Publications

sindbis and middelburg old world alphaviruses associated with neurologic disease in horses, south africa.	old world alphaviruses were identified in 52 of 623 horses with febrile or neurologic disease in south africa. five of 8 sindbis virus infections were mild; 2 of 3 fatal cases involved co-infections. of 44 middelburg virus infections, 28 caused neurologic disease; 12 were fatal. middelburg virus likely has zoonotic potential.	26583836
climate, environmental and socio-economic change: weighing up the balance in vector-borne disease transmission.	arguably one of the most important effects of climate change is the potential impact on human health. while this is likely to take many forms, the implications for future transmission of vector-borne diseases (vbds), given their ongoing contribution to global disease burden, are both extremely important and highly uncertain. in part, this is owing not only to data limitations and methodological challenges when integrating climate-driven vbd models and climate change projections, but also, perhap ...	25688012
approaches to the treatment of disease induced by chikungunya virus.	chikungunya virus, a re-emerging mosquito-borne alphavirus, causes fever, rash and persistent arthralgia/arthritis in humans. severe outbreaks have occurred resulting in infections of millions of people in southeast asia and africa. currently there are no antiviral drugs or vaccines for prevention and treatment of chikungunya infections. herein we report the current status of research on antiviral drugs and vaccines for chikungunya virus infections.	24434329
biological transmission of arboviruses: reexamination of and new insights into components, mechanisms, and unique traits as well as their evolutionary trends.	among animal viruses, arboviruses are unique in that they depend on arthropod vectors for transmission. field research and laboratory investigations related to the three components of this unique mode of transmission, virus, vector, and vertebrate host, have produced an enormous amount of valuable information that may be found in numerous publications. however, despite many reviews on specific viruses, diseases, or interests, a systematic approach to organizing the available information on all f ...	16223950
receptors and tropisms of envelope viruses.	envelope virus replication begins with receptor binding, followed by fusion of the viral envelope with the cell membrane. the binding and fusion steps are usually mediated by envelope proteins. the ability of envelope proteins of a particular virus to bind and fuse with target cells defines the host range of the virus, known as 'viral tropism'. the mechanism(s) of fusion by the viral envelope is largely categorized as either ph-dependent or ph-independent. by redirecting the binding specificitie ...	21804908
protective and pathogenic responses to chikungunya virus infection.	chikungunya virus (chikv) is an arbovirus responsible for causing epidemic outbreaks of human disease characterized by painful and often debilitating arthralgia. recently chikv has moved into the caribbean and the americas resulting in massive outbreaks in naïve human populations. given the importance of chikv as an emerging disease, a significant amount of effort has gone into interpreting the virus-host interactions that contribute to protection or virus-induced pathology following chikv infec ...	26366337
development & evaluation of biotinylated dna probe for clinical diagnosis of chikungunya infection in patients' acute phase serum & csf samples.	the resurgence of chikungunya virus (chikv) in the indian ocean islands and india has drawn worldwide attention due to its explosive nature, high morbidity and complex clinico-pathological manifestations. the early confirmatory diagnosis of chikv is essential for management as well as control of unprecedented epidemics. the present study describes the development and evaluation of a highly sensitive and specific e1 structural gene specific biotinylated dna probe for detection of chikungunya viru ...	24056565
chikungunya virus and prospects for a vaccine.	in 2004, chikungunya virus (chikv) re-emerged from east africa to cause devastating epidemics of debilitating and often chronic arthralgia that have affected millions of people in the indian ocean basin and asia. more limited epidemics initiated by travelers subsequently occurred in italy and france, as well as human cases exported to most regions of the world, including the americas where chikv could become endemic. because chikv circulates during epidemics in an urban mosquito-human cycle, con ...	23151166
the three-dimensional structure of frozen-hydrated nudaurelia capensis beta virus, a t = 4 insect virus.	the three-dimensional structure of nudaurelia capensis beta virus (n beta v) was reconstructed to 3.2-nm resolution from images of frozen-hydrated virions. the distinctly icosahedral capsid (approximately 40-nm diameter) contains 240 copies of a single 61-kda protein subunit arranged with t = 4 lattice symmetry. the outer surface of unstained virions compares remarkably well with that previously observed in negatively stained specimens. inspection of the density map, volume estimates, and model ...	1712620
virus infection, antiviral immunity, and autoimmunity.	as a group of disorders, autoimmunity ranks as the third most prevalent cause of morbidity and mortality in the western world. however, the etiology of most autoimmune diseases remains unknown. although genetic linkage studies support a critical underlying role for genetics, the geographic distribution of these disorders as well as the low concordance rates in monozygotic twins suggest that a combination of other factors including environmental ones are involved. virus infection is a primary fac ...	23947356
human bocavirus in patients with encephalitis, sri lanka, 2009-2010.	we identified human bocavirus (hbov) dna by pcr in cerebrospinal fluid from adults and children with encephalitis in sri lanka. hbov types 1, 2, and 3 were identified among these cases. phylogenetic analysis of hbov1 strain sequences found no subclustering with strains previously identified among encephalitis cases in bangladesh.	24188380
reconstruction of h3n2 influenza virus based virosome in-vitro.	virosomes are virus like particles (vlp) assembled in-vitro. influenza virosomes maintain the cell binding and membrane fusion activity of the wild type virus but are devoid of viral genetic material or internal proteins. influenza virosomes mimic the natural antigen presentation route of the influenza virus.	23825736
oncolytic virotherapy for ovarian cancer.	in the past two decades, more than 20 viruses with selective tropism for tumor cells have been developed as oncolytic viruses (ovs) for treatments of a variety of malignancies. of these viruses, eleven have been tested in human ovarian cancer models in preclinical studies. so far, nine phase i or ii clinical trials have been conducted or initiated using four different types of ovs in patients with recurrent ovarian cancers. in this article, we summarize the different ovs that are being assessed ...	25977900
virotherapy, gene transfer and immunostimulatory monoclonal antibodies.	malignant cells are susceptible to viral infection and consequent cell death. virus-induced cell death is endowed with features that are known to stimulate innate and adaptive immune responses. thus danger signals emitted by cells succumbing to viral infection as well as viral nucleic acids are detected by specific receptors, and tumor cell antigens can be routed to professional antigen-presenting cells. the anticancer immune response triggered by viral infection is frequently insufficient to er ...	23243597
prime-boost approaches to tuberculosis vaccine development.	four individuals die from active tb disease each minute, while at least 2 billion are latently infected and at risk for disease reactivation. bcg, the only licensed tb vaccine, is effective in preventing childhood forms of tb; however its poor efficacy in adults, emerging drug-resistant tb strains and tedious chemotherapy regimes, warrant the development of novel prophylactic measures. designing safe and effective vaccines against tb will require novel approaches on several levels, including the ...	23176655
innate antiviral immunity in drosophila.	the study of drosophila, and other genetically tractable insects, has expanded our understanding of innate immunity and more recently antiviral innate mechanisms. the drosophila antiviral program includes inflammatory signaling cascades as well as antiviral rna silencing and autophagy. this review will highlight the recent discoveries in antiviral immunity in insects and will reveal some of the lessons learned.	20137906
oncolytic viruses for cancer therapy: overcoming the obstacles.	targeted therapy of cancer using oncolytic viruses has generated much interest over the past few years in the light of the limited efficacy and side effects of standard cancer therapeutics for advanced disease. in 2006, the world witnessed the first government-approved oncolytic virus for the treatment of head and neck cancer. it has been known for many years that viruses have the ability to replicate in and lyse cancer cells. although encouraging results have been demonstrated in vitro and in a ...	20543907
impact of protein kinase pkr in cell biology: from antiviral to antiproliferative action.	the double-stranded rna-dependent protein kinase pkr is a critical mediator of the antiproliferative and antiviral effects exerted by interferons. not only is pkr an effector molecule on the cellular response to double-stranded rna, but it also integrates signals in response to toll-like receptor activation, growth factors, and diverse cellular stresses. in this review, we provide a detailed picture on how signaling downstream of pkr unfolds and what are the ultimate consequences for the cell fa ...	17158706
interferon-inducible antiviral effectors.	since the discovery of interferons (ifns), considerable progress has been made in describing the nature of the cytokines themselves, the signalling components that direct the cell response and their antiviral activities. gene targeting studies have distinguished four main effector pathways of the ifn-mediated antiviral response: the mx gtpase pathway, the 2',5'-oligoadenylate-synthetase-directed ribonuclease l pathway, the protein kinase r pathway and the isg15 ubiquitin-like pathway. as discuss ...	18575461
combined structural, biochemical and cellular evidence demonstrates that both fgdf motifs in alphavirus nsp3 are required for efficient replication.	recent findings have highlighted the role of the old world alphavirus non-structural protein 3 (nsp3) as a host defence modulator that functions by disrupting stress granules, subcellular phase-dense rna/protein structures formed upon environmental stress. this disruption mechanism was largely explained through nsp3-mediated recruitment of the host g3bp protein via two tandem fgdf motifs. here, we present the 1.9 å resolution crystal structure of the ntf2-like domain of g3bp-1 in complex with a ...	27383630
virus entry, assembly, budding, and membrane rafts.	as intracellular parasites, viruses rely heavily on the use of numerous cellular machineries for completion of their replication cycle. the recent discovery of the heterogeneous distribution of the various lipids within cell membranes has led to the proposal that sphingolipids and cholesterol tend to segregate in microdomains called membrane rafts. the involvement of membrane rafts in biosynthetic traffic, signal transduction, and endocytosis has suggested that viruses may also take advantage of ...	12794191
nucleocapsid-independent specific viral rna packaging via viral envelope protein and viral rna signal.	for any of the enveloped rna viruses studied to date, recognition of a specific rna packaging signal by the virus's nucleocapsid (n) protein is the first step described in the process of viral rna packaging. in the murine coronavirus a selective interaction between the viral transmembrane envelope protein m and the viral ribonucleoprotein complex, composed of n protein and viral rna containing a short cis-acting rna element, the packaging signal, determines the selective rna packaging into virus ...	12584316
rna interference-mediated antiviral defense in insects.	small interfering rna (sirna)-mediated rna interference (rnai) pathways are critical for the detection and inhibition of rna virus replication in insects. recent work has also implicated rnai pathways in the establishment of persistent virus infections and in the control of dna virus replication. accumulating evidence suggests that diverse double-stranded rnas produced by rna and dna viruses can trigger rnai responses yet many viruses have evolved mechanisms to inhibit rnai defenses. therefore, ...	26034705
enhancement of enveloped virus entry by phosphatidylserine.	enveloped virus vectors are used in a wide variety of applications. we have discovered that treatment of cultured cells with phosphatidylserine (ps) liposomes can increase virus vector infection by up to 20-fold. this effect does not abrogate virus receptor requirements, is specific to ps compared to other phospholipids, and is limited to enveloped viruses. furthermore, the enhancement of infection does not occur through increases in virus receptor levels or virus binding, indicating that virus ...	16103200
seroepidemiology of selected arboviruses in febrile patients visiting selected health facilities in the lake/river basin areas of lake baringo, lake naivasha, and tana river, kenya.	arboviruses cause emerging and re-emerging infections affecting humans and animals. they are spread primarily by blood-sucking insects such as mosquitoes, ticks, midges, and sandflies. changes in climate, ecology, demographic, land-use patterns, and increasing global travel have been linked to an upsurge in arboviral disease. outbreaks occur periodically followed by persistent low-level circulation.	25700043
picornavirus morphogenesis.	the picornaviridae represent a large family of small plus-strand rna viruses that cause a bewildering array of important human and animal diseases. morphogenesis is the least-understood step in the life cycle of these viruses, and this process is difficult to study because encapsidation is tightly coupled to genome translation and rna replication. although the basic steps of assembly have been known for some time, very few details are available about the mechanism and factors that regulate this ...	25184560
self-assembly approaches to nanomaterial encapsulation in viral protein cages.	a perspective on abiotic material encapsulation inside virus capsids is provided. the emphasis is on the physical principles of virus assembly relevant to packaging, strategies for encapsulation and capsid modification, and on emerging applications.	19809586
structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme.	recent work has identified three distinct classes of viral membrane fusion proteins based on structural criteria. in addition, there are at least four distinct mechanisms by which viral fusion proteins can be triggered to undergo fusion-inducing conformational changes. viral fusion proteins also contain different types of fusion peptides and vary in their reliance on accessory proteins. these differing features combine to yield a rich diversity of fusion proteins. yet despite this staggering div ...	18568847
undiagnosed acute viral febrile illnesses, sierra leone.	sierra leone in west africa is in a lassa fever-hyperendemic region that also includes guinea and liberia. each year, suspected lassa fever cases result in submission of ≈500-700 samples to the kenema government hospital lassa diagnostic laboratory in eastern sierra leone. generally only 30%-40% of samples tested are positive for lassa virus (lasv) antigen and/or lasv-specific igm; thus, 60%-70% of these patients have acute diseases of unknown origin. to investigate what other arthropod-borne an ...	24959946
interferon-stimulated genes and their antiviral effector functions.	many viruses trigger the type i interferon (ifn) system, leading to the transcription of hundreds of interferon-stimulated genes (isgs). the products of these isgs exert numerous antiviral effector functions, many of which are still not fully described. recent efforts have been aimed at identifying which isgs are antiviral and further characterizing their mechanisms of action. ifn effectors vary widely in their magnitude of inhibitory activity and display combinatorial antiviral properties. coll ...	22328912
autophagy in cell death: an innocent convict?	the visualization of autophagosomes in dying cells has led to the belief that autophagy is a nonapoptotic form of programmed cell death. this concept has now been evaluated using cells and organisms deficient in autophagy genes. most evidence indicates that, at least in cells with intact apoptotic machinery, autophagy is primarily a pro-survival rather than a pro-death mechanism. this review summarizes the evidence linking autophagy to cell survival and cell death, the complex interplay between ...	16200202
stress granules and virus replication.	viruses are dependent on the cellular translation machinery for protein synthesis. part of the innate immune response to infection is activation of the stress kinase pkr which phosphorylates the alpha subunit of the initiation factor eif2. this results in inhibition of translation and is intended to block virus replication. a downstream effect of translational shutoff involves the formation of cytoplasmic granules, termed stress granules (sgs), that contain mrnas, initiation factors, ribosomal s ...	26388931
antiviral actions of interferons.	tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (ifns), as well as strategies evolved by viruses to antagonize the actions of ifns. furthermore, advances made while elucidating the ifn system have contributed significantly to our understanding in multiple areas of virology and molecular cell biology, ranging from pathways of signal transduction to the biochemical mechanisms of transcriptional and translational control to the molecula ...	11585785
a prolyl-isomerase mediates dopamine-dependent plasticity and cocaine motor sensitization.	synaptic plasticity induced by cocaine and other drugs underlies addiction. here we elucidate molecular events at synapses that cause this plasticity and the resulting behavioral response to cocaine in mice. in response to d1-dopamine-receptor signaling that is induced by drug administration, the glutamate-receptor protein metabotropic glutamate receptor 5 (mglur5) is phosphorylated by microtubule-associated protein kinase (mapk), which we show potentiates pin1-mediated prolyl-isomerization of m ...	23911326
a genome-wide rnai screen reveals that mrna decapping restricts bunyaviral replication by limiting the pools of dcp2-accessible targets for cap-snatching.	bunyaviruses are an emerging group of medically important viruses, many of which are transmitted from insects to mammals. to identify host factors that impact infection, we performed a genome-wide rnai screen in drosophila and identified 131 genes that impacted infection of the mosquito-transmitted bunyavirus rift valley fever virus (rvfv). dcp2, the catalytic component of the mrna decapping machinery, and two decapping activators, ddx6 and lsm7, were antiviral against disparate bunyaviruses in ...	23824541
the relationship between metabolism and the autophagy machinery during the innate immune response.	the innate immune response is shaped by multiple factors, including both traditional autophagy and lc3-associated phagocytosis (lap). as the autophagic machinery is engaged during times of nutrient stress, arising from scarcity or pathogens, we examine how autophagy, specifically lap, and cellular metabolism together influence macrophage function and the innate immune response.	23747248
metabolism of amyloid β peptide and pathogenesis of alzheimer's disease.	the conversion of what has been interpreted as "normal brain aging" to alzheimer's disease (ad) via transition states, i.e., preclinical ad and mild cognitive impairment, appears to be a continuous process caused primarily by aging-dependent accumulation of amyloid β peptide (aβ) in the brain. this notion however gives us a hope that, by manipulating the aβ levels in the brain, we may be able not only to prevent and cure the disease but also to partially control some very significant aspects of ...	23883611
optogenetic inhibition of synaptic release with chromophore-assisted light inactivation (cali).	optogenetic techniques provide effective ways of manipulating the functions of selected neurons with light. in the current study, we engineered an optogenetic technique that directly inhibits neurotransmitter release. we used a genetically encoded singlet oxygen generator, minisog, to conduct chromophore assisted light inactivation (cali) of synaptic proteins. fusions of minisog to vamp2 and synaptophysin enabled disruption of presynaptic vesicular release upon illumination with blue light. in c ...	23889931
the small gtpase arf1 modulates arp2/3-mediated actin polymerization via pick1 to regulate synaptic plasticity.	inhibition of arp2/3-mediated actin polymerization by pick1 is a central mechanism to ampa receptor (ampar) internalization and long-term depression (ltd), although the signaling pathways that modulate this process in response to nmda receptor (nmdar) activation are unknown. here, we define a function for the gtpase arf1 in this process. we show that arf1-gtp binds pick1 to limit pick1-mediated inhibition of arp2/3 activity. expression of mutant arf1 that does not bind pick1 leads to reduced sur ...	23889934
architecture and biogenesis of plus-strand rna virus replication factories.	plus-strand rna virus replication occurs in tight association with cytoplasmic host cell membranes. both, viral and cellular factors cooperatively generate distinct organelle-like structures, designated viral replication factories. this compartmentalization allows coordination of the different steps of the viral replication cycle, highly efficient genome replication and protection of the viral rna from cellular defense mechanisms. electron tomography studies conducted during the last couple of y ...	24175228
rna-based mechanisms regulating host-virus interactions.	rna interference (rnai) is an ancient process by which non-coding rnas regulate gene expression in a sequence-specific manner. the core components of rnai are small regulatory rnas, approximately 21-30 nucleotides in length, including small interfering rnas (sirnas) and micrornas (mirnas). the past two decades have seen considerable progress in our understanding of the molecular mechanisms underlying the biogenesis of sirnas and mirnas. recent advances have also revealed the crucial regulatory r ...	23550641
tumor-specific targeting with modified sindbis viral vectors: evaluation with optical imaging and positron emission tomography in vivo.	sindbis virus (sinv) infect tumor cells specifically and systemically throughout the body. sindbis vectors are capable of expressing high levels of transduced suicide genes and thus efficiently produce enzymes for prodrug conversion in infected tumor cells. the ability to monitor suicide gene expression levels and viral load in patients, after administration of the vectors, would significantly enhance this tumor-specific therapeutic option.	22847302
transfer and expression of small interfering rnas in mammalian cells using lentiviral vectors.	rna interference is a convenient tool for modulating gene expression. the widespread application of rna interference is made difficult because of the imperfections of the methods used for efficient target cell delivery of whatever genes are under study. one of the most convenient and efficient gene transfer and expression systems is based on the use of lentiviral vectors, which direct the synthesis of small hairpin rnas (shrnas), the precursors of sirnas. the application of these systems enables ...	23819033
virus infections in the nervous system.	virus infections usually begin in peripheral tissues and can invade the mammalian nervous system (ns), spreading into the peripheral (pns) and more rarely the central (cns) nervous systems. the cns is protected from most virus infections by effective immune responses and multilayer barriers. however, some viruses enter the ns with high efficiency via the bloodstream or by directly infecting nerves that innervate peripheral tissues, resulting in debilitating direct and immune-mediated pathology. ...	23601101
monitoring neuronal excitability at the synapse.	mammalian target of rapamycin (mtor) is a key player at the synapse regulating local translation and long-lasting synaptic plasticity. now, a new study by sosanya et al. (2013. j. cell biol. http://dx.doi.org/10.1083/jcb.201212089) investigates the molecular mechanism of how mtor suppresses local protein synthesis of a key potassium channel at activated synapses.	23836926
degradation of high affinity hud targets releases kv1.1 mrna from mir-129 repression by mtorc1.	little is known about how a neuron undergoes site-specific changes in intrinsic excitability during neuronal activity. we provide evidence for a novel mechanism for mtorc1 kinase-dependent translational regulation of the voltage-gated potassium channel kv1.1 messenger rna (mrna). we identified a microrna, mir-129, that repressed kv1.1 mrna translation when mtorc1 was active. when mtorc1 was inactive, we found that the rna-binding protein, hud, bound to kv1.1 mrna and promoted its translation. un ...	23836929
transgene-mediated suppression of the rna interference pathway in aedes aegypti interferes with gene silencing and enhances sindbis virus and dengue virus type 2 replication.	rna interference (rnai) is the major innate antiviral pathway in aedes aegypti that responds to replicating arboviruses such as dengue virus (denv) and sindbis virus (sinv). on the one hand, the mosquito's rnai machinery is capable of completely eliminating denv2 from ae. aegypti. on the other, transient silencing of key genes of the rnai pathway increases replication of sinv and denv2, allowing the viruses to temporally overcome dose-dependent midgut infection and midgut escape barriers (meb) m ...	23331493
polio, still lurking in the shadows.		23325224
specificity of resistance to dengue virus isolates is associated with genotypes of the mosquito antiviral gene dicer-2.	in contrast to the prevailing view that invertebrate immunity relies on broad-spectrum recognition and effector mechanisms, intrinsic genetic compatibility between invertebrate hosts and their pathogens is often highly specific in nature. solving this puzzle requires a better understanding of the molecular basis underlying observed patterns of invertebrate host-pathogen genetic specificity, broadly referred to as genotype-by-genotype interactions. here, we identify an invertebrate immune gene in ...	23193131
retargeting vesicular stomatitis virus glycoprotein pseudotyped lentiviral vectors with enhanced stability by in situ synthesized polymer shell.	the ability to introduce transgenes with precise specificity to the desired target cells or tissues is key to a more facile application of genetic therapy. here, we describe a novel method using nanotechnology to generate lentiviral vectors with altered recognition of host cell receptor specificity. briefly, the infectivity of the vesicular stomatitis virus glycoprotein (vsv-g) pseudotyped lentiviral vectors was shielded by a thin polymer shell synthesized in situ onto the viral envelope, and ne ...	23327104
mossy fiber-ca3 synapses mediate homeostatic plasticity in mature hippocampal neurons.	network activity homeostatically alters synaptic efficacy to constrain neuronal output. however, it is unclear how such compensatory adaptations coexist with synaptic information storage, especially in established networks. here, we report that in mature hippocampal neurons in vitro, network activity preferentially regulated excitatory synapses within the proximal dendrites of ca3 neurons. these homeostatic synapses exhibited morphological, functional, and molecular signatures of the specialized ...	23312519
discovery of host-viral protein complexes during infection.	viruses have co-evolved with their hosts, developing effective approaches for hijacking and manipulating host cellular processes. therefore, for their efficient replication and spread, viruses depend on dynamic and temporally regulated interactions with host proteins. the rapid identification of host proteins targeted by viral proteins during infection provides significant insights into mechanisms of viral protein function. the resulting discoveries often lead to unique and innovative hypotheses ...	23996249
small creatures use small rnas to direct antiviral defenses.	antiviral rna silencing has been recognized as an important defense mechanism in arthropods against rna viruses. however, the role of this pathway in dna virus infection remains largely unexplored. a report in this issue of the european journal of immunology provides new insight into the role of rna silencing in antiviral defense against dna viruses. huang and zhang [eur. j. immunol. 2013. 137-146] found that the dsdna virus white spot syndrome virus, an agriculturally important pathogen of shri ...	23322691
delivery systems for gene therapy.	the structure of dna was unraveled by watson and crick in 1953, and two decades later arber, nathans and smith discovered dna restriction enzymes, which led to the rapid growth in the field of recombinant dna technology. from expressing cloned genes in bacteria to expressing foreign dna in transgenic animals, dna is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. gene therapy provides ...	23901186
amyloid-β peptide: dr. jekyll or mr. hyde?	amyloid-β peptide (aβ) is considered a key protein in the pathogenesis of alzheimer's disease (ad) because of its neurotoxicity and capacity to form characteristic insoluble deposits known as senile plaques. aβ derives from amyloid-β protein precursor (aβpp), whose proteolytic processing generates several fragments including aβ peptides of various lengths. the normal function of aβpp and its fragments remains poorly understood. while some fragments have been suggested to have a function in norma ...	22735675
novel gene delivery systems.	gene therapy is an emerging field in medical and pharmaceutical sciences because of its potential in treating chronic diseases like cancer, viral infections, myocardial infarctions, and genetic disorders. application of gene therapy is limited because of lack of suitable methods for proper introduction of genes into cells and therefore, this is an area of interest for most of the researchers. to achieve successful gene therapy, development of proper gene delivery systems could be one of the most ...	23799200
experimental vaccines against potentially pandemic and highly pathogenic avian influenza viruses.	influenza a viruses continue to emerge and re-emerge, causing outbreaks, epidemics and occasionally pandemics. while the influenza vaccines licensed for public use are generally effective against seasonal influenza, issues arise with production, immunogenicity, and efficacy in the case of vaccines against pandemic and emerging influenza viruses, and highly pathogenic avian influenza virus in particular. thus, there is need of improved influenza vaccines and vaccination strategies. this review di ...	23440999
reminiscence of our research on membrane phospholipids in mammalian cells by using the novel technology.	by using "our devised up-to-the-second technique" over 30 years ago, we succeeded in the first isolation in the world of the three different kinds of mammalian cell mutants defective in the biosynthesis on each of phosphatidylserine (ps), cardiolipin (cl) and sphingomyelin (sm) from the parental cho cells. as the results, we found that during the biosyntheses of ps and sm, the biosynthetic precursor or the final lipids are transported from their synthesized intracellular organelles to the plasma ...	23229749
reemergence of chikungunya virus in cambodia.	chikungunya virus (chikv), probably asian genotype, was first detected in cambodia in 1961. despite no evidence of acute or recent chikv infections since 2000, real-time reverse transcription pcr of serum collected in 2011 detected chikv, east central south african genotype. spatiotemporal patterns and phylogenetic clustering indicate that the virus probably originated in thailand.	23171736
structural and dynamic determinants of type i interferon receptor assembly and their functional interpretation.	type i interferons (ifns) form a network of homologous cytokines that bind to a shared, heterodimeric cell surface receptor and engage signaling pathways that activate innate and adaptive immune responses. the ability of ifns to mediate differential responses through the same cell surface receptor has been subject of a controversial debate and has important medical implications. during the past decade, a comprehensive insight into the structure, energetics, and dynamics of ifn recognition by its ...	23046138
host cell factors in filovirus entry: novel players, new insights.	filoviruses cause severe hemorrhagic fever in humans with high case-fatality rates. the cellular factors exploited by filoviruses for their spread constitute potential targets for intervention, but are incompletely defined. the viral glycoprotein (gp) mediates filovirus entry into host cells. recent studies revealed important insights into the host cell molecules engaged by gp for cellular entry. the binding of gp to cellular lectins was found to concentrate virions onto susceptible cells and mi ...	23342362
p bodies, stress granules, and viral life cycles.	eukaryotic mrnas are in a dynamic equilibrium between different subcellular locations. translating mrnas can be found in polysomes, mrnas stalled in translation initiation accumulate in stress granules and mrnas targeted for degradation or translation repression can accumulate in p bodies. partitioning of mrnas between polysomes, stress granules, and p bodies affects rates of translation and mrna degradation. host proteins within p bodies and stress granules can enhance or limit viral infection, ...	18407064
viral and developmental cell fusion mechanisms: conservation and divergence.	membrane fusion is a fundamental requirement in numerous developmental, physiological, and pathological processes in eukaryotes. so far, only a limited number of viral and cellular fusogens, proteins that fuse membranes, have been isolated and characterized. despite the diversity in structures and functions of known fusogens, some common principles of action apply to all fusion reactions. these can serve as guidelines in the search for new fusogens, and may allow the formulation of a cross-speci ...	18194649
cytopathogenesis and inhibition of host gene expression by rna viruses.	many viruses interfere with host cell function in ways that are harmful or pathological. this often results in changes in cell morphology referred to as cytopathic effects. however, pathogenesis of virus infections also involves inhibition of host cell gene expression. thus the term "cytopathogenesis," or pathogenesis at the cellular level, is meant to be broader than the term "cytopathic effects" and includes other cellular changes that contribute to viral pathogenesis in addition to those chan ...	11104816
role of antibodies in controlling viral disease: lessons from experiments of nature and gene knockouts.		11024107
epidermal growth factor and membrane trafficking. egf receptor activation of endocytosis requires rab5a.	activated epidermal growth factor receptors recruit various intracellular proteins leading to signal generation and endocytic trafficking. although activated receptors are rapidly internalized into the endocytic compartment and subsequently degraded in lysosomes, the linkage between signaling and endocytosis is not well understood. here we show that egf stimulation of nr6 cells induces a specific, rapid and transient activation of rab5a. egf also enhanced translocation of the rab5 effector, earl ...	11062256
leader proteinase of the beet yellows closterovirus: mutation analysis of the function in genome amplification.	the beet yellows closterovirus leader proteinase (l-pro) possesses a c-terminal proteinase domain and a nonproteolytic n-terminal domain. it was found that although l-pro is not essential for basal-level replication, deletion of its n-terminal domain resulted in a 1, 000-fold reduction in rna accumulation. mutagenic analysis of the n-terminal domain revealed its structural flexibility except for the 54-codon-long, 5'-terminal element in the corresponding open reading frame that is critical for e ...	11000252
essential and dispensable virus-encoded replication elements revealed by efforts to develop hypoviruses as gene expression vectors.	we have investigated whether hypoviruses, viral agents responsible for virulence attenuation (hypovirulence) of the chestnut blight fungus cryphonectria parasitica, could serve as gene expression vectors. the infectious cdna clone of the prototypic hypovirus chv1-ep713 was modified to generate 20 different vector candidates. although transient expression was achieved for a subset of vectors that contained the green fluorescent protein gene from aequorea victoria, long-term expression (past day 8 ...	10906211
translational control of viral gene expression in eukaryotes.	as obligate intracellular parasites, viruses rely exclusively on the translational machinery of the host cell for the synthesis of viral proteins. this relationship has imposed numerous challenges on both the infecting virus and the host cell. importantly, viruses must compete with the endogenous transcripts of the host cell for the translation of viral mrna. eukaryotic viruses have thus evolved diverse mechanisms to ensure translational efficiency of viral mrna above and beyond that of cellular ...	10839817
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 ...	17035522
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 ...	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 ...	22319551
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 ...	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 ...	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 ...	21927636
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 ...	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 ...	21424383
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 ...	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 ...	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 ...	21382555
thematic issue on how autophagosomes find their targets.		21178396
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.	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 ...	21640425
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 ...	21248839
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 ...	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 ...	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 ...	11726686
tackling the most difficult diseases. genetics and genomics open new strategies to fight vector-borne diseases.		11600446
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 ...	20942857
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 ...	21172614
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 ...	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; ( ...	19641503
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' ...	22889221
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 ...	22901540
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 ...	22980330
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 ...	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 ...	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 ...	22897054
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 ...	22723639
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 ...	22915114