The method of frequency tagging allowed us to separate the EEG re

The method of frequency tagging allowed us to separate the EEG responses to the attended and ignored stimuli

and directly compare steady-state visual evoked potential (SSVEP) amplitudes elicited by each stimulus before and after cue onset. We found that younger adults show a clear attentional enhancement of SSVEP amplitude in the post-cue interval, while older adults’ SSVEP responses to attended and ignored stimuli do not differ. Thus, in situations where attentional selection cannot be spatially resolved, older adults show a deficit see more in selection that is not shared by young adults. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“The germline JAK2 haplotype 46/1, tagged by the ‘C’ allele of single-nucleotide polymorphism (SNP) rs12343867 (C/T), has been associated with JAK2V617F (VF)-positive myeloproliferative neoplasms. SNP rs12343867 was genotyped using bone marrow DNA in 226 consecutive patients with essential thrombocythemia (ET) with concomitant analysis of VF allele burden. The incidence of the 46/1-linked C allele was significantly higher in ET (genotype: CC 15%, CT 52%, TT 33%; C-allele frequency: 41%) than in population

AZD0156 mw controls (P<0.01). Genotype distributions were similar among VF-positive/VF-negative patients (genotype: CC 18/11%, CT 52/53%, TT 30/36%; C-allele: 44/38%; P = 0.29). Haplotype 46/1 frequency was remarkably similar when comparing VF-negative patients to those with <10% VF allele burden, but significantly higher in the presence of >10% VF allele burden (genotype: CC 11/13/38%, CT 53/56/38%,

TT 36/31/24%; C-allele frequency: 38/41/57%; P<0.01). The clinical features of 46/1-positive and-negative ET were indistinguishable, including blood counts, rate of thrombosis/disease transformation and survival. We conclude that JAK2 haplotype 46/1 confers susceptibility to developing ET independent of VF mutational status and does not seem to further affect the clinical phenotype or prognosis. Leukemia (2010) 24, 110-114; doi:10.1038/leu.2009.226; published online 22 October 2009″
“Considering the multiplicity of symptoms associated with multiple sclerosis (MS), there is possibility that hypocretin system function might be involved in the pathogenesis of the disease. The current study aimed to Ribociclib supplier investigate the hypocretin-1 levels in cerebrospinal fluid (CSF) of MS patients in relation to different neurological deficit measures including: Ambulation Index (AI), Expanded Disability Status Scale (EDSS), Fatigue Severity Scale (FSS), and Epworth Sleepiness Scale (ESS) in relapse-onset MS patients. 53 subjects were included into the study: 38 patients with a diagnosis of MS and 15 healthy controls. Among MS patients, 25 had relapsing-remitting and 13 secondary progressive MS. CSF hypocretin-1 levels did not differ between MS patients and healthy controls (p > 0.05). A positive correlation between hypocretin-1 level and fatigue level was found in MS patients (p < 0.

Similar results were seen after blocking the biological effects o

Similar results were seen after blocking the biological effects of the CCL5 receptors. In conclusion, we have identified an important proinflammatory

role for activated intrahepatic V alpha 14iNKT cells in positively influencing hepatic CCL5 production to promote acute liver inflammation and injury. Therefore, our findings highlight the blockade of CCL5 interaction with a cognate receptor(s) as an important potential strategy to alleviate liver pathology associated with replication-defective adenovirus infection.”
“Patients selleck products with implanted SynchroMed spinal infusion pumps (Medtronic, Inc., Minneapolis, MN) routinely undergo magnetic resonance imaging at our institution. In August 2008, Medtronic issued an urgent medical device correction report regarding several pumps. Because of the rare potential “”for a delay in the return of proper drug infusion”" and “”for a delay in the logging of motor stall events,”" “”a patient’s pump must be interrogated after MRI exposure in order to confirm proper pump functionality.”" This is particularly important in patients receiving intrathecal baclofen, for whom a delay in return of proper

pump infusion could lead to life-threatening selleckchem baclofen withdrawal syndrome. The objective of this report is to present our experience and protocol of performing magnetic resonance imaging in patients with implanted SynchroMed EL pumps.

We retrospectively reviewed records of 86 patients with implanted SynchroMed EL spinal infusion pumps who underwent 112 examinations on 1.5-T magnetic resonance imaging scanners from September 1, 1998 to July 7, 2004.

No SynchroMed EL pumps were damaged by magnetic resonance imaging, and the programmable settings remained unchanged in all patients.

Our data suggest that SynchroMed EL pump malfunction is indeed rare after routine clinical 1.5-T magnetic resonance imaging

examinations. However, based on the Medtronic correction report, we perform pump interrogation before and after imaging.”
“Immune responses and the components of protective immunity following norovirus infection in humans are poorly understood. Although antibody responses following norovirus infection have been partially characterized, T cell responses in humans remain largely undefined. In contrast, T cells have been shown to be essential for viral clearance of mouse Adenosine norovirus (MNV) infection. In this paper, we demonstrate that CD4(+) T cells secrete gamma interferon (IFN-gamma) in response to stimulation with MNV virus-like particles (VLPs) after MNV infection, supporting earlier reports for norovirus-infected mice and humans. Utilizing this model, we immunized mice with alphavirus vectors (Venezuelan equine encephalitis [VEE] virus replicon particles [VRPs]) expressing Norwalk virus (NV) or Farmington Hills virus (FH) virus-like particles to evaluate T cell epitopes shared between human norovirus strains.

Barium levels in other tissues including the cerebrum, cerebellum

Barium levels in other tissues including the cerebrum, cerebellum, heart, liver and kidney were undetectably low in both groups.

Conclusions: Our results demonstrate for the first time that low-dose barium administered PHA-848125 by drinking water specifically distributes to inner ears resulting in severe ototoxicity with degeneration of inner ears in mice. (C) 2012 Elsevier Inc. All rights reserved.”
“The adrenal glands (AGs) are endocrine organs essential for life. They undergo a fetal to adult developmental maturation process, occurring in rats during the first postnatal month.

The molecular modifications underlying these ontogenic changes are essentially unknown. Here we report the results of a comparative proteomic analysis performed on

neonatal (Postnatal day 3) versus adult (Postnatal day 30) AGs, searching for proteins with a relative higher abundance at each age. We have identified a subset of proteins with relevant expression in each developmental period using 2-DE and DIGE analysis. The identified proteins belong to several functional categories, including proliferation/differentiation, cell metabolism, and steroid biosynthesis. To study if the changes in the proteome are correlated with changes at the mRNA level, we have randomly selected several proteins with differential expression and measured their relative mRNA levels click here using quantitative RT-PCR. Cell-cycle regulating proteins (retinoblastoma binding protein 9 and prohibitin) with contrasting effects on proliferation are expressed differentially in neonatal and adult AG. Progesterone metabolizing enzymes, up-regulated in

the neonatal gland, might contribute to the hyporesponsiveness of the adrenal cortex characteristic of this developmental period. We have also observed in the adult gland a marked up-regulation of enzymes involved in NAD(P)H production, thus providing the reducing power necessary for steroid hormone biosynthesis.”
“Background: Controversy persists as to whether all calf vein thrombi should be treated Dynein with anticoagulation or observed with duplex surveillance. We performed a systematic review of the literature to assess whether data could support either approach, followed by examination of its natural history by stratifying results according to early dot propagation, pulmonary emboli (PE), recurrence, and postthrombotic syndrome (PTS).

Methods: A total of 1513 articles were reviewed that were published from January 1975 to August 2010 using computerized database searches of PubMed, Cochrane Controlled Trials Register, and extensive cross-references. English-language studies specifically examining calf deep vein thrombosis (C-DVT) defined as axial and/or muscular veins of the calf, not involving the popliteal vein, were included. Papers were independently reviewed by two investigators (E.M., F.L.) and quality graded based on nine methodologic standards reporting on four outcome parameters.

In addition, cells transfected with miR-K10a showed less inductio

In addition, cells transfected with miR-K10a showed less induction Selleck Silmitasertib of apoptosis by annexin V staining and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assays. Finally, the downregulation of TWEAKR by miR-K10a in primary human endothelial cells resulted in a decrease in levels of expression of the proinflammatory cytokines interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) in response to TWEAK. These results identify and validate an important cellular target

of KSHV miRNAs. Furthermore, we demonstrate that a viral miRNA protects cells from apoptosis and suppresses a proinflammatory response, which may have significant implications in the complex context of KS lesions.”
“A growing body of evidence has demonstrated a role for group II metabotropic glutamate receptors (mGluRs) in the reinforcing effects of cocaine.

These receptors are important given their location in limbic-related areas, and their ability to control the release of glutamate and other neurotransmitters. They are also potential targets for novel pharmacotherapies for cocaine addiction. The present study investigated the impact of chronic cocaine self-administration (9.0 mg/kg/session for 100 sessions, 900 mg/kg total intake) on the densities of group II mGluRs, as assessed with in vitro receptor autoradiography, HKI-272 datasheet in the striatum of adult male rhesus monkeys. Binding of [(3)H]LY341495 to group II mGluRs in control animals was heterogeneous, with a medial

to lateral gradient in binding density. Significant elevations in the density of group II mGluRs following chronic cocaine self-administration Carteolol HCl were measured in the dorsal, central and ventral portions of the caudate nucleus (P < 0.05), compared to controls. No differences in receptor density were observed between the groups in either the putamen or nucleus accumbens. These data demonstrate that group II mGluRs in the dorsal striatum are more sensitive to the effects of chronic cocaine exposure than those in the ventral striatum. Cocaine-induced dysregulation of the glutamate system, and its consequent impact on plasticity and synaptic remodeling, will likely be an important consideration in the development of novel pharmacotherapies for cocaine addiction. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Although the herpes simplex virus type 1 (HSV-1) genome might be expected to induce a DNA damage response, the ATR kinase is not activated in infected cells. We previously proposed that spatial uncoupling of ATR from its interaction partner, ATRIP, could be the basis for inactivation of the ATR kinase in infected cells; however, we now show that ATR and ATRIP are in fact both recruited to HSV-1 replication compartments and can be coimmunoprecipitated from infected-cell lysates. ATRIP and replication protein A (RPA) are recruited to the earliest detectable prereplicative sites, stage II microfoci.

“BackgroundDeep dermatophytosis

“BackgroundDeep dermatophytosis Necrostatin-1 ic50 is a

severe and sometimes life-threatening fungal infection caused by dermatophytes. It is characterized by extensive dermal and subcutaneous tissue invasion and by frequent dissemination to the lymph nodes and, occasionally, the central nervous system. The condition is different from common superficial dermatophyte infection and has been reported in patients with no known immunodeficiency. Patients are mostly from North African, consanguineous, multiplex families, which strongly suggests a mendelian genetic cause.

MethodsWe studied the clinical features of deep dermatophytosis in 17 patients with no known immunodeficiency from eight unrelated Tunisian, Algerian, and Moroccan families. Because CARD9 (caspase recruitment domain-containing protein 9) deficiency has been reported in an Iranian family with invasive fungal infections, we also sequenced CARD9 in the patients.

ResultsFour patients

died, at 28, 29, 37, and 39 years of age, with clinically active deep dermatophytosis. No other severe infections, fungal or otherwise, were reported in the surviving patients, who ranged in age from 37 to 75 years. The 15 Algerian and Tunisian patients, from seven unrelated families, had a homozygous Q289X CARD9 allele, due to a founder effect. The 2 Moroccan siblings were homozygous for the R101C CARD9 allele. Oxymatrine Both alleles are rare deleterious variants. The familial segregation of these alleles see more was consistent with autosomal recessive inheritance and complete clinical penetrance.

ConclusionsAll the patients with deep dermatophytosis had autosomal recessive CARD9 deficiency. Deep dermatophytosis appears to be an important clinical manifestation of CARD9 deficiency. (Funded by Agence Nationale pour la Recherche and others.)

Dermatophyte infections

are unusual but can cause serious invasive disease. In this report, autosomal recessive CARD9 deficiency indicated a potential genetic susceptibility to deep dermatophytosis, a severe invasive fungal infection. Deep dermatophytosis is a rare, invasive, sometimes life-threatening, fungal infection caused by dermatophytes.(1) These filamentous fungi are ubiquitous and usually cause benign infections that are limited to keratinized tissues and lead to onychomycosis, tinea corporis, tinea cruris, tinea pedis, or tinea capitis.(2) In deep dermatophytosis, dermatophytes invade the dermis and hypodermis and disseminate to the skin, hair, nails, lymph nodes, and brain.(3) Deep dermatophytosis has been reported in patients with the human immunodeficiency virus and patients who are receiving immunosuppressive therapy.(3) It was first described in 1959 in otherwise apparently healthy persons as dermatophytic disease.(1) Forty-five cases have been reported …

Their electrophysiological behavior may serve as indicator of chr

Their electrophysiological behavior may serve as indicator of chronic ethanol effects on the cerebellum. Here, we studied the effects of ethanol consumption through breastfeeding on motor behavior, histology and PCs electrophysiology. Mice with different maternal drinking regimen (ethanol, E or sucrose, S) during prenatal (E/and S/) and postnatal period (/E and/S) were compared. Motor performance in the runway and rotarod tests Blasticidin S price was significantly worse in mice exposed to ethanol prenatally (E/E and E/S) than in mice exposed to sucrose (S/S), with a limited influence,

if any, of mother regimen during lactation (E/S vs E/E). A loss of 20-25% of PCs was found for both E/S and E/E compared to S/S mice but PC numbers were similar in S/E and S/S. Mean PC spontaneous simple spike firing rate and rhythmicity were higher in E/S and E/E than in S/S but there was no difference between S/E and S/S. Complex spike frequency was similar in all groups. In contrast, complex spike duration and the related pause induced on the simple spike firing were shorter in E/E and in E/S, but no difference was found between S/E and S/S. We conclude that cerebellar dysfunction induced by maternal ethanol consumption in mice depends

upon the drinking regimen during pregnancy and not during lactation. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Stochasticity is one of the most important properties in gene expression. Noise originates from two sources: Bindarit research buy thermal fluctuation inherent in the system (intrinsic noise) and variabilities in factors external to the system that usually result to the fluctuation in the kinetic parameters (extrinsic noise). This paper studies analytically the stationary fluctuation of the number of protein molecules through a mathematical model involving both sources of noises. The results in this paper show that the two sources of noises interlock to each other to generate total fluctuation

in protein numbers. In particular, the extrinsic noises effect the total fluctuation in multiple ways, including the extrinsic fluctuation, the correlation with intrinsic noise, the alternation of the time averaging (-)-p-Bromotetramisole Oxalate of transcription and translation. and the amplification of the total fluctuation by an impact factor. The impact factor is pronounced when the fluctuations in the degradation rates of mRNA or protein are large. Moreover, the extrinsic noise to the translational rate generates large fluctuation when the translational efficiency is too low. which is contrast to the translational bursting in high translational efficiency because of intrinsic noise. These results suggest that it is important to control the mRNA and protein degradation rate as well as the translational efficiency in order to attenuate the fluctuation in gene expression in the present of both intrinsic and extrinsic noises. (c) 2008 Elsevier Ltd. All rights reserved.

This similarity has to be taken into account when searching for b

This similarity has to be taken into account when searching for biomarkers of renal disease.”
“Background/Aims: An epidemiological survey of endemic Immunology & Inflammation inhibitor nephropathy (EN) was performed in endemic Croatian areas and the current prevalence was compared to that reported for the same villages several decades ago. Methods: A total of 2,487 adult farmers from 6 endemic

villages and 3 non-endemic villages were enrolled. An extensive epidemiological questionnaire, clinical examination and laboratory analyses of blood and urine were performed. According to the modified WHO criteria, participants were classified into diseased, suspected of having EN, and those at risk of developing EN. Results: The overall prevalence of EN in the Croatian areas was 1.0%, ranging between 0.3 and 2.3% in different villages. Those suspected of having

EN amounted to 3.9%. In the endemic villages a decreasing trend in the prevalence of EN was observed comparable to the results obtained in previous surveys. It is interesting to note that no EN patients were recorded in the endemic village of Dubocac. Conclusion: The prevalence of EN in the endemic Croatian areas appears to be decreasing. For the first time, we failed to detect any EN patients CA4P concentration in a village that was previously considered endemic, which might indicate that EN is diminishing. Copyright (C) 2011 S. Karger AG, Basel”
“About 860 G-protein-coupled receptors (GPCRs) mediate their

actions via heterotrimeric Selleckchem Decitabine G-proteins. Their activation releases G alpha from G beta lambda subunits. The type of G alpha subunit dictates the major signalling proteins involved: adenylyl cyclase, PLC and rhoGEF. The rostral ventrolateral medulla (RVLM), containing the rostral C1 (rC1) cell group, sets and maintains the tonic and reflex control of blood pressure and a plethora of inputs converge onto these neurons. We determined the relative abundance of 10 G alpha subunit mRNAs, representing the four major families, within the RVLM, using quantitative RT-PCR. In situ hybridisation (ISH) combined with immunohistochemistry (IHC) was used to quantify and compare this expression in rC1 with that in the A1 and A5 cell groups. The relative abundance of G alpha subunit mRNAs and a comparison of gene expression levels were quantitatively determined in normotensive and hypertensive rat strains. All 10 G alpha mRNAs were detected in the RVLM of Sprague-Dawley (SD) rats with relative abundance such that G alpha s > G alpha i2 > G alpha o > G alpha q > G alpha L > G alpha 11 > G alpha i3 > G alpha i1 > G alpha 12 > G alpha 13. The high abundance of G alpha mRNAs signalling via adenylyl cyclase indicates the importance of associated GPCRs.

The nonstructural NSs protein is the primary IFN antagonist encod

The nonstructural NSs protein is the primary IFN antagonist encoded by Bunyamwera virus (BUNV), the prototype of the Orthobunyavirus genus

and the family Bunyaviridae. The NSs protein interferes with RNA polymerase II-mediated transcription, thereby inhibiting cellular mRNA production, including IFN mRNAs. A selleck recombinant virus, rBUNdelNSs, that is unable to express the NSs protein does not inhibit cellular transcription and is a strong IFN inducer. We report here that cells stimulated into the antiviral state by IFN-beta treatment were protected against wild-type BUNV and rBUNdelNSs infection but addition of IFN-beta after infection had little effect on the replication cycle of either virus. By screening a panel of cell lines that overexpressed individual IFN-stimulated genes, we found that protein kinase click here R (PKR), MTAP44, and particularly viperin appreciably restricted BUNV replication. The enzymatic activities of PKR and viperin were required for their inhibitory activities. Taken together, our data show that the restriction of BUNV replication mediated by IFN is an accumulated effect of at least three IFN-stimulated genes that probably act on different stages of the viral replication cycle.”
“Previous studies have

shown that lesions of the peripheral vestibular system result in electrophysiological dysfunction in the hippocampus. Given the importance of glutamate as a neurotransmitter in the hippocampus, it was predicted that bilateral vestibular deafferentation (BVD) would alter the expression of NMDA and AMPA receptors in this area of the brain. However, the results of studies conducted to date are inconsistent. In this study, we performed principal component analysis (PCA) on the expression of the NR1, NR2B, GluR1, GluR2 and GluR3 glutamate receptor subunits, as well as calmodulin kinase II alpha. (CaMKII alpha) and phosphorylated CaMKII alpha (pCaMKII alpha),

in the rat CM, CA2/3 and dentate gyrus (DG) subregions of the hippocampus, at 6 months following BVD, using western blotting. The expressions of the different Florfenicol glutamate receptor subunits, in terms of NMDA versus AMPA receptor subunits, as well as CaMKII alpha and pCaMKII alpha, were tightly correlated, and this was shown again the loading plots. However, the pattern of the contributions of each protein to the first 2 principal components appeared to be inverted for the BVD group compared to the sham group. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Long-term changes in the hypothalamic-pituitary-adrenal (HPA) axis as a result of early life stress could be related to the development of substance use disorders during adulthood.

These data confirm that nitric oxide donors have potential therap

These data confirm that nitric oxide donors have potential therapeutic utility to increase glucose uptake in humans, but that SNP only achieves this in supratherapeutic doses. Further study to delineate mechanisms and the therapeutic window is warranted. (C)

2009 Elsevier Inc. All rights reserved.”
“The phosphoinositide 3-kinase/Akt pathway is an important signalling pathway governing cell survival and proliferation in acute myeloid leukaemia (AML). As full activation of Akt requires phosphorylation on both threonine 308 (Thr308) and serine 473 (Ser473) residues, we studied the level of phosphorylation on the both sites in 58 AML samples by flow cytometry. The ratio of the mean fluorescence intensity of Thr308 and Ser473 represented a continuum ranging from 0.3 to 5.6 and from 0.4 to 2.87, respectively. There Blasticidin S in vivo were no significant correlations between age, gender, French-American-British classification, leukocytosis, FLT3-ITD and Akt phosphorylation. However, the level of phosphorylation on Thr308, but not on Ser473, was significantly correlated with high-risk karyotype. Thr308(high) patients had Tozasertib nmr significantly shorter overall survival (11 vs 47 months; P = 0.01), event-free survival (9 vs 26 months; P = 0.005) and relapse-free survival (10 months vs not reached; P = 0.02) than Thr308(low) patients. Neither screening for

AKT1 E17K mutation nor changes in the level of PTEN expression and phosphorylation could be linked to increased phosphorylation on Thr308 in high-risk cytogenetic AML cells. However, PP2A activity was significantly reduced in high-risk samples compared with intermediate-risk samples. Moreover, the specific Akt inhibitor, Akti-1/2, inhibited cell

proliferation and clonogenic properties, and induced apoptosis in AML cells with high-risk cytogenetics, suggesting that Akt may represent a therapeutic target in high-risk AML. Leukemia (2009) 23, 1029-1038; doi: 10.1038/leu.2008.395; published online 22 January 2009″
“Mitochondria triclocarban recently have emerged as important sites in controlling NO levels within the cell. In this study, the synthesis of nitric oxide (NO) from nitrite and its degradation by mitochondria isolated from Arabidopsis thaliana were examined. Oxygen and NO concentrations in the reaction medium were measured with specific electrodes. Nitrite inhibited the respiration of isolated A. thaliana mitochondria, in competition with oxygen, an effect that was abolished or potentiated when electron flow occurred via alternative oxidase (AOX) or cytochrome c oxidase (COX), respectively. The production of NO from nitrite was detected electrochemically only under anaerobiosis because of a superoxide-dependent process of NO degradation. Electron leakage from external NAD(P)H dehydrogenases contributed the most to NO degradation as higher rates of Amplex Red-detected H(2)O(2) production and NO consumption were observed in NAD(P)H-energized mitorchondria.

It was concluded that the results from the NIH mouse protection t

It was concluded that the results from the NIH mouse protection test using 9 mice per dilution are in good agreement with the results obtained

using 18 mice per dilution. Therefore, nine animals per dilution is a suitable number to meet the statistical requirement for valid assays. (c) 2009 Elsevier B.V. All rights reserved.”
“There is increasing evidence that sleep may be involved in memory consolidation. However, there remain comparatively few studies that have explored the relationship between sleep and memory reconsolidation. At present study, we tested the effects of rapid eye movement sleep deprivation (RSD) on the reconsolidation of cued (experiment 1) and contextual (experiment 2) fear memory in rats. Behaviour procedure involved four

training phases: habituation, fear Rabusertib manufacturer conditioning, reactivation and test. Rats were subjected to 6 h RSD starting either immediately after reactivation or 6 It later. The control rats were returned to their home cages immediately after reactivation and left undisturbed. Contrary to those hypotheses speculating a potential role of sleep in reconsolidation, we found that post-reactivation RSD whether from 0 to 6 It or 6 to 12 h had no effect on the reconsolidation of both cued and contextual fear memory. However, our present results did not exclude the potential roles of non-rapid eye movement sleep in the Selleckchem VX-770 reconsolidation of fear memory or sleep in the reconsolidation of other memory paradigms. (C) 2009 Elsevier Celecoxib Ireland Ltd. All rights reserved.”
“Human respiratory syncytial virus (HRSV) is the major pathogen leading to respiratory disease in infants and neonates worldwide. An effective vaccine has not yet been developed against this virus, despite considerable efforts in basic and clinical research. HRSV replication

is independent of the nuclear RNA processing constraints, since the virus genes are adapted to the cytoplasmic transcription, a process performed by the viral RNA-dependent RNA polymerase. This study shows that meaningful nuclear RNA polymerase II dependent expression of the HRSV nucleoprotein (N) and phosphoprotein (F) proteins can only be achieved with the optimization of their genes, and that the intracellular localization of N and P proteins changes when they are expressed out of the virus replication context. Immunization tests performed in mice resulted in the induction of humoral immunity using the optimized genes. This result was not observed for the non-optimized genes. In conclusion, optimization is a valuable tool for improving expression of HRSV genes in DNA vaccines. (c) 2009 Elsevier B.V. All rights reserved.