bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA Sensing-Independent Inhibition of Herpes Simplex Virus 1 Replication by DAI/ZBP1
Authors: Pham Thanh H. , Kwon Ki Mun , Kim Young-Eui , Kim Kyeong Kyu , Ahn Jin-Hyun 
Published: January 2013

ABSTRACT
DNA-dependent activator of interferon regulatory factor (DAI) acts as a cytosolic B-form DNA sensor that induces type I interferons. However, DAI is not required for DNA sensing in certain cell types due to redundancy of the DNA sensing system. Here, we investigated the effect of DAI on herpes simplex virus 1 (HSV-1) infection in HepG2 hepatocellular carcinoma cells. DAI transcription was induced after gamma interferon (IFN-γ) treatment or HSV-1 infection. HSV-1 replication was enhanced by DAI knockdown, and ectopic DAI expression repressed viral replication in a manner requiring the Zβ and D3 domains, but not the Zα domain. This activity of DAI was more prominent at low multiplicity of infection (MOI) and correlated with the reduced expression of viral immediate-early genes. Consistently, DAI repressed the activation of ICP0 promoter in reporter gene assays. DAI knockdown did not affect the B-DNA-mediated IFN-β transcription and IRF3 activation, and overexpression of DAI and RIP1 did not enhance NF-κB activation by B-DNA treatment, demonstrating that DAI is not essential for the B-DNA-mediated IFN production in HepG2 cells. DAI colocalized with ICP0 in a subset of nuclear and cytoplasmic foci in infected cells and interacted with ICP0 in coimmunoprecipitation assays. The anti-HSV-1 effect of DAI was not observed in ICP0-deleted mutant virus infection at a high MOI in HepG2 cells and mouse embryonic fibroblasts. Degradation of IFI16 and PML by ICP0 was enhanced in infection of DAI-knockdown cells. Collectively, these results demonstrate that DAI can suppress HSV-1 growth independent of DNA sensing through mechanisms involving suppression of viral genomes and regulation of ICP0.
Influenza A Virus NS1 Induces G0/G1Cell Cycle Arrest by Inhibiting the Expression and Activity of RhoA Protein
Authors: Jiang Wei , Wang Qingtao , Chen Shuai , Gao Shijuan , Song Liping , Liu Pengyu , Huang Wenlin 
Published: January 2013

ABSTRACTInfluenza A virus is an important pathogenic virus known to induce host cell cycle arrest in G0/G1phase and create beneficial conditions for viral replication. However, how the virus achieves arrest remains unclear. We investigated the mechanisms underlying this process and found that the nonstructural protein 1 (NS1) is required. Based on this finding, we generated a viable influenza A virus (H1N1) lacking the entire NS1 gene to study the function of this protein in cell cycle regulation. In addition to some cell cycle regulators that were changed, the concentration and activity of RhoA protein, which is thought to be pivotal for G1/S phase transition, were also decreased with overexpressing NS1. And in the meantime, the phosphorylation level of cell cycle regulator pRb, downstream of RhoA kinase, was decreased in an NS1-dependent manner. These findings indicate that the NS1 protein induces G0/G1cell cycle arrest mainly through interfering with the RhoA/pRb signaling cascade, thus providing favorable conditions for viral protein accumulation and replication. We further investigated the NS1 protein of avian influenza virus (H5N1) and found that it can also decrease the expression and activity of RhoA, suggesting that the H5N1 virus may affect the cell cycle through the same mechanism. The NS1/RhoA/pRb cascade, which can induce the G0/G1cell cycle arrest identified here, provides a unified explanation for the seemingly different NS1 functions involved in viral replication events. Our findings shed light on the mechanism of influenza virus replication and open new avenues for understanding the interaction between pathogens and hosts.
Human Cytomegalovirus UL34 Binds to Multiple Sites within the Viral Genome
Authors: Liu Ziqi , Biegalke Bonita J. 
Published: January 2013

ABSTRACT
The human cytomegalovirus UL34 gene encodes a sequence-specific DNA binding protein that downregulates expression of the viral immune evasion gene US3. Analysis of the viral genome identified 14 potential UL34 binding sites. Using mobility shift experiments, UL34 bound to all predicted sites that were assayed (7 of 14). Furthermore, the UL34 binding site present within the regulatory region of the US9 gene downregulates expression in a manner similar to that seen for the US3 gene.
Responding rapidly to service level violations using virtual appliances
Authors: Bairavasundaram Lakshmi N. , Soundararajan Gokul , Mathur Vipul , Voruganti Kaladhar , Srinivasan Kiran 
Published: January 2013

One of the key goals in the data center today is providing storage services with service-level objectives (SLOs) for performance metrics such as latency and throughput. Meeting such SLOs is challenging due to the dynamism observed in these environments. In this position paper, we propose dynamic instantiation of virtual appliances, that is, virtual machines with storage functionality, as a mechanism to meet storage SLOs efficiently.
In order for dynamic instantiation to be realistic for rapidlychanging environments, it should be automated. Therefore, an important goal of this paper is to show that such automation is feasible. We do so through a caching case study. Specifically, we build the automation framework for dynamically instantiating virtual caching appliances. This framework identifies sets of interfering workloads that can benefit from caching, determines the cache-size requirements of workloads, non-disruptively migrates the application to use the cache, and warms the cache to quickly return to acceptable service levels. We show through an experiment that this approach addresses SLO violations while using resources efficiently.
Early Visual Responses Predict Conscious Face Perception within and between Subjects during Binocular Rivalry
Authors: Sandberg Kristian , Bahrami Bahador , Kanai Ryota , Barnes Gareth Robert , Overgaard Morten , Rees Geraint 
Published: January 2013

Abstract
Previous studies indicate that conscious face perception may be related to neural activity in a large time window around 170–800 msec after stimulus presentation, yet in the majority of these studies changes in conscious experience are confounded with changes in physical stimulation. Using multivariate classification on MEG data recorded when participants reported changes in conscious perception evoked by binocular rivalry between a face and a grating, we showed that only MEG signals in the 120–320 msec time range, peaking at the M170 around 180 msec and the P2m at around 260 msec, reliably predicted conscious experience. Conscious perception could not only be decoded significantly better than chance from the sensors that showed the largest average difference, as previous studies suggest, but also from patterns of activity across groups of occipital sensors that individually were unable to predict perception better than chance. In addition, source space analyses showed that sources in the early and late visual system predicted conscious perception more accurately than frontal and parietal sites, although conscious perception could also be decoded there. Finally, the patterns of neural activity associated with conscious face perception generalized from one participant to another around the times of maximum prediction accuracy. Our work thus demonstrates that the neural correlates of particular conscious contents (here, faces) are highly consistent in time and space within individuals and that these correlates are shared to some extent between individuals.
Jesus and the minjung revisited: The Legacy of Ahn Byung-Mu (1922-1996)
Authors: Küster Volker 
Published: January 2013

AbstractAhn Byung-Mu was not only one of the leading theological thinkers of 20th century Korea, a mediator between Western, especially German theological tradition and Korean Christianity, but also a persistent regime critique under South Korea's development dictatorship of the 1970s and 80s. Originally a New Testament scholar he also became one of the founding fathers of minjung theology by giving this political theology in the Korean context a biblical foundation. In his studies on the Gospel of Mark, Ahn advocates the thesis that German historical-critical exegesis viewed the Markan ochlos from the perspective of form criticism as a dramatic element similar to the “antique choir”, thereby failing to acknowledge its social and theological significance. In contrast, he emphasizes Jesus' unconditional commitment to the ochlos, which is displayed in the Gospel of Mark. The Galilean ochlos, an amorphous, and in its membership varying group of people from the Galilean lower class, is the addressee of Jesus' mission. The article reconstructs Ahn Byung Mu's theological way of thinking and tackles the question how his legacy can be re-contextualized.
An integrative, synergistic reading of Romans 1-3
Authors: Spitaler Peter 
Published: January 2013

AbstractThe purpose of this article is to analyze a theme cluster that meanders through the narrative fabric of Romans 1-3—the justice of God and the justice and injustice of people. The article (1) describes the literary scope and theological content of the theme cluster statements; (2) examines the plausibility of a relationship between humans and God; (3) critiques traditional interpretations of Paul's diverse descriptions of conduct; and (4) explains the intricacies of the theme cluster from the perspective of “synergy.” As a contextual reading strategy, synergy explores the complementary nature of the theme cluster. The analysis leads to the conclusion: a pessimistic anthropology attributed to Paul overshadows his statements about human and divine justice.
NeuroDNet - an open source platform for constructing and analyzing neurodegenerative disease networks
Authors: Vasaikar Suhas V , Padhi Aditya K , Jayaram Bhyravabhotla , Gomes James 
Published: January 2013

Abstract

Background
Genetic networks control cellular functions. Aberrations in normal cellular function are caused by mutations in genes that disrupt the fine tuning of genetic networks and cause disease or disorder. However, the large number of signalling molecules, genes and proteins that constitute such networks, and the consequent complexity of interactions, has restrained progress in research elucidating disease mechanisms. Hence, carrying out a systematic analysis of how diseases alter the character of these networks is important. We illustrate this through our work on neurodegenerative disease networks. We created a database, NeuroDNet, which brings together relevant information about signalling molecules, genes and proteins, and their interactions, for constructing neurodegenerative disease networks.

Description
NeuroDNet is a database with interactive tools that enables the creation of interaction networks for twelve neurodegenerative diseases under one portal for interrogation and analyses. It is the first of its kind, which enables the construction and analysis of neurodegenerative diseases through protein interaction networks, regulatory networks and Boolean networks. The database has a three-tier architecture - foundation, function and interface. The foundation tier contains the human genome data with 23857 protein-coding genes linked to more than 300 genes reported in clinical studies of neurodegenerative diseases. The database architecture was designed to retrieve neurodegenerative disease information seamlessly through the interface tier using specific functional information. Features of this database enable users to extract, analyze and display information related to a disease in many different ways.

Conclusions
The application of NeuroDNet was illustrated using three case studies. Through these case studies, the construction and analyses of a PPI network for angiogenin protein in amyotrophic lateral sclerosis, a signal-gene-protein interaction network for presenilin protein in Alzheimer's disease and a Boolean network for a mammalian cell cycle was demonstrated. NeuroDNet is accessible at http://bioschool.iitd.ac.in/NeuroDNet/.
Quantitative low mechanical index contrast-enhanced endoscopic ultrasound for the differential diagnosis of chronic pseudotumoral pancreatitis and pancreatic cancer
Authors: Gheonea Dan Ionuţ , Streba Costin Teodor , Ciurea Tudorel , Săftoiu Adrian 
Published: January 2013

Abstract

Background
Second-generation intravenous blood-pool ultrasound contrast agents are increasingly used in endoscopic ultrasound (EUS) for characterization of microvascularization, differential diagnosis of benign and malignant focal lesions, as well as improved staging and guidance of therapeutic procedures.

Methods
The aim of our study was to prospectively compare the vascularisation patterns in chronic pseudotumoral pancreatitis and pancreatic cancer using quantitative low mechanical index (MI) contrast-enhanced EUS. We included 51 patients with chronic pseudotumoral pancreatitis (n = 19) and pancreatic cancer (n = 32). Perfusion imaging started with a bolus injection of Sonovue (2.4 ml), followed by analysis in the early arterial (wash-in) and late venous (wash-out) phase. Perfusion analysis was performed by post-processing of the raw data (time intensity curve [TIC] analysis). TIC analysis was performed inside the tumor and the pancreatic parenchyma, with depiction of the dynamic vascular pattern generated by specific software. Statistical analysis was performed on raw data extracted from the TIC analysis. Final diagnosis was based on a combination of EUS-FNA, surgery and follow-up of minimum 6 months in negative cases.

Results
The sensitivity and specificity of low MI contrast enhanced EUS using TIC were sensitivity and specificity of low MI contrast enhanced EUS using TIC analysis were 93.75% (95% CI = 77.77 - 98.91%) and 89.47% (95% CI = 65.46 - 98.15%), respectively. Pseudotumoral chronic pancreatitis showed in the majority of cases a hypervascular appearance in the early arterial phase of contrast-enhancement, with a dynamic enhancement pattern similar with the rest of the parenchyma. Statistical analysis of the resulting series of individual intensities revealed no statistically relevant differences (p = .78). Pancreatic adenocarcinoma was usually a hypovascular lesion, showing low contrast-enhancement during the early arterial and also during the late venous phase of contrast-enhancement, also lower than the normal surrounding parenchyma. We found statistically significant differences in values during TIC analysis (p < .001).

Conclusions
Low MI contrast enhanced EUS technique is expected to improve the differential diagnosis of focal pancreatic lesions. However, further multicentric randomized studies will confirm the exact role of the technique and its place in imaging assessment of focal pancreatic lesions.
Genetic manipulation of longevity-related genes as a tool to regulate yeast life span and metabolite production during winemaking
Authors: Orozco Helena , Matallana Emilia , Aranda Agustín 
Published: January 2013

Abstract

Background
Yeast viability and vitality are essential for different industrial processes where the yeast Saccharomyces cerevisiae is used as a biotechnological tool. Therefore, the decline of yeast biological functions during aging may compromise their successful biotechnological use. Life span is controlled by a variety of molecular mechanisms, many of which are connected to stress tolerance and genomic stability, although the metabolic status of a cell has proven a main factor affecting its longevity. Acetic acid and ethanol accumulation shorten chronological life span (CLS), while glycerol extends it.

Results
Different age-related gene classes have been modified by deletion or overexpression to test their role in longevity and metabolism. Overexpression of histone deacetylase SIR2 extends CLS and reduces acetate production, while overexpression of SIR2 homolog HST3 shortens CLS, increases the ethanol level, and reduces acetic acid production. HST3 overexpression also enhances ethanol tolerance. Increasing tolerance to oxidative stress by superoxide dismutase SOD2 overexpression has only a moderate positive effect on CLS. CLS during grape juice fermentation has also been studied for mutants on several mRNA binding proteins that are regulators of gene expression at the posttranscriptional level; we found that NGR1 and UTH4 deletions decrease CLS, while PUF3 and PUB1 deletions increase it. Besides, the pub1 Δ mutation increases glycerol production and blocks stress granule formation during grape juice fermentation. Surprisingly, factors relating to apoptosis, such as caspase Yca1 or apoptosis-inducing factor Aif1, play a positive role in yeast longevity during winemaking as their deletions shorten CLS.

Conclusions
Manipulation of regulators of gene expression at both transcriptional (i.e., sirtuins) and posttranscriptional (i.e., mRNA binding protein Pub1) levels allows to modulate yeast life span during its biotechnological use. Due to links between aging and metabolism, it also influences the production profile of metabolites of industrial relevance.
Ascaris co-infection does not alter malaria-induced anaemia in a cohort of Nigerian preschool children
Authors: Abanyie Francisca A , McCracken Courtney , Kirwan Patrick , Molloy Síle F , Asaolu Samuel O , Holland Celia V , Gutman Julie , Lamb Tracey J 
Published: January 2013

AbstractBackgroundCo-infection with malaria and intestinal parasites such asAscaris lumbricoidesis common. Malaria parasites induce a pro-inflammatory immune response that contributes to the pathogenic sequelae, such as malarial anaemia, that occur in malaria infection.Ascarisis known to create an anti-inflammatory immune environment which could, in theory, counteract the anti-malarial inflammatory immune response, minimizing the severity of malarial anaemia. This study examined whetherAscarisco-infection can minimize the severity of malarial anaemia.MethodsData from a randomized controlled trial on the effect of antihelminthic treatment in Nigerian preschool-aged (6–59 months) children conducted in 2006–2007 were analysed to examine the effect of malaria andAscarisco-infection on anaemia severity. Children were enrolled and tested for malaria, helminths and anaemia at baseline, four, and eight months. Six hundred and ninety subjects were analysed in this study. Generalized linear mixed models were used to assess the relationship between infection status andAscarisandPlasmodiumparasite intensity on severity of anaemia, defined as a haemoglobin less than 11 g/dL.ResultsMalaria prevalence ranged from 35-78% over the course of this study. Of the malaria-infected children, 55% were co-infected withAscarisat baseline, 60% were co-infected four months later and 48% were co-infected eight months later, underlining the persistent prevalence of malaria-nematode co-infections in this population. Over the course of the study the percentage of anaemic subjects in the population ranged between 84% at baseline and 77% at the eight-month time point. The odds of being anaemic were four to five times higher in children infected with malaria compared to those without malaria.Ascarisinfection alone did not increase the odds of being anaemic, indicating that malaria was the main cause of anaemia in this population. There was no significant difference in the severity of anaemia between children singly infected with malaria and co-infected with malaria andAscaris.ConclusionIn this cohort of Nigerian preschool children, malaria infection was the major contributor to anaemia status.Ascarisco-infection neither exacerbated nor ameliorated the severity of malarial anaemia.
Proteomic analysis of ERK1/2-mediated human sickle red blood cell membrane protein phosphorylation
Authors: Soderblom Erik J , Thompson J Will , Schwartz Evan A , Chiou Edward , Dubois Laura G , Moseley M Arthur , Zennadi Rahima 
Published: January 2013

Abstract

Background
In sickle cell disease (SCD), the mitogen-activated protein kinase (MAPK) ERK1/2 is constitutively active and can be inducible by agonist-stimulation only in sickle but not in normal human red blood cells (RBCs). ERK1/2 is involved in activation of ICAM-4-mediated sickle RBC adhesion to the endothelium. However, other effects of the ERK1/2 activation in sickle RBCs leading to the complex SCD pathophysiology, such as alteration of RBC hemorheology are unknown.

Results
To further characterize global ERK1/2-induced changes in membrane protein phosphorylation within human RBCs, a label-free quantitative phosphoproteomic analysis was applied to sickle and normal RBC membrane ghosts pre-treated with U0126, a specific inhibitor of MEK1/2, the upstream kinase of ERK1/2, in the presence or absence of recombinant active ERK2. Across eight unique treatment groups, 375 phosphopeptides from 155 phosphoproteins were quantified with an average technical coefficient of variation in peak intensity of 19.8%. Sickle RBC treatment with U0126 decreased thirty-six phosphopeptides from twenty-one phosphoproteins involved in regulation of not only RBC shape, flexibility, cell morphology maintenance and adhesion, but also glucose and glutamate transport, cAMP production, degradation of misfolded proteins and receptor ubiquitination. Glycophorin A was the most affected protein in sickle RBCs by this ERK1/2 pathway, which contained 12 unique phosphorylated peptides, suggesting that in addition to its effect on sickle RBC adhesion, increased glycophorin A phosphorylation via the ERK1/2 pathway may also affect glycophorin A interactions with band 3, which could result in decreases in both anion transport by band 3 and band 3 trafficking. The abundance of twelve of the thirty-six phosphopeptides were subsequently increased in normal RBCs co-incubated with recombinant ERK2 and therefore represent specific MEK1/2 phospho-inhibitory targets mediated via ERK2.

Conclusions
These findings expand upon the current model for the involvement of ERK1/2 signaling in RBCs. These findings also identify additional protein targets of this pathway other than the RBC adhesion molecule ICAM-4 and enhance the understanding of the mechanism of small molecule inhibitors of MEK/1/2/ERK1/2, which could be effective in ameliorating RBC hemorheology and adhesion, the hallmarks of SCD.