bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulation of surface processes
Authors: Jónsson Hannes
Published: January 2011

Computer simulations of surface processes can reveal unexpected insight regarding atomic-scale structure and transitions. Here, the strengths and weaknesses of some commonly used approaches are reviewed as well as promising avenues for improvements. The electronic degrees of freedom are usually described by gradient-dependent functionals within Kohn–Sham density functional theory. Although this level of theory has been remarkably successful in numerous studies, several important problems require a more accurate theoretical description. It is important to develop new tools to make it possible to study, for example, localized defect states and band gaps in large and complex systems. Preliminary results presented here show that orbital density-dependent functionals provide a promising avenue, but they require the development of new numerical methods and substantial changes to codes designed for Kohn–Sham density functional theory. The nuclear degrees of freedom can, in most cases, be described by the classical equations of motion; however, they still pose a significant challenge, because the time scale of interesting transitions, which typically involve substantial free energy barriers, is much longer than the time scale of vibrations—often 10 orders of magnitude. Therefore, simulation of diffusion, structural annealing, and chemical reactions cannot be achieved with direct simulation of the classical dynamics. Alternative approaches are needed. One such approach is transition state theory as implemented in the adaptive kinetic Monte Carlo algorithm, which, thus far, has relied on the harmonic approximation but could be extended and made applicable to systems with rougher energy landscape and transitions through quantum mechanical tunneling.
Optimal feeding and swimming gaits of biflagellated organisms
Authors: Tam Daniel , Hosoi A. E.
Published: January 2011

Locomotion is widely observed in life at micrometric scales and is exhibited by many eukaryotic unicellular organisms. Motility of such organisms can be achieved through periodic deformations of a tail-like projection called the eukaryotic flagellum. Although the mechanism allowing the flagellum to deform is largely understood, questions related to the functional significance of the observed beating patterns remain unresolved. Here, we focus our attention on the stroke patterns of biflagellated phytoplanktons resembling the green algaChlamydomonas. Such organisms have been widely observed to beat their flagella in two different ways—a breaststroke and an undulatory stroke—both of which are prototypical of general beating patterns observed in eukaryotes. We develop a general optimization procedure to determine the existence of optimal swimming gaits and investigate their functional significance with respect to locomotion and nutrient uptake. Both the undulatory and the breaststroke represent local optima for efficient swimming. With respect to the generation of feeding currents, we found the breaststroke to be optimal and to enhance nutrient uptake significantly, particularly when the organism is immersed in a gradient of nutrients.
Visual influence on path integration in darkness indicates a multimodal representation of large-scale space
Authors: Tcheang Lili , Bülthoff Heinrich H. , Burgess Neil
Published: January 2011

Our ability to return to the start of a route recently performed in darkness is thought to reflect path integration of motion-related information. Here we provide evidence that motion-related interoceptive representations (proprioceptive, vestibular, and motor efference copy) combine with visual representations to form a single multimodal representation guiding navigation. We used immersive virtual reality to decouple visual input from motion-related interoception by manipulating the rotation or translation gain of the visual projection. First, participants walked an outbound path with both visual and interoceptive input, and returned to the start in darkness, demonstrating the influences of both visual and interoceptive information in a virtual reality environment. Next, participants adapted to visual rotation gains in the virtual environment, and then performed the path integration task entirely in darkness. Our findings were accurately predicted by a quantitative model in which visual and interoceptive inputs combine into a single multimodal representation guiding navigation, and are incompatible with a model of separate visual and interoceptive influences on action (in which path integration in darkness must rely solely on interoceptive representations). Overall, our findings suggest that a combined multimodal representation guides large-scale navigation, consistent with a role for visual imagery or a cognitive map.
Stable structural color patterns displayed on transparent insect wings
Authors: Shevtsova Ekaterina , Hansson Christer , Janzen Daniel H. , Kjærandsen Jostein
Published: January 2011

Color patterns play central roles in the behavior of insects, and are important traits for taxonomic studies. Here we report striking and stable structural color patterns—wing interference patterns (WIPs)—in the transparent wings of small Hymenoptera and Diptera, patterns that have been largely overlooked by biologists. These extremely thin wings reflect vivid color patterns caused by thin film interference. The visibility of these patterns is affected by the way the insects display their wings against various backgrounds with different light properties. The specific color sequence displayed lacks pure red and matches the color vision of most insects, strongly suggesting that the biological significance of WIPs lies in visual signaling. Taxon-specific color patterns are formed by uneven membrane thickness, pigmentation, venation, and hair placement. The optically refracted pattern is also stabilized by microstructures of the wing such as membrane corrugations and spherical cell structures that reinforce the pattern and make it essentially noniridescent over a large range of light incidences. WIPs can be applied to map the micromorphology of wings through direct observation and are useful in several fields of biology. We demonstrate their usefulness as identification patterns to solve cases of cryptic species complexes in tiny parasitic wasps, and indicate their potentials for research on the genetic control of wing development through direct links between the transregulatory wing landscape and interference patterns we observe in
Drosophila
model species. Some species display sexually dimorphic WIPs, suggesting sexual selection as one of the driving forces for their evolution.
Ethotic arguments and fallacies: The credibility function in multi-agent dialogue systems
Authors: Walton Douglas N.
Published: January 2011

In this paper, it is shown how formal dialectic can be extended to model multi-agent argumentation in which each participant is an agent. An agent is viewed as a participant in a dialogue who not only has goals, and the capability for actions, but who also has stable characteristics of types that can be relevant to an assessment of some of her arguments used in that dialogue. When agents engage in argumentation in dialogues, each agent has a credibility function that can be adjusted upwards or downwards by certain types of arguments brought forward by the other agent in the dialogue. One type is the argument against the person or argumentum ad hominem, in which personal attack on one party's character is used to attack his argument. Another is the appeal to expert opinion, traditionally associated with the informal fallacy called the argumentum ad verecundiam. In any particular case, an agent will begin a dialogue with a given degree of credibility, and what is here called the credibility function will affect the plausibility of the arguments put forward by that agent. In this paper, an agent is shown to have specific character traits that are vital to properly judging how this credibility function should affect the plausibility of her arguments, including veracity, prudence, sincerity and openness to opposed arguments. When one of these traits is a relevant basis for an adjustment in a credibility function, there is a shift to a subdialogue in which the argumentation in the case is re-evaluated. In such a case, it is shown how the outcome can legitimately be a reduction in the credibility rating of the arguer who was attacked. Then it is shown how the credibility function should be brought into an argument evaluation in the case, yielding the outcome that the argument is assigned a lower plausibility value.
Two microscopes are better than one
Authors: Leslie Mitch
Published: January 2011

Researchers reveal way to sharpen vision of double-microscope technique.
Enhancement of visible He2 emission by infrared laser excitation of He metastable atoms in atmospheric-pressure plasma jet
Authors: Urabe Keiichiro , Motomura Hideki , Sakai Osamu , Tachibana Kunihide
Published: January 2011

We observed bright red emission at an intersection of an infrared (IR) laser beam and an atmospheric-pressure plasma jet (APPJ). The APPJ had a coaxial dielectric barrier discharge configuration and generated a plasma plume in a He gas flow ejected into air from a glass capillary. Although the laser-beam wavelength was 1083 nm corresponding to He I (23P–23S) atomic transition, the enhanced red emission peaked in the visible region at 640 nm and had broad bandwidth corresponding to He2
molecular transition. This result indicates that the IR laser excitation of He metastable (23S) atoms leads to selective formation of excited He2
molecules from excited He (23P) atoms. The 640 nm emission intensity decreased as the laser beam moved downstream in the plasma plume, because of the quenching effects on the excited He atoms and the excited He2 molecules by air entrainment. We believe that the He2
molecular formation follows two potential curves of He2 (f 
3Σu or f 
3Πu) and
states, overcoming a potential hump by three-body collision processes.
Laser Thomson scattering for low-temperature plasmas
Authors: Muraoka K , Kono A
Published: January 2011

In recent years, low-temperature discharge plasmas with electron temperatures around a few eV have been actively studied and used for fundamental discharge physics research and industrial process applications. Here the electron density and temperature (and sometimes also the electron energy distribution function) are the most fundamental parameters that dictate the fates of these discharge plasmas and this information is of utmost importance. Laser Thomson scattering, which was developed for high-temperature plasmas in the early 1960s, has gained widespread use in the low-temperature plasma community since the late 1970s and has now matured as an established method of plasma diagnostics. Scattering diagnostic techniques for high-temperature plasmas have had to be modified to accommodate particular situations and constraints, such as laser perturbation of plasmas, low electron densities and the presence of material surfaces near to the plasmas. In this review, starting from a basic description of the technique, we outline some of the most salient results, which would not have been obtained without it, in discharges ranging from high-pressure to low-pressure gases, and near to material surfaces. Also, the signal-to-noise ratio and future potential of the method are discussed.
Deposition temperature effect of RF magnetron sputtered molybdenum oxide films on the power conversion efficiency of bulk-heterojunction solar cells
Authors: Fan Xi , Fang Guojia , Qin Pingli , Sun Nanhai , Liu Nishuang , Zheng Qiao , Cheng Fei , Yuan Longyan , Zhao Xingzhong
Published: January 2011

We have reported efficient bulk-heterojunction (regioregular poly (3-hexylthiophene) : (6,6)-phenyl C61 butyric acid methyl ester (P3HT : PCBM)) solar cells with MoO3 as a hole-selective layer deposited at different substrate temperatures from 100 °C to 400 °C by radio-frequency magnetron sputtering. The structure, morphology, optical and electrical properties of the MoO3 films deposited at different substrate temperatures are also investigated. MoO3 thin films deposited at 200 °C and below are amorphous in nature. However, the films deposited at 300 °C and 400 °C exhibit the presence of monoclinic Mo9O26 and orthorhombic MoO3, respectively. The electrical resistivity values of the MoO3 thin films are close to each other from 100 to 300 °C and decrease from 2.7 × 106 to 2.6 × 105 Ω cm with increasing substrate temperature from 300 to 400 °C. X-ray photoelectron spectroscopy core level analysis reveals the presence of Mo6+ oxidation state only in the films. We found that the optical band gap of MoO3 has reduced from 3.82 to 3.67 eV with decreasing substrate temperature from 400 to 100 °C. This decrease in band gap reduces the potential barrier between FTO and P3HT : PCBM, leading to an increase in the short circuit photocurrent density from 8.51 mA cm−2 to 9.50 mA cm−2 and an increase in efficiency of ∼20.7%.
Lifting group actions and nonnegative curvature
Authors: Grove Karsten , Ziller Wolfgang
Published: January 2011

We examine the question when a group acting by cohomogeneity one on the base of a principal

G
\operatorname {G}

-bundle can be lifted to the total space and commutes with the action by

G
\operatorname {G}

. We answer this question completely when the base of the principle bundle is

4
4

-dimensional.
Does Microfinance Reduce Rural Poverty? Evidence Based on Household Panel Data from Northern Ethiopia
Authors: Berhane Guush , Gardebroek Cornelis
Published: January 2011

Evidence on the long‐term impacts of microfinance credit is scarce. We use a unique four‐round panel dataset on farm households in northern Ethiopia that had access to microfinance, observed on two key poverty indicators: household consumption and housing improvements. Fixed‐effects and random trend models are used to reduce potential selection biases due to time‐invariant unobserved heterogeneity and individual trends therein. Results show that borrowing indeed causally increased consumption and housing improvements. A flexible specification that takes into account repeated borrowings also suggests that borrowing has cumulative long‐term effects on these outcomes, implying that short‐term impact estimates may underestimate credit effects.
Short‐ and long‐term treatment of dilutional hyponatraemia with satavaptan, a selective arginine vasopressin V2‐receptor antagonist: the DILIPO study
Authors: Aronson Doron , Verbalis Joseph G. , Mueller Matthias , Krum Henry ,   on behalf of the DILIPO investigators
Published: January 2011

Aims

Arginine vasopressin (AVP) V2 receptor antagonism is a new approach to the management of hyponatraemia in congestive heart failure (CHF). The aim of this study was to investigate the efficacy and safety of satavaptan, an oral AVP V2‐receptor antagonist, in patients with dilutional hyponatraemia.

Methods and results

A total of 118 patients (90 with CHF) with dilutional hyponatraemia (serum sodium 115–132 mmol/L) were randomized to double‐blind treatment with placebo or to 25 or 50 mg/day of satavaptan for 4 days, followed by non‐comparative open‐label satavaptan therapy for up to 343 days. The response rate (sodium ≥135 mmol/L and/or an increase in ≥5 mmol/L above baseline) was significantly higher with satavaptan 50 mg than with placebo (61.0 vs. 26.8%; P= 0.0035), with a trend towards significance with satavaptan 25 mg (48.6%, P= 0.0599). Median times to response were 3.30 and 2.79 days with satavaptan 25 and 50 mg/day, respectively, both shorter than placebo (>4 days; P= 0.0278 and P= 0.0004, respectively). Satavaptan therapy was effective in CHF patients, with response rates higher with both satavaptan 25 mg/day (53.6%) and 50 mg/day (57.1%) than with placebo (23.5%; P= 0.019 and P= 0.009, respectively). Sodium responses were maintained during open‐label therapy after a temporary study drug discontinuation period. Higher rates of adverse events occurred with the 50 mg/day dose, including rapid correction of hyponatraemia.

Conclusions

In patients with dilutional hyponatraemia, V2 receptor antagonism with satavaptan was effective in increasing serum sodium concentrations. The long‐term open‐label treatment results demonstrate sustained efficacy of satavaptan in maintaining normal sodium levels.

Trial Registration

clinicaltrials.gov Identifier: NCT00274326
A case of acute psittacosis with severe abdominal pain
Authors: Homma Takahiro , Yamaguchi Toshiyuki , Komatsu Nobuo , Hashimoto Shinichi , Doki Yoshinori , Senda Kazutaka , Yoshimura Naoki , Miyashita Naoyuki
Published: January 2011

We report the case of a psittacosis patient with severe abdominal pain who subsequently developed acute respiratory failure. The main symptoms of psittacosis are considered to be upper respiratory inflammation and influenza-like symptoms. However, it should be emphasized that digestive symptoms can be prominent in psittacosis patients. Early diagnosis of this condition is difficult and there is a need for an effective method for rapid diagnosis.
Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein
Authors: Zhao Bin , Li Li , Lu Qing , Wang Lloyd H. , Liu Chen-Ying , Lei Qunying , Guan Kun-Liang
Published: January 2011

The Yes-associated protein (YAP) is a transcription coactivator that plays a crucial role in organ size control by promoting cell proliferation and inhibiting apoptosis. The Hippo tumor suppressor pathway inhibits YAP through phosphorylation-induced cytoplasmic retention and degradation. Here we report a novel mechanism of YAP regulation by angiomotin (AMOT) family proteins via a direct interaction. Knockdown of AMOT family protein AMOTL2 in polarized Madin-Darby canine kidney (MDCK) cells leads to YAP activation, as indicated by decreased YAP tight junction localization, attenuated YAP phosphorylation, accumulation of nuclear YAP, and induction of YAP target gene expression. Transcriptional coactivator with PDZ-binding motif (TAZ), the YAP paralog, is also regulated by AMOT in a similar fashion. Furthermore, AMOTL2 knockdown results in loss of cell contact inhibition in a manner dependent on the functions of YAP and TAZ. Our results indicate a potential tumor-suppressing role of AMOT family proteins as components of the Hippo pathway, and demonstrate a novel mechanism of YAP and TAZ inhibition by AMOT-mediated tight junction localization. These observations provide a potential link between the Hippo pathway and cell contact inhibition.
Whole-Cell Patch-Clamp Analysis of Adult Drosophila Photoreceptors: FIGURE 1.
Authors: Dolph Patrick , Nair Amit , Raghu Padinjat
Published: January 2011

INTRODUCTION

Adult Drosophila have a compound eye composed of approximately 750 repeating units, called ommatidia, packed together to form the retina. Each ommatidium is a precise arrangement of 19 cells: eight photoreceptors (primary sensory neurons) and 11 accessory cells. Analysis of visual physiology in Drosophila photoreceptors has been central to understanding a number of important areas of modern biology including the G-protein-coupled receptor cycle, phosphoinositide signaling, and calcium signaling. Analysis of photoreceptor performance and synaptic transmission also can be studied using Drosophila photoreceptors as a model system. Electrophysiological analysis of responses to light is a powerful tool for characterizing and understanding visual transduction in Drosophila photoreceptors. The ommatidia can be dissociated to generate healthy cells under a limited set of conditions. The basolateral plasma membrane of the photoreceptors then becomes accessible to a patch pipette and light responses can be recorded in a whole-cell configuration. This approach has principally been used to study the activity of the light-activated channels in voltage-clamped photoreceptors.
Whole-Genome Amplification Using Φ29 DNA Polymerase
Authors: Burtt Noël P.
Published: January 2011

INTRODUCTION

The cornerstones of any genetic analysis study are the quality and quantity of the DNA samples. DNA is a precious limited resource, and in human disease studies the accessibility of sample DNA is often governed by the isolation method and the human source. Additionally, forensic analysis and archaeological research are generally infeasible without intact sample DNA. Therefore, mechanisms to preserve or enhance the quantity of the DNA stock are crucial to the success of these studies. Historically, to preserve and maintain DNA stocks, costly and labor-intensive Epstein-Barr-virus-transformed cell lines were produced. The creation of cell lines can be valuable for a number of reasons in addition to creating a renewable resource of DNA, but the cost and effort to create them, as well as the requirement of intact cells to begin with, limit the utility of this approach. More recently, whole-genome amplification (WGA), utilizing the unique property of the enzyme Φ29 DNA polymerase, has been used to generate robust high-fidelity copies of the genome. As described in this protocol, WGA using Φ29 DNA polymerase allows unbiased representation of the genome via multiple-strand displacement, followed by rolling-circle amplification on random primers.
Synthesis of Cationic Polysaccharides and Use for In Vitro Transfection: FIGURE 1.
Authors: Yudovin-Farber Ira , Eliyahu Hagit , Domb Abraham J.
Published: January 2011

INTRODUCTION

Polycations are effective nonviral carriers for gene delivery systems. These carriers vary in molecular weight, polymer structure, polymer:DNA ratio, molecular architecture, and the ability to introduce target-specific moieties. Polycations are capable of complexing various plasmids and transfecting them into different cells to produce a high yield of a desired protein. Cationic polysaccharides are attractive candidates for gene delivery. They are natural or semi-natural, nontoxic, biodegradable, and biocompatible materials that can be modified for improved physicochemical properties. Cationic polysaccharides are synthesized by conjugation of various oligoamines to oxidized polysaccharides via reductive amination. These conjugates have been rigorously tested for gene delivery in cultured cells and in animals. From more than 300 polysaccharide-oligoamine derivatives tested, only dextran-spermine (D-SPM) was found to be highly effective in gene transfection, both in vitro and in vivo. This protocol describes the synthesis of cationic polysaccharides and their use for DNA transfection in vitro.
Organ Culture and Immunostaining of Mouse Embryonic Kidneys
Authors: Barak Hila , Boyle Scott C.
Published: January 2011

INTRODUCTION

The study of organogenesis in mammals allows investigation of a wide variety of basic cell biological processes in the context of the intact organ. This has become especially important in the age of genetics, as the consequences of gene deletion or mutation in the mouse can be directly linked to human congenital abnormalities. The ability to culture some organs ex vivo during development has emerged as an important tool to understand how tissues are constructed and the signaling pathways that regulate these processes. It has been especially useful in organs that grow via branching morphogenic mechanisms, such as the lung and kidney. Here we demonstrate isolation, ex vivo growth, and fluorescent immunostaining of mouse embryonic day 12.5 (E12.5) kidneys. To demonstrate nephron formation using live imaging, we have isolated and cultured kidneys from mice carrying a green fluorescent protein (GFP) transgene driven by the Hes1 promoter, which is expressed early in the developing nephron. We also provide a protocol for robust imaging of multiple kidney structures in the whole-mount setting. These techniques serve as a basic platform for the analysis of branching morphogenesis and nephron formation in genetic mouse models or in response to exogenous factors, such as agonists or inhibitors, which can be directly added to the culture medium.
Reversion-Reporter Transgenes to Analyze All Six Base-Substitution Pathways in Arabidopsis
Authors: Bollmann Stephanie R. , Tominey Colin M. , Hoffman Peter D. , Hoffman Taylor M.C. , Hays John B.
Published: January 2011

To expand the repertoire of Arabidopsis (Arabidopsis thaliana) mutation-reporter transgenes, we constructed six mutant alleles in the same codon of the β-glucuronidase-encoding GUS transgene. Each allele reverts to GUS  + only via a particular one of the six transition/transversion pathways. AcV5 epitope tags, fused carboxyl terminal to the inactive GUS– proteins, enabled semiquantitative immunoassays in plant protein extracts. Spontaneous G:C→T:A transversions, previously not measured using reporter transgenes, were quite frequent. This may reflect mispairing of adenine with 8-oxoguanine in DNA attacked by endogenous oxyradicals. Spontaneous G:C→A:T was modest and other reversions were relatively low, as reported previously. Frequencies of ultraviolet C-induced TT→TC and TC→TT reversions were both high. With increased transgene copy number, spontaneous G:C→T:A reversions increased but ultraviolet C-induced reversions decreased. Frequencies of some reversion events were reduced among T4 versus T3 generation plants. Based on these and other analyses of sources of experimental variation, we propose guidelines for the employment of these lines to study genotoxic stress in planta.
Loss-of-Function Mutation of REDUCED WALL ACETYLATION2 in Arabidopsis Leads to Reduced Cell Wall Acetylation and Increased Resistance to Botrytis cinerea
Authors: Manabe Yuzuki , Nafisi Majse , Verhertbruggen Yves , Orfila Caroline , Gille Sascha , Rautengarten Carsten , Cherk Candice , Marcus Susan E. , Somerville Shauna , Pauly Markus , Knox J. Paul , Sakuragi Yumiko , Scheller Henrik Vibe
Published: January 2011

Nearly all polysaccharides in plant cell walls are O-acetylated, including the various pectic polysaccharides and the hemicelluloses xylan, mannan, and xyloglucan. However, the enzymes involved in the polysaccharide acetylation have not been identified. While the role of polysaccharide acetylation in vivo is unclear, it is known to reduce biofuel yield from lignocellulosic biomass by the inhibition of microorganisms used for fermentation. We have analyzed four Arabidopsis (Arabidopsis thaliana) homologs of the protein Cas1p known to be involved in polysaccharide O-acetylation in Cryptococcus neoformans. Loss-of-function mutants in one of the genes, designated REDUCED WALL ACETYLATION2 (RWA2), had decreased levels of acetylated cell wall polymers. Cell wall material isolated from mutant leaves and treated with alkali released about 20% lower amounts of acetic acid when compared with the wild type. The same level of acetate deficiency was found in several pectic polymers and in xyloglucan. Thus, the rwa2 mutations affect different polymers to the same extent. There were no obvious morphological or growth differences observed between the wild type and rwa2 mutants. However, both alleles of rwa2 displayed increased tolerance toward the necrotrophic fungal pathogen Botrytis cinerea.
Genetic evidence for a single stock of the deep‐sea teleost Beryx decadactylus in the North Atlantic Ocean as inferred from mtDNA control region analysis
Authors: Friess C. , Sedberry G. R.
Published: January 2011

Mitochondrial control region sequences of 141 alfonsino Beryx decadactylus sampled off the coast of South Carolina were compared with 164 sequences from B. decadactylus collected in the Azores for inferring population structure and demographic history of this deep‐water teleost in the North Atlantic Ocean. Analysis of molecular variance showed that 100% of the genetic variation was found within populations, indicating an absence of population structure (ΦST = −0· 003). Neutrality tests and mismatch distribution analyses of pooled sequences suggested that B. decadactylus in the North Atlantic Ocean have undergone population expansion. These results may indicate that transatlantic gene flow occurs, possibly through passive drift of larvae or adult migration. The potential of a shared stock between the eastern and western North Atlantic Ocean will need to be considered if a directed fishery for B. decadactylus were to develop in the U.S.A.
Exploring the effect of microsatellite size homoplasy on reconstruction of phylogenetic relationships of picote splitfin Zoogoneticus quitzeoensis
Authors: Boto L. , Domínguez‐Domínguez O. , Doadrio I.
Published: January 2011

This study explores the effects of microsatellite size homoplasies on the reconstruction of phylogenetic relationships and estimates of population parameters as the fixation index (FST) using as a case study a truncated microsatellite from the picote splitfin Zoogoneticus quitzeoensis. The results suggest that the use of imperfect microsatellites may have only a minor effect in phylogenetic and population studies.
Does river of origin influence the early marine migratory performance of Salmo salar?
Authors: Plantalech manel‐la N. , Chittenden C. M. , ØKland F. , Thorstad E. B. , Davidsen J. G. , Sivertsgård R. , McKinley R. S. , Finstad B.
Published: January 2011

The early marine migratory behaviour of two populations of hatchery‐reared Atlantic salmon Salmo salar was compared in a common‐garden experiment. Post‐smolts from a river in a long fjord (Lærdal River, 144 km from the open coastline, n = 79) and a short fjord (Flekke River, 20 km from the open coastline, n = 80) in western Norway were tagged with acoustic transmitters and released during the spring of 2005 and 2006 in the inner part of the Hardangerfjord system (Opo River mouth, 179 km from the open coastline). The migratory behaviour of the tagged fish was monitored by acoustic listening stations in the fjord system up to 167 km from the release site. The Lærdal fish began migrating before the Flekke fish and had higher progression rates in the middle part of the fjord system. A greater number of Lærdal fish was detected along the most direct migratory route and in the outermost part of the Hardangerfjord system, which is indicative of a higher survival. The results from this study demonstrate differences in early marine migratory behaviour between S. salar from two different stocks and suggest that the distance a S. salar population travels to reach the open coastline may influence its early marine migratory behaviour and performance. The selective pressures of marine predation and arrival time at feeding areas in the ocean may be stronger for stocks with a longer inshore migration, creating more efficient migrants over time.
Loss of RUNX3 expression by histone deacetylation is associated with biliary tract carcinogenesis
Authors: Shio Seiji , Kodama Yuzo , Ida Hiroshi , Shiokawa Masahiro , Kitamura Koji , Hatano Etsuro , Uemoto Shinji , Chiba Tsutomu
Published: January 2011

RUNX3 is a candidate tumor suppressor gene localized in 1p36, a region frequently inactivated through hypermethylation, histone modulation, and other processes in various human tumors. In this study, to elucidate a causal link between RUNX3 expression and biliary tract cancer, we investigated 17 human biliary cancer specimens. In addition, to examine roles of RUNX3 in biliary tract cancer, we restored silenced RUNX3 in the human biliary cancer cell line Mz‐ChA‐2 using a histone deacetylase inhibitor. Thirteen of 17 human cancer specimens exhibited suppressed RUNX3 expression compared with normal biliary ducts. Moreover, the decreased RUNX3 expression was related to a lower accumulation of acetylated histone H3 associated with RUNX3. In in vitro experiments, vorinostat, a member of a new class of highly potent histone deacetylase inhibitors, restored RUNX3 expression in Mz‐ChA‐2 cells. Furthermore, vorinostat‐induced RUNX3 significantly enhanced p21 expression and growth inhibition of Mz‐ChA‐2 cells through restoration of TGF‐β signaling. These data suggest the significance of histone deacetylation‐associated suppression of RUNX3 expression in biliary tract carcinogenesis. Furthermore, vorinostat might hold promise for treating biliary tract cancer through enhancement of TGF‐β signaling by restoration of RUNX3. (Cancer Sci 2011; 102: 776–783)
Increased c‐Myc activity and DNA damage in hematopoietic progenitors precede myeloproliferative disease in Spa‐1‐deficiency
Authors: Tanaka Hiroki , Tamura Akitoshi , Sekai Miho , Hamazaki Yoko , Minato Nagahiro
Published: January 2011

Mice deficient for Spa‐1 encoding Rap GTPase‐activating protein develop myeloproliferative disorder (MPD) of late onset with frequent blast crises. The mechanisms for MPD development as well as the reasons for long latency, however, remain elusive. We demonstrate here that preleukemic, disease‐free Spa‐1−/− mice show reduced steady‐state hematopoiesis and attenuated resistance to whole body γ‐ray irradiation, which are attributable to the sustained p53 response in hematopoietic progenitor cells (HPCs). Preleukemic Spa‐1−/− HPCs show c‐Myc overexpression with increased p19Arf as well as enhanced γH2AX expression with activation of Atm/Chk pathway. We also show that deregulated Rap signaling in the absence of Spa‐1 enhances post‐transcriptional c‐Myc stability and induces DNA damage in a p38MAPK‐dependent manner, leading to p53 activation. Genetic studies indicate that the introduction of p53+/− and p53−/− mutations in Spa‐1−/− mice results in the acceleration of typical MPD and rapid development of blastic leukemia, respectively. These results suggest that increased c‐Myc expression and DNA damage in HPCs precede MPD development in Spa‐1−/− mice, and the resulting p53 response functions as a barrier for the onset of MPD and blast crises progression. (Cancer Sci 2011; 102: 784–791)
Fbxw7β resides in the endoplasmic reticulum membrane and protects cells from oxidative stress
Authors: Matsumoto Akinobu , Tateishi Yuki , Onoyama Ichiro , Okita Yasutaka , Nakayama Keiko , Nakayama Keiichi I.
Published: January 2011

Oxidative stress has been implicated in cancer initiation and progression. Fbxw7 (also known as Fbw7, SEL‐10, hCdc4, or hAgo) is the F‐box protein subunit of an Skp1–Cul1–F‐box (SCF)‐type ubiquitin ligase complex that plays a central role in the degradation of oncoproteins such as c‐Myc, c‐Jun, Notch, and cyclin E. Fbxw7 is therefore thought to function as a tumor suppressor, and indeed the Fbxw7 gene is frequently mutated in many human malignancies. The Fbxw7 gene locus encodes three protein isoforms: Fbxw7α, Fbxw7β, and Fbxw7γ. Whereas Fbxw7α and Fbxw7γ are resident in the nucleus, Fbxw7β shows a cytoplasmic distribution suggestive of localization to the endoplasmic reticulum (ER). The specific function of Fbxw7β has remained unknown, however. We now show that Fbxw7β contains a putative transmembrane domain near its NH2‐terminus, and topological analysis revealed that Fbxw7β is inserted in the ER membrane. Fbxw7β assembled with Skp1, Cul1, and Rbx1 to form an SCF complex, although the efficiency of this process appeared lower than that for Fbxw7α or Fbxw7γ. To explore the physiological role of Fbxw7β, we generated mice specifically lacking this isoform of Fbxw7. Although these animals did not exhibit any apparent abnormalities in development, primary cultures of neurons prepared from the mutant mice were more vulnerable to oxidative stress than were those prepared from wild‐type mice. Conversely, overexpression of Fbxw7β rendered cells resistant to oxidative stress, without affecting sensitivity to ER stress or other apoptosis‐inducing agents. Our results thus suggest that Fbxw7β contributes to the protection of cells from oxidative stress. (Cancer Sci 2011; 102: 749–755)
Clinical presentation, evolution, and prognosis of precursor B‐cell lymphoblastic lymphoma in trials LMT96, EORTC 58881, and EORTC 58951
Authors: Ducassou Stéphane , Ferlay Céline , Bergeron Christophe , Girard Sandrine , Laureys Geneviève , Pacquement Hélène , Plantaz Dominique , Lutz Patrick , Vannier Jean‐Pierre , Uyttebroeck Anna , Bertrand Yves
Published: January 2011

In children, lymphoblastic lymphomas represent 30% of Non‐Hodgkin lymphomas (NHL), and approximately 15% are precursor B‐cell lymphomas (PBLL). Our study evaluated their main clinical characteristics, evolution, and prognosis in three trials. From 1989 to 2008, 53 children with PBLL (median age 7·75 years) were included in three protocols: Malignant Lymphoma Therapy (LMT) 96, European Organization for Research and Treatment of Cancer (EORTC) 58881, and EORTC 58951 using Berlin‐Frankfürt‐Münster‐derived acute lymphoblastic leukaemia (ALL) therapy. There were 10 stage I disease, 9 stage II, 9 stage III and 25 stage IV. Clinical presentation was heterogeneous with a majority of bone lesions and cutaneous or subcutaneous manifestations. At diagnosis 23 patients had bone marrow involvement, and only three had central nervous system involvement. The median follow‐up was 74 months. At last follow‐up, 45 patients were in continuous complete remission, whereas eight had progressed or had relapsed (7 Stages IV and 1 Stage III) and died. Two patients had a secondary neoplasia, and are still alive. Disease stage was a major prognostic factor, with better overall survival (OS) and event‐free survival (EFS) (P < 0·05) rates observed in patients with Stage I to III as compared to those with Stage IV. Treatment with protocols derived from ALL therapy are efficient with an 82% EFS and an 85% OS at 5 years.
Improving the quality of general surgical operation notes in accordance with the Royal College of Surgeons guidelines: a prospective completed audit loop study
Authors: Singh Rahul , Chauhan Robert , Anwar Suhail
Published: January 2011

Aims and objectives  Accurate documentation of surgical operation notes is crucial as it facilitates the post‐operative management of the patients. It also serves as an important medico‐legal document for any discrepancies or disputes. The objectives of this study were twofold: to compare operation note documentation against guidelines published in Good Surgical Practice by the Royal College of Surgeons of England (RCS Eng), 2008, and to improve adherence to these guidelines, through educating surgeons and the introduction of theatre aide‐memoires.

Method  We prospectively identified 100 general surgical patients operated between February 2010 and July 2010. Equal numbers of upper gastroenterology, colorectal and vascular patients were selected. We audited operation note documentation against the RCS Eng guidelines. Our findings were presented at the trust clinical governance meeting. Areas with deficient documentation were highlighted. In addition to educating surgeons, aide‐memoires were subsequently introduced in the operating theatres and our practice was re‐audited.

Results  A total of 18 RCS Eng guidelines were identified and audited. The first audit cycle revealed poor areas in documentation of ‘emergency/elective procedure’ (36%), ‘time of operation’ (36%), ‘date of operation’ (87%), ‘assistant’ (87%) and ‘post‐operative management’ (88%). After educating surgeons and introducing aide‐memoires in theatres, the results were re‐audited with an equal number of patients. The re‐audit demonstrated a clear improvement in four out of five deficient areas with compliance reaching almost up to 100%.

Conclusion  Operation note documentation is of paramount importance, it has medical and legal implications. Educating surgeons and providing aide‐memoires in theatres clearly improved documentation of operation notes in compliance with the RCS Eng guidelines.
How to improve specific databases for clinical data in rare diseases? The example of hereditary haemorrhagic telangiectasia
Authors: Decullier Evelyne , Dupuis‐Girod Sophie , Plauchu Henri , Perret Jacques , Chapuis François
Published: January 2011

Introduction  The objectives of reference centres for rare diseases are multiple and mainly concern disease management and coordination between specialties, but they also have to improve knowledge through epidemiological studies and biomedical research. A first database was created by the hereditary haemorrhagic telangiectasia network to achieve these objectives, but facing a lack of data entered in the first database, we established a new database, named CIROCO (Clinical Investigation for the Rendu‐Osler Cohort). This new database was constructed after the first database assessment.

Methods  We listed all difficulties encountered in the first database. We focused on three themes: database technical characteristics, database design (the number and characteristics of variables and the overall structure) and data entry. Based on this expertise, we defined the characteristics that should lead to an optimization of the database. We then compared the performance of these databases in terms of available data.

Results  The first database had 1273 fields spread out on 14 forms. A total of 838 patients was entered from 2001 to 2005 and among the 1273 fields, 205 (16%) had no data at all. The new database gathered 362 fields from the first database and 173 new fields. These fields were rearranged into 443 variables. A total of 1410 patients directly seen by the clinicians were entered. For patients seen by clinicians each variable used for defining the disease was available for at least 93% of patients.

Conclusion  Items to be included in a specific database should be carefully selected in order to achieve good results and an epidemiological utility.
Behavioural and emotional problems in people with severe and profound intellectual disability
Authors: Forster S. , Gray K. M. , Taffe J. , Einfeld S. L. , Tonge B. J.
Published: January 2011

Background  People with severe and profound levels of intellectual disability (ID) are frequently examined as a single group in research. However, these two groups may be significantly different, particularly in the area of emotional and behavioural difficulties.

Method  The Developmental Behaviour Checklist (DBC) was completed by parents and caregivers of 107 people with severe ID and 22 people with profound ID at four time periods across 12 years. Regression analyses were used to examine trends in sub‐scale scores across time and groups.

Results  Significant differences between the groups of people with severe and profound ID were found. People with profound ID had significantly lower scores across all sub‐scales except Social Relating. This was usually related to fewer items being selected as present for people with profound ID, as opposed to the scores being attributable to lower item severity scores.

Conclusions  There are significant differences between groups of people with severe and profound ID in scores on the DBC, indicating differences in behavioural and emotional problems. Caution should be exercised by researchers treating these two disparate groups as a single group, and by practitioners translating such findings into practice.
Hepatitis C infection among recent initiates to injecting in England 2000–2008: Is a national hepatitis C action plan making a difference?
Authors: Hope V. , Parry J. V. , Marongui A. , Ncube F.
Published: January 2011

Summary.  Around 80% of hepatitis C virus (HCV) infections in England are among injecting drug users (IDUs). The HCV Action Plan launched in 2004 includes targets to reduce HCV prevalence in recent initiates (those starting injecting in the preceding 3 years), and to increase HCV voluntary confidential testing (VCT). The Action Plan’s impact is examined using surveillance data from recent initiates participating in an annual survey of IDUs in contact with specialist services across England, 2000–2008. Participants provided an oral fluid sample (tested for anti‐HCV) and completed a short questionnaire (including HCV VCT and result of last test). Overall, anti‐HCV prevalence among the recent initiates was 18% (619/3463); in 2004, it was 20% (59/291), other than being lower in 2000 [11%, 73/672, adjusted odds ratio (AOR) = 0.63 95%CI 0.42–0.93] there was no change over time. Prevalence increased with age; was higher among those ever imprisoned, using a needle exchange, and having a HCV VCT; and varied by region. Overall, 42% (1460) had ever had a HCV VCT; in 2004 uptake was 45% (130/291) having increased from 26% (175/672, AOR = 0.57 95%CI 0.42–0.77) in 2000, and it rose to 62% (197/320, AOR = 2.12 95%CI 1.50–2.99) in 2008. The proportion of anti‐HCV‐positive IDUs aware of their infection was higher in 2006–2008 than in earlier years. The HCV Action Plan has probably helped increase recent initiates’ uptake of HCV VCT and the proportion of those diagnosed with HCV infection. However, its impact on HCV transmission is unclear. There is a need to reinvigorate, and improve coverage of, interventions to prevent HCV transmission.
Increase of weakly acidic gas esophagopharyngeal reflux (EPR) and swallowing‐induced acidic/weakly acidic EPR in patients with chronic cough responding to proton pump inhibitors
Authors: Kawamura O. , Shimoyama Y. , Hosaka H. , Kuribayashi S. , Maeda M. , Nagoshi A. , Zai H. , Kusano M.
Published: January 2011

Background  Gastro‐esophageal reflux disease (GERD)‐related chronic cough (CC) may have multifactorial causes. To clarify the characteristics of esophagopharyngeal reflux (EPR) events in CC patients whose cough was apparently influenced by gastro‐esophageal reflux (GER), we studied patients with CC clearly responding to full‐dose proton pump inhibitor (PPI) therapy (CC patients).

Methods  Ten CC patients, 10 GERD patients, and 10 healthy controls underwent 24‐h ambulatory pharyngo‐esophageal impedance and pH monitoring. Weakly acidic reflux was defined as a decrease of pH by >1 unit with a nadir pH >4. In six CC patients, monitoring was repeated after 8 weeks of PPI therapy. The number of each EPR event and the symptom association probability (SAP) were calculated. Symptoms were evaluated by a validated GERD symptom questionnaire.

Key Results  Weakly acidic gas EPR and swallowing‐induced acidic/weakly acidic EPR only occurred in CC patients, and the numbers of such events was significantly higher in the CC group than in the other two groups (P < 0.05, respectively). Symptom association probability analysis revealed a positive association between GER and cough in three CC patients. Proton pump inhibitor therapy abolished swallowing‐induced acidic/weakly acidic EPR, reduced weakly acidic gas EPR, and improved symptoms (all P < 0.05).

Conclusions & Inferences  Most patients with CC responding to PPI therapy had weakly acidic gas EPR and swallowing‐induced acidic/weakly acidic EPR. A direct effect of acidic mist or liquid refluxing into the pharynx may contribute to chronic cough, while cough may also arise indirectly from reflux via a vago‐vagal reflex in some patients.
Intimate Adherence by Enteropathogenic Escherichia coli Modulates TLR5 Localization and Proinflammatory Host Response in Intestinal Epithelial Cells
Authors: Salazar‐Gonzalez H. , Navarro‐Garcia F.
Published: January 2011

Enteropathogenic Escherichia coli (EPEC) causes diarrhoeal disease by altering enterocyte physiology and producing mucosal inflammation. Many details concerning the host response against EPEC remain unknown. We evaluated the role of EPEC virulence factors on the inflammatory response through an analysis of bacterial recognition, cell signalling, and cytokine production using an in vitro epithelial cell infection model. Interestingly, we found that EPEC infection recruits Toll‐like receptor 5 (TLR5) to the cell surface. We confirmed that type 3 secretion system (T3SS) and flagellin (FliC) are necessary for efficient extracellular regulated kinases 1 and 2 (ERK1/2) activation and found that intimin could down‐regulate this pathway. Besides flagellin, intimin was required to keep nuclear factor kappa B (NF‐κB) activated during infection. EPEC infection activated tumour necrosis factor alpha (TNF‐α) production and induced interleukin (IL)‐1β and IL‐8 release. Virulence factors such as intimin, T3SS, EspA and fliC were required for IL‐1β secretion, whereas intimin and T3SS participated in IL‐8 release. Flagellin was essential for late secretion of TNF‐α and IL‐8 and intimin stimulated cytokine secretion. Initial adherence limited TNF‐α release, whereas late attachment sustained TNF‐α secretion. We conclude that intimin modulates TLR5 activation and intimate adherence alters the proinflammatory response.