of thalamocortical projections from the motor thalamic nuclei of the rat: a single neuron-tracing study using viral vectors.the axonal arborization of single motor thalamic neurons was examined in rat brain using a viral vector expressing membrane-targeted palmitoylation site-attached green fluorescent protein (palgfp). we first divided the ventral anterior-ventral lateral motor thalamic nuclei into 1) the rostromedial portion, which was designated inhibitory afferent-dominant zone (iz) with intense glutamate decarboxylase immunoreactivity and weak vesicular glutamate transporter 2 immunoreactivity, and 2) the caudol ...200919174446
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