This model is extended in this paper through coupling of the one-

This model is extended in this paper through coupling of the one-dimensional axisymmetric mass transport equations in tissue and blood to quantify the effects of vasomotion on mass transport to tissue. The results show that over a wide parameter range, surrounding those values calculated from

experimental data, vasomotion does inhibit mass transport to tissue in a one-dimensional axisymmetric blood vessel by an amount that is predominantly dependent upon the amplitude of oscillation and that increases rapidly at larger oscillation amplitudes. (C) 2012 Elsevier Ltd. All rights reserved.”
“Evidence suggests that Bleomycin 30-50% of patients suffering from major depressive disorder (MDD) Capmatinib price are classified as suffering from treatment resistant depression (TRD) as they have an inadequate response to standard antidepressants. A key feature of this patient population is the increased incidence of co-morbid symptoms like anxiety and pain. Recognizing that current standards of care are largely focused on monoaminergic

mechanisms of action (MOAs), innovative approaches to drug discovery for TRD are targeting glutamate hyperfunction.

Here we describe the in vitro and in vivo profile of GRN-529, a novel negative allosteric modulator (NAM) of metabotropic glutamate receptor 5 (mGluR5). In cell based pharmacology assays, GRN-529 is a high affinity (Ki 5.4 nM), potent (IC50 3.1 nM) and selective (>1000-fold selective vs mGluR1) mGluR5 NAM. Acute administration of GRN-529 (0.1-30 mg/kg p.o.) had dose-dependent efficacy across a therapeutically BCKDHA relevant battery of animal models, comprising depression (decreased immobility time in tail suspension and forced swim tests) and 2 of the co-morbid symptoms overrepresented in TRD, namely anxiety (attenuation of stress-induced

hyperthermia, and increased punished crossings in the four plate test) and pain (reversal of hyperalgesia due to sciatic nerve ligation or inflammation). The potential side effect liability of GRN-529 was also assessed using preclinical models: GRN-529 had no effect on rat sexual behavior or motor co-ordination (rotarod), however it impaired cognition in mice (social odor recognition). Efficacy and side effects of GRN-529 were compared to standard of care agents (antidepressant, anxiolytic or analgesics) and the tool mGluR5 NAM, MTEP. To assess the relationship between target occupancy and efficacy, ex vivo receptor occupancy was measured in parallel with efficacy testing. This revealed a strong correlation between target engagement, exposure and efficacy across behavioral endpoints, which supports the potential translational value of PET imaging to dose selection in patients.

For the precipitating stage, the 3-months old offspring were admi

For the precipitating stage, the 3-months old offspring were administered

MPTP for 7 days, to simulate the changes that occur during aging. The weights and motor activity of the offspring, check details high performance liquid chromatography (HPLC) striatal dopamine and its metabolites and Western blot for tyrosine hydroxylase (TH) were determined. Offspring exposed to prenatal MPTP showed lower birth weights that eventually recovered. Prenatal MPTP also reduced motor activity by 10-30%, striatal TH by 38%, dopamine by 14%, homovanillic acid by 16.5% and 3-methoxytyramine by 66%. The postnatal MPTP was more potent in the prenatal MPTP-exposed offspring. MPTP at 10, 20 and 30 mg/kg, dose-relatedly, reduced striatal TH by 9.4%, 48.6% and 82.4% in the prenatal-phosphate buffered saline (PBS) mice and by 48%, 78.7% and 92.7% in the prenatal-MPTP groups. More importantly, postnatal MPTP at 10 mg/kg that showed slight effects on DA, DOPAC, HVA and 3-MT in the prenatal-PBS offspring, showed 69.9%, 80.0%, 48.4% and 65.4% reductions in the prenatal-MPTP mice. The selleck chemical study may identify a new model for PD, and

the outcome suggests that some cases of idiopathic PD may have a fetal basis in which early subtle nigrostriatal impairments occurred and PD symptoms are precipitated later by deteriorating changes in the nigrostriatum, that would not caused symptoms in individuals with normal nigrostriatal system. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Viruses have evolved an assortment of mechanisms for regulating the Akt signaling pathway to establish a cellular environment more favorable for viral replication. Myxoma virus (MYXV)

is a rabbit-specific poxvirus that encodes many immunomodulatory factors, including an ankyrin repeat-containing host range protein termed M-T5 that functions to regulate tropism of MYXV for rabbit lymphocytes and certain human cancer cells. MYXV permissiveness in these human cancer cells is dependent upon the direct interaction between M-T5 and Akt, which has been shown to induce the kinase activity of Akt. In this study, an array of compounds that selectively to manipulate Akt signaling was screened and we show that only a subset of Akt inhibitors significantly decreased the ability of MYXV to replicate in previously permissive human cancer cells. Furthermore, reduced viral replication efficiency was correlated with lower levels of phosphorylated Akt. In contrast, the PP2A-specific phosphatase inhibitor okadaic acid promoted increased Akt kinase activation and rescued MYXV replication in human cancer cells that did not previously support viral replication. Finally, phosphorylation of Akt at residue Thr308 was shown to dictate the physical interaction between Akt and M-T5, which then leads to phosphorylation of Ser473 and permits productive MYXV replication in these human cancer cells.

Findings: Follicular fluid and serum were collected at the time o

Findings: Follicular fluid and serum were collected at the time of follicular aspiration in in vitro fertilisation without (Natural cycle IVF, n = 24) and with (conventional gonadotropin stimulated IVF, n = 31) gonadotropin stimulation.

The concentration of the extra-ovarian hormones prolactin and cortisol were analysed by immunoassays.

Results: Median serum prolactin and cortisol concentrations were 12.3 ng/mL and 399 nmol/L without versus 32.2 ng/mL and 623 nmol/L with gonadotropin stimulation. The corresponding concentrations in follicular fluid were 20.6 ng/mL and 445 nmol/L versus 28.8 ng/ml and 456 nmol/L for prolactin and cortisol. As a consequence, mean follicular fluid: serum ratios were significantly reduced under gonadotropin Elacridar cell line stimulation (prolactin p = 0.0138, cortisol p = 0.0001). As an enhanced blood-follicular permeability and transportation, induced by gonadotropin stimulation, would result in increased instead of decreased follicular fluid: serum ratios as found in this study, it can be assumed that this does not affect extra-ovarian protein and steroid hormones as illustrated by prolactin and cortisol.

Conclusions: The model of serum follicular fluid: serum ratio of hormones, produced outside the ovaries, did check details not reveal

a gonadotropin induced increased blood-follicular transportation MAPK inhibitor capacity. Therefore it can be assumed that the effect of gonadotropins on follicular endocrine function is not due to an increased ovarian permeability of extra-ovarian hormones.”
“Background: Oocyte-specific genes play critical

roles in oogenesis, folliculogenesis and early embryonic development. The objectives of this study were to characterize the expression of a novel oocyte-specific gene encoding an F-box protein during ovarian development in rainbow trout, and identify its potential interacting partners in rainbow trout oocytes.

Methods: Through analysis of expressed sequence tags (ESTs) from a rainbow trout oocyte cDNA library, a novel transcript represented by ESTs only from the oocyte library was identified. The complete cDNA sequence for the novel gene (named fbxoo) was obtained by assembling sequences from an EST clone and a 5′RACE product. The expression and localization of fbxoo mRNA and protein in ovaries of different developmental stages were analyzed by quantitative real time PCR, immunoblotting, in situ hybridization and immunohistochemistry. Identification of Fbxoo binding proteins was performed by yeast two-hybrid screening.

Results: fbxoo mRNA is specifically expressed in mature oocytes as revealed by tissue distribution analysis. The fbxoo cDNA sequence is 1,996 bp in length containing an open reading frame, which encodes a predicted protein of 514 amino acids.

Rates of adverse events during follow-up were similar in the two

Rates of adverse events during follow-up were similar in the two study groups.

CONCLUSIONS

The initiation of antiretroviral therapy during tuberculosis BAY 1895344 therapy significantly improved survival and provides further impetus

for the integration of tuberculosis and HIV services. (ClinicalTrials.gov number, NCT00398996.)”
“We evaluated the efficacy of rhesus theta-defensin 1 (RTD-1), a novel cyclic antimicrobial peptide, as a prophylactic antiviral in a mouse model of severe acute respiratory syndrome (SARS) coronavirus (CoV) lung disease. BALB/c mice exposed to a mouse-adapted strain of SARS-CoV demonstrated 100% survival and modest reductions in lung pathology without reductions in virus titer when treated with two intranasal doses of RTD-1, while mortality in untreated mice was similar to 75%. RTD-1-treated, SARS-CoV-infected mice displayed altered lung tissue cytokine responses 2 and 4 days postinfection compared to those of untreated animals, suggesting that one possible mechanism of action for RTD-1 is immunomodulatory.”
“BACKGROUND

Tuberculosis screening is recommended for people with human immunodeficiency virus (HIV) infection to facilitate early diagnosis and safe initiation of antiretroviral therapy and isoniazid preventive therapy. No internationally accepted, evidence-based guideline addresses the optimal means of conducting such screening,

although screening for chronic cough is common.

METHODS

We consecutively enrolled people with HIV infection from eight outpatient clinics in Cambodia, Thailand, CHIR-99021 and Vietnam. For each patient, three samples of sputum and one each of urine, stool, blood, and lymph-node see more aspirate (for patients with lymphadenopathy) were obtained for mycobacterial culture.

We compared the characteristics of patients who received a diagnosis of tuberculosis (on the basis of having one or more specimens that were culture-positive) with those of patients who did not have tuberculosis to derive an algorithm for screening and diagnosis.

RESULTS

Tuberculosis was diagnosed in 267 (15%) of 1748 patients (median CD4+ T-lymphocyte count, 242 per cubic millimeter; interquartile range, 82 to 396). The presence of a cough for 2 or 3 weeks or more during the preceding 4 weeks had a sensitivity of 22 to 33% for detecting tuberculosis. The presence of cough of any duration, fever of any duration, or night sweats lasting 3 or more weeks in the preceding 4 weeks was 93% sensitive and 36% specific for tuberculosis. In the 1199 patients with any of these symptoms, a combination of two negative sputum smears, a normal chest radiograph, and a CD4+ cell count of 350 or more per cubic millimeter helped to rule out a diagnosis of tuberculosis, whereas a positive diagnosis could be made only for the 113 patients (9%) with one or more positive sputum smears; mycobacterial culture was required for most other patients.

(C) 2009 Elsevier B V

All rights reserved “
“Recent

(C) 2009 Elsevier B.V.

All rights reserved.”
“Recent research revealed that patients with spatial hemineglect show deficits in the judgment of the subjective vertical and horizontal. Systematic deviations in the subjective axes have been demonstrated in the visual and tactile modality, indicating a supramodal spatial orientation deficit. Further, the magnitude of the bias was shown to be modulated by head- and body-position. The present study investigated the effect of passive lateral head inclination on the subjective visual and tactile vertical and horizontal in neglect patients, control patients with left- or right-sided brain damage without neglect and healthy controls. Subjects performed visual- and tactile-spatial judgments of axis LB-100 chemical structure orientations in an upright head orientation and with lateral head inclination 25 degrees in clockwise (CW) or counterclockwise (CCW) direction. Neglect patients displayed a marked variability as well as a systematic tilt in their spatial judgments. In line with a multisensory spatial orientation deficit their subjective vertical and horizontal was tilted CCW in the visual and in the tactile modality, while such DMXAA in vitro a tilt was not evident in any other subject group. Furthermore, lateral head inclination had a differential effect in neglect patients, but not in control subjects. Neglect patients’ judgments were modulated in the direction of the head tilt (‘A-effect’). That is, a CCW inclination further

increased

the CCW spatial bias whereas a CW inclination decreased the spatial bias and thus led to approximately normal performance. The increased A-effect might be caused by a pathologically strong attraction of the subjective vertical by an idiotropic vector relying on the actual head orientation, as a consequence selleckchem of impaired processing of gravitational information in neglect patients. (C) 2010 Elsevier Ltd. All rights reserved.”
“Influenza A virus isolation is undertaken routinely in embryonated chicken eggs, but to improve virus detection various cell lines can be used. The CACO-2 cell line was compared to the MDCK cell line and embryonated chicken eggs for the isolation of H1N1, H1N2, H3N2 swine influenza A virus subtypes from clinical specimens.

From 2006 to 2008, 104 influenza A samples found positive by PCR from 42 respiratory outbreaks in Italian swine farms were examined by virus isolation. Sixty swine influenza A viruses were isolated (16 H1N1, 28 H1N2 and 16 H3N2) and their growth behaviour on the different substrates was examined. 16/16 H1N1, 28/28 H1N2 and 8/16 of H3N2 viruses were isolated from the CACO-2 cell line, while 7/16 H1N1, 3/28 H1N2 and 16/16 H3N2 viruses were isolated using embryonated chicken eggs. Only 9/16 H1N1, 1/28 H1N2 and 6/16 H3N2 viruses replicated in MDCK cells. A link was found between viral hemagglutinin and the isolation rate on the various substrates. The CACO-2 line was statistically more sensitive (Fisher’s exact test, p < 0.


“Innate immune recognition of microbe-associated molecular


“Innate immune recognition of microbe-associated molecular patterns by multiple families of pattern-recognition molecules such as Toll-like receptors and Nod-like receptors

instructs the innate and adaptive immune system to protect the host from pathogens while also acting to establish a beneficial mutualism with commensal organisms. Although this task has been thought to be performed mainly by specialized antigen-presenting cells such as dendritic cells, recent observations point to the idea that innate immune recognition by stromal cells has AR-13324 price important implications for the regulation of mucosal homeostasis as well as for the initiation of innate and adaptive immunity.”
“Natural infection with simian retrovirus (SRV) has long been recognized in rhesus macaques (RMs) and may result in an AIDS-like disease. Importantly, SRV infections persist as a problem in recently imported macaques. Therefore, there is a clear need to control SRV spread in macaque colonies. We developed a recombinant vesicular stomatitis virus (VSV)-SRV vaccine consisting of replication-competent hybrid VSVs that express SRV gag and

env in separate vectors. The goal of this study was to assess the immunogenicity and protective efficacy of the VSV-SRV serotype 2 vaccine prime-boost approach in RMs. The VSV-SRV vector (expressing either SRV gag or env) vaccines were intranasally administered in 4 RMs, followed by a boost 1 month after BMS202 the first vaccination. Four RMs served as controls and received the VSV vector alone. Two months after the boost, all animals were intravenously challenged with SRV-2 and monitored for PIK3C2G 90 days.

After the SRV-2 challenge, all four controls became infected, and viral loads (VLs) ranged from 106 to 108 SRV RNA copies/ml of plasma. Two animals in the control group developed simian AIDS within 7 to 8 weeks postinfection and were euthanized. Anemia and weight loss were observed in the remaining controls. During acute infection, severe B-cell depletion and no significant changes in T-cell population were observed in the control group. Control RMs with greater preservation of B cells and lower VLs survived longer. SRV-2 was undetectable in vaccinated animals, which remained healthy, with no clinical or biological signs of infection and preservation of B cells. Our study showed that the VSV-SRV vaccine is a strong approach for preventing clinically relevant type D retrovirus infection and disease in RMs, with protection of 4/4 RMs from SRV infection and prevention of B-cell destruction. B-cell protection was the strongest correlate of the long-term survival of all vaccinated and control RMs.”
“Cushing syndrome (CS) is the classic condition of cortisol dysregulation, and cortisol dysregulation is the prototypic finding in Major Depressive Disorder (MDD).

An intact INR element was required for proficient ICP4 activation

An intact INR element was required for proficient ICP4 activation of the late promoter in the absence of TFIIA. Because TFIIA is known to stabilize the binding of both TATA binding protein (TBP) and TFIID to the TATA box of core promoters and ICP4 has been shown to interact with TFIID, we tested the ability of ICP4 to find more stabilize the binding of either TBP or TFIID to the TATA box of representative early, late, and INR-mutated late promoters (tk, gC, and gC8, respectively). Utilizing DNase I footprinting analysis, we found

that ICP4 was able to facilitate TFIIA stabilized binding of TBP to the TATA box of the early tk promoter. Using mutant ICP4 proteins, the ability to stabilize the binding of TBP to both the wild-type and the INR-mutated gC promoters was located in the amino-terminal region of ICP4. When TFIID was substituted for TBP, ICP4 could stabilize the binding of TFIID to the TATA box of the wild-type gC promoter. ICP4, however, could not effectively stabilize TFIID binding to the TATA box of the INR-mutated late promoter. The additional

activities of TFIIA were required to stabilize the binding of TFIID to the INR-mutated late promoter. Collectively, these data suggest that TFIIA may be dispensable for ICP4 activation of the wild-type late promoter because ICP4 can substitute for TFIIA’s ability to stabilize the binding of TFIID to the TATA box. In the absence of a functional INR, ICP4 can no longer stabilize TFIID binding to the TATA box of the late promoter and requires the additional Tozasertib price activities of TFIIA. The stabilized binding of TFIID by TFIIA may in turn allow ICP4 to more check efficiently activate transcription from non-INR containing

promoters.”
“Dendritic and axonal processes are input and output sites, respectively, of neuronal information, and detailed visualization of these processes may be indispensable for elucidating the neuronal circuits and revealing the principles of neuronal functions. To establish a method for completely visualizing dendritic processes, we first developed green fluorescent protein (GFP)-based proteins and, by using lentivirus with a neuron-specific promoter, examined whether or not the protein fully visualized the dendritic processes of infected neurons. When GFP with a palmitoylation (palGFP) or myristoylation/palmitoylation site (myrGFP) was expressed in rat brain with lentiviruses, myrGFP labeled dendritic membrane better than palGFP. Subsequently, dendrite-targeting efficiencies of three basolateral membrane-sorting and three putative dendrite-targeting domains, which were attached to myrGFP C-terminus, were examined in striatonigral GABAergic and corticothalamic glutamatergic neurons, and in cultured cortical neurons. Of the six domains, C-terminal cytoplasmic domain of low density lipoprotein receptor (LDLRCT) was most efficient in targeting the protein to dendrites, showing 8.5-15-fold higher efficiency in striatonigral neurons compared with myrGFP.

Our group previously reported a high rate of infection and need f

Our group previously reported a high rate of infection and need for secondary interventions in obese patients with prosthetic femorofemoral accesses. We now report a series of patients who underwent placement of a prosthetic axilloaxillary loop access. This study presents our technique and

evaluates our results, particularly as they relate to the obese patient.

Methods. From January 1998 to May 2006, 34 prosthetic axilloaxillary loop accesses were placed in 32 patients with ESRD. Eleven patients (12 accesses) were obese, as defined by a body mass index 2:30 kg/m(2). Median follow-up was 16 months. Kaplan-Meier find more analysis was used to determine primary and secondary patency as well as patient survival for the entire cohort and for the obese and nonobese Evofosfamide patient cohorts. Survival curves were compared using the log-rank test for equality over strata.

Results. The secondary patency rate was 59% at 1 year (median, 18 months). The 1-year patient survival was 69%. Infection occurred in 15% patients. Comparison of the obese vs nonobese cohorts demonstrated no statistically significant

difference in 1-year primary patency (36% vs 10%, P = .17) or secondary patency (71% vs 65%, P = .34). There were no infections in the obese cohort.

Conclusion: These data show that the prosthetic axilloaxillary loop access has acceptable outcomes and should be considered the tertiary vascular access procedure of choice in the obese patient on hemodialysis.”
“Objective: To evaluate the results of the expanded National Venous Screening Program (NVSP) as administered by the American Venous Forum.

Methods. Eighty-three physicians across 40 states participated in screening Americans for venous disease. The NVSP instrument included demographics, venous thromboembolism (VTE) risk assessment, quality-of-life (QOL) assessment, duplex ultrasound scan for reflux and obstruction,

Pazopanib clinical trial and clinical inspection. Participants received educational materials and a report card to give their physician.

Results: A total of 2234 individuals underwent screening (mean, 26 people/site; range, 4-42). Demographic data observed included mean age of 60 years (range, 17-93 years); 77% female; 80% Caucasian; mean BMI of 29 (range, 11-68); 40% current or previous smoker; and 24% taking antiplatelet therapy and 4% taking warfarin. If placed in a situation conducive for VTE, 40% of participants were low risk, 22% were moderate risk, 21% were high risk, and 17% were very high risk. On a venous QOL assessment, 17% had a combined total score for all 11 questions of “”very limited”" or “”impossible to do.”" Reflux or obstruction was noted in 37% and 5% of participants, respectively. CEAP class 0 to 6 was 29%, 29%, 23%, 10%, 9%, 1.5%, 0.5%, respectively.

Discussion: Despite a dramatic expansion in the second annual NSVP (from 17 to 83 centers), the presence of venous disease observed in a larger screened population continues to be high.

(C) 2011 Elsevier Ltd All rights reserved “
“Objectives: A

(C) 2011 Elsevier Ltd. All rights reserved.”
“Objectives: A variety of protective

strategies during repeat sternotomy been proposed; however, it remains unclear for which patients they are warranted.

Methods: We identified adults undergoing repeat median sternotomy for routine cardiac surgery at our institution between January 1, 1996, and December 31, 2007. The operative notes and perioperative outcomes were reviewed.

Results: Of the 2555 patients, 1537 (60%) had undergone previous coronary artery bypass grafting, Tucidinostat cost 700 (27%) previous mitral valve surgery, and 643 (25%) previous aortic valve replacement (AVR). Sixty-one patients (2%) had prior mediastinal radiotherapy, and 424 (17%) had more than one previous sternotomy. In 231 patients, 267 injuries (9.0%) occurred. Injury occurred during sternotomy in 87 patients (33%) and during FAK inhibitor prepump dissection in 135 (51%). The hospital mortality rate was 6.5% among those without injury and 18.5% among those with injury (P < .001); when injury occurred during sternal division, the mortality rate was 25%. Injuries were

more common after previous coronary artery bypass grafting (11% with previous coronary artery bypass grafting vs 7% without, P = .0012) but not previous AVR, mitral valve surgery, or aortic surgery. Injury was also more common when the current operation was AVR (10% with AVR vs 8% without, P = .04) or aortic surgery (14% vs 8%, P = .004). On multivariate analysis, previous radiotherapy (odds ratio, 4.9), a greater number of previous sternotomies (odds ratio 1.7), and a patent internal thoracic artery (odds ratio, 1.8) predicted injury. Injury was an independent risk factor of hospital death (odds ratio, 2.6).

Conclusions:

Particular attention to protective strategies should be considered during reoperative sternotomy among patients with multiple previous sternotomies, previous mediastinal radiotherapy, and those with patent internal thoracic artery grafts. (J Thorac Cardiovasc Surg 2010;140:1028-35)”
“Glucocorticoids mafosfamide (GC) are necessary for normal life but elevated levels of GC have been implicated in the development of several neurological diseases and psychiatric disorders. Nowadays, it is well known that high levels of GC in the central nervous system (CNS) generate an increase in the production of reactive oxygen species (ROS), derived mainly from the nitric oxide (NO) pathway. Accordingly, there is an increase of L-arginine (L-Arg.) availability. This report reviews the evidence that D-arginine (D-Arg.) induces normalization of L-Arg. resulting in protection against GC neurotoxic actions in the hippocampus.

Analyses of reaction times in the I-SZT group showed

Analyses of reaction times in the I-SZT group showed www.selleckchem.com/products/isrib-trans-isomer.html semantic compatibility effect (URV-EW) in the LH and semantic memory activation effect (RV-URV) as well as semantic compatibility effect in the RH. The h-SZT group showed semantic memory activation but no semantic compatibility effect in the LH, the RH pattern resembling that of the I-SZT group. The magnitude of the LH semantic compatibility effect was inversely correlated with SPQ total scores and SPQ Cognitive-perceptual factor. Thus. RH semantic processes are effective and there is a deficit in LH focused activation in schizotypy. (C) 2010 Elsevier Ireland Ltd. All

rights reserved.”
“VPg uridylylation is essential for picornavirus RNA replication. The VPg uridylylation reaction consists of the binding of VPg to 3D polymerase (3D(pol)) and the transfer of UMP by 3D(pol) to the hydroxyl group of the third amino acid Tyr of VPg. Previous studies suggested that different picornaviruses employ distinct mechanisms during VPg binding and uridylylation. Here, we report a novel site (Site-311, located at the base

of the palm domain of EV71 3D(pol)) that is essential for EV71 VPg uridylylation as well as viral replication. Ala substitution of amino acids (T313, F314, www.selleckchem.com/products/tpca-1.html and I317) at Site-311 reduced the VPg uridylylation activity of 3D(pol) by>90%. None of the Site-311 mutations affected the RNA elongation activity of 3D(pol), which indicates that Site-311 does not directly participate in RNA polymerization. However, mutations that abrogated VPg uridylylation significantly reduced the VPg binding ability of 3D(pol), which suggests that Site-311 is a potential VPg binding site on enterovirus 71 (EV71) 3D(pol). Mutation of a polymerase active site in 3D(pol) and Site-311 in 3D(pol) remarkably enables trans complementation to restore VPg uridylylation. In contrast, two distinct Site-311 mutants do not cause trans complementation in vitro. These results indicate that Site-311 is a VPg binding site

that stabilizes the PRKACG VPg molecule during the VPg uridylylation process and suggest a two-molecule model for 3D(pol) during EV71 VPg uridylylation, such that one 3D(pol) presents the hydroxyl group of Tyr3 of VPg to the polymerase active site of another 3D(pol), which in turn catalyzes VPg -> VPg-pU conversion. For genome-length RNA, the Site-311 mutations that reduced VPg uridylylation were lethal for EV71 replication, which indicates that Site-311 is a potential antiviral target.”
“Bunyamwera virus (BUNV) is the prototype virus for both the genus Orthobunyavirus and the family Bunyaviridae. BUNV has a tripartite, negative-sense RNA genome. The coding region of each segment is flanked by untranslated regions (UTRs) that are partially complementary. The UTRs play an important role in the virus life cycle by promoting transcription, replication, and encapsidation of the viral genome.