bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA barcoding Australasian chondrichthyans: results and potential uses in conservation
Authors: Ward Robert D. , Holmes Bronwyn H. , White William T. , Last Peter R.
Published: January 2008

DNA barcoding – sequencing a region of the mitochondrial cytochrome c oxidase 1 gene (cox1) – promises a rapid and accurate means of species identification, and of any life history stage. For sharks and rays, it may offer a ready means of identifying legal or illegal shark catches, including shark fins taken for the profitable shark fin market. Here it is shown that an analysis of sequence variability in a 655 bp region of cox1 from 945 specimens of 210 chondrichthyan species from 36 families permits the discrimination of 99.0% of these species. Only the two stingarees Urolophus sufflavus and U. cruciatus could not be separated, although these could be readily distinguished from eight other congeners. The average Kimura 2 parameter distance separating individuals within species was 0.37%, and the average distance separating species within genera was 7.48%. Two specimens that clustered with congeners rather than with their identified species-cluster were noted: these could represent instances of hybridisation (although this has not be documented for chondrichthyans), misidentification or mislabelling. It is concluded that cox1 barcoding can be used to identify shark and ray species with a very high degree of accuracy. The sequence variability characteristics of individuals of five species (Aetomylaeus nichofii, Dasyatis kuhlii, Dasyatis leylandi, Himantura gerrardi and Orectolobus maculatus) were consistent with cryptic speciation, and it is suggested that these five taxa be subjected to detailed taxonomic examination to confirm or refute this suggestion. The present barcoding study holds out great hope for the ready identification of sharks, shark products and shark fins, and also highlights some taxonomic issues that need to be investigated further.
Phylogeography of a threatened freshwater fish (Mogurnda adspersa) in eastern Australia: conservation implications
Authors: Faulks Leanne K. , Gilligan Dean M. , Beheregaray Luciano B.
Published: January 2008

Phylogeography is a field that has the potential to provide an integrative approach to the conservation of threatened species. The southern purple spotted gudgeon, Mogurnda adspersa, is a small freshwater fish that was once common and widely distributed throughout south-eastern Australia. However, habitat alteration has dramatically reduced the size and the range of Murray–Darling Basin populations, which are now classified as endangered. Here patterns of genetic structure and evolutionary history of M. adspersa in southern Queensland and the Murray–Darling Basin are elucidated using three regions of the mitochondrial DNA, the ATPase 6 and 8 and the control region. Murray–Darling Basin populations are characterised by lineages with highly localised endemism, very low genetic diversity and restricted gene flow. Phylogenetic reconstructions show that Murray–Darling Basin populations comprise a monophyletic clade that possibly originated by range expansion from the coast around 1.6 million years ago. It is proposed that the divergent Murray–Darling Basin clade is of high conservation priority and requires separate management. The present study further exemplifies the role of drainage rearrangement in driving evolutionary diversification in Australian freshwater fishes, an historical process with profound implications for conservation management.
The basic colour terms of Lower Sorbian and Upper Sorbian and their typological relevance
Authors: Hippisley Andrew , Davies Ian , Corbett Greville G.
Published: January 2008

Berlin & Kay’s basic colour term framework claims that there is an ordering in the diachronic development of languages’ colour systems. One generalisation is that primary colours, WHITE, BLACK, RED, YELLOW, GREEN, BLUE, are lexical­ised before derived colours, which are perceptual blends, e.g. ORANGE is the blend of YELLOW and RED. The colour systems of Lower Sorbian and Upper Sorbian offer an important typological contribution. It is already known that primary colour space can contract upon the emergence of a basic derived term; our findings indicate that derived categories also shift as colour systems develop. Tsakhur offers corroborating evidence.
Orientation as a strategy of spatial reference
Authors: Terrill Angela , Burenhult Niclas
Published: January 2008

This paper explores a strategy of spatial expression which utilizes orientation, a way of describing the spatial relationship of entities by means of reference to their facets. We present detailed data and analysis from two languages, Jahai (Mon-Khmer, Malay Peninsula) and Lavukaleve (Papuan isolate, Solomon Is­lands), and supporting data from five more languages, to show that the orienta­tion strategy is a major organizing principle in these languages. This strategy has not previously been recognized in the literature as a unitary phenomenon, and the languages which employ it present particular challenges to existing ty­pol­ogies of spatial frames of reference.
Energy Efficient Correlated Data Aggregation for Wireless Sensor Networks
Authors: Park Seung-Jong , Sivakumar Raghupathy
Published: January 2008

Data aggregations from Sensors to a sink in wireless sensor networks (WSNs) are typically characterized by correlation along the spatial, semantic, and temporal dimensions. Exploiting such correlation when performing data aggregation can result in considerable improvements in the bandwidth and energy performance of WSNs. For the sensors-to-sink data delivery, we first explore two theoretical solutions: the shortest path tree (SPT) and the minimum spanning tree (MST) approaches. To approximate the optimal solution (MST) in case of perfect correlation among data, we propose a new aggregation which combines the minimum dominating set (MDS) with the shortest path tree (SPT) in order to aggregate correlated data. To reduce the redundancy among correlated data and simplify the synchronization among transmission, the proposed aggregation takes two stages: local aggregation among sensors around a node in the MDS and global aggregation among sensors in the MDS. Finally, using discrete event simulations, we show that the proposed aggregation outperforms the SPT and closely approximates the centralized optimal solution, the MST, with less amount of overhead and in a decentralized fashion.
A Combined Localization and Geographic Routing Algorithm for Rapidly-Deployed Wireless Sensor Networks
Authors: Qu Hui , Wicker Stephen B.
Published: January 2008

We consider a network of randomly-deployed, low-cost sensors and a single powerful sink node. A partition-based localization algorithm is proposed in which the sink node imparts sector-based location information through the phased-array transmission of a series of beacons. One-hop neighbor information is used by each sensor in a series of sector-partitioning routines to identify the sub-sector in which it resides. A geographic routing algorithm is then proposed which uses the sector-based localization results as the basis for a routing algorithm. Simulation results indicate that the performance of our localization algorithm improves with node density, and that the performance of the combined localization and routing algorithm in the presence of severe measurement noise is comparable with that provided by the same routing algorithm using perfect location information.
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

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

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.
Evolutionary dynamics of nematode operons: Easy come, slow go
Authors: Qian Wenfeng , Zhang Jianzhi
Published: January 2008

Operons are widespread in prokaryotes, but are uncommon in eukaryotes, except nematode worms, where ∼15% of genes reside in over 1100 operons in the model organism Caenorhabditis elegans. It is unclear how operons have become abundant in nematode genomes. The “one-way street” hypothesis asserts that once formed by chance, operons are very difficult to break, because the breakage would leave downstream genes in an operon without a promoter, and hence, unexpressed. To test this hypothesis, we analyzed the presence and absence of C. elegans operons in Caenorhabditis briggsae, Caenorhabditis remanei, and Caenorhabditis brenneri, using Pristionchus pacificus and Brugia malayi as outgroups, and identified numerous operon gains and losses. Coupled with experimental examination of trans-splicing patterns, our comparative genomic analysis revealed diverse molecular mechanisms of operon losses, including inversion, insertion, and relocation, but the presence of internal promoters was not found to facilitate operon losses. In several cases, the data allowed inference of mechanisms by which downstream genes are expressed after operon breakage. We found that the rate of operon gain is ∼3.3 times that of operon loss. Thus, the evolutionary dynamics of nematode operons is better described as “easy come, slow go,” rather than a “one-way street.” Based on a mathematic model of operon gains and losses and additional assumptions, we projected that the number of operons in C. elegans will continue to rise by 6%–18% in future evolution before reaching equilibrium between operon gains and losses.
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

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

Lolium 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

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

The 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

Neutralization 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

Intermediate 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

The 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

Human 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

The 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

The 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

Mammals 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.
Challenges and strategies of increasing the production and use of Cochrane reviews: the Argentinean experience
Authors: Ciapponi Agustín
Published: January 2008

The Cochrane Collaboration (CC), established in 1993, is an internationally renowned initiative dedicated to improving health care for the world's population. In the late 1990s, the Iberoamerican Cochrane Centre (IbCC) was created to promote the CC in Latin America. Because the production and use of Cochrane reviews were still low in 2002, Argentina implemented specific strategies and a model to expand the IbCC. The objective of this article was to describe strategies to increase the production and use of Cochrane reviews in Argentina. Methods used included surveys delivered to primary health care workers to provide data about their knowledge and use of the CC, and about the production of titles, protocols, and systematic reviews published in the Cochrane Library.

Our survey showed that only 51% of a selected population of primary healthcare workers knew about the CC and only 23% knew about the Argentine Cochrane centre. In the previous year, 60% had never used the CC. To overcome these challenges, we used seven types of complementary strategies: (1) networking, (2) dissemination, (3) training, (4) support to Cochrane members, (5) strategic alliances, (6) research, and (7) fund‐raising. An improvement in the production and use of Cochrane reviews was seen in Argentina, and the set of aforementioned strategies could be partly responsible for this increase. Multi‐level networking, training and an appropriate centre's mother institution could be the most important interventions. More research is needed to explore this hypothesis. Lessons learned on this first evaluation will help us to continue with the development of the CC in Argentina.
Exploring heterogeneity in meta‐analyses: needs, resources and challenges
Authors: Xu Hairong , Platt Robert W. , Luo Zhong‐Cheng , Wei Shuqin , Fraser William D.
Published: January 2008

The investigation of heterogeneity remains an essential but difficult issue in the conduct of meta‐analysis. We reviewed standard and graphical methods used to explore heterogeneity in meta‐analysis and publications from January 2005 to April 2007 regarding meta‐analyses that focused on perinatal health topics. We assessed their approaches to the investigation of heterogeneity, including: (1) whether statistical testing for heterogeneity was performed and, if so, which test was used, (2) how a finding of statistically significant heterogeneity was handled, and (3) how the analyses were conducted in the presence of heterogeneity.
Improving systematic reviews for clinicians: a journal editor's view
Authors: Scott James R.
Published: January 2008

Evidence‐based medicine implies that randomised controlled trials, meta‐analyses and systematic reviews will be used by clinicians to determine the most appropriate therapy for patients. Cochrane reviews are the prototype of systematic reviews, but they are not optimally utilised by physicians in the United States. This may be related to lack of access, unfamiliarity with the format, and the perception that they are impractical for actual patient care. An opportunity exists to criticise and improve systematic reviews, and changes are suggested to make them more user‐friendly.
Strategies for improving the quality of health care in maternal and child health in low‐ and middle‐income countries: an overview of systematic reviews
Authors: Althabe Fernando , Bergel Eduardo , Cafferata María Luisa , Gibbons Luz , Ciapponi Agustín , Alemán Alicia , Colantonio Lisandro , Palacios Alvaro Rodríguez
Published: January 2008

There are many systematic reviews of continuing education programmes and educational strategies for quality improvement in health care. Most of the reviewed studies are one‐off evaluations rather than impact evaluations with long‐term follow‐up. There are few systematic reviews of organisational, financial and regulatory interventions, and few high‐quality studies. These interventions are probably as or more important than educational strategies, although they are less well evaluated. Few studies have been undertaken in low‐ and middle‐income countries (LMIC) or that address maternal and child health (MCH). Thus, the results of the available studies and reviews need to be interpreted cautiously when applied to LMIC.

Interactive workshops, reminders and multifaceted interventions can improve professional practice, and they generally have moderate effects. Educational outreach visits consistently improve prescribing but have variable effects on other behaviours. Audit and feedback interventions have variable effects on professional practice, but most often these are small to moderate effects. Mass‐media and patient‐mediated interventions may change professional practice. Multifaceted interventions that combine several quality‐improvement strategies are also effective but may not be more so than single interventions. While all of these strategies are applicable to MCH in LMIC, the applicability of the results to rural settings, in particular, may be limited. Use of these strategies could exacerbate inequalities, and this should be taken into consideration when planning implementation. Scaling up and sustainability may be difficult to achieve in LMIC contexts and need careful consideration.

The use of financial interventions has not been well studied; financial incentives and disincentives may be difficult to use effectively and efficiently, although their impact on practice needs to be considered. Organisational interventions are likely to be important, given that there are often underlying organisational or system problems. Regulatory interventions have not been well evaluated, but may sometimes be both inexpensive and effective. There are no ‘magic bullets’ or simple solutions for ensuring the quality of health care services. Interventions should be selected or tailored to address the underlying reasons for a failure to deliver effective services. Decision‐makers should select the most appropriate interventions for specific problems. This requires a governance structure that clearly assigns responsibility for quality‐improvement activities, priority setting, selection and design of interventions, and evaluation.
AtNFXL1, an Arabidopsis homologue of the human transcription factor NF‐X1, functions as a negative regulator of the trichothecene phytotoxin‐induced defense response
Authors: Asano Tomoya , Masuda Daisuke , Yasuda Michiko , Nakashita Hideo , Kudo Toshiaki , Kimura Makoto , Yamaguchi Kazuo , Nishiuchi Takumi
Published: January 2008

Trichothecenes are a closely related family of phytotoxins that are produced by phytopathogenic fungi. In Arabidopsis, expression of AtNFXL1, a homologue of the putative human transcription repressor NF‐X1, was significantly induced by application of type A trichothecenes, such as T‐2 toxin. An atnfxl1 mutant growing on medium lacking trichothecenes showed no phenotype, whereas a hypersensitivity phenotype was observed in T‐2 toxin‐treated atnfxl1 mutant plants. Microarray analysis indicated that several defense‐related genes (i.e. WRKYs, NBS‐LRRs, EDS5, ICS1, etc.) were upregulated in T‐2 toxin‐treated atnfxl1 mutants compared with wild‐type plants. In addition, enhanced salicylic acid (SA) accumulation was observed in T‐2 toxin‐treated atnfxl1 mutants, which suggests that AtNFXL1 functions as a negative regulator of these defense‐related genes via an SA‐dependent signaling pathway. We also found that expression of AtNFXL1 was induced by SA and flg22 treatment. Moreover, the atnfxl1 mutant was less susceptible to a compatible phytopathogen, Pseudomonas syringae pv. tomato strain DC3000 (Pst DC3000). Taken together, these results indicate that AtNFXL1 plays an important role in the trichothecene response, as well as the general defense response in Arabidopsis.
The SUMO E3 ligase, AtSIZ1, regulates flowering by controlling a salicylic acid‐mediated floral promotion pathway and through affects on FLC chromatin structure
Authors: Jin Jing Bo , Jin Yin Hua , Lee Jiyoung , Miura Kenji , Yoo Chan Yul , Kim Woe‐Yeon , Van Oosten Michael , Hyun Youbong , Somers David E. , Lee Ilha , Yun Dae‐Jin , Bressan Ray A. , Hasegawa Paul M.
Published: January 2008

Loss‐of‐function siz1 mutations caused early flowering under short days. siz1 plants have elevated salicylic acid (SA) levels, which are restored to wild‐type levels by expressing nahG, bacterial salicylate hydroxylase. The early flowering of siz1 was suppressed by expressing nahG, indicating that SIZ1 represses the transition to flowering mainly through suppressing SA‐dependent floral promotion signaling under short days. Previous results have shown that exogenous SA treatment does not suppress late flowering of autonomous pathway mutants. However, the siz1 mutation accelerated flowering time of an autonomous pathway mutant, luminidependens, by reducing the expression of FLOWERING LOCUS C (FLC), a floral repressor. This result suggests that SIZ1 promotes FLC expression, possibly through an SA‐independent pathway. Evidence indicates that SIZ1 is required for the full activation of FLC expression in the late‐flowering FRIGIDA background. Interestingly, increased FLC expression and late flowering of an autonomous pathway mutant, flowering locus d (fld), was not suppressed by siz1, suggesting that SIZ1 promotes FLC expression by repressing FLD. Consistent with this, SIZ1 facilitates sumoylation of FLD that can be suppressed by mutations in three predicted sumoylation motifs in FLD (i.e. FLDK3R). Furthermore, expression of FLDK3R in fld protoplasts strongly reduced FLC transcription compared with expression of FLD, and this affect was linked to reduced acetylation of histone 4 in FLC chromatin. Taken together, the results suggest that SIZ1 is a floral repressor that not only represses the SA‐dependent pathway, but also promotes FLC expression by repressing FLD activity through sumoylation, which is required for full FLC expression in a FRIGIDA background.
Effect of nasal steroid treatment on airway inflammation determined by exhaled nitric oxide in allergic schoolchildren with perennial rhinitis and asthma
Authors: Pedroletti Christophe , Lundahl Joachim , Alving Kjell , Hedlin Gunilla
Published: January 2008

Rhinitis is common in asthmatic schoolchildren who are allergic to animal dander and constantly and indirectly exposed to these allergens in their everyday environment. As a patho‐physiological linkage between nasal and bronchial inflammation has been proposed to exist, the primary objective of this study was to determine whether nasal administration of mometasone furoate (MSNF) can reduce bronchial inflammation, as reflected in the level of exhaled nitric oxide (FENO) in asthmatic schoolchildren with dander allergy and mild‐to‐moderate rhinitis. Forty such children were assigned randomly to be treated for 4 wk with MSNF or placebo, employing a double‐blind procedure. FENO was the primary end‐point measured and secondary end‐points were nasal levels of NO, the concentration of eosinophilic cationic protein (ECP) in nasal lavage, the relative numbers of eosinophils in blood, forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF) and scoring of symptoms. There was no significant difference in the FENO values of the treated and control groups at any time‐point, whereas the nasal level of ECP was lower in the treated group compared with placebo (p = 0.05) on both days 7 and 28, and compared with baseline for the treated group (p = 0.06 on day 7, p = 0.02 on day 28). Furthermore, the mean blood eosinophil count decreased in the treated group, which also demonstrated lower scores for nasal symptoms compared with placebo, but neither of these differences were statistically significant. FEV1, PEF and nasal levels of NO remained unchanged in both groups. Four weeks of nasal treatment with MSNF had no effect on bronchial inflammation, as reflected by exhaled NO, whereas signs of nasal and systemic eosinophil activation were reduced. Thus, nasal administration of a steroid as a strategy to reduce asthmatic inflammation remains questionable in mild‐to‐moderately severe cases of perennial rhinitis and asthma.
Cord blood hemopoietic progenitor profiles predict acute respiratory symptoms in infancy
Authors: Fernandes Rochelle , Kusel Merci , Cyr Michael , Sehmi Roma , Holt Kathryn , Holt Barbara , Kebadze Tatiana , Johnston Sebastian L. , Sly Peter , Denburg Judah A. , Holt Patrick
Published: January 2008

Atopy is characterized by eosinophilic inflammation associated with recruitment of eosinophil/basophil (Eo/B) progenitors. We have previously shown that Eo/B progenitor phenotypes are altered in cord blood (CB) in infants at high risk of atopy/asthma, and respond to maternal dietary intervention during pregnancy. As respiratory tract viral infections have been shown to induce wheeze in infancy, we investigated the relationship between CB progenitor function and phenotype and acute respiratory illness (ARI), specifically wheeze and fever. CB from 39 high‐risk infants was studied by flow cytometry for CD34+ progenitor phenotype and by ex vivo Eo/B‐colony forming unit (CFU) responses to cytokine stimulation in relation to ARI in the first year of life. A consistent relationship was observed between increased numbers of granulocyte/macrophage (GM)‐colony‐stimulating factor (CSF)‐ and IL‐3‐responsive Eo/B‐CFU in CB and the frequency/characteristics of ARI during infancy. Comparable associations were found between ARI and CB IL‐3R+ and GM‐CSFR+CD34+ cell numbers. Conversely, a reciprocal decrease in the proportion of CB IL‐5R+ cells was found in relation to the clinical outcomes. The elevation of IL‐3/GM‐CSF‐responsive Eo/B progenitors in high‐risk infants in relation to ARI outcomes suggests a mechanism for the increased severity of inflammatory responses in these subjects following viral infection.
Attributes and views of families with food allergic children recruited from allergy clinics and from a consumer organization
Authors: Hu Wendy , Loblay Robert , Ziegler John , Kemp Andrew
Published: January 2008

A significant body of food allergy research has been conducted with families recruited from consumer organizations (COs). However, there has been no systematic comparison of the characteristics of such families with those attending specialist allergy clinics (ACs), nor have parental views on food allergy COs been examined in detail. To address these questions, 44 families with food allergic children recruited from hospital clinics and 25 families recruited from a CO: (i) completed a survey with items concerning demographic details, allergy features, and sources of allergy information, and (ii) participated in qualitative interviews and focus groups concerning their experiences. Significant differences were found in reported number of food allergies and nut allergy, seeking of second opinions, adrenaline autoinjector possession (but not use) and sources of food allergy information. Parents valued COs as sources of practical information and emotional support, but viewed advice which did not acknowledge their individual circumstances and heightened anxiety from contact with other anxious parents as being unhelpful. Research conducted with CO members is valuable, but may have limited generalizability to other populations. To supplement the information and support provided by ACs, all parents should be given the opportunity to join a CO, with guidance from their clinician towards those aspects of membership which are most likely to be helpful.