bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relevance of the Interaction between Alphaherpesvirus UL3.5 and UL48 Proteins for Virion Maturation and Neuroinvasion
Authors: Fuchs Walter , Granzow Harald , Klupp Barbara G. , Karger Axel , Michael Kathrin , Maresch Christina , Klopfleisch Robert , Mettenleiter Thomas C. 
Published: June 2007

ABSTRACT

The UL3.5 and UL48 genes, which are conserved in most alphaherpesvirus genomes, are important for maturation of pseudorabies virus (PrV) particles in the cytoplasm of infected cells (W. Fuchs, B. G. Klupp, H. J. Rziha, and T. C. Mettenleiter, J. Virol. 70:3517-3527, 1996; W. Fuchs, H. Granzow, B. G. Klupp, M. Kopp and T. C. Mettenleiter, J. Virol. 76:6729-6742, 2002). In bovine herpesvirus 1 (BoHV-1), the homologous gene products pUL3.5 and pUL48 have been demonstrated to interact physically (N. Lam and G. Letchworth, J. Virol. 74:2876-2884, 2000). Moreover, BoHV-1 pUL3.5 partially complemented a pUL3.5 defect in PrV (W. Fuchs, H. Granzow, and T. C. Mettenleiter, J. Virol. 71:8886-8892, 1997). By using coimmunoprecipitation and yeast two-hybrid studies, we observed a similar interaction between pUL3.5 and pUL48 of PrV, as well as a heterologous interaction between the PrV and BoHV-1 gene products. The relevant domain could be confined to the first 43 amino acids of PrV pUL3.5. Unlike its BoHV-1 homologue, PrV pUL3.5 is processed by proteolytic cleavage, and only an abundant 14-kDa fragment consisting of amino acids 1 to ≥116 could be detected by peptide mass fingerprint analysis of purified wild-type PrV particles, which also contain the pUL48 tegument component. To determine the biological relevance of the protein-protein interaction, pUL3.5-, pUL48-, and double-negative PrV mutants were analyzed in parallel. All deletion mutants were replication competent but exhibited significantly reduced plaque sizes and virus titers in cultured rabbit kidney cells compared to wild-type and rescued viruses, which correlated with a delayed neuroinvasion in intranasally infected mice. Remarkably, the defects of the double-negative mutant were similar to those of pUL48-negative virus. Electron microscopy of cells infected with either deletion mutant revealed the retention of naked nucleocapsids in the cytoplasm and the absence of mature virus particles. In summary, our studies for the first time demonstrate the relevance of the pUL3.5-pUL48 interaction for secondary envelopment of an alphaherpesvirus, give a molecular basis for the observed
trans
-complementation between the PrV and BHV-1 pUL3.5 homologs, yield conclusive evidence for the incorporation of a proteolytically processed pUL3.5 into PrV virions, and demonstrate the importance of both proteins for neuroinvasion and neurovirulence of PrV.
Enterocyte Proliferation and Intestinal Hyperplasia Induced by Simian Virus 40 T Antigen Require a Functional J Domain
Authors: Rathi Abhilasha V. , Sáenz Robles M. Teresa , Pipas James M. 
Published: June 2007

ABSTRACT
Transgenic mice expressing the simian virus 40 large T antigen (TAg) in enterocytes develop intestinal hyperplasia that progresses to dysplasia with age. This induction requires TAg action on the retinoblastoma (Rb) family of tumor suppressors and is independent of the p53 pathway. In cell culture systems, the inactivation of Rb proteins requires both a J domain in TAg that interacts with hsc70 and an LXCXE motif that directs association with Rb proteins. Together these elements are sufficient to release E2Fs from their association with Rb family members. We have generated transgenic mice that express a J domain mutant (D44N) in villus enterocytes. In contrast to wild-type TAg, the D44N mutant is unable to induce enterocyte proliferation. Histological and morphological examination revealed that mice expressing the J domain mutant have normal intestines without loss of growth control. Unlike mice expressing wild-type TAg, mice expressing D44N do not reduce the protein levels of p130 and are also unable to dissociate p130-E2F DNA binding complexes. Furthermore, mice expressing D44N in a null p130 background are still unable to develop hyperplasia. These studies demonstrate that the ectopic proliferation of enterocytes by TAg requires a functional J domain and suggest that the J domain is necessary to inactivate all three pRb family members.
The C Terminus of Hepatitis C Virus NS4A Encodes an Electrostatic Switch That Regulates NS5A Hyperphosphorylation and Viral Replication
Authors: Lindenbach Brett D. , Prágai Béla M. , Montserret Roland , Beran Rudolf K. F. , Pyle Anna M. , Penin François , Rice Charles M. 
Published: June 2007

ABSTRACTHepatitis C virus (HCV) nonstructural protein 4A (NS4A) is only 54 amino acids (aa) in length, yet it is a key regulator of the essential serine protease and RNA helicase activities of the NS3-4A complex, as well as a determinant of NS5A phosphorylation. Here we examine the structure and function of the C-terminal acidic region of NS4A through site-directed mutagenesis of a Con1 subgenomic replicon and through biophysical characterization of a synthetic peptide corresponding to this region. Our genetic studies revealed that in 8 of the 15 C-terminal residues of NS4A, individual Ala substitutions or charge reversal substitutions led to severe replication phenotypes, as well as decreased NS5A hyperphosphorylation. By selecting for replication-competent mutants, several second-site changes in NS3 were identified and shown to suppress these defects in replication and NS5A hyperphosphorylation. Circular-dichroism spectroscopy and nuclear magnetic resonance spectroscopy on a peptide corresponding to the C-terminal 19 aa of NS4A revealed that this region can adopt an alpha-helical conformation, but that this folding requires neutralization of a cluster of acidic residues. Taken together, these data suggest that the C terminus of NS4A acts as a dynamic regulator of NS3-4A interaction, NS5A hyperphosphorylation, and HCV replicase activity.
Structural Features of the Scaffold Interaction Domain at the N Terminus of the Major Capsid Protein (VP5) of Herpes Simplex Virus Type 1
Authors: Huang Eugene , Perkins Edward M. , Desai Prashant 
Published: June 2007

ABSTRACTProtein-protein interactions drive the assembly of the herpes simplex virus type 1 capsid. A key interaction occurs between the C terminus of the scaffold protein and the N terminus of the major capsid protein (VP5). Results from alanine-scanning mutagenesis of hydrophobic residues in the N terminus of VP5 revealed seven residues (I27, L35, F39, L58, L65, L67, and L71) that reside in two predicted alpha helices (helix 122-42and helix 258-72) that are important for this bimolecular interaction. The goal of the present study was to further characterize the VP5 scaffold interaction domain (SID). Amino acids at the seven positions were replaced with L, M, V or P (I27); I, M, V, or P (L35, L58, L65, L67, and L71); and H, W, Y, or L (F39). Replacement with a hydrophobic side chain did not affect the interaction with scaffold protein in yeast cells or the ability of a virus specifying the mutation from replicating in cells. The mutation to the proline side chain abolished the interaction in all cases and was lethal for virus replication. Mutant viruses with proline substitutions in helix 122-42at positions 27 and 35 assembled large open capsid shells that did not attain closure. Proline substitutions in helix 258-72at either position 59, 65, or 67 abolished the accumulation of VP5 protein, and, at 58 and 71, although VP5 did accumulate, capsid shells were not assembled. Thus, the second SID, SID2, is highly structured, and this alpha helix (helix 258-72) is likely involved in capsomere-capsomere interactions during shell accretion. Conserved glycine G59 in helix 258-72was also mutated. G59 may act as a flexible “hinge” in helix 258-72because decreasing the movement of this side chain by replacement with valine impaired capsid assembly. Thus, the N terminus of VP5 and the alpha helices embedded in this domain, as in the capsid shell proteins of some double-stranded DNA phages, are a key regulator of shell accretion and stabilization.
Expression and Characterization of a Minimal Hepatitis C Virus Glycoprotein E2 Core Domain That Retains CD81 Binding
Authors: McCaffrey Kathleen , Boo Irene , Poumbourios Pantelis , Drummer Heidi E. 
Published: June 2007

ABSTRACTThe hepatitis C virus glycoprotein E2 receptor-binding domain is encompassed by amino acids 384 to 661 (E2661) and contains two hypervariable sequences, HVR1 and HVR2. E2 sequence comparisons revealed a third variable region, located between residues 570 and 580, that varies widely between genotypes, designated here as igVR, the intergenotypic variable region. A secreted E2661glycoprotein with simultaneous deletions of the three variable sequences retained its ability to bind CD81 and conformation-dependent monoclonal antibodies (MAbs) and displayed enhanced binding to a neutralizing MAb directed to E2 immunogenic domain B. Our data provide insights into the E2 structure by suggesting that the three variable regions reside outside a conserved E2 core.
Differential Inhibition of Long Interspersed Element 1 by APOBEC3 Does Not Correlate with High-Molecular-Mass-Complex Formation or P-Body Association
Authors: Niewiadomska Anna Maria , Tian Chunjuan , Tan Lindi , Wang Tao , Sarkis Phuong Thi Nguyen , Yu Xiao-Fang 
Published: June 2007

ABSTRACT
The human cytidine deaminase APOBEC3G (A3G) and other APOBEC3 proteins exhibit differential inhibitory activities against diverse endogenous retroelements and retroviruses, including Vif-deficient human immunodeficiency virus type 1. The potential inhibitory activity of human APOBEC proteins against long interspersed element 1 (LINE-1) has not been fully evaluated. Here, we demonstrate inhibition of LINE-1 by multiple human APOBEC3 cytidine deaminases, including previously unreported activity for A3DE and A3G. More ancient members of APOBEC, cytidine deaminases AID and APOBEC2, had no detectable activity against LINE-1. A3A, which did not form high-molecular-mass (HMM) complexes and interacted poorly with P bodies, was the most potent inhibitor of LINE-1. A3A specifically recognizes LINE-1 RNA but not the other cellular RNAs tested. However, in the presence of LINE-1, A3A became associated with HMM complexes containing LINE-1 RNA. The ability of A3A to recognize LINE-1 RNA required its catalytic domain and was important for its LINE-1 suppression. Although the mechanism of LINE-1 restriction did not seem to involve DNA editing, A3A inhibited the accumulation of nascent LINE-1 DNA, suggesting interference with LINE-1 reverse transcription and/or integration or intracellular movement of LINE-1 ribonucleoprotein. Thus, association with P bodies or cellular HMM complexes could not predict the potency of APOBEC3 anti-LINE-1 activities. The catalytic domain of APOBEC3 proteins may be important for proper folding and target factors such as RNA or protein interaction in addition to cytidine deamination.
Effect of tadalafil on anaerobic performance indices in healthy athletes
Authors: Guidetti L , Emerenziani G P , Gallotta M C , Pigozzi F , Di Luigi L , Baldari C 
Published: June 2007

Objective:Given the therapeutic and non-therapeutic use of the tadalafil, (phosphodiesterase-5 inhibitor, PDE-5i), we examined its effects on anaerobic performance indices.Methods:In total, 12 well-trained subjects reported to the laboratory on two occasions 1 week apart to perform a 30 s Wingate anaerobic power test (WAnT) on a bicycle ergometer. The day before the WAnT, the subjects were double-blinded to receive an oral dose of tadalafil (20 mg) or placebo. Blood lactate value at rest and 1, 3, 6 and 10 minutes of recovery phase, mean power, peak power, time to peak power and fatigue index were assessed for each WAnT.Results:Blood lactate values at the 3-min recovery WAnT increased significantly in the tadalafil condition (mean (SD) 13.9 (1.7)v12.8 (1.3) mmol/l; p<0.05) and time to peak power decreased significantly (6.3 (1.3)v5.7 (1.5) s; p = 0.05). No differences were observed in any other parameters between the two conditions.Conclusion:The primary finding of this investigation was that the administration of a single dose of a long-term PDE-5i does not substantially influence anaerobic performance indices. However, results demonstrated both an increase in lactate values at the 3-min point of the recovery phase and a decrease in time to peak power.
Circuit weight training and cardiac morphology: a trial with magnetic resonance imaging
Authors: Camargo M D , Stein R , Ribeiro J P , Schvartzman P R , Rizzatti M O , Schaan B D 
Published: June 2007

Background:Aerobic training (AT) and circuit weight training (CWT) improve peak oxygen uptake (VO2peak). During CWT the circulatory system is exposed to higher pressure, which could induce left ventricle morphological adaptations, possibly distinct from those derived from aerobic training.Objective:To compare the effects of aerobic training and CWT upon morphological and functional cardiac adaptations detected by magnetic resonance imaging.Methods:Twenty healthy sedentary individuals were randomly assigned to participate in a 12-week programme of aerobic training (n = 6), CWR (n = 7) or no intervention (n = 7, controls). Training programmes consisted of 36 sessions, 35 min each, 3 times per week, at 70% of maximal heart rate, and CWT included series of resistance exercises performed at 60% of 1 maximal repetition. Cardiopulmonary exercise testing and cardiac magnetic resonance imaging were performed before and after the intervention.Results:There was a similar improvement in VO2peakfollowing aerobic training (mean (SD) increment: 12 (4)%) and CWT (12 (4)%), while there was no change in the control group. Aerobic training (12 (6)%) and CWT (16 (5)%) improved strength in the lower limbs, and only CWT resulted in improvement of 13 (4)% in the strength of the upper limbs. However, there were no detectable changes in left ventricular mass, end-diastolic volume, stroke volume or ejection fraction.Conclusion:In previously sedentary individuals, short-term CWT and aerobic training induce similar improvement in functional capacity without any adaptation in cardiac morphology detectable by cardiac magnetic resonance imaging.
EpCAM is predominantly expressed in high grade and advanced stage urothelial carcinoma of the bladder
Authors: Brunner A , Prelog M , Verdorfer I , Tzankov A , Mikuz G , Ensinger C 
Published: June 2007

Background:EpCAM is an adhesion molecule of the basolateral membranes in a variety of epithelial cells. Over-expression has been detected in many epithelial tumours and has been associated with high stage, high grade and a worse survival in some tumour types.Aims:To assess the prognostic value of EpCAM in urothelial carcinoma of the bladder.Methods:EpCAM expression was analysed by immunohistochemistry using a monoclonal antibody (clone VU-1D9) on a tissue microarray comprising 99 urothelial carcinomas of the bladder diagnosed between 1994 and 1997.Results:A significant relationship between high grade, advanced stage, and EpCAM expression was found, and expression of EpCAM was associated with a worse overall survival when compared to EpCAM negative tumours (p = 0.033). Multivariate analysis showed that EpCAM expression was not an independent prognostic factor for overall survival in urothelial carcinoma of the bladder.Conclusion:EpCAM expression is associated with advanced stage, high grade and poor overall survival in urothelial carcinoma of the bladder, but lacks an independent prognostic significance. The strong association with high grade tumours suggests a possible role during tumour progression and makes EpCAM a potential target for antibody mediated therapy.
CAVITY SCALING: AUTOMATED REFINEMENT OF CAVITY-AWARE MOTIFS IN PROTEIN FUNCTION PREDICTION
Authors: CHEN BRIAN Y. , BRYANT DREW H. , FOFANOV VIACHESLAV Y. , KRISTENSEN DAVID M. , CRUESS AMANDA E. , KIMMEL MAREK , LICHTARGE OLIVIER , KAVRAKI LYDIA E. 
Published: June 2007

Algorithms for geometric and chemical comparison of protein substructure can be useful for many applications in protein function prediction. These motif matching algorithms identify matches of geometric and chemical similarity between well-studied functional sites, motifs, and substructures of functionally uncharacterized proteins, targets. For the purpose of function prediction, the accuracy of motif matching algorithms can be evaluated with the number of statistically significant matches to functionally related proteins, true positives (TPs), and the number of statistically insignificant matches to functionally unrelated proteins, false positives (FPs). Our earlier work developed cavity-aware motifs which use motif points to represent functionally significant atoms and C-spheres to represent functionally significant volumes. We observed that cavity-aware motifs match significantly fewer FPs than matches containing only motif points. We also observed that high-impact C-spheres, which significantly contribute to the reduction of FPs, can be isolated automatically with a technique we call Cavity Scaling. This paper extends our earlier work by demonstrating that C-spheres can be used to accelerate point-based geometric and chemical comparison algorithms, maintaining accuracy while reducing runtime. We also demonstrate that the placement of C-spheres can significantly affect the number of TPs and FPs identified by a cavity-aware motif. While the optimal placement of C-spheres remains a diffcult open problem, we compared two logical placement strategies to better understand C-sphere placement.
Improving Lesion-Symptom Mapping
Authors: Rorden Chris , Karnath Hans-Otto , Bonilha Leonardo 
Published: June 2007

Abstract
Measures of brain activation (e.g., changes in scalp electrical potentials) have become the most popular method for inferring brain function. However, examining brain disruption (e.g., examining behavior after brain injury) can complement activation studies. Activation techniques identify regions involved with a task, whereas disruption techniques are able to discover which regions are crucial for a task. Voxel-based lesion mapping can be used to determine relationships between behavioral measures and the location of brain injury, revealing the function of brain regions. Lesion mapping can also correlate the effectiveness of neurosurgery with the location of brain resection, identifying optimal surgical targets. Traditionally, voxel-based lesion mapping has employed the chi-square test when the clinical measure is binomial and the Student's t test when measures are continuous. Here we suggest that the Liebermeister approach for binomial data is more sensitive than the chi-square test. We also suggest that a test described by Brunner and Munzel is more appropriate than the t test for nonbinomial data because clinical and neuropsychological data often violate the assumptions of the t test. We test our hypotheses comparing statistical tests using both simulated data and data obtained from a sample of stroke patients with disturbed spatial perception. We also developed software to implement these tests (MRIcron), made freely available to the scientific community.
Disentangling Sequential Effects of Stimulus- and Response-related Conflict and Stimulus-Response Repetition using Brain Potentials
Authors: Wendt Mike , Heldmann Marcus , Münte Thomas F. , Kluwe Rainer H. 
Published: June 2007

Abstract
Conflict monitoring theory holds that detection of conflicts in information processing by the anterior cingulate cortex (ACC) results in processing adaptation that minimizes subsequent conflict. Applying an Eriksen f lanker task with four stimuli mapped onto two responses, we investigated whether such modulation occurs only after response-related or also after stimulus-related conflict, focusing on the N2 component of the event-related potential. Contrasting with previous findings, both stimulus- and response-related conflict elicited enhancement of the N2, suggesting that the ACC is sensitive to conflict at both the stimulus and the response level. However, neither type of conflict resulted in reduced conflict effects on the following trial when stimulus-response (S-R) sequence effects were controlled by excluding identical S-R repetition trials. Identical S-R repetitions were associated with facilitated processing, thus demonstrating that inclusion of these trials in the analysis may mimic results predicted by the conflict adaptation hypothesis.
Neural Correlates of Promotion and Prevention Goal Activation: An fMRI Study using an Idiographic Approach
Authors: Eddington Kari M. , Dolcos Florin , Cabeza Roberto , R. Krishnan K. Ranga , Strauman Timothy J. 
Published: June 2007

Abstract
Regulatory focus theory [Higgins, E. T. Beyond pleasure and pain. American Psychologist, 52, 1280–1300, 1997] postulates two social-cognitive motivational systems, the promotion and prevention systems, for self-regulation of goal pursuit. However, the neural substrates of promotion and prevention goal activation remain unclear. Drawing on several literatures, we hypothesized that priming promotion versus prevention goals would activate areas in the left versus right prefrontal cortex (PFC), respectively, and that activation in these areas would be correlated with individual differences in chronic regulatory focus. Sixteen participants underwent functional magnetic resonance imaging while engaged in a depth-of-processing task, during which they were exposed incidentally to their own promotion and prevention goals. Task-related cortical activation was consistent with previous studies. At the same time, incidental priming of promotion goals was associated with left orbital PFC activation, and activation in this area was stronger for individuals with a chronic promotion focus. Findings regarding prevention goal priming were not consistent with predictions. The data illustrate the centrality of self-regulation and personal goal pursuit within the multilayered process of social cognition.
Disgust and Happiness Recognition Correlate with Anteroventral Insula and Amygdala Volume Respectively in Preclinical Huntington's Disease
Authors: Kipps C. M. , Duggins A. J. , McCusker E. A. , Calder A. J. 
Published: June 2007

Abstract
Patients with Huntington's disease (HD) can show disproportionate impairments in recognizing facial signals of disgust, but the neural basis of this deficit remains unclear. Functional imaging studies have implicated the anterior insula in the ability to recognize disgust, but have identified other structures as well, including the basal ganglia. In view of variable insula and basal ganglia volume changes in HD, we used voxel-based morphometry to map regional variations in gray matter (GM) volume in participants carrying the mutation for HD, and correlated this with their performance on a test of facial emotion recognition for six basic emotions (disgust, fear, anger, happiness, sadness, surprise). The volume of the anteroventral insula was strongly correlated with performance on the disgust recognition task. The amygdala volume (bilaterally) correlated with the ability to recognize happy facial expressions. There was marked specificity of the regional correlations for the emotion involved. Recognition of other emotion expressions, or more general cognitive or motor performance as measured by a standardized rating scale, did not correlate with regional brain volume in this group. Control participants showed no effect for any measure. The strong linear correlations for disgust and happiness recognition imply direct involvement of the anterior insula in disgust appreciation, and a similar role for the amygdala in recognizing happy facial expressions. The absence of a significant correlation with the basal ganglia suggests a less critical role for these structures in disgust recognition than has previously been suggested. The findings also highlight the role of neurodegenerative diseases combined with statistical imaging techniques in elucidating the brain basis of behavior and cognition.