bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amino acid residues 201-205 in C-terminal acidic tail region plays a crucial role in antibacterial activity of HMGB1
Authors: Gong Wei , Li Yuan , Chao Fan , Huang Gang , He Fengtian 
Published: September 2009

Abstract

Background
Antibacterial activity is a novel function of high-mobility group box 1 (HMGB1). However, the functional site for this new effect is presently unknown.

Methods and Results
In this study, recombinant human HMGB1 A box and B box (rHMGB1 A box, rHMGB1 B box), recombinant human HMGB1 (rHMGB1) and the truncated C-terminal acidic tail mutant (tHMGB1) were prepared by the prokaryotic expression system. The C-terminal acidic tail (C peptide) was synthesized, which was composed of 30 amino acid residues. Antibacterial assays showed that both the full length rHMGB1 and the synthetic C peptide alone could efficiently inhibit bacteria proliferation, but rHMGB1 A box and B box, and tHMGB1 lacking the C-terminal acidic tail had no antibacterial function. These results suggest that C-terminal acidic tail is the key region for the antibacterial activity of HMGB1. Furthermore, we prepared eleven different deleted mutants lacking several amino acid residues in C-terminal acidic tail of HMGB1. Antibacterial assays of these mutants demonstrate that the amino acid residues 201-205 in C-terminal acidic tail region is the core functional site for the antibacterial activity of the molecule.

Conclusion
In sum, these results define the key region and the crucial site in HMGB1 for its antibacterial function, which is helpful to illustrating the antibacterial mechanisms of HMGB1.
The relationship between the evolution of microRNA targets and the length of their UTRs
Authors: Cheng Chao , Bhardwaj Nitin , Gerstein Mark 
Published: September 2009

Abstract

Background
MicroRNAs (miRNAs) are endogenous small RNA molecules that modulate the gene expression at the post-transcription levels in many eukaryotic cells. Their widespread and important role in animals is gauged by estimates that ~25% of all genes are miRNA targets.

Results
We perform a systematic investigation of the relationship between miRNA regulation and their targets' evolution in two mammals: human and mouse. We find genes with longer 3' UTRs are regulated by more distinct types of miRNAs. These genes correspondingly tend to have slower evolutionary rates at the protein level. Housekeeping genes are another class of genes that evolve slowly. However, they have a distinctly different type of regulation, with shorter 3'UTRs to avoid miRNA targeting.

Conclusion
Our analysis suggests a two-way evolutionary mechanism for miRNA targets on the basis of their cellular roles and the length of their 3' UTRs. Functionally critical genes that are spatially or temporally expressed are stringently regulated by miRNAs. While housekeeping genes, however conserved, are selected to have shorter 3'UTRs to avoid miRNA regulation.
An open-label, 1-year extension study of the long-term safety and efficacy of once-daily OROS® hydromorphone in patients with chronic cancer pain
Authors: Hanna Magdi , Tuca Alberto , Thipphawong John 
Published: September 2009

Abstract

Background
Opioid analgesics have proven efficacy in the short-term management of chronic cancer pain, but data on their long-term use is more limited. OROS® hydromorphone is a controlled-release formulation of oral hydromorphone that may be particularly well suited to long-term management of chronic cancer pain because it provides stable plasma concentrations and consistent analgesia with convenient once-daily dosing. The objective of this study (DO-118X) was to characterise the pain control achieved with long-term repeated dosing of OROS® hydromorphone in patients with chronic cancer pain.

Methods
In this multicentre, phase III, open-label, single treatment, 1-year extension study, OROS® hydromorphone was administered to 68 patients with moderate-to-severe chronic cancer pain, who had successfully completed a short-term equivalence study, and whose pain was controlled with a stable dose of medication (≥ 8 mg OROS® hydromorphone or equivalent controlled-release morphine). Patients were started on the dose of OROS® hydromorphone equivalent to the opioid dose on which they achieved dose-stable pain control in the equivalence study; dose adjustments were made as necessary and breakthrough pain medication was permitted. Efficacy was assessed with the Brief Pain Inventory (BPI) and patient and investigator global evaluations of treatment effectiveness. No formal statistical analysis was done.

Results
The mean (standard deviation) duration of exposure to study medication was 139 (129.9) days and the mean (standard deviation) average daily consumption of OROS® hydromorphone was 43.7 (28.14) mg/day. All scores were maintained at a mild to moderate severity throughout the study; however, BPI scores for pain at its worst, pain at its least, pain on average, pain right now, and pain relief were slightly worsened at end point compared with baseline. Mean BPI pain interference with daily activities and patient and investigator global evaluation scores also remained generally stable. Treatment effectiveness was rated as fair to good throughout the study. The most frequently reported adverse events were nausea (n = 24, 35.3%), constipation (n = 22, 32.4%), and vomiting (n = 15, 22.1%).

Conclusion
The results of this extension study suggest that long-term repeated dosing with once-daily OROS® hydromorphone can be beneficial in the continuing management of persistent, moderate-to-severe cancer pain.
Development of a fluorescent quantitative real-time polymerase chain reaction assay for the detection of Goose parvovirus in vivo
Authors: Yang Jin-Long , Cheng An-Chun , Wang Ming-Shu , Pan Kang-Cheng , Li Min , Guo Yu-Fei , Li Chuan-Feng , Zhu De-Kang , Chen Xiao-Yue 
Published: September 2009

Abstract

Background
Goose parvovirus (GPV) is a Dependovirus associated with latent infection and mortality in geese. Currently, it severely affects geese production worldwide. The objective of this study was to develop a fluorescent quantitative real-time polymerase chain reaction (PCR) (FQ-PCR) assay for fast and accurate quantification of GPV DNA in infected goslings, which can aid in the understanding of the regular distribution pattern and the nosogenesis of GPV in vivo.

Results
The detection limit of the assay was 2.8 × 101 standard DNA copies, with a sensitivity of 3 logs higher than that of the conventional gel-based PCR assay targeting the same gene. The real-time PCR was reproducible, as shown by satisfactory low intraassay and interassay coefficients of variation.

Conclusion
The high sensitivity, specificity, simplicity, and reproducibility of the GPV fluorogenic PCR assay, combined with a high throughput, make this method suitable for a broad spectrum of GPV etiology-related applications.
Real-Time Quantitative Polymerase Chain Reaction Detection of Minimal Residual Disease by Standardized WT1 Assay to Enhance Risk Stratification in Acute Myeloid Leukemia: A European LeukemiaNet Study
Authors: Cilloni Daniela , Renneville Aline , Hermitte Fabienne , Hills Robert K. , Daly Sarah , Jovanovic Jelena V. , Gottardi Enrico , Fava Milena , Schnittger Susanne , Weiss Tamara , Izzo Barbara , Nomdedeu Josep , van der Heijden Adrian , van der Reijden Bert A. , Jansen Joop H. , van der Velden Vincent H.J. , Ommen Hans , Preudhomme Claude , Saglio Giuseppe , Grimwade David 
Published: September 2009

Purpose Risk stratification in acute myeloid leukemia (AML) is currently based on pretreatment characteristics. It remains to be established whether relapse risk can be better predicted through assessment of minimal residual disease (MRD). One proposed marker is the Wilms tumor gene WT1, which is overexpressed in most patients with AML, thus providing a putative target for immunotherapy, although in the absence of a standardized assay, its utility for MRD monitoring remains controversial. Patients and Methods Nine published and in-house real-time quantitative polymerase chain reaction WT1 assays were systematically evaluated within the European LeukemiaNet; the best-performing assay was applied to diagnostic AML samples (n = 620), follow-up samples from 129 patients treated with intensive combination chemotherapy, and 204 normal peripheral blood (PB) and bone marrow (BM) controls. Results Considering relative levels of expression detected in normal PB and BM, WT1 was sufficiently overexpressed to discriminate ≥ 2-log reduction in transcripts in 46% and 13% of AML patients, according to the respective follow-up sample source. In this informative group, greater WT1 transcript reduction after induction predicted reduced relapse risk (hazard ratio, 0.54 per log reduction; 95% CI, 0.36 to 0.83; P = .004) that remained significant when adjusted for age, WBC count, and cytogenetics. Failure to reduce WT1 transcripts below the threshold limits defined in normal controls by the end of consolidation also predicted increased relapse risk (P = .004). Conclusion Application of a standardized WT1 assay provides independent prognostic information in AML, lending support to incorporation of early assessment of MRD to develop more robust risk scores, to enhance risk stratification, and to identify patients who may benefit from allogeneic transplantation.
Cost Effectiveness and Screening Interval of Lipid Screening in Hodgkin's Lymphoma Survivors
Authors: Chen Aileen B. , Punglia Rinaa S. , Kuntz Karen M. , Mauch Peter M. , Ng Andrea K. 
Published: September 2009

Purpose Survivors of Hodgkin's lymphoma (HL) who received mediastinal irradiation have an increased risk of coronary heart disease. We evaluated the cost effectiveness of lipid screening in survivors of HL and compared different screening intervals. Methods We developed a decision-analytic model to evaluate lipid screening in a hypothetical cohort of 30-year-old survivors of HL who survived 5 years after mediastinal irradiation. We compared the following strategies: no screening, and screening at 1-, 3-, 5-, or 7-year intervals. Screen-positive patients were treated with statins. Markov models were used to calculate life expectancy, quality-adjusted life expectancy, and lifetime costs. Baseline probabilities, transition probabilities, and utilities were derived from published studies and US population data. Costs were estimated from Medicare fee schedules and the medical literature. Sensitivity analyses were performed. Results Using an incremental cost-effectiveness ratio (ICER) threshold of $100,000 per quality-adjusted life-year (QALY) saved, lipid screening at every interval was cost effective relative to a strategy of no screening. When comparing screening intervals, a 3-year interval was cost effective relative to a 5-year interval, but annual screening, relative to screening every 3 years, had an ICER of more than $100,000/QALY saved. Factors with the most influence on the results included risk of cardiac events/death after HL, efficacy of statins in reducing cardiac events/death, and costs of statins. Conclusion Lipid screening in survivors of HL, with statin therapy for screen-positive patients, improves survival and is cost effective. A screening interval of 3 years seems reasonable in the long-term follow-up of survivors of HL.
Casting for Racial Harmony: Strategies of Redemption in Caleen Sinnette Jennings’s Double Play
Authors: Erickson Peter 
Published: September 2009

This article engages debates surrounding colour-bind and race-transcendent casting as they are articulated in Caleen Sinette Jennings's intertwined two-play sequence Playing Juliet/Casting Othello . Staged in 1998, the sequence activates three distinct meanings of the word 'casting'. The first of these is the metadramatic casting of characters in Playing Juliet/Casting Othello's play-within-the-play, which engages the recent developments in the history of racially-inflected Shakespearean casting practices: having black actors play black characters (a shift in racial realignment signified by Paul Robeson's performances as Othello in the first half of the twentieth century) and colour-blind casting of black actors in conventionally 'white' Shakespearean roles. The second meaning concerns the racially variant romantic relationships explored by the play's characters as themselves, in which they essentially 'audition' for prospective partners: the outcome of which exerts a shaping force in the play's resolution. The third meaning of 'casting' under consideration involves the concept of 'casting about' in the sense of the search for racial harmony in the casting of Shakespearean roles, and how these choices shape meanings. Through a consideration of these three angles, the article explores Jennings's treatment of the gendered asymmetry in the racially-inflected casting choices presented in her two plays, in which the two casting practices of colour-blind casting and racial realignment are pitted against each other. The final result is that the black man who is cast as Othello is uncritically celebrated at the expense of the black woman who plays the problematic role of Juliet.
Broken Spears or Broken Bones: Evolution of the Most Famous Line in Nahuatl
Authors: Schwaller John F. , Leon-Pórtilla Miguel 
Published: September 2009

Arguably the line “Broken Spears” is the most famous in Nahuatl. Any undergraduate student who has taken a course in Latin American history, literature, or anthropology has in all likelihood come across the line. It, of course, comes from the title of Miguel Leon-Portilla's book of the same name. The line appears in a description of Tlatelolco following the destruction of the city by the Spanish in the conquest of Mexico:
Broken spears lie in the roadsWe have torn our hair in our griefThe houses are roofless now, and their wallsAre red with blood.This evocative image has dominated much of the imagination of two generations of college students.
Balance of power – dynamic regulation of chromatin in plant development
Authors: Lafos Marcel , Schubert Daniel 
Published: September 2009

Abstract
Chromatin states profoundly determine and maintain gene activity and gene repression in eukaryotic organisms. Regulation of chromatin involves chromatin remodeling, chromatin modifications and exchange of chromatin components and is linked to DNA methylation in some cases. In plants and other organisms, chromatin proteins control many developmental pathways, integrate changes in the environment and can confer a cellular memory of these cues. Here, we review the molecular mechanisms that provide a dynamic regulation of chromatin in a cell. In addition, we discuss how chromatin needs to be flexibly regulated during plant growth to confer stable expression states that can occasionally be reset, e.g., owing to changes in the environment and progression of development.
Chemotaxis: how bacteria use memory
Authors: Vladimirov Nikita , Sourjik Victor 
Published: September 2009

Abstract
Bacterial chemotaxis represents one of the simplest and best studied examples of unicellular behavior. Chemotaxis allows swimming bacterial cells to follow chemical gradients in the environment by performing temporal comparisons of ligand concentrations. The process of chemotaxis in the model bacterium Escherichia coli has been studied in great molecular detail over the past 40 years, using a large range of experimental tools to investigate physiology, genetics and biochemistry of the system. The abundance of quantitative experimental data enabled detailed computational modeling of the pathway and theoretical analyses of such properties as robustness and signal amplification. Because of the temporal mode of gradient sensing in bacterial chemotaxis, molecular memory is an essential component of the chemotaxis pathway. Recent studies suggest that the memory time scale has been evolutionary optimized to perform optimal comparisons of stimuli while swimming in the gradient. Moreover, noise in the adaptation system, which results from variations of the adaptation rate both over time and among cells, might be beneficial for the overall chemotactic performance of the population.
The epigenetic bottleneck of neurodegenerative and psychiatric diseases
Authors: Sananbenesi Farahnaz , Fischer Andre 
Published: September 2009

Abstract
The orchestrated expression of genes is essential for the development and survival of every organism. In addition to the role of transcription factors, the availability of genes for transcription is controlled by a series of proteins that regulate epigenetic chromatin remodeling. The two most studied epigenetic phenomena are DNA methylation and histone-tail modifications. Although a large body of literature implicates the deregulation of histone acetylation and DNA methylation with the pathogenesis of cancer, recently epigenetic mechanisms have also gained much attention in the neuroscientific community. In fact, a new field of research is rapidly emerging and there is now accumulating evidence that the molecular machinery that regulates histone acetylation and DNA methylation is intimately involved in synaptic plasticity and is essential for learning and memory. Importantly, dysfunction of epigenetic gene expression in the brain might be involved in neurodegenerative and psychiatric diseases. In particular, it was found that inhibition of histone deacetylases attenuates synaptic and neuronal loss in animal models for various neurodegenerative diseases and improves cognitive function. In this article, we will summarize recent data in the novel field of neuroepigenetics and discuss the question why epigenetic strategies are suitable therapeutic approaches for the treatment of brain diseases.
Mechanistic insights in light-induced cAMP production by photoactivated adenylyl cyclase alpha (PACα)
Authors: Looser Jens , Schröder-Lang Saskia , Hegemann Peter , Nagel Georg 
Published: September 2009

Abstract
The flagellate Euglena gracilis contains as photoreceptor complex a heterotetrameric light-sensitive adenylyl cyclase (AC), consisting of the flavoproteins PACα and PACβ. Previously, we demonstrated the functional expression of PACα and PACβ in oocytes from Xenopus laevis and of PACα in different animal cell types. Both yielded a blue light-induced increase of cellular [cAMP]. Here, we report that the action spectrum of PACα is flavoprotein-typical, with maxima at ∼380 and ∼470 nm. Mutational analysis of PACα yields a model for its structure and function. PACα shows a basal AC activity in the dark which is unaffected by mutating the conserved tyrosines in the two flavin-binding domains (F1, F2), Y60 in F1 and Y472 in F2. Y60 in F1 is, however, essential for photoactivation as light-stimulation of cyclase activity is completely lost in the F1 mutant Y60F. This effect does not occur in the respective mutation in F2 (Y472F). Mutating the two cyclase domains (C1, C2) indicated that C1 and C2 form a heterodimeric catalytic center as in mammalian class III cyclases. Interaction of C1 with C2 in the same molecule could be excluded as coexpression of non-functional C1 and C2 mutants restored light-induced cyclase activity. Our results strongly suggest an intermolecular dimerization of C1 and C2 domains on PACα for a functional enzyme.
Protein carboxyl methylation and the biochemistry of memory
Authors: Li Zhu , Stock Jeffry B. 
Published: September 2009

Abstract
Bacterial chemotaxis is mediated by two reversible protein modification chemistries: phosphorylation and carboxyl methylation. Attractants bind to membrane chemoreceptors that control the activity of a protein kinase which acts in turn to control flagellar motor activity. Coordinate changes in receptor carboxyl methylation provide a negative feedback mechanism that serves a memory function. Protein carboxyl methylation might play an analogous role in the nervous system. Two protein carboxyl methyltransferases serve to regulate signal transduction pathways in eukaryotic cells. One is highly expressed in the Purkinje layer of the cerebellum where it methyl esterifies prenylated cysteine residues at the carboxyl-termini of Ras-related and heterotrimeric G-proteins. The other is abundant throughout the brain where it methylates the carboxyl-terminus of protein phosphatase 2A. The phosphatase methyltransferase and the protein methylesterase that reverses phosphatase methylation are structurally related to the corresponding bacterial chemotaxis methylating and demethylating enzymes. Recent results indicate that deficiencies in phosphatase methylation play an important role in the etiology of Alzheimer's disease.
Memory and neural networks on the basis of color centers in solids
Authors: Winnacker Albrecht , Osvet Andres 
Published: September 2009

Abstract
Optical data recording is one of the most widely used and efficient systems of memory in the non-living world. The application of color centers in this context offers not only systems of high speed in writing and read-out due to a high degree of parallelism in data handling but also a possibility to set up models of neural networks. In this way, systems with a high potential for image processing, pattern recognition and logical operations can be constructed. A limitation to storage density is given by the diffraction limit of optical data recording. It is shown that this limitation can at least in principle be overcome by the principle of spectral hole burning, which results in systems of storage capacities close to the human brain system.
The mechanism of ATP-dependent RNA unwinding by DEAD box proteins
Authors: Hilbert Manuel , Karow Anne R. , Klostermeier Dagmar 
Published: September 2009

Abstract
DEAD box proteins catalyze the ATP-dependent unwinding of double-stranded RNA (dsRNA). In addition, they facilitate protein displacement and remodeling of RNA or RNA/protein complexes. Their hallmark feature is local destabilization of RNA duplexes. Here, we summarize current data on the DEAD box protein mechanism and present a model for RNA unwinding that integrates recent data on the effect of ATP analogs and mutations on DEAD box protein activity. DEAD box proteins share a conserved helicase core with two flexibly linked RecA-like domains that contain all helicase signature motifs. Variable flanking regions contribute to substrate binding and modulate activity. In the presence of ATP and RNA, the helicase core adopts a compact, closed conformation with extensive interdomain contacts and high affinity for RNA. In the closed conformation, the RecA-like domains form a catalytic site for ATP hydrolysis and a continuous RNA binding site. A kink in the backbone of the bound RNA locally destabilizes the duplex. Rearrangement of this initial complex generates a hydrolysis- and unwinding-competent state. From this complex, the first RNA strand can dissociate. After ATP hydrolysis and phosphate release, the DEAD box protein returns to a low-affinity state for RNA. Dissociation of the second RNA strand and reopening of the cleft in the helicase core allow for further catalytic cycles.