“
“The fifth instar larvae of the silkworm Bombyx mori L were exposed to selected high temperatures (35 and 40 degrees C) in order to understand the changes in the level of catalase activity in the three tissues of fat body, midgut

and haemolymph of the five selected bivoltine breeds and their 9 quantitative traits, namely larval weight, cocoon weight, shell weight, shell ratio, filament length, filament weight, denier, renditta and effective rearing rate (ERR), also the correlation between them under high temperature conditions were examined. Catalase activity resulting in fat body revealed a positive correlation between the control (28 +/- 1 GDC-0994 degrees C) and 40 +/- 1 degrees C. The CSR2 breed showed the most level of thermotolerance and catalase activity, compared with the CSR4, JROP, NB4D2 and KA breeds. It was found that the level of catalase activity in fat body may be a reliable biochemical index to recognize thermotolerant breeds in order to develop resistant hybrids for tropical areas. (C) 2010 Elsevier Ltd. All rights reserved.”
“BACKGROUND: AG1478 is an epithelial growth factor receptor tyrosine kinase inhibitor. Epithelial growth factor receptor regulates the expression of cadherin in

cells via its action on beta-catenin, and N-cadherin selleck kinase inhibitor downregulation promotes infiltration and cerebrospinal fluid (CSF) dissemination of glioma cells.

OBJECTIVE: To confirm whether AG1478 might have indirect effects on N-cadherin upregulation and whether, in addition to exhibiting an antitumor effect, AG1478 might also exert protective effects against infiltration and CSF dissemination.

METHODS: Green fluorescent protein (GFP) was introduced Vorinostat into C6 cells to obtain C6-GFP, and N-cadherin was introduced into C6-GFP to obtain C6-GFP-NCH. To confirm N-cadherin upregulation and the anti-infiltrative effect of AG1478 in vitro, we conducted Western

blotting, aggregation assays, and Matrigel infiltration experiments. To confirm whether AG1478 exerted preventive effects against infiltration and CSF dissemination in vivo, in addition to exerting an antitumor effect, AG1478 was administered via various routes to rat C6-GFP inoculation models.

RESULTS: In vitro experiments demonstrated that AG1478 could indirectly upregulate N-cadherin in C6-GFP and reduced infiltration to the level of C6-GFP-NCH. In in vivo experiments, intrathecal administration of AG1478 inhibited CSF dissemination but did not prevent infiltration. Direct administration into the tumor mass demonstrated antitumor and anti-infiltration effects and inhibited CSF dissemination in each cistern, except at the convexity. Direct and intrathecal administration was the best treatment, resulting in significantly reduced numbers of disseminated cells in the CSF smear test.

CONCLUSION: AG1478 was highly effective both when administered intrathecally and when inoculated directly into the tumor mass.

These results suggest that the antiangiogenic activity of KR-31831 is mediated through VEGFR2 and microPET serves as a useful molecular imaging tool for evaluation of a newly developed angiogenesis inhibitor, KR-31831. (C) 2012 Elsevier Inc. All rights reserved.”
“Research on methamphetamine (MA) toxicity primarily focuses on the possibility Blebbistatin molecular weight that some of the behavioural problems in human MA users might be caused by damage to brain

dopamine neurones. However, animal data also indicate that MA can damage brain serotonin neurones, and it has been suggested that cognitive problems and aggression in MA users might be explained by serotonergic damage. As information on the brain serotonin system in human find more MA users is fragmentary, our objective was to determine whether protein levels of serotonin transporter (SERT), a key marker of serotonin neurones, are decreased in brain of chronic MA users.

SERT immunoreactivity was measured using an immunoblotting procedure in autopsied brain of 16 chronic MA users testing positive for the drug in blood and brain and matched controls.

SERT levels were non-significantly decreased (-14% to -33%) in caudate, putamen and thalamus (normal in hippocampus), and, unlike

the robust striatal dopamine reduction, there was marked overlap between control and MA user ranges. Concentrations of SERT were significantly decreased (-23% to -39%) in orbitofrontal and occipital cortices (normal in frontopolar and temporal cortices).

Our data suggest that MA might modestly damage brain serotonin neurones and/or inhibit SERT protein expression, with cerebral cortex being more affected than sub-cortical regions. The SERT reduction in orbitofrontal cortex complements other data suggesting involvement of this area in MA-related behaviour. Decreased selleck compound brain SERT could also be related to the clinical finding that treatment with a selective serotonin re-uptake inhibitor might increase

relapse to MA.”
“Twenty years ago, scientists predicted that better understanding of fiber development would lead to novel ways to engineer superior cotton fiber. Advances in genetic resources, DNA markers, DNA sequence information, and gene expression data have indeed provided new insights into fiber initiation, elongation and maturation. Many exciting applications of this knowledge offer the potential to select better cotton genotypes more effectively in mainstream breeding programs or engineer genotypes with improved agronomic and/or quality traits. Here, we discuss recent progress in understanding genes involved in fiber development, and their regulation and manipulation to engineer improved fibers. Better understanding of quantitative trait loci/gene interactions that influence fiber quality and yield may help to tailor superior cotton genotypes to diverse environments.

Univariate analysis

was done to compare 24-hour urine composition between white and Asian/Pacific Islander stone formers. We performed multivariate linear regression adjusted for possible confounders, including age, gender, body mass index, hypertension, diabetes mellitus, thiazide use, potassium citrate use and 24-hour urine chemistry (volume, pH, calcium, citrate, creatinine, oxalate, magnesium, phosphate, potassium, sodium, sulfate and uric acid).

Results: Included in analysis were 371 white and 91 Asian/Pacific Islander patients. On univariate analysis Asian/Pacific Islander patients excreted significantly greater uric acid, and significantly less citrate, magnesium, phosphate and creatinine than white patients. On multivariate analysis Asian/Pacific Islander patients excreted significantly greater uric acid, and significantly less urine citrate, Mdm2 inhibitor phosphate, creatinine and volume than white patients.

Conclusions: Significant differences exist in 24-hour urine

chemistry between white and Asian/PI stone formers. Knowledge of these differences would be useful to evaluate and treat these patients, and prevent stone recurrence.”
“Purpose: We examined whether stone composition in pregnant women reflects peculiar pathophysiological conditions.

Materials and Methods: We analyzed in detail the composition of stones from 244 pregnant women 17 to 44 years old and from 5,712 nonpregnant women in the same age range, as recorded between January 1991 and December 2007. Clinical features were also recorded. All stones were analyzed by morphological examination coupled with check details infrared spectroscopy. The 2 patient groups were compared by clinical and biochemical characteristics.

Results: Stone episodes in pregnant women manifested mainly in trimesters 2 and 3 (39% and 46%, respectively). Spontaneous passage was noted in 81% of pregnant vs 47% of nonpregnant women (p < 0.0001). Calcium phosphate, mainly in the form of carbapatite, was the main stone component Selleck Ilomastat in 65.6% of pregnant vs 31.4% of nonpregnant women (p <

0.0001). Octacalcium phosphate pentahydrate, a transition phase in calcium phosphate stone formation, was found in a 5-fold higher proportion in carbapatite stones in pregnant than in nonpregnant women, a finding also suggesting recent stone formation during pregnancy.

Conclusions: The composition of stones manifesting during pregnancy clearly differs from that of stones formed in nonpregnant women of childbearing age, suggesting a different pathophysiology specific to the pregnant state. In view of the pH dependency of calcium phosphate stones factors that increase the physiological elevation in maternal urinary calcium excretion and pH are likely to have a role in the preferential formation of calcium phosphate stones during pregnancy.

We find that the interplay between the dispersal directionality NVP-BSK805 in vivo and network topology has important consequences on relative species abundance patterns and the distribution of alpha diversity. (C) 2008 Elsevier Ltd. All rights reserved.”
“Background Sudden death can occur as a consequence of cardiac- conduction abnormalities in the neuromuscular disease myotonic dystrophy type 1. The determinants of the risk of sudden death remain imprecise.

Methods We assessed whether the electrocardiogram (ECG) was useful in predicting sudden death in 406 adult patients with genetically

confirmed myotonic dystrophy type 1. A patient was characterized as having a severe abnormality if the ECG had at least one of the following features: rhythm other than sinus, PR interval of 240 msec or more, QRS duration of 120 msec or more, or second-degree or third-degree atrioventricular block.

Results Patients with severe abnormalities according to the entry ECG were older

than patients without severe abnormalities, had more severe skeletal-muscle impairment, and were more likely to have heart failure, left ventricular systolic dysfunction, or atrial tachyarrhythmia. Such patients were more likely to receive a pacemaker MK-4827 molecular weight or an implantable cardioverter-defibrillator during the follow-up period. During a mean follow-up period of 5.7 years, 81 patients died; there were 27 sudden deaths, 32 deaths from progressive neuromuscular respiratory failure, 5 nonsudden deaths from cardiac

causes, and 17 deaths from other causes. Among the 17 patients who died suddenly in whom postcollapse rhythm was evaluated, a ventricular tachyarrhythmia was observed in 9. A severe ECG abnormality (relative risk, 3.30; 95% confidence interval [CI], 1.24 to 8.78) and a clinical diagnosis of atrial tachyarrhythmia (relative risk, 5.18; 95% CI, 2.28 to 11.77) were independent risk factors for sudden death.

Conclusions Patients with adult myotonic dystrophy type 1 are at high risk for arrhythmias and sudden death. A severe abnormality on the 4EGI-1 nmr ECG and a diagnosis of an atrial tachyarrhythmia predict sudden death.”
“Phenomenological computational models of tissue regeneration and bone healing have been only partially successful in predicting experimental observations. This may be a result of simplistic modeling of cellular activity. Furthermore, phenomenological models are limited when considering the effects of combined physical and biological interventions. In this study, a new model of cell and tissue differentiation, using a more mechanistic approach, is presented and applied to fracture repair. The model directly couples cellular mechanisms to mechanical stimulation during bone healing and is based on the belief that the cells act as transducers during tissue regeneration.

For women, the overall pattern showed that drinking above the sensible limits increased the risk of psychiatric disorders in general, especially for anxiety disorders where women drinking above the sensible drinking limits had a risk of 2.00 (confidence interval: 1.31-3.04) compared to women drinking below the sensible drinking limits. For men, the risk functions were slightly U-shaped; thus, a weekly low or moderate alcohol intake seemed to

have a protective effect towards developing psychiatric disorders. The findings suggest sex differences in the association between alcohol consumption and risk of psychiatric disorders. AZD9291 price (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Purpose: Saw palmetto extracts are used to treat lower urinary tract symptoms in men despite level I evidence that saw palmetto is ineffective in reducing these lower urinary tract symptoms. We determined whether higher doses of saw palmetto as studied in the CAMUS (Complementary and Alternative Medicine for Urologic Symptoms) trial affect serum prostate specific antigen levels.

Materials and Methods: The CAMUS

trial was a randomized, placebo controlled, double-blind, multicenter, North American trial conducted between June 5, 2008 and October 10, 2012, in which 369 men older than 45 years with an AUA symptom score of 8 to 24 were randomly assigned to placebo or dose escalation of saw Barasertib palmetto, which consisted of 320 mg for the first 24 weeks, 640 mg for the next 24 weeks and 960 mg for the last 24 weeks of this 72-week trial. Serum prostate specific antigen levels were obtained at baseline and at weeks 24, Sclareol 48 and 72, and were compared between treatment groups using the pooled t test and Fisher’s exact test.

Results: Serum prostate specific antigen was similar at baseline for the placebo (mean +/- SD 1.93 +/- 1.59 ng/ml) and saw palmetto groups (2.20

+/- 1.95, p = 0.16). Changes in prostate specific antigen during the study were similar, with a mean change in the placebo group of 0.16 +/- 1.08 ng/ml and 0.23 +/- 0.83 ng/ml in the saw palmetto group (p = 0.50). In addition, no differential effect on serum prostate specific antigen was observed between treatment arms when the groups were stratified by baseline prostate specific antigen.

Conclusions: Saw palmetto extract does not affect serum prostate specific antigen more than placebo, even at relatively high doses.”
“Results of a human post mortem study performed by our own group have suggested that the transcription factor NEUROD2, which plays a role in neuronal development, as well as in the development of anxiety and risk behavior in mice, might be a susceptibility factor for addictive disorders. Therefore the aim of the present study was to analyze a possible relation between genetic variants in the NEUROD2 gene and alcohol dependence in a sample of the Munich Gene Bank of Alcoholism (MGBA).

In EAs, the major alleles of five variants (CHRNA5-rs3841324-22 bp-insertion-allele, CHRNA5-rs615470-C-allele, CHRNA3-rs6495307-C-allele, CHRNA3-rs2869546-T-allele, and CHRNB4-rs11637890-C-allele) PD0332991 datasheet were associated with significantly greater perseverative responses (P = 0.003-0.017) and perseverative errors (P = 0.004-0.026; recessive effect). Among EAs homozygous for the major alleles of each of these five variants, current smokers made fewer perseverative responses and perseverative errors

than did past smokers. Significant interactive effects of four variants (rs3841324, rs615470, rs6495307, and rs2869546) and current smoking on cognitive flexibility were observed (perseverative responses (P = 0.010-0.044); perseverative errors (P = 0.017-0.050)). However, in AAs, 10 variants in this gene cluster showed no apparent effects on cognitive flexibility. These findings suggest that variation in the CHRNA5-CHRNA3-CHRNB4 gene cluster influences cognitive flexibility differentially in AAs and EAs and that current

smoking moderates this effect. These findings could account in part for differences in ND risk associated with these variants in AAs and EAs. Neuropsychopharmacology (2010) 35, 2211-2224; doi:10.1038/npp.2010.95; published online 14 July 2010″
“Herpes simplex virus 1 AP26113 ic50 (HSV-1) is a well-adapted human pathogen that can invade the peripheral nervous system and persist there as a lifelong latent infection. Despite their ubiquity, only one natural isolate of HSV-1 (strain 17) has been sequenced. Using Illumina high-throughput sequencing of viral

DNA, we obtained the genome sequences of both a laboratory strain (F) and a low-passage clinical isolate (H129). These data demonstrated the extent of interstrain variation across the entire genome of HSV-1 in both coding and noncoding regions. We found many amino acid differences distributed across the proteome of the new strain F sequence and the previously known strain 17, demonstrating the spectrum of variability among wild-type HSV-1 proteins. DAPT The clinical isolate, strain H129, displays a unique anterograde spread phenotype for which the causal mutations were completely unknown. We have defined the sequence differences in H129 and propose a number of potentially causal genes, including the neurovirulence protein ICP34.5 (RL1). Further studies will be required to demonstrate which change(s) is sufficient to recapitulate the spread defect of strain H129. Unexpectedly, these data also revealed a frameshift mutation in the UL13 kinase in our strain F isolate, demonstrating how deep genome sequencing can reveal the full complement of background mutations in any given strain, particularly those passaged or plaque purified in a laboratory setting.

At intensities from TT50% to TW25%, variables associated with brain activity seem to explain most of the RPE slope, and RPE (+HR and+RR) seems to predict the TE.”
“Background For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years.

Methods In the worldwide Adjuvant Tamoxifen: Longer Danusertib cost Against Shorter (ATLAS) trial, 12 894 women with early

breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1: 1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all BMS-754807 manufacturer women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633.

Findings Among women with ER-positive disease, allocation to continue

tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0.002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0.01), and reduced overall mortality (639 deaths vs 722 deaths, p=0.01). The reductions in adverse breast cancer outcomes appeared to be less MCC950 research buy extreme before than after year 10 (recurrence rate ratio [RR] 0.90 [95% CI 0.79-1.02] during years 5-9 and 0.75 [0.62-0.90] in later years; breast cancer mortality

RR 0.97 [0.79-1.18] during years 5-9 and 0.71 [0.58-0.88] in later years). The cumulative risk of recurrence during years 5-14 was 21.4% for women allocated to continue versus 25.1% for controls; breast cancer mortality during years 5-14 was 12.2% for women allocated to continue versus 15.0% for controls (absolute mortality reduction 2.8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12 894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0.99 [0.89-1.10]; p=0.84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1.87 (95% CI 1.13-3.07, p=0.01 [including 0.2% mortality in both treatment groups]), stroke 1.06 (0.83-1.36), ischaemic heart disease 0.76 (0.60-0.95, p=0.02), and endometrial cancer 1.74 (1.30-2.34, p=0.0002). The cumulative risk of endometrial cancer during years 5-14 was 3.1% (mortality 0.

Reallocation of these resources (“”attention switching”") was delayed in older adults. The present study examined the influence of the competition for attentional resources by comparing trials performed with and without the concurrent task.

Methods. Unpredictable platfonn perturbations were used to evoke rapid forward stepping reactions in healthy young and older adults. Challenging obstacles and/or step targets increased

demands for accurate foot motion in some trials. A concurrent tracking task was performed in half of the trials.

Results. Although participants looked down more frequently in the absence of the tracking task, the ability to clear the obstacle or land on the step target and other spatiotemporal selleck chemicals features of the stepping reactions were largely unaffected. There was. however, one notable exception: In older adults. the duration and amplitude of the “”anticipatory postural Cell Cycle inhibitor adjustment”" that preceded loot lift were reduced in tracking trials. resulting in increased lateral center-of-mass motion.

Conclusion. Impaired attention switching apparently compromised the control of lateral stability during stepping reactions in older adults, and may be an important contributor to increased risk of falling.”
“In this work, we attempt to extend to the schizophrenia’s

research the evidence that different frequency bands may emerge from different Sources during early-stage visual processing, in a mental state-specific manner, while subjects are passively viewing a visual stimulus. We applied standard pattern reversal stimulation (checker-board), a task with low cognitive demands, Coupled to a dense EEG recording system to estimate the neural correlates of the evoked theta, alpha, beta, beta 1, and gamma frequency band responses by means of brain electrical tomography (BET). After filtering the evoked activity using different band-passes, a very different Picture about the Current Sources during P100 will emerge. The results showed notable differences between the two groups. In healthy Subjects we localized the significances in the anterior cingulate, caudate nucleus, thalamus, precuneous region, and superior parietal that were more

active for gamma band. In patients with schizophrenia differences occupy the hippocampus, parahippocampus, thalamus, midbrain, precuneus, and superior science parietal regions. Most areas were more active for gamma band except precuneous and superior parietal region more active for theta and alpha frequency band. These sets of regions, in both groups, reflect events that are parallel to and partly independent of the P100 component, while in the schizophrenia, these regions have been previous linked to the major symptoms of the disease. We concluded that this result provides important evidence indicating that the Proposed method is able to differentiate electrophysiological patterns in healthy Subjects from those in patients with schizophrenia. (c) 2008 Elsevier Ireland Ltd.

c.v. injected Val(8)-GLP-1(7-36) on the A beta fragment-induced impairment of in vivo hippocampal L-LTP and spatial learning and memory in rats. The results showed that (1) A beta 1-40 (5 nmol) injection did not affect the baseline field excitatory postsynaptic potentials

SB431542 mw (fEPSPs), but significantly suppressed multiple high frequency stimulation (HFS)-induced L-LTP in hippocampal CA1 region; (2) Val(8)-GLP-1(7-36) (0.05 pmol) administration alone did not affect the baseline synaptic transmission and the maintenance of L-LTP; (3) pretreatment with Val(8)-GLP-1(7-36) (0.05 pmol) effectively prevented A beta 1-40-induced deficit of L-LTP; (4) i.c.v. injection of 5 nmol A beta 1-40 resulted in a significant decline learning a spatial Morris water maze (MWM) test; (5) Val(8)-GLP-1(7-36) (0.05 pmol) administration alone did not affect spatial learning in this task, while pretreatment with Val(8)-GLP-1(7-36) effectively reversed the impairment of spatial learning and memory induced by A beta 1-40. At the same time, the swim speeds and escape latencies of rats among all groups in the visible platform tests did not show any difference. These results suggest that increase of GLP-1 signalling in the brain may be a promising strategy to ameliorate the degenerative Selleck E7080 processes

observed in AD. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) has been proposed to change conformations in association with RNA synthesis and to interact with cellular proteins. In vitro, the RdRp can initiate de novo from the ends of

single-stranded RNA or extend a primed RNA template. The interactions between the Delta 1 loop and thumb domain in NS5B are required for de novo initiation, although it is unclear whether these interactions are within an NS5B monomer or are part of a higher-order NS5B oligomeric complex. This work seeks to address how polymerase conformation and/or oligomerization affects de novo initiation. We have shown that an increasing enzyme concentration increases de novo initiation by the genotype 1b and 2a RdRps while primer extension reactions are not affected or inhibited under similar conditions. Initiation-defective mutants of the HCV Levetiracetam polymerase can increase de novo initiation by the wild-type (WT) polymerase. GTP was also found to stimulate de novo initiation. Our results support a model in which the de novo initiation-competent conformation of the RdRp is stimulated by oligomeric contacts between individual subunits. Using electron microscopy and single-molecule reconstruction, we attempted to visualize the low-resolution conformations of a dimer of a de novo initiation-competent HCV RdRp.”
“Redox processes associated with controlled generation of reactive oxygen species (ROS) by NADPH oxidase (Nox) add an essential level of regulation to signaling pathways underlying physiological processes.

The objective of this study was to investigate the effects of curcuminoid mixture and individual constituents on spatial learning and memory in an amyloid-beta (A beta) peptide-infused rat model of AD and on the expression of PSD-95, synaptophysin and camkIV. Curcuminoid mixture showed a memory-enhancing effect in rats displaying AD-like neuronal loss only at 30 mg/kg, whereas individual components were effective Nec-1s cost at 3-30 mg/kg. A shorter duration treatment with

test compounds showed that the curcuminoid mixture and bisdemethoxycurcumin increased PSD-95 expression in the hippocampus at 3-30 mg/kg, with maximum effect at a lower dose (3 mg/kg) with respective values of 470.5 and 587.9%. However, after Y-27632 purchase a longer duration treatment, two other compounds (demethoxycurcumin and curcumin) also increased PSD-95 to 331.7 and 226.2% respectively at 30 mg/kg. When studied for their effect on synaptophysin in the hippocampus after the longer duration treatment, the curcuminoid mixture and all three individual constituents increased synaptophysin expression. Of these, demethoxycurcumin

was the most effective showing a 350.1% increase (P<0.01) at 30 mg/kg compared to the neurotoxin group. When studied for their effect on camkIV expression after longer treatment in the hippocampus, only demethoxycurcumin at 30 mg/kg increased levels to 421.2%. These compounds salvaged PSD-95, synaptophysin and camkIV expression levels in the hippocampus in the rat AD model, which suggests multiple target sites with the potential of curcuminoids in spatial memory enhancing and disease modifying in AD. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Flaviviruses transmitted by arthropods represent a tremendous disease burden for humans, causing millions of infections annually. All vector-borne flaviviruses studied to date suppress host innate responses to infection by inhibiting alpha/beta interferon (IFN-alpha/beta)-mediated JAK-STAT signal transduction.

The viral nonstructural protein NS5 of some flaviviruses functions as the major IFN antagonist, associated with inhibition BV-6 of IFN-dependent STAT1 phosphorylation (pY-STAT1) or with STAT2 degradation. West Nile virus (WNV) infection prevents pY-STAT1 although a role for WNV NS5 in IFN antagonism has not been fully explored. Here, we report that NS5 from the virulent NY99 strain of WNV prevented pY-STAT1 accumulation, suppressed IFN-dependent gene expression, and rescued the growth of a highly IFN-sensitive virus (Newcastle disease virus) in the presence of IFN, suggesting that this protein can function as an efficient IFN antagonist. In contrast, NS5 from Kunjin virus (KUN), a naturally attenuated subtype of WNV, was a poor suppressor of pY-STAT1. Mutation of a single residue in KUN NS5 to the analogous residue in WNV-NY99 NS5 (S653F) rendered KUN NS5 an efficient inhibitor of pY-STAT1.