bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene limiting cadmium accumulation in rice
Authors: Ueno Daisei , Yamaji Naoki , Kono Izumi , Huang Chao Feng , Ando Tsuyu , Yano Masahiro , Ma Jian Feng
Published: September 2010

Intake of toxic cadmium (Cd) from rice caused Itai-itai disease in the past and it is still a threat for human health. Therefore, control of the accumulation of Cd from soil is an important food-safety issue, but the molecular mechanism for the control is unknown. Herein, we report a gene (
OsHMA3
) responsible for low Cd accumulation in rice that was isolated from a mapping population derived from a cross between a high and low Cd-accumulating cultivar. The gene encodes a transporter belonging to the P
1B
-type ATPase family, but shares low similarity with other members. Heterologous expression in yeast showed that the transporter from the low-Cd cultivar is functional, but the transporter from the high-Cd cultivar had lost its function, probably because of the single amino acid mutation. The transporter is mainly expressed in the tonoplast of root cells at a similar level in both the low and high Cd-accumulating cultivars. Overexpression of the functional gene from the low Cd-accumulating cultivar selectively decreased accumulation of Cd, but not other micronutrients in the grain. Our results indicated that OsHMA3 from the low Cd-accumulating cultivar limits translocation of Cd from the roots to the above-ground tissues by selectively sequestrating Cd into the root vacuoles.
Climate not to blame for African civil wars
Authors: Buhaug Halvard
Published: September 2010

Vocal actors within policy and practice contend that environmental variability and shocks, such as drought and prolonged heat waves, drive civil wars in Africa. Recently, a widely publicized scientific article appears to substantiate this claim. This paper investigates the empirical foundation for the claimed relationship in detail. Using a host of different model specifications and alternative measures of drought, heat, and civil war, the paper concludes that climate variability is a poor predictor of armed conflict. Instead, African civil wars can be explained by generic structural and contextual conditions: prevalent ethno-political exclusion, poor national economy, and the collapse of the Cold War system.
In vivo pair correlation analysis of EGFP intranuclear diffusion reveals DNA-dependent molecular flow
Authors: Hinde Elizabeth , Cardarelli Francesco , Digman Michelle A. , Gratton Enrico
Published: September 2010

No methods proposed thus far have the capability to measure overall molecular flow in the nucleus of living cells. Here, we apply the pair correlation function analysis (pCF) to measure molecular anisotropic diffusion in the interphase nucleus of live cells. In the pCF method, we cross-correlate fluctuations at several distances and locations within the nucleus, enabling us to define migration paths and barriers to diffusion. We use monomeric EGFP as a prototypical inert molecule and measure flow in and between different nuclear environments. Our results suggest that there are two disconnect molecular flows throughout the nucleus associated with high and low DNA density regions. We show that different density regions of DNA form a networked channel that allows EGFP to diffuse freely throughout, however with restricted ability to traverse the channel. We also observe rare and sudden bursts of molecules traveling across DNA density regions with characteristic time of ≈300 ms, suggesting intrinsic localized change in chromatin structure. This is a unique in vivo demonstration of the intricate chromatin network showing channel directed diffusion of an inert molecule with high spatial and temporal resolution.
Rigid amphipathic fusion inhibitors, small molecule antiviral compounds against enveloped viruses
Authors: St.Vincent Mireille R. , Colpitts Che C. , Ustinov Alexey V. , Muqadas Muhammad , Joyce Michael A. , Barsby Nicola L. , Epand Raquel F. , Epand Richard M. , Khramyshev Stanislav A. , Valueva Olga A. , Korshun Vladimir A. , Tyrrell D. Lorne J. , Schang Luis M.
Published: September 2010

Antiviral drugs targeting viral proteins often result in prompt selection for resistance. Moreover, the number of viral targets is limited. Novel antiviral targets are therefore needed. The unique characteristics of fusion between virion envelopes and cell membranes may provide such targets. Like all fusing bilayers, viral envelopes locally adopt hourglass-shaped stalks during the initial stages of fusion, a process that requires local negative membrane curvature. Unlike cellular vesicles, however, viral envelopes do not redistribute lipids between leaflets, can only use the energy released by virion proteins, and fuse to the extracellular leaflets of cell membranes. Enrichment in phospholipids with hydrophilic heads larger than their hydrophobic tails in the convex outer leaflet of vesicles favors positive curvature, therefore increasing the activation energy barrier for fusion. Such phospholipids can increase the activation barrier beyond the energy provided by virion proteins, thereby inhibiting viral fusion. However, phospholipids are not pharmacologically useful. We show here that a family of synthetic rigid amphiphiles of shape similar to such phospholipids, RAFIs (rigid amphipathic fusion inhibitors), inhibit the infectivity of several otherwise unrelated enveloped viruses, including hepatitis C and HSV-1 and -2 (lowest apparent IC
50
48 nM), with no cytotoxic or cytostatic effects (selectivity index > 3,000) by inhibiting the increased negative curvature required for the initial stages of fusion.
Viral terminal protein directs early organization of phage DNA replication at the bacterial nucleoid
Authors: Muñoz-Espín Daniel , Holguera Isabel , Ballesteros-Plaza David , Carballido-López Rut , Salas Margarita
Published: September 2010

The mechanism leading to protein-primed DNA replication has been studied extensively in vitro. However, little is known about the in vivo organization of the proteins involved in this fundamental process. Here we show that the terminal proteins (TPs) of phages ϕ29 and PRD1, infecting the distantly related bacteria
Bacillus subtilis
and
Escherichia coli
, respectively, associate with the host bacterial nucleoid independently of other viral-encoded proteins. Analyses of phage ϕ29 revealed that the TP N-terminal domain (residues 1–73) possesses sequence-independent DNA-binding capacity and is responsible for its nucleoid association. Importantly, we show that in the absence of the TP N-terminal domain the efficiency of ϕ29 DNA replication is severely affected. Moreover, the TP recruits the phage DNA polymerase to the bacterial nucleoid, and both proteins later are redistributed to enlarged helix-like structures in an MreB cytoskeleton-dependent way. These data disclose a key function for the TP in vivo: organizing the early viral DNA replication machinery at the cell nucleoid.
Scaling expectations for the time to establishment of complex adaptations
Authors: Lynch Michael
Published: September 2010

Although the vast majority of research in evolutionary biology is focused on adaption, a general theory for the population-genetic mechanisms by which complex adaptations are acquired remains to be developed. The issue explored here is the procurement of novel traits that specifically require multiple mutations to achieve a fitness advantage. By highlighting the roles played by the forces of mutation, recombination, and random genetic drift, and drawing from observations on the joint constraints on these factors, the ways in which rates of acquisition of specific types of adaptations scale with population size are explored. These general results provide insight into a number of ongoing controversies regarding the molecular basis of adaptation, including the adaptive utility of recombination and the role of drift in the passage through adaptive valleys.
High income improves evaluation of life but not emotional well-being
Authors: Kahneman Daniel , Deaton Angus
Published: September 2010

Recent research has begun to distinguish two aspects of subjective well-being. Emotional well-being refers to the emotional quality of an individual's everyday experience—the frequency and intensity of experiences of joy, stress, sadness, anger, and affection that make one's life pleasant or unpleasant. Life evaluation refers to the thoughts that people have about their life when they think about it. We raise the question of whether money buys happiness, separately for these two aspects of well-being. We report an analysis of more than 450,000 responses to the Gallup-Healthways Well-Being Index, a daily survey of 1,000 US residents conducted by the Gallup Organization. We find that emotional well-being (measured by questions about emotional experiences yesterday) and life evaluation (measured by Cantril's Self-Anchoring Scale) have different correlates. Income and education are more closely related to life evaluation, but health, care giving, loneliness, and smoking are relatively stronger predictors of daily emotions. When plotted against log income, life evaluation rises steadily. Emotional well-being also rises with log income, but there is no further progress beyond an annual income of ~$75,000. Low income exacerbates the emotional pain associated with such misfortunes as divorce, ill health, and being alone. We conclude that high income buys life satisfaction but not happiness, and that low income is associated both with low life evaluation and low emotional well-being.
Photoelastic Measurements of Polymer Insert Stress in the Knee Prostheses Designed for High/Deep Flexion
Authors: Lawi A. , Takiguchi J. , Hasegawa M. , Hirokawa S. , Todo M. , Hotokebuchi T.
Published: September 2010

This paper presents the experimental results of photoelasticity for determining the magnitude and distribution of stresses on the polyethylene insert of the knee prostheses designed for high/deep knee flexion. The prostheses used in our experiment were a conventional posterior stabiliser knee, Scorpio NRG (Non‐Restricted Geometry, Stryker Co., USA) and CFK (Complete Flexion Knee, Japan Medical Material Co., Japan), which we have developed to enable the patient to make a complete knee flexion (i.e. seiza in Japanese). Prior to the photoelastic experiment, we had introduced the forces exerted on the knee joint during ascending from deep knee flexion. Here we took squatting as an example of deep knee flexion instead of seiza because ascending from seiza contains complex modalities. The introduced data in terms of knee angles and joint forces were applied to the photoelastic models. The results demonstrated that after the knee angle became larger than 90°, the shear stresses on the post and cam of NRG were higher than those on the ball and socket of CFK. We conclude that the design and the configuration of CFK is acceptable at deep knee flexion from a load‐bearing viewpoint.
Influence of Force and Torque Feedback on Operator Performance in a VR‐Based Suturing Task
Authors: Santos-Carreras L. , Beira R. , Sengül A. , Gassert R. , Bleuler H.
Published: September 2010

The introduction of Minimally Invasive Surgery (MIS) has revolutionised surgical care, considerably improving the quality of many surgical procedures. Technological advances, particularly in robotic surgery systems, have reduced the complexity of such an approach, paving the way for even less invasive surgical trends. However, the fact that haptic feedback has been progressively lost through this transition is an issue that to date has not been solved. Whereas traditional open surgery provides full haptic feedback, the introduction of MIS has eliminated the possibility of direct palpation and tactile exploration. Nevertheless, these procedures still provide a certain amount of force feedback through the rigid laparoscopic tool. Many of the current telemanipulated robotic surgical systems in return do not provide full haptic feedback, which to a certain extent can be explained by the requirement of force sensors integrated into the tools of the slave robot and actuators in the surgeon’s master console. In view of the increased complexity and cost, the benefit of haptic feedback is open to dispute. Nevertheless, studies have shown the importance of haptic feedback, especially when visual feedback is unreliable or absent. In order to explore the importance of haptic feedback for the surgeon’s master console of a novel teleoperated robotic surgical system, we have identified a typical surgical task where performance could potentially be improved by haptic feedback, and investigate performance with and without this feedback. Two rounds of experiments are performed with 10 subjects, six of them with a medical background. Results show that feedback conditions, including force feedback, significantly improve task performance independently of the operator’s suturing experience. There is, however, no further significant improvement when torque feedback is added. Consequently, it is deduced that force feedback in translations improves subject’s dexterity, while torque feedback might not further benefit such a task.
Effects of Penning ionization on the discharge patterns of atmospheric pressure plasma jets
Authors: Li Qing , Zhu Wen-Chao , Zhu Xi-Ming , Pu Yi-Kang
Published: September 2010

Atmospheric pressure plasma jets, generated in a coaxial dielectric barrier discharge configuration, have been investigated with different flowing gases. Discharge patterns in different tube regions were compared in the flowing gases of helium, neon and krypton. To explain the difference of these discharge patterns, a theoretical analysis is presented to reveal the possible basic processes. A comparison of experimental and theoretical results identifies that Penning ionization is mainly responsible for the discharge patterns of helium and neon plasma jets.
Stable single-mode distributed feedback quantum cascade laser with surface metal grating
Authors: Zhang W , Wang L J , Zhang J C , Zhang Q D , Li L , Liu J Q , Liu F Q , Wang Z G
Published: September 2010

A design of single-mode distributed feedback quantum cascade lasers (DFB-QCLs) with surface metal grating is described. A rigorous modal expansion theory is adopted to analyse the interaction between the waveguide mode and the surface plasmon wave for different grating parameters. A stable single-mode operation can be obtained in a wide range of grating depths and duty cycles. The single-mode operation of surface metal grating DFB-QCLs at room temperature for λ = 8.5 µm is demonstrated. The device shows a side-mode suppression ratio of above 20 dB. A linear tuning of wavelength with temperature indicates the stable single-mode operation without mode hopping.
Bond characterization by detection and manipulation of particle mobility in an optical evanescent field biosensor
Authors: van Ommering Kim , Koets Marjo , Paesen Rik , van IJzendoorn Leo J , Prins Menno W J
Published: September 2010

We present an optical biosensor technology that integrates the tethered particle motion technique and the magnetic tweezer technique. The goal is to quantify the three-dimensional mobility of bound particle labels and to characterize the bond between the particle and the surface. We show, using a series of four different lengths of dsDNA (105–590 bp), that plots of the height as a function of the in-plane particle position reflect the bond length and bond flexibility. We analyse ensembles of bound particles and show that the height displacement is at maximum the bond length, but that non-specific sticking causes large variations between particles. We also measured the height of bound particles under the influence of magnetic forces. A magnetic gradient force towards the surface brought particles on average closer to the surface, but a magnetic gradient force away from the surface did not bring all particles away from the surface. We show that the latter can be explained by magnetic anisotropy in the particles. Our results demonstrate that mobility detection of bound particle labels in an evanescent field is a promising technique to characterize the bond between a particle and a surface in a biosensor system.
Influence of fleet renewal and trawl development on landings per unit effort of the Danish northern shrimp (Pandalus borealis) fishery
Authors: Eigaard Ole Ritzau , Munch-Petersen Sten
Published: September 2010

Eigaard, O. R., and Munch-Petersen, S. 2011. Influence of fleet renewal and trawl development on landings per unit effort of the Danish northern shrimp (Pandalus borealis) fishery. – ICES Journal of Marine Science, 68: 26–31. Recent stock assessments of the Pandalus stock in the Skagerrak (ICES Division IIIa) and the Norwegian Deep (Division IVa east) have relied largely on a time-series of landings per unit effort (lpue) calculated from Danish logbook data. Because of fleet renewal and trawl-size changes, the relationship between nominal effort data as recorded in logbooks (days fishing) and effective effort is likely to have changed, so to standardize the nominal lpue time-series, trawl-size development has been taken into account using generalized linear modelling. As logbooks do not provide trawl-size information, this standardization was made possible by retrieving technical trawl and vessel data from industry order books. These data demonstrated an approximately linear relationship between vessel engine power and Pandalus trawl size, so validated the use of vessel horsepower from the logbooks as a proxy for an unknown trawl size. Standardized lpue time-series for the past 20 years indicated a lesser increase in stock size than nominal lpue, the modelling results demonstrating that vessel lpue increased by 9.5% with each 100 hp of engine power.
Runx2 in human breast carcinoma: its potential roles in cancer progression
Authors: Onodera Yoshiaki , Miki Yasuhiro , Suzuki Takashi , Takagi Kiyoshi , Akahira Jun‐ichi , Sakyu Takuya , Watanabe Mika , Inoue Satoshi , Ishida Takanori , Ohuchi Noriaki , Sasano Hironobu
Published: September 2010

Runx2 has been proposed as one of the pivotal factors in the process of osteogenesis and metastasis in human malignancies including breast cancer, but its details have not been evaluated. Therefore, in this study, we evaluated its expression in human breast cancer using immunohistochemistry. One hundred and thirty‐seven formalin‐fixed and paraffin‐embedded breast cancer specimens were used in this analysis of immunohistochemical study. Immunoreactivity was evaluated using the labeling index (LI). Runx2 immunoreactivity was detected in both carcinoma and stromal cells, as well as non‐pathological ductal cells. The nuclear LI of Runx2 in carcinoma cells was associated with the clinical stage, histological grade and HER2 status of the patients examined. In addition, among the patients not associated with distant metastasis, those with high Runx2 LI demonstrated a significantly worse clinical outcome than those with a low LI. This was more pronounced in the group of estrogen receptor (ER)‐negative cases. In addition, both univariate and multivariate analyses demonstrated that the Runx2 LI in breast carcinoma cells turned out an independent prognostic factor. Results of our present study demonstrated that Runx2 plays very important roles in the progression of breast cancer, especially in those of ER‐negative cases. (Cancer Sci 2010; 101: 2670–2675)
The limits of endoscopy in the diagnosis of oesophagitis, gastritis and duodenitis
Authors: WILKINSON S. P.
Published: September 2010

Endoscopy alone, without histology, has poor sensitivity and specificity for diagnosing diffuse mucosal diseases of the oesophagus, stomach and duodenum. Erosive lesions with exudate at the distal end of the oesophagus are a reliable sign of oesophagitis, but are present in only approximately 50% of patients with gastro‐oesophageal reflux. Erythema and friability are unreliable are subject to considerable inter‐observer variation. Numerous macroscopic abnormalities of the gastric and duodenal mucosa have been identified, but these show no consistent histological pattern.
Disturbed upper gastrointestinal sensation: an important abnormality?
Authors: MALAGELADA J.‐R.
Published: September 2010

The relationship between disturbed upper gastro‐intestinal motility and symptoms of heartburn and dyspepsia varies. For example, in some symptomatic patients abnormal motor events are not detected, whereas, conversely, impaired motor patterns may be recorded in patients who are asymptomatic. Nociceptive visceral afferents arising in the gut transmit peripheral sensations to the brain. It has been postulated that variations in sensory afferent activity are responsible for the inconsistent expression of disturbed upper gastrointestinal motility. Several studies have demonstrated that patients with so‐called functional symptoms, which appear to arise from normal gut regions, exhibit a lower perception threshold to stimuli that distend the gut. Such visceral hypersensitivity could explain the occurrence of symptoms in the absence of demonstrable physiological or morphological abnormalities. Evidence that variations in visceral sensory afferent activity constitute an important disease mechanism is not conclusive. In certain conditions such as non‐cardiac chest pain and functional dyspepsia, visceral hypersensitivity provides a useful hypothetical framework. Not only has this framework established a basis for previously unexplained symptoms, but perhaps more importantly it has stimulated research to develop novel pharmacological agents to modulate nociception. The challenge is now to establish putative pathogenetic links between aberrant sensory activity and disturbed upper gastrointestinal motility, and also to locate the neural abnormalities along the gut‐brain axis.
New trials of pharmacological therapy for endoscopy‐negative gastro‐oesophageal reflux disease
Authors: KAHRILAS P. J.
Published: September 2010

Gastro‐oesophageal reflux disease describes patients with disease due to gastro‐oesophageal acid reflux regardless of the presence or absence of oesophagitis. In patients with endoscopy‐positive reflux disease, symptoms and complications occur due to reflux in association with clear‐cut oesophagitis, that is, mucosal breaks evident in the distal oesophagus with endoscopy. On the other hand, in patients with endoscopy‐negative reflux disease, symptoms and complications due to reflux occur in the absence of clear‐cut mucosal breaks. Most investigations of reflux disease therapy have focused on endoscopy‐positive disease. This is, at least in part, owing to the relative ease and reproducibility of disease staging; both disease severity and resolution can be endoscopically defined and graded. These studies indicate that erosive oesophagitis is a chronic condition, subject to relapse within 6 months following the cessation of healing therapy in as many as 80% of patients. Both the potency of anti‐secretory therapy required for healing and the certainty of relapse are proportional to the severity of endoscopically‐defined oesophagitis. Few reliable data exist on treatment efficacy in endoscopy‐negative disease because of a paucity of data on its natural history and inconsistency in defining outcome measures. Nonetheless, disease morbidity, with its associated impairment in quality of life, is determined by symptoms of reflux disease, irrespective of the presence or absence of oesophagitis, and symptom control is a prime objective of therapy for reflux disease.
Better definition of endoscopy‐negative acid reflux disease
Authors: RUNE S. J.
Published: September 2010

Endoscopy‐negative acid reflux disease is the term used to define the group of patients experiencing heartburn as the predominant symptom with no visible abnormalities at endoscopy. Such patients are not uncommon, and it is interesting to see what characterizes this disease entity. New data from clinical trials have provided information that gives answers to some very relevant questions, such as: the relationship between endoscopy‐negative heartburn and oesophageal acid exposure; the association between acid exposure and age; gender and body weight index; the association between hiatal hernia and reflux disease; the course of disease during placebo treatment and its association with degree of acid reflux: and, finally, the influence of reflux disease on quality of life.
New information relevant to long‐term management of endoscopy‐negative reflux disease
Authors: LUNDELL L.
Published: September 2010

Despite the fact that the endoscopic appearance of the mucosa is normal in the majority of patients who present with moderate to severe symptoms of acid reflux, valid clinical information on both the natural course of endoscopy‐negative reflux disease and the need for and design of long‐term therapy is still lacking. The aim of this study was to determine the natural course of endoscopy‐negative acid reflux disease over a period of 6 months; to determine whether 10 mg omeprazole once daily is sufficient to control symptoms in patients with symptomatic acid reflux disease, when given either as a strict daily dose or at the discretion of the patient (on‐demand therapy); and to compare the efficacy of 10 and 20 mg omeprazole with that of placebo, in resolving symptoms. A total of 495 patients with endoscopy‐negative acid reflux disease were recruited to compare 10 mg omeprazole daily with placebo, the clinical endpoint being unwillingness to continue in the study due to insufficient symptom control (i.e. heartburn). In a parallel study, 424 patients were randomized, after initial treatment with acid inhibition therapy to maintain symptom control during on‐demand therapy, to 10 or 20 mg omeprazole daily, or placebo. The Psychological General Well‐Being Index was used to compare the quality of life of patients in remission with those suffering a relapse. In the study in which continuous treatment with 10 mg omeprazole daily was compared with placebo, 48% of the patients allocated to placebo were in clinical remission after 6 months compared with 73% of those randomized to omeprazole (P < 0.01). Furthermore, heartburn, the predominant acid reflux symptom, was completely controlled in 80% of omeprazole‐treated patients, compared with 51% of those receiving placebo. In the parallel on‐demand study, 56% of patients allocated to placebo (although consuming significantly more antacids) had adequate symptom control and thus remained in the study for 6 months. In patients receiving either 10 or 20 mg omeprazole daily, 69 and 83%, respectively, experienced adequate symptom control (P = 0.01 and P < 0.01, respectively, compared with placebo). Mean scores on the Psychological General Well‐Being Index of 105.3 ± 2.0 (S.E.M.) were seen in patients in clinical remission, compared with 98.3 ± 2.6 in those experiencing relapse of reflux symptoms (P < 0.05). When studied over a 6‐month period, about half of endoscopy‐negative reflux patients required drug intervention to achieve symptom control. In these patients continuous maintenance therapy with 10 mg omeprazole daily considerably increased the proportion of those experiencing symptom control. Another viable therapeutic strategy in such patients appears to be on‐demand therapy using 20 mg omeprazole.
Review article: Epithelial disposition of antigen
Authors: LAMM M. E.
Published: September 2010

Exogenous antigens can impinge upon the luminal surface of mucous membranes and to a limited degree, can even penetrate into the lamina propria. As a result of infection, microbial antigens can be present in mucosal epithelium or lamina propria. At all three levels (lumen, epithelium, lamina propria), locally produced antibodies, principally immunoglobulin A (IgA), can combine with antigens. As a result, antigens can be prevented from attaching to the epithelium, viruses can be neutralized inside epithelial cells and immune complexes in the lamina propria can be excreted into the lumen. As the Fc portion of IgA is specialized to facilitate epithelial transport of IgA rather than to activate inflammatory mediator systems (as is the case with other classes of immunoglobulin), the predominance of IgA among mucosal antibodies serves to limit the degree of local inflammation following antigen‐antibody reactions.
Review article: Intestinal permeability in Crohn's disease
Authors: MEDDINGS J. B.
Published: September 2010

Measurements of intestinal permeability (IP) may help in determining susceptibility for the development of Crohn's disease or for imminent relapse in patients with the disease. It is now apparent that a subset of patients at high risk for the development of Crohn's disease have either increased baseline IP or an exaggerated response to environmental agents that increase IP. These, coupled with observations that increased IP in patients at risk for the development of Crohn's disease is associated with an abnormal immunological phenotype, lend support to the hypothesis that increased IP is a very early event in the genesis of Crohn's disease.
Review article: Local and systemic regulation of mucosal immunity
Authors: MAYER L.
Published: September 2010

An increased interest in mucosal immunity has stemmed from the identification of novel T‐cell populations and developments in oral vaccines and oral tolerance. The development of physiological inflammation is antigen driven. Upon recognition of antigen, the lamina propria (LP) is populated with lymphocytes and activated peripheral cells acquire the capacity to home to the gut. Antigen entry to the gut is via follicle‐associated epithelium or M cells. The antigen now interacts with macrophages or CD4+ cells, and go on to the Peyer's patch where B cells undergo a transforming growth factor β (TGF‐β)‐mediated isotope switch to immunoglobulin (Ig) A. TGF‐β may also play a role in the development of oral tolerance. The intestinal epithelium is seen as the site for the activation of CD8+ suppressor cells. Controlled inflammation is therefore explained by the interaction of LP lymphocytes and intra‐epithelial cells (IEC). IECs are capable of extending processes that express regulatory surface molecules coupled with antigen processed from luminal uptake. CD8+ T‐cell activation is favoured over CD4+ T‐cell activation due to the size of the antigenic binding peptide. The result is suppressed inflammation. Other antigen‐presenting cells (APCs) and dendritic cells may also contribute to local immunosuppression.
Review article: Chemokine production by intestinal epithelial cells: a therapeutic target in inflammatory bowel disease?
Authors: VAN DEVENTER S. J. H.
Published: September 2010

The intestinal epithelium plays an important role in the recognition of pathogenic organisms and in the recruitment of inflammatory cells to the mucosa. Epithelial chemokine production may constitute a key target in future therapies for inflammatory bowel disease (IBD).

Chemokines are divided into two subfamilies, the C‐C family and C‐X‐C family. Most C‐C chemokines target mononuclear cells and many C‐X‐C chemokines attract neutrophils. Interleukin‐8 (IL‐8), a C‐X‐C chemokine, acts as a motor for the recruitment of neutrophils into the non‐inflamed mucosa and is present in both enterocytes and mucosal inflammatory cells. Epithelial cells may be the first to signal the presence of pathogens, as well as contributing to IL‐8 production in IBD. Data have also shown that intestinal epithelial cells are able to respond to IL‐1β and tumour necrosis factor‐alpha (TNF‐α) at concentrations known to occur in the inflamed mucosa. Monocyte chemotactic protein‐1 (MCP‐1), a member of the C‐C chemokine family, is noticeably increased in IBD. These data show that C‐X‐C and C‐C chemokines are equally important properties of mucosal epithelial cells.

The effects of two anti‐inflammatory drugs (dexamethasone and cyclosporin) on chemokine production are significantly different and this provides a rationale for combination therapy.
Comparative analysis of pyrosequencing and QMC‐PCR in conjunction with high resolution melting for KRAS/BRAF mutation detection
Authors: Ibrahem Salih , Seth Rashmi , O’Sullivan Brendan , Fadhil Wakkas , Taniere Philippe , Ilyas Mohammad
Published: September 2010

Mutation detection is important in cancer management. Several methods are available of which high resolution melting (HRM) analysis and pyrosequencing are the most versatile. We undertook a comparative analysis of these techniques. The methods are:

 To compare the limit of detection (LOD), mutations in KRAS (codon 12/13 hotspot) and BRAF (V600E hotspot) were tested. DNA mixtures containing mutant alleles at a frequency of around 25%/12.5%/6%/3%/ 1.5%/0.8% were analysed.

 To compare frequency of mutation detection, 22 DNA samples (nine high quality samples from cell lines, 13 low quality samples from formalin‐fixed paraffin‐embedded tissue) were tested for three hotspots in KRAS (codons 12/13, 61 and 146) and two hotspots in BRAF (V600E and exon 11).

HRM analysis of KRAS (codon12/13) and BRAF (V600E) showed that 3% and 1.5% mutant alleles respectively could be reliably detected whilst pyrosequencing reliably detected 6% mutant alleles in each case. Of 110 tests performed on 22 DNA samples, in 109 cases HRM and pyrosequencing gave identical results. Two of the samples tested had previously been called as wild type for KRAS by direct Sanger sequencing but were found to be mutant by both HRM and pyrosequencing.

Both HRM and pyrosequencing can detect small numbers of mutant alleles although HRM has a lower limit of detection. Both are suitable for use in mutation detection and are both more sensitive than Sanger sequencing.
Field test for environmental correlates of dispersal in hedgehogsErinaceus europaeus
Authors: C. Patrick Doncaster , Carlo Rondinini , Paul C. D. Johnson
Published: September 2010

We report a field experiment designed to explore the responses by hedgehogs to novel and unfavourable terrain, which they encounter when dispersing between fragmented local populations in farmland. We identified four replicate sites as unused by hedgehogs, but lying between existing populations and containing locally abundant food. At each site, we released six hedgehogs from distant sources at 2‐day intervals and monitored their subsequent dispersals over 20 days by radio‐tracking. We compared movement trajectories under this treatment to those of 29 hedgehogs released at two sites known to support abundant hedgehogs. A third treatment comprised 20 unmanipulated hedgehogs at three sites. We estimated habitat use and proximity to habitats by comparing each observed trajectory to simulated random walks of equal length. We sought differences between treatments in movement and habitat use from nested analysis of variance.

No two trajectories of any translocated hedgehogs followed the same route; most involved little change in body weight, and took the animal into or through existing populations. Hedgehogs moved substantially further and faster on average from the unfavourable than from the favourable sites. They showed a significantly stronger attraction to habitat edges, which therefore acted as corridors, and a significant proportion of them stayed closer to roads and to urban habitat than random expectation. Habitat preferences also shifted significantly towards urban and away from arable areas. Six were predated, and two killed by road traffic. At least three returned to their release point, withP < 0·05 of this occurring by chance.

In this region, natural dispersals between populations up to 4 km apart are rare events. We have shown, however, that hedgehogs are capable of travelling distances of up to 3·8 km from a release point, and up to 9·9 km in total, compared to an average home range span of 0·8 km, and it appears that none of the local populations in the study area are out of reach of neighbours.
Safe early discharge for patients undergoing high dose chemotherapy with or without stem cell transplantation: a prospective analysis of clinical variables predictive for complications after treatment
Authors: Mank Arno , van der Lelie Johannes , de Vos Rien , Kersten Marie Jóse
Published: September 2010

Aim.  To identify which patient groups can be safely discharged early after high dose chemotherapy.

Background.  Until recently, the standard of care for patients with haematological malignancies who have been treated with high dose chemotherapy has been to hospitalise them until neutrophil recovery and clinical improvement. Over the past years, a more liberal approach has resulted in a tendency to discharge patients earlier. However, currently it is unclear which clinical variables are important and which patient groups are most suitable to be discharged early.

Design.  Prospective cohort study.

Methods.  The study group of 55 patients underwent 82 admission periods for a total of 2269 patient days, which could be classified into four categories: induction treatment, consolidation treatment and autologous or allogeneic stem cell transplantation. Different clinical variables potentially interfering with early discharge were subsequently analysed for their association with each treatment group.

Results.  The median duration of admission was 27 days. The incidence of fever (82·9%) and use of intravenous antibiotics (79·3%) was high in all treatment groups. The only statistically significant differences between groups were found for performance status and mucositis. In the patient group undergoing consolidation chemotherapy for acute myeloid leukaemia, the performance status was better and mucositis was less severe. The decline in performance status and the severity of mucositis were as expected most obvious 10–14 days after the start of chemotherapy.

Conclusion.  Patients undergoing consolidation chemotherapy appear to be the most suitable candidates for early discharge, especially in the first‐week postchemotherapy treatment. Early discharge can also be considered in patients with a good performance status in the autologous stem cell transplantation group, directly after transplantation.

Relevance to clinical practice.  An important factor in developing an early discharge programme is a good infrastructure, both at home and in the hospital.
The perception of friendship in adults with Down syndrome
Authors: Watt K. J. , Johnson P. , Virji‐Babul N.
Published: September 2010

Background  Measuring the perception of friendship in adults with Down syndrome (DS) has long been a research challenge. While there have been studies investigating the number of friends children with DS have in, the study of how adults with DS view the concept of friendship has been relatively unexplored. The aim of this study was to evaluate the perception of friendship in adults with DS using a visually based scale.

Methods  Sixty‐six individuals participated in this study: 22 adults with DS, 22 typical mental age (MA) matched children and 22 typical adults matched for chronological age (CA). We administered a visually based Friendship scale made up of photographs depicting social interactions between individuals or groups. The scale was composed of two parts. In Part 1 participants were shown two photographs and asked to select the photograph that best depicted friends. In Part 2 participants were asked to view one photograph and asked, ‘Is it okay for friends to do this?’

Results  Adults with DS scored lower on the Friendship scale in comparison with the CA and MA matched groups. Adults with DS made more errors in identifying ‘friends’ from ‘non‐friends’ but were equally able to distinguish friendly behaviours and actions from non‐friendly behaviours as their CA and MA matched peers. Individuals with DS were more likely to incorrectly identify photographs depicting a teacher, or a mother with a child as friends. Actions or behaviours that depicted subtle negative emotions were also incorrectly identified.

Conclusions  These results are an important first step in understanding the perception of friendship and social behaviours related to friendship in adults with DS.
Dynamic changes of canopy‐scale mesophyll conductance to CO2 diffusion of sunflower as affected by CO2 concentration and abscisic acid
Authors: SCHÄUFELE RUDI , SANTRUCEK JIRI , SCHNYDER HANS
Published: September 2010

Leaf‐level measurements have shown that mesophyll conductance (gm) can vary rapidly in response to CO2 and other environmental factors, but similar studies at the canopy‐scale are missing. Here, we report the effect of short‐term variation of CO2 concentration on canopy‐scale gm and other CO2 exchange parameters of sunflower (Helianthus annuus L.) stands in the presence and absence of abscisic acid (ABA) in their nutrient solution. gm was estimated from gas exchange and on‐line carbon isotope discrimination (Δobs) in a 13CO2/12CO2 gas exchange mesocosm. The isotopic contribution of (photo)respiration to stand‐scale Δobs was determined with the experimental approach of Tcherkez et al. Without ABA, short‐term exposures to different CO2 concentrations (Ca 100 to 900 µmol mol−1) had little effect on canopy‐scale gm. But, addition of ABA strongly altered the CO2‐response: gm was high (approx. 0.5 mol CO2 m−2 s−1) at Ca < 200 µmol mol−1 and decreased to <0.1 mol CO2 m−2 s−1 at Ca >400 µmol mol−1. In the absence of ABA, the contribution of (photo)respiration to stand‐scale Δobs was high at low Ca (7.2‰) and decreased to <2‰ at Ca > 400 µmol mol−1. Treatment with ABA halved this effect at all Ca.
Prevalence of bronchial asthma in schoolchildren in Oslo, Norway
Authors: Skjønsberg O. H. , Clench‐Aas J. , Leegaard J. , Skarpaas I. J. K. , Giæver P. , Bartonova A. , Moseng J.
Published: September 2010

In 1993, 4521 schoolchildren in Oslo, Norway, participated in a European study on air pollution and respiratory health. Incorporated in the primary questionnaire were five questions taken from a study performed 12 years earlier on 1772 schoolchildren in the same city. The response rate was 85% in 1993 vs 95% in 1981. The current and cumulative prevalences of doctor‐diagnosed asthma in 1993 were 4.2% and 8.0%, respectively, compared to 2.2% (P<0.01) and 3.4% (P<0.01) in 1981. Attacks of breathlessness during the last 3 years were experienced by 7.1% in 1993 and 3.3% in 1981 (P<0.05). Wheezing or breathlessness on exposure to pollen in 1993 and 1981 was reported by 6.1% and 3.7% (P<0.01), respectively; to animals by 4.0% and 2.8% (P<0.05); and to exercise by 10.2% and 4.8% (P<0.01). The prevalence of occasional wheezing and the cumulative prevalence of doctor‐diagnosed eczema, urticaria, and hay fever were not significantly altered. To summarize, a higher prevalence of both doctor‐diagnosed asthma and symptoms of obstructive airways disease was reported by children attending primary school in Oslo in 1993 than 12 years earlier. No increase was observed in the prevalence of other atopic diseases.
Studies on shared antigenic/allergenic components among fungi
Authors: Verma J. , Sridhara S. , Singh B. P. , Gangal S. V.
Published: September 2010

Fungal allergens have been found to be one of the most prevalent aeroallergens in India. Knowledge of shared/unique components among different fungi is necessary for proper diagnosis and treatment of patients allergic to fungi. In the present study, crude extracts (CE) of 11 common fungi (Alternaria alternata, Aspergillus flavus, Asp. fumigatus, Asp. niger, Asp. tamarii, Asp. versicolor, Cladosporium herbarum, Curvularia lunata, Mucor hiemalis, Penicillium citrinum, and Fusarium solani) were characterized by isoelectric focusing (IEF), SDS‐PAGE, and immunoblot. On IEF (pI 3–9), the number of protein bands was found to be greatest (46) in M. hiemalis extract. SDS‐PAGE exhibited a varied number of bands, generally 18–40, with mol. mass ranging from 14 to 100 kDa. IgG‐specific immunoprint using rabbit anti‐F. solani CF antibodies demonstrated a mol. mass distribution of shared antigenic proteins of 14–100 kDa in most of the fungi. Shared allergenicity was observed in a number of allergenic proteins in fungal extracts with mol. mass ranging between 14 and 70 kDa on IgE‐specific immunoblot using pooled sera of patients allergic to Fusarium. A 45‐kDa protein was found to be common among these fungi on immunoblot with patients as well as with rabbit antibodies. F. solani CF extract contained more antigenic/allergenic proteins than F. solani CE. It was concluded that F. solani CF shared several antigenic/allergenic components with CE of other common fungi. This fact needs to be taken into account when fungal extracts are used in diagnosis and immunotherapy of allergic patients.
Diagnostic work‐up for food‐dependent, exercise‐induced anaphylaxis
Authors: Romano A. , di Fonso M. , Giuffreda F. , Quaratino D. , Papa G. , Palmieri V. , Zeppilli P. , Venuti A.
Published: September 2010

Fourteen patients with suspected food‐dependent, exercise‐induced anaphylaxis (EIAn) were subjected to prick tests with commercial food extracts and common airborne allergens, prick + prick tests with fresh foods, determination of total IgE levels, and specific IgE for 31 foods (CAP System FEIA RAST). All were positive for two or more foods; 10 presented hypersensitivity to 11 or more foods. On the basis of these findings, history data, and responses to food‐exercise challenges (treadmill stress tests 90 min after meals containing none of the suspected foods and none associated with skin‐test and/or RAST positivity) and suspected food‐exercise challenges (SFECs — administered after meals containing the suspected food), three patients were diagnosed as having specific food‐dependent EIAn (for wheat in two cases, tomato in one). In nine others, the presence of specific IgE for numerous foods (including those suspected on the basis of histories and utilized in the SFECs) suggests involvement of specific food hypersensitivity, although SFEC confirmation could not be obtained. Avoidance of all foods associated with test positivity 4 h before exercise has prevented all further EIAn episodes in these 12 patients. In two others, the reactions did not appear to be related to IgE directed against specific food allergens, and these subjects have eliminated further reactions by avoiding all meals for the 4 h preceding exercise. These findings emphasize the importance of allergologic testing with a wide panel of food allergens (including foods used for seasoning, such as garlic or parsley) in all patients with suspected food‐dependent EIAn. Prick + prick tests with fresh foods and the CAP System RAST disclosed numerous hypersensitivities.
Ventilation in homes infested by house‐dust mites
Authors: Sundell J. , Wickman M. , Pershagen G. , Nordvall S. L.
Published: September 2010

Thirty single‐family homes with either high (≥ 2000 ng/g) or low (≤ 1000 ng/g) house‐dust mite (HDM) allergen levels in mattress dust were examined for ventilation, thermal climate, and air quality (formaldehyde and total volatile organic compounds (TVOC). Elevated concentrations of HDM allergen in mattress and floor dust were associated with the difference in absolute humidity between indoor and outdoor air, as well as with low air‐change rates of the home, particularly the bedroom. No correlation was found between concentration of TVOC or formaldehyde in bedroom air and HDM allergen concentration. In regions with a cold winter climate, the air‐change rate of the home and the infiltration of outdoor air into the bedroom appear to be important for the infestation of HDM.