bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Surgery a Risk Factor for Creutzfeldt-Jakob Disease? Outcome Variation by Control Choice and Exposure Assessments
Authors: Barash Jed A. , Johnson Blair T. , Gregorio David I. 
Published: January 2008

Objective.To determine whether methodological differences explain divergent results in case-control studies examining surgery as a risk factor for Creutzfeldt-Jakob disease (CJD).Methods.After case-control studies were systematically identified using PubMed, we performed a homogeneity analysis and applied models to effect sizes (odds ratio [OR] with 95% confidence interval [CI]) using 2 parameters: type of control subject used and consistency of data ascertainment. The hospitals and communities were located in Europe, Japan, and Australia. Patients were CJD case subjects and age- and sex-matched control subjects in the hospital or community. Because of the natural history of the disease, CJD subjects are not considered reliable sources of information for these studies. Therefore, individuals who are considered close to the subjects and who have knowledge of their medical history, including spouses and relatives, are necessarily identified as proxy informants for the surgical record of the case subjects.Results.Overall, the effect sizes lacked homogeneity (P<.0001). Three studies that used control subjects from the community revealed a significantly elevated risk of CJD for patients who underwent surgery (OR, 1.82; 95% CI, 1.41-2.35 [P<.0001 ]), whereas 3 investigations that used control subjects from the hospital revealed a significantly reduced risk (OR, 0.69; 95% CI, 0.52-0.90 [P = .0069]). Two studies that used proxy informants to acquire information about case subjects and control subjects (consistent ascertainment) found that the risk of CJD was significantly lower in those subjects who underwent surgery (OR, 0.65; 95% CI, 0.48-0.87 [P = .0043]). Conversely, 4 studies in which proxy informants acted only on behalf of case subjects (inconsistent data ascertainment) found a significant positive association between surgery and CJD (OR, 1.67; 95% CI, 1.32-2.12 [P<.0001 ]). Both models fit the data very well, leaving no remaining variance in effect sizes to explain.Conclusion.Variation in the type of control subjects used and in exposure assessment in case-control studies may partially explain conflicting data regarding the association between surgery and CJD. However, there was almost complete confounding of these 2 parameters, making interpretation more difficult. Planning of future investigations must carefully consider these design elements.
Colorstock, SScolor, Ratón: RNA alignment visualization tools
Authors: Bendaña Yuri R. , Holmes Ian H. 
Published: January 2008

Abstract
Summary: Interactive examination of RNA multiple alignments for covariant mutations is a useful step in non-coding RNA sequence analysis. We present three parallel implementations of an RNA visualization metaphor: Colorstock, a command-line script using ANSI terminal color; SScolor, a Perl script that generates static HTML pages; and Ratón, an AJAX web application generating dynamic HTML. Each tool can be used to color RNA alignments by secondary structure and to visually highlight compensatory mutations in stems.
Availability: All source code is freely available under the GPL. The source code can be downloaded and a prototype of Ratón can be accessed at http://biowiki.org/RnaAlignmentViewers
Contact: ihh@berkeley.edu
Flexible informatics for linking experimental data to mathematical models via DataRail
Authors: Saez-Rodriguez Julio , Goldsipe Arthur , Muhlich Jeremy , Alexopoulos Leonidas G. , Millard Bjorn , Lauffenburger Douglas A. , Sorger Peter K. 
Published: January 2008

Abstract
Motivation: Linking experimental data to mathematical models in biology is impeded by the lack of suitable software to manage and transform data. Model calibration would be facilitated and models would increase in value were it possible to preserve links to training data along with a record of all normalization, scaling, and fusion routines used to assemble the training data from primary results.
Results: We describe the implementation of DataRail, an open source MATLAB-based toolbox that stores experimental data in flexible multi-dimensional arrays, transforms arrays so as to maximize information content, and then constructs models using internal or external tools. Data integrity is maintained via a containment hierarchy for arrays, imposition of a metadata standard based on a newly proposed MIDAS format, assignment of semantically typed universal identifiers, and implementation of a procedure for storing the history of all transformations with the array. We illustrate the utility of DataRail by processing a newly collected set of ∼22 000 measurements of protein activities obtained from cytokine-stimulated primary and transformed human liver cells.
Availability: DataRail is distributed under the GNU General Public License and available at http://code.google.com/p/sbpipeline/
Contact: sbpipeline@hms.harvard.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Cloning and Characterization of Naringenin 8-Prenyltransferase, a Flavonoid-Specific Prenyltransferase of Sophora flavescens
Authors: Sasaki Kanako , Mito Kouji , Ohara Kazuaki , Yamamoto Hirobumi , Yazaki Kazufumi 
Published: January 2008

Abstract
Prenylated flavonoids are natural compounds that often represent the active components in various medicinal plants and exhibit beneficial effects on human health. Prenylated flavonoids are hybrid products composed of a flavonoid core mainly attached to either 5-carbon (dimethylallyl) or 10-carbon (geranyl) prenyl groups derived from isoprenoid (terpenoid) metabolism, and the prenyl groups are crucial for their biological activity. Prenylation reactions in vivo are crucial coupling processes of two major metabolic pathways, the shikimate-acetate and isoprenoid pathways, in which these reactions are also known as a rate-limiting step. However, none of the genes responsible for the prenylation of flavonoids has been identified despite more than 30 years of research in this field. We have isolated a prenyltransferase gene from Sophora flavescens, SfN8DT-1, responsible for the prenylation of the flavonoid naringenin at the 8-position, which is specific for flavanones and dimethylallyl diphosphate as substrates. Phylogenetic analysis shows that SfN8DT-1 has the same evolutionary origin as prenyltransferases for vitamin E and plastoquinone. The gene expression of SfN8DT-1 is strictly limited to the root bark where prenylated flavonoids are solely accumulated in planta. The ectopic expression of SfN8DT-1 in Arabidopsis thaliana resulted in the formation of prenylated apigenin, quercetin, and kaempferol, as well as 8-prenylnaringenin. SfN8DT-1 represents the first flavonoid-specific prenyltransferase identified in plants and paves the way for the identification and characterization of further genes responsible for the production of this large and important class of secondary metabolites.
Metabolic Profiles ofLolium perenneAre Differentially Affected by Nitrogen Supply, Carbohydrate Content, and Fungal Endophyte Infection
Authors: Rasmussen Susanne , Parsons Anthony J. , Fraser Karl , Xue Hong , Newman Jonathan A. 
Published: January 2008

AbstractLolium perenne cultivars differing in their capacity to accumulate water soluble carbohydrates (WSCs) were infected with three strains of fungal Neotyphodium lolii endophytes or left uninfected. The endophyte strains differed in their alkaloid profiles. Plants were grown at two different levels of nitrogen (N) supply in a controlled environment. Metabolic profiles of blades were analyzed using a variety of analytical methods. A total of 66 response variables were subjected to a principle components analysis and factor rotation. The first three rotated factors (46% of the total variance) were subsequently analyzed by analysis of variance. At high N supply nitrogenous compounds, organic acids and lipids were increased; WSCs, chlorogenic acid (CGA), and fibers were decreased. The high-sugar cultivar ‘AberDove’ had reduced levels of nitrate, most minor amino acids, sulfur, and fibers compared to the control cultivar ‘Fennema’, whereas WSCs, CGA, and methionine were increased. In plants infected with endophytes, nitrate, several amino acids, and, magnesium were decreased; WSCs, lipids, some organic acids, and CGA were increased. Regrowth of blades was stimulated at high N, and there was a significant endophyte × cultivar interaction on regrowth. Mannitol, a fungal specific sugar alcohol, was significantly correlated with fungal biomass. Our findings suggest that effects of endophytes on metabolic profiles of L. perenne can be considerable, depending on host plant characteristics and nutrient supply, and we propose that a shift in carbon/N ratios and in secondary metabolite production as seen in our study is likely to have impacts on herbivore responses.
A Comparison of Two Nicotiana attenuata Accessions Reveals Large Differences in Signaling Induced by Oral Secretions of the Specialist Herbivore Manduca sexta
Authors: Wu Jianqiang , Hettenhausen Christian , Schuman Meredith C. , Baldwin Ian T. 
Published: January 2008

Abstract
Genetic variation within and among populations provides the raw material for evolution. Although many studies describe inter- and intraspecific variation of defensive metabolites, little is known about variation among plant populations within early signaling responses elicited by herbivory or by herbivore oral secretions (OS) introduced into wounds during feeding. In this study, we compare the OS-elicited early responses as well as the antiherbivore defensive metabolites in two accessions of the wild tobacco Nicotiana attenuata and show that, compared with an accession collected from Utah, an Arizona accession has lower herbivore-elicited activity of the salicylic acid-induced protein kinase, an important mitogen-activated protein kinase involved in herbivore resistance. These differences in salicylic acid-induced protein kinase activity were associated with substantially different levels of OS-elicited jasmonic acid, jasmonic acid-isoleucine conjugate, and ethylene bursts. Gene expression level polymorphism (ELP) determines phenotypic variation among populations, and we found the two accessions to have significantly different ELPs in the genes involved in early signaling responses to herbivory. In addition, we found differences between the Utah and the Arizona accessions in the concentrations of several secondary metabolites that contribute to N. attenuata's direct and indirect defenses. This study demonstrates significant natural variation in regulatory elements that mediate plant responses to herbivore attack, highlighting the role of ELP in producing a diversity of plant defense phenotypes.
Relevance of the flavin binding to the stability and folding of engineered cholesterol oxidase containing noncovalently bound FAD
Authors: Caldinelli Laura , Iametti Stefania , Barbiroli Alberto , Fessas Dimitrios , Bonomi Francesco , Piubelli Luciano , Molla Gianluca , Pollegioni Loredano 
Published: January 2008

AbstractThe flavoprotein cholesterol oxidase (CO) from Brevibacterium sterolicum is a monomeric flavoenzyme containing one molecule of FAD cofactor covalently linked to His69. The elimination of the covalent link following the His69Ala substitution was demonstrated to result in a significant decrease in activity, in the midpoint redox potential of the flavin, and in stability with respect to the wild‐type enzyme, but does not modify the overall structure of the enzyme. We used CO as a model system to dissect the changes due to the elimination of the covalent link between the flavin and the protein (by comparing the wild‐type and H69A CO holoproteins) with those due to the elimination of the cofactor (by comparing the holo‐ and apoprotein forms of H69A CO). The apoprotein of H69A CO lacks the characteristic tertiary structure of the holoprotein and displays larger hydrophobic surfaces; its urea‐induced unfolding does not occur by a simple two‐state mechanism and is largely nonreversible. Minor alterations in the flavin binding region are evident between the native and the refolded proteins, and are likely responsible for the low refolding yield observed. A model for the equilibrium unfolding of H69A CO that also takes into consideration the effects of cofactor binding and dissociation, and thus may be of general significance in terms of the relationships between cofactor uptake and folding in flavoproteins, is presented.
Structure–function analyses involving palindromic analogs of tritrypticin suggest autonomy of anti‐endotoxin and antibacterial activities
Authors: Kaur Kanwal J. , Sarkar Pampi , Nagpal Sushma , Khan Tarique , Salunke Dinakar M. 
Published: January 2008

AbstractNeutralization of invading pathogens by gene‐encoded peptide antibiotics has been suggested to manifest in a variety of different modes. Some of these modes require internalization of the peptide through a pathway that involves LPS‐mediated uptake of the peptide antibiotics. Many proline/tryptophan‐rich cationic peptides for which this mode has been invoked do, indeed, show LPS (endotoxin) binding. If the mechanism of antibiotic action involves the LPS‐mediated pathway, a positive correlation ought to manifest between the binding to LPS, its neutralization, and the bacterial killing. No such correlation was evident based on our studies involving minimal active analogs of tritrypticin. The anti‐endotoxin activities of these analogs appear not to relate directly to their antibiotic potential. The two palindromic analogs of tritrypticin, NT7 (RRFPWWW) and CT7 (WWWPFRR), showed comparable antibacterial activities. However, while NT7 exhibited anti‐endotoxin activity, CT7 did not. The LPS binding of two tritrypticin analogs correlated with their corresponding structures, but the antibacterial activities did not. Further structure–function analysis indicated specific structural implications of the antibacterial activity at the molecular level. Studies involving designed analogs of NT7 incorporating either rigid or flexible linkers between the specifically distanced hydrophobic and cationic clusters modulate the LPS binding. On the other hand, not knowing the target receptor for antibacterial activity is a drawback since the precise epitope for antibacterial activity is not definable. It is apparent that the anti‐endotoxin and antibacterial activities represent two independent functions of tritrypticin, consistent with the emerging multifunctionality in the nature of cathelicidins.
Conformational pH dependence of intermediate states during oligomerization of the human prion protein
Authors: Gerber Remo , Tahiri‐Alaoui Abdessamad , Hore P.J. , James William 
Published: January 2008

AbstractIntermediate states are key to understanding the molecular mechanisms governing protein misfolding. The human prion protein (PrP) can follow various misfolding pathways, and forms a soluble β‐sheet‐rich oligomer under acidic, mildly denaturing, high salt conditions. Here we describe a fast conformational switch from the native α‐monomer to monomeric intermediate states under oligomer‐forming conditions, followed by a slower oligomerization process. We observe a pH dependence of the secondary structure of these intermediate forms, with almost native‐like α‐helical secondary structure at pH 4.1 and predominantly β‐sheet characteristics at pH 3.6. NMR spectroscopy differentiates these intermediate states from the native protein and indicates dynamic rearrangements of secondary structure elements characteristic of a molten globule. The α‐helical intermediate formed at pH 4.1 can convert to the β‐sheet conformation at pH 3.6 but not vice versa, and neither state can be reconverted to an α‐monomer. The presence of methionine rather than valine at codon 129 accelerates the rate of oligomer formation from the intermediate state.
Protein structure and oligomerization are important for the formation of export‐competent HIV‐1 Rev–RRE complexes
Authors: Edgcomb Stephen P. , Aschrafi Angelique , Kompfner Elizabeth , Williamson James R. , Gerace Larry , Hennig Mirko 
Published: January 2008

AbstractThe translation of the unspliced and partially spliced viral mRNAs that encode the late, structural proteins of HIV‐1 depends on the viral‐protein Rev. Oligomeric binding of Rev to the Rev response element (RRE) in these mRNAs promotes their export from the nucleus and thus controls their expression. Here, we compared the effects of hydrophobic to hydrophilic mutations within the oligomerization domain of Rev using assays for oligomeric RNA binding, protein structure, and export from the nucleus. Oligomeric RNA binding alone does not correlate well with RNA transport activity in the subset of mutants. However, protein structure as judged by CD spectroscopy does correlate well with Rev function. The oligomeric assembly of Rev‐L18T is impaired but exhibits minor defects in structure and retains a basal level of activity in vivo. The prevalence of L18T in infected individuals suggests a positive selection mechanism for L18T modulation of Rev activity that may delay the onset of AIDS.
Structural characterization of human general transcription factor TFIIF in solution
Authors: Akashi Satoko , Nagakura Shinjiro , Yamamoto Seiji , Okuda Masahiko , Ohkuma Yoshiaki , Nishimura Yoshifumi 
Published: January 2008

AbstractHuman general transcription factor IIF (TFIIF), a component of the transcription pre‐initiation complex (PIC) associated with RNA polymerase II (Pol II), was characterized by size‐exclusion chromatography (SEC), electrospray ionization mass spectrometry (ESI‐MS), and chemical cross‐linking. Recombinant TFIIF, composed of an equimolar ratio of α and β subunits, was bacterially expressed, purified to homogeneity, and found to have a transcription activity similar to a natural one in the human in vitro transcription system. SEC of purified TFIIF, as previously reported, suggested that this protein has a size >200 kDa. In contrast, ESI‐MS of the purified sample gave a molecular size of 87 kDa, indicating that TFIIF is an αβ heterodimer, which was confirmed by matrix‐assisted laser desorption/ionization (MALDI) MS of the cross‐linked TFIIF components. Recent electron microscopy (EM) and photo‐cross‐linking studies showed that the yeast TFIIF homolog containing Tfg1 and Tfg2, corresponding to the human α and β subunits, exists as a heterodimer in the PIC, so the human TFIIF is also likely to exist as a heterodimer even in the PIC. In the yeast PIC, EM and photo‐cross‐linking studies showed different results for the mutual location of TFIIE and TFIIF along DNA. We have examined the direct interaction between human TFIIF and TFIIE by ESI‐MS, SEC, and chemical cross‐linking; however, no direct interaction was observed, at least in solution. This is consistent with the previous photo‐cross‐linking observation that TFIIF and TFIIE flank DNA separately on both sides of the Pol II central cleft in the yeast PIC.
The solution structure of ribosomal protein S17E from Methanobacterium thermoautotrophicum: A structural homolog of the FF domain
Authors: Wu Bin , Yee Adelinda , Huang Yuanpeng J. , Ramelot Theresa A. , Cort John R. , Semesi Anthony , Jung Jin‐Won , Lee Weontae , Montelione Gaetano T. , Kennedy Michael A. , Arrowsmith Cheryl H. 
Published: January 2008

AbstractThe ribosomal protein S17E from the archaeon Methanobacterium thermoautotrophicum is a component of the 30S ribosomal subunit. S17E is a 62‐residue protein conserved in archaea and eukaryotes and has no counterparts in bacteria. Mammalian S17E is a phosphoprotein component of eukaryotic ribosomes. Archaeal S17E proteins range from 59 to 79 amino acids, and are about half the length of the eukaryotic homologs which have an additional C‐terminal region. Here we report the three‐dimensional solution structure of S17E. S17E folds into a small three‐helix bundle strikingly similar to the FF domain of human HYPA/FBP11, a novel phosphopeptide‐binding fold. S17E bears a conserved positively charged surface acting as a robust scaffold for molecular recognition. The structure of M. thermoautotrophicum S17E provides a template for homology modeling of eukaryotic S17E proteins in the family.
Solution structure of ribosomal protein L40E, a unique C4 zinc finger protein encoded by archaeon Sulfolobus solfataricus
Authors: Wu Bin , Lukin Jonathan , Yee Adelinda , Lemak Alexander , Semesi Anthony , Ramelot Theresa A. , Kennedy Michael A. , Arrowsmith Cheryl H. 
Published: January 2008

AbstractThe ribosomal protein L40E from archaeon Sulfolobus solfataricus is a component of the 50S ribosomal subunit. L40E is a 56‐residue, highly basic protein that contains a C4 zinc finger motif, CRKC_X10_CRRC. Homologs are found in both archaea and eukaryotes but are not present in bacteria. Eukaryotic genomes encode L40E as a ubiquitin‐fusion protein. L40E was absent from the crystal structure of euryarchaeota 50S ribosomal subunit. Here we report the three‐dimensional solution structure of L40E by NMR spectroscopy. The structure of L40E is a three‐stranded β‐sheet with a simple β2β1β3 topology. There are two unique characteristics revealed by the structure. First, a large and ordered β2–β3 loop twists to pack across the one side of the protein. L40E contains a buried polar cluster comprising Lys19, Lys20, Cys22, Asn29, and Cys36. Second, the surface of L40E is almost entirely positively charged. Ten conserved basic residues are positioned on the two sides of the surface. It is likely that binding of zinc is essential in stabilizing the tertiary structure of L40E to act as a scaffold to create a broad positively charged surface for RNA and/or protein recognition.
Solution structure of Ca2+‐free rat α‐parvalbumin
Authors: Henzl Michael T. , Tanner John J. 
Published: January 2008

AbstractMammals express two parvalbumins—an α isoform and a β isoform. In rat, the α‐parvalbumin (α‐PV) exhibits superior divalent ion affinity. For example, the standard free energies for Ca2+ binding differ by 5.5 kcal/mol in 0.15 M KCl (pH 7.4). High‐resolution structures of the Ca2+‐bound proteins provide little insight into this disparity, prompting a structural analysis of the apo‐proteins. A recent analysis of rat β‐PV suggested that Ca2+ removal provokes substantial conformational changes—reorientation of the C, D, and E helices; reorganization of the hydrophobic core; reduced interdomain contact; and remodeling of the AB domain. The energetic penalty attendant to reversing these changes, it was suggested, could contribute to the attenuated divalent ion‐binding signature of that protein. That hypothesis is supported by data presented herein, describing the solution structure and peptide backbone dynamics of Ca2+‐free rat α‐PV. In marked contrast to rat β‐PV, the apo‐ and Ca2+‐loaded forms of the rat α isoform are quite similar. Significant structural differences appear to be confined to the loop regions of the molecule. This finding implies that the α‐PV isoform enjoys elevated divalent ion affinity because the metal ion‐binding events do not require major structural rearrangement and the concomitant sacrifice of binding energy.