| engineered hepatitis b virus surface antigen l protein particles for in vivo active targeting of splenic dendritic cells. | dendritic cells (dcs) are key regulators of adaptive t-cell responses. by capturing exogenous antigens and presenting antigen-derived peptides via major histocompatibility complex molecules to naïve t cells, dcs induce antigen-specific immune responses in vivo. in order to induce effective host immune responses, active delivery of exogenous antigens to dcs is considered important for future vaccine development. we recently generated bionanocapsules (bncs) consisting of hepatitis b virus surface ... | 2012 | 22848163 |
| structure of the surface layer of the methanogenic archaean methanosarcina acetivorans. | archaea have a self-assembling proteinaceous surface (s-) layer as the primary and outermost boundary of their cell envelopes. the s-layer maintains structural rigidity, protects the organism from adverse environmental elements, and yet provides access to all essential nutrients. we have determined the crystal structure of one of the two "homologous" tandem polypeptide repeats that comprise the methanosarcina acetivorans s-layer protein and propose a high-resolution model for a microbial s-layer ... | 2012 | 22753492 |
| bugs and drugs: oncolytic virotherapy in combination with chemotherapy. | single agent therapies are rarely successful in treating cancer, particularly at metastatic or end stages, and survival rates with monotherapies alone are generally poor. the combination of multiple therapies to treat cancer has already driven significant improvements in the standard of care treatments for many types of cancers. the first combination treatments exploited for cancer therapy involved the use of several cytotoxic chemotherapy agents. later, with the development of more targeted age ... | 0 | 21740354 |
| mitophagy: mechanisms, pathophysiological roles, and analysis. | abstract mitochondria are essential organelles that regulate cellular energy homeostasis and cell death. the removal of damaged mitochondria through autophagy, a process called mitophagy, is thus critical for maintaining proper cellular functions. indeed, mitophagy has been recently proposed to play critical roles in terminal differentiation of red blood cells, paternal mitochondrial degradation, neurodegenerative diseases, and ischemia or drug-induced tissue injury. removal of damaged mitochond ... | 0 | 22944659 |
| wing shape as an indicator of larval rearing conditions for aedes albopictus and aedes aegypti (diptera: culicidae). | estimating a mosquito's vector competence, or likelihood of transmitting disease, if it takes an infectious bloodmeal, is an important aspect of predicting when and where outbreaks of infectious diseases will occur. vector competence can be affected by rearing temperature and inter- and intraspecific competition experienced by the individual mosquito during its larval development. this research investigates whether a new morphological indicator of larval rearing conditions, wing shape, can be us ... | 0 | 22897054 |
| evidence for a genetic and physical interaction between nonstructural proteins ns1 and ns4b that modulates replication of west nile virus. | flavivirus ns1 is a nonstructural glycoprotein that is expressed on the cell surface and secreted into the extracellular space. despite its transit through the secretory pathway, ns1 is an essential gene linked to early viral rna replication. how this occurs has remained a mystery given the disparate localization of ns1 and the viral rna replication complex, as the latter is present on the cytosolic face of the endoplasmic reticulum (er). we recently identified an n-terminal di-amino acid motif ... | 2012 | 22553322 |
| autophagic clearance of sin nombre hantavirus glycoprotein gn promotes virus replication in cells. | hantavirus glycoprotein precursor (gpc) is posttranslationally cleaved into two glycoproteins, gn and gc. cells transfected with plasmids expressing either gpc or both gn and gc revealed that gn is posttranslationally degraded. treatment of cells with the autophagy inhibitors 3-methyladenine, ly-294002, or wortmanin rescued gn degradation, suggesting that gn is degraded by the host autophagy machinery. confocal microscopic imaging showed that gn is targeted to autophagosomes for degradation by a ... | 2012 | 22553339 |
| autophagy: an emerging immunological paradigm. | autophagy is a fundamental eukaryotic process with multiple cytoplasmic homeostatic roles, recently expanded to include unique stand-alone immunological functions and interactions with nearly all parts of the immune system. in this article, we review this growing repertoire of autophagy roles in innate and adaptive immunity and inflammation. its unique functions include cell-autonomous elimination of intracellular microbes facilitated by specific receptors. other intersections of autophagy with ... | 0 | 22723639 |
| how do viruses interact with stress-associated rna granules? | | 2012 | 22761570 |
| overexpression of serum response factor in astrocytes improves neuronal plasticity in a model of early alcohol exposure. | neuronal plasticity deficits underlie many of the cognitive problems seen in fetal alcohol spectrum disorders (fasd). we have developed a ferret model showing that early alcohol exposure leads to a persistent disruption in ocular dominance (od) plasticity. recently, we showed that this deficit could be reversed by overexpression of serum response factor (srf) in the primary visual cortex during the period of monocular deprivation (md). surprisingly, this restoration was observed throughout the e ... | 2012 | 22742904 |
| viral flice inhibitory protein of rhesus monkey rhadinovirus inhibits apoptosis by enhancing autophagosome formation. | rhesus monkey rhadinovirus (rrv) is a gamma-2 herpesvirus closely related to human herpesvirus 8 (hhv8). rrv encodes viral flice inhibitory protein (vflip), which has death effector domains. little is known about rrv vflip. this study intended to examine its function in apoptosis. here we found that rrv vflip inhibits apoptosis induced by tumor necrosis factor-α (tnf-α) and cycloheximide. in hela cells with vflip expression, the cleavage of poly [adp-ribose] polymerase 1 (parp-1) and activities ... | 2012 | 22745754 |
| disrupted cortical function underlies behavior dysfunction due to social isolation. | stressful events during early childhood can have a profound lifelong influence on emotional and cognitive behaviors. however, the mechanisms by which stress affects neonatal brain circuit formation are poorly understood. here, we show that neonatal social isolation disrupts molecular, cellular, and circuit developmental processes, leading to behavioral dysfunction. neonatal isolation prevented long-term potentiation and experience-dependent synaptic trafficking of α-amino-3-hydroxy-5-methylisoxa ... | 2012 | 22706303 |
| variability in detection and quantification of interferon β-1b-induced neutralizing antibodies. | interferon-beta (ifnb) therapy for multiple sclerosis can lead to the induction of neutralizing antibodies (nabs) against ifnb. various methods are used for detection and quantification of nabs. | 2012 | 22703536 |
| θ-defensins: cyclic peptides with endless potential. | θ-defensins, the only cyclic peptides of animal origin, have been isolated from the leukocytes of rhesus macaques and baboons. their biogenesis is unusual because each peptide is an 18-residue chimera formed by the head-to-tail splicing of nonapeptides derived from two separate precursors. θ-defensins have multiple arginines and a ladder-like tridisulfide array spanning their two antiparallel β-strands. human θ-defensin genes contain a premature stop codon that prevents effective translation of ... | 2012 | 22700960 |
| multiple approaches to investigate the transport and activity-dependent release of bdnf and their application in neurogenetic disorders. | studies utilizing genetic and pharmacological manipulations in rodent models and neuronal cultures have revealed myriad roles of brain-derived neurotrophic factor (bdnf). currently, this knowledge of bdnf function is being translated into improvement strategies for several debilitating neurological disorders in which bdnf abnormalities play a prominent role. common among the bdnf-related disorders are irregular trafficking and release of mature bdnf (mbdnf) and/or its prodomain predecessor, prob ... | 2012 | 22720171 |
| covalent protein modification with isg15 via a conserved cysteine in the hinge region. | the ubiquitin-like protein isg15 (interferon-stimulated gene of 15 kda) is strongly induced by type i interferons and displays antiviral activity. as other ubiquitin-like proteins (ubls), isg15 is post-translationally conjugated to substrate proteins by an isopeptide bond between the c-terminal glycine of isg15 and the side chains of lysine residues in the substrates (isgylation). isg15 consists of two ubiquitin-like domains that are separated by a hinge region. in many orthologs, this region co ... | 2012 | 22693631 |
| sumoylation and phosphorylation of gluk2 regulate kainate receptor trafficking and synaptic plasticity. | phosphorylation or sumoylation of the kainate receptor (kar) subunit gluk2 have both individually been shown to regulate kar surface expression. however, it is unknown whether phosphorylation and sumoylation of gluk2 are important for activity-dependent kar synaptic plasticity. we found that protein kinase c–mediated phosphorylation of gluk2 at serine 868 promotes gluk2 sumoylation at lysine 886 and that both of these events are necessary for the internalization of gluk2-containing kars that occ ... | 0 | 22522402 |
| epitope insertion at the n-terminal molecular switch of the rabbit hemorrhagic disease virus t = 3 capsid protein leads to larger t = 4 capsids. | viruses need only one or a few structural capsid proteins to build an infectious particle. this is possible through the extensive use of symmetry and the conformational polymorphism of the structural proteins. using virus-like particles (vlp) from rabbit hemorrhagic disease virus (rhdv) as a model, we addressed the basis of calicivirus capsid assembly and their application in vaccine design. the rhdv capsid is based on a t=3 lattice containing 180 identical subunits (vp1). we determined the stru ... | 2012 | 22491457 |
| effects of manipulating apoptosis on sindbis virus infection of aedes aegypti mosquitoes. | improved control of vector-borne diseases requires an understanding of the molecular factors that determine vector competence. apoptosis has been shown to play a role in defense against viruses in insects and mammals. although some observations suggest a correlation between apoptosis and resistance to arboviruses in mosquitoes, there is no direct evidence tying apoptosis to arbovirus vector competence. to determine whether apoptosis can influence arbovirus replication in mosquitoes, we manipulat ... | 2012 | 22438551 |
| insights into the roles of local translation from the axonal transcriptome. | much of our knowledge on the roles of intra-axonal translation derives from the characterization of a small number of individual mrnas that were found to be localized in axons. however, two recent studies, using large-scale approaches to provide a more comprehensive characterization of the axonal transcriptome, have led to the discovery of thousands of axonal mrnas. the apparent abundance of mrnas in axons raises the possibility that local translation has many more functions than previously thou ... | 0 | 22773949 |
| green tea polyphenol egcg sensing motif on the 67-kda laminin receptor. | we previously identified the 67-kda laminin receptor (67lr) as the cell-surface receptor conferring the major green tea polyphenol (-)-epigallocatechin-3-o-gallate (egcg) responsiveness to cancer cells. however, the underlying mechanism for interaction between egcg and 67lr remains unclear. in this study, we investigated the possible role of egcg-67lr interaction responsible for its bioactivities. | 2012 | 22666419 |
| inhibition and avoidance of mrna degradation by rna viruses. | the cellular mrna decay machinery plays a major role in regulating the quality and quantity of gene expression in cells. this machinery involves multiple enzymes and pathways that converge to promote the exonucleolytic decay of mrnas. the transcripts made by rna viruses are susceptible to degradation by this machinery and, in fact, can be actively targeted. thus, to maintain gene expression and replication, rna viruses have evolved a number of strategies to avoid and/or inactivate aspects of the ... | 2012 | 22626865 |
| the small hydrophobic protein of the human respiratory syncytial virus forms pentameric ion channels. | the small hydrophobic (sh) protein is encoded by the human respiratory syncytial virus. its absence leads to viral attenuation in the context of whole organisms, and it prevents apoptosis in infected cells. herein, we have examined the structure of sh protein in detergent micelles and in lipid bilayers, by solution nmr and attenuated total reflection-fourier transform infrared spectroscopy, respectively. we found that sh protein has a single α-helical transmembrane domain and forms homopentamers ... | 2012 | 22621926 |
| the contribution of rodent models to the pathological assessment of flaviviral infections of the central nervous system. | members of the genus flavivirus are responsible for a spectrum of important neurological syndromes in humans and animals. rodent models have been used extensively to model flavivirus neurological disease, to discover host-pathogen interactions that influence disease outcome, and as surrogates to determine the efficacy and safety of vaccines and therapeutics. in this review, we discuss the current understanding of flavivirus neuroinvasive disease and outline the host, viral and experimental facto ... | 2012 | 22592957 |
| s-scam/magi-2 is an essential synaptic scaffolding molecule for the glua2-containing maintenance pool of ampa receptors. | synaptic plasticity, the cellular basis of learning and memory, involves the dynamic trafficking of ampa receptors (ampars) into and out of synapses. one of the remaining key unanswered aspects of ampar trafficking is the mechanism by which synaptic strength is preserved despite protein turnover. in particular, the identity of ampar scaffolding molecule(s) involved in the maintenance of glua2-containing ampars is completely unknown. here we report that the synaptic scaffolding molecule (s-scam; ... | 0 | 22593065 |
| multiple interferon stimulated genes synergize with the zinc finger antiviral protein to mediate anti-alphavirus activity. | the zinc finger antiviral protein (zap) is a host factor that mediates inhibition of viruses in the filoviridae, retroviridae and togaviridae families. we previously demonstrated that zap blocks replication of sindbis virus (sinv), the prototype alphavirus in the togaviridae family at an early step prior to translation of the incoming genome and that synergy between zap and one or more interferon stimulated genes (isgs) resulted in maximal inhibitory activity. the present study aimed to identify ... | 2012 | 22615998 |
| pd-1/pd-l1 blockade can enhance hiv-1 gag-specific t cell immunity elicited by dendritic cell-directed lentiviral vaccines. | exhaustion of cd8(+) t cells and upregulation of programmed death 1 (pd-1), a negative regulator of t cell activation, are characteristic features of individuals chronically infected with human immunodeficiency virus type 1. in a previous study, we showed in mice that a dendritic cell-directed lentiviral vector (dclv) system encoding the human immunodeficiency virus (hiv)-1 gag protein was an efficient vaccine modality to induce a durable gag-specific t cell immune response. in this study, we de ... | 2012 | 22588271 |
| beneficial effects of fucoidan in patients with chronic hepatitis c virus infection. | to evaluate the effects of fucoidan, a complex sulfated polysaccharide extract from marine seaweed, on hepatitis c virus (hcv) rna load both in vitro and in vivo. | 0 | 22611316 |
| homeostatic synaptic scaling is regulated by protein sumoylation. | homeostatic scaling allows neurons to alter synaptic transmission to compensate for changes in network activity. here, we show that suppression of network activity with tetrodotoxin, which increases surface expression of ampa receptors (ampars), dramatically reduces levels of the desumoylating (where sumo is small ubiquitin-like modifier) enzyme senp1, leading to a consequent increase in protein sumoylation. overexpression of the catalytic domain of senp1 prevents this scaling effect, and we ide ... | 2012 | 22582390 |
| cross-protective immunity against o'nyong-nyong virus afforded by a novel recombinant chikungunya vaccine. | emerging mosquito-borne alphavirus infections caused by chikungunya virus (chikv) or o'nyong-nyong virus (onnv) are responsible for sporadic and sometimes explosive urban outbreaks. currently, there is no licensed vaccine against either virus. we have developed a highly attenuated recombinant chikv candidate vaccine (chikv/ires) that in preclinical studies was demonstrated to be safe, immunogenic and efficacious. in this study we investigated the potential of this vaccine to induce cross-protect ... | 2012 | 22583812 |
| chikungunya virus-induced autophagy delays caspase-dependent cell death. | autophagy is an important survival pathway and can participate in the host response to infection. studying chikungunya virus (chikv), the causative agent of a major epidemic in india, southeast asia, and southern europe, we reveal a novel mechanism by which autophagy limits cell death and mortality after infection. we use biochemical studies and single cell multispectral assays to demonstrate that direct infection triggers both apoptosis and autophagy. chikv-induced autophagy is mediated by the ... | 2012 | 22508836 |
| complexity of the microglial activation pathways that drive innate host responses during lethal alphavirus encephalitis in mice. | microglia express multiple tlrs (toll-like receptors) and provide important host defence against viruses that invade the cns (central nervous system). although prior studies show these cells become activated during experimental alphavirus encephalitis in mice to generate cytokines and chemokines that influence virus replication, tissue inflammation and neuronal survival, the specific prrs (pattern recognition receptors) and signalling intermediates controlling microglial activation in this setti ... | 2012 | 22471445 |
| temperature-sensitive mutants and revertants in the coronavirus nonstructural protein 5 protease (3clpro) define residues involved in long-distance communication and regulation of protease activity. | positive-strand rna virus genomes are translated into polyproteins that are processed by viral proteases to yield functional intermediate and mature proteins. coronaviruses (covs) carry genes that encode an nsp5 protease (also known as 3clpro or mpro) responsible for 11 maturation cleavages. the nsp5 structure contains two chymotrypsin-like domains (d1 and d2) and a unique domain (d3), and forms functional dimers. however, little is known of interactions or communication across the structure of ... | 2012 | 22345451 |
| genetic divergence of rotavirus nonstructural protein 4 results in distinct serogroup-specific viroporin activity and intracellular punctate structure morphologies. | nonstructural protein 4 (nsp4) viroporin activity is critical for the replication and assembly of serogroup a rotavirus (rva); however, the dramatic primary sequence divergence of nsp4s across serogroups raises the possibility that viroporin activity is not a common feature among rvs. we tested for nsp4 viroporin activity from divergent strains, including rva (ec and ty-1), rvb (idir), and rvc (cowden). canonical viroporin motifs were identified in rva, rvb, and rvc nsp4s, but the arrangement of ... | 2012 | 22357281 |
| translational control of the activation of transcription factor nf-κb and production of type i interferon by phosphorylation of the translation factor eif4e. | type i interferon is an integral component of the antiviral response, and its production is tightly controlled at the levels of transcription and translation. the eukaryotic translation-initiation factor eif4e is a rate-limiting factor whose activity is regulated by phosphorylation of ser209. here we found that mice and fibroblasts in which eif4e cannot be phosphorylated were less susceptible to virus infection. more production of type i interferon, resulting from less translation of nfkbia mrna ... | 2012 | 22544393 |
| a novel small molecule inhibitor of influenza a viruses that targets polymerase function and indirectly induces interferon. | influenza viruses continue to pose a major public health threat worldwide and options for antiviral therapy are limited by the emergence of drug-resistant virus strains. the antiviral cytokine, interferon (ifn) is an essential mediator of the innate immune response and influenza viruses, like many viruses, have evolved strategies to evade this response, resulting in increased replication and enhanced pathogenicity. a cell-based assay that monitors ifn production was developed and applied in a hi ... | 2012 | 22577360 |
| avian influenza rapidly induces antiviral genes in duck lung and intestine. | ducks are the natural reservoir of influenza a and survive infection by most strains. to characterize the duck immune response to influenza, we sought to identify innate immune genes expressed early in an infection. we used suppressive subtractive hybridization (ssh) to construct 3 libraries enriched in differentially expressed genes from lung rna of a duck infected with highly pathogenic avian influenza virus a/vietnam/1203/04 (h5n1), or lung and intestine rna of a duck infected with low pathog ... | 2012 | 22534314 |
| specific targeting of human interleukin (il)-13 receptor α2-positive cells with lentiviral vectors displaying il-13. | the ability to selectively and efficiently target transgene delivery to specific cell types in vitro and in vivo remains one of the formidable challenges in gene therapy. lentiviral vectors have several advantages that make them attractive as gene delivery vehicles and their tropism can be altered through pseudotyping, allowing transgene delivery to specific populations of cells. the human interleukin-13 receptor α2 (il-13rα2) is uniquely overexpressed in many different human tumors, making it a ... | 2012 | 22612657 |
| antibody-directed lentiviral gene transduction for live-cell monitoring and selection of human ips and hes cells. | the identification of stem cells within a mixed population of cells is a major hurdle for stem cell biology--in particular, in the identification of induced pluripotent stem (ips) cells during the reprogramming process. based on the selective expression of stem cell surface markers, a method to specifically infect stem cells through antibody-conjugated lentiviral particles has been developed that can deliver both visual markers for live-cell imaging as well as selectable markers to enrich for ip ... | 2012 | 22536330 |
| phosphorylation of rpt6 regulates synaptic strength in hippocampal neurons. | it has become increasingly evident that protein degradation via the ubiquitin proteasome system plays a fundamental role in the development, maintenance and remodeling of synaptic connections in the cns. we and others have recently described the activity-dependent regulation of proteasome activity and recruitment of proteasomes into spine compartments involving the phosphorylation of the 19s atpase subunit, rpt6, by the plasticity kinase ca(2+)/calmodulin-dependent protein kinase ii α (camkiiα) ... | 0 | 22496558 |
| the n-end rule pathway. | the n-end rule pathway is a proteolytic system in which n-terminal residues of short-lived proteins are recognized by recognition components (n-recognins) as essential components of degrons, called n-degrons. known n-recognins in eukaryotes mediate protein ubiquitylation and selective proteolysis by the 26s proteasome. substrates of n-recognins can be generated when normally embedded destabilizing residues are exposed at the n terminus by proteolytic cleavage. n-degrons can also be generated thr ... | 2012 | 22524314 |
| usp18 promotes conventional cd11b+ dendritic cell development. | dendritic cells (dcs) represent the key cells linking innate and adaptive immune responses. it is critical to understand the molecular factors regulating dc differentiation. usp18 is an ifn-inducible member of the ubiquitin-specific protease family, which deconjugates ubiquitin-like modifier isg15 from target proteins and competitively inhibits ifn-α/β-induced jak/stat activation. this study demonstrates that the frequency of conventional cd11b(+) dcs in the spleen of usp18(-/-) mice was signifi ... | 2012 | 22491252 |
| histone h3 lysine 9 di-methylation as an epigenetic signature of the interferon response. | effective antiviral immunity depends on the ability of infected cells or cells triggered with virus-derived nucleic acids to produce type i interferon (ifn), which activates transcription of numerous antiviral genes. however, disproportionately strong or chronic ifn expression is a common cause of inflammatory and autoimmune diseases. we describe an epigenetic mechanism that determines cell type-specific differences in ifn and ifn-stimulated gene (isg) expression in response to exogenous signals ... | 2012 | 22412156 |
| theranostic potential of oncolytic vaccinia virus. | biological cancer therapies, such as oncolytic, or replication-selective viruses have advantages over traditional therapeutics as they can employ multiple different mechanisms to target and destroy cancers (including direct cell lysis, immune activation and vascular collapse). this has led to their rapid recent clinical development. however this also makes their pre-clinical and clinical study complex, as many parameters may affect their therapeutic potential and so defining reason for treatment ... | 2012 | 22509200 |
| autophagy and mechanisms of effective immunity. | macroautophagy (autophagy) is a cellular pathway facilitating several critical functions. first, autophagy is a major pathway of degradation. it enables elimination of microbes that have invaded intracellular compartments. in addition, it promotes degradation of damaged cellular content, thereby acting to limit inflammatory signals. second, autophagy is a major trafficking pathway, shuttling content between the cytosol and the lysosomal compartment. given these two key roles, autophagy can have ... | 2012 | 22566941 |
| modulation of gsk-3β activity in venezuelan equine encephalitis virus infection. | alphaviruses, including venezuelan equine encephalitis virus (veev), cause disease in both equine and humans that exhibit overt encephalitis in a significant percentage of cases. features of the host immune response and tissue-specific responses may contribute to fatal outcomes as well as the development of encephalitis. it has previously been shown that veev infection of mice induces transcription of pro-inflammatory cytokines genes (e.g., ifn-γ, il-6, il-12, inos and tnf-α) within 6 h. gsk-3β ... | 2012 | 22496857 |
| novel inhibitors of neurotropic alphavirus replication that improve host survival in a mouse model of acute viral encephalitis. | arboviral encephalitis is a potentially devastating human disease with no approved therapies that target virus replication. we previously discovered a novel class of thieno[3,2-b]pyrrole-based inhibitors active against neurotropic alphaviruses such as western equine encephalitis virus (weev) in cultured cells. in this report, we describe initial development of these novel antiviral compounds, including bioisosteric replacement of the 4h-thieno[3,2-b]pyrrole core with indole to improve metabolic ... | 2012 | 22428985 |
| the immunology of neurodegeneration. | while immune responses in neurodegeneration were regarded as little more than a curiosity a decade ago, they are now increasingly moving toward center stage. factors driving this movement include the recognition that most of the relevant immune molecules are produced within the brain, that microglia are proficient immune cells shaping neuronal circuitry and fate, and that systemic immune responses affect brain function. we will review this complex field from the perspective of neurons, extra-neu ... | 2012 | 22466657 |
| cell death pathways and autophagy in the central nervous system and its involvement in neurodegeneration, immunity and central nervous system infection: to die or not to die--that is the question. | death rules our lives. in this short paper, we summarize new insights into molecular mechanisms of neurodegeneration. here we review the most important processes of cell death: apoptosis and oncosis. we focus on autophagy, which is pivotal for neuronal homeostasis, in the context of neurodegeneration, infection and immunity. its dysfunction has been linked to several neurodegenerative diseases such as parkinson's, huntington's and alzheimer's diseases. our understanding is still incomplete, but ... | 0 | 22385237 |
| nonstructural protein 2 of porcine reproductive and respiratory syndrome virus inhibits the antiviral function of interferon-stimulated gene 15. | type i interferon (alpha/beta interferon [ifn-α/β]) stimulates the expression of interferon-stimulated gene 15 (isg15), which encodes a ubiquitin-like protein, isg15. free isg15 and isg15 conjugates function in diverse cellular pathways, particularly regulation of antiviral innate immune responses. in this study, we demonstrate that isg15 overexpression inhibits porcine reproductive and respiratory syndrome virus (prrsv) replication in cell culture and that the antiviral activity of interferon i ... | 2012 | 22258253 |
| sindbis virus infectivity improves during the course of infection in both mammalian and mosquito cells. | alphaviruses are enveloped, single-stranded positive sense rna viruses that are transmitted by an arthropod vector to a wide host range, including avian and mammalian species. arthropods and vertebrates have different cellular environments and this may cause the different cellular pathologies that are observed between the invertebrate vector and vertebrate hosts in both whole organisms and cultured cell lines. in this report, we used sindbis virus and examined mosquito and mammalian cell lines f ... | 2012 | 22484152 |
| atm kinase is activated by sindbis viral vector infection. | sindbis virus is a prototypic member of the alphavirus genus, togaviridae family. sindbis replication results in cellular cytotoxicity, a feature that has been exploited by our laboratory for treatment of in vivo tumors. understanding the interactions between sindbis vectors and the host cell can lead to better virus production and increased efficacy of gene therapy vectors. here we present studies investigating a possible cellular response to genotoxic effects of sindbis vector infection. the a ... | 2012 | 22475743 |
| virus recognition by toll-7 activates antiviral autophagy in drosophila. | innate immunity is highly conserved and relies on pattern recognition receptors (prrs) such as toll-like receptors (identified through their homology to drosophila toll) for pathogen recognition. although drosophila toll is vital for immune recognition and defense, roles for the other eight drosophila tolls in immunity have remained elusive. here we have shown that toll-7 is a prr both in vitro and in adult flies; loss of toll-7 led to increased vesicular stomatitis virus (vsv) replication and m ... | 2012 | 22464169 |
| dengue virus infection of the aedes aegypti salivary gland and chemosensory apparatus induces genes that modulate infection and blood-feeding behavior. | the female aedes aegypti salivary gland plays a pivotal role in bloodmeal acquisition and reproduction, and thereby dengue virus (denv) transmission. it produces numerous immune factors, as well as immune-modulatory, vasodilatory, and anti-coagulant molecules that facilitate blood-feeding. to assess the impact of denv infection on salivary gland physiology and function, we performed a comparative genome-wide microarray analysis of the naïve and denv infection-responsive a. aegypti salivary gland ... | 2012 | 22479185 |
| sindbis virus induces the production of a novel class of endogenous sirnas in aedes aegypti mosquitoes. | small rna regulatory pathways are used to control the activity of transposons, regulate gene expression and resist infecting viruses. we examined the biogenesis of mrna-derived endogenous short-interfering rnas (endo-sirnas) in the disease vector mosquito aedes aegypti. under standard conditions, mrna-derived endo-sirnas were produced from the bidirectional transcription of tail-tail overlapping gene pairs. upon infection with the alphavirus, sindbis virus (sinv), another class of mrna-derived e ... | 2012 | 22458920 |
| a proteome map of primary cultured rat schwann cells. | schwann cells (scs) are the principal glial cells of the peripheral nervous system with a wide range of biological functions. scs play a key role in peripheral nerve regeneration and are involved in several hereditary peripheral neuropathies. the objective of this study was to gain new insight into the whole protein composition of scs. | 2012 | 22443529 |
| aggrephagy: selective disposal of protein aggregates by macroautophagy. | protein aggregation is a continuous process in our cells. some proteins aggregate in a regulated manner required for different vital functional processes in the cells whereas other protein aggregates result from misfolding caused by various stressors. the decision to form an aggregate is largely made by chaperones and chaperone-assisted proteins. proteins that are damaged beyond repair are degraded either by the proteasome or by the lysosome via autophagy. the aggregates can be degraded by the p ... | 2012 | 22518139 |
| dengue virus infection perturbs lipid homeostasis in infected mosquito cells. | dengue virus causes ∼50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. during its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. this phenomenon is observed both in human and vector-derived cells. using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus ... | 2012 | 22457619 |
| two-photon scanning microscopy of in vivo sensory responses of cortical neurons genetically encoded with a fluorescent voltage sensor in rat. | a fluorescent voltage sensor protein "flare" was created from a kv1.4 potassium channel with yfp situated to report voltage-induced conformational changes in vivo. the rna virus sindbis introduced flare into neurons in the binocular region of visual cortex in rat. injection sites were selected based on intrinsic optical imaging. expression of flare occurred in the cell bodies and dendritic processes. neurons imaged in vivo using two-photon scanning microscopy typically revealed the soma best, di ... | 2012 | 22461770 |
| neuromuscular manifestations of west nile virus infection. | the most common neuromuscular manifestation of west nile virus (wnv) infection is a poliomyelitis syndrome with asymmetric paralysis variably involving one (monoparesis) to four limbs (quadriparesis), with or without brainstem involvement and respiratory failure. this syndrome of acute flaccid paralysis may occur without overt fever or meningoencephalitis. although involvement of anterior horn cells in the spinal cord and motor neurons in the brainstem are the major sites of pathology responsibl ... | 2012 | 22461779 |
| transmission dynamics of an insect-specific flavivirus in a naturally infected culex pipiens laboratory colony and effects of co-infection on vector competence for west nile virus. | we established a laboratory colony of culex pipiens mosquitoes from eggs collected in colorado and discovered that mosquitoes in the colony are naturally infected with culex flavivirus (cxfv), an insect-specific flavivirus. in this study we examined transmission dynamics of cxfv and effects of persistent cxfv infection on vector competence for west nile virus (wnv). we found that vertical transmission is the primary mechanism for persistence of cxfv in cx. pipiens, with venereal transmission pot ... | 2012 | 22425062 |
| anopheles gambiae antiviral immune response to systemic o'nyong-nyong infection. | mosquito-borne viral diseases cause significant burden in much of the developing world. although host-virus interactions have been studied extensively in the vertebrate host, little is known about mosquito responses to viral infection. in contrast to mosquitoes of the aedes and culex genera, anopheles gambiae, the principal vector of human malaria, naturally transmits very few arboviruses, the most important of which is o'nyong-nyong virus (onnv). here we have investigated the a. gambiae immune ... | 2012 | 22428080 |
| synthesis and biological evaluation of a series of thieno-expanded tricyclic purine 2'-deoxy nucleoside analogues. | introducing structural diversity into the nucleoside scaffold for use as potential chemotherapeutics has long been considered an important approach to drug design. in that regard, we have designed and synthesized a number of innovative 2'-deoxy expanded nucleosides where a heteroaromatic thiophene spacer ring has been inserted in between the imidazole and pyrimidine ring systems of the natural purine scaffold. the synthetic efforts towards realizing the expanded 2'-deoxy-guanosine and -adenosine ... | 2012 | 22464686 |
| self-assembly of viral capsid protein and rna molecules of different sizes: requirement for a specific high protein/rna mass ratio. | virus-like particles can be formed by self-assembly of capsid protein (cp) with rna molecules of increasing length. if the protein "insisted" on a single radius of curvature, the capsids would be identical in size, independent of rna length. however, there would be a limit to length of the rna, and one would not expect rna much shorter than native viral rna to be packaged unless multiple copies were packaged. on the other hand, if the protein did not favor predetermined capsid size, one would ex ... | 2011 | 22205731 |
| cellular pharmacology of protein kinase mζ (pkmζ) contrasts with its in vitro profile: implications for pkmζ as a mediator of memory. | a number of recent studies have used pharmacological inhibitors to establish a role for protein kinase mζ (pkmζ) in synaptic plasticity and memory. these studies use zeta inhibitory peptide (zip) and chelerythrine as inhibitors of pkmζ to block long term potentiation and memory; staurosporine is used as a negative control to show that a nonspecific kinase inhibitor does not block long term potentiation and memory. here, we show that neither zip nor chelerythrine inhibits pkmζ in cultured cells o ... | 2012 | 22378786 |
| lateral diffusion and exocytosis of membrane proteins in cultured neurons assessed using fluorescence recovery and fluorescence-loss photobleaching. | membrane proteins such as receptors and ion channels undergo active trafficking in neurons, which are highly polarised and morphologically complex. this directed trafficking is of fundamental importance to deliver, maintain or remove synaptic proteins. super-ecliptic phluorin (sep) is a ph-sensitive derivative of egfp that has been extensively used for live cell imaging of plasma membrane proteins(1-2). at low ph, protonation of sep decreases photon absorption and eliminates fluorescence emissio ... | 2012 | 22395448 |
| virus maturation. | we examine virus maturation of selected nonenveloped and enveloped single-stranded rna viruses, retroviruses, bacteriophages, and herpesviruses. processes associated with maturation in the rna viruses range from subtle (nodaviruses and picornaviruses) to dramatic (tetraviruses and togaviruses). the elaborate assembly and maturation pathway of hiv is discussed in contrast to the less sophisticated but highly efficient processes associated with togaviruses. bacteriophage assembly and maturation ar ... | 2012 | 22404678 |
| the role of bcl-2 family proteins in therapy responses of malignant astrocytic gliomas: bcl2l12 and beyond. | glioblastoma (gbm) is a highly aggressive and lethal brain cancer with a median survival of less than two years after diagnosis. hallmarks of gbm tumors include soaring proliferative indices, high levels of angiogenesis, diffuse invasion into normal brain parenchyma, resistance toward therapy-induced apoptosis, and pseudopallisading necrosis. despite the recent advances in neurosurgery, radiation therapy, and the development of targeted chemotherapeutic regimes, gbm remains one of the deadliest ... | 2012 | 22431925 |
| palmitoylation by dhhc5/8 targets grip1 to dendritic endosomes to regulate ampa-r trafficking. | palmitoylation, a key regulatory mechanism controlling protein targeting, is catalyzed by dhhc-family palmitoyl acyltransferases (pats). impaired pat activity is linked to neurodevelopmental and neuropsychiatric disorders, suggesting critical roles for palmitoylation in neuronal function. however, few substrates for specific pats are known, and functional consequences of palmitoylation events are frequently uncharacterized. here, we identify the closely related pats dhhc5 and dhhc8 as specific r ... | 0 | 22325201 |
| crystallography, evolution, and the structure of viruses. | my undergraduate education in mathematics and physics was a good grounding for graduate studies in crystallographic studies of small organic molecules. as a postdoctoral fellow in minnesota, i learned how to program an early electronic computer for crystallographic calculations. i then joined max perutz, excited to use my skills in the determination of the first protein structures. the results were even more fascinating than the development of techniques and provided inspiration for starting my ... | 2012 | 22318719 |
| protein phosphatase 1 subunit ppp1r15a/gadd34 regulates cytokine production in polyinosinic:polycytidylic acid-stimulated dendritic cells. | in response to inflammatory stimulation, dendritic cells (dcs) have a remarkable pattern of differentiation that exhibits specific mechanisms to control the immune response. here we show that in response to polyriboinosinic:polyribocytidylic acid (pi:c), dcs mount a specific integrated stress response during which the transcription factor atf4 and the growth arrest and dna damage-inducible protein 34 (gadd34/ppp1r15a), a phosphatase 1 (pp1) cofactor, are expressed. in agreement with increased ga ... | 2012 | 22315398 |
| a tlr4 agonist synergizes with dendritic cell-directed lentiviral vectors for inducing antigen-specific immune responses. | tlr4 agonists can be used as adjuvants to trigger innate immune responses of antigen-presenting cells (apcs) such as dendritic cells (dcs) to enhance vaccine-specific immunity. adjuvant effects of tlr4 agonists are mediated by downstream signaling controlled by both myd88 and trif adapter proteins. in this study, we investigated the adjuvanting capacity of glucopyranosyl lipid a (gla), a chemically synthesized tlr4 agonist, to boost antigen-specific immunity elicited by dc-directed lentiviral ve ... | 2012 | 22314134 |
| risk for emergence of dengue and chikungunya virus in israel. | | 0 | 22305194 |
| reprogramming axonal behavior by axon-specific viral transduction. | the treatment of axonal disorders, such as diseases associated with axonal injury and degeneration, is limited by the inability to directly target therapeutic protein expression to injured axons. current gene therapy approaches rely on infection and transcription of viral genes in the cell body. here, we describe an approach to target gene expression selectively to axons. using a genetically engineered mouse containing epitope-labeled ribosomes, we find that neurons in adult animals contain ribo ... | 2012 | 22278412 |
| arbovirus-derived pirnas exhibit a ping-pong signature in mosquito cells. | the sirna pathway is an essential antiviral mechanism in insects. whether other rna interference pathways are involved in antiviral defense remains unclear. here, we report in cells derived from the two main vectors for arboviruses, aedes albopictus and aedes aegypti, the production of viral small rnas that exhibit the hallmarks of ping-pong derived piwi-associated rnas (pirnas) after infection with positive or negative sense rna viruses. furthermore, these cells produce endogenous pirnas that m ... | 2012 | 22292064 |
| otub1 overexpression in mesangial cells is a novel regulator in the pathogenesis of glomerulonephritis through the decrease of dcn level. | otub1 is a member of otus (ovarian-tumor-domain-containing proteases), a deubiquitinating enzymes family (dubs), which was shown as a proteasome-associated dub to be involved in the proteins ub-dependent degradation. it has been reported that otub1 was expressed in kidney tissue. but its concrete cellular location and function in the kidney remain unclear. decorin (dcn) in mesangial cells (mc) is considered to be a potentially important factor for antagonizing glomerulonephritides, and its degra ... | 2012 | 22279542 |
| expression of the c-type lectins dc-sign or l-sign alters host cell susceptibility for the avian coronavirus, infectious bronchitis virus. | infectious bronchitis virus (ibv), an avian coronavirus, is a cause of great economic loss in the poultry industry. the virus mainly infects respiratory epithelium, but can be also detected in other organs. the functional receptor for the virus has not been found and field strains of ibv do not infect conventional cell lines. recently, it has been shown that the c-type lectins dc-sign/l-sign can promote entry of several coronaviruses. here we examine whether dc-sign/l-sign are entry determinants ... | 2012 | 22340967 |
| viral polymerases. | viral polymerases play a central role in viral genome replication and transcription. based on the genome type and the specific needs of particular virus, rna-dependent rna polymerase, rna-dependent dna polymerase, dna-dependent rna polymerase, and dna-dependent rna polymerases are found in various viruses. viral polymerases are generally active as a single protein capable of carrying out multiple functions related to viral genome synthesis. specifically, viral polymerases use variety of mechanis ... | 0 | 22297518 |
| hur function in disease. | the cytoplasmic events that control mammalian gene expression, primarily mrna stability and translation, potently influence the cellular response to internal and external signals. the ubiquitous rna-binding protein (rbp) hur is one of the best-studied regulators of cytoplasmic mrna fate. through its post-transcriptional influence on specific target mrnas, hur can alter the cellular response to proliferative, stress, apoptotic, differentiation, senescence, inflammatory and immune stimuli. in ligh ... | 2012 | 22201738 |
| principles of virus structural organization. | viruses, the molecular nanomachines infecting hosts ranging from prokaryotes to eukaryotes, come in different sizes, shapes, and symmetries. questions such as what principles govern their structural organization, what factors guide their assembly, how these viruses integrate multifarious functions into one unique structure have enamored researchers for years. in the last five decades, following caspar and klug's elegant conceptualization of how viruses are constructed, high-resolution structural ... | 0 | 22297509 |
| oncolytic virus therapy for glioblastoma multiforme: concepts and candidates. | twenty years of oncolytic virus development have created a field that is driven by the potential promise of lasting impact on our cancer treatment repertoire. with the field constantly expanding-more than 20 viruses have been recognized as potential oncolytic viruses-new virus candidates continue to emerge even as established viruses reach clinical trials. they all share the defining commonalities of selective replication in tumors, subsequent tumor cell lysis, and dispersion within the tumor. m ... | 0 | 22290260 |
| a virological view of innate immune recognition. | the innate immune system uses multiple strategies to detect viral infections. because all viruses rely on host cells for their synthesis and propagation, the molecular features used to detect viral infections must be unique to viruses and absent from host cells. research in the past decade has advanced our understanding of various cell-intrinsic and cell-extrinsic modes of virus recognition. this review examines the innate recognition from the point of view of virus invasion and replication stra ... | 0 | 22994491 |
| clonal propagation of phyllanthus amarus: a hepatoprotector. | the micropropagation protocol for phyllanthus amarus, an important medicinal herb used widely for the treatment of hepatitis in ethnomedicinal systems, was standardized with shoot tip and single node explants. | 0 | 22438668 |
| pkmζ is necessary and sufficient for synaptic clustering of psd-95. | the persistent activity of protein kinase mzeta (pkmζ), a brain-specific, constitutively active protein kinase c isoform, maintains synaptic long-term potentiation (ltp). structural remodeling of the postsynaptic density is believed to contribute to the expression of ltp. we therefore examined the role of pkmζ in reconfiguring psd-95, the major postsynaptic scaffolding protein at excitatory synapses. in primary cultures of hippocampal neurons, pkmζ activity was critical for increasing the size o ... | 2011 | 22378468 |
| the mosquito aedes aegypti has a large genome size and high transposable element load but contains a low proportion of transposon-specific pirnas. | the pirna pathway has been shown in model organisms to be involved in silencing of transposons thereby providing genome stability. in d. melanogaster the majority of pirnas map to these sequences. the medically important mosquito species aedes aegypti has a large genome size, a high transposon load which includes miniature inverted repeat transposable elements (mites) and an expansion of the pirna biogenesis genes. studies of transgenic lines of ae. aegypti have indicated that introduced transpo ... | 2011 | 22171608 |
| deciphering the multifaceted relationship between oncolytic viruses and natural killer cells. | despite active research in virotherapy, this apparently safe modality has not achieved widespread success. the immune response to viral infection appears to be an essential factor that determines the efficacy of oncolytic viral therapy. the challenge is determining whether the viral-elicited immune response is a hindrance or a tool for viral treatment. nk cells are a key component of innate immunity that mediates antiviral immunity while also coordinating tumor clearance. various reports have su ... | 2011 | 22312364 |
| recent insights into the involvement of progranulin in frontotemporal dementia. | progranulin is a widely expressed protein that is involved in the regulation of multiple biological processes, including embryogenesis, host defense, and wound repair. in the central nervous system, progranulin is constitutively expressed at modest levels in neurons and microglia, but shows dramatic microglial immunoreactivity in degenerative diseases that exhibit prominent neuroinflammation. in addition to the role that pgrn plays in the periphery, its expression is of critical importance in br ... | 0 | 22654721 |
| virus-derived sirnas and pirnas in immunity and pathogenesis. | cellular organisms have evolved related pathways for the biogenesis and function of small interfering rnas (sirnas), micrornas and piwi-interacting rnas (pirnas). these distinct classes of small rnas guide specific gene silencing at both transcriptional and posttranscriptional levels by serving as specificity determinants. small rnas of virus and host origins have been found to modulate virus–host interactions by rna interference (rnai), leading to antiviral immunity or viral pathogenesis. deep ... | 0 | 22180767 |
| rna-based immunity terminates viral infection in adult drosophila in the absence of viral suppression of rna interference: characterization of viral small interfering rna populations in wild-type and mutant flies. | replication of viral rna genomes in fruit flies and mosquitoes induces the production of virus-derived small interfering rnas (sirnas) to specifically reduce virus accumulation by rna interference (rnai). however, it is unknown whether the rna-based antiviral immunity (rvi) is sufficiently potent to terminate infection in adult insects as occurs in cell culture. we show here that, in contrast to robust infection by flock house virus (fhv), infection with an fhv mutant (fhvδb2) unable to express ... | 2011 | 21957285 |
| stress granules in the viral replication cycle. | as intracellular parasites, viruses require a host cell in order to replicate. however, they face a series of cellular responses against infection. one of these responses is the activation of the double-stranded rna (dsrna)-activated protein kinase r (pkr). pkr phosphorylates the α subunit of eukaryotic translation initiation factor 2 (eif2α), which in turn results in global protein synthesis inhibition and formation of stress granules (sgs). recent studies have shown that sgs can interfere with ... | 2011 | 22163347 |
| positive reinforcement for viruses. | virus-cell membrane fusion requires a critical transition from positive to negative membrane curvature. st. vincent et al. (2010), in pnas, designed a class of antivirals that targets this transition. these rigid amphipathic fusion inhibitors are active against an array of enveloped viruses. | 0 | 21035726 |
| death, autoantigen modifications, and tolerance. | autoantibodies present in the serum of patients with a variety of inflammatory diseases have proven useful as diagnostic markers and as probes with which to elucidate biochemical and signaling pathways. the mechanisms governing the generation of autoantibodies remain elusive, constituting a critical missing link in our understanding of rheumatologic illnesses. several lines of experimentation in recent years have strongly implicated events surrounding cell death in this process. this review will ... | 2000 | 11094420 |
| modulation of nucleotide sensitivity of atp-sensitive potassium channels by phosphatidylinositol-4-phosphate 5-kinase. | atp-sensitive potassium channels (k(atp) channels) regulate cell excitability in response to metabolic changes. k(atp) channels are formed as a complex of a sulfonylurea receptor (surx), a member of the atp-binding cassette protein family, and an inward rectifier k(+) channel subunit (kir6.x). membrane phospholipids, in particular phosphatidylinositol (pi) 4,5-bisphosphate (pip(2)), activate k(atp) channels and antagonize atp inhibition of k(atp) channels when applied to inside-out membrane patc ... | 0 | 10639183 |
| arf6 is required for growth factor- and rac-mediated membrane ruffling in macrophages at a stage distal to rac membrane targeting. | activation of rac1, a member of the rho family of gtpases, is associated with multiple cellular responses, including membrane ruffling and focal complex formation. the mechanisms by which rac1 is coupled to these functional responses are not well understood. it was recently shown that arf6, a gtpase implicated in cytoskeletal alterations and a membrane recycling pathway, is required for rac1-dependent phagocytosis in macrophages (q. zhang et al., j. biol. chem. 273:19977-19981, 1998). to determi ... | 0 | 10567541 |
| a visual screen of a gfp-fusion library identifies a new type of nuclear envelope membrane protein. | the nuclear envelope (ne) is a distinct subdomain of the er, but few membrane components have been described that are specific to it. we performed a visual screen in tissue culture cells to identify proteins targeted to the ne. this approach does not require assumptions about the nature of the association with the ne or the physical separation of ne and er. we confirmed that screening a library of fusions to the green fluorescent protein can be used to identify proteins targeted to various subco ... | 0 | 10402458 |
| mechanisms of arthropod transmission of plant and animal viruses. | a majority of the plant-infecting viruses and many of the animal-infecting viruses are dependent upon arthropod vectors for transmission between hosts and/or as alternative hosts. the viruses have evolved specific associations with their vectors, and we are beginning to understand the underlying mechanisms that regulate the virus transmission process. a majority of plant viruses are carried on the cuticle lining of a vector's mouthparts or foregut. this initially appeared to be simple mechanical ... | 0 | 10066833 |
| does nitric oxide play a critical role in viral infections? | | 0 | 9573217 |
| translational readthrough in the hdc mrna generates a novel branching inhibitor in the drosophila trachea. | a central question in the development of many branched tubular organs, including the drosophila trachea, concerns the mechanisms and molecules that control the number and pattern of new branches arising from preexisting vessels. we report on a branching inhibitor, fusion-6 (fus-6) produced by specialized tracheal cells to prevent neighboring cells from branching. in fus-6 mutants, cells that are normally quiescent acquire the branching fate and form an increased number of sprouts emanating from ... | 0 | 9531534 |
| arf6 targets recycling vesicles to the plasma membrane: insights from an ultrastructural investigation. | we have shown previously that the adp-ribosylation factor (arf)-6 gtpase localizes to the plasma membrane and intracellular endosomal compartments. expression of arf6 mutants perturbs endosomal trafficking and the morphology of the peripheral membrane system. however, another study on the distribution of arf6 in subcellular fractions of chinese hamster ovary (cho) cells suggested that arf6 did not localize to endosomes labeled after 10 min of horseradish peroxidase (hrp) uptake, but instead was ... | 0 | 9456320 |
| agonist-induced pkc phosphorylation regulates gluk2 sumoylation and kainate receptor endocytosis. | the surface expression and regulated endocytosis of kainate (ka) receptors (kars) plays a critical role in neuronal function. pkc can modulate kar trafficking, but the sites of action and molecular consequences have not been fully characterized. small ubiquitin-like modifier (sumo) modification of the kar subunit gluk2 mediates agonist-evoked internalization, but how kar activation leads to gluk2 sumoylation is unclear. here we show that ka stimulation causes rapid phosphorylation of gluk2 by pk ... | 2011 | 22089239 |