bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Variation among
Staphylococcus aureus
Strains from Bovine Milk and Their Relevance to Methicillin-Resistant Isolates from Humans
Authors: Hata Eiji , Katsuda Ken , Kobayashi Hideki , Uchida Ikuo , Tanaka Kiyoshi , Eguchi Masashi 
Published: April 2010

ABSTRACT

In genetic analysis of bovine
Staphylococcus aureus
isolates that are recognized as an important pathogenic bacterium in bovine mastitis, multilocus sequence typing (MLST) showed strong correlation to the results of pulsed-field gel electrophoresis,
coa
PCR-restriction fragment length polymorphism (RFLP),
spa
typing, and the coagulase serotyping method. According to MLST results, strains derived from sequence type 97 (ST97) and ST705 were suggested as not only dominant bovine
S. aureus
lineages in Japan but also pandemic bovine
S. aureus
lineages. Although both lineages seem to be distantly related to each other by phylogenetic analysis, both had common characteristics, i.e.,
lukM/lukF
′
-PV
and coagulase serotype VI. These characteristics were very rare among minor bovine strains and human strains and may contribute to the host specificity of these lineages. Four methicillin-resistant
S. aureus
(MRSA) isolates were first confirmed from bovine milk in Japan; these isolates showed geno- and serotypes that were identical or similar to those of human MRSA isolates in Japan (ST5, staphylococcal cassette chromosome
mec
type II [SCC
mec
II], Spa type t002 or t375, and coagulase serotype II, and ST89, SCC
mec
IIIa, Spa type t5266, and coagulase serotype I). ST5 and ST89 are uncommon among bovine isolates in the world, whereas these STs are common among human MRSA isolates in Japan.
Quantitative Proteomics Analysis Reveals BAG3 as a Potential Target To Suppress Severe Acute Respiratory Syndrome Coronavirus Replication
Authors: Zhang Liang , Zhang Zhi-Ping , Zhang Xian-En , Lin Fu-Sen , Ge Feng 
Published: April 2010

ABSTRACT
The discovery of a novel coronavirus (CoV) as the causative agent of severe acute respiratory syndrome (SARS) has highlighted the need for a better understanding of CoV replication. The replication of SARS-CoV is highly dependent on host cell factors. However, relatively little is known about the cellular proteome changes that occur during SARS-CoV replication. Recently, we developed a cell line expressing a SARS-CoV subgenomic replicon and used it to screen inhibitors of SARS-CoV replication. To identify host proteins important for SARS-CoV RNA replication, the protein profiles of the SARS-CoV replicon cells and parental BHK21 cells were compared using a quantitative proteomic strategy termed “stable-isotope labeling by amino acids in cell culture-mass spectrometry” (SILAC-MS). Our results revealed that, among the 1,081 host proteins quantified in both forward and reverse SILAC measurements, 74 had significantly altered levels of expression. Of these, significantly upregulated BCL2-associated athanogene 3 (BAG3) was selected for further functional studies. BAG3 is involved in a wide variety of cellular processes, including cell survival, cellular stress response, proliferation, migration, and apoptosis. Our results show that inhibition of BAG3 expression by RNA interference led to significant suppression of SARS-CoV replication, suggesting the possibility that upregulation of BAG3 may be part of the machinery that SARS-CoV relies on for replication. By correlating the proteomic data with these functional studies, the findings of this study provide important information for understanding SARS-CoV replication.
Structure/Function Analysis of the Vaccinia Virus F18 Phosphoprotein, an Abundant Core Component Required for Virion Maturation and Infectivity
Authors: Wickramasekera Nadi T. , Traktman Paula 
Published: April 2010

ABSTRACT

Poxvirus virions, whose outer membrane surrounds two lateral bodies and a core, contain at least 70 different proteins. The F18 phosphoprotein is one of the most abundant core components and is essential for the assembly of mature virions. We report here the results of a structure/function analysis in which the role of conserved cysteine residues, clusters of charged amino acids and clusters of hydrophobic/aromatic amino acids have been assessed. Taking advantage of a recombinant virus in which F18 expression is IPTG (isopropyl-β-
d
-thiogalactopyranoside) dependent, we developed a transient complementation assay to evaluate the ability of mutant alleles of F18 to support virion morphogenesis and/or to restore the production of infectious virus. We have also examined protein-protein interactions, comparing the ability of mutant and WT F18 proteins to interact with WT F18 and to interact with the viral A30 protein, another essential core component. We show that F18 associates with an A30-containing multiprotein complex
in vivo
in a manner that depends upon clusters of hydrophobic/aromatic residues in the N′ terminus of the F18 protein but that it is not required for the assembly of this complex. Finally, we confirmed that two PSSP motifs within F18 are the sites of phosphorylation by cellular proline-directed kinases
in vitro
and
in vivo
. Mutation of both of these phosphorylation sites has no apparent impact on virion morphogenesis but leads to the assembly of virions with significantly reduced infectivity.
Protein Kinase A Phosphorylation Activates Vpr-Induced Cell Cycle Arrest during Human Immunodeficiency Virus Type 1 Infection
Authors: Barnitz R. Anthony , Wan Fengyi , Tripuraneni Vinay , Bolton Diane L. , Lenardo Michael J. 
Published: April 2010

ABSTRACT

Infection with human immunodeficiency virus type 1 (HIV-1) causes an inexorable depletion of CD4
+
T cells. The loss of these cells is particularly pronounced in the mucosal immune system during acute infection, and the data suggest that direct viral cytopathicity is a major factor. Cell cycle arrest caused by the HIV-1 accessory protein Vpr is strongly correlated with virus-induced cell death, and phosphorylation of Vpr serine 79 (S79) is required to activate G
2
/M cell cycle blockade. However, the kinase responsible for phosphorylating Vpr remains unknown. Our bioinformatic analyses revealed that S79 is part of a putative phosphorylation site recognized by protein kinase A (PKA). We show here that PKA interacts with Vpr and directly phosphorylates S79. Inhibition of PKA activity during HIV-1 infection abrogates Vpr cell cycle arrest. These findings provide new insight into the signaling event that activates Vpr cell cycle arrest, ultimately leading to the death of infected T cells.
An Antibody Directed against the Fusion Peptide of Junín Virus Envelope Glycoprotein GPC Inhibits pH-Induced Membrane Fusion
Authors: York Joanne , Berry Jody D. , Ströher Ute , Li Qunnu , Feldmann Heinz , Lu Min , Trahey Meg , Nunberg Jack H. 
Published: April 2010

ABSTRACT
The arenavirus envelope glycoprotein (GPC) initiates infection in the host cell through pH-induced fusion of the viral and endosomal membranes. As in other class I viral fusion proteins, this process proceeds through a structural reorganization in GPC in which the ectodomain of the transmembrane fusion subunit (G2) engages the host cell membrane and subsequently refolds to form a highly stable six-helix bundle structure that brings the two membranes into apposition for fusion. Here, we describe a G2-directed monoclonal antibody, F100G5, that prevents membrane fusion by binding to an intermediate form of the protein on the fusion pathway. Inhibition of syncytium formation requires that F100G5 be present concomitant with exposure of GPC to acidic pH. We show that F100G5 recognizes neither the six-helix bundle nor the larger trimer-of-hairpins structure in the postfusion form of G2. Rather, Western blot analysis using recombinant proteins and a panel of alanine-scanning GPC mutants revealed that F100G5 binding is dependent on an invariant lysine residue (K283) near the N terminus of G2, in the so-called fusion peptide that inserts into the host cell membrane during the fusion process. The F100G5 epitope is located in the internal segment of the bipartite GPC fusion peptide, which also contains four conserved cysteine residues, raising the possibility that this fusion peptide may be highly structured. Collectively, our studies indicate that F100G5 identifies an on-path intermediate form of GPC. Binding to the transiently exposed fusion peptide may interfere with G2 insertion into the host cell membrane. Strategies to effectively target fusion peptide function in the endosome may lead to novel classes of antiviral agents.
Caveolin-1 Modulates HIV-1 Envelope-Induced Bystander Apoptosis through gp41
Authors: Wang Xiao Mei , Nadeau Peter E. , Lo Yung-Tsun , Mergia Ayalew 
Published: April 2010

ABSTRACTHuman immunodeficiency virus (HIV) envelope (Env)-mediated bystander apoptosis is known to cause the progressive, severe, and irreversible loss of CD4+T cells in HIV-1-infected patients. Env-induced bystander apoptosis has been shown to be gp41 dependent and related to the membrane hemifusion between envelope-expressing cells and target cells. Caveolin-1 (Cav-1), the scaffold protein of specific membrane lipid rafts called caveolae, has been reported to interact with gp41. However, the underlying pathological or physiological meaning of this robust interaction remains unclear. In this report, we examine the interaction of cellular Cav-1 and HIV gp41 within the lipid rafts and show that Cav-1 modulates Env-induced bystander apoptosis through interactions with gp41 in SupT1 cells and CD4+T lymphocytes isolated from human peripheral blood. Cav-1 significantly suppressed Env-induced membrane hemifusion and caspase-3 activation and augmented Hsp70 upregulation. Moreover, a peptide containing the Cav-1 scaffold domain sequence markedly inhibited bystander apoptosis and apoptotic signal pathways. Our studies shed new light on the potential role of Cav-1 in limiting HIV pathogenesis and the development of a novel therapeutic strategy in treating HIV-1-infected patients.
Synchronous bidirectional endoscopy for iron deficiency anaemia: is it appropriate for patients under 50?
Authors: Landy J , Macfarlane B 
Published: April 2010

Abstract

Background
UK guidelines1 suggest investigation with bidirectional endoscopy (BDE) (upper endoscopy and colonoscopy) in the same sedative episode is a reasonable approach for the investigation of iron deficiency anaemia. There are few data regarding such investigation for iron deficiency anaemia (IDA) in young men.

Objective
To assess the use of synchronous BDE for IDA in men and in women &lt;50; and to compare the effectiveness of synchronous BDE in the investigation of iron deficiency anaemia in patients &lt;50 years with those &gt;50 years.

Methods
Our endoscopy database was searched for all synchronous bidirectional endoscopies that were undertaken for the indication of iron deficiency anaemia between 2003 and 2009. Age, gender and endoscopic findings were retrieved for each procedure. Significant findings were defined as cancer, grade 3 oesophagitis (Savory Miller classification), oesophageal stricture, Barrett’s oesophagus, ulcer, arteriovenous malformation, colitis, and colonic polyps &gt;1 cm.

Results
558 patients underwent synchronous BDE for iron deficiency anaemia between 2003 and 2009. A significant finding in those &gt;50 years was found in 24.6% vs 11.3% of patients &lt;50 years (OR 2.5, 95% CI 1.3 to 5.0). In men under 50 years a significant finding was present in 20.6%. Dual pathology was present in 1.5% of patients over 50 vs 1.3% under 50 years.

Conclusions
Our findings suggest that synchronous BDE is an appropriate means of investigation for iron deficiency anaemia in patients &gt;50 and for men &lt;50 years old.
ATRP grafting of oligo(ethylene glycol) methacrylates from gold surface — Effect of monomer size on grafted chain and EO unit densities
Authors: Jin Zhilin , Brash John L. , Zhu Shiping 
Published: April 2010

Oligo(ethylene glycol) methacrylate (OEGMA) was grafted from Au surface via surface-initiated atom-transfer radical polymerization (s-ATRP). The initiator density was adjusted by the mole fractions of surface-attachable ATRP initiator and diluting agent. Three OEGMA monomers of Mr 300, 475, and 1100 were used. The Au surfaces before and after modification were characterized by water contact angle and ellipsometry. The effect of monomer Mr and initiator density on surface chain density and EO unit density was investigated. It was found that at low initiator density (mole fraction of initiator of 2%–5%), poly(OEGMA) grafts had comparable surface chain density independent of OEGMA Mr. However, at high initiator density (mole fraction of initiator >10%), poly(OEGMA)1100 had obviously lower chain densities than poly(OEGMA)300 and poly(OEGMA)475, which could be attributed to the size difference of the monomers. The short chain length and low surface chain density of poly(OEGMA)1100 resulted in its relatively low surface EO unit density.
UNDERSTANDING DISTAL TRANSCRIPTIONAL REGULATION FROM SEQUENCE, EXPRESSION AND INTERACTOME PERSPECTIVES
Authors: RAO ARVIND , STATES DAVID J. , HERO ALFRED O. , ENGEL JAMES DOUGLAS 
Published: April 2010

Gene regulation in eukaryotes involves a complex interplay between the proximal promoter and distal genomic elements (such as enhancers) which work in concert to drive precise spatio-temporal gene expression. The experimental localization and characterization of gene regulatory elements is a very complex and resource-intensive process. The computational identification of regulatory regions that confer spatiotemporally specific tissue-restricted expression of a gene is thus an important challenge for computational biology. One of the most popular strategies for enhancer localization from DNA sequence is the use of conservation-based prefiltering and more recently, the use of canonical (transcription factor motifs) or de novo tissue-specific sequence motifs. However, there is an ongoing effort in the computational biology community to further improve the fidelity of enhancer predictions from sequence data by integrating other, complementary genomic modalities. In this work, we propose a framework that complements existing methodologies for prospective enhancer identification. The methods in this work are derived from two key insights: (i) that chromatin modification signatures can discriminate proximal and distally located regulatory regions and (ii) the notion of promoter-enhancer cross-talk (as assayed in 3C/5C experiments) might have implications in the search for regulatory sequences that co-operate with the promoter to yield tissue-restricted, gene-specific expression.
The interaction of deformation and metamorphic reactions
Authors: Hobbs Bruce E. , Ord Alison , Spalla Maria Iole , Gosso Guido , Zucali Michele 
Published: April 2010

Abstract

Feedback relations between deformation and metamorphic mineral reactions, derived using the principles of non-equilibrium thermodynamics, indicate that mineral reactions progress to completion in high-strain areas, driven by energy dissipated from inelastic deformation. These processes, in common with other time-dependent geological processes, lead to both strain, and strain-rate, hardening/softening in rate-dependent materials. In particular, strain-rate softening leads to the formation of shear zones, folds and boudins by non-Biot mechanisms. Strain-softening alone does not produce folding or boudinage and results in low-strain shear zones; strain-rate softening is necessary to produce realistic strains and structures. Reaction–mechanical feedback relations operating at the scale of 10–100 m produce structures similar to those that arise from thermal–mechanical feedback relations at coarser (kilometre) scales and reaction–diffusion–mechanical feedback relations at finer (millimetre) scales. The dominance of specific processes at various length scales but the development of similar structures by all coupled processes leads to scale invariance. The concept of non-equilibrium mineral stability diagrams is introduced. In principle, deformation influences the position of mineral stability fields relative to equilibrium stability fields; the effect is negligible for the
quartz
→
coesite
reaction but may be important for others. Application of these results to the development of structures and mineral reactions in the Italian Alps is discussed.
Argon enters the retentive zone: reassessment of diffusion parameters for K-feldspar in the South Cyclades Shear Zone, Ios, Greece
Authors: Forster M. A. , Lister G. S. 
Published: April 2010

Abstract

40
Ar/
39
Ar apparent age spectra have been measured for unusually retentive potassium feldspars (K-feldspar) from the South Cyclades Shear Zone, Ios, Greece. Our results imply that the Argon Partial Retention Zone (Ar PRZ) for the most retentive domains in potassium K-feldspar can expand into the ductile regime, even when temperatures in excess of about 400–450 °C apply. In such cases K-feldspar could be used as a geochronometer to estimate the timing and duration of deformation and metamorphism events. Therefore, we have reassessed traditional methods used to analyse Arrhenius plots by simulating the effect of step-heating experiments on argon loss. Fractal multidomain diffusion models were used, with theoretical distributions of diffusion domain size and volume. We discovered a Fundamental Asymmetry Principle that offers objective constraints on slope fitting to allow an analysis to be consistent with the multidomain diffusion hypothesis, and which consistently leads to the estimation of higher activation energies. Reanalysis of existing datasets is encouraged to allow reassessment of the significance of the average values reported. Retentive diffusion parameters for K-feldspar might prove to be commonplace.
Versatile system-level memory-aware platform description approach for embedded MPSoCs
Authors: Pyka Robert , Klein Felipe , Marwedel Peter , Mamagkakis Stylianos 
Published: April 2010

In this paper, we present a novel system modeling language which targets primarily the development of source-level multiprocessor memory aware optimizations.
In contrast to previous system modeling approaches this approach tries to model the whole system and especially the memory hierarchy in a structural and semantically accessible way. Previous approaches primarily support generation of simulators or retargetable code selectors and thus concentrate on pure behavioral models or describe only the processor instruction set in a semantically accessible way, A simple, database-like, interface is offered to the optimization developer, which in conjunction with the MACCv2 framework enables rapid development of source-level architecture independent optimizations.
Semi-automatic derivation of timing models for WCET analysis
Authors: Schlickling Marc , Pister Markus 
Published: April 2010

Embedded systems are widely used for supporting our every day life. In the area of safety-critical systems human life often depends on the system's correct behavior. Many of such systems are hard real-time systems, so that the notion of correctness not only means functional correctness. They additionally have to obey stringent timing constraints, i.e. timely task completion under all circumstances is essential. An example for such a safety-critical system is the flight control computer in an airplane, which is responsible for stability, attitude and path control.
In order to derive guarantees on the timing behavior of hard real-time systems, the worst-case execution time (WCET) of each task in the system has to be determined. Saarland University and AbsInt GmbH have successfully developed the aiT WCET analyzer for computing safe upper bounds on the WCET of a task. The computation is mainly based on abstract interpretation of timing models of the processor and its periphery. Such timing models are currently hand-crafted by human experts. Therefore their implementation is a time-consuming and error-prone process.
Modern processors or system controllers are automatically synthesized out of formal hardware specifications like VHDL or Verilog. Besides the system' functional behavior, such specifications provide all information needed for the creation of a timing model. But due to their size and complexity, manually examining the sources is even more complex than only looking at the processor manuals. Moreover, this would not reduce the effort nor the probability of implementation errors.
To face this problem, this paper proposes a method for semi-automatically deriving suitable timing models out of formal hardware specifications in VHDL that fit to the tool chain of the aiT WCET analyzer. By this, we reduce the creation time of timing models from months to weeks.
An efficient code update scheme for DSP applications in mobile embedded systems
Authors: Li Weijia , Zhang Youtao 
Published: April 2010

DSP processors usually provide dedicated address generation units (AGUs) to assist address computation. By carefully allocating variables in the memory, DSP compilers take advantage of AGUs and generate efficient code with compact size and improved performance. However, DSP applications running on mobile embedded systems often need to be updated after their initial releases. Studies showed that small changes at the source code level may significantly change the variable layout in the memory and thus the binary code, which causes large energy overheads to mobile embedded systems that patch through wireless or satellite communication, and often pecuniary burden to the users.
In this paper, we propose an update-conscious code update scheme to effectively reduce patch size. It first performs incremental offset assignment based on a recent variable coalescing heuristic, and then summarizes the code difference using two types of update primitives. Our experimental results showed that using update-conscious code update can greatly improve code similarity and thus reduce the update script sizes.
Rescue of p53 Function by Small-Molecule RITA in Cervical Carcinoma by Blocking E6-Mediated Degradation
Authors: Zhao Carolyn Ying , Szekely Laszlo , Bao Wenjie , Selivanova Galina 
Published: April 2010

Abstract
Proteasomal degradation of p53 by human papilloma virus (HPV) E6 oncoprotein plays a pivotal role in the survival of cervical carcinoma cells. Abrogation of HPV-E6–dependent p53 destruction can therefore be a good strategy to combat cervical carcinomas. Here, we show that a small-molecule reactivation of p53 and induction of tumor cell apoptosis (RITA) is able to induce the accumulation of p53 and rescue its tumor suppressor function in cells containing high-risk HPV16 and HPV18 by inhibiting HPV-E6–mediated proteasomal degradation. RITA blocks p53 ubiquitination by preventing p53 interaction with E6-associated protein, required for HPV-E6–mediated degradation. RITA activates the transcription of proapoptotic p53 targets Noxa, PUMA, and BAX, and repressed the expression of pro-proliferative factors CyclinB1, CDC2, and CDC25C, resulting in p53-dependent apoptosis and cell cycle arrest. Importantly, RITA showed substantial suppression of cervical carcinoma xenografts in vivo. These results provide a proof of principle for the treatment of cervical cancer in a p53-dependent manner by using small molecules that target p53. Cancer Res; 70(8); 3372–81. ©2010 AACR.
Cbl-b and Itch: Key Regulators of Peripheral T-cell Tolerance
Authors: Venuprasad K. 
Published: April 2010

Abstract
E3 ligases Cbl-b and Itch have emerged as dominant “tolerogenic” regulators of T cells because their deficiency results in severe autoimmune diseases. Cbl-b and Itch ligase activity regulate T-cell anergy and development of Foxp3+ regulatory T cells (Treg) in the periphery by modulating key components of T-cell receptor (TCR) and transforming growth factor-β (TGF-β) signaling. Manipulation of Cbl-b and Itch activities may provide unique opportunities to develop future therapies for immune disorders such as autoimmunity and cancer. Cancer Res; 70(8); 3009–12. ©2010 AACR.