| next-generation optical technologies for illuminating genetically targeted brain circuits. | emerging technologies from optics, genetics, and bioengineering are being combined for studies of intact neural circuits. the rapid progression of such interdisciplinary "optogenetic" approaches has expanded capabilities for optical imaging and genetic targeting of specific cell types. here we explore key recent advances that unite optical and genetic approaches, focusing on promising techniques that either allow novel studies of neural dynamics and behavior or provide fresh perspectives on clas ... | 0 | 17035522 |
| structure determination of clathrin coats to subnanometer resolution by single particle cryo-electron microscopy. | clathrin triskelions can assemble into lattices of different shapes, sizes and symmetries. for many years, the structures of clathrin lattices have been studied by single particle cryo-electron microscopy, which probed the architecture of the d6 hexagonal barrel clathrin coat at the molecular level. by introducing additional image processing steps we have recently produced a density map for the d6 barrel clathrin coat at subnanometer resolution, enabling us to generate an atomic model for this l ... | 2006 | 16908193 |
| postsynaptic inositol 1,4,5-trisphosphate signaling maintains presynaptic function of parallel fiber-purkinje cell synapses via bdnf. | the maintenance of synaptic functions is essential for neuronal information processing, but cellular mechanisms that maintain synapses in the adult brain are not well understood. here, we report an activity-dependent maintenance mechanism of parallel fiber (pf)-purkinje cell (pc) synapses in the cerebellum. when postsynaptic metabotropic glutamate receptor (mglur) or inositol 1,4,5-trisphosphate (ip(3)) signaling was chronically inhibited in vivo, pf-pc synaptic strength decreased because of a d ... | 2006 | 16709674 |
| relationships between host viremia and vector susceptibility for arboviruses. | using a threshold model where a minimum level of host viremia is necessary to infect vectors affects our assessment of the relative importance of different host species in the transmission and spread of these pathogens. other models may be more accurate descriptions of the relationship between host viremia and vector infection. under the threshold model, the intensity and duration of the viremia above the threshold level is critical in determining the potential numbers of infected mosquitoes. a ... | 0 | 16739425 |
| animal virus schemes for translation dominance. | viruses have adapted a broad range of unique mechanisms to modulate the cellular translational machinery to ensure viral translation at the expense of cellular protein synthesis. many of these promote virus-specific translation by use of molecular tags on viral mrna such as internal ribosome entry sites (ires) and genome-linked viral proteins (vpg) that bind translation machinery components in unusual ways and promote rna circularization. this review describes recent advances in understanding so ... | 0 | 22319551 |
| manipulation or capitulation: virus interactions with autophagy. | autophagy is a homeostatic process that functions to balance cellular metabolism and promote cell survival during stressful conditions by delivering cytoplasmic components for lysosomal degradation and subsequent recycling. during viral infection, autophagy can act as a surveillance mechanism that delivers viral antigens to the endosomal/lysosomal compartments that are enriched in immune sensors. additionally, activated immune sensors can signal to activate autophagy. to evade this antiviral act ... | 2011 | 22051604 |
| enhanced sumoylation and senp-1 protein levels following oxygen and glucose deprivation in neurones. | here, we show that oxygen and glucose deprivation (ogd) causes increased small ubiquitin-like modifier (sumo)-1 and sumo-2/3 conjugation to substrate proteins in cultured hippocampal neurones. surprisingly, the sumo protease senp-1, which removes sumo from conjugated proteins, was also increased by ogd, suggesting that the neuronal response to ogd involves a complex interplay between sumoylation and desumoylation. importantly, decreasing global sumoylation in cultured hippocampal neurones by ove ... | 2011 | 21989481 |
| next generation sequencing technologies for insect virus discovery. | insects are commonly infected with multiple viruses including those that cause sublethal, asymptomatic, and latent infections. traditional methods for virus isolation typically lack the sensitivity required for detection of such viruses that are present at low abundance. in this respect, next generation sequencing technologies have revolutionized methods for the discovery and identification of new viruses from insects. here we review both traditional and modern methods for virus discovery, and o ... | 2011 | 22069519 |
| translation without eif2 promoted by poliovirus 2a protease. | poliovirus rna utilizes eif2 for the initiation of translation in cell free systems. remarkably, we now describe that poliovirus translation takes place at late times of infection when eif2 is inactivated by phosphorylation. by contrast, translation directed by poliovirus rna is blocked when eif2 is inactivated at earlier times. thus, poliovirus rna translation exhibits a dual mechanism for the initiation of protein synthesis as regards to the requirement for eif2. analysis of individual poliovi ... | 2011 | 22003403 |
| virtual high-throughput screening identifies mycophenolic acid as a novel rna capping inhibitor. | the rna guanylyltransferase (gtase) is involved in the synthesis of the (m7)gppp-rna cap structure found at the 5' end of eukaryotic mrnas. gtases are members of the covalent nucleotidyl transferase superfamily, which also includes dna and rna ligases. gtases catalyze a two-step reaction in which they initially utilize gtp as a substrate to form a covalent enzyme-gmp intermediate. the gmp moiety is then transferred to the diphosphate end of the rna transcript in the second step of the reaction t ... | 2011 | 21935470 |
| viral vector-based therapeutic cancer vaccines. | most viruses are naturally immunogenic and can be engineered to express tumor antigen transgenes. moreover, many types of recombinant viruses have been shown to infect professional antigen-presenting cells, specifically dendritic cells, and express their transgenes. this enhanced presentation of tumor antigens to the immune system has led to an increase in the frequency and avidity of cytotoxic t lymphocytes that target tumor cells expressing the tumor antigen(s) encoded in the vaccine vector. l ... | 0 | 21952287 |
| rig-i like receptors and their signaling crosstalk in the regulation of antiviral immunity. | during virus infection, multiple immune signaling pathways are triggered, both within the host cell and bystander cells of an infected tissue. these pathways act in concert to mediate innate antiviral immunity and to initiate the inflammatory response against infection. the rig-i-like receptor (rlr) family of pattern recognition receptors (prrs) is a group of cytosolic rna helicase proteins that can identify viral rna as nonself via binding to pathogen associated molecular patter (pamp) motifs w ... | 0 | 21949557 |
| autophagy in the control and pathogenesis of viral infection. | autophagy is an evolutionary conserved cell process that plays a central role in eukaryotic cell metabolism. constitutive autophagy allows cells to ensure their energy needs are met during times of starvation, degrade long-lived cellular proteins, and recycle organelles. in addition, autophagy and its machinery can also be utilized to degrade intracellular pathogens, and this function likely represents one of the earliest eukaryotic defense mechanisms against viral pathogens. within the past dec ... | 0 | 21927636 |
| role of micrornas in insect host-microorganism interactions. | micrornas (mirnas) have appeared as important regulators of various biological processes including development, cancer, immunity, and host-microorganism interactions. accumulating evidence demonstrates the differential expression of host mirnas upon infection by various microorganisms and the involvement of microorganism-encoded mirnas in host manipulation. some of these alterations could be part of a host response to an infection to limit replication and dissemination of the microorganism or, c ... | 2011 | 21886625 |
| geometric measures of large biomolecules: surface, volume, and pockets. | geometry plays a major role in our attempts to understand the activity of large molecules. for example, surface area and volume are used to quantify the interactions between these molecules and the water surrounding them in implicit solvent models. in addition, the detection of pockets serves as a starting point for predictive studies of biomolecule-ligand interactions. the alpha shape theory provides an exact and robust method for computing these geometric measures. several implementations of t ... | 2011 | 21823134 |
| the transferrin receptor and the targeted delivery of therapeutic agents against cancer. | traditional cancer therapy can be successful in destroying tumors, but can also cause dangerous side effects. therefore, many targeted therapies are in development. the transferrin receptor (tfr) functions in cellular iron uptake through its interaction with transferrin. this receptor is an attractive molecule for the targeted therapy of cancer since it is upregulated on the surface of many cancer types and is efficiently internalized. this receptor can be targeted in two ways: 1) for the delive ... | 2011 | 21851850 |
| viruses, autophagy genes, and crohn's disease. | the etiology of the intestinal disease crohn's disease involves genetic factors as well as ill-defined environmental agents. several genetic variants linked to this disease are associated with autophagy, a process that is critical for proper responses to viral infections. while a role for viruses in this disease remains speculative, accumulating evidence indicate that this possibility requires serious consideration. in this review, we will examine the three-way relationship between viruses, auto ... | 2011 | 21994779 |
| clinical profile of chikungunya patients during the epidemic of 2007 in kerala, india. | the association of the present chikungunya pandemic with a mutation in the chik virus is already established in many parts of the world, including kerala. kerala was one of the worst-affected states of india in the chikungunya epidemic of 2006-2007. it is important to discuss the clinical features of patients affected by chikungunya fever in the context of this change in the epidemiology of the disease. | 0 | 21887052 |
| strategies for viral rna stability: live long and prosper. | eukaryotic cells have a powerful rna decay machinery that plays an important and diverse role in regulating both the quantity and the quality of gene expression. viral rnas need to successfully navigate around this cellular machinery to initiate and maintain a highly productive infection. recent work has shown that viruses have developed a variety of strategies to accomplish this, including inherent rna shields, hijacking host rna stability factors, incapacitating the host decay machinery and ch ... | 0 | 21640425 |
| larval habitat characteristics of the genus anopheles (diptera: culicidae) and a checklist of mosquitoes in guilan province, northern iran. | ecological data are important in the vector control management of mosquitoes. there is scattered published information about the larval habitat characteristics and ecology of the genus anopheles (diptera: culicidae) in iran and most of available data is in relation to malaria vectors in southern iran. | 2011 | 22808409 |
| neuroprotection: the emerging concept of restorative neural stem cell biology for the treatment of neurodegenerative diseases. | during the past decades neural stem cells have been considered as an alternative source of cells to replace lost neurons and nsc transplantation has been indicated as a promising treatment for neurodegenerative disorders. nevertheless, the current understanding of nsc biology suggests that, far from being mere spare parts for cell replacement therapies, nscs could play a key role in the pharmacology of neuroprotection and become protagonists of innovative treatments for neurodegenerative disease ... | 0 | 22131940 |
| a versatile valve-enabled microfluidic cell co-culture platform and demonstration of its applications to neurobiology and cancer biology. | a versatile microfluidic platform allowing co-culture of multiple cell populations in close proximity with separate control of their microenvironments would be extremely valuable for many biological applications. here, we report a simple and compact microfluidic platform that has these desirable features and allows for real-time, live-cell imaging of cell-cell interactions. using a pneumatically/hydraulically controlled poly(dimethylsiloxane) (pdms) valve barrier, distinct cell types can be cult ... | 0 | 21424383 |
| exposure of neurons to excitotoxic levels of glutamate induces cleavage of the rna editing enzyme, adenosine deaminase acting on rna 2, and loss of glur2 editing. | ampa receptors are glutamate receptors that are tetramers of various combinations of glur1-4 subunits. ampa receptors containing glur1, 3 and 4 are ca2+ permeable, however, ampa receptors containing even a single subunit of glur2 are ca2+ impermeable. most ampa receptors are ca2+ impermeable due to the presence of glur2. glur2 confers special properties on ampa receptors through the presence of arginine at the pore apex; other subunits (glur1, 3, 4) contain glutamine at the pore apex and allow c ... | 2011 | 21620933 |
| profile of charles m. rice. | | 2011 | 21502493 |
| differential cycling rates of kv4.2 channels in proximal and distal dendrites of hippocampal ca1 pyramidal neurons. | the heterogeneous expression of voltage-gated channels in dendrites suggests that neurons perform local microdomain computations at different regions. it has been shown that a-type k(+) channels have a nonuniform distribution along the primary apical dendrite in ca1 pyramidal neurons, increasing with distance from the soma. kv4.2 channels, which are responsible for the somatodendritic a-type k(+) current in ca1 pyramidal neurons, shape local synaptic input, and regulate the back-propagation of a ... | 2011 | 21472817 |
| the atg6/vps30/beclin 1 ortholog bec-1 mediates endocytic retrograde transport in addition to autophagy in c. elegans. | autophagy and endocytosis are dynamic and tightly regulated processes that contribute to many fundamental aspects of biology including survival, longevity, and development. however, the molecular links between autophagy and endocytosis are not well understood. here, we report that bec-1, the c. elegans ortholog of atg6/vps30/beclin1, a key regulator of the autophagic machinery, also contributes to endosome function. in particular we identify a defect in retrograde transport from endosomes to the ... | 2011 | 21183797 |
| experience-dependent structural plasticity in the cortex. | synapses are the fundamental units of neuronal circuits. synaptic plasticity can occur through changes in synaptic strength, as well as through the addition/removal of synapses. two-photon microscopy in combination with fluorescence labeling offers a powerful tool to peek into the living brain and follow structural reorganization at individual synapses. time-lapse imaging depicts a dynamic picture in which experience-dependent plasticity of synaptic structures varies between different cortical r ... | 0 | 21397343 |
| green tea polyphenol sensing. | green tea polyphenols have emerged over the past two decades as an important dietary factor for health promotion. there is considerable evidence that tea polyphenols, in particular (-)-epigallocatechin-3-gallate (egcg) inhibit carcinogenesis. however, the mechanisms for the cancer-preventive activity of egcg are not completely characterized and many features remain to be elucidated. recently we have identified a cell-surface egcg receptor and the relating molecules that confer egcg responsivenes ... | 0 | 21422740 |
| requirement for plk2 in orchestrated ras and rap signaling, homeostatic structural plasticity, and memory. | ras and rap small gtpases are important for synaptic plasticity and memory. however, their roles in homeostatic plasticity are unknown. here, we report that polo-like kinase 2 (plk2), a homeostatic suppressor of overexcitation, governs the activity of ras and rap via coordination of their regulatory proteins. plk2 directs elimination of ras activator rasgrf1 and rap inhibitor spar via phosphorylation-dependent ubiquitin-proteasome degradation. conversely, plk2 phosphorylation stimulates ras inhi ... | 0 | 21382555 |
| thematic issue on how autophagosomes find their targets. | | 0 | 21178396 |
| diverse roles of host rna binding proteins in rna virus replication. | plus-strand +rna viruses co-opt host rna-binding proteins (rbps) to perform many functions during viral replication. a few host rbps have been identified that affect the recruitment of viral +rnas for replication. other subverted host rbps help the assembly of the membrane-bound replicase complexes, regulate the activity of the replicase and control minus- or plus-strand rna synthesis. the host rbps also affect the stability of viral rnas, which have to escape cellular rna degradation pathways. ... | 2011 | 21505273 |
| the inside out of lentiviral vectors. | lentiviruses induce a wide variety of pathologies in different animal species. a common feature of the replicative cycle of these viruses is their ability to target non-dividing cells, a property that constitutes an extremely attractive asset in gene therapy. in this review, we shall describe the main basic aspects of the virology of lentiviruses that were exploited to obtain efficient gene transfer vectors. in addition, we shall discuss some of the hurdles that oppose the efficient genetic modi ... | 2011 | 22049307 |
| autophagy in immunity and inflammation. | autophagy is an essential, homeostatic process by which cells break down their own components. perhaps the most primordial function of this lysosomal degradation pathway is adaptation to nutrient deprivation. however, in complex multicellular organisms, the core molecular machinery of autophagy - the 'autophagy proteins' - orchestrates diverse aspects of cellular and organismal responses to other dangerous stimuli such as infection. recent developments reveal a crucial role for the autophagy pat ... | 0 | 21248839 |
| pancreatic cancer gene therapy: from molecular targets to delivery systems. | the continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. targets-both protein coding and non-coding-are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. delivery vehicles based on viral or non-viral systems as well ... | 2011 | 24212620 |
| central neural pathways for thermoregulation. | central neural circuits orchestrate a homeostatic repertoire to maintain body temperature during environmental temperature challenges and to alter body temperature during the inflammatory response. this review summarizes the functional organization of the neural pathways through which cutaneous thermal receptors alter thermoregulatory effectors: the cutaneous circulation for heat loss, the brown adipose tissue, skeletal muscle and heart for thermogenesis and species-dependent mechanisms (sweatin ... | 2011 | 21196160 |
| the endoplasmic reticulum protein folding factory and its chaperones: new targets for drug discovery? | cytosolic heat shock proteins have received significant attention as emerging therapeutic targets. much of this excitement has been triggered by the discovery that hsp90 plays a central role in the maintenance and stability of multifarious oncogenic membrane receptors and their resultant tyrosine kinase activity. numerous studies have dealt with the effects of small molecules on chaperone- and stress-related pathways of the endoplasmic reticulum (er). however, unlike cytosolic chaperones, relati ... | 0 | 20942857 |
| evaluation of species distribution model algorithms for fine-scale container-breeding mosquito risk prediction. | the present work evaluates the use of species distribution model (sdm) algorithms to classify high densities of small container-breeding aedes mosquitoes (diptera: culicidae) on a fine scale in the bermuda islands. weekly ovitrap data collected by the department of health, bermuda for the years 2006 and 2007 were used for the models. the models evaluated included the algorithms bioclim, domain, garp (genetic algorithm for rule-set prediction), logistic regression and maxent (maximum entropy). mo ... | 2010 | 21198711 |
| homeostatic scaling requires group i mglur activation mediated by homer1a. | homeostatic scaling is a non-hebbian form of neural plasticity that maintains neuronal excitability and informational content of synaptic arrays in the face of changes of network activity. here, we demonstrate that homeostatic scaling is dependent on group i metabotropic glutamate receptor activation that is mediated by the immediate early gene homer1a. homer1a is transiently upregulated during increases in network activity and evokes agonist-independent signaling of group i mglurs that scales d ... | 0 | 21172614 |
| depletion of beclin-1 due to proteolytic cleavage by caspases in the alzheimer's disease brain. | the beclin-1 protein is essential for the initiation of autophagy, and recent studies suggest this function may be compromised in alzheimer's disease (ad). in addition, in vitro studies have supported a loss of function of beclin-1 due to proteolytic modification by caspases. in the present study, we examined whether caspase-cleavage of beclin-1 occurs in the ad brain by designing a site-directed caspase-cleavage antibody based upon a known cleavage site within the protein at position d149. we c ... | 2010 | 21081164 |
| no signaling and s-nitrosylation regulate pten inhibition in neurodegeneration. | the phosphatase pten governs the phosphoinositide 3-kinase (pi3k)/akt signaling pathway which is arguably the most important pro-survival pathway in neurons. recently, pten has also been implicated in multiple important cns functions such as neuronal differentiation, plasticity, injury and drug addiction. it has been reported that loss of pten protein, accompanied by akt activation, occurs under excitotoxic conditions (stroke) as well as in alzheimer's (ad) brains. however the molecular signals ... | 2010 | 21067594 |
| investigating the mechanisms underlying neuronal death in ischemia using in vitro oxygen-glucose deprivation: potential involvement of protein sumoylation. | it is well established that brain ischemia can cause neuronal death via different signaling cascades. the relative importance and interrelationships between these pathways, however, remain poorly understood. here is presented an overview of studies using oxygen-glucose deprivation of organotypic hippocampal slice cultures to investigate the molecular mechanisms involved in ischemia. the culturing techniques, setup of the oxygen-glucose deprivation model, and analytical tools are reviewed. the au ... | 0 | 19029060 |
| bh3-only proteins in apoptosis and beyond: an overview. | bh3-only bcl-2 family proteins are effectors of canonical mitochondrial apoptosis. they discharge their pro-apoptotic functions through bh1-3 pro-apoptotic proteins such as bax and bak, while their activity is suppressed by bh1-4 anti-apoptotic bcl-2 family members. the precise mechanism by which bh3-only proteins mediate apoptosis remains unresolved. the existing data are consistent with three mutually non-exclusive models (1) displacement of bh1-3 proteins from complexes with bh1-4 proteins; ( ... | 0 | 19641503 |
| combination of active specific immunotherapy or adoptive antibody or lymphocyte immunotherapy with chemotherapy in the treatment of cancer. | successful treatment of cancer patients with a combination of monoclonal antibodies (mab) and chemotherapeutic drugs has spawned various other forms of additional combination therapies, including vaccines or adoptive lymphocyte transfer combined with chemotherapeutics. these therapies were effective against established tumors in animal models and showed promising results in initial clinical trials in cancer patients, awaiting testing in larger randomized controlled studies. although combination ... | 2008 | 18925393 |
| comparative genomics of small rna regulatory pathway components in vector mosquitoes. | small rna regulatory pathways (srrps) control key aspects of development and anti-viral defense in metazoans. members of the argonaute family of catalytic enzymes degrade target rnas in each of these pathways. srrps include the microrna, small interfering rna (sirna) and piwi-type gene silencing pathways. mosquitoes generate viral sirnas when infected with rna arboviruses. however, in some mosquitoes, arboviruses survive antiviral rna interference (rnai) and are transmitted via mosquito bite to ... | 2008 | 18801182 |
| esf-embo symposium: antiviral applications of rna interference. | | 2008 | 18801178 |
| diversity of degradation signals in the ubiquitin-proteasome system. | the ubiquitin-proteasome system degrades an enormous variety of proteins that contain specific degradation signals, or 'degrons'. besides the degradation of regulatory proteins, almost every protein suffers from sporadic biosynthetic errors or misfolding. such aberrant proteins can be recognized and rapidly degraded by cells. structural and functional data on a handful of degrons allow several generalizations regarding their mechanism of action. we focus on different strategies of degron recogni ... | 0 | 18698327 |
| predominance of six different hexanucleotide recoding signals 3' of read-through stop codons. | redefinition of uag, uaa and uga to specify a standard amino acid occurs in response to recoding signals present in a minority of mrnas. this 'read-through' is in competition with termination and is utilized for gene expression. one of the recoding signals known to stimulate read-through is a hexanucleotide sequence of the form caryya 3' adjacent to the stop codon. the present work finds that of the 91 unique viral sequences annotated as read-through, 90% had one of six of the 64 possible codons ... | 0 | 11972340 |
| misreading of termination codons in eukaryotes by natural nonsense suppressor trnas. | translational stop codon readthrough provides a regulatory mechanism of gene expression that is extensively utilised by positive-sense ssrna viruses. the misreading of termination codons is achieved by a variety of naturally occurring suppressor trnas whose structure and function is the subject of this survey. all of the nonsense suppressors characterised to date (with the exception of selenocysteine trna) are normal cellular trnas that are primarily needed for reading their cognate sense codons ... | 0 | 11726686 |
| tackling the most difficult diseases. genetics and genomics open new strategies to fight vector-borne diseases. | | 0 | 11600446 |
| gene targeting in mosquito cells: a demonstration of 'knockout' technology in extrachromosomal gene arrays. | gene targeting would offer a number of advantages over current transposon-based strategies for insect transformation. these include freedom from both position effects associated with quasi-random integration and concerns over transgene instability mediated by endogenous transposases, independence from phylogenetic restrictions on transposon mobility and the ability to generate gene knockouts. | 2001 | 11513755 |
| expression of plasmid-based shrna against the e1 and nsp1 genes effectively silenced chikungunya virus replication. | chikungunya virus (chikv) is a re-emerging alphavirus that causes chikungunya fever and persistent arthralgia in humans. currently, there is no effective vaccine or antiviral against chikv infection. therefore, this study evaluates whether rna interference which targets at viral genomic level may be a novel antiviral strategy to inhibit the medically important chikv infection. | 2012 | 23056297 |
| vipr hmm: a hidden markov model for detecting recombination with microbial detection microarrays. | current methods in diagnostic microbiology typically focus on the detection of a single genomic locus or protein in a candidate agent. the presence of the entire microbe is then inferred from this isolated result. problematically, the presence of recombination in microbial genomes would go undetected unless other genomic loci or protein components were specifically assayed. microarrays lend themselves well to the detection of multiple loci from a given microbe; furthermore, the inherent nature o ... | 2012 | 23044542 |
| autophagy and selective deployment of atg proteins in antiviral defense. | autophagy is an evolutionarily ancient process eukaryotic cells utilize to remove and recycle intracellular material in order to maintain cellular homeostasis. in metazoans, the autophagy machinery not only functions in this capacity but also has evolved to perform a diverse repertoire of intracellular transport and regulatory functions. in response to virus infections, the autophagy machinery degrades viruses, shuttles viral pathogen-associated molecular patterns to endosomes containing toll-li ... | 2012 | 23042773 |
| testing of novel dengue virus 2 vaccines in african green monkeys: safety, immunogenicity, and efficacy. | the immunogenicity and safety of three novel host-range vaccines containing deletions in the transmembrane domain of dengue virus serotype 2 (dv2) e glycoprotein were evaluated in african green monkeys. the shorter transmembrane domains are capable of functionally spanning an insect but not a mammalian cell membrane, resulting in production of viral mutants that have reduced infectivity in mammalian hosts but efficient growth in insect cells. groups of four monkeys received one dose each of test ... | 2012 | 22890035 |
| living on the edge with too many mouths to feed: why dopamine neurons die. | although genes, protein aggregates, environmental toxins, and other factors associated with parkinson's disease (pd) are widely distributed in the nervous system and affect many classes of neurons, a consistent feature of pd is the exceptional and selective vulnerability of dopamine (da) neurons of the snc. what is it about these neurons, among all other neurons in the brain, that makes them so susceptible in pd? we hypothesize that a major contributory factor is the unique cellular architecture ... | 2012 | 23008164 |
| pathogenic characterization of a cervical lymph node derived from a patient with kawasaki disease. | kawasaki disease (kd) is the most common cause of multisystem vasculitis in childhood. although cervical lymphadenitis is one of the major symptoms in kd, lymph node biopsy is rarely performed, because kd is usually diagnosed by clinical symptoms. a cervical lymph node biopsy was taken from a girl aged 1 year and 8 months who had suspected lymphoma, but she was diagnosed with kd after the biopsy. the cervical lymph node specimen was analyzed with multivirus real-time pcr that can detect >160 vir ... | 2012 | 23071864 |
| rnase l triggers autophagy in response to viral infections. | autophagy is a programmed homeostatic response to diverse types of cellular stress that disposes of long-lived proteins, organelles, and invading microbes within double-membraned structures called autophagosomes. the 2',5'-oligoadenylate/rnase l system is a virus-activated host rnase pathway that disposes of or processes viral and cellular single-stranded rnas. here we report that activation of rnase l during viral infections induces autophagy. accordingly, infections with encephalomyocarditis v ... | 2012 | 22875977 |
| translational repression precedes and is required for zap-mediated mrna decay. | translational repression and mrna degradation are two major mechanisms for post-transcriptional regulation of gene expression. the detailed relationship between these two processes is not yet well established. zinc-finger antiviral protein (zap) inhibits the replication of certain viruses, including human immunodeficiency virus 1, by binding directly to specific viral mrnas and recruiting cellular mrna degradation machinery to degrade the target mrna. here, we report that zap also inhibits the t ... | 2012 | 23023399 |
| role of bunyamwera orthobunyavirus nss protein in infection of mosquito cells. | bunyamwera orthobunyavirus is both the prototype and study model of the bunyaviridae family. the viral nss protein seems to contribute to the different outcomes of infection in mammalian and mosquito cell lines. however, only limited information is available on the growth of bunyamwera virus in cultured mosquito cells other than the aedes albopictus c6/36 line. | 2012 | 23029584 |
| intrahepatic infiltrating nk and cd8 t cells cause liver cell death in different phases of dengue virus infection. | elevated liver enzyme level is an outstanding feature in patients with dengue. however, the pathogenic mechanism of liver injury has not been clearly demonstrated. in this study, employing a mouse model we aimed to investigate the immunopathogenic mechanism of dengue liver injury. immunocompetent c57bl/6 mice were infected intravenously with dengue virus strain 16681. infected mice had transient viremia, detectable viral capsid gene and cleaved caspase 3 in the liver. in the mean time, nk cell a ... | 2012 | 23050007 |
| replication of respiratory syncytial virus is inhibited by the host defense molecule viperin. | respiratory syncytial virus (rsv) is an important viral pathogen of otitis media, bronchiolitis, and pneumonia. as infection of the upper airways is a precondition for the development of these diseases, understanding rsv pathogenesis and the host response induced by rsv in this niche may enable the development of novel therapeutic strategies against this virus. we have used a microarray approach and showed that expression of the gene that encodes the antiviral protein viperin was significantly u ... | 2012 | 23018837 |
| potential vaccines and post-exposure treatments for filovirus infections. | viruses of the family filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. while many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward ... | 2012 | 23170176 |
| west nile virus (wnv) replication is independent of autophagy in mammalian cells. | autophagy is a homeostatic process responsible for recycling cytosolic proteins and organelles. moreover, this pathway contributes to the cell's intrinsic innate defenses. while many viruses have evolved mechanisms to antagonize the antiviral effects of the autophagy pathway, others subvert autophagy to facilitate replication. here, we have investigated the role of autophagy in west nile virus (wnv) replication. experiments in cell lines derived from a variety of sources, including the kidney, l ... | 2012 | 23029249 |
| everybody wins! poland hosts thrilling competitions of viruses, rnai and football teams. | the esf-embo conference on 'antiviral rnai: from molecular biology towards applications' took place in june 2012 in pultusk, poland. it brought together scientists working at the interface of rnai and virus infections in different organisms, covering the complete range from basic mechanisms of rna silencing to rnai-based antiviral therapy. | 2012 | 22986551 |
| a neuron-specific role for autophagy in antiviral defense against herpes simplex virus. | type i interferons (ifns) are considered to be the universal mechanism by which viral infections are controlled. however, many ifn-stimulated genes (isgs) rely on antiviral pathways that are toxic to host cells, which may be detrimental in nonrenewable cell types, such as neurons. we show that dorsal root ganglionic (drg) neurons produced little type i ifns in response to infection with a neurotropic virus, herpes simplex type 1 (hsv-1). further, type i ifn treatment failed to completely block h ... | 0 | 22980330 |
| overexpression of membrane proteins in mammalian cells for structural studies. | the number of structures of integral membrane proteins from higher eukaryotes is steadily increasing due to a number of innovative protein engineering and crystallization strategies devised over the last few years. however, it is sobering to reflect that these structures represent only a tiny proportion of the total number of membrane proteins encoded by a mammalian genome. in addition, the structures determined to date are of the most tractable membrane proteins, i.e., those that are expressed ... | 2012 | 22963530 |
| effects of larval rearing temperature on immature development and west nile virus vector competence of culex tarsalis. | temperature is known to induce changes in mosquito physiology, development, ecology, and in some species, vector competence for arboviruses. since colonized mosquitoes are reared under laboratory conditions that can be significantly different from their field counterparts, laboratory vector competence experiments may not accurately reflect natural vector-virus interactions. | 2012 | 22967798 |
| preparation of bioactive interferon alpha-loaded polysaccharide nanoparticles using a new approach of temperature-induced water phase/water-phase emulsion. | the aim of this study was to develop a temperature-induced polyethylene glycol (peg) water phase/polysaccharide water-phase emulsion approach for preparing interferon alpha-2b (ifnα-2b)-loaded polysaccharide nanoparticles. ifnα-2b was first added to a mixture of an aqueous solution of peg and polysaccharide. the mixture solution was stirred in a magnetic stirrer at a rate of 2000 rpm for 45 seconds at 0°c ± 0.5°c. the solution was then prefrozen at different temperatures. the polysaccharide and ... | 2012 | 22973103 |
| nlrs, inflammasomes, and viral infection. | nlr proteins are innate immune sensors that respond to microbial infection. upon pathogen infection, some nlr proteins form large complexes, called inflammasomes, which activate caspase-1 and induce the production of active il-1β and il-18. activation of inflammasomes can also lead to an inflammatory cell death program, named pyroptosis. in this review, we will discuss the role of various nlr proteins in sensing different viral infections, as well as the strategies used by several rna and dna vi ... | 2012 | 22581934 |
| pamps and damps: signal 0s that spur autophagy and immunity. | pathogen-associated molecular pattern molecules (pamps) are derived from microorganisms and recognized by pattern recognition receptor (prr)-bearing cells of the innate immune system as well as many epithelial cells. in contrast, damage-associated molecular pattern molecules (damps) are cell-derived and initiate and perpetuate immunity in response to trauma, ischemia, and tissue damage, either in the absence or presence of pathogenic infection. most pamps and damps serve as so-called 'signal 0s' ... | 0 | 22889221 |
| macrophage autophagy in immunity to cryptococcus neoformans and candida albicans. | autophagy is used by eukaryotes in bulk cellular material recycling and in immunity to intracellular pathogens. we evaluated the role of macrophage autophagy in the response to cryptococcus neoformans and candida albicans, two important opportunistic fungal pathogens. the autophagosome marker lc3 (microtubule-associated protein 1 light chain 3 alpha) was present in most macrophage vacuoles containing c. albicans. in contrast, lc3 was found in only a few vacuoles containing c. neoformans previous ... | 2012 | 22710871 |
| intracytoplasmic trapping of influenza virus by a lipophilic derivative of aglycoristocetin. | we report on a new anti-influenza virus agent, sa-19, a lipophilic glycopeptide derivative consisting of aglycoristocetin coupled to a phenylbenzyl-substituted cyclobutenedione. in madin-darby canine kidney cells infected with influenza a/h1n1, a/h3n2, or b virus, sa-19 displayed a 50% antivirally effective concentration of 0.60 μm and a selectivity index (ratio of cytotoxic versus antiviral concentration) of 112. sa-19 was 11-fold more potent than unsubstituted aglycoristocetin and was active i ... | 2012 | 22740402 |
| large ribosomal protein 4 increases efficiency of viral recoding sequences. | expression of retroviral replication enzymes (pol) requires a controlled translational recoding event to bypass the stop codon at the end of gag. this recoding event occurs either by direct suppression of termination via the insertion of an amino acid at the stop codon (readthrough) or by alteration of the mrna reading frame (frameshift). here we report the effects of a host protein, large ribosomal protein 4 (rpl4), on the efficiency of recoding. using a dual luciferase reporter assay, we found ... | 2012 | 22718819 |
| fighting mycobacteria through isgylation. | | 2012 | 22940737 |
| comprehensive proteomic analysis of nonintegrin laminin receptor interacting proteins. | human nonintegrin laminin receptor is a multifunctional protein acting as an integral component of the ribosome and a cell surface receptor for laminin-1. the laminin receptor is overexpressed in several human cancers and is also the cell surface receptor for several viruses and pathogenic prion proteins, making it a pathologically significant protein. this study focused on the proteomic characterization of laminin receptor interacting proteins from mus musculus. the use of affinity chromatograp ... | 2012 | 22909348 |
| west nile virus growth is independent of autophagy activation. | west nile virus (wnv) is an arthropod-borne virus with a worldwide distribution that causes neurologic disease and death. autophagy is a cellular homeostatic mechanism involved in antiviral responses but can be subverted to support viral growth as well. we show that autophagy is induced by wnv infection in cell culture and in primary neuron cultures. following wnv infection, lysosomes co-localize with autophagosomes resulting in lc3b-ii turnover and autolysosomal acidification. however, activati ... | 2012 | 22939285 |
| heterozygous tbk1 mutations impair tlr3 immunity and underlie herpes simplex encephalitis of childhood. | childhood herpes simplex virus-1 (hsv-1) encephalitis (hse) may result from single-gene inborn errors of tlr3 immunity. tlr3-dependent induction of ifn-α/β or ifn-λ is crucial for protective immunity against primary hsv-1 infection in the central nervous system (cns). we describe here two unrelated children with hse carrying different heterozygous mutations (d50a and g159a) in tbk1, the gene encoding tank-binding kinase 1, a kinase at the crossroads of multiple ifn-inducing signaling pathways. b ... | 2012 | 22851595 |
| hepatitis c virus translation preferentially depends on active rna replication. | hepatitis c virus (hcv) rna initiates its replication on a detergent-resistant membrane structure derived from the endoplasmic reticulum (er) in the hcv replicon cells. by performing a pulse-chase study of bru-labeled hcv rna, we found that the newly-synthesized hcv rna traveled along the anterograde-membrane traffic and moved away from the er. presumably, the rna moved to the site of translation or virion assembly in the later steps of viral life cycle. in this study, we further addressed how h ... | 2012 | 22937067 |
| arf6-gef brag1 regulates jnk-mediated synaptic removal of glua1-containing ampa receptors: a new mechanism for nonsyndromic x-linked mental disorder. | activity-dependent modifications of excitatory synapses contribute to synaptic maturation and plasticity, and are critical for learning and memory. consequently, impairments in synapse formation or synaptic transmission are thought to be responsible for several types of mental disabilities. brag1 is a guanine nucleotide exchange factor for the small gtp-binding protein arf6 that localizes to the postsynaptic density of excitatory synapses. mutations in brag1 have been identified in families with ... | 0 | 22915114 |
| activity based protein profiling to detect serine hydrolase alterations in virus infected cells. | activity-based protein profiling (abpp) is a newly emerging technique that uses active site-directed probes to monitor the functional status of enzymes. serine hydrolases are one of the largest families of enzymes in mammals. more than 200 serine hydrolases have been identified, but little is known about their specific roles. serine hydrolases are involved in a variety of physiological functions, including digestion, immune response, blood coagulation, and reproduction. abpp has been used recent ... | 2012 | 23024641 |
| dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro. | dengue virus (denv) is a global disease threat for which there are no approved antivirals or vaccines. establishing state-of-the-art screening systems that rely on fluorescent or luminescent reporters may accelerate the development of anti-denv therapeutics. however, relatively few reporter denv platforms exist. here, we show that denv can be genetically engineered to express a green fluorescent protein or firefly luciferase. reporter viruses are infectious in vitro and in vivo and are sensitive ... | 2012 | 22908290 |
| degradation of host micrornas by poxvirus poly(a) polymerase reveals terminal rna methylation as a protective antiviral mechanism. | the life cycle of several viruses involves host or virally encoded small noncoding rnas, which play important roles in posttranscriptional regulation. small noncoding rnas include micrornas (mirnas), which modulate the transcriptome, and small interfering rnas (sirnas), which are involved in pathogen defense in plants, worms, and insects. we show that insect and mammalian poxviruses induce the degradation of host mirnas. the virally encoded poly(a) polymerase, which polyadenylates viral transcri ... | 0 | 22901540 |
| translational regulation of anopheles gambiae mrnas in the midgut during plasmodium falciparum infection. | malaria is caused by plasmodium parasites, which are transmitted via the bites of infected anopheline mosquitoes. midgut invasion is a major bottleneck for plasmodium development inside the mosquito vectors. malaria parasites in the midgut are surrounded by a hostile environment rich in digestive enzymes, while a rapidly responding immune system recognizes plasmodium ookinetes and recruits killing factors from the midgut and surrounding tissues, dramatically reducing the population of invading o ... | 2012 | 22857387 |
| retinoblastoma protein induction by hiv viremia or ccr5 in monocytes exposed to hiv-1 mediates protection from activation-induced apoptosis: ex vivo and in vitro study. | we have previously described an antiapoptotic steady-state gene expression profile in circulating human monocytes from asymptomatic viremic hiv(+) donors, but the mechanism associated with this apoptosis resistance remains to be fully elucidated. here, we show that rb1 activation is a dominant feature of apoptosis resistance in monocytes exposed to hiv-1 in vivo (as measured ex vivo) and in vitro. monocytes from asymptomatic viremic hiv(+) individuals show a positive correlation between levels o ... | 2012 | 22701041 |
| identification of a novel antiviral inhibitor of the flavivirus guanylyltransferase enzyme. | arthropod-borne flavivirus infection causes serious morbidity and mortality worldwide, but there are currently no effective antiflaviviral chemotherapeutics available for human use. therefore, it is critical that new therapeutics against virus-specific targets be developed. to identify new compounds that may be used as broadly active flavivirus therapeutics, we have performed a high-throughput screening of 235,456 commercially available compounds for small-molecule inhibitors of the dengue virus ... | 2012 | 22674988 |
| identification of novel host cell binding partners of oas1b, the protein conferring resistance to flavivirus-induced disease in mice. | oas1b was previously identified as the product of the flv(r) allele that confers flavivirus-specific resistance to virus-induced disease in mice by an uncharacterized, rnase l-independent mechanism. to gain insights about the mechanism by which oas1b specifically reduces the efficiency of flavivirus replication, cellular protein interaction partners were identified and their involvement in the oas1b-mediated flavivirus resistance mechanism was analyzed. initial difficulties in getting the two-hy ... | 2012 | 22623793 |
| a single mutation in the glycophorin a binding site of hepatitis a virus enhances virus clearance from the blood and results in a lower fitness variant. | hepatitis a virus (hav) has previously been reported to bind to human red blood cells through interaction with glycophorin a. residue k221 of vp1 and the surrounding vp3 residues are involved in such an interaction. this capsid region is specifically recognized by the monoclonal antibody h7c27. a monoclonal antibody-resistant mutant with the mutation g1217d has been isolated. in the present study, the g1217d mutant was characterized physically and biologically in comparison with the parental hm1 ... | 2012 | 22593170 |
| tracking expression and subcellular localization of rna and protein species using high-throughput single cell imaging flow cytometry. | we report a high-throughput application of multispectral imaging flow cytometry (mifc) for analyzing the expression and localization of both rna and protein molecules in a heterogeneous population of cells. the approach was developed using polyadenylated nuclear (pan) rna, an abundant, noncoding rna expressed by kaposi's sarcoma-associated herpesvirus (kshv) during the lytic phase of infection. high levels of pan rna are, in part, dependent on its interaction with poly(a)-binding protein c1 (pab ... | 2012 | 22745225 |
| a graph theory method for determination of cryo-em image focuses. | accurate determination of micrograph focuses is essential for averaging multiple images to reach high-resolution 3-d reconstructions in electron cryo-microscopy (cryo-em). current methods use iterative fitting of focus-dependent simulated power spectra to the power spectra of experimental images, with the fitting performed independently for different images. here we have developed a novel graph theory based method in which the rotational average focus and individual angular sector focuses of all ... | 2012 | 22842112 |
| matching biochemical and functional efficacies confirm zip as a potent competitive inhibitor of pkmζ in neurons. | pkmζ is an autonomously active, atypical protein kinase c (apkc) isoform that is both necessary and sufficient for maintaining long-term potentiation (ltp) and long-term memory. the myristoylated ζ-pseudosubstrate peptide, zip, potently inhibits pkmζ biochemically in vitro, within cultured cells, and within neurons in hippocampal slices, and reverses ltp maintenance and erases long-term memory storage. a recent study (wu-zhang et al., 2012), however, suggested zip was not effective on a pkmζ fus ... | 2012 | 22846225 |
| a novel coding-region rna element modulates infectious dengue virus particle production in both mammalian and mosquito cells and regulates viral replication in aedes aegypti mosquitoes. | dengue virus (denv) is an enveloped flavivirus with a positive-sense rna genome transmitted by aedes mosquitoes, causing the most important arthropod-borne viral disease affecting humans. relatively few cis-acting rna regulatory elements have been described in the denv coding-region. here, by introducing silent mutations into a denv-2 infectious clone, we identify the conserved capsid-coding region 1 (ccr1), an rna sequence element that regulates viral replication in mammalian cells and to a gre ... | 2012 | 22840606 |
| interaction of endogenous tau protein with synaptic proteins is regulated by n-methyl-d-aspartate receptor-dependent tau phosphorylation. | amyloid-β and tau protein are the two most prominent factors in the pathology of alzheimer disease. recent studies indicate that phosphorylated tau might affect synaptic function. we now show that endogenous tau is found at postsynaptic sites where it interacts with the psd95-nmda receptor complex. nmda receptor activation leads to a selective phosphorylation of specific sites in tau, regulating the interaction of tau with fyn and the psd95-nmda receptor complex. based on our results, we propose ... | 2012 | 22833681 |
| neurogranin targets calmodulin and lowers the threshold for the induction of long-term potentiation. | calcium entry and the subsequent activation of camkii trigger synaptic plasticity in many brain regions. the induction of long-term potentiation (ltp) in the ca1 region of the hippocampus requires a relatively high amount of calcium-calmodulin. this requirement is usually explained, based on in vitro and theoretical studies, by the low affinity of camkii for calmodulin. an untested hypothesis, however, is that calmodulin is not randomly distributed within the spine and its targeting within the s ... | 2012 | 22848456 |
| targeted gene transfer of different genes to presynaptic and postsynaptic neocortical neurons connected by a glutamatergic synapse. | genetic approaches to analyzing neuronal circuits and learning would benefit from a technology to first deliver a specific gene into presynaptic neurons, and then deliver a different gene into an identified subset of their postsynaptic neurons, connected by a specific synapse type. here, we describe targeted gene transfer across a neocortical glutamatergic synapse, using as the model the projection from rat postrhinal to perirhinal cortex. the first gene transfer, into the presynaptic neurons in ... | 2012 | 22820303 |
| loss of stress response as a consequence of viral infection: implications for disease and therapy. | herein, we propose that viral infection can induce a deficient cell stress response and thereby impairs stress tolerance and makes tissues vulnerable to damage. having a valid paradigm to address the pathological impacts of viral infections could lead to effective new therapies for diseases that have previously been unresponsive to intervention. host response to viral infections can also lead to autoimmune diseases like type 1 diabetes. in the case of newcastle disease virus, the effects of vira ... | 2012 | 22797944 |
| identifying host factors that regulate viral infection. | | 2012 | 22807672 |
| regulation of the autophagic bcl-2/beclin 1 interaction. | autophagy is an intracellular degradation process responsible for the delivery of cellular material to the lysosomes. one of the key mechanisms for control of autophagy is the modulation of the interaction between the autophagic protein beclin 1 and the members of the anti-apoptotic bcl-2 family (e.g., bcl-2, bcl-xl and mcl-1). this binding is regulated by a variety of proteins and compounds that are able to enhance or inhibit the bcl-2/beclin 1 interaction in order to repress or activate autoph ... | 2012 | 24710477 |
| antiviral activity of a small molecule deubiquitinase inhibitor occurs via induction of the unfolded protein response. | ubiquitin (ub) is a vital regulatory component in various cellular processes, including cellular responses to viral infection. as obligate intracellular pathogens, viruses have the capacity to manipulate the ubiquitin (ub) cycle to their advantage by encoding ub-modifying proteins including deubiquitinases (dubs). however, how cellular dubs modulate specific viral infections, such as norovirus, is poorly understood. to examine the role of dubs during norovirus infection, we used wp1130, a small ... | 2012 | 22792064 |
| extended jak activation and delayed stat1 dephosphorylation contribute to the distinct signaling profile of cns neurons exposed to interferon-gamma. | although interferon-gamma (ifn-γ) plays a critical role in the noncytolytic elimination of many neurotropic viral infections, the signaling response to this cytokine has not been extensively characterized in primary cns neurons. we previously demonstrated that the ifn-γ response at the signaling and gene expression levels is temporally extended in primary mouse hippocampal neurons, as compared to the transient response of primary mouse embryonic fibroblasts (mef). we hypothesize that the protrac ... | 2012 | 22769061 |
| autophagy and immunity - insights from human herpesviruses. | the herpesviruses are a family of double-stranded dna viruses that infect a wide variety of organisms. having co-evolved with their hosts over millennia, herpesviruses have developed a large repertoire of mechanisms to manipulate normal cellular processes for their own benefit. consequently, studies on these viruses have made important contributions to our understanding of fundamental biological processes. here we describe recent research on the human herpesviruses that has contributed to our un ... | 2012 | 22783253 |