TitleAbstractYear(sorted descending)
neuroimmunology of central nervous system viral infections: the cells, molecules and mechanisms involved.viral infections of the central nervous system (cns) necessitate rapid, yet tightly controlled responses to contain viral spread while limiting tissue damage. all cns resident cell types are equipped with pattern recognition receptors (prrs) to respond to viruses. the resulting activation of ifn-alpha/beta, pro-inflammatory cytokines and chemokines is dependent on the virus replication strategy, tropism and prr distribution. although ifn-alpha/beta induced antiviral mediators are essential to re ...200818562249
comparison of slow and fast neocortical neuron migration using a new in vitro model.mutations, toxic insults and radiation exposure are known to slow or arrest the migration of cortical neurons, in most cases by unknown mechanisms. the movement of migrating neurons is saltatory, reflecting the intermittent movement of the nucleus (nucleokinesis) within the confines of the plasma membrane. each nucleokinetic movement is analogous to a step. thus, average migration speed could be reduced by lowering step frequency and/or step distance.200818534012
complex responses to a diverse environment.a report on the keystone symposium 'innate immunity: signaling mechanisms', keystone, usa, 24-29 february, 2008.200818533049
bcl-2 family members: dual regulators of apoptosis and autophagy.the essential autophagy protein and haplo-insufficient tumor suppressor, beclin 1, interacts with several cofactors (ambra1, bif-1, uvrag) to activate the lipid kinase vps34, thereby inducing autophagy. in normal conditions, beclin 1 is bound to and inhibited by bcl-2 or the bcl-2 homolog bcl-x(l). this interaction involves a bcl-2 homology 3 (bh3) domain in beclin 1 and the bh3 binding groove of bcl-2/bcl-x(l). other proteins containing bh3 domains, called bh3-only proteins, can competitively d ...200818497563
a transgenic sensor strain for monitoring the rnai pathway in the yellow fever mosquito, aedes aegypti.the rna interference pathway functions as an antiviral defense in invertebrates. in order to generate a phenotypic marker which "senses" the status of the rnai pathway in aedes aegypti, transgenic strains were developed to express egfp and dsred marker genes in the eye, as well as double-stranded rna homologous to a portion of the egfp gene. transgenic "sensor" mosquitoes exhibited robust eye-specific dsred expression with little egfp, indicating rnai-based silencing. cloning and high-throughput ...200818549956
bhlh-pas family transcription factor methoprene-tolerant plays a key role in jh action in preventing the premature development of adult structures during larval-pupal metamorphosis.the biological actions of juvenile hormones are well studied; they regulate almost all aspects of an insect's life. however, the molecular actions of these hormones are not well understood. recent studies in the red flour beetle, tribolium castaneum, demonstrated the utility of this insect as a model system to study jh action. these studies confirmed that the bhlh-pas family transcription factor, methoprene-tolerant (tcmet,) plays a key role in jh action during larval stages. in this study, we i ...200818450431
can essential fatty acids reduce the burden of disease(s)?coronary heart disease, stroke, diabetes mellitus, hypertension, cancer, depression schizophrenia, alzheimer's disease, and collagen vascular diseases are low-grade systemic inflammatory conditions that are a severe burden on health care resources. essential fatty acids (efas) and their metabolites: eicosapentaenoic acid (epa), docosahexaenoic acid (dha), gamma-linolenic acid (gla), dihomo-gamma-linolenic acid (dgla), and arachidonic acid (aa) and their products: prostaglandin e1, prostacyclin, ...200818348729
p72 dead box rna helicase is required for optimal function of the zinc-finger antiviral protein.the zinc-finger antiviral protein (zap) specifically inhibits the replication of many viruses by preventing the accumulation of viral mrnas in the cytoplasm. zap directly binds to the viral mrnas and recruits the rna exosome to degrade the target rna. in the present study, we identified the p72 dead box rna helicase, but not the highly similar rna helicase p68, as a zap-interacting protein. the binding domain of zap was mapped to its n-terminal portion, whereas both the n- and c-terminal domains ...200818334637
recycle or die: the role of autophagy in cardioprotection.autophagy is a highly conserved cellular process responsible for the degradation of long-lived proteins and organelles. autophagy occurs at low levels under normal conditions, but is upregulated in response to stress such as nutrient deprivation, hypoxia, mitochondrial dysfunction, and infection. upregulation of autophagy may be beneficial to the cell by recycling of proteins to generate free amino acids and fatty acids needed to maintain energy production, by removing damaged organelles, and by ...200818353358
identification of a coronavirus transcription enhancer.coronavirus (cov) transcription includes a discontinuous mechanism during the synthesis of sub-genome-length minus-strand rnas leading to a collection of mrnas in which the 5' terminal leader sequence is fused to contiguous genome sequences. it has been previously shown that transcription-regulating sequences (trss) preceding each gene regulate transcription. base pairing between the leader trs (trs-l) and the complement of the body trs (ctrs-b) in the nascent rna is a determinant factor during ...200818272586
autophagy and antiviral immunity.autophagy is an ancient pathway designed to maintain cellular homeostasis by degrading long-lived proteins and organelles in the cytosol. recent studies demonstrate that autophagy is utilized by the cells of the innate and adaptive immune systems to combat viral infections. autophagy plays a key role in recognizing signatures of viral infection, and represents a critical effector mechanism to restrict viral replication. on the other hand, autophagosomes have been exploited by certain viruses as ...200818262399
exploring systemic rna interference in insects: a genome-wide survey for rnai genes in tribolium.rna interference (rnai) is a highly conserved cellular mechanism. in some organisms, such as caenorhabditis elegans, the rnai response can be transmitted systemically. some insects also exhibit a systemic rnai response. however, drosophila, the leading insect model organism, does not show a robust systemic rnai response, necessitating another model system to study the molecular mechanism of systemic rnai in insects.200818201385
parkin protects dopaminergic neurons against microtubule-depolymerizing toxins by attenuating microtubule-associated protein kinase activation.mitogen-activated protein kinases, originally known as microtubule-associated protein (map) kinases, are activated in response to a variety of stimuli. here we report that microtubule-depolymerizing agents such as colchicine or nocodazole induced strong activation of map kinases including jnk, erk, and p38. this effect was markedly attenuated by parkin, whose mutations are linked to parkinson disease (pd). our previous study has shown that parkin stabilizes microtubules through strong interactio ...200819074146
eating the enemy within: autophagy in infectious diseases.autophagy is emerging as a central component of antimicrobial host defense against diverse viral, bacterial, and parasitic infections. in addition to pathogen degradation, autophagy has other functions during infection such as innate and adaptive immune activation. as an important host defense pathway, microbes have also evolved mechanisms to evade, subvert, or exploit autophagy. additionally, some fungal pathogens harness autophagy within their own cells to promote pathogenesis. this review wil ...200818772897
bacteria in the intestine, helpful residents or enemies from within? 200818474643
nontemplated terminal nucleotidyltransferase activity of double-stranded rna bacteriophage phi6 rna-dependent rna polymerase.the replication and transcription of double-stranded rna (dsrna) viruses occur within a polymerase complex particle in which the viral genome is enclosed throughout the entire life cycle of the virus. a single protein subunit in the polymerase complex is responsible for the template-dependent rna polymerization activity. the isolated polymerase subunit of the dsrna bacteriophage phi6 was previously shown to replicate and transcribe given rna molecules. in this study, we show that this enzyme als ...200818614640
gene expression studies in mosquitoes.research on gene expression in mosquitoes is motivated by both basic and applied interests. studies of genes involved in hematophagy, reproduction, olfaction, and immune responses reveal an exquisite confluence of biological adaptations that result in these highly-successful life forms. the requirement of female mosquitoes for a bloodmeal for propagation has been exploited by a wide diversity of viral, protozoan and metazoan pathogens as part of their life cycles. identifying genes involved in h ...200819161831
complement and its role in protection and pathogenesis of flavivirus infections.the complement system is a family of serum and cell surface proteins that recognize pathogen-associated molecular patterns, altered-self ligands, and immune complexes. activation of the complement cascade triggers several antiviral functions including pathogen opsonization and/or lysis, and priming of adaptive immune responses. in this review, we will examine the role of complement activation in protection and/or pathogenesis against infection by flaviviruses, with an emphasis on experiments wit ...200819388173
analysis of the survival of venezuelan equine encephalomyelitis virus and possible viral simulants in liquid compare the inactivation rate of venezuelan equine encephalomyelitis (vee) virus in liquids to that of sindbis virus (sv, another alphavirus) and to a bacteriophage (ms2) generally used as a viral simulant in the development of countermeasures in biodefense.200819146486
independent regulation of reovirus membrane penetration and apoptosis by the mu1 phi domain.apoptosis plays an important role in the pathogenesis of reovirus encephalitis. reovirus outer-capsid protein mu1, which functions to penetrate host cell membranes during viral entry, is the primary regulator of apoptosis following reovirus infection. ectopic expression of full-length and truncated forms of mu1 indicates that the mu1 phi domain is sufficient to elicit a cell death response. to evaluate the contribution of the mu1 phi domain to the induction of apoptosis following reovirus infect ...200819112493
rapid, bidirectional remodeling of synaptic nmda receptor subunit composition by a-type k+ channel activity in hippocampal ca1 pyramidal neurons.the transient, a-type k+ current (ia) controls the excitability of ca1 pyramidal neuron dendrites by regulating the back-propagation of action potentials and by shaping synaptic input. dendritic a-type k+ channels are targeted for modulation during long-term potentiation (ltp) and we have recently shown that activity-dependent internalization of the a-type channel subunit kv4.2 enhances synaptic currents. however, the effect of changes in ia on the ability to induce subsequent synaptic plasticit ...200819038222
yellow fever vaccine induces integrated multilineage and polyfunctional immune responses.correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. this impedes the development of novel vaccines to incurable diseases such as hiv and cancer. in this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (yf) vaccine 17d (yf17d) in a cohort of 40 volunteers followed for up to 1 yr after vaccination. we show that immunization with yf17d leads to an integrated immune r ...200819047440
alphavirus-derived small rnas modulate pathogenesis in disease vector mosquitoes.mosquito-borne viruses cause significant levels of morbidity and mortality in humans and domesticated animals. maintenance of mosquito-borne viruses in nature requires a biological transmission cycle that involves alternating virus replication in a susceptible vertebrate and mosquito host. although the vertebrate infection is acute and often associated with disease, continual transmission of these viruses in nature depends on the establishment of a persistent, nonpathogenic infection in the mosq ...200819047642
west nile virus-specific cd4 t cells exhibit direct antiviral cytokine secretion and cytotoxicity and are sufficient for antiviral protection.cd4 t cells have been shown to be necessary for the prevention of encephalitis during west nile virus (wnv) infection. however, the mechanisms used by ag-specific cd4 t cells to protect mice from wnv encephalitis remain incompletely understood. contrary to the belief that cd4 t cells are protective because they merely maintain the cd8 t cell response and improve ab production, in this study we provide evidence for the direct antiviral activity of cd4 t cells that functions to protect the host fr ...200819050276
a critical role of a cellular membrane traffic protein in poliovirus rna replication.replication of many rna viruses is accompanied by extensive remodeling of intracellular membranes. in poliovirus-infected cells, er and golgi stacks disappear, while new clusters of vesicle-like structures form sites for viral rna synthesis. virus replication is inhibited by brefeldin a (bfa), implicating some components(s) of the cellular secretory pathway in virus growth. formation of characteristic vesicles induced by expression of viral proteins was not inhibited by bfa, but they were functi ...200819023417
molecular basis of the regulation of beclin 1-dependent autophagy by the gamma-herpesvirus 68 bcl-2 homolog m11.gamma-herpesviruses (gammahvs), including important human pathogens such as epstein barr virus, kaposi's sarcoma-associated hv, and the murine gammahv68, encode homologs of the antiapoptotic, cellular bcl-2 (cbcl-2) to promote viral replication and pathogenesis. the precise molecular details by which these proteins function in viral infection are poorly understood. autophagy, a lysosomal degradation pathway, is inhibited by the interaction of cbcl-2s with a key autophagy effector, beclin 1, and ...200818797192
sars-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum.positive-strand rna viruses, a large group including human pathogens such as sars-coronavirus (sars-cov), replicate in the cytoplasm of infected host cells. their replication complexes are commonly associated with modified host cell membranes. membrane structures supporting viral rna synthesis range from distinct spherular membrane invaginations to more elaborate webs of packed membranes and vesicles. generally, their ultrastructure, morphogenesis, and exact role in viral replication remain to b ...200818798692
light-induced rescue of breathing after spinal cord injury.paralysis is a major consequence of spinal cord injury (sci). after cervical sci, respiratory deficits can result through interruption of descending presynaptic inputs to respiratory motor neurons in the spinal cord. expression of channelrhodopsin-2 (chr2) and photostimulation in neurons affects neuronal excitability and produces action potentials without any kind of presynaptic inputs. we hypothesized that after transducing spinal neurons in and around the phrenic motor pool to express chr2, ph ...200819005051
the role of autophagy in mammalian development: cell makeover rather than cell death.autophagy is important for the degradation of bulk cytoplasm, long-lived proteins, and entire organelles. in lower eukaryotes, autophagy functions as a cell death mechanism or as a stress response during development. however, autophagy's significance in vertebrate development, and the role (if any) of vertebrate-specific factors in its regulation, remains unexplained. through careful analysis of the current autophagy gene mutant mouse models, we propose that in mammals, autophagy may be involved ...200818804433
semliki forest virus strongly reduces mosquito host defence signaling.the alphavirus genus within the togaviridae family contains several important mosquito-borne arboviruses. other than the antiviral activity of rnai, relatively little is known about alphavirus interactions with insect cell defences. here we show that semliki forest virus (sfv) infection of aedes albopictus-derived u4.4 mosquito cells reduces cellular gene expression. activation prior to sfv infection of pathways involving stat/imd, but not toll signaling reduced subsequent virus gene expression ...200818811601
isolation of human monoclonal antibodies by mammalian cell display.due to their low immunogenicity in patients, humanized or fully human mabs are becoming increasingly important for the treatment of a growing number of diseases, including cancer, infections, and immune disorders. here, we describe a technology allowing for the rapid isolation of fully human mabs. in contrast to previously described methods, b cells specific for an antigen of interest are directly isolated from peripheral blood mononuclear cells (pbmc) of human donors. recombinant, antigen-speci ...200818812621
ross river virus envelope glycans contribute to type i interferon production in myeloid dendritic cells.alphaviruses are mosquito-transmitted viruses that cause significant human disease, and understanding how these pathogens successfully transition from the mosquito vector to the vertebrate host is an important area of research. previous studies demonstrated that mosquito and mammalian-cell-derived alphaviruses differentially induce type i interferons (alpha/beta interferon [ifn-alpha/beta]) in myeloid dendritic cells (mdcs), where the mosquito cell-derived virus is a poor inducer of ifn-alpha/be ...200818922878
effects of inducing or inhibiting apoptosis on sindbis virus replication in mosquito cells.sindbis virus (sinv) is a mosquito-borne virus in the genus alphavirus, family togaviridae. like most alphaviruses, sinvs exhibit lytic infection (apoptosis) in many mammalian cell types, but are generally thought to cause persistent infection with only moderate cytopathic effects in mosquito cells. however, there have been several reports of apoptotic-like cell death in mosquitoes infected with alphaviruses or flaviviruses. given that apoptosis has been shown to be an antiviral response in othe ...200818931060
immune response during acute chandipura viral infection in experimentally infected susceptible mice.age dependent susceptibility was observed in chandipura virus (chpv) infected mice through intravenous and intraperitoneal route. adult mice were susceptible only through intracerebral route of infection. immature neuron and some other biological variables including immature immune system are considered to be important factor for age related susceptibility in some diseases. as chandipura virus infects both young and adult mice brain through intracerebral route the role of immune system during pe ...200818937835
bidirectional regulation of kainate receptor surface expression in hippocampal neurons.kainate receptors (kars) are crucial for the regulation of both excitatory and inhibitory neurotransmission, but little is known regarding the mechanisms controlling kar surface expression. we used super ecliptic phluorin (sep)-tagged kar subunit glur6a to investigate real-time changes in kar surface expression in hippocampal neurons. sindbis virus-expressed sep-glur6 subunits efficiently co-assembled with native kar subunits to form heteromeric receptors. diffuse surface-expressed dendritic sep ...200818955488
a protein that replaces the entire cellular eif4f complex.the eif4f cap-binding complex mediates the initiation of cellular mrna translation. eif4f is composed of eif4e, which binds to the mrna cap, eif4g, which indirectly links the mrna cap with the 43s pre-initiation complex, and eif4a, which is a helicase necessary for initiation. viral nucleocapsid proteins (n) function in both genome replication and rna encapsidation. surprisingly, we find that hantavirus n has multiple intrinsic activities that mimic and substitute for each of the three peptides ...200818971945
genome 3'-end repair in dengue virus type 2.genomes of rna viruses encounter a continual threat from host cellular ribonucleases. therefore, viruses have evolved mechanisms to protect the integrity of their genomes. to study the mechanism of 3'-end repair in dengue virus-2 in mammalian cells, a series of 3'-end deletions in the genome were evaluated for virus replication by detection of viral antigen ns1 and by sequence analysis. limited deletions did not cause any delay in the detection of ns1 within 5 d. however, deletions of 7-10 nucle ...200818974278
size alters susceptibility of vectors to dengue virus infection and dissemination.the size of arthropod vectors may affect their ability to transmit pathogens. here we test the hypothesis that body size alters the susceptibility of aedes aegypti and aedes albopictus mosquitoes to dengue virus (denv) infection and subsequent dissemination throughout the body of the mosquito. after feeding on blood containing known quantities of virus, smaller-sized females were significantly more likely to become infected and to disseminate virus than larger individuals. the effects of size we ...200818981505
ex vivo promoter analysis of antiviral heat shock cognate 70b gene in anopheles gambiae.the anopheles gambiae heat shock cognate gene (hsc70b) encodes a constitutively expressed protein in the hsp70 family and it functions as a molecular chaperone for protein folding. however, the expression of hsc70b can be further induced by certain stimuli such as heat shock and infection. we previously demonstrated that the an. gambiae hsc70b is induced during o'nyong-nyong virus (onnv) infection and subsequently suppresses onnv replication in the mosquito. to further characterize the inducibil ...200818986525
therapeutic and prophylactic applications of alphavirus vectors.alphavirus vectors are high-level, transient expression vectors for therapeutic and prophylactic use. these positive-stranded rna vectors, derived from semliki forest virus, sindbis virus and venezuelan equine encephalitis virus, multiply and are expressed in the cytoplasm of most vertebrate cells, including human cells. part of the genome encoding the structural protein genes, which is amplified during a normal infection, is replaced by a transgene. three types of vector have been developed: vi ...200819000329
discovery of frameshifting in alphavirus 6k resolves a 20-year enigma.the genus alphavirus includes several potentially lethal human viruses. additionally, species such as sindbis virus and semliki forest virus are important vectors for gene therapy, vaccination and cancer research, and important models for virion assembly and structural analyses. the genome encodes nine known proteins, including the small '6k' protein. 6k appears to be involved in envelope protein processing, membrane permeabilization, virion assembly and virus budding. in protein gels, 6k migrat ...200818822126
mouse mammary tumor virus uses mouse but not human transferrin receptor 1 to reach a low ph compartment and infect cells.mouse mammary tumor virus (mmtv) is a ph-dependent virus that uses mouse transferrin receptor 1 (tfr1) for entry into cells. previous studies demonstrated that mmtv could induce ph 5-dependent fusion-from-with of mouse cells. here we show that the mmtv envelope-mediated cell-cell fusion requires both the entry receptor and low ph (ph 5). although expression of the mmtv envelope and tfr1 was sufficient to mediate low ph-dependent syncytia formation, virus infection required trafficking to a low p ...200818829060
passive immunization reduces murine cytomegalovirus-induced brain pathology in newborn mice.human cytomegalovirus (hcmv) is the most frequent cause of congenital viral infections in humans and frequently leads to long-term central nervous system (cns) abnormalities that include learning disabilities, microcephaly, and hearing loss. the pathogenesis of the cns infection has not been fully elucidated and may arise as a result of direct damage of cmv-infected neurons or indirectly secondary to inflammatory response to infection. we used a recently established model of mouse cmv (mcmv) inf ...200818842707
functional pseudotyping of human immunodeficiency virus type 1 vectors by western equine encephalitis virus envelope glycoprotein.we investigated the ability of western equine encephalitis virus envelope glycoproteins (weev gp) to pseudotype lentiviral vectors. the titers of weev gp-pseudotyped human immunodeficiency virus type 1 (hiv) ranged as high as 8.0 x 10(4) iu/ml on permissive cells. sera from weev-infected mice specifically neutralized these pseudotypes; cell transduction was also sensitive to changes in ph. the host range of the pseudotyped particles in vitro was somewhat limited, which is atypical for most alpha ...200818842711
beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian atg14 and uvrag.class iii phosphatidylinositol 3-kinase (pi3-kinase) regulates multiple membrane trafficking. in yeast, two distinct pi3-kinase complexes are known: complex i (vps34, vps15, vps30/atg6, and atg14) is involved in autophagy, and complex ii (vps34, vps15, vps30/atg6, and vps38) functions in the vacuolar protein sorting pathway. atg14 and vps38 are important in inducing both complexes to exert distinct functions. in mammals, the counterparts of vps34, vps15, and vps30/atg6 have been identified as vp ...200818843052
effect of host cell lipid metabolism on alphavirus replication, virion morphogenesis, and infectivity.the alphavirus sindbis virus (sinv) causes encephalomyelitis in mice. lipid-containing membranes, particularly cholesterol and sphingomyelin (sm), play important roles in virus entry, rna replication, glycoprotein transport, and budding. levels of sm are regulated by sphingomyelinases (smases). acid smase (asmase) deficiency results in the lipid storage disease type a niemann-pick disease (npd-a), mimicked in mice by interruption of the asmase gene. we previously demonstrated that asmase-deficie ...200818845681
a sindbis virus replicon-based dna vaccine encoding the rabies virus glycoprotein elicits immune responses and complete protection in mice from lethal challenge.a sindbis virus replicon-based dna vaccine encoding rabies virus glycoprotein (g) was developed by subcloning rabies g gene into a sindbis virus replicon-based vaccine vector (palpha). the self-amplification of rna transcripts and translation efficiency of rabies g was analyzed in palpha-rab-g-transfected mammalian cells using rt-pcr, sds-page and western blot analysis. the transfected cells also showed induction of apoptosis which is an important event in the enhancement of immune responses. fu ...200818848857
density-dependent competitive suppression of sylvatic dengue virus by endemic dengue virus in cultured mosquito cells.mosquito-borne dengue viruses are maintained in two discrete transmission cycles: a sylvatic cycle between nonhuman primates and sylvatic aedes mosquitoes, and an endemic cycle between humans and peridomestic aedes (primarily ae. aegypti and ae. albopictus). most sylvatic strains are genetically distinct from endemic strains, and human infections with sylvatic strains have been detected only rarely. interestingly, sylvatic strains replicate as well as endemic strains in ae. aegypti and experimen ...200818620509
evidence for interferon production and its correlation with yf 17dd vaccine virus yields in primary chick embryo cells.early experiments have resulted in the establishment of an efficient methodology for the production of a yellow fever vaccine in chicken embryo fibroblasts (cef) using the 17dd virus strain [freire, m.s., mann, g.f., marchevsky, r.s., yamamura, a.m., almeida, l.f., jabor, a.v., malachias, j.m., coutinho, e.s., galler, r., 2005. production of yellow fever 17dd vaccine virus in primary culture of chicken embryo fibroblasts: yields, thermo and genetic stability, attenuation and immunogenicity. vacc ...200818621087
host restriction factors blocking retroviral replication.retroviruses are highly successful intracellular parasites, and as such they are found in nearly all branches of life. some are relatively benign, but many are highly pathogenic and can cause either acute or chronic diseases. therefore, there is tremendous selective pressure on the host to prevent retroviral replication, and for this reason cells have evolved a variety of restriction factors that act to inhibit or block the viruses. this review is a survey of the best-characterized restriction f ...200818624631
analysis of venezuelan equine encephalitis replicon particles packaged in different coats.the venezuelan equine encephalitis (vee) virus replicon system was used to produce virus-like replicon particles (vrp) packaged with a number of different vee-derived glycoprotein (gp) coats. the gp coat is believed to be responsible for the cellular tropism noted for vrp and it is possible that different vee gp coats may have different affinities for cells. we examined vrp packaged in four different vee gp coats for their ability to infect cells in vitro and to induce both humoral and cellular ...200818628938
differential cholesterol binding by class ii fusion proteins determines membrane fusion properties.the class ii fusion proteins of the alphaviruses and flaviviruses mediate virus infection by driving the fusion of the virus membrane with that of the cell. these fusion proteins are triggered by low ph, and their structures are strikingly similar in both the prefusion dimer and the postfusion homotrimer conformations. here we have compared cholesterol interactions during membrane fusion by these two groups of viruses. using cholesterol-depleted insect cells, we showed that fusion and infection ...200818632857
bluetongue virus: dissection of the polymerase complex.bluetongue is a vector-borne viral disease of ruminants that is endemic in tropical and subtropical countries. since 1998 the virus has also appeared in europe. partly due to the seriousness of the disease, bluetongue virus (btv), a member of genus orbivirus within the family reoviridae, has been a subject of intense molecular study for the last three decades and is now one of the best understood viruses at the molecular and structural levels. btv is a complex non-enveloped virus with seven stru ...200818632949
cd8+ t lymphocytes control murine cytomegalovirus replication in the central nervous system of newborn animals.human cmv infection of the neonatal cns results in long-term neurologic sequelae. to define the pathogenesis of fetal human cmv cns infections, we investigated mechanisms of virus clearance from the cns of neonatal balb/c mice infected with murine cmv (mcmv). virus titers peaked in the cns between postnatal days 10-14 and infectious virus was undetectable by postnatal day 21. congruent with virus clearance was the recruitment of cd8(+) t cells into the cns. depletion of cd8(+) t cells resulted i ...200818641350
bh3 domains define selective inhibitory interactions with bhrf-1 and kshv bcl-2.the epstein-barr and kaposi's sarcoma gamma-herpesviruses (kshvs) are associated with certain cancers, and encode b-cell leukemia/lymphoma 2 (bcl-2) homologs, bhrf-1 and kshv bcl-2, respectively. little is known, however, about the molecular interactions allowing viral bcl-2 homologs to mediate their anti-apoptotic function. cellular anti-apoptotic proteins, such as bcl-2 and mcl-1, prevent death via selective interactions with pro-death bh3-only proteins. to investigate whether bhrf-1 and kshv ...200818084238
antibodies play a greater role than immune cells in heterologous protection against secondary dengue virus infection in a mouse model.the four serotypes of dengue virus (denv1-4) are causative agents of dengue fever and dengue hemorrhagic fever/dengue shock syndrome (dhf/dss). previous denv infection is a risk factor for dhf/dss during subsequent infection by a different serotype. nonetheless, most primary and secondary denv infections are asymptomatic. to investigate the possible mechanisms of immune protection in vivo, 129/pas mice lacking ifn-alpha/beta and -gamma receptors (ag129) were used to model secondary infection usi ...200818774583
human alpha-defensins inhibit bk virus infection by aggregating virions and blocking binding to host cells.bk virus (bkv) is a polyomavirus that establishes a lifelong persistence in most humans and is a major impediment to success of kidney grafts. the function of the innate immune system in bkv infection and pathology has not been investigated. here we examine the role of antimicrobial defensins in bkv infection of vero cells. our data show that alpha-defensin human neutrophil protein 1 (hnp1) and human alpha-defensin 5 (hd5) inhibit bkv infection by targeting an early event in the viral lifecycle. ...200818782756
role of cellular glycosaminoglycans and charged regions of viral g protein in human metapneumovirus infection.human metapneumovirus (hmpv) is an important cause of lower respiratory tract disease, particularly in infants and young children. hmpv has two major glycoproteins, g and f, which are responsible for virus attachment and membrane fusion, respectively. we investigated the role of cellular glycosaminoglycans (gags) and g protein in hmpv infection. the pretreatment of hmpv with soluble heparin markedly inhibited the infection of hep-2 cells. recombinant g protein, comprising the extracellular domai ...200818786997
trypanosoma cruzi infection is enhanced by vector saliva through immunosuppressant mechanisms mediated by lysophosphatidylcholine.trypanosoma cruzi, the etiological agent of chagas disease, is transmitted by bug feces deposited on human skin during a blood meal. however, parasite infection occurs through the wound produced by insect mouthparts. saliva of the triatominae bug rhodnius prolixus is a source of lysophosphatidylcholine (lpc). here, we tested the role of both triatomine saliva and lpc on parasite transmission. we show that vector saliva is a powerful inducer of cell chemotaxis. a massive number of inflammatory ce ...200818794282
targeted cell entry of lentiviral vectors.retargeting of lentiviral vector entry to cell types of interest is a key factor in improving the safety and efficacy of gene transfer. in this study we show that the retargetable envelope glycoproteins of measles virus (mv), namely, the hemagglutinin (h) responsible for receptor recognition and the fusion protein (f), can pseudotype human immunodeficiency virus 1 (hiv-1) vectors when their cytoplasmic tails are truncated. we then pseudotyped hiv-1 vectors with mv glycoproteins displaying on h e ...200818578012
activity-induced polo-like kinase 2 is required for homeostatic plasticity of hippocampal neurons during epileptiform activity.homeostatic plasticity mechanisms stabilize the activity of a neuron or neuronal circuit during prolonged periods of increased network activity and have been proposed to function in the prevention of epilepsy. how homeostatic plasticity is achieved at the molecular level during hyperactivity states in general, and during epileptiform activity in particular, is unclear. using organotypic hippocampal slice cultures as a model system, we found that the protein kinase polo-like kinase 2 (plk2) was i ...200818579731
alphavirus replicon particles acting as adjuvants promote cd8+ t cell responses to co-delivered antigen.alphavirus replicon particles induce strong antibody and cd8+ t cell responses to expressed antigens in numerous experimental systems. we have recently demonstrated that venezuelan equine encephalitis virus replicon particles (vrp) possess adjuvant activity for systemic and mucosal antibody responses. in this report, we demonstrate that vrp induced an increased and balanced serum igg subtype response to co-delivered antigen, with simultaneous induction of antigen-specific igg1 and igg2a antibodi ...200818582997
[isolation of influenza virus a (orthomyxoviridae, influenza a virus), dhori virus (orthomyxoviridae, thogotovirus), and newcastle's disease virus (paromyxoviridae, avulavirus) on the malyi zhemchuzhnyi island in the north-western area of the caspian sea].the paper presents the results of the 2003 and 2006 environmental virological monitoring surveys on the malyi zhemchuzhnyi island where a large breeding colony of sea gull (laridae) is located. in the past several years, expansion of cormorants (phalacrocorax carbo) has enhanced the intensity of populational interactions. the investigators isolated 13 strains of influenza a virus (orthomyxoviridae, influenza a virus) subtype h13n1 (from sea gulls (n = 4), cormorants (n = 9) 1 strain of dhori vir ...200818590134
targeting lentiviral vectors to antigen-specific immunoglobulins.gene transfer into b cells by lentivectors can provide an alternative approach to managing b lymphocyte malignancies and autoreactive b cell-mediated autoimmune diseases. these pathogenic b cell populations can be distinguished by their surface expression of monospecific immunoglobulin. development of a novel vector system to deliver genes to these specific b cells could improve the safety and efficacy of gene therapy. we have developed an efficient method to target lentivectors to monospecific ...200818590376
the dynamic envelope of a fusion class ii virus. e3 domain of glycoprotein e2 precursor in semliki forest virus provides a unique contact with the fusion protein alphaviruses, here represented by semliki forest virus, infection requires an acid-responsive spike configuration to facilitate membrane fusion. the creation of this relies on the chaperone function of glycoprotein e2 precursor (p62) and its maturation cleavage into the small external e3 and the membrane-anchored e2 glycoproteins. to reveal how the e3 domain of p62 exerts its control of spike functions, we determine the structure of a p62 cleavage-impaired mutant virus particle (sql) by elect ...200818596032
preferential cytolysis of peripheral memory cd4+ t cells by in vitro x4-tropic human immunodeficiency virus type 1 infection before the completion of reverse transcription.cd4+ t-cell depletion is the hallmark of aids pathogenesis. multiple mechanisms may contribute to the death of productively infected cd4+ t cells and innocent-bystander cells. in this study, we characterize a novel mechanism in which human immunodeficiency virus type 1 (hiv-1) infection preferentially depletes peripheral memory cd4+ t cells before the completion of reverse transcription. using a recombinant hiv-1 carrying the green fluorescent protein reporter gene, we demonstrate that memory cd ...200818596085
molecular defects caused by temperature-sensitive mutations in semliki forest virus nsp1.alphavirus replicase protein nsp1 has multiple functions during viral rna synthesis. it catalyzes methyltransferase and guanylyltransferase activities needed in viral mrna capping, attaches the viral replication complex to cytoplasmic membranes, and is required for minus-strand rna synthesis. two temperature-sensitive (ts) mutations in semliki forest virus (sfv) were previously identified within nsp1: ts10 (e529d) and ts14 (d119n). recombinant viruses containing these individual mutations reprod ...200818596091
survival of enveloped and non-enveloped viruses on surfaces compared with other micro-organisms and impact of suboptimal disinfectant exposure.survival of enveloped and non-enveloped viruses was compared with that of bacteria, yeasts and mycobacteria when dried on the surface of polyvinyl chloride test carriers in the presence or absence of an organic matrix. the efficacy of glutaraldehyde and accelerated hydrogen peroxide (ahp) disinfectants was evaluated. reovirus, a non-enveloped virus, persisted and had a rf of 2 after 30 days whereas enterococcus faecalis had an rf of 4 over the same time period. the other test organisms (sindbis ...200818602193
vaccinia virus e3 protein prevents the antiviral action of isg15.the ubiquitin-like modifier isg15 is one of the most predominant proteins induced by type i interferons (ifn). in this study, murine embryo fibroblast (mefs) and mice lacking the gene were used to demonstrate a novel role of isg15 as a host defense molecule against vaccinia virus (vacv) infection. in mefs, the growth of replication competent western reserve (wr) vacv strain was affected by the absence of isg15, but in addition, virus lacking e3 protein (vvdeltae3l) that is unable to grow in isg1 ...200818604270
the aedes aegypti toll pathway controls dengue virus infection.aedes aegypti, the mosquito vector of dengue viruses, utilizes its innate immune system to ward off a variety of pathogens, some of which can cause disease in humans. to date, the features of insects' innate immune defenses against viruses have mainly been studied in the fruit fly drosophila melanogaster, which appears to utilize different immune pathways against different types of viruses, in addition to an rna interference-based defense system. we have used the recently released whole-genome s ...200818604274
nitrosylation of isg15 prevents the disulfide bond-mediated dimerization of isg15 and contributes to effective isgylation.the expression of the ubiquitin-like molecule isg15 (ucrp) and protein modification by isg15 (isgylation) are strongly activated by interferon, genotoxic stress, and pathogen infection, suggesting that isg15 plays an important role in innate immune responses. inducible nitric-oxide synthase (inos) is induced by the similar stimuli as isg15 and enhances the production of nitric oxide (no), a pleiotropic free radical with antipathogen activity. here, we report that cysteine residues (cys-76 and -1 ...200818606809
ubiquitination is required for effective replication of coxsackievirus b3.protein ubiquitination and/or degradation by the ubiquitin/proteasome system (ups) have been recognized as critical mechanisms in the regulation of numerous essential cellular functions. the importance of the ups in viral pathogenesis has become increasingly apparent. using murine cardiomyocytes, we have previously demonstrated that the ups plays a key role in the replication of coxsackievirus b3 (cvb3), an important human pathogen associated with various diseases. to further elucidate the under ...200818612413
genetic determinants of sindbis virus mosquito infection are associated with a highly conserved alphavirus and flavivirus envelope sequence.wild-type sindbis virus (sinv) strain mre16 efficiently infects aedes aegypti midgut epithelial cells (mec), but laboratory-derived neurovirulent sinv strain te/5'2j infects mec poorly. sinv determinants for mec infection have been localized to the e2 glycoprotein. the e2 amino acid sequences of mre16 and te/5'2j differ at 60 residue sites. to identify the genetic determinants of mec infection of mre16, the te/5'2j virus genome was altered to contain either domain chimeras or more focused nucleo ...200818160430
cis- and trans-acting functions of brome mosaic virus protein 1a in genomic rna1 replication.rna viruses employ a combination of mechanisms to regulate their gene expression and replication. brome mosaic virus (bmv) is a tripartite positive-strand rna virus used to study the requirements for virus infection. bmv genomic rna1 encodes protein 1a, which contains a methyltransferase (mt) domain and a helicase domain that are required for replication. 1a forms a complex with the 2a rna-dependent rna polymerase for the replication and transcription of all bmv rnas. rna1 expressed with 2a from ...200818160434
alpha/beta interferon inhibits cap-dependent translation of viral but not cellular mrna by a pkr-independent mechanism.the alpha/beta interferon (ifn-alpha/beta) response is critical for host protection against disseminated replication of many viruses, primarily due to the transcriptional upregulation of genes encoding antiviral proteins. previously, we determined that infection of mice with sindbis virus (sb) could be converted from asymptomatic to rapidly fatal by elimination of this response (k. d. ryman et al., j. virol. 74:3366-3378, 2000). probing of the specific antiviral proteins important for ifn-mediat ...200818160435
synthetic heterovalent inhibitors targeting recognition e3 components of the n-end rule pathway.multivalent binding allows high selectivity and affinity in a ligand-protein interaction. the n-end rule pathway is a ubiquitin (ub)-dependent proteolytic system in which specific e3s, called n-recognins, mediate ubiquitylation through the recognition of types 1 and 2, destabilizing n-terminal residues of substrates. we recently identified a set of e3 ub ligases (named ubr1-ubr7) containing the 70-residue ubr box, and we demonstrated that ubr1, ubr2, ubr4, and ubr5 can bind to destabilizing n-te ...200818162545
envelope protein palmitoylations are crucial for murine coronavirus assembly.the coronavirus assembly process encloses a ribonucleoprotein genome into vesicles containing the lipid-embedded proteins s (spike), e (envelope), and m (membrane). this process depends on interactions with membranes that may involve palmitoylation, a common posttranslational lipidation of cysteine residues. to determine whether specific palmitoylations influence coronavirus assembly, we introduced plasmid dnas encoding mouse hepatitis coronavirus (mhv) s, e, m, and n (nucleocapsid) into 293t ce ...200818184706
experimental infection of aedes sollicitans and aedes taeniorhynchus with two chimeric sindbis/eastern equine encephalitis virus vaccine candidates.two chimeric vaccine candidates for eastern equine encephalitis virus (eeev) were developed by inserting the structural protein genes of either a north american (na) or south american (sa) eeev into a sindbis virus (sinv) backbone. to assess the effect of chimerization on mosquito infectivity, experimental infections of two potential north american bridge vectors of eeev, aedes sollicitans and ae. taeniorhynchus, were attempted. both species were susceptible to oral infection with all viruses af ...200818187790
autophagy in the pathogenesis of disease.autophagy is a lysosomal degradation pathway that is essential for survival, differentiation, development, and homeostasis. autophagy principally serves an adaptive role to protect organisms against diverse pathologies, including infections, cancer, neurodegeneration, aging, and heart disease. however, in certain experimental disease settings, the self-cannibalistic or, paradoxically, even the prosurvival functions of autophagy may be deleterious. this review summarizes recent advances in unders ...200818191218
intra-axonal translation and retrograde trafficking of creb promotes neuronal survival.during development of the nervous system, axons and growth cones contain mrnas such as beta-actin, cofilin and rhoa, which are locally translated in response to guidance cues. intra-axonal translation of these mrnas results in local morphological responses; however, other functions of intra-axonal mrna translation remain unknown. here, we show that axons of developing mammalian neurons contain mrna encoding the camp-responsive element (cre)-binding protein (creb). creb is translated within axons ...200818193038
the inflammatory cytokine, interleukin-1 beta, mediates loss of astroglial glutamate transport and drives excitotoxic motor neuron injury in the spinal cord during acute viral encephalomyelitis.astrocytes remove glutamate from the synaptic cleft via specific transporters, and impaired glutamate reuptake may promote excitotoxic neuronal injury. in a model of viral encephalomyelitis caused by neuroadapted sindbis virus (nsv), mice develop acute paralysis and spinal motor neuron degeneration inhibited by the ampa receptor antagonist, nbqx. to investigate disrupted glutamate homeostasis in the spinal cord, expression of the main astroglial glutamate transporter, glt-1, was examined. glt-1 ...200818194440
yellow fever virus ns3 plays an essential role in virus assembly independent of its known enzymatic flaviviruses it has been proposed that there is a coupling between genome replication and virion assembly and that nonstructural proteins are involved in this process. it was previously reported that mutations in yellow fever virus (yfv) nonstructural protein ns2a blocked production of infectious virus and that this block could be released by a suppressor mutation in ns3. here, based on studies using a yfv replicon-based trans-packaging system as well as full-length yfv cdna, we report that m ...200818199634
activity of the small modified amino acid alpha-hydroxy glycineamide on in vitro and in vivo human immunodeficiency virus type 1 capsid assembly and infectivity.upon maturation of the human immunodeficiency virus type 1 (hiv-1) virion, proteolytic cleavage of the gag precursor protein by the viral protease is followed by morphological changes of the capsid protein p24, which will ultimately transform the virus core from an immature spherical to a mature conical structure. virion infectivity is critically dependent on the optimal semistability of the capsid cone structure. we have reported earlier that glycineamide (g-nh(2)), when added to the culture me ...200818644965
molecular engineering of viral gene delivery vehicles.viruses can be engineered to efficiently deliver exogenous genes, but their natural gene delivery properties often fail to meet human therapeutic needs. therefore, engineering viral vectors with new properties, including enhanced targeting abilities and resistance to immune responses, is a growing area of research. this review discusses protein engineering approaches to generate viral vectors with novel gene delivery capabilities. rational design of viral vectors has yielded successful advances ...200818647114
protein kinase a mediates activity-dependent kv4.2 channel trafficking.the a-type potassium channel subunit kv4.2 influences hippocampal function through regulation of dendritic excitability, and changes in kv4.2 surface expression alter synaptic plasticity. recent data from our laboratory demonstrate that egfp (enhanced green fluorescent protein)-tagged kv4.2 channels located in dendritic spines are internalized in an activity-dependent manner after synaptic stimulation and during chemically induced long-term potentiation. however, the molecular trigger for kv4.2 ...200818650329
effector cd4+ t-cell involvement in clearance of infectious herpes simplex virus type 1 from sensory ganglia and spinal primary infection, cd8(+) t cells are important for clearance of infectious herpes simplex virus (hsv) from sensory ganglia. in this study, evidence of cd4(+) t-cell-mediated clearance of infectious hsv type 1 (hsv-1) from neural tissues was also detected. in immunocompetent mice, hsv-specific cd4(+) t cells were present in sensory ganglia and spinal cords coincident with hsv-1 clearance from these sites and remained detectable at least 8 months postinfection. neural cd4(+) t cells isolated a ...200818667492
murine coronavirus mouse hepatitis virus is recognized by mda5 and induces type i interferon in brain macrophages/microglia.the coronavirus mouse hepatitis virus (mhv) induces a minimal type i interferon (ifn) response in several cell types in vitro despite the fact that the type i ifn response is important in protecting the mouse from infection in vivo. when infected with mhv, mice deficient in ifn-associated receptor expression (ifnar(-/-)) became moribund by 48 h postinfection. mhv also replicated to higher titers and exhibited a more broad tissue tropism in these mice, which lack a type i ifn response. interestin ...200818667505
kv4 accessory protein dppx (dpp6) is a critical regulator of membrane excitability in hippocampal ca1 pyramidal neurons.a-type k+ currents have unique kinetic and voltage-dependent properties that allow them to finely tune synaptic integration, action potential (ap) shape and firing patterns. in hippocampal ca1 pyramidal neurons, kv4 channels make up the majority of the somatodendritic a-type current. studies in heterologous expression systems have shown that kv4 channels interact with transmembrane dipeptidyl-peptidase-like proteins (dppls) to regulate the surface trafficking and biophysical properties of kv4 ch ...200818667548
ras signaling mechanisms underlying impaired glur1-dependent plasticity associated with fragile x syndrome.fragile x syndrome, caused by the loss of fmr1 gene function and loss of fragile x mental retardation protein (fmrp), is the most commonly inherited form of mental retardation. the syndrome is characterized by associative learning deficits, reduced risk of cancer, dendritic spine dysmorphogenesis, and facial dysmorphism. however, the molecular mechanism that links loss of function of fmr1 to the learning disability remains unclear. here, we report an examination of small gtpase ras signaling and ...200818667617
the capsid-coding region hairpin element (chp) is a critical determinant of dengue virus and west nile virus rna synthesis.dengue virus (denv) and west nile virus (wnv) are members of the flavivirus genus of positive-strand rna viruses. rna sequences and structures, primarily in the untranslated regions, have been shown to modulate flaviviral gene expression and genome replication. previously, we demonstrated that a structure in the denv coding region (chp) enhances translation start codon selection and is required for viral replication. here we further characterize the role of the chp in the denv life cycle. we dem ...200818676000
downregulation of protein disulfide isomerase in sepsis and its role in tumor necrosis factor-alpha release.protein disulfide isomerase (pdi) is an important factor for the protein modification step in the post-translational event. pdi plays an essential role in cell survival under various stress conditions. it has been reported that pdi can serve as a negative regulator of nuclear factor-kappa-b (nf-kappab) and that it can inhibit lipopolysaccharide (lps)-induced proinflammatory cytokine production in macrophages. thus, pdi may be an intracellular anti-inflammatory molecule. although we have previous ...200818680601
oncolytic vaccinia virus: from bedside to benchtop and back.the field of oncolytic viral therapy has undergone a major shift in focus in the last few years. less research has been directed at making incremental improvements in original vectors based mainly on strains of adenovirus and hsv; instead a variety of different viral strains have been suggested as potential backbones for future oncolytic viruses (including newcastle disease virus, reovirus, vesicular stomatitis virus, polio virus, retrovirus, sindbis virus, picornavirus, mumps and measles virus) ...200818683104
different types of nsp3-containing protein complexes in sindbis virus-infected cells.alphaviruses represent a serious public health threat and cause a wide variety of diseases, ranging from severe encephalitis, which can result in death or neurological sequelae, to mild infection, characterized by fever, skin rashes, and arthritis. in the infected cells, alphaviruses express only four nonstructural proteins, which function in the synthesis of virus-specific rnas and in modification of the intracellular environment. the results of our study suggest that sindbis virus (sinv) infec ...200818684830
the requirement of reactive oxygen intermediates for lymphocytic choriomeningitis virus binding and growth.multiple viruses induce reactive oxygen intermediate (roi) generation during infection that plays an important role in growth. we have examined the importance of roi during lymphocytic choriomeningitis virus (lcmv) infection of immortalized bhk-21 cells and murine peritoneal macrophages. within 15 min of virus addition, intracellular roi levels increased. to examine the contribution of roi to lcmv infection, cells were pretreated with antioxidant prior to virus addition. antioxidant treatment in ...200818691729
chimeric alphavirus vaccine candidates for chikungunya.chikungunya virus (chikv) is an emerging alphavirus that has caused major epidemics in india and islands off the east coast of africa since 2005. importations into europe and the americas, including one that led to epidemic transmission in italy during 2007, underscore the risk of endemic establishment elsewhere. because there is no licensed human vaccine, and an attenuated investigational new drug product developed by the u.s. army causes mild arthritis in some vaccinees, we developed chimeric ...200818692107
trafficking and intracellular atpase activity of human ecto-nucleotidase ntpdase3 and the effect of er-targeted ntpdase3 on protein folding.ecto-nucleoside triphosphate diphosphohydrolases, ntpdase1 (cd39) and ntpdase3, are integral plasma membrane proteins that hydrolyze extracellular nucleotides, thereby modulating the function of purinergic receptors. during processing in the secretory pathway, the active sites of ecto-nucleotidases are located in the lumen of vesicular compartments, thus raising the question whether the ecto-nucleotidases affect the atp-dependent processes in these compartments, including protein folding in the ...200818693757
pathogenic role of natural killer t and natural killer cells in acetaminophen-induced liver injury in mice is dependent on the presence of dimethyl sulfoxide.dimethyl sulfoxide (dmso) is commonly used in biological studies to dissolve drugs and enzyme inhibitors with low solubility. although dmso is generally thought of as being relatively inert, it can induce biological effects that are often overlooked. an example that highlights this potential problem is found in a recent report demonstrating a pathogenic role for natural killer t (nkt) and natural killer (nk) cells in acetaminophen-induced liver injury (aili) in c57bl/6 mice in which dmso was use ...200818712839
a duplex real-time reverse transcriptase polymerase chain reaction assay for the detection of st. louis encephalitis and eastern equine encephalitis viruses.a duplex taqman real-time reverse transcriptase polymerase chain reaction (pcr) assay was developed for the detection of st. louis encephalitis virus (slev) and eastern equine encephalitis virus (eeev), for use in human and vector surveillance. the respective targets selected for the assay were the conserved ns5 and e1 genes of the 2 viruses. because of the insufficient number of ns5 sequences from slev strains in the genbank database, we determined the sequence of an approximately 1-kb region f ...200818715737
regulation of postsynaptic rapgap spar by polo-like kinase 2 and the scfbeta-trcp ubiquitin ligase in hippocampal neurons.the ubiquitin-proteasome pathway (upp) regulates synaptic function, but little is known about specific upp targets and mechanisms in mammalian synapses. we report here that the scf(beta-trcp) complex, a multisubunit e3 ubiquitin ligase, targets the postsynaptic spine-associated rap gtpase activating protein (spar) for degradation in neurons. spar degradation by scf(beta-trcp) depended on the activity-inducible protein kinase polo-like kinase 2 (plk2). in the presence of plk2, spar physically ass ...200818723513
cre-dependent expression of multiple transgenes in isolated neurons of the adult forebrain.transgenic mice with mosaic, golgi-staining-like expression of enhanced green fluorescent protein (egfp) have been very useful in studying the dynamics of neuronal structure and function. in order to further investigate the molecular events regulating structural plasticity, it would be useful to express multiple proteins in the same sparse neurons, allowing co-expression of functional proteins or co-labeling of subcellular compartments with other fluorescent proteins. however, it has been diffic ...200818725976
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