bluuebunny/crossref_metadata_2025 huggingface dataset:
The Earth, Source of Health and Hazards: An Introduction to Medical Geology
Authors: Skinner H. Catherine W.
Published: April 2007

Insidious hazards that affect humans and other living creatures are addressed in this review. Debilitation and disease that may arise from naturally occurring gases, minerals, and elements create problems with characteristics that inhibit progress toward adequate and immediate solutions: (a) Human or animal reactions are delayed, not detected until long after the original exposure; (b) sporadic or continual low-level exposures to the minor or trace amounts of offending materials via the atmosphere, hydrosphere, and lithosphere are difficult to evaluate; (c) the air, water, and food consumed may contain hazardous substances that go unnoticed; and (d) health reactions depend on bioavailability of the hazard and susceptibility of the individual. The etiology of many chronic diseases from exposure to earth materials—asbestos disease, As- and Se-induced cancers, and other disabilities—are suspected, but precise mechanisms of induction are presently unknown. Stipulation of disease from Earth-based hazardous materials requires collaboration of Earth and biomedical scientists to avert, or at least ameliorate, future disease and debilitation.
Biogeochemistry of Glacial Landscape Systems
Authors: Anderson Suzanne Prestrud
Published: April 2007

Glaciers affect biogeochemistry of landscapes through their sediments. Glacial erosion rates are high and the sediments produced are distinctively fine grained, hence glaciers can be thought of as producers of mineral surface area. Although this mineral surface area is highly reactive, temperature limits chemical weathering fluxes from glaciers and their surroundings. More significant effects may be associated with silt deposited in loess and on continental margins. Thick deposits in both settings contribute to carbon cycling through both silicate weathering and organic carbon burial. The impact of glaciers on biogeochemical cycles will be long-lasting, as the legacy of glacial erosion processes continues as long as sediment yields are elevated.
Chondrites and the Protoplanetary Disk
Authors: Scott Edward R.D.
Published: April 2007

Major advances in deciphering the record of nebula processes in chondrites can be attributed to analytical improvements that allow coordinated isotopic and mineralogical studies of components in chondrites and to a wealth of new meteorites from hot and cold deserts. These studies have identified a few rare pristine chondrites that largely escaped heating and alteration in asteroids, which have matrices composed of submicrometer-sized grains of enstatite and forsterite and amorphous silicates, as found in comets. Isotopic analyses of components in pristine chondrites using short-lived nuclide chronometers, Pb-Pb dating, and oxygen isotopes aided by laboratory and theoretical studies of chondrites and differentiated meteorites have provided key constraints on the processes that shaped the early solar system. These processes were once thought to have followed one another sequentially over a period of several million years: chondrule formation; planetesimal accretion; alteration, metamorphism, and melting in planetesimals; and finally, high-velocity collisions between asteroids. Radiometric dating shows, however, that these processes overlapped so that chondrules were still forming in the nebula several million years after early-formed planetesimals had melted and collided. Chondrites are extraordinary mixtures of presolar and solar nebula materials and asteroidal debris.
Models of Deltaic and Inner Continental Shelf Landform Evolution
Authors: Fagherazzi Sergio , Overeem Irina
Published: April 2007

The morphology of passive continental shelves is dictated by the input of sediments from rivers and their redistribution by waves, currents, and gravity-driven flows. The pathways followed by sediments sculpt a landscape whose diversity is rarely matched on Earth's surface. Sediments are released to the shelf from triangularly shaped, elongated, and dendritic deltas. Barrier islands rise from gently sloping areas, tidal channels dissect flats and saltmarshes, fine sediments form broad convex deposits, and shallow submarine valleys convey sediments and water to the deep ocean. This morphological diversity is based on two main building elements: water and sediments. Fluxes of water and sediments are particularly suitable to be modeled with numerical methods based on the continuum hypothesis and hydrodynamics theory. In recent years, a series of models have been developed to explore and understand the formation of shelf landforms from the dynamics of sediment transport. Herein we present an overview of the most recent results on the modeling of deltaic and inner-shelf morphodynamics.
Permo-Triassic Collision, Subduction-Zone Metamorphism, and Tectonic Exhumation Along the East Asian Continental Margin
Authors: Ernst W.G. , Tsujimori Tatsuki , Zhang Ruth , Liou J.G.
Published: April 2007

Convergent plate motion at ∼320–210 Ma generated the Tongbai-Dabie-Sulu (east-central China)-Imjingang-Gyeonggi (central Korea)-Renge-Suo (Southwestern Japan)-Sikhote-Alin orogen along the paleo-Pacific edge of cratonal Asia. This amalgamated belt reflects collision between the Sino-Korean and Yangtze cratons on the SW portion, and accretion of outboard oceanic arcs ± sialic fragments against the NE margin. Subducted Proterozoic-Paleozoic continental and oceanic crustal complexes underwent high- and ultrahigh-pressure metamorphism at low to moderate temperatures. Tectonic slices of sialic crust episodically disengaged from the downgoing plate and, driven by buoyancy, ascended rapidly to midcrustal levels from depths exceeding 90–200 km after continental collision in east-central China plus or minus Korea, and from ∼30–50 km after arrival of far-traveled oceanic terranes in SW Japan and the Russian Far East. On achieving neutral buoyancy and stalling out at 10–20 km depth, later doming, gravitational collapse, and erosion exposed parts of the high- and ultrahigh-pressure complexes. This curvilinear orogen has been segmented and offset by major and minor transverse faults. Also, regional backarc spreading opened marginal basins behind the Permo-Triassic convergent suture zone, further disturbing portions oceanward.
Microsampling and Isotopic Analysis of Igneous Rocks: Implications for the Study of Magmatic Systems
Authors: Davidson J.P. , Morgan D.J. , Charlier B.L.A. , Harlou R. , Hora J.M.
Published: April 2007

Isotopic fingerprinting has long been used to trace magmatic processes and the components that contribute to magmas. Recent technological improvements have provided an opportunity to analyze isotopic compositions on the scale of individual crystals, and consequently to integrate isotopic and geochemical tracing with textural and petrographic observations. It has now become clear that mineral phases are commonly not in isotopic equilibrium with their host glass/groundmass. Isotopic ratios recorded from core to rim of a mineral grain reflect the progressive changes in the magma composition from which the mineral crystallized. The sense of these changes and the relationship between isotopic composition and petrographic features, such as dissolution surfaces, can be used to constrain magma evolution pathways involving open system processes such as magma mixing, contamination and recharge.
Long-Term Perspectives on Giant Earthquakes and Tsunamis at Subduction Zones
Authors: Satake Kenji , Atwater Brian F.
Published: April 2007

Histories of earthquakes and tsunamis, inferred from geological evidence, aid in anticipating future catastrophes. This natural warning system now influences building codes and tsunami planning in the United States, Canada, and Japan, particularly where geology demonstrates the past occurrence of earthquakes and tsunamis larger than those known from written and instrumental records. Under favorable circumstances, paleoseismology can thus provide long-term advisories of unusually large tsunamis. The extraordinary Indian Ocean tsunami of 2004 resulted from a fault rupture more than 1000 km in length that included and dwarfed fault patches that had broken historically during lesser shocks. Such variation in rupture mode, known from written history at a few subduction zones, is also characteristic of earthquake histories inferred from geology on the Pacific Rim.
Comparative Assessment of the Association Information Captured by SNP Tagging
Authors: Nothnagel Michael , Wollstein Andreas , Krawczak Michael
Published: April 2007

Exploiting the association between single nucleotide polymorphisms (SNP) can potentially reduce the costs of association mapping of common disease genes. Different methods have been proposed for deﬁning subsets of SNPs as proxies (or tagSNPs) for other SNPs, some of which rely upon a model of haplotype blocks. Other approaches only consider the pair-wise correlation between markers as a basis for selecting tagSNPs. Yet another, recently proposed model-based method takes marker heterozygosity and genetic distance into account in order to maximize the expected utility of a marker set to map frequent, but unobserved genetic variants. We compared these tagging approaches with regard to their ability to correlate tagSNPs and bi-allelic, potentially disease-causing genetic variants. We used the CEU sample of chromosome 19 from the HapMap project for an initial comparison, and demonstrated a comparable performance of both approaches but a difference in terms of tagSNPs selected and variants captured. In any case, we conclude that a considerable loss of information appears to be inherent to any type of SNP tagging, even when dense marker sets are available for SNP selection.
Linkage Analysis of a Cluster-Based Quantitative Phenotype Constructed from Pulmonary Function Test Data in 27 Multigenerational Families with Multiple Asthmatic Members
Authors: Reilly Cavan , Miller Michael B. , Liu Yuhong , Oetting William S. , King Richard , Blumenthal Malcolm
Published: April 2007

Objective: To identify genes involved in phenotypes that increase one’s risk for developing asthma, a complex disease that is likely genetically heterogeneous. Unlike other approaches to locus discovery in the presence of heterogeneity, this method seeks loci that segregate in all or most ascertained families while recognizing that other genes and environmental factors that modify the action of the common gene may vary across families. Methods: The method is based on seeking groups of families that differ, between groups, in the way affected idndividuals express the genotype. Then we use the distance of each individual to the cluster center for his family to define a quantitative trait. This quantitative trait is then subjected to a genome scan using variance components methods. Results: The method is applied to a data set of 27 multigenerational families with asthma, and a novel locus at 2q33 (at 210 cM) is identified. Conclusions: The proposed method has the potential to identify loci near genes that increase risk for asthma related phenotypes. The method could be used for other complex disorders that exhibit locus heterogeneity.
Twin Birth Weight Standards
Authors: Gielen Marij , Lindsey Patrick J. , Derom Catherine , Loos Ruth J.F. , Derom Robert , Nijhuis Jan G. , Vlietinck Robert
Published: April 2007

Objective: The aim of this study was to present customized twin-specific birth weight standards. The relative contribution of gestational age, maternal factors, twin factors and placental factors to the birth weight was evaluated in a multivariate approach. Subjects and Methods: Perinatal data were obtained from 10,177 live-born twins from the East Flanders Prospective Twin Survey. Of 8,454 twins (4,227 pairs), of whom all data were available, the birth weights at different gestational ages were analyzed using a non-linear multivariate gaussian regression. Results: All considered covariates influenced birth weight of twins significantly, with the exception of sex of the co-twin and mode of conception and delivery. At 37 weeks of gestation, a difference of >1 kg existed between favourable and adverse prenatal environment. Up to 40 weeks, sex, site of the umbilical cord, parity, and birth order had a greater influence on birth weight than zygosity, chorionicity and fusion of the placentas. From 34 weeks on, the birth weight of the second-born twin deviated and after 40 weeks, birth weight of monozygotic monochorionic twins dropped, while the other twins continued to grow. Conclusion: Customized twin-specific birth weight standards, which take these covariates into account, offer the opportunity for a better assessment of the influence of birth weight of the twin on neonatal health in future research. Already the Developmental Origins of Health and Disease hypothesis showed that these prenatal conditions might also be important for the follow-up of the twin.
Role of Abdominal Muscles Activity on Duration and Severity of Hypoxemia Episodes in Mechanically Ventilated Preterm Infants
Authors: Esquer Cristian , Claure Nelson , D’Ugard Carmen , Wada Yoshiro , Bancalari Eduardo
Published: April 2007

Background: Episodes of hypoxemia are often observed in ventilated preterm infants. The factors that determine their duration, severity and the failure of the mechanical breaths to maintain ventilation have not been fully defined. Objective: To determine the relation between activity of the abdominal muscles and the duration and severity of hypoxemia episodes in ventilated preterm infants. Methods: Clinically stable ventilated preterm infants weighing between 500 and 1,000 g at birth, who presented with frequent episodes of hypoxemia, were studied. Recordings of arterial oxygen saturation (SpO2), tidal volume and abdominal surface electromyography were obtained during 4 h to assess the temporal relationship between activation of abdominal musculature with the onset, duration and severity of hypoxemia episodes. Results: In 15 infants, GA (mean ± SD) 25 ± 1.5 weeks, BW 697 ± 141 g, age 37 ± 14 days, synchronized intermittent mandatory ventilation rate 17 ± 6 breaths/min, peak inspiratory pressure 18 ± 1.9 cm H2O, positive end-expiratory pressure 4.8 ± 0.6 cm H2O, and fraction of inspired oxygen (FiO2) 0.4 ± 0.1 were studied. These infants presented with 7.2 ± 4.4 episodes of hypoxemia (SpO2 <88%) per hour. The number of abdominal muscle contractions per episode correlated with the duration and severity of the episodes of hypoxemia. The episode duration increased by 14 ± 18 s per abdominal muscle contraction. The lowest SpO2 reached during an episode of hypoxemia decreased by 1.7 ± 1.4% for every abdominal muscle contraction. Conclusions: These data document a relationship between abdominal muscles contraction and the duration and severity of hypoxemia episodes in ventilated preterm infants. These findings can explain the failure of mechanical ventilation to prevent their occurrence or decrease their severity.
Current Status of Surgery for Pancreatic Cancer
Authors: Hirata Koichi , Egawa Shinichi , Kimura Yasutoshi , Nobuoka Takayuki , Oshima Hidenori , Katsuramaki Tadashi , Mizuguchi Toru , Furuhata Tomohisa
Published: April 2007

Background: In Japan the annual incidence of pancreatic cancer has increased over the last decade, but no advancement has been made in the long-term prognosis after resection. The significant differences in the surgical procedures between Western countries and Japan have been discussed. Therefore, an adequate comparison and analysis of the data from Japan, Europe and the USA is required. This review evaluates many important published reports from Japan which influence surgical procedure. Methods: Several important highlights and controversies regarding the concept of surgical treatment and surgical procedure are discussed comparing the results in Japan with those in Western countries. Results: No significant difference in diagnostic strategy using various imaging methods was observed between Japan and Europe. The stage classification for pancreatic cancer by the Japanese Pancreatic Society (JPS) seems to be superior to others, because the results on long-term prognosis after pancreatectomy of cases with pancreatic head cancer, diagnosed as tubular adenocarcinoma, has been arranged logically. Pancreatectomy with extended radical dissection is recommended in Japan, but several clinical studies from Europe and the USA suggest that this is ineffective. The basic concepts of this controversy have recently come closer altogether. Scientific clinical trials for instance on the necessity of adjuvant treatment, etc., are now on-going. Conclusion: The characteristics on diagnosis and treatment of pancreatic cancer in Japan are described. The JPS registration system for pancreatic cancer can provide much more information, i.e. dependency on diagnostic methods, highly frequent sites of lymph node and of distant metastases, the prognosis of small pancreatic cancers, etc. The indication for any surgical treatments should be limited to cases with the possibility of cancer free margins.
Why Not Share Rather Than Own?
Authors: Belk Russell
Published: April 2007

Sharing is an alternative form of distribution to commodity exchange and gift giving. Compared to these alternative modes, sharing can foster community, save resources, and create certain synergies. Yet outside of our immediate families, we do little sharing. Even within the family, there is increased privatization. This article addresses impediments to sharing as well as incentives that may encourage more sharing of both tangible and intangible goods. Two recent developments, the Internet and intellectual property rights doctrines, are locked in a battle that will do much to determine the future of sharing. Businesses may lead the way with virtual corporations outsourcing the bulk of their operations. Whether virtual consumers sharing some of their major possessions are a viable counterpart remains an open question.
Consumers and the State since the Second World War
Authors: Hilton Matthew
Published: April 2007

In the twentieth century, consumption became a political project intimately bound up with the state. By the 1950s, governments across the world worked to promote a vision of consumer society based around access and participation—affluence for all—rather than choice and luxury for the few. This vision of consumerism was tied in with the geopolitics of the cold war but was also constitutive of other globalizing trends that connected not only Western Europe to North America but also both sides of the Iron Curtain as well as the global South and North. The article analyzes the development of, and compares the differences in, the various consumer protection regimes that emerged in the latter half of the century. It points to processes of convergence in consumer politics across the globe that saw the development of consumer political thinking in the Soviet bloc and the development of supranational protection regimes at the European level. In more recent decades, the politics of consumer society based upon access and the collective has been eclipsed by a politics that emphasizes choice and the individual. Such a change represents a profound shift in the relations between consumers, citizens, and governments.
Separated by a Common Language
Authors: Marsh Abigail A. , Elfenbein Hillary Anger , Ambady Nalini
Published: April 2007

The expression of nonverbal cues may differ systematically across cultures. Common cues used in distinct ways cross-culturally may be termed nonverbal accents. The data in this study indicate that nonverbal accents can help perceivers to distinguish the nationality of expressers. In Study 1, American participants could determine the nationality of Australian and American adults with above-chance accuracy when viewing their emotional expressions but not neutral expressions. In Study 2, American participants could also determine the nationality of Australians and Americans seen walking or waving in greeting. The accuracy of nationality judgments was also correlated with the extent to which Australian targets were perceived to conform to stereotypes about Australians. It is argued that nonverbal accents may be a mechanism that perceivers can use to apply group stereotypes.
Factors Affecting the US Current Account: An Historical Decomposition
Authors: Barrell R. , Holland D. , Hurst I.
Published: April 2007

The US current account deficit was around 6½ per cent of GDP in 2006, having risen by 2 per cent of GDP since 2002 when the dollar reached its peak and started to decline. Between the peak in 2002 and the last quarter of 2006 the dollar fell by 13.4 per cent in effective terms using 2003 trade weights, and it might have been expected that the current account would have improved. However, over the same period the household savings rate fell by more than 4 per cent of personal incomes and private sector investment rose by 0.6 per cent of GDP. At the same time, the public sector deficit improved by around 1 per cent of GDP, but this was not enough to offset the major decline in net savings in the private sector. These domestic imbalances have been partly responsible for the deterioration in the current account, and appear to have more than offset the impacts of the decline in the dollar. In addition, since 2002 the oil price has risen and this has led to a significant deterioration in the US current account.
Influence of Strategy Choice on Spatial Performance in Apparel Design
Authors: Gitimu Priscilla N. , Workman Jane E.
Published: April 2007

This study investigates how performance on a spatial task in apparel design was influenced by use of strategy. The sample consisted of 278 undergraduate apparel design students from six universities in the United States. Instruments used to collect data were the Apparel Spatial Visualization Test (ASVT) and Use of Strategy Questionnaire. Use of strategy influenced performance on the ASVT. Some strategies were superior to others by the fact that they led to a higher percentage of correct responses on the ASVT, for example, landmark extraction, checking, and previous knowledge. Because use of strategies influenced performance on a spatial task, further research could investigate methods of training students in the choice of appropriate strategies.
Social Support, Research Interest, Stress, and Research Productivity of Textiles and Apparel Faculty
Authors: Kim Hye-Shin , Pedersen Elaine , Cloud Rinn
Published: April 2007

This study examines the relationship between work stress and research productivity among faculty members in the field of textiles and apparel. Work stress and research productivity were studied in relation to four antecedent variables: collegial or institutional support, chair's support, professional organization support, and research interest. In addition, rank, institution type, position description, expertise, and degrees offered were examined in relation to the variables. Data from 173 members of the International Textile and Apparel Association (ITAA) classified as assistant professors ( n = 63), associate professors ( n = 63), and professors ( n = 47) were analyzed. Results show research interests to be the only significant factor to influence research productivity. No variables in this study significantly influenced work stress. Respondents with higher research productivity were from 4-year, land-grant institutions with graduate programs and had a lower teaching load. Further investigation in examining research productivity of faculty members is recommended.
The NIH R03 Award
Authors: Langhorst Diane M. , Svikis Dace S.
Published: April 2007

Social workers in academic and agency settings have the opportunity to do funded research using the National Institutes of Health (NIH) R03 small grant mechanism designed for discrete, clearly defined projects that can be completed within a 1- to 2-year time period with limited funding. This article describes the R03 mechanism and provides a guide for the developmental steps in writing a successful grant application. It identifies the recent NIH program announcements titled Research on Social Work Practice and Concepts in Health as an extraordinary opportunity for social work researchers seeking R03 funding. The R03 is ideal for new researchers, and the experience of one of the authors illustrates the decision-making and skill-development processes involved in submitting a successful grant proposal.
Problematic Phrases in the Conclusions of Published Outcome Studies
Authors: Rubin Allen , Parrish Danielle
Published: April 2007

Objective: This study examined the extent to which conclusions of published outcome studies contain phrases that could be misconstrued as implying more empirical support than is warranted. Methods: All articles (N = 138) reporting outcome studies from 2000 to 2005 in two social work research journals and two topical database searches were assessed regarding research design, findings, and wording of conclusions. Substantial interrater agreement was indicated by kappa values of .95 for research design, 1.00 for nature of findings, and .70 for wording of conclusions. Results: Of the articles, 70% used designs that do not warrant making conclusive causal inferences, and 60% of articles with those designs contained phrases that could be misconstrued or exploited as implying an inflated evidence-based status. Conclusion: To prevent evidence-based practice from becoming a meaningless shibboleth, authors, reviewers, and editors should become vigilant in avoiding wording that could be misconstrued as implying more empirical support than is warranted.
Mapping Patterns of Perceptions
Authors: Davis Tamara S.
Published: April 2007

Unclear definitions and limited system-level assessment measures inhibit cultural responsiveness in children's mental health. This study explores an alternative method to conceptualize and assess cultural competence in four children's mental health systems of care communities from family and professional perspectives. Concept Mapping was used to generate relational maps reflecting indicators of cultural competence and pattern match comparisons within and across communities. Differences and similarities in conceptualizations and participant group comparisons of average statement ratings on three criteria were found among communities. An aggregated map containing 117 statements within 15 clusters of cultural competence is presented. Concept mapping offers promise for contextually conceptualizing and assessing cultural competence. Implications for practice in systems of care are discussed.
The Development and Preliminary Validation of the Adolescent Domain Screening Inventory
Authors: Corrigan Matthew J. , Loneck Barry , Videka Lynn
Published: April 2007

The objective of this study was to develop a screen assessing domains in at-risk and substance-using adolescents. The Adolescent Domain Screening Inventory (ADSI) consists of four subscales: school, family, community, and individual or peer. A convenience sample of 6,661 youths was employed. Analyses included concurrent criterion validity, known instrument construct validity, convergent construct validity, cut points, and gender and race correlations. Concurrent criterion validity correlations range from r = .85 to r = .95. Correlation for known instrument validity is r = .56 and convergent construct validity is r = .49. Cut points produced positive predictive values ranging from .46 to .53. The ADSI demonstrated a general applicability across gender and race. The ADSI is an instrument demonstrating acceptable psychometric properties.
A novel bifunctional N-acetylglutamate synthase-kinase from Xanthomonas campestris that is closely related to mammalian N-acetylglutamate synthase
Authors: Qu Qiuhao , Morizono Hiroki , Shi Dashuang , Tuchman Mendel , Caldovic Ljubica
Published: April 2007

Background

In microorganisms and plants, the first two reactions of arginine biosynthesis are catalyzed by N-acetylglutamate synthase (NAGS) and N-acetylglutamate kinase (NAGK). In mammals, NAGS produces an essential activator of carbamylphosphate synthetase I, the first enzyme of the urea cycle, and no functional NAGK homolog has been found. Unlike the other urea cycle enzymes, whose bacterial counterparts could be readily identified by their sequence conservation with arginine biosynthetic enzymes, mammalian NAGS gene was very divergent, making it the last urea cycle gene to be discovered. Limited sequence similarity between E. coli NAGS and fungal NAGK suggests that bacterial and eukaryotic NAGS, and fungal NAGK arose from the fusion of genes encoding an ancestral NAGK (argB) and an acetyltransferase. However, mammalian NAGS no longer retains any NAGK catalytic activity.

Results

We identified a novel bifunctional N-acetylglutamate synthase and kinase (NAGS-K) in the Xanthomonadales order of gamma-proteobacteria that appears to resemble this postulated primordial fusion protein. Phylogenetic analysis indicated that xanthomonad NAGS-K is more closely related to mammalian NAGS than to other bacterial NAGS. We cloned the NAGS-K gene from Xanthomonas campestis, and characterized the recombinant NAGS-K protein. Mammalian NAGS and its bacterial homolog have similar affinities for substrates acetyl coenzyme A and glutamate as well as for their allosteric regulator arginine.

Conclusion

The close phylogenetic relationship and similar biochemical properties of xanthomonad NAGS-K and mammalian NAGS suggest that we have identified a close relative to the bacterial antecedent of mammalian NAGS and that the enzyme from X. campestris could become a good model for mammalian NAGS in structural, biochemical and biophysical studies.
Efficient pairwise RNA structure prediction using probabilistic alignment constraints in Dynalign
Authors: Harmanci Arif Ozgun , Sharma Gaurav , Mathews David H
Published: April 2007

Background

Joint alignment and secondary structure prediction of two RNA sequences can significantly improve the accuracy of the structural predictions. Methods addressing this problem, however, are forced to employ constraints that reduce computation by restricting the alignments and/or structures (i.e. folds) that are permissible. In this paper, a new methodology is presented for the purpose of establishing alignment constraints based on nucleotide alignment and insertion posterior probabilities. Using a hidden Markov model, posterior probabilities of alignment and insertion are computed for all possible pairings of nucleotide positions from the two sequences. These alignment and insertion posterior probabilities are additively combined to obtain probabilities of co-incidence for nucleotide position pairs. A suitable alignment constraint is obtained by thresholding the co-incidence probabilities. The constraint is integrated with Dynalign, a free energy minimization algorithm for joint alignment and secondary structure prediction. The resulting method is benchmarked against the previous version of Dynalign and against other programs for pairwise RNA structure prediction.

Results

The proposed technique eliminates manual parameter selection in Dynalign and provides significant computational time savings in comparison to prior constraints in Dynalign while simultaneously providing a small improvement in the structural prediction accuracy. Savings are also realized in memory. In experiments over a 5S RNA dataset with average sequence length of approximately 120 nucleotides, the method reduces computation by a factor of 2. The method performs favorably in comparison to other programs for pairwise RNA structure prediction: yielding better accuracy, on average, and requiring significantly lesser computational resources.

Conclusion

Probabilistic analysis can be utilized in order to automate the determination of alignment constraints for pairwise RNA structure prediction methods in a principled fashion. These constraints can reduce the computational and memory requirements of these methods while maintaining or improving their accuracy of structural prediction. This extends the practical reach of these methods to longer length sequences. The revised Dynalign code is freely available for download.
Statistical significance of quantitative PCR
Authors: Karlen Yann , McNair Alan , Perseguers Sébastien , Mazza Christian , Mermod Nicolas
Published: April 2007

Background

PCR has the potential to detect and precisely quantify specific DNA sequences, but it is not yet often used as a fully quantitative method. A number of data collection and processing strategies have been described for the implementation of quantitative PCR. However, they can be experimentally cumbersome, their relative performances have not been evaluated systematically, and they often remain poorly validated statistically and/or experimentally. In this study, we evaluated the performance of known methods, and compared them with newly developed data processing strategies in terms of resolution, precision and robustness.

Results

Our results indicate that simple methods that do not rely on the estimation of the efficiency of the PCR amplification may provide reproducible and sensitive data, but that they do not quantify DNA with precision. Other evaluated methods based on sigmoidal or exponential curve fitting were generally of both poor resolution and precision. A statistical analysis of the parameters that influence efficiency indicated that it depends mostly on the selected amplicon and to a lesser extent on the particular biological sample analyzed. Thus, we devised various strategies based on individual or averaged efficiency values, which were used to assess the regulated expression of several genes in response to a growth factor.

Conclusion

Overall, qPCR data analysis methods differ significantly in their performance, and this analysis identifies methods that provide DNA quantification estimates of high precision, robustness and reliability. These methods allow reliable estimations of relative expression ratio of two-fold or higher, and our analysis provides an estimation of the number of biological samples that have to be analyzed to achieve a given precision.
Toward the automated generation of genome-scale metabolic networks in the SEED
Authors: DeJongh Matthew , Formsma Kevin , Boillot Paul , Gould John , Rycenga Matthew , Best Aaron
Published: April 2007

Background

Current methods for the automated generation of genome-scale metabolic networks focus on genome annotation and preliminary biochemical reaction network assembly, but do not adequately address the process of identifying and filling gaps in the reaction network, and verifying that the network is suitable for systems level analysis. Thus, current methods are only sufficient for generating draft-quality networks, and refinement of the reaction network is still largely a manual, labor-intensive process.

Results

We have developed a method for generating genome-scale metabolic networks that produces substantially complete reaction networks, suitable for systems level analysis. Our method partitions the reaction space of central and intermediary metabolism into discrete, interconnected components that can be assembled and verified in isolation from each other, and then integrated and verified at the level of their interconnectivity. We have developed a database of components that are common across organisms, and have created tools for automatically assembling appropriate components for a particular organism based on the metabolic pathways encoded in the organism's genome. This focuses manual efforts on that portion of an organism's metabolism that is not yet represented in the database. We have demonstrated the efficacy of our method by reverse-engineering and automatically regenerating the reaction network from a published genome-scale metabolic model for Staphylococcus aureus. Additionally, we have verified that our method capitalizes on the database of common reaction network components created for S. aureus, by using these components to generate substantially complete reconstructions of the reaction networks from three other published metabolic models (Escherichia coli, Helicobacter pylori, and Lactococcus lactis). We have implemented our tools and database within the SEED, an open-source software environment for comparative genome annotation and analysis.

Conclusion

Our method sets the stage for the automated generation of substantially complete metabolic networks for over 400 complete genome sequences currently in the SEED. With each genome that is processed using our tools, the database of common components grows to cover more of the diversity of metabolic pathways. This increases the likelihood that components of reaction networks for subsequently processed genomes can be retrieved from the database, rather than assembled and verified manually.
Large-scale RNAi screens identify novel genes that interact with the C. elegans retinoblastoma pathway as well as splicing-related components with synMuv B activity
Authors: Ceron Julian , Rual Jean-François , Chandra Abha , Dupuy Denis , Vidal Marc , van den Heuvel Sander
Published: April 2007

Background

Theretinoblastomatumor suppressor (Rb) acts in a conserved pathway that is deregulated in most human cancers. Inactivation of the single Rb-related gene inCaenorhabditis elegans, lin-35, has only limited effects on viability and fertility, yet causes changes in cell-fate and cell-cycle regulation when combined with inactivation of specific other genes. For instance,lin-35Rb is a synthetic multivulva (synMuv) class B gene, which causes a multivulva phenotype when inactivated simultaneously with a class A or C synMuv gene.

Results

We used the ORFeome RNAi library to identify genes that interact withC. elegans lin-35Rb and identified 57 genes that showed synthetic or enhanced RNAi phenotypes inlin-35mutants as compared torrf-3anderi-1RNAi hypersensitive mutants. Based on characterizations of a deletion allele, the syntheticlin-35interactorzfp-2was found to suppress RNAi and to cooperate withlin-35Rb in somatic gonad development. Interestingly, ten splicing-related genes were found to function similar tolin-35Rb, as synMuv B genes that prevent inappropriate vulval induction. Partial inactivation of specific spliceosome components revealed further similarities withlin-35Rb functions in cell-cycle control, transgene expression and restricted expression of germline granules.

Conclusion

We identified an extensive series of candidatelin-35Rb interacting genes and validatedzfp-2as a novellin-35synthetic lethal gene. In addition, we observed a novel role for a subset of splicing components inlin-35Rb-controlled processes. Our data support novel hypotheses about possibilities for anti-cancer therapies and multilevel regulation of gene expression.
Coordinate regulation of DNA methyltransferase expression during oogenesis
Authors: Lucifero Diana , La Salle Sophie , Bourc'his Déborah , Martel Josée , Bestor Timothy H , Trasler Jacquetta M
Published: April 2007

Background

Normal mammalian development requires the action of DNA methyltransferases (DNMTs) for the establishment and maintenance of DNA methylation within repeat elements and imprinted genes. Here we report the expression dynamics of Dnmt3a and Dnmt3b, as well as a regulator of DNA methylation, Dnmt3L, in isolated female germ cells.

Results

Our results indicate that these enzymes are coordinately regulated and that their expression peaks during the stage of postnatal oocyte development when maternal methylation imprints are established. We find that Dnmt3a, Dnmt3b, Dnmt3L and Dnmt1o transcript accumulation is related to oocyte diameter. Furthermore, DNMT3L deficient 15 dpp oocytes have aberrantly methylated Snrpn, Peg3 and Igf2r DMRs, but normal IAP and LINE-1 methylation levels, thereby highlighting a male germ cell specific role for DNMT3L in the establishment of DNA methylation at repeat elements. Finally, real-time RT-PCR analysis indicates that the depletion of either DNMT3L or DNMT1o in growing oocytes results in the increased expression of the de novo methyltransferase Dnmt3b, suggesting a potential compensation mechanism by this enzyme for the loss of one of the other DNA methyltransferases.

Conclusion

Together these results provide a better understanding of the developmental regulation of Dnmt3a, Dnmt3b and Dnmt3L at the time of de novo methylation during oogenesis and demonstrate that the involvement of DNMT3L in retrotransposon silencing is restricted to the male germ line. This in turn suggests the existence of other factors in the oocyte that direct DNA methylation to transposons.
Development of the mammalian liver and ventral pancreas is dependent on GATA4
Authors: Watt Alistair J , Zhao Roong , Li Jixuan , Duncan Stephen A
Published: April 2007

Background

In the mouse, the parenchyma of both the liver and ventral pancreas is specified from adjacent domains of the ventral foregut endoderm. GATA4, a zinc finger transcription factor, is strongly expressed in these endodermal domains and molecular analyses have implicated GATA4 in potentiating liver gene expression during the onset of hepatogenesis. We therefore hypothesized that GATA4 has an integral role in controlling the early stages of pancreatic and liver development.

Results

To determine whether GATA4 contributes to development of either the pancreas or liver we characterized the formation of pancreatic and hepatic tissues in embryos derived from Gata4
-/- ES cells by tetraploid embryo complementation. In the absence of GATA4, development of the liver and ventral pancreas was disrupted. At embryonic day (E) 9.5, the liver bud failed to expand although, contrary to expectations, the hepatic endoderm was able to form a pseudo-stratified epithelial liver bud that expressed hepatic genes. Moreover, as we had shown previously, the embryos lacked septum transversum mesenchyme suggesting that liver defects may be cell non-autonomous. Analyses of pancreatic development revealed a complete absence of the ventral but not the dorsal pancreas in Gata4
-/- embryos. Moreover, Gata6
-/- embryos displayed a similar, although less dramatic phenotype, suggesting a critical role for multiple GATA factors at the earliest stages of ventral pancreas development.

Conclusion

This study defines integral roles for GATA factors in controlling early development of the mammalian liver and pancreas.
Rybp, a polycomb complex-associated protein, is required for mouse eye development
Authors: Pirity Melinda K , Wang Wei-Lin , Wolf Louise V , Tamm Ernst R , Schreiber-Agus Nicole , Cvekl Ales
Published: April 2007

Background

Rybp (Ring1 and YY1 binding protein) is a zinc finger protein which interacts with the members of the mammalian polycomb complexes. Previously we have shown that Rybp is critical for early embryogenesis and that haploinsufficiency of Rybp in a subset of embryos causes failure of neural tube closure. Here we investigated the requirement for Rybp in ocular development using four in vivo mouse models which resulted in either the ablation or overexpression of Rybp.

Results

Our results demonstrate that loss of a single Rybp allele in conventional knockout mice often resulted in retinal coloboma, an incomplete closure of the optic fissure, characterized by perturbed localization of Pax6 but not of Pax2. In addition, about one half of Rybp-/- <-> Rybp+/+ chimeric embryos also developed retinal colobomas and malformed lenses. Tissue-specific transgenic overexpression of Rybp in the lens resulted in abnormal fiber cell differentiation and severe lens opacification with increased levels of AP-2α and Sox2, and reduced levels of βA4-crystallin gene expression. Ubiquitous transgenic overexpression of Rybp in the entire eye caused abnormal retinal folds, corneal neovascularization, and lens opacification. Additional changes included defects in anterior eye development.

Conclusion

These studies establish Rybp as a novel gene that has been associated with coloboma. Other genes linked to coloboma encode various classes of transcription factors such as BCOR, CBP, Chx10, Pax2, Pax6, Six3, Ski, Vax1 and Vax2. We propose that the multiple functions for Rybp in regulating mouse retinal and lens development are mediated by genetic, epigenetic and physical interactions between these genes and proteins.
Evolutionary proteomics identifies amino acids essential for ligand-binding of the cytokinin receptor CHASE domain
Authors: Heyl Alexander , Wulfetange Klaas , Pils Birgit , Nielsen Nicola , Romanov Georgy A , Schmülling Thomas
Published: April 2007

Background

In plants the hormone cytokinin is perceived by members of a small cytokinin receptor family, which are hybrid sensor histidine kinases. While the immediate downstream signaling pathway is well characterized, the domain of the receptor responsible for ligand binding and which residues are involved in this process has not been determined experimentally.

Results

Using a live cell hormone-binding assay, we show that cytokinin is bound by a receptor domain predicted to be extracellular, the so called CHASE (cyclases, histidine kinase associated sensory extracellular) domain. The CHASE domain occurs not only in plant cytokinin receptors but also in numerous orphan receptors in lower eukaryotes and bacteria. Taking advantage of this fact, we used an evolutionary proteomics approach to identify amino acids important for cytokinin binding by looking for residues conserved in cytokinin receptors, but not in other receptors. By comparing differences in evolutionary rates, we predicted five amino acids within the plant CHASE domains to be crucial for cytokinin binding. Mutagenesis of the predicted sites and subsequent binding assays confirmed the relevance of four of the selected amino acids, showing the biological significance of site-specific evolutionary rate differences.

Conclusion

This work demonstrates the use of a bioinformatic analysis to mine the huge set of genomic data from different taxa in order to generate a testable hypothesis. We verified the hypothesis experimentally and identified four amino acids which are to a different degree required for ligand-binding of a plant hormone receptor.
DNA repair gene XRCC1 polymorphisms and bladder cancer risk
Authors: Sak Sei Chung , Barrett Jennifer H , Paul Alan B , Bishop D Timothy , Kiltie Anne E
Published: April 2007

Background

Cigarette smoking and chemical occupational exposure are the main known risk factors for bladder transitional cell carcinoma (TCC). Oxidative DNA damage induced by carcinogens present in these exposures requires accurate base excision repair (BER). The XRCC1 protein plays a crucial role in BER by acting as a scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein structure or function or create alternatively spliced proteins which may influence BER efficiency and hence affect individual susceptibility to bladder cancer. Recent epidemiological studies have shown inconsistent associations between these polymorphisms and bladder cancer. To clarify the situation, we conducted a comprehensive analysis of 14 XRCC1 polymorphisms in a case-control study involving more than 1100 subjects.

Results

We found no evidence of an association between any of the 14 XRCC1 polymorphisms and bladder cancer risk. However, we found carriage of the variant Arg280His allele to be marginally associated with increased bladder cancer risk compared to the wild-type genotype (adjusted odds ratio [95% confidence interval], 1.50 [0.98–2.28], p = 0.06). The association was stronger for current smokers such that individuals carrying the variant 280His allele had a two to three-fold increased risk of bladder cancer compared to those carrying the wildtype genotype (p = 0.09). However, the evidence for gene-environment interaction was not statistically significant (p = 0.45).

Conclusion

We provide no evidence of an association between polymorphisms in XRCC1 and bladder cancer risk, although our study had only limited power to detect the association for low frequency variants, such as Arg280His.