bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of glucose and meal ingestion on incretin secretion in Japanese subjects with normal glucose tolerance
Authors: Yamane Shunsuke , Harada Norio , Hamasaki Akihiro , Muraoka Atsushi , Joo Erina , Suzuki Kazuyo , Nasteska Daniela , Tanaka Daisuke , Ogura Masahito , Harashima Shin‐ichi , Inagaki Nobuya
Published: July 2011

Aims/Introduction:  Gastric inhibitory polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) are the major incretins; their secretion after various nutrient loads are well‐evaluated in Caucasians. However, little is known of the relationship between incretin secretion and differing nutritional loading in Japanese subjects. In the present study, we evaluated GIP and GLP‐1 secretion in Japanese subjects with normal glucose tolerance (NGT) after glucose loading (75 g glucose and 17 g glucose) and meal ingestion.

Materials and Methods:  A total of 10 Japanese NGT subjects participated in 75 g oral glucose tolerance test (OGTT), 17 g OGTT and meal tolerance test (MTT). Plasma glucose (PG), serum insulin (IRI), serum C‐peptide (CPR), plasma total GIP, and plasma total GLP‐1 levels during OGTT and MTT were determined.

Results:  Area under the curve (AUC)‐GIP was increased in proportion to the amount of glucose, and was highest in MTT, showing that GIP secretion is also stimulated by nutrients other than glucose, such as lipid. In contrast, although the larger glucose load tended to induce a larger GLP‐1 release, AUC‐GLP‐1 was not significantly different among the three loading tests (75 g OGTT, 17 g OGTT, MTT) irrespective of the kind or amount of nutrition load.

Conclusions:  Our results suggest that nutritional composition might have a greater effect on GIP secretion than that on GLP‐1 secretion in Japanese NGT subjects. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00143.x, 2012)
Risk factors for early childhood caries in disadvantaged populations
Authors: Arora Amit , Schwarz Eli , Blinkhorn Anthony Stevenson
Published: June 2011

Early childhood caries is a significant international public health problem. The aim of this paper was to review the current evidence of the risk factors for dental caries in disadvantaged children under 6 years of age. Medline, Cochrane, and PubMed database searches were conducted. Systematic reviews were used where available, or meta‐analyses; randomized, controlled trials; and cohort, case‐control, and cross‐sectional studies (in that order). Studies were restricted to those published in English from 1990 to October 2010. Early childhood caries has a complex etiology with biological, behavioral, and sociodemographic influences. Evidence suggests that young children are most likely to develop caries if Streptococcus mutans is acquired at an early age, although this is influenced by other factors, such as oral hygiene, fluoride, diet, dental visit patterns, socioeconomic status, ethnicity, and health literacy. Etiological pathways should be taken into consideration when designing interventions to prevent dental caries in disadvantaged preschool children.
Light effect on the stability of β-lapachone in solution: pathways and kinetics of degradation
Authors: Cunha-Filho Marcílio S S , Estévez-Braun Ana , Pérez-Sacau Elisa , Echezarreta-López Ma Magdalena , Martínez-Pacheco Ramón , Landín Mariana
Published: June 2011

Objectives

The purpose of this work was to study the chemical stability of the new antitumoral β-lapachone (βLAP) to determine the degradation pathway/s of the molecule and the degradation kinetics in addition to identifying several degradation products.

Method  Samples of βLAP in solution were stored under conditions of darkness and illumination at 40°C at which the pseudo-first order rate constants for the βLAP degradation were determined. Furthermore, drug degraded solutions were concentrated and purified using Sephadex LH-20 and preparative thin-layer chromatography and degradation products were identified by nuclear magnetic resonance spectroscopy.

Key findings

The results revealed that βLAP shows two different degradation routes: hydrolysis in the dark and photolysis under the light. The βLAP exposure to light accelerated the drug degradation about 140 fold, compared with the samples stored in the absence of light. The hydrolysis produced hydroxylapachol as the main degradation product. The photolysis yielded phthalic acid, 6-hydroxy-3methylene-3H-isobenzofuran-1-one and a benzomacrolactone together with a complex mixture of other phthalate-derivatives such as 2-(2-carboxy-acetyl)-benzoic acid.

Conclusions

This study provides useful information for the development of βLAP dosage forms, their storage, manipulation and quality control.
A note on the estimation of the Pareto efficient set for multiobjective matrix permutation problems
Authors: Brusco Michael J. , Steinley Douglas
Published: June 2011

There are a number of important problems in quantitative psychology that require the identification of a permutation of the n rows and columns of an n × n proximity matrix. These problems encompass applications such as unidimensional scaling, paired‐comparison ranking, and anti‐Robinson forms. The importance of simultaneously incorporating multiple objective criteria in matrix permutation applications is well recognized in the literature; however, to date, there has been a reliance on weighted‐sum approaches that transform the multiobjective problem into a single‐objective optimization problem. Although exact solutions to these single‐objective problems produce supported Pareto efficient solutions to the multiobjective problem, many interesting unsupported Pareto efficient solutions may be missed. We illustrate the limitation of the weighted‐sum approach with an example from the psychological literature and devise an effective heuristic algorithm for estimating both the supported and unsupported solutions of the Pareto efficient set.
How should we question young children's understanding of aspectuality?
Authors: Waters Gillian M. , Beck Sarah R.
Published: June 2011

In two experiments, we investigated whether 4‐ to 5‐year‐old children's ability to demonstrate their understanding of aspectuality was influenced by how the test question was phrased. In Experiment 1, 60 children chose whether to look or feel to gain information about a hidden object (identifiable by sight or touch). Test questions referred either to the perceptual aspect of the hidden object (e.g., whether it was red or blue), the modality dimension (e.g., what colour it was), or the object's identity (e.g., which one it was). Children who heard the identity question performed worse than those who heard the aspect or dimension question. Further investigation in Experiment 2 (N= 23) established that children's difficulty with the identity question was not due to a problem recalling the objects. We discuss how the results of these methodological investigations impact on researchers’ assessment of the development of aspectuality understanding.
Judging judges: How do children weigh the importance of capability and objectivity for being a good decision maker?
Authors: Mills Candice M. , Landrum Asheley R.
Published: June 2011

Two studies examined developmental differences in how children weigh capability and objectivity when evaluating potential judges. In Study 1, 84 6‐ to 12‐year‐olds and adults were told stories about pairs of judges that varied in capability (i.e., perceptual capacity) and objectivity (i.e., the relationship to a contestant) and were asked to predict which judge would be more accurate. Participants generally preferred capable over incapable judges. Additionally, 10‐ and 12‐year‐olds adjusted their preferences for the most capable judge based on objectivity information. Seventy 6‐ and 8‐year‐olds participated in Study 2, which was similar to Study 1 except that the judges could both seem incapable unless children understood how different decisions require different kinds of perceptual capabilities. While 8‐year‐olds chose judges based on the relevance of the perceptual capability, 6‐year‐olds struggled, seeming to be distracted by the valence of the judges’ relationships to the contestants. Overall, these results support that there are important shifts in how children evaluate decision makers from early to middle childhood.
Numerical Predictions of the Effect of Rotation on Fluid Flow and Heat Transfer in an Engine-Similar Two-Pass Internal Cooling Channel With Smooth and Ribbed Walls
Authors: Schüler M. , Dreher H.-M. , Neumann S. O. , Weigand B. , Elfert M.
Published: June 2011

In the present study, a two-pass internal cooling channel with engine-similar cross-sections was investigated numerically. The channel featured a trapezoidal inlet pass, a sharp 180 deg bend, and a nearly rectangular outlet pass. Calculations were done for a configuration with smooth walls and walls equipped with 45 deg skewed ribs (P/e=10, e/dh=0.1) at a Reynolds number of Re=50,000. The present study focused on the effect of rotation on fluid flow and heat transfer. The investigated rotation numbers were Ro=0.0 and 0.10. The computations were performed by solving the Reynolds-averaged Navier–Stokes equations (Reynolds-averaged Navier–Stokes method) with the commercial finite-volume solver FLUENT using a low-Re shear stress transport (SST) k-ω turbulence model. The numerical grids were block-structured hexahedral meshes generated with POINTWISE. Flow field measurements were independently performed at German Aerospace Centre Cologne using particle image velocimetry. In the smooth channel, rotation had a large impact on secondary flows. Especially, rotation induced vortices completely changed the flow field. Rotation also changed flow impingement on the tip and the outlet pass sidewall. Heat transfer in the outlet pass was strongly altered by rotation. In contrast to the smooth channel, rotation showed less influence on heat transfer in the ribbed channel. This is due to a strong secondary flow field induced by the ribs. However, in the outlet pass, Coriolis forces markedly affected the rib induced secondary flow field. The influence of rotation on heat transfer was visible in particular in the bend region and in the second pass directly downstream of the bend.
A Fast Correction for Elastic Quarter-Space Applied to 3D Modeling of Edge Contact Problems
Authors: Guilbault Raynald
Published: July 2011

Applying the Hertz theory to some non-Hertzian contact problems can produce acceptable results. Nevertheless, including the influence of free surfaces requires numerical methods, many of which are based on the Boussinesq–Cerruti solution. This paper presents a new approach, which is better capable of releasing quarter-space free surfaces from shear and normal internal stresses without engendering any increase in calculation times. The mirrored pressure for shear correction is multiplied by a correction factor (ψ), which accounts for the normal load. The expression ψ is derived from the Hetényi correction process, and the resulting displacements show an enhanced correspondence with validation finite element method models; with an imposed fluctuating pressure, the maximum edge displacement error was −21.90% for a shear load correction (Poisson coefficient ν=0.3), and introducing the ψ factor reduced the deviation to −9.55%, while for ν of 0.15, the maximum error was −11.30%, which was reduced to +0.60% with the ψ factor. This study introduces the factor ψ in a 3D elastic contact algorithm. The resulting calculation scheme is then able to simulate any point or line contact problems. Compared with coincident ends and sharp edge contact validation values, the model shows high conformity levels.
Numerical Analysis of Transport Phenomena in Resistance Spot Welding Process
Authors: Li YongBing , Lin ZhongQin , Shen Qi , Lai XinMin
Published: July 2011

Resistance spot welding (RSW) is a very complicated process involving electromagnetic, thermal, fluid flow, mechanical, and metallurgical variables. Since weld nugget area is closed and unobservable using experimental means, numerical methods are generally used to reveal the nugget formation mechanism. Traditional RSW models focus on the electrothermal behaviors in the nugget and do not have the ability to model mass transport caused by induced magnetic forces in the molten nugget. In this paper, a multiphysics model, which comprehensively considers the coupling of electric, magnetic, thermal, and flow fields during RSW, temperature-dependent physical properties, and phase transformation, is used to investigate the heat and mass transport laws in the weld nugget and to reveal the interaction of the heat and mass transports and their evolutions. Results showed that strong and complicated mass transport appears in the weld nugget and substantially changed the heat transport laws and, therefore, would be able to substantially affect the hardening, segregation, and residual stress of the weld. Compared with the traditional models which could not consider the mass transport, the multiphysics model proposed in this paper could simulate the RSW process with higher accuracy and more realities.
Classical and quantum responsivities of geometrically asymmetric metal-vacuum-metal junctions used for the rectification of infrared and optical radiations
Authors: Mayer A. , Chung M. S. , Lerner P. B. , Weiss B. L. , Miskovsky N. M. , Cutler P. H.
Published: June 2011

The authors study the rectification properties of geometrically asymmetric metal-vacuum-metal junctions in which a combination of static and oscillating biases is established between a cathode that is extended by a hemispherical protrusion and a flat anode. The static current-voltage characteristics of this device are established using a transfer-matrix methodology. The rectification properties of the device are, however, analyzed in the framework of a classical model that is based on the Taylor-expansion of static current-voltage data. This enables the impedance and the classical responsivity of the device to be established. The authors then investigate how the impedance and the classical responsivity of this junction are affected by the work function of the materials, the gap spacing between the cathode and the anode, and the aspect ratio of the protrusion. They also consider the efficiency with which the energy of incident radiations can be converted using this device. The authors finally compare the responsivity obtained using this classical approach with the quantum responsivity one can define from the currents actually achieved in an oscillating barrier. This work provides additional insight for the development of a device that could be used for the energy conversion of infrared and optical radiations.
Atomic structure and optical properties of InAs submonolayer depositions in GaAs
Authors: Lenz Andrea , Eisele Holger , Becker Jonas , Schulze Jan-Hindrik , Germann Tim D. , Luckert Franziska , Pötschke Konstantin , Lenz Ernst , Ivanova Lena , Strittmatter André , Bimberg Dieter , Pohl Udo W. , Dähne Mario
Published: June 2011

Using cross-sectional scanning tunneling microscopy and photoluminescence spectroscopy, the atomic structure and optical properties of submonolayer depositions of InAs in GaAs are studied. The submonolayer depositions are formed by a cycled deposition of 0.5 monolayers InAs with GaAs spacer layers of different thicknesses between 1.5 and 32 monolayers. The microscopy images exhibit InAs-rich agglomerations with widths around 5 nm and heights of up to 8 monolayers. A lateral agglomeration density in the 1012 cm−2 range is found. During the capping of the InAs depositions a vertical segregation occurs, for which a segregation coefficient of ∼0.73 was determined. In the case of thin GaAs spacer layers, the observed segregation forms vertically connected agglomerations. The photoluminescence spectra exhibit peaks with linewidths below 10 meV and show a considerable dependence of the peak energy on the spacer thickness, even up to 32 monolayers GaAs, indicating a long range electronic coupling.
Improved computer‐aided detection of small polyps in CT colonography using interpolation for curvature estimationa)
Authors: Liu Jiamin , Kabadi Suraj , Van Uitert Robert , Petrick Nicholas , Deriche Rachid , Summers Ronald M.
Published: June 2011

Purpose

: Surface curvatures are important geometric features for the computer‐aided analysis and detection of polyps in CT colonography (CTC). However, the general kernel approach for curvature computation can yield erroneous results for small polyps and for polyps that lie on haustral folds. Those erroneous curvatures will reduce the performance of polyp detection. This paper presents an analysis of interpolation's effect on curvature estimation for thin structures and its application on computer‐aided detection of small polyps in CTC.

Methods

: The authors demonstrated that a simple technique, image interpolation, can improve the accuracy of curvature estimation for thin structures and thus significantly improve the sensitivity of small polyp detection in CTC.

Results

: Our experiments showed that the merits of interpolating included more accurate curvature values for simulated data, and isolation of polyps near folds for clinical data. After testing on a large clinical data set, it was observed that sensitivities with linear, quadratic B‐spline and cubic B‐spline interpolations significantly improved the sensitivity for small polyp detection.

Conclusions

: The image interpolation can improve the accuracy of curvature estimation for thin structures and thus improve the computer‐aided detection of small polyps in CTC.
Superelastic Effect in Polycrystalline Ferrous Alloys
Authors: Omori T. , Ando K. , Okano M. , Xu X. , Tanaka Y. , Ohnuma I. , Kainuma R. , Ishida K.
Published: June 2011

A superelastic alloy formed from common elements operates over a wide temperature window.
Rotary Photon Drag Enhanced by a Slow-Light Medium
Authors: Franke-Arnold Sonja , Gibson Graham , Boyd Robert W. , Padgett Miles J.
Published: June 2011

A spinning slow-light medium (ruby) crystal is used to enhance the rotation of light.
Characterization of an Autoinducer of Penicillin Biosynthesis in Penicillium chrysogenum
Authors: Martín Jorge , García-Estrada Carlos , Rumbero Ángel , Recio Eliseo , Albillos Silvia M. , Ullán Ricardo V. , Martín Juan-Francisco
Published: July 2011

Filamentous fungi produce an impressive variety of secondary metabolites; many of them have important biological activities. The biosynthesis of these secondary metabolites is frequently induced by plant-derived external elicitors and appears to also be regulated by internal inducers, which may work in a way similar to that of bacterial autoinducers. The biosynthesis of penicillin in
Penicillium chrysogenum
is an excellent model for studying the molecular mechanisms of control of gene expression due to a good knowledge of the biochemistry and molecular genetics of β-lactam antibiotics and to the availability of its genome sequence and proteome. In this work, we first developed a plate bioassay that allows direct testing of inducers of penicillin biosynthesis using single colonies of
P. chrysogenum
. Using this bioassay, we have found an inducer substance in the conditioned culture broths of
P. chrysogenum
and
Acremonium chrysogenum
. No inducing effect was exerted by γ-butyrolactones, jasmonic acid, or the penicillin precursor δ-(
l
-α-aminoadipyl)-
l
-cysteinyl-
d
-valine. The conditioned broth induced penicillin biosynthesis and transcription of the
pcbAB
,
pcbC
, and
penDE
genes when added at inoculation time, but its effect was smaller if added at 12 h and it had no effect when added at 24 h, as shown by Northern analysis and
lacZ
reporter studies. The inducer molecule was purified and identified by mass spectrometry (MS) and nuclear magnetic resonance (NMR) as 1,3-diaminopropane. Addition of pure 1,3-diaminopropane stimulated the production of penicillin by about 100% compared to results for the control cultures. Genes for the biosynthesis of 1,3-diaminopropane have been identified in the
P. chrysogenum
genome.
Regime Shift and Microbial Dynamics in a Sequencing Batch Reactor for Nitrification and Anammox Treatment of Urine
Authors: Bürgmann Helmut , Jenni Sarina , Vazquez Francisco , Udert Kai M.
Published: July 2011

The microbial population and physicochemical process parameters of a sequencing batch reactor for nitrogen removal from urine were monitored over a 1.5-year period. Microbial community fingerprinting (automated ribosomal intergenic spacer analysis), 16S rRNA gene sequencing, and quantitative PCR on nitrogen cycle functional groups were used to characterize the microbial population. The reactor combined nitrification (ammonium oxidation)/anammox with organoheterotrophic denitrification. The nitrogen elimination rate initially increased by 400%, followed by an extended period of performance degradation. This phase was characterized by accumulation of nitrite and nitrous oxide, reduced anammox activity, and a different but stable microbial community. Outwashing of anammox bacteria or their inhibition by oxygen or nitrite was insufficient to explain reactor behavior. Multiple lines of evidence, e.g., regime-shift analysis of chemical and physical parameters and cluster and ordination analysis of the microbial community, indicated that the system had experienced a rapid transition to a new stable state that led to the observed inferior process rates. The events in the reactor can thus be interpreted to be an ecological regime shift. Constrained ordination indicated that the pH set point controlling cycle duration, temperature, airflow rate, and the release of nitric and nitrous oxides controlled the primarily heterotrophic microbial community. We show that by combining chemical and physical measurements, microbial community analysis and ecological theory allowed extraction of useful information about the causes and dynamics of the observed process instability.
Analysis and Manipulation of Aspartate Pathway Genes for
l
-Lysine Overproduction from Methanol by Bacillus methanolicus
Authors: Nærdal Ingemar , Netzer Roman , Ellingsen Trond E. , Brautaset Trygve
Published: July 2011

We investigated the regulation and roles of six aspartate pathway genes in
l
-lysine overproduction in
Bacillus methanolicus
:
dapG
, encoding aspartokinase I (AKI);
lysC
, encoding AKII;
yclM
, encoding AKIII;
asd
, encoding aspartate semialdehyde dehydrogenase;
dapA
, encoding dihydrodipicolinate synthase; and
lysA
, encoding
meso
-diaminopimelate decarboxylase. Analysis of the wild-type strain revealed that
in vivo lysC
transcription was repressed 5-fold by
l
-lysine and induced 2-fold by
dl
-methionine added to the growth medium. Surprisingly,
yclM
transcription was repressed 5-fold by
dl
-methionine, while the
dapG
,
asd
,
dapA
, and
lysA
genes were not significantly repressed by any of the aspartate pathway amino acids. We show that the
l
-lysine-overproducing classical
B. methanolicus
mutant NOA2#13A52-8A66 has—in addition to a
hom-1
mutation—chromosomal mutations in the
dapG
coding region and in the
lysA
promoter region. No mutations were found in its
dapA
,
lysC
,
asd
, and
yclM
genes. The mutant
dapG
gene product had abolished feedback inhibition by
meso
-diaminopimelate
in vitro
, and the
lysA
mutation was accompanied by an elevated (6-fold)
lysA
transcription level
in vivo
. Moreover,
yclM
transcription was increased 16-fold in mutant strain NOA2#13A52-8A66 compared to the wild-type strain. Overexpression of wild-type and mutant aspartate pathway genes demonstrated that all six genes are important for
l
-lysine overproduction as tested in shake flasks, and the effects were dependent on the genetic background tested. Coupled overexpression of up to three genes resulted in additive (above 80-fold) increased
l
-lysine production levels.
Characterization of Planctomyces limnophilus and Development of Genetic Tools for Its Manipulation Establish It as a Model Species for the Phylum Planctomycetes
Authors: Jogler Christian , Glöckner Frank Oliver , Kolter Roberto
Published: July 2011

Planctomycetes
represent a remarkable clade in the domain
Bacteria
because they play crucial roles in global carbon and nitrogen cycles and display cellular structures that closely parallel those of eukaryotic cells. Studies on
Planctomycetes
have been hampered by the lack of genetic tools, which we developed for
Planctomyces limnophilus
.
Biosynthesis of a Complex Yersiniabactin-Like Natural Product via the
mic
Locus in Phytopathogen Ralstonia solanacearum
Authors: Kreutzer Martin F. , Kage Hirokazu , Gebhardt Peter , Wackler Barbara , Saluz Hans P. , Hoffmeister Dirk , Nett Markus
Published: July 2011

A genome mining study in the plant pathogenic bacterium
Ralstonia solanacearum
GMI1000 unveiled a polyketide synthase/nonribosomal peptide synthetase gene cluster putatively involved in siderophore biosynthesis. Insertional mutagenesis confirmed the respective locus to be operational under iron-deficient conditions and spurred the isolation of the associated natural product. Bioinformatic analyses of the gene cluster facilitated the structural characterization of this compound, which was subsequently identified as the antimycoplasma agent micacocidin. The metal-chelating properties of micacocidin were evaluated in competition experiments, and the cellular uptake of gallium-micacocidin complexes was demonstrated in
R. solanacearum
GMI1000, indicating a possible siderophore role. Comparative genomics revealed a conservation of the micacocidin gene cluster in defined, but globally dispersed phylotypes of
R. solanacearum
.
A Plant-Produced Pfs230 Vaccine Candidate Blocks Transmission of Plasmodium falciparum
Authors: Farrance Christine E. , Rhee Amy , Jones R. Mark , Musiychuk Konstantin , Shamloul Moneim , Sharma Satish , Mett Vadim , Chichester Jessica A. , Streatfield Stephen J. , Roeffen Will , van de Vegte-Bolmer Marga , Sauerwein Robert W. , Tsuboi Takafumi , Muratova Olga V. , Wu Yimin , Yusibov Vidadi
Published: June 2011

Plasmodium falciparum
is transmitted to a new host after completing its sexual cycle within a mosquito. Developing vaccines against the parasite sexual stages is a critical component in the fight against malaria. We are targeting multiple proteins of
P. falciparum
which are found only on the surfaces of the sexual forms of the parasite and where antibodies against these proteins have been shown to block the progression of the parasite's life cycle in the mosquito and thus block transmission to the next human host. We have successfully produced a region of the Pfs230 antigen in our plant-based transient-expression system and evaluated this vaccine candidate in an animal model. This plant-produced protein, 230CMB, is expressed at approximately 800 mg/kg in fresh whole leaf tissue and is 100% soluble. Administration of 230CMB with >90% purity induces strong immune responses in rabbits with high titers of transmission-blocking antibodies, resulting in a greater than 99% reduction in oocyst counts in the presence of complement, as determined by a standard membrane feeding assay. Our data provide a clear perspective on the clinical development of a Pfs230-based transmission-blocking malaria vaccine.
Global Transcriptome Changes Underlying Colony Growth in the Opportunistic Human Pathogen Aspergillus fumigatus
Authors: Gibbons John G. , Beauvais Anne , Beau Remi , McGary Kriston L. , Latgé Jean-Paul , Rokas Antonis
Published: July 2011

Aspergillus fumigatus
is the most common and deadly pulmonary fungal infection worldwide. In the lung, the fungus usually forms a dense colony of filaments embedded in a polymeric extracellular matrix. To identify candidate genes involved in this biofilm (BF) growth, we used RNA-Seq to compare the transcriptomes of BF and liquid plankton (PL) growth. Sequencing and mapping of tens of millions sequence reads against the
A. fumigatus
transcriptome identified 3,728 differentially regulated genes in the two conditions. Although many of these genes, including the ones coding for transcription factors, stress response, the ribosome, and the translation machinery, likely reflect the different growth demands in the two conditions, our experiment also identified hundreds of candidate genes for the observed differences in morphology and pathobiology between BF and PL. We found an overrepresentation of upregulated genes in transport, secondary metabolism, and cell wall and surface functions. Furthermore, upregulated genes showed significant spatial structure across the
A. fumigatus
genome; they were more likely to occur in subtelomeric regions and colocalized in 27 genomic neighborhoods, many of which overlapped with known or candidate secondary metabolism gene clusters. We also identified 1,164 genes that were downregulated. This gene set was not spatially structured across the genome and was overrepresented in genes participating in primary metabolic functions, including carbon and amino acid metabolism. These results add valuable insight into the genetics of biofilm formation in
A. fumigatus
and other filamentous fungi and identify many relevant, in the context of biofilm biology, candidate genes for downstream functional experiments.
Autotrophic Methanotrophy in Verrucomicrobia: Methylacidiphilum fumariolicumSolV Uses the Calvin-Benson-Bassham Cycle for Carbon Dioxide Fixation
Authors: Khadem Ahmad F. , Pol Arjan , Wieczorek Adam , Mohammadi Seyed S. , Francoijs Kees-Jan , Stunnenberg Henk G. , Jetten Mike S. M. , Op den Camp Huub J. M.
Published: July 2011

Genome data of the extreme acidophilic verrucomicrobial methanotroph
Methylacidiphilum fumariolicum
strain SolV indicated the ability of autotrophic growth. This was further validated by transcriptome analysis, which showed that all genes required for a functional Calvin-Benson-Bassham (CBB) cycle were transcribed. Experiments with
13
CH
4
or
13
CO
2
in batch and chemostat cultures demonstrated that CO
2
is the sole carbon source for growth of strain SolV. In the presence of CH
4
, CO
2
concentrations in the headspace below 1% (vol/vol) were growth limiting, and no growth was observed when CO
2
concentrations were below 0.3% (vol/vol). The activity of the key enzyme of the CBB cycle, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), measured with a
13
C stable-isotope method was about 70 nmol CO
2
fixed · min
−1
· mg of protein
−1
. An immune reaction with antibody against the large subunit of RuBisCO on Western blots was found only in the supernatant fractions of cell extracts. The apparent native mass of the RuBisCO complex in strain SolV was about 482 kDa, probably consisting of 8 large (53-kDa) and 8 small (16-kDa) subunits. Based on phylogenetic analysis of the corresponding RuBisCO gene, we postulate that RuBisCO of the verrucomicrobial methanotrophs represents a new type of form I RuBisCO.
Regulated Shift from Helical to Polar Localization of Listeria monocytogenesCell Wall-Anchored Proteins
Authors: Bruck Serawit , Personnic Nicolas , Prevost Marie-Christine , Cossart Pascale , Bierne Hélène
Published: July 2011

Many virulence factors of Gram-positive bacterial pathogens are covalently anchored to the peptidoglycan (PG) by sortase enzymes. However, for rod-shaped bacteria little is known about the spatiotemporal organization of these surface proteins in the cell wall. Here we report the three-dimensional (3D) localization of the PG-bound virulence factors InlA, InlH, InlJ, and SvpA in the envelope ofListeria monocytogenesunder different growth conditions. We found that all PG-anchored proteins are positioned along the lateral cell wall in nonoverlapping helices. However, these surface proteins can also become localized at the pole and asymmetrically distributed when specific regulatory pathways are activated. InlA and InlJ are enriched at poles when expressed at high levels in exponential-phase bacteria. InlA and InlH, which are σBdependent, specifically relocalize to the septal cell wall and subsequently to the new pole in cells entering stationary phase. The accumulation of InlA and InlH in the septal region also occurs when oxidative stress impairs bacterial growth. In contrast, the iron-dependent protein SvpA is present at the old pole and is excluded from the septum and new pole of bacteria grown under low-iron conditions. We conclude thatL. monocytogenesrapidly reorganizes the spatial localization of its PG proteins in response to changes in environmental conditions such as nutrient deprivation or other stresses. This dynamic control would distribute virulence factors at specific sites during the infectious process.
Differential Accumulation of
nif
Structural Gene mRNA in Azotobacter vinelandii
Authors: Hamilton Trinity L. , Jacobson Marty , Ludwig Marcus , Boyd Eric S. , Bryant Donald A. , Dean Dennis R. , Peters John W.
Published: July 2011

Northern analysis was employed to investigate mRNA produced by mutant strains of
Azotobacter vinelandii
with defined deletions in the
nif
structural genes and in the intergenic noncoding regions. The results indicate that intergenic RNA secondary structures effect the differential accumulation of transcripts, supporting the high Fe protein-to-MoFe protein ratio required for optimal diazotrophic growth.
Identification of a Chemoreceptor Zinc-Binding Domain Common to Cytoplasmic Bacterial Chemoreceptors
Authors: Draper Jenny , Karplus Kevin , Ottemann Karen M.
Published: July 2011

We report the identification and characterization of a previously unidentified protein domain found in bacterial chemoreceptors and other bacterial signal transduction proteins. This domain contains a motif of three noncontiguous histidines and one cysteine, arranged as
H
xx[WFYL]x
21-28
C
x[LFMVI]Gx[WFLVI]x
18-27
H
xxx
H
(boldface type indicates residues that are nearly 100% conserved). This domain was first identified in the soluble
Helicobacter pylori
chemoreceptor TlpD. Using inductively coupled plasma mass spectrometry on heterologously and natively expressed TlpD, we determined that this domain binds zinc with a subfemtomolar dissociation constant. We thus named the domain CZB, for chemoreceptor zinc binding. Further analysis showed that many bacterial signaling proteins contain the CZB domain, most commonly proteins that participate in chemotaxis but also those that participate in c-di-GMP signaling and nitrate/nitrite sensing, among others. Proteins bearing the CZB domain are found in several bacterial phyla. The variety of signaling proteins using the CZB domain suggests that it plays a critical role in several signal transduction pathways.
Genome Sequence of the Ethanol-Producing Zymomonas mobilis subsp. mobilis Lectotype Strain ATCC 10988
Authors: Pappas Katherine M. , Kouvelis Vassili N. , Saunders Elizabeth , Brettin Thomas S. , Bruce David , Detter Chris , Balakireva Mariya , Han Cliff S. , Savvakis Giannis , Kyrpides Nikos C. , Typas Milton A.
Published: July 2011

Zymomonas mobilis
ATCC 10988 is the type strain of the
Z. mobilis
subsp.
mobilis
taxon, members of which are some of the most rigorous ethanol-producing bacteria. Isolated from
Agave
cactus fermentations in Mexico, ATCC 10988 is one of the first
Z. mobilis
strains to be described and studied. Its robustness in sucrose-substrate fermentations, physiological characteristics, large number of plasmids, and overall genomic plasticity render this strain important to the study of the species. Here we report the finishing and annotation of the ATCC 10988 chromosomal and plasmid genome.
Performance of the LightCycler SeptiFast Test M
grade
in Detecting Microbial Pathogens in Purulent Fluids
Authors: Sancho-Tello Silvia , Bravo Dayana , Borrás Rafael , Costa Elisa , Muñoz-Cobo Beatriz , Navarro David
Published: June 2011

The performance of the LightCycler SeptiFast (SF) assay was compared to that of culture methods in the detection of microorganisms in 43 purulent fluids from patients with pyogenic infections. The SF assay was more sensitive than the culture methods (86% versus 61%, respectively), irrespective of whether the infections were mono- or polymicrobial.
CD4-Like Immunological Function by CD4
−
T Cells in Multiple Natural Hosts of Simian Immunodeficiency Virus
Authors: Vinton Carol , Klatt Nichole R. , Harris Levelle D. , Briant Judith A. , Sanders-Beer Brigitte E. , Herbert Richard , Woodward Ruth , Silvestri Guido , Pandrea Ivona , Apetrei Cristian , Hirsch Vanessa M. , Brenchley Jason M.
Published: June 2011

Many species of African nonhuman primates are natural hosts for individual strains of simian immunodeficiency virus (SIV). These infected animals do not, however, develop AIDS. Here we show that multiple species of African nonhuman primate species characteristically have low frequencies of CD4
+
T cells and high frequencies of both T cells that express only the alpha-chain of CD8 and double-negative T cells. These subsets of T cells are capable of eliciting functions generally associated with CD4
+
T cells, yet these cells lack surface expression of the CD4 protein and are, therefore, poor targets for SIV
in vivo
. These data demonstrate that coevolution with SIV has, in several cases, involved downregulation of receptors for the virus by otherwise-susceptible host target cells. Understanding the genetic factors that lead to downregulation of these receptors may lead to therapeutic interventions that mimic this modulation in progressive infections.
Novel Histone H3 Binding Protein ORF158L from the Singapore Grouper Iridovirus
Authors: Tran Bich Ngoc , Chen Liming , Liu Yang , Wu Jinlu , Velázquez-Campoy Adrián , Sivaraman J. , Hew Choy Leong
Published: June 2011

Singapore grouper iridovirus (SGIV), a major pathogen of concern for grouper aquaculture, has a double-stranded DNA (dsDNA) genome with 162 predicted open reading frames, for which a total of 62 SGIV proteins have been identified. One of these, ORF158L, bears no sequence homology to any other known protein. Knockdown of
orf158L
using antisense morpholino oligonucleotides resulted in a significant decrease in virus yield in grouper embryonic cells. ORF158L was observed in nuclei and virus assembly centers of virus-infected cells. This observation led us to study the structure and function of ORF158L. The crystal structure determined at 2.2-Å resolution reveals that ORF158L partially exhibits a structural resemblance to the histone binding region of antisilencing factor 1 (Asf1), a histone H3/H4 chaperon, despite the fact that there is no significant sequence identity between the two proteins. Interactions of ORF158L with the histone H3/H4 complex and H3 were demonstrated by isothermal titration calorimetry (ITC) experiments. Subsequently, the results of ITC studies on structure-based mutants of ORF158L suggested Arg67 and Ala93 were key residues for histone H3 interactions. Moreover, a combination of approaches of ORF158L knockdown and isobaric tags/mass spectrometry for relative and absolute quantifications (iTRAQ) revealed that ORF158L may be involved in both the regulation and the expression of histone H3 and H3 methylation. Our present studies suggest that ORF158L may function as a histone H3 chaperon, enabling it to control host cellular gene expression and to facilitate viral replication.
Prospective Outcomes of Injury Study: recruitment, and participant characteristics, health and disability status
Authors: Derrett Sarah , Davie Gabrielle , Ameratunga Shanthi , Wyeth Emma , Colhoun Sarah , Wilson Suzanne , Samaranayaka Ari , Lilley Rebbecca , Hokowhitu Brendan , Hansen Paul , Langley John
Published: July 2011

The Prospective Outcomes of Injury Study aims to identify predictors of disability following injury. Participants were selected from the entitlement claims register of New Zealand's no-fault compensation insurer, the Accident Compensation Corporation, and followed up by interview for 2 years. This report describes changes to intended Prospective Outcomes of Injury Study methods and key characteristics of the cohort, with an emphasis on general health and disability before injury and soon afterwards. There were 2856 injured participants in the first interview, which occurred 3.2 months (median) after injury. The recruitment period was extended to enable inclusion of sufficient Māori participants. At the first interview, most participants were experiencing worse health status and increased disability compared to before injury, despite less than one-third reporting admission to hospital because of their injury. Analysis of outcome predictors related to post-injury function, disability and return-to-work soon after injury and 1 year later is now under way.
Comparison of clinical outcome of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations
Authors: Won Young-Woong , Han Ji-Youn , Lee Geon Kook , Park Seog-Yun , Lim Kun Young , Yoon Kyong-Ah , Yun Tak , Kim Heung Tae , Lee Jin Soo
Published: July 2011

Aims

Deletion of exon 19 of the epidermal growth factor receptor (EGFR) and mutation of exon 21 are the most commonEGFRmutations and predict higher response to EGFR tyrosine kinase inhibitors (TKI). Accumulating data show clinical differences in both response and survival between these twoEGFRmutations. This study investigated the clinical impact ofEGFRexon 19 deletion and L858R mutation by retrospectively analysing the clinical outcome of patients with advanced non-small-cell lung cancer (NSCLC) treated with EGFR TKI.

Methods

Patients harbouringEGFRexon 19 deletion or L858R mutations and who had received gefitinib or erlotinib treatment were identified. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were determined for the two groups.EGFRmutation was determined by PCR-based direct sequencing.

Results

The study indentified 87 patients harbouringEGFRexon 19 deletion (n=61) or L858R mutation (n=26) who were treated with either gefitinib (n=83) or erlotinib (n=4). Patients with exon 19 deletion had significantly longer PFS, compared with patients with L858R mutation (9.3 vs 6.9 months, p=0.02). In a multivariate Cox regression model,EGFRexon 19 deletion was independently predictive of longer PFS (p=0.02). However, no significant differences in RR (64% vs 62%, p=0.83) and OS (17.7 vs 20.5 months, p=0.65) were observed between these two mutations.

Conclusions

While no significant difference in OS was observed betweenEGFRexon 19 deletion and L858R mutation,EGFRexon 19 deletion was predictive of longer PFS following EGFR TKI treatment in patients with advanced NSCLC.
Recent advances in opioid prescription for chronic non-cancer pain
Authors: Snidvongs Saowarat , Mehta Vivek
Published: July 2011

Chronic pain is pain that persists past the normal time of healing, and is seen as a common problem with a significant socioeconomic impact. Pharmacological management for chronic non-cancer pain also involves the prescription of opioids, with the aim of an improved quality of life for the patient. New guidelines have been published to aid prescribing clinicians improve opioid safety and patient care, and include recommendations on when to refer patients to a pain specialist. In recent years there has been a rapid increase in opioid prescription in the UK and USA, prompting further concern regarding opioid abuse and side effects. Opioid use may also result in physical dependence and tolerance. Earlier recognition and diagnosis of unwanted effects of long term opioid use is needed, such as opioid induced suppression of the hypothalamic–pituitary–gonadal axis, and opioid induced immunosuppression. Patients may themselves discontinue opioids, however, due to minor side effects. Recent advances in opioid prescription include the increasing use of transdermal preparations and extended release, oral, once daily preparations. New formulations of existing drugs have been developed, as well as a new chemical entity. Abuse deterrent formulations and delivery systems may prevent the artificial acceleration of drug delivery and reduce the potential for opioid addiction. Overdose concerns and the potential for fatal overdose may necessitate mandatory training for all clinicians who prescribe opioids. Despite the widespread use of opioids in the management of chronic non-cancer pain, significant research gaps remain. An improvement in the evidence base for its prescription is required.
Effect of losartan on proteinuria and urinary angiotensinogen excretion in non-diabetic patients with chronic kidney disease
Authors: Lee Yu-Ji , Cho Seong , Kim Sung Rok , Jang Hye Ryoun , Lee Jung Eun , Huh Wooseong , Kim Dae Joong , Oh Ha Young , Kim Yoon-Goo
Published: June 2011

Purpose

Activation of the rennin–angiotensin system (RAS) is thought to contribute to hypertension and proteinuria, and eventually to the progression of chronic kidney disease (CKD). Recent evidence suggests that urinary angiotensinogen (UAGT) excretion reflects activation of the intrarenal RAS. This study was performed to determine the effect of losartan on proteinuria and UAGT excretion in non-diabetic patients with CKD with non-nephrotic-range proteinuria.

Study design

Thirty-two patients with non-nephrotic-range proteinuria (0.045–0.23 g/mmol creatinine) and normal renal function between April 2005 and April 2006 were randomised to a losartan (n=17) or a control (n=15) group. Patients in the losartan group received losartan 50 mg/day, and the doses were titrated up to 100 mg/day after 6 weeks. Serum and urinary angiotensinogen concentrations were measured by sandwich ELISA. The primary end point was the percentage change in proteinuria. The secondary end points were changes in estimated glomerular filtration rate and UAGT excretion. The follow-up period was 24 months.

Results

Baseline characteristics in the two groups were similar. After 24 months, losartan had reduced urinary protein excretion by 43% (from mean±SD 0.13±0.04 to 0.073±0.03 g/mmol, p<0.0001), but proteinuria had not changed in the control group. The percentage change in mean arterial pressure did not differ between the groups. Losartan decreased logarithmically converted UAGT excretion (from 1.58±0.47 to 1.00±0.52, p=0.001). Estimated glomerular filtration rate decreased significantly only in the control group.

Conclusion

Losartan significantly decreased proteinuria and UAGT excretion, and preserved renal function in non-diabetic patients with CKD.
EXCHANGE RATE AND STOCK PRICE INTERACTION IN MAJOR ASIAN MARKETS: EVIDENCE FOR INDIVIDUAL COUNTRIES AND PANELS ALLOWING FOR STRUCTURAL BREAKS
Authors: LEAN HOOI HOOI , NARAYAN PARESH , SMYTH RUSSELL
Published: July 2011

This article examines the relationship between exchange rates and stock prices in eight Asian countries. We test for cointegration and Granger causality for both individual countries using the Gregory and Hansen cointegration test that accommodates a structural break in the cointegrating vector, and for a panel using the Westerlund panel Lagrange multiplier (LM) cointegration test that allows for multiple structural breaks in the level of the individual cointegrating equations. Our results for individual countries suggest that the only country for which exchange rates and stock prices are cointegrated over the entire period is Korea where there is a weak long-run unidirectional Granger causality running from exchange rates to stock prices. Employing the panel LM cointegration test with multiple structural breaks, we find that exchange rates and stock prices are not cointegrated. We conclude that for the eight Asian countries, exchange rates and stock prices primarily have only a contemporaneous effect on each other that is reflected in the short-run intertemporal comovements between these financial variables.
MODELING EFFECTS OF TOXICANT ON UNINFECTED CELLS, INFECTED CELLS AND IMMUNE RESPONSE IN THE PRESENCE OF VIRUS
Authors: DUBEY B. , DUBEY UMA S. , HUSSAIN J.
Published: July 2011

In this paper, two mathematical models are proposed and analyzed. The first one deals with the interaction of uninfected cells, infected cells, viruses and immune response within humans. The second one deals with the effects of environmental toxicant on the first model. In each case, sufficient conditions for local stability and global stability of the equilibria are obtained, computer simulations are performed and the result is biologically interpreted. It has been seen that the environmental toxicant has detrimental effects on healthy cells, infected cells as well as on the immune response of the body.