bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms Governing the Selection of Translation Initiation Sites on Foot-and-Mouth Disease Virus RNA
Authors: Pöyry Tuija A. A. , Jackson Richard J. 
Published: August 2011

ABSTRACT

Translation initiation dependent on the foot-and-mouth disease virus (FMDV) internal ribosome entry site (IRES) occurs at two sites (Lab and Lb), 84 nucleotides (nt) apart.
In vitro
translation of an mRNA comprising the IRES and Lab-Lb intervening segment fused to a chloramphenicol acetyltransferase (CAT) reporter has been used to study the parameters influencing the ratio of the two products and the combined product yield as measures of relative initiation site usage and productive ribosome recruitment, respectively. With wild-type mRNA, ∼40% of initiation occurred at the Lab site, which was increased to 90% by optimization of its context, but decreased to 20% by mutations that reduced downstream secondary structure, with no change in recruitment in either case. Inserting 5 nt into the pyrimidine-rich tract located just upstream of the Lab site increased initiation at this site by 75% and ribosome recruitment by 50%. Mutating the Lab site to RCG or RUN codons decreased recruitment by 20 to 30% but stimulated Lb initiation by 20 to 40%. An antisense oligodeoxynucleotide annealing across the Lab site inhibited initiation at both sites. These and related results lead to the following conclusions. Recruitment by the wild-type IRES is limited by its short oligopyrimidine tract. At least 90% of internal ribosome entry occurs at the Lab AUG, but initiation at this site is restricted by its poor context, despite a counteracting effect of downstream secondary structure. Initiation at the Lb site is by ribosomes that access it by linear scanning from the original entry site, and not by an independent entry process.
Low-pH-Dependent Changes in the Conformation and Oligomeric State of the Prefusion Form of Herpes Simplex Virus Glycoprotein B Are Separable from Fusion Activity
Authors: Dollery Stephen J. , Wright Catherine C. , Johnson David C. , Nicola Anthony V. 
Published: August 2011

ABSTRACT

The cellular requirements for activation of herpesvirus fusion and entry remain poorly understood. Low pH triggers change in the antigenic reactivity of the prefusion form of the herpes simplex virus (HSV) fusion protein gB in virions, both
in vitro
and during viral entry via endocytosis (S. Dollery et al., J. Virol. 84:3759–3766, 2010). However, the mechanism and magnitude of gB conformational change are not clear. Here we show that the conformation and oligomeric state of gB with mutations in the bipartite fusion loops were similarly altered despite the fusion-inactivating mutations. Together with previous studies, this suggests that fusion loop mutants undergo conformational changes but are defective for fusion because they fail to make productive contact with the outer leaflet of the host target membrane. A direct, reversible effect of low pH on the structure of gB was detected by fluorescence spectroscopy. A soluble form of gB containing cytoplasmic tail sequences (s-gB) was triggered by mildly acidic pH to undergo changes in tryptophan fluorescence emission, hydrophobicity, antigenic conformation, and oligomeric structure and thus resembled the prefusion form of gB in the virion. In contrast, soluble gB730, for which the postfusion crystal structure is known, was only marginally affected by pH using these measures. The results underscore the importance of using a prefusion form of gB to assess the activation and extent of conformation change. Further, acidic pH had little to no effect on the conformation or hydrophobicity of gD or on gD's ability to bind nectin-1 or HVEM receptors. Our results support a model in which endosomal low pH serves as a cellular trigger of fusion by activating conformational changes in the fusion protein gB.
Deposition of gold nanoparticles on organo-kaolinite — Application in electrocatalysis for carbon monoxide oxidation
Authors: Letaief Sadok , Pell Wendy , Detellier Christian 
Published: August 2011

The clay mineral kaolinite was used as support of gold nanoparticles for heterogeneous catalysis of oxidation reactions, particularly of carbon monoxide oxidation. The application of clay minerals in the preparation of new functional materials provides an alternative approach for the use of these abundant raw materials. To improve the physicochemical properties of kaolinite, as well as to ensure a strong immobilization of the adsorbed species, kaolinite was functionalized by grafting 2-amino-2-methyl-1,3-propanediol on the internal and external surfaces of the octahedral sheets by reaction with the aluminol groups. Gold nanoparticles were then deposited on the external surfaces of the fine particles of the functionalized kaolinite. The resulting gold kaolinite nanohybrid material was characterized by various physicochemical techniques. X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, and energy-dispersive X-ray spectrometry confirmed that gold was effectively reduced to the metallic state during adsorption onto the external surfaces of the modified kaolinite. The gold nanoparticles have a narrow size distribution: more than 88% are less than 4 nm in diameter. Gold nanoparticles deposited on kaolinite catalyze the electro-oxidation of carbon monoxide in alkaline solution at room temperature.
C/EBPα, C/EBPα Oncoproteins, or C/EBPβ Preferentially Bind NF-κB p50 Compared with p65, Focusing Therapeutic Targeting on the C/EBP:p50 Interaction
Authors: Dooher Julia E. , Paz-Priel Ido , Houng Simone , Baldwin Albert S. , Friedman Alan D. 
Published: August 2011

Abstract
Canonical nuclear factor kappaB (NF-κB) activation signals stimulate nuclear translocation of p50:p65, replacing inhibitory p50:p50 with activating complexes on chromatin. C/EBP interaction with p50 homodimers provides an alternative pathway for NF-κB target gene activation, and interaction with p50:p65 may enhance gene activation. We previously found that C/EBPα cooperates with p50, but not p65, to induce Bcl-2 transcription and that C/EBPα induces Nfkb1/p50, but not RelA/p65, transcription. Using p50 and p65 variants containing the FLAG epitope at their N- or C-termini, we now show that C/EBPα, C/EBPα myeloid oncoproteins, or the LAP1, LAP2, or LIP isoforms of C/EBPβ have markedly higher affinity for p50 than for p65. Deletion of the p65 transactivation domain did not increase p65 affinity for C/EBPs, suggesting that unique residues in p50 account for specificity, and clustered mutation of HSDL in the “p50 insert” lacking in p65 weakens interaction. Also, in contrast to Nfkb1 gene deletion, absence of the RelA gene does not reduce Bcl-2 or Cebpa RNA in unstimulated cells or prevent interaction of C/EBPα with the Bcl-2 promoter. Saturating mutagenesis of the C/EBPα basic region identifies R300 and nearby residues, identical in C/EBPβ, as critical for interaction with p50. These findings support the conclusion that C/EBPs activate NF-κB target genes via contact with p50 even in the absence of canonical NF-κB activation and indicate that targeting C/EBP:p50 rather than C/EBP:p65 interaction in the nucleus will prove effective for inflammatory or malignant conditions, alone or synergistically with agents acting in the cytoplasm to reduce canonical NF-κB activation. Mol Cancer Res; 9(10); 1395–405. ©2011 AACR.
Data Quality Control Based on Self-Consistency
Authors: Steinacker Reinhold , Mayer Dieter , Steiner Andrea 
Published: August 2011

Abstract
Conducting meteorological measurements, one is always confronted with a wide variety of different types of errors and with the decision of how to correct data for further use, if necessary. The selection of an adequate quality control (QC) procedure out of a wide range of methodologies depends on the properties of the observed parameter such as spatial or temporal consistency. But the intended data application (e.g., model-independent data analysis) or the availability of prior knowledge also has to be taken into account. The herein-presented self-consistent and model-independent QC process makes use of the spatial and temporal consistency of meteorological parameters. It is applicable to measurements featuring a high degree of autocorrelation with regard to the resolution of the observational network in space and time. The presented QC procedure can mathematically be expressed as an optimization problem minimizing the curvature of the analyzed field. This results in a matrix equation that can be solved without needing to converge iterations. Based on the resulting deviations and, if applied, on their impacts on the cost function, station values are accepted, corrected, or identified as outliers and hence dismissed. Furthermore, it is pointed out that this method is able to handle complicated station distributions, such as clustered stations or inhomogeneous station densities. This QC method is not only an appropriate tool for case studies but also for model validation and has been proving itself as a preprocessing tool for operational meso- and micrometeorological analyses.
Estimation of Ambiguity in Ensemble Forecasts
Authors: Eckel F. Anthony , Allen Mark S. , Sittel Matthew C. 
Published: August 2011

Abstract
Ambiguity is uncertainty in the prediction of forecast uncertainty, or in the forecast probability of a specific event, associated with random error in an ensemble forecast probability density function. In ensemble forecasting ambiguity arises from finite sampling and deficient simulation of the various sources of forecast uncertainty. This study introduces two practical methods of estimating ambiguity and demonstrates them on 5-day, 2-m temperature forecasts from the Japan Meteorological Agency’s Ensemble Prediction System. The first method uses the error characteristics of the calibrated ensemble as well as the ensemble spread to predict likely errors in forecast probability. The second method applies bootstrap resampling on the ensemble members to produce multiple likely values of forecast probability. Both methods include forecast calibration since ambiguity results from random and not systematic errors, which must be removed to reveal the ambiguity. Additionally, use of a more robust calibration technique (improving beyond just correcting average errors) is shown to reduce ambiguity. Validation using a low-order dynamical system reveals that both estimation methods have deficiencies but exhibit some skill, making them candidates for application to decision making—the subject of a companion paper.
Occipital arteriovenous malformations and migraine
Authors: Galletti Francesca , Sarchielli Paola , Hamam Mohamed , Costa Cinzia , Cupini Letizia M , Cardaioli Gabriela , Belcastro Vincenzo , Eusebi Paolo , Lunardi Pierpaolo , Calabresi Paolo 
Published: August 2011

Background: Headache has been reported to be the first clinical presentation in several patients with cerebral arteriovenous malformations (AVMs). Headache associated with AVMs often shows characteristics of migraine with and without aura. Angiographic characteristics of AVMs, such as their location, could determine the ‘migraine-like’ features of attacks. Methods: We performed an observational study of the clinical and angiographic characteristics of a cohort of 40 consecutive patients with AVMs who had been admitted to our institute for endovascular embolization over a 4-year period. Headache was characterized according to ICHD-II criteria. The relationship between headaches and the angioarchitectural features of AVMs was also analysed. Results: Migraine-like headache was the first clinical manifestation in 22.5% of patients. The location of the malformation was significantly associated with migraine-like presentation (p = 0.03) and the occipital lobe was the predominant site. Conclusions: An occipital location may be linked with spreading depression, a pathogenic mechanism of migraine. Headache associated with arteriovenous malformations in the occipital lobe, although secondary in nature, could have clinical features similar to migraine.
Implementing a low-cost web-based clinical trial management system for community studies: a case study
Authors: Geyer John , Myers Kathleen , Vander Stoep Ann , McCarty Carolyn , Palmer Nancy , DeSalvo Amy 
Published: August 2011

Background Clinical trials with multiple intervention locations and a single research coordinating center can be logistically difficult to implement. Increasingly, web-based systems are used to provide clinical trial support with many commercial, open source, and proprietary systems in use. New web-based tools are available which can be customized without programming expertise to deliver web-based clinical trial management and data collection functions. Purpose To demonstrate the feasibility of utilizing low-cost configurable applications to create a customized web-based data collection and study management system for a five intervention site randomized clinical trial establishing the efficacy of providing evidence-based treatment via teleconferencing to children with attention-deficit hyperactivity disorder. The sites are small communities that would not usually be included in traditional randomized trials. A major goal was to develop database that participants could access from computers in their home communities for direct data entry. Methods Discussed is the selection process leading to the identification and utilization of a cost-effective and user-friendly set of tools capable of customization for data collection and study management tasks. Results An online assessment collection application, template-based web portal creation application, and web-accessible Access 2007 database were selected and customized to provide the following features: schedule appointments, administer and monitor online secure assessments, issue subject incentives, and securely transmit electronic documents between sites. Each tool was configured by users with limited programming expertise. As of June 2011, the system has successfully been used with 125 participants in 5 communities, who have completed 536 sets of assessment questionnaires, 8 community therapists, and 11 research staff at the research coordinating center. Limitations Total automation of processes is not possible with the current set of tools as each is loosely affiliated, creating some inefficiency. This system is best suited to investigations with a single data source e.g., psychosocial questionnaires. Conclusions New web-based applications can be used by investigators with limited programming experience to implement user-friendly, efficient, and cost-effective tools for multi-site clinical trials with small distant communities. Such systems allow the inclusion in research of populations that are not usually involved in clinical trials.
RNAexinv: An extended inverse RNA folding from shape and physical attributes to sequences
Authors: Avihoo Assaf , Churkin Alexander , Barash Danny 
Published: August 2011

Abstract

Background
RNAexinv is an interactive java application that performs RNA sequence design, constrained to yield a specific RNA shape and physical attributes. It is an extended inverse RNA folding program with the rationale behind that the generated sequences should not only fold into a desired structure, but they should also exhibit favorable attributes such as thermodynamic stability and mutational robustness. RNAexinv considers not only the secondary structure in order to design sequences, but also the mutational robustness and the minimum free energy. The sequences that are generated may not fully conform with the given RNA secondary structure, but they will strictly conform with the RNA shape of the given secondary structure and thereby take into consideration the recommended values of thermodynamic stability and mutational robustness that are provided.

Results
The output consists of designed sequences that are generated by the proposed method. Selecting a sequence displays the secondary structure drawings of the target and the predicted fold of the sequence, including some basic information about the desired and achieved thermodynamic stability and mutational robustness. RNAexinv can be used successfully without prior experience, simply specifying an initial RNA secondary structure in dot-bracket notation and numerical values for the desired neutrality and minimum free energy. The package runs under LINUX operating system. Secondary structure predictions are performed using the Vienna RNA package.

Conclusions
RNAexinv is a user friendly tool that can be used for RNA sequence design. It is especially useful in cases where a functional stem-loop structure of a natural sequence should be strictly kept in the designed sequences but a distant motif in the rest of the structure may contain one more or less nucleotide at the expense of another, as long as the global shape is preserved. This allows the insertion of physical observables as constraints. RNAexinv is available at http://www.cs.bgu.ac.il/~RNAexinv.
Accurate and fast estimation of taxonomic profiles from metagenomic shotgun sequences
Authors: Liu Bo , Gibbons Theodore , Ghodsi Mohammad , Treangen Todd , Pop Mihai 
Published: August 2011

Abstract

Background
A major goal of metagenomics is to characterize the microbial composition of an environment. The most popular approach relies on 16S rRNA sequencing, however this approach can generate biased estimates due to differences in the copy number of the gene between even closely related organisms, and due to PCR artifacts. The taxonomic composition can also be determined from metagenomic shotgun sequencing data by matching individual reads against a database of reference sequences. One major limitation of prior computational methods used for this purpose is the use of a universal classification threshold for all genes at all taxonomic levels.

Results
We propose that better classification results can be obtained by tuning the taxonomic classifier to each matching length, reference gene, and taxonomic level. We present a novel taxonomic classifier MetaPhyler (http://metaphyler.cbcb.umd.edu), which uses phylogenetic marker genes as a taxonomic reference. Results on simulated datasets demonstrate that MetaPhyler outperforms other tools commonly used in this context (CARMA, Megan and PhymmBL). We also present interesting results by analyzing a real metagenomic dataset.

Conclusions
We have introduced a novel taxonomic classification method for analyzing the microbial diversity from whole-metagenome shotgun sequences. Compared with previous approaches, MetaPhyler is much more accurate in estimating the phylogenetic composition. In addition, we have shown that MetaPhyler can be used to guide the discovery of novel organisms from metagenomic samples.
Genome-Wide association study identifies candidate genes for Parkinson's disease in an Ashkenazi Jewish population
Authors: Liu Xinmin , Cheng Rong , Verbitsky Miguel , Kisselev Sergey , Browne Andrew , Mejia-Sanatana Helen , Louis Elan D , Cote Lucien J , Andrews Howard , Waters Cheryl , Ford Blair , Frucht Steven , Fahn Stanley , Marder Karen , Clark Lorraine N , Lee Joseph H 
Published: August 2011

AbstractBackgroundTo date, nine Parkinson disease (PD) genome-wide association studies in North American, European and Asian populations have been published. The majority of studies have confirmed the association of the previously identified genetic risk factors,SNCAandMAPT, and two studies have identified three new PD susceptibility loci/genes (PARK16, BST1andHLA-DRB5). In a recent meta-analysis of datasets from five of the published PD GWAS an additional 6 novel candidate genes (SYT11, ACMSD, STK39, MCCC1/LAMP3, GAKandCCDC62/HIP1R) were identified. Collectively the associations identified in these GWAS account for only a small proportion of the estimated total heritability of PD suggesting that an 'unknown' component of the genetic architecture of PD remains to be identified.MethodsWe applied a GWAS approach to a relatively homogeneous Ashkenazi Jewish (AJ) population from New York to search for both 'rare' and 'common' genetic variants that confer risk of PD by examining any SNPs with allele frequencies exceeding 2%. We have focused on a genetic isolate, the AJ population, as a discovery dataset since this cohort has a higher sharing of genetic background and historically experienced a significant bottleneck. We also conducted a replication study using two publicly available datasets from dbGaP. The joint analysis dataset had a combined sample size of 2,050 cases and 1,836 controls.ResultsWe identified the top 57 SNPs showing the strongest evidence of association in the AJ dataset (p < 9.9 × 10-5). Six SNPs located within gene regions had positive signals in at least one other independent dbGaP dataset:LOC100505836(Chr3p24),LOC153328/SLC25A48(Chr5q31.1),UNC13B(9p13.3),SLCO3A1(15q26.1),WNT3(17q21.3) andNSF(17q21.3). We also replicated published associations for the gene regionsSNCA(Chr4q21; rs3775442, p = 0.037),PARK16(Chr1q32.1; rs823114 (NUCKS1), p = 6.12 × 10-4),BST1(Chr4p15; rs12502586, p = 0.027),STK39(Chr2q24.3; rs3754775, p = 0.005), andLAMP3(Chr3; rs12493050, p = 0.005) in addition to the two most common PD susceptibility genes in the AJ populationLRRK2(Chr12q12; rs34637584, p = 1.56 × 10-4) andGBA(Chr1q21; rs2990245, p = 0.015).ConclusionsWe have demonstrated the utility of the AJ dataset in PD candidate gene and SNP discovery both by replication in dbGaP datasets with a larger sample size and by replicating association of previously identified PD susceptibility genes. Our GWAS study has identified candidate gene regions for PD that are implicated in neuronal signalling and the dopamine pathway.
Reduction in host-finding behaviour in fungus-infected mosquitoes is correlated with reduction in olfactory receptor neuron responsiveness
Authors: George Justin , Blanford Simon , Domingue Michael J , Thomas Matthew B , Read Andrew F , Baker Thomas C 
Published: August 2011

Abstract

Background
Chemical insecticides against mosquitoes are a major component of malaria control worldwide. Fungal entomopathogens formulated as biopesticides and applied as insecticide residual sprays could augment current control strategies and mitigate the evolution of resistance to chemical-based insecticides.

Methods

Anopheles stephensi mosquitoes were exposed to Beauveria bassiana or Metarhizium acridum fungal spores and sub-lethal effects of exposure to fungal infection were studied, especially the potential for reductions in feeding and host location behaviours related to olfaction. Electrophysiological techniques, such as electroantennogram, electropalpogram and single sensillum recording techniques were then employed to investigate how fungal exposure affected the olfactory responses in mosquitoes.

Results
Exposure to B. bassiana caused significant mortality and reduced the propensity of mosquitoes to respond and fly to a feeding stimulus. Exposure to M. acridum spores induced a similar decline in feeding propensity, albeit more slowly than B. bassiana exposure. Reduced host-seeking responses following fungal exposure corresponded to reduced olfactory neuron responsiveness in both antennal electroantennogram and maxillary palp electropalpogram recordings. Single cell recordings from neurons on the palps confirmed that fungal-exposed behavioural non-responders exhibited significantly impaired responsiveness of neurons tuned specifically to 1-octen-3-ol and to a lesser degree, to CO2.

Conclusions
Fungal infection reduces the responsiveness of mosquitoes to host odour cues, both behaviourally and neuronally. These pre-lethal effects are likely to synergize with fungal-induced mortality to further reduce the capacity of mosquito populations exposed to fungal biopesticides to transmit malaria.