bluuebunny/crossref_metadata_2025 huggingface dataset:
NetMatch: a Cytoscape plugin for searching biological networks
Authors: Ferro A. , Giugno R. , Pigola G. , Pulvirenti A. , Skripin D. , Bader G. D. , Shasha D.
Published: February 2007

Summary: NetMatch is a Cytoscape plugin which allows searching biological networks for subcomponents matching a given query. Queries may be approximate in the sense that certain parts of the subgraph-query may be left unspecified. To make the query creation process easy, a drawing tool is provided. Cytoscape is a bioinformatics software platform for the visualization and analysis of biological networks.

Availability: The full package, a tutorial and associated examples are available at the following web sites: http://alpha.dmi.unict.it/~ctnyu/netmatch.html, http://baderlab.org/Software/NetMatch

Contact:  ferro@dmi.unict.it
Disease-specific genomic analysis: identifying the signature of pathologic biology
Authors: Nicolau Monica , Tibshirani Robert , Børresen-Dale Anne-Lise , Jeffrey Stefanie S.
Published: February 2007

Motivation: Genomic high-throughput technology generates massive data, providing opportunities to understand countless facets of the functioning genome. It also raises profound issues in identifying data relevant to the biology being studied.

Results: We introduce a method for the analysis of pathologic biology that unravels the disease characteristics of high dimensional data. The method, disease-specific genomic analysis (DSGA), is intended to precede standard techniques like clustering or class prediction, and enhance their performance and ability to detect disease. DSGA measures the extent to which the disease deviates from a continuous range of normal phenotypes, and isolates the aberrant component of data. In several microarray cancer datasets, we show that DSGA outperforms standard methods. We then use DSGA to highlight a novel subdivision of an important class of genes in breast cancer, the estrogen receptor (ER) cluster. We also identify new markers distinguishing ductal and lobular breast cancers. Although our examples focus on microarrays, DSGA generalizes to any high dimensional genomic/proteomic data.

Contact:  ssj@standford.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
A Novel Major Facilitator Superfamily Protein at the Tonoplast Influences Zinc Tolerance and Accumulation in Arabidopsis
Authors: Haydon Michael J. , Cobbett Christopher S.
Published: February 2007

Zinc (Zn) is an essential micronutrient required by all cells but is toxic in excess. We have identified three allelic Zn-sensitive mutants of Arabidopsis (Arabidopsis thaliana). The gene, designated ZINC-INDUCED FACILITATOR1 (ZIF1), encodes a member of the major facilitator superfamily of membrane proteins, which are found in all organisms and transport a wide range of small, organic molecules. Shoots of zif1 mutants showed increased accumulation of Zn but not other metal ions. In combination with mutations affecting shoot-to-root Zn translocation, zif1 hma2 hma4 triple mutants accumulated less Zn than the wild type but remained Zn sensitive, suggesting that the zif1 Zn-sensitive phenotype is due to altered Zn distribution. zif1 mutants were also more sensitive to cadmium but less sensitive to nickel. ZIF1 promoter-β-glucuronidase fusions were expressed throughout the plant, with strongest expression in young tissues, and predominantly in the vasculature in older tissues. ZIF1 expression was highly induced by Zn and, to a lesser extent, by manganese. A ZIF1-green fluorescent protein fusion protein localized to the tonoplast in transgenic plants. MTP1 has been identified as a tonoplast Zn transporter and a zif1-1 mtp1-1 double mutant was more sensitive to Zn than either of the single mutants, suggesting ZIF1 influences a distinct mechanism of Zn homeostasis. Overexpression of ZIF1 conferred increased Zn tolerance and interveinal leaf chlorosis in some transgenic lines in which ZIF1 expression was high. We propose that ZIF1 is involved in a novel mechanism of Zn sequestration, possibly by transport of a Zn ligand or a Zn ligand complex into vacuoles.
AGF1, an AT-Hook Protein, Is Necessary for the Negative Feedback ofAtGA3ox1Encoding GA 3-Oxidase
Authors: Matsushita Akane , Furumoto Tsuyoshi , Ishida Sarahmi , Takahashi Yohsuke
Published: February 2007

Negative feedback is a fundamental mechanism of organisms to maintain the internal environment within tolerable limits. Gibberellins (GAs) are essential regulators of many aspects of plant development, including seed germination, stem elongation, and flowering. GA biosynthesis is regulated by the feedback mechanism in plants. GA 3-oxidase (GA3ox) catalyzes the final step of the biosynthetic pathway to produce the physiologically active GAs. Here, we found that only the AtGA3ox1 among the AtGA3ox family of Arabidopsis (Arabidopsis thaliana) is under the regulation of GA-negative feedback. We have identified a cis-acting sequence responsible for the GA-negative feedback of AtGA3ox1 using transgenic plants. Furthermore, we have identified an AT-hook protein, AGF1 (for the AT-hook protein of GA feedback regulation), as a DNA-binding protein for the cis-acting sequence of GA-negative feedback. The mutation in the cis-acting sequence abolished both GA-negative feedback and AGF1 binding. In addition, constitutive expression of AGF1 affected GA-negative feedback in Arabidopsis. Our results suggest that AGF1 plays a role in the homeostasis of GAs through binding to the cis-acting sequence of the GA-negative feedback of AtGA3ox1.
Three‐Dimensional Surface Texture Characterization of Portland Cement Concrete Pavements
Authors: Abbas Ala , Kutay M. Emin , Azari Haleh , Rasmussen Robert
Published: February 2007

Abstract: This article investigates the effectiveness of different mathematical methods in describing the three‐dimensional surface texture of Portland cement concrete (PCC) pavements. Ten PCC field cores of varying surface textures were included in the analysis. X‐ray Computed Tomography (CT) was used to scan the upper portion of these cores, resulting in a stack of two‐dimensional grayscale images. Image processing techniques were utilized to isolate the void pixels from the solid pixels and reconstruct the three‐dimensional surface topography. The resulting three‐dimensional surfaces were reduced to two‐dimensional “map of heights” images, whereby the grayscale intensity of each pixel within the image represented the vertical location of the surface at that point with respect to the lowest point on the surface. The “map of heights” images were analyzed using four mathematical methods, namely the Hessian model, the Fast Fourier transform (FFT), the wavelet analysis, and the power spectral density (PSD). Results obtained using these methods were compared to the mean profile depth (MPD) computed in accordance with ASTM E1845.
Integration of Simulation‐Based Cost Model and Multi‐Criteria Evaluation Model for Bid Price Decisions
Authors: Wang Wei‐Chih , Dzeng Ren‐Jye , Lu Yu‐Huang
Published: February 2007

Abstract:  Several criteria affect bidding decisions. Current bidding models determine a markup based on a fixed project construction cost. This work presents a novel bid price determination procedure that is built by integrating a simulation‐based cost model and a multi‐criteria evaluation model. The cost model is used to consider cost uncertainties and generate a bid price cumulative distribution, whereas the multi‐criteria evaluation model applies pairwise comparisons and fuzzy integrals to reflect bidder preferences regarding decision criteria. The relationship between the two models is based on a practical phenomenon in that a bidder has a high probability of winning when criteria evaluations favor his bid, and, consequently, the bidder would bid a low price, and vice versa. The merits of the proposed procedure are demonstrated by its application to two construction projects in Taiwan.
The Effect of Electrical Stimulation and Lesioning of the Anterior Thalamic Nucleus on Kainic Acid–Induced Focal Cortical Seizure Status in Rats
Authors: Takebayashi Seiji , Hashizume Kiyotaka , Tanaka Tatsuya , Hodozuka Akira
Published: February 2007

Summary:  Purpose: The present study aimed to clarify the effect of electrical stimulation and lesioning of the anterior nucleus of the thalamus (ANT) on kainic acid (KA)–induced focal cortical seizures in a rat model. To address the mechanism underlying these anticonvulsant actions, cerebral glucose metabolism after ANT electrical stimulation and lesioning was also examined.

Methods: Wistar rats were divided into five major groups: control (n = 9), unilateral (n = 9), and bilateral (n = 9) ANT electrical stimulation, and unilateral (n = 9) and bilateral (n = 9) ANT lesioning. After KA injection, average clinical‐seizure frequencies in each group were measured. Electrical stimulation of ANT was introduced after induction of seizure status epilepticus. Stimulation was on for 30 min and off for 30 min per 60‐min cycle. Local cerebral glucose utilization (LCGU) was also measured by using [14C] 2‐deoxyglucose autoradiography in three groups of rats: control (n = 7), bilateral ANT stimulation (n = 7), and bilateral ANT lesioning (n = 7).

Results: Unilateral ANT electrical stimulation and lesioning significantly reduced clinical seizure frequency, compared with control animals. Strikingly, no animals treated with bilateral ANT procedures demonstrated any clinical seizure. LCGU was markedly increased in the sensorimotor cortex, striatum, thalamus, mammillary body, and midbrain tegmentum of control group rats after KA injection, but no increase in LCGU was noted in rats treated with bilateral ANT lesioning or stimulation.

Conclusions: The electrical stimulation and lesioning of ANT suppressed focal cortical clinical seizures induced by KA injection. Additionally, an analysis of cerebral metabolic changes indicated that these procedures might suppress the function as amplifier and synchronizer of seizure activity.
Impaired Functional Status and Echocardiographic Abnormalities Signifying Global Dysfunction Enhance the Prognostic Significance of Previously Unrecognized Myocardial Infarction Detected by Electrocardiography
Authors: Ammar Khawaja Afzal , Makwana Ravindrakumar , Jacobsen Steven J. , Kors Jan A. , Burnett John C. , Redfield Margaret M. , Yawn Barbara P. , Rodeheffer Richard J.
Published: February 2007

Background: The relationship between electrocardiographic unrecognized myocardial infarction (UMI), abnormal functional status, echocardiographic abnormalities, and mortality has not been evaluated.

Methods: A population‐based random sample of 2042 Olmsted County residents, age ≥45 years, was studied by self‐administered questionnaire, chart review, ECG and echocardiogram, and 5 year follow‐up for all‐cause mortality. UMI (n = 81) was diagnosed if ECG‐MI criteria were met without previous documented myocardial infarction. Functional Status was assessed by the Goldman Specific Activity Scale.

Results: UMI subjects had an increased prevalence of abnormal functional status compared to no MI controls (22% vs 11%, P < 0.05). This association was independent of sex, obesity, smoking, diabetes, and pulmonary disease. It became insignificant after stratifying for echocardiographic abnormalities. Compared to no MI controls, UMI subjects with impaired functional status had a higher mortality hazard ratio (HR 7.2; P<0.0001) than those without impaired functional status (HR 2.7; P = 0.02). In UMI subjects with impaired functional status and any echocardiographic abnormality signifying global ventricular dysfunction (systolic or diastolic dysfunction, left atrial or left ventricular enlargement), the mortality risk was even higher (HR 9.5; P<0.001) and persisted in multivariate analyses. This increased mortality risk was unaffected by adjustment for regional wall motion abnormalities.

Conclusions: The assessment of impaired functional status and echocardiographic abnormalities improves the prognostic significance of UMI. Even in the absence of regional wall motion abnormalities, structural abnormalities of global dysfunction may play a role in mediating the increased mortality associated with UMI.
Significance of Lead Strength during Exercise Testing
Authors: Polizos George , Ellestad Myrvin H.
Published: February 2007

Background: The aim of the study was to evaluate the contribution of relative lead strengths to exercise‐induced ECG changes (ST depression) to predict the degree of myocardial ischemia as compared to the angiograms. This was accomplished by comparing the magnitude of ST depression to the ST/R ratio. Studies have shown that the diagnostic strength of a lead is directly related to the R wave amplitude1 and that sensitivity is significantly improved.

Methods: Three hundred patients, who underwent treadmill exercise testing and coronary angiography revealing significant coronary narrowing (≥70% luminal diameter narrowing), were studied, along with 150 patients clear of significant coronary artery disease (<70% luminar diameter narrowing). Our goal was to determine the correlation between the relative lead strengths, using a constructed ST/R ratio, to exercise induced ECG changes (ST depression) to predict the presence of myocardial ischemia as compared to angiographic findings. Using a cutoff of 0.1 for the ST/R ratio, our data were compared to the sensitivity and specificity of 1.0 mm ST depression.

Results: Overall sensitivity was improved for the ST/R ratio (84% vs 78%), while specificity was slightly decreased (81% vs 92%) in comparison to standard ST depression. When differentiating between R wave amplitudes, those with R wave ≤ 10 mm showed significantly improved sensitivity (88% vs 54%) and a minor decrease in specificity (90% vs 92%). In those with R wave ≥ 20 mm, the sensitivity of ST depression was higher (88% vs 71%) but the ST/R ratio was much more specific (88% vs 46%). No significant difference was observed when differentiating between male and female patients.

Conclusion: We found that the correction of ST depression for R wave amplitude results in improved sensitivity in patients with low R waves and specificity in patients with very tall R waves (R ≥ 20 mm).
Child Mortality and Socioeconomic Status: An Examination of Differentials by Migration Status in South Africa
Authors: Thomas Kevin J. A.
Published: February 2007

This study examines child mortality and socioeconomic status among migrants and nonmigrants. It also examines child mortality by migration status in all quintiles of socioeconomic status, comparing immigrants to the native-born and internal migrants to nonmigrants. The results show that among migrants, child mortality decreased faster as socioeconomic status increased than among nonmigrants. The results also show a crossover in the likelihood of child mortality by immigration status as socioeconomic status increased. In the poorest socioeconomic quintiles immigrants had a greater likelihood of child mortality than the native-born while in the wealthiest quintiles child mortality was greater among the native-born.
Theorizing Migration Policy: Is There a Third Way?
Authors: Boswell Christina
Published: February 2007

This article critically reviews theories of migration policy according to two criteria: methodological rigor and explanatory plausibility. It finds that political economy accounts are theoretically robust, but at the price of oversimplification. Neo-institutional theories offer more sophisticated accounts, but fall short on a number of methodological and explanatory counts. As an alternative, this article suggests a theory focusing on the functional imperatives of the state in the area of migration, which shape its responses to societal interests and institutional structures.
Migration Estimation Based on the Labour Force Survey: An EU-15 Perspective
Authors: Martí Mónica , Ródenas Carmen
Published: February 2007

It can be observed in the research that the European Union Labour Force Survey (EU LFS) only allows a satisfactory estimation of the stocks of non-nationals or those born abroad in some countries, whereas it proves to be less than adequate in most of them with regard to migration flows. We believe that this very limited success is due to a twofold statistical problem of imprecision and bias, which is intensified by the embarrassing question of answer impossible. These difficulties exist among the Member States to a greater or lesser degree, depending on the characteristics of the migratory domain and the particular features that the EU LFS acquires in each country.
Wealth in Middle and Old Age in Mexico: The Role of International Migration
Authors: Wong Rebeca , Palloni Alberto , Soldo Beth J.
Published: February 2007

This article examines the impact that past migration to the U.S. has on the current economic well-being of individuals in middle or old age who have returned to Mexico. A priori, the net effect of U.S. migration on wealth among return migrants is difficult to predict; there are counteracting factors that can affect wealth positively or negatively. Using data from the Mexican Health and Aging Study 2001 and correcting for selection factors, the long-term effect of U.S. migration for return migrants was found consistently positive in terms of their accumulated personal wealth at middle and old age. This article speculates about the possible mechanisms that can explain this apparent advantage.
Politics, Not Economic Interests: Determinants of Migration Policies in the European Union
Authors: Hix Simon , Noury Abdul
Published: February 2007

In this article we examine the determinants of European Union (EU) migration policies. We look at the passage of six pieces of migration and immigrant integration legislation in the fifth European Parliament (1999–2004). Based on the sixty-one roll-call votes on these bills we create a “migration score” for each Member of the European Parliament. We then use regression analysis to investigate the determinants of these scores. We find that the strongest determinants of policy outcomes on migration issues in this arena are the left-right preferences of EU legislators. These are stronger predictors than the economic preferences of national parties' constituents or the economic interests or political preferences of the member states.
Neighborhood and School Factors in the School Performance of Immigrants' Children
Authors: Pong Suet-ling , Hao Lingxin
Published: February 2007

This article examines the effects of neighborhoods and schools on the achievement gaps between adolescents of different nativities and ethnicities. We show that neighborhood and school conditions are better for natives' than for immigrants' children, and they are the worst for Hispanic immigrants. Using cross-classified hierarchical models, we find that introducing neighborhood and school characteristics helps to account for the disadvantage of Mexican immigrants' children but to reveal the advantage of Filipino immigrants' children, compared to native non-Hispanic Whites. Neighborhood and school effects are not universal: they influence school performance of immigrants' children more than that of natives' children.
Variation of the Recirculation Length of Newtonian and Non-Newtonian Power-Law Fluids in Laminar Flow Through a Suddenly Expanded Axisymmetric Geometry
Authors: Nag Debabrata , Datta Amitava
Published: February 2007

A numerical study has been carried out for the laminar flow of Newtonian and non-Newtonian power-law fluids through a suddenly expanded axisymmetric geometry. Mathematical correlations are proposed for the prediction of the length of the recirculating eddy in terms of Reynolds number, expansion ratio and rheological parameters. A wide range of expansion ratios (1.25⩽ER⩽8.0) has been covered for the Newtonian fluid and both the shear-thinning and shear-thickening flow characteristic fluids have been considered for the non-Newtonian fluids.
A Functional Correlation for the Primary Breakup Processes of Liquid Sheets Emerging From Air-Assist Atomizers
Authors: Sivadas V. , Heitor M. V. , Fernandes Rui
Published: February 2007

The study aims to highlight a general relationship between the characteristic variables of liquid sheet breakup and the principal forces of the flow domain. To accomplish this objective, an experimental investigation on air-assisted liquid sheets was carried out for a range of liquid-to-air velocities. The associated spray angle, breakup frequency, and breakup length were measured by exploiting high-speed imaging techniques. The results demonstrate that, when the stability variables are related to the liquid–air momentum flux ratio, a high correlation was attained for a range of flow conditions where capillary instability is insignificant.
Flip-Chip Underfill
Packaging Considering Capillary Force, Pressure Difference, and Inertia
Effects
Authors: Lin Chao-Ming , Chang Win-Jin , Fang Te-Hua
Published: February 2007

This study aims to enhance the flow rate and reduce the filling time in flip-chip underfill packaging by combining capillary force, pressure difference, and inertia effects. In the designed underfill apparatus, the capillary force effect is developed by surface tension, the pressure difference between the inlet and the outlet is established using a pump or a vacuum, and the inertia force is achieved via circular rotation. The governing equations containing the three analyzed effects are derived and solved using a dimensionless technique. The analytical results indicate that for the general gap height of approximately 10-1000μm, the pressure difference and inertia effects dominate the driving force and provide a significant reduction in the filling time. However, for a gap height of less than 1μm, the driving force is dominated by the capillary effect. The present results confirm that the productivity of the flip-chip underfill packaging process can be enhanced through the appropriate control of the capillary force, pressure difference, and inertia effects.
Numerical Simulation of Laminar Flow and Heat Transfer Inside a Microchannel With One Dimpled Surface
Authors: Wei X. J. , Joshi Y. K. , Ligrani P. M.
Published: February 2007

Steady, laminar flow and heat transfer, inside a rectangular microchannel with a dimpled bottom surface, are numerically studied. The microchannel is 50×10−6m(50μm) deep and 200×10−6m(200μm) wide. The dimples are placed in a single row along the bottom wall with a pitch of 150×10−6m(150μm). The dimple depth is 20×10−6m(20μm), and the dimple footprint diameter is 98×10−6m(98μm). Fully developed periodic velocity and temperature boundary conditions are used at the inlet and outlet of one unit cell of the dimpled microchannel. Key flow structures such as recirculating flow and secondary flow patterns and their development along the flow directions are identified. The impact of these flow structures on the heat transfer is described. Heat transfer augmentations (relative to a channel with smooth walls) are present both on the bottom-dimpled surface, and on the sidewalls of the channel. The pressure drops in the laminar-microscale flow are either equivalent to, or less than, values produced in smooth channels with no dimples. It is concluded that dimples, proven to be an effective passive heat transfer augmentation for macroscale channels, can also be used to enhance heat transfer inside microchannels.
A Study of Deformation Mechanism During Nanoindentation Creep in Tin-Based Solder Balls
Authors: Shibutani Tadahiro , Yu Qiang , Shiratori Masaki
Published: February 2007

As the shrinkage and integration of devices, the creep behavior of tin-based alloys becomes important with microscales. In this paper, the behavior of creep deformation in solder alloys during a nanoindentation test was examined. Nanoindentation creep test was carried out for tin-based solder balls. Obtained results summarized as follows: (i) The stress exponent for power-law creep estimated can be evaluated from the evolution of hardness. These values obtained in the early stage corresponds with that of bulk within the range of high strain rate. (ii) The stress sensitivity decreases after stress relaxation in nanoindentation creep tests. The saturated value is 1 in three solder balls. (iii) The morphology of indented surface consists of three parts: initial indentation, power-law creep, and granular surface. It suggests that the transition from power-law creep to diffusion creep takes place. (iv) Finite element method analysis reveals stress and strain concentration appears in the vicinity of the tip. Strain field remains self-similar as the indentation proceeds. (v) The gradient of triaxial stresses below the tip in a nanoindentation test accelerates the creep strain rate due to the diffusive flow, relatively.
Genetic Diversity and Potential Function of Microbial Symbionts Associated with Newly Discovered Species of
Osedax
Polychaete Worms
Authors: Goffredi Shana K. , Johnson Shannon B. , Vrijenhoek Robert C.
Published: February 2007

We investigated the genetic diversity of symbiotic bacteria associated with two newly discovered species of
Osedax
from Monterey Canyon, CA, at 1,017-m (
Osedax
Monterey Bay sp. 3 “rosy” [
Osedax
sp. MB3]) and 381-m (
Osedax
Monterey Bay sp. 4 “yellow collar”) depths. Quantitative PCR and clone libraries of 16S rRNA gene sequences identified differences in the compositions and abundances of bacterial phylotypes associated with the newly discovered host species and permitted comparisons between adult
Osedax frankpressi
and juveniles that had recently colonized whalebones implanted at 2,891 m. The newly discovered
Osedax
species hosted
Oceanospirillales
symbionts that are related to
Gammaproteobacteria
associated with the previously described
O. frankpressi
and
Osedax rubiplumus
(S. K. Goffredi, V. J. Orphan, G. W. Rouse, L. Jahnke, T. Embaye, K. Turk, R. Lee, and R. C. Vrijenhoek, Environ. Microbiol. 7:1369-1378, 2005). In addition,
Osedax
sp. MB3 hosts a diverse and abundant population of additional bacteria dominated by
Epsilonproteobacteria
. Ultrastructural analysis of symbiont-bearing root tissues verified the enhanced microbial diversity of
Osedax
sp. MB3. Root tissues from the newly described host species and
O. frankpressi
all exhibited collagenolytic enzyme activity, which covaried positively with the abundance of symbiont DNA and negatively with mean adult size of the host species. Members of this unusual genus of bone-eating worms may form variable associations with symbiotic bacteria that allow for the observed differences in colonization and success in whale fall environments throughout the world's oceans.
Comparison of Levels of Inactivation of Two Isolates of
Giardia lamblia
Cysts by UV Light
Authors: Li Dong , Craik Stephen A. , Smith Daniel W. , Belosevic Miodrag
Published: February 2007

The effects of 254-nm UV irradiation on two human isolates (WB and H3) of
Giardia lamblia
cysts were assessed using a collimated beam protocol and a Mongolian gerbil model. The levels of infection of cysts in the gerbils were assessed based on the presence of cysts in feces and the presence and activity of trophozoites in the small intestine of inoculated gerbils. The results suggest that there were differences in the infectivities of the WB and H3 isolates, as well as in susceptibilities of the parasites to UV light. Without UV exposure, gerbils were more readily infected by isolate H3 cysts. After UV exposure of the cysts, however, the gerbils were more susceptible to isolate WB cysts.
Plasmid Replicon Typing of Commensal and Pathogenic
Escherichia coli
Isolates
Authors: Johnson Timothy J. , Wannemuehler Yvonne M. , Johnson Sara J. , Logue Catherine M. , White David G. , Doetkott Curt , Nolan Lisa K.
Published: February 2007

Despite the critical role of plasmids in horizontal gene transfer, few studies have characterized plasmid relatedness among different bacterial populations. Recently, a multiplex PCR replicon typing protocol was developed for classification of plasmids occurring in members of the
Enterobacteriaceae
. Here, a simplified version of this replicon typing procedure which requires only three multiplex panels to identify 18 plasmid replicons is described. This method was used to screen 1,015
Escherichia coli
isolates of avian, human, and poultry meat origin for plasmid replicon types. Additionally, the isolates were assessed for their content of several colicin-associated genes. Overall, a high degree of plasmid variability was observed, with 221 different profiles occurring among the 1,015 isolates examined. IncFIB plasmids were the most common type identified, regardless of the source type of
E. coli
. IncFIB plasmids occurred significantly more often in avian pathogenic
E. coli
(APEC) and retail poultry
E. coli
(RPEC) than in uropathogenic
E. coli
(UPEC) and avian and human fecal commensal
E. coli
isolates (AFEC and HFEC, respectively). APEC and RPEC were also significantly more likely than UPEC, HFEC, and AFEC to possess the colicin-associated genes
cvaC
,
cbi
, and/or
cma
in conjunction with one or more plasmid replicons. The results suggest that
E. coli
isolates contaminating retail poultry are notably similar to APEC with regard to plasmid profiles, with both generally containing multiple plasmid replicon types in conjunction with colicin-related genes. In contrast, UPEC and human and avian commensal
E. coli
isolates generally lack the plasmid replicons and colicin-related genes seen in APEC and RPEC, suggesting limited dissemination of such plasmids among these bacterial populations.
Genome Survey Sequencing of the Wine Spoilage YeastDekkera (Brettanomyces) bruxellensis
Authors: Woolfit Megan , Rozpędowska Elżbieta , Piškur Jure , Wolfe Kenneth H.
Published: February 2007

The hemiascomycete yeastDekkera bruxellensis, also known asBrettanomyces bruxellensis, is a major cause of wine spoilage worldwide. Wines infected withD. bruxellensisdevelop distinctive, unpleasant aromas due to volatile phenols produced by this species, which is highly ethanol tolerant and facultatively anaerobic. Despite its importance, however,D. bruxellensishas been poorly genetically characterized until now. We performed genome survey sequencing of a wine strain ofD. bruxellensisto obtain 0.4× coverage of the genome. We identified approximately 3,000 genes, whose products averaged 49% amino acid identity to theirSaccharomyces cerevisiaeorthologs, with similar intron contents. Maximum likelihood phylogenetic analyses suggest that the relationship betweenD. bruxellensis,S. cerevisiae, andCandida albicansis close to a trichotomy. The estimated rate of chromosomal rearrangement inD. bruxellensisis slower than that calculated forC. albicans, while its rate of amino acid evolution is somewhat higher. The proteome ofD. bruxellensisis enriched for transporters and genes involved in nitrogen and lipid metabolism, among other functions, which may reflect adaptations to its low-nutrient, high-ethanol niche. We also identified an adenyl deaminase gene that has high similarity to a gene in bacteria of theBurkholderia cepaciaspecies complex and appears to be the result of horizontal gene transfer. These data provide a resource for further analyses of the population genetics and evolution ofD. bruxellensisand of the genetic bases of its physiological capabilities.
Drosophila melanogaster Thor
and Response to
Candida albicans
Infection
Authors: Levitin A. , Marcil A. , Tettweiler G. , Laforest M. J. , Oberholzer U. , Alarco A. M. , Thomas D. Y. , Lasko P. , Whiteway M.
Published: February 2007

We used
Drosophila melanogaster
macrophage-like Schneider 2 (S2) cells as a model to study cell-mediated innate immunity against infection by the opportunistic fungal pathogen
Candida albicans
. Transcriptional profiling of S2 cells coincubated with
C. albicans
cells revealed up-regulation of several genes. One of the most highly up-regulated genes during this interaction is the
D. melanogaster
translational regulator 4E-BP encoded by the
Thor
gene. Analysis of
Drosophila 4E
-
BP

null

mutant survival upon infection with
C. albicans
showed that 4E-BP plays an important role in host defense, suggesting a role for translational control in the
D. melanogaster
response to
C. albicans
infection.
Characterization of the Proteasome Accessory Factor (paf) Operon inMycobacterium tuberculosis
Authors: Festa Richard A. , Pearce Michael J. , Darwin K. Heran
Published: February 2007

In a previous screen forMycobacterium tuberculosismutants that are hypersusceptible to reactive nitrogen intermediates (RNI), two genes associated with theM. tuberculosisproteasome were identified. One of these genes,pafA(proteasomeaccessoryfactor A), encodes a protein of unknown function. In this work, we determined thatpafAis in an operon with two additional genes,pafBandpafC. In order to assess the contribution of these genes to RNI resistance, we isolated mutants with transposon insertions inpafBandpafC. In contrast to thepafAmutant, thepafBandpafCmutants were not severely sensitized to RNI, butpafBandpafCwere nonetheless required for full RNI resistance. We also found that PafB and PafC interact with each other and that each is likely required for the stability of the other protein inM. tuberculosis. Finally, we show that the presence of PafA, but not PafB or PafC, regulates the steady-state levels of three proteasome substrates. Taken together, these data demonstrate that PafA, but not PafB or PafC, is critical for maintaining the steady-state levels of known proteasome substrates, whereas all three proteins appear to play a role in RNI resistance.
The Nuclear Quadrupole Moment of 14N from Accurate Electric Field Gradient Calculations and Microwave Spectra of NP Molecule
Authors: Kellö Vladimir , Sadlej Andrzej J.
Published: February 2007

Extensive series of relativistic coupled cluster calculations of the electric field gradient at N in NP has been carried out. The accurate value of the calculated electric field gradient, combined with the highly accurate experimental value of the nuclear quadrupole coupling constant for the 14N nucleus, gives the 'molecular' value of the nuclear quadrupole moment Q(14N) = 20.46 mb. This result perfectly agrees with the value (20.44 ± 0.03 mb) determined from atomic calculations and atomic spectra. The present study involves also extensive investigations of basis sets which must be used in highly accurate calculations of electric field gradients.
Changes in bone remodelling and antifracture efficacy of intermittent bisphosphonate therapy: implications from clinical studies with ibandronate
Authors: Papapoulos S E , Schimmer R C
Published: February 2007

Bisphosphonates reduce the rate of bone resorption and bone remodelling. Given daily, they decrease the risk of fractures in postmenopausal osteoporosis. When bisphosphonates were given at extended drug-free intervals this antifracture efficacy was generally not seen. This may be due to the different pattern of bone remodelling changes. Data from randomised clinical studies of ibandronate, given orally or intravenously, at different doses and for variable time intervals to women with osteoporosis were examined to explore the relationship between intermittent bisphosphonate therapy, changes in bone resorption and fracture risk. The magnitude of the reduction of the rate of bone resorption at the end of the drug-free interval rather than its fluctuation pattern after bisphosphonate administration determines antifracture efficacy, provided that these fluctuations occur within the premenopausal range. Prolongation of the drug-free interval beyond 2 weeks should be compensated by a dose higher than the cumulative daily dose.
Muscle metaboreflex attenuates spontaneous heart rate baroreflex sensitivity during dynamic exercise
Authors: Sala-Mercado Javier A. , Ichinose Masashi , Hammond Robert L. , Ichinose Tomoko , Pallante Marco , Stephenson Larry W. , O'Leary Donal S. , Iellamo Ferdinando
Published: February 2007

Hypoperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex. Dynamic exercise attenuates spontaneous baroreflex sensitivity (SBRS) in the control of heart rate (HR) during rapid, spontaneous changes in blood pressure (BP). Our objective was to determine whether muscle metaboreflex activation (MRA) further diminishes SBRS. Conscious dogs were chronically instrumented for measurement of HR, cardiac output, mean arterial pressure, and left ventricular systolic pressure (LVSP) at rest and during mild (3.2 km/h) or moderate (6.4 km/h at 10% grade) dynamic exercise before and after MRA (via partial reduction of hindlimb blood flow). SBRS was evaluated as the slopes of the linear relations (LRs) between HR and LVSP during spontaneous sequences of at least three consecutive beats when HR changed inversely vs. pressure (expressed as beats·min−1·mmHg−1). During mild exercise, these LRs shifted upward, with a significant decrease in SBRS (−3.0 ± 0.4 vs. −5.2 ± 0.4, P < 0.05 vs. rest). MRA shifted LRs upward and rightward and decreased SBRS (−2.1 ± 0.1, P < 0.05 vs. mild exercise). Moderate exercise shifted LRs upward and rightward and significantly decreased SBRS (−1.2 ± 0.1, P < 0.05 vs. rest). MRA elicited further upward and rightward shifts of the LRs and reductions in SBRS (−0.9 ± 0.1, P < 0.05 vs. moderate exercise). We conclude that dynamic exercise resets the arterial baroreflex to higher BP and HR as exercise intensity increases. In addition, increases in exercise intensity, as well as MRA, attenuate SBRS.
Erythrocyte-associated transients in capillary Po2: an isovolemic hemodilution study in the rat spinotrapezius muscle
Authors: Barker Matthew C. , Golub Aleksander S. , Pittman Roland N.
Published: February 2007

Mathematical simulations of oxygen delivery to tissue from capillaries that take into account the particulate nature of blood flow predict the existence of oxygen tension (Po2) gradients between erythrocytes (RBCs). As RBCs and plasma alternately pass an observation point, these gradients are manifested as rapid fluctuations in Po2, also known as erythrocyte-associated transients (EATs). The impact of hemodilution on EATs and oxygen delivery at the capillary level of the microcirculation has yet to be elucidated. Therefore, in the present study, phosphorescence quenching microscopy was used to measure EATs and Po2 in capillaries of the rat spinotrapezius muscle at the following systemic hematocrits (Hctsys): normal (39%) and after moderate (HES1; 27%) or severe (HES2; 15%) isovolemic hemodilution using a 6% hetastarch solution. A 532-nm laser, generating 10-μs pulses concentrated onto a 0.9-μm spot, was used to obtain plasma Po2 values 100 times/s at points along surface capillaries of the muscle. Mean capillary Po2 (Pc[Formula: see text]; means ± SE) significantly decreased between conditions (normal: 56 ± 2 mmHg, n = 45; HES1: 47 ± 2 mmHg, n = 62; HES2: 27 ± 2 mmHg, n = 52, where n = capillary number). In addition, the magnitude of Po2 transients (ΔPo2) significantly decreased with hemodilution (normal: 19 ± 1 mmHg, n = 45; HES1: 11 ± 1 mmHg, n = 62; HES2: 6 ± 1 mmHg, n = 52). Results suggest that the decrease in Pc[Formula: see text] and ΔPo2 with hemodilution is primarily dependent on Hctsys and subsequent microvascular compensations.
Mechanoelectric feedback leads to conduction slowing and block in acutely dilated atria: a modeling study of cardiac electromechanics
Authors: Kuijpers Nico H. L. , ten Eikelder Huub M. M. , Bovendeerd Peter H. M. , Verheule Sander , Arts Theo , Hilbers Peter A. J.
Published: February 2007

Atrial fibrillation, a common cardiac arrhythmia, is promoted by atrial dilatation. Acute atrial dilatation may play a role in atrial arrhythmogenesis through mechanoelectric feedback. In experimental studies, conduction slowing and block have been observed in acutely dilated atria. In the present study, the influence of the stretch-activated current ( Isac) on impulse propagation is investigated by means of computer simulations. Homogeneous and inhomogeneous atrial tissues are modeled by cardiac fibers composed of segments that are electrically and mechanically coupled. Active force is related to free Ca2+ concentration and sarcomere length. Simulations of homogeneous and inhomogeneous cardiac fibers have been performed to quantify the relation between conduction velocity and Isac under stretch. In our model, conduction slowing and block are related to the amount of stretch and are enhanced by contraction of early-activated segments. Conduction block can be unidirectional in an inhomogeneous fiber and is promoted by a shorter stimulation interval. Slowing of conduction is explained by inactivation of Na+ channels and a lower maximum upstroke velocity due to a depolarized resting membrane potential. Conduction block at shorter stimulation intervals is explained by a longer effective refractory period under stretch. Our observations are in agreement with experimental results and explain the large differences in intra-atrial conduction, as well as the increased inducibility of atrial fibrillation in acutely dilated atria.
Activators of the PKA and PKG pathways attenuate RhoA-mediated suppression of the KDR current in cerebral arteries
Authors: Luykenaar Kevin D. , Welsh Donald G.
Published: February 2007

This study tested whether activation of protein kinase A (PKA) and G (PKG) pathways would attenuate the ability of RhoA to suppress the delayed rectifier K+ (KDR) current and limit agonist-induced depolarization and constriction. Smooth muscle cells from rat cerebral arteries were enzymatically isolated, and whole cell KDR currents were monitored with conventional patch-clamp electrophysiology. The KDR current averaged 21.2 ± 2.3 pA/pF (mean ± SE) at +40 mV and was potently inhibited by UTP. Current suppression was eliminated in the presence of C3 exoenzyme, confirming that this modulation is dependent on RhoA. Activation of PKA (dibutyryl-cAMP, forskolin) or PKG (dibutyryl-cGMP, sodium nitroprusside, nitric oxide) similarly abolished the ability of UTP to suppress KDR and did so without effect on baseline current. Using pressure myography techniques, we stripped cerebral arteries of endothelium and preconstricted them with UTP; these were subsequently shown to hyperpolarize and dilate to both forskolin and sodium nitroprusside. An increase in KV channel activity was found to partly underlie these associated changes, as constriction to 4-aminopyridine (KDR channel blocker) was greater after PKA or PKG activation. We conclude from our electrophysiological and functional observations that the PKA and PKG pathways attenuate the ability of UTP to depolarize and constrict cerebral arteries in part by minimizing the RhoA-mediated suppression of the KDR current.
Regulation of Ca2+and electrical alternans in cardiac myocytes: role of CAMKII and repolarizing currents
Authors: Livshitz Leonid M. , Rudy Yoram
Published: February 2007

Alternans of cardiac repolarization is associated with arrhythmias and sudden death. At the cellular level, alternans involves beat-to-beat oscillation of the action potential (AP) and possibly Ca2+transient (CaT). Because of experimental difficulty in independently controlling the Ca2+and electrical subsystems, mathematical modeling provides additional insights into mechanisms and causality. Pacing protocols were conducted in a canine ventricular myocyte model with the following results: 1) CaT alternans results from refractoriness of the sarcoplasmic reticulum Ca2+release system; alternation of the L-type calcium current has a negligible effect; 2) CaT-AP coupling during late AP occurs through the sodium-calcium exchanger and underlies AP duration (APD) alternans; 3) increased Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity extends the range of CaT and APD alternans to slower frequencies and increases alternans magnitude; its decrease suppresses CaT and APD alternans, exerting an antiarrhythmic effect; and 4) increase of the rapid delayed rectifier current ( IKr) also suppresses APD alternans but without suppressing CaT alternans. Thus CaMKII inhibition eliminates APD alternans by eliminating its cause (CaT alternans) while IKrenhancement does so by weakening CaT-APD coupling. The simulations identify combined CaMKII inhibition and IKrenhancement as a possible antiarrhythmic intervention.
Endothelial senescence after high-cholesterol, high-fat diet challenge in baboons
Authors: Shi Qiang , Hubbard Gene B. , Kushwaha Rampratap S. , Rainwater David , Thomas Charles A. , Leland M. Michelle , VandeBerg John L. , Wang Xing L.
Published: February 2007

Increasing evidence indicates that replicative senescence and premature endothelial senescence could contribute to endothelial dysfunction. This study aims at testing the hypothesis that a high-fat diet may lead to premature vascular endothelial senescence in a nonhuman primate model. We isolated endothelial cells from left and right femoral arteries in 10 baboons before and after a 7-wk high-fat dietary treatment. We compared the morphological alterations, replicative capacities, and senescence-associated β-galactosidase activities (SA-β-gal) at these two time points. We found that high-fat diet increased the prevalence of endothelial senescence. Endothelial replicative capacities declined dramatically, and SA-β-gal activities increased significantly in postdietary challenge. There was no change in telomeric length using quantitative flow fluorescence in situ hybridization analysis, suggesting that some stressors lead to cell senescence independent of telomere dysfunction. Our findings that high-fat diet causes endothelial damage through the premature senescence suggest a novel mechanism for the diet-induced endothelial dysfunction.
Bone morphogenetic protein type 2 receptor gene therapy attenuates hypoxic pulmonary hypertension
Authors: Reynolds Ann M. , Xia Wei , Holmes Mark D. , Hodge Sandra J. , Danilov Sergei , Curiel David T. , Morrell Nicholas W. , Reynolds Paul N.
Published: February 2007

Idiopathic pulmonary arterial hypertension (PAH) is characterized by proliferation of pulmonary vascular endothelial and smooth muscle cells causing increased vascular resistance and right heart failure. Mutations in the bone morphogenetic protein receptor type 2 (BMPR2) are believed to cause the familial form of the disease. Reduced expression of BMPR2 is also noted in secondary PAH. Recent advances in the therapy of PAH have improved quality of life and survival, but many patients continue to do poorly. The possibility of treating PAH via improving BMPR2 signaling is thus a rational consideration. Such an approach could be synergistic with or additive to current treatments. We developed adenoviral vectors containing the BMPR2 gene. Transfection of cells in vitro resulted in upregulation of SMAD signaling and reduced cell proliferation. Targeted delivery of vector to the pulmonary vascular endothelium of rats substantially reduced the pulmonary hypertensive response to chronic hypoxia, as reflected by reductions in pulmonary artery and right ventricular pressures, right ventricular hypertrophy, and muscularization of distal pulmonary arterioles. These data provide further evidence for a role for BMPR2 in PAH and provide a rationale for the development of therapies aimed at improving BMPR2 signaling.