bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a conserved membrane localization domain within numerous large bacterial protein toxins
Authors: Geissler Brett , Tungekar Rehman , Satchell Karla J. F.
Published: March 2010

Vibrio cholerae
is the causative agent of the diarrheal disease cholera. Many virulence factors contribute to intestinal colonization and disease including the Multifunctional Autoprocessing RTX toxin (MARTX
Vc
). The Rho-inactivation domain (RID) of MARTX
Vc
is responsible for inactivating the Rho-family of small GTPases, which leads to depolymerization of the actin cytoskeleton. Based on a deletion analysis of RID to determine the minimal functional domain, we have identified a subdomain at the N terminus of RID that is homologous to the membrane targeting C1 domain of
Pasteurella multocida
toxin. A GFP fusion to this subdomain from RID colocalized with a plasma membrane marker when transiently expressed within HeLa cells and can be found in the membrane fraction following subcellular fractionation. This C1-like subdomain is present in multiple families of bacterial toxins, including all of the clostridial glucosyltransferase toxins and various MARTX toxins. GFP-fusions to these homologous domains are also membrane associated, indicating that this is a conserved membrane localization domain (MLD). We have identified three residues (Y23, S68, R70) as necessary for proper localization of one but not all MLDs. In addition, we found that substitution of the RID MLD with the MLDs from two different effector domains from the
Vibrio vulnificus
MARTX toxin restored RID activity, indicating that there is functional overlap between these MLDs. This study describes the initial recognition of a family of conserved plasma membrane-targeting domains found in multiple large bacterial toxins.
Kinetics of brain nicotine accumulation in dependent and nondependent smokers assessed with PET and cigarettes containing11C-nicotine
Authors: Rose Jed E. , Mukhin Alexey G. , Lokitz Stephen J. , Turkington Timothy G. , Herskovic Joseph , Behm Frederique M. , Garg Sudha , Garg Pradeep K.
Published: March 2010

Tobacco smoking is a chronic, relapsing disorder that constitutes one of the primary preventable causes of death in developed countries. Two of the popular hypotheses to explain the development and maintenance of strong nicotine dependence in cigarette smokers posit (i) a rapid brain nicotine accumulation during cigarette smoking and/or (ii) puff-associated spikes in brain nicotine concentration. To address these hypotheses, we investigated the dynamics of nicotine accumulation in the smoker's brain during actual cigarette smoking using PET with 3-s temporal resolution and11C-nicotine loaded into cigarettes. The results of the study, performed in 13 dependent smokers (DS) and 10 nondependent smokers (NDS), suggest that puff-associated spikes in the brain nicotine concentration do not occur during habitual cigarette smoking. Despite the presence of a puff-associated oscillation in the rate of nicotine accumulation, brain nicotine concentration gradually increases during cigarette smoking. The results further suggest that DS have a slower process of brain nicotine accumulation than NDS because they have slower nicotine washout from the lungs and that DS have a tendency to compensate for their slower rate of brain nicotine accumulation compared with NDS by inhaling a larger volume of smoke. For these reasons, smokers’ dependence on cigarette smoking, or the resistance of NDS to becoming dependent, cannot be explained solely by a faster brain nicotine accumulation.
Disrupted-in-Schizophrenia-1 expression is regulated by β-site amyloid precursor protein cleaving enzyme-1–neuregulin cascade
Authors: Seshadri Saurav , Kamiya Atsushi , Yokota Yukako , Prikulis Ingrid , Kano Shin-ichi , Hayashi-Takagi Akiko , Stanco Amelia , Eom Tae-Yeon , Rao Sarada , Ishizuka Koko , Wong Philip , Korth Carsten , Anton E. S. , Sawa Akira
Published: March 2010

Neuregulin-1 (NRG1) and Disrupted-in-Schizophrenia-1 (DISC1) are promising susceptibility factors for schizophrenia. Both are multifunctional proteins with roles in a variety of neurodevelopmental processes, including progenitor cell proliferation, migration, and differentiation. Here, we provide evidence linking these factors together in a single pathway, which is mediated by ErbB receptors and PI3K/Akt. We show that signaling by NRG1 and NRG2, but not NRG3, increase expression of an isoform of DISC1 in vitro. Receptors ErbB2 and ErbB3, but not ErbB4, are responsible for transducing this effect, and PI3K/Akt signaling is also required. In NRG1 knockout mice, this DISC1 isoform is selectively reduced during neurodevelopment. Furthermore, a similar decrease in DISC1 expression is seen in β-site amyloid precursor protein cleaving enzyme–1 (BACE1) knockout mice, in which NRG1/Akt signaling is reportedly impaired. In contrast to neuronal DISC1 that was reported and characterized, expression of DISC1 in other types of cells in the brain has not been addressed. Here we demonstrate that DISC1, like NRG and ErbB proteins, is expressed in neurons, astrocytes, oligodendrocytes, microglia, and radial progenitors. These findings may connect NRG1, ErbBs, Akt, and DISC1 in a common pathway, which may regulate neurodevelopment and contribute to susceptibility to schizophrenia.
Structural characterization of the Z RING-eIF4E complex reveals a distinct mode of control for eIF4E
Authors: Volpon Laurent , Osborne Michael J. , Capul Althea A. , de la Torre Juan C. , Borden Katherine L. B.
Published: March 2010

The eukaryotic translation initiation factor eIF4E, a potent oncogene, is highly regulated. One class of eIF4E regulators, including eIF4G and the 4E-binding proteins (4E-BPs), interact with eIF4E using a conserved YXXXXLΦ-binding site. The structural basis of this interaction and its regulation are well established. Really Interesting New Gene (RING) domain containing proteins, such as the promyelocytic leukemia protein PML and the arenaviral protein Z, represent a second class of eIF4E regulators that inhibit eIF4E function by decreasing eIF4E’s affinity for its m
7
G cap ligand. To elucidate the structural basis of this inhibition, we determined the structure of Z and studied the Z-eIF4E complex using NMR methods. We show that Z interacts with eIF4E via a novel binding site, which has no homology with that of eIF4G or the 4E-BPs, and is different from the RING recognition site used in the ubiquitin system. Z and eIF4G interact with distinct parts of eIF4E and differentially alter the conformation of the m
7
G cap-binding site. Our results provide a molecular basis for how PML and Z RINGs reduce the affinity of eIF4E for the m
7
G cap and thereby act as key inhibitors of eIF4E function. Furthermore, our findings provide unique insights into RING protein interactions.
Exposing the hidden complexity of stoichiometric and catalytic metathesis reactions by elucidation of Mg-Zn hybrids
Authors: Hevia Eva , Chua Jonathan Z. , García-Álvarez Pablo , Kennedy Alan R. , McCall Matthew D.
Published: March 2010

Studying seemingly simple metathesis reactions between ZnCl2andtBuMgCl has, surprisingly, revealed a much more complex chemistry involving mixed magnesium-zinc compounds that could be regarded as Mg-Zn hybrids. Thus, the reaction of equimolar amounts of ZnCl2andtBuMgCl reveals the formation of the unprecedented mixed Mg-Zn complex [(THF)4Mg(μ-Cl)2Zn(tBu)(Cl)] (1), as a result of the co-complexation of the two anticipated exchange products of the metathesis. This magnesium zincate adopts a contacted ion-pair structure, closely related to Knochel’s pioneering “Turbo” Grignard reagents. Furthermore, a second coproduct identified in this reaction is the solvent-separated mixed magnesium-zinc chloride complex [{Mg(THF)6}2+{Zn2Cl6}2-] (3) that critically diminishes the amount of ZnCl2available for the intended metathesis reaction to take place. In another surprising result, when the reaction is carried out by using an excess of 3 M equivalents of the Grignard reagent (closer to the catalytic conditions employed by synthetic chemists), solvent-separated magnesium trialkyl zincate [{Mg2Cl3(THF)6}+{Zn(tBu)3}-] (4) is obtained that can be viewed as a model for the active species involved in the increasingly important organic transformations of Grignard reagents catalysed by ZnCl2. Furthermore, preliminary reactivity studies reveal that complex4can be used as an effective new reagent for direct Zn-I exchange reactions that allow the preparation and structural identification of the magnesium tris(aryl) zincate [{Mg2Cl3(THF)6}+{Zn(p-Tol)3}-] (5) that represents the first example of complete 3-fold activation of a zincate in a Zn-I exchange reaction which, in turn, can efficiently be used as a precursor for Negishi cross-coupling reactions.
Spatiotemporal control of nanooptical excitations
Authors: Aeschlimann Martin , Bauer Michael , Bayer Daniela , Brixner Tobias , Cunovic Stefan , Dimler Frank , Fischer Alexander , Pfeiffer Walter , Rohmer Martin , Schneider Christian , Steeb Felix , Strüber Christian , Voronine Dmitri V.
Published: March 2010

The most general investigation and exploitation of light-induced processes require simultaneous control over spatial and temporal properties of the electromagnetic field on a femtosecond time and nanometer length scale. Based on the combination of polarization pulse shaping and time-resolved two-photon photoemission electron microscopy, we demonstrate such control over nanoscale spatial and ultrafast temporal degrees of freedom of an electromagnetic excitation in the vicinity of a nanostructure. The time-resolved cross-correlation measurement of the local photoemission yield reveals the switching of the nanolocalized optical near-field distribution with a lateral resolution well below the diffraction limit and a temporal resolution on the femtosecond time scale. In addition, successful adaptive spatiotemporal control demonstrates the flexibility of the method. This flexible simultaneous control of temporal and spatial properties of nanophotonic excitations opens new possibilities to tailor and optimize the light–matter interaction in spectroscopic methods as well as in nanophotonic applications.
Directly patternable, highly conducting polymers for broad applications in organic electronics
Authors: Yoo Joung Eun , Lee Kwang Seok , Garcia Andres , Tarver Jacob , Gomez Enrique D. , Baldwin Kimberly , Sun Yangming , Meng Hong , Nguyen Thuc-Quyen , Loo Yueh-Lin
Published: March 2010

Postdeposition solvent annealing of water-dispersible conducting polymers induces dramatic structural rearrangement and improves electrical conductivities by more than two orders of magnitude. We attain electrical conductivities in excess of 50 S/cm when polyaniline films are exposed to dichloroacetic acid. Subjecting commercially available poly(ethylene dioxythiophene) to the same treatment yields a conductivity as high as 250 S/cm. This process has enabled the wide incorporation of conducting polymers in organic electronics; conducting polymers that are not typically processable can now be deposited from solution and their conductivities subsequently enhanced to practical levels via a simple and straightforward solvent annealing process. The treated conducting polymers are thus promising alternatives for metals as source and drain electrodes in organic thin-film transistors as well as for transparent metal oxide conductors as anodes in organic solar cells and light-emitting diodes.
X-raying galaxies: A Chandra legacy
Authors: Wang Q. Daniel
Published: March 2010

This presentation reviews Chandra’s major contribution to the understanding of nearby galaxies. After a brief summary on significant advances in characterizing various types of discrete x-ray sources, the presentation focuses on the global hot gas in and around galaxies, especially normal ones like our own. The hot gas is a product of stellar and active galactic nuclear feedback—the least understood part in theories of galaxy formation and evolution. Chandra observations have led to the first characterization of the spatial, thermal, chemical, and kinetic properties of the gas in our galaxy. The gas is concentrated around the galactic bulge and disk on scales of a few kiloparsec. The column density of chemically enriched hot gas on larger scales is at least an order magnitude smaller, indicating that it may not account for the bulk of the missing baryon matter predicted for the galactic halo according to the standard cosmology. Similar results have also been obtained for other nearby galaxies. The x-ray emission from hot gas is well correlated with the star formation rate and stellar mass, indicating that the heating is primarily due to the stellar feedback. However, the observed x-ray luminosity of the gas is typically less than a few percent of the feedback energy. Thus the bulk of the feedback (including injected heavy elements) is likely lost in galaxy-wide outflows. The results are compared with simulations of the feedback to infer its dynamics and interplay with the circumgalactic medium, hence the evolution of galaxies.
Antenna mixing in photosynthetic membranes from
Phaeospirillum molischianum
Authors: Mascle-Allemand Camille , Duquesne Katia , Lebrun Regine , Scheuring Simon , Sturgis James N.
Published: March 2010

We have investigated the adaptation of the light-harvesting system of the photosynthetic bacterium
Phaeospirillum molischianum
(DSM120) to very low light conditions. This strain is able to respond to changing light conditions by differentially modulating the expression of a family of
puc
operons that encode for peripheral light-harvesting complex (LH2) polypeptides. This modulation can result in a complete shift between the production of LH2 complexes absorbing maximally near 850 nm to those absorbing near 820 nm. In contradiction to prevailing wisdom, analysis of the LH2 rings found in the photosynthetic membranes during light adaptation are shown to have intermediate spectral and electrostatic properties. By chemical cross-linking and mass-spectrometry we show that individual LH2 rings and subunits can contain a mixture of polypeptides derived from the different operons. These observations show that polypeptide synthesis and insertion into the membrane are not strongly coupled to LH2 assembly. We show that the light-harvesting complexes resulting from this mixing could be important in maintaining photosynthetic efficiency during adaptation.
Recovery of PEX1-Gly843Asp peroxisome dysfunction by small-molecule compounds
Authors: Zhang Rui , Chen Li , Jiralerspong Sarn , Snowden Ann , Steinberg Steven , Braverman Nancy
Published: March 2010

Zellweger spectrum disorder (ZSD) is a heterogeneous group of diseases with high morbidity and mortality caused by failure to assemble normal peroxisomes. There is no therapy for ZSD, but management is supportive. Nevertheless, one-half of the patients have a phenotype milder than classic Zellweger syndrome and exhibit a progressive disease course. Thus, patients would benefit if therapies became available and were instituted early. Recent reports indicate several interventions that result in partial peroxisome recovery in ZSD fibroblasts. To identify drugs that recover peroxisome functions, we expressed a GFP-peroxisome targeting signal 1 reporter in fibroblasts containing the common disease allele, PEX1-p.Gly843Asp. The GFP reporter remained cytosolic at baseline, and improvement in peroxisome functions was detected by the redistribution of the GFP reporter from the cytosol to the peroxisome. We established a high-content screening assay based on this phenotype assay and evaluated 2,080 small molecules. The cells were cultured in chemical for 2 days and then, were fixed and imaged by epifluorescent microscopy on a high-content imaging platform. We identified four compounds that partially recover matrix protein import, and we confirmed three using independent assays. Our results suggest that PEX1-p.G843D is a misfolded protein amenable to chaperone therapy.
HO
•
radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases
Authors: Bergeron François , Auvré Frédéric , Radicella J. Pablo , Ravanat Jean-Luc
Published: March 2010

Reaction of HO
•
radicals with double-stranded calf thymus DNA produces high levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and, to a minor extent, 8-oxo-7,8-dihydro-2′-deoxyadenosine (8-oxodAdo). Formation of the hydroxylated purine lesions is explained by addition of HO
•
to the C8 position of the purine moiety. It has been reported that tandem lesions containing a formylamine residue neighboring 8-oxodGuo could be produced through addition of a transiently generated pyrimidine peroxyl radical onto the C8 of an adjacent purine base. Formation of such tandem lesions accounted for ≈10% of the total 8-oxodGuo. In the present work we show that addition of HO
•
onto the C8 of purine accounts for only ∼5% of the generated 8-oxodGuo. About 50% of the 8-hydroxylated purine lesions, including 8-oxodGuo and 8-oxodAdo, are involved in tandem damage and are produced by peroxyl addition onto the C8 of a vicinal purine base. In addition, the remaining 45% of the 8-oxodGuo are produced by an electron transfer reaction, providing an explanation for the higher yield of formation of 8-oxodGuo compared to 8-oxodAdo. Interestingly, we show that >40% of the 8-oxodGuo involved in tandem lesions is refractory to excision by DNA glycosylases. Altogether our results demonstrate that, subsequently to a single oxidation event, peroxidation reactions significantly increase the yield of formation of hydroxylated purine modifications, generating a high proportion of tandem lesions partly refractory to base excision repair.
Contrasting effects of different maternal diets on sexually dimorphic gene expression in the murine placenta
Authors: Mao Jiude , Zhang Xia , Sieli Paizlee T. , Falduto Michael T. , Torres Karen E. , Rosenfeld Cheryl S.
Published: March 2010

Diet during pregnancy influences the future health of a woman's offspring, with outcomes differing depending on the child's sex. Because the placenta buffers the fetus from the mother, we examined the impact of diet and fetal sex on placental gene expression in mice fed either a very-high-fat, low-fat, chow diet of intermediate caloric density. At day 12.5 of pregnancy, placental RNA was extracted and analyzed by microarray. The expression of 1,972 genes was changed more than 2-fold (
P
< 0.05) in comparisons across diet in at least one of the three groups. Female placentae demonstrated more striking alterations in gene expression in response to maternal diet than male placentae. Notably, each diet provided a distinctive signature of sexually dimorphic genes, with expression generally higher in genes (651 out of 700) from female placentae than those from male placentae. Several genes normally considered as characteristic of kidney function were affected by diet, including genes regulating ion balance and chemoreception. The placenta also expressed most of the known olfactory receptor genes (
Olfr
), which may allow the placenta to sense odorant molecules and other minor dietary components, with transcript levels of many of these genes influenced by diet and fetal sex. In conclusion, gene expression in the murine placenta is adaptive and shaped by maternal diet. It also exhibits pronounced sexual dimorphism, with placentae of females more sensitive to nutritional perturbations than placentae of males.
Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes
Authors: Lukowski Robert , Rybalkin Sergei D. , Loga Florian , Leiss Veronika , Beavo Joseph A. , Hofmann Franz
Published: March 2010

It has been suggested that cGMP kinase I (cGKI) dampens cardiac hypertrophy. We have compared the effect of isoproterenol (ISO) and transverse aortic constriction (TAC) on hypertrophy in WT [control (CTR)] mice, total cGKI-KO mice, and cGKIβ rescue mice (βRM) lacking cGKI specifically in cardiomyocytes (CMs). Infusion of ISO did not change the expression of cGKI in the hearts of CTR mice or βRM but raised the heart weight by ∼20% in both. An identical hypertrophic growth response was measured in CMs from CTR mice and βRM and in isolated adult CMs cultured with or without 1 μM ISO. In both genotypes, ISO infusion induced similar changes in the expression of hypertrophy-associated cardiac genes and significant elevation of serum atrial natriuretic peptide and total cardiac cGMP. No differences in cardiac hypertrophy were obtained by 7-day ISO infusion in 4- to 6-week-old conventional cGKI-KO and CTR mice. Furthermore, TAC-induced hypertrophy of CTR mice and βRM was not different and did not result in changes of the cGMP-hydrolyzing phosphodiesterase activities in hypertropic hearts or CMs. These results strongly suggest that cardiac myocyte cGKI does not affect the development of heart hypertrophy induced by pressure overload or chronic ISO infusion.
A
Drosophila
behavioral mutant,
down and out
(
dao
), is defective in an essential regulator of Erg potassium channels
Authors: Fergestad Tim , Sale Harinath , Bostwick Bret , Schaffer Ashleigh , Ho Lingling , Robertson Gail A. , Ganetzky Barry
Published: March 2010

To signal properly, excitable cells must establish and maintain the correct balance of various types of ion channels that increase or decrease membrane excitability. The mechanisms by which this balance is regulated remain largely unknown. Here, we describe a regulatory mechanism uncovered by a
Drosophila
behavioral mutant,
down and out
(
dao
). At elevated temperatures,
dao
loss-of-function mutants exhibit seizures associated with spontaneous bursts of neural activity. This phenotype closely resembles that of
seizure
mutations, which impair activity of ether-a-go-go-related gene (Erg)-type potassium channels. Conversely, neural over-expression of wild-type Dao confers dominant temperature-sensitive paralysis with kinetics reminiscent of
paralytic
sodium-channel mutants. The over-expression phenotype of
dao
is suppressed in a
seizure
mutant background, suggesting that Dao acts by an effect on Erg channels. In support of this hypothesis, functional expression of Erg channels in a heterologous system is dependent on the presence of Dao. These results indicate that Dao has an important role in establishing the proper level of neuronal membrane excitability by regulating functional expression of Erg channels.
Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis
Authors: Joyce-Shaikh Barbara , Bigler Michael E. , Chao Cheng-Chi , Murphy Erin E. , Blumenschein Wendy M. , Adamopoulos Iannis E. , Heyworth Paul G. , Antonenko Svetlana , Bowman Edward P. , McClanahan Terrill K. , Phillips Joseph H. , Cua Daniel J.
Published: March 2010

DNAX adaptor protein 12 (DAP12) is a trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells. Absence of functional Dap12 results in osteoclast defects and bone abnormalities. Because DAP12 has no extracelluar binding domains, it must pair with cell surface receptors for signal transduction. There are at least 15 known DAP12-associating cell surface receptors with distinct temporal and cell type–specific expression patterns. Our aim was to determine which receptors may be important in DAP12-associated bone pathologies. Here, we identify myeloid DAP12-associating lectin (MDL)-1 receptor (also known as CLEC5A) as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation. Activation of MDL-1 leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joint and promotes bone erosion. Functional blockade of MDL-1 receptor via Mdl1 deletion or treatment with MDL-1-Ig fusion protein reduces the clinical signs of autoimmune joint inflammation. These findings suggest that MDL-1 receptor may be a therapeutic target for treatment of immune-mediated skeletal disorders.
Pulmonary dendritic cells: thinking globally, acting locally
Authors: Randall Troy D.
Published: March 2010

The phrase “think globally, act locally” was coined in the early 1970s and directed individuals to clean up their local environment with the ultimate goal of improving the health of the entire planet. Several recent studies indicate that similar considerations apply to the immune system, in which small numbers of leukocytes, such as pulmonary dendritic cells, can modify the local immune environment in the lung and promote a positive outcome for the organism.
Serial measurement of the N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) predicts poor outcome in a patient with congenitally corrected transposition of the great arteries (ccTGA)
Authors: Raedle‐Hurst Tanja M. , Hosse Meryem , Abdul‐Khaliq Hashim
Published: March 2010

The usefulness of natriuretic peptides to assess myocardial function in patients with a systemic morphological right ventricle is still unclear. In this report we describe the clinical course of a young woman with congenitally corrected transposition of the great arteries (ccTGA) who suffered from a progressive deterioration of myocardial function after child birth despite intensive medical treatment and additional cardiac resynchronization therapy. In this woman, serial measurement of NT‐proBNP levels was related to the velocity time integral over the aortic valve and indicated worsening of the patient's haemodynamic status and finally death.
Infliximab for refractory ulcerative proctitis
Authors: BOUGUEN G. , ROBLIN X. , BOURREILLE A. , FEIER L. , FILIPPI J. , NANCEY S. , BRETAGNE J.‐F. , FLOURIÉ B. , HÉBUTERNE X. , BIGARD M.‐A. , SIPROUDHIS L. , PEYRIN‐BIROULET L.
Published: March 2010

Aliment Pharmacol Ther 31, 1178–1185

Background  Efficacy of infliximab in treating ulcerative proctitis remains unknown.

Aim  To evaluate the clinical, biological and endoscopic efficacy of infliximab therapy in refractory proctitis.

Methods  The charts of 420 patients treated with infliximab for ulcerative colitis were reviewed. Thirteen patients were treated with infliximab for refractory ulcerative proctitis in six referral centres between 2005 and 2009.

Results  Following infliximab therapy induction, 9/13 patients (69%) had a complete response (defined as absence of diarrhoea and blood), 2/13 (15%) had a partial response and 2/13 (15%) were primary nonresponders. The median follow‐up was 17 months (range, 3–48). Among the 11 patients with clinical response after infliximab induction therapy, 9 (82%) patients maintained response at last follow‐up. Disappearance of rectal disorders was observed in all nine patients who maintained clinical response at last follow‐up. Following infliximab induction therapy, the mean CRP level fell from 12.8 mg/L to 4.7 mg/L. Endoscopic evaluation was performed before and after infliximab in seven patients, showing an improvement in mucosal lesions in four patients, persistent mild endoscopic activity in two patients and no improvement in one patient. One patient underwent proctocolectomy.

Conclusion  Infliximab therapy seems to be effective in inducing and maintaining a clinical response in refractory ulcerative proctitis.
Favourable outcome of patients with childhood acute promyelocytic leukaemia after treatment with reduced cumulative anthracycline doses
Authors: Creutzig Ursula , Zimmermann Martin , Dworzak Michael , Urban Christian , Henze Günter , Kremens Bernhard , Lakomek Max , Bourquin Jean‐Pierre , Stary Jan , Reinhardt Dirk
Published: March 2010

Acute promyelocytic leukaemia (APL) treatment often includes high cumulative doses of anthracyclines, which can cause long‐term cardiotoxicity. Here, we report the favourable outcome in 81 paediatric APL patients treated according to the consecutive acute myeloid leukaemia‐Berlin/Frankfurt/Muenster (AML‐BFM) trials ‐93/‐98/‐2004 with an anthracycline‐cytarabine regimen in combination with all‐trans‐retinoid acid (ATRA). Outcomes achieved by treatment with a reduced cumulative anthracycline dose (350 mg/m2) were comparable to those reported for studies with higher doses. Five‐year overall survival of the total cohort was 89 ± 4% and event‐free survival (pEFS) was 73 ± 6%. Overall survival was similar when comparing AML‐BFM trial periods (trial 93: 88 ± 8%, 98: 85 ± 7% and 2004: 94 ± 8%, P(logrank) = 0·63). Seventy‐five (93%) patients achieved complete remission. Most fatal events occurred during the first 6 weeks of treatment. Long‐term cardiotoxicity was observed in one patient. Two patients suffered from secondary haematological malignancies. Salvage treatment was effective in 7/9 patients (78%) with relapsed APL, who now are long‐term survivors after second line combination treatment with arsenic trioxide (4/7 patients) and stem cell transplantation (5/7 patients). Our results demonstrate that – combined with ATRA – a lower cumulative anthracycline dose can be used safely to maintain high cure rates and promote the reduction of long‐term sequelae, such as cardiotoxicity in APL patients.
QBOL: a new EU project focusing on DNA barcoding of Quarantine organisms
Authors: Bonants P. , Groenewald E. , Rasplus J. Y. , Maes M. , De Vos P. , Frey J. , Boonham N. , Nicolaisen M. , Bertacini A. , Robert V. , Barker I. , Kox L. , Ravnikar M. , Tomankova K. , Caffier D. , Li M. , Armstrong K. , Freitas‐Astúa J. , Stefani E. , Cubero J. , Mostert L.
Published: March 2010

In 2009 a new three year EU funded project (QBOL) started on DNA barcoding of important plant pests. An international consortium of 20 partners (universities, research institutes, and phytosanitary organizations) from around the world, coordinated by Plant Research International (Wageningen, the Netherlands), will collect DNA barcodes from many plant pathogenic quarantine organisms, store these sequences in a database accessible over the internet, develop a DNA bank and train end‐users. All these activities should help National Plant Protection Services in the correct identification and detection of plant pathogenic quarantine organisms.
Acoustic detection of regulated pests in hardwood material
Authors: Chesmore D. , Schofield J.
Published: March 2010

Early detection of invasive species of wood boring Coleoptera in imported plants and plant products is of considerable importance due to the potential environmental impact and high cost of eradication if the species becomes established. Detection is made difficult as in the majority of cases, there is little or no evidence of the presence of larvae inside the imported material. Acoustic methods can be employed to detect movement and feeding activity and also identify the species if it has distinctive feeding characteristics. This paper reports on progress into the design and preliminary testing of practical devices for use by plant health inspectors.
Determination of cycle cut off in real‐time PCR for the detection of regulated plant pathogens
Authors: Chandelier A. , Planchon V. , Oger R.
Published: March 2010

Given the high importance of an accurate detection for quarantine plant pathogens, and the risk of false positive or false negative results, a detection method must be correctly validated. A statistical procedure has been developed to determine the cycle cut off and the corresponding limit of detection in real‐time PCR, considering a risk of false positive results of 1% and a probability of detection of 95%. The procedure presented in this paper is easy to develop and can be applied to any plant pathogen to be detected by real‐time PCR.
Potential of the electronic‐nose for the diagnosis of bacterial and fungal diseases in fruit trees
Authors: Spinelli F. , Noferini M. , Vanneste J. L. , Costa G.
Published: March 2010

The electronic‐nose instrumentation has advanced rapidly during the past decade, as the need for highly sensitive, fast and accurate analytical measurements have considerably stimulated the interest in developing these sensors as diagnostic tools. Given that the pathogen‐induced plant responses also include changes in emission of volatiles, the electronic‐nose may represent a powerful and operator‐friendly alternative for rapid and reliable screening of asymptomatic plant material. In the present study, the electronic nose EOS835(Sacmi, Imola, Italy), based on metal oxide semiconductors, was used. EOS835was able to detect asymptomatic apple and pear plants experimentally infected withErwinia amylovora(fire blight). The electronic nose was also successfully tested for discriminatingBotrytisandSclerotiniarots on both green and yellow kiwifruits. Even if the electronic‐nose can be successfully used in experimental conditions for early diagnosis of both pre‐ and post‐harvest diseases, its practical application in open fields, nurseries and packing houses still requires further studies.
Organisation of proficiency testing for plant health diagnostic tests: the experience of FAPAS®
Authors: Reynolds A. , Owen L.
Published: March 2010

Proficiency testing (PT) is an established quality assurance measure and is based on the comparison of laboratories’ results in an inter‐laboratory trial. It highlights problems in laboratory analysis and is an educational tool to help improve data quality. This article describes how PT is organised by FAPAS®. FAPAS® is an international PT provider (external quality assessments) for food chemistry, food microbiology, genetically modified material and water/environmental samples. Since 2007, FAPAS® have organized plant health proficiency tests in conjunction with the Plant Pest and Disease Identification Programme at the Food and Environment Research Agency (Fera). Up until 2009, FAPAS® has organised seven plant health proficiency tests that covered the identification of lyophilised bacteria, viruses in leaves and fungi in agar plugs. In 2009, FAPAS® organized over 10 plant health proficiency tests under the banner of ‘PhytoPAS’, including Potato spindle tuber viroid, Phytophthora ramorum, Thrips palmi, Erwinia amylovora, Clavibacter michiganensis subsp. sepedonicus, etc. DNA extracts, cyst nematodes (Globodera pallida) and slides/immunofluorescence (IF) slides have been added to the programme. The organization of the plant health proficiency tests follows a similar pattern. Suitable test materials are prepared and tested for quality before distribution to requesting participants. Laboratories usually have 1–2 months to analyze their samples and return their results. A report is then compiled for issue to laboratories and these contain all results in an anonymous form, so that laboratories can compare their results with those of other participants. If a laboratory’s performance is unsatisfactory then it is up to them to investigate the situation. Thus, the primary purpose of PT is the detection of inaccuracy in a laboratory’s results, so that they can investigate the problems and initiate corrective procedures.
The EPPO pest risk analysis scheme: comments on using risk scales
Authors: MacLeod A.
Published: March 2010

The pest risk assessment component of the EPPO pest risk analysis (PRA) scheme requires many factors to be considered before the overall risk from a pest or pest‐pathway combination is estimated. Each risk factor to consider appears as a question in the risk assessment stage of the PRA scheme. The way in which risk factors are rated within the EPPO scheme are described and compared with two pest risk assessment systems from North America that use rank‐order measures to represent composite risk factors during the risk assessment process. It is concluded that a description or metric for each division of a scale that describes the risk factor, for example area occupied, frequency of occurrence and likelihood of an event, would help risk assessors to use the EPPO PRA scheme and should make the risk assessment stage of the scheme more consistent, leading to improved PRAs.
The demarcation of Globodera rostochiensis and Globodera pallida infestations in fields for seed potatoes, using a Monte Carlo approach
Authors: Schomaker C. H. , Been T. H.
Published: March 2010

A Monte Carlo approach was utilized to calculate the size of the demarcation unit, necessary to cover infestations with Globodera rostochiensis and Globodera pallida (PCN), detected with the new EU‐sampling method. Results from 90 sampled fields were used to obtain frequency distributions of the central population density (CPD), the length and width gradients of infestation foci and the distance between ‘primary’ and ‘secondary’ foci within one field section in the direction of cultivation. With a simulation model written in R, a free software environment for statistical computing, the dimensions of the demarcation unit were calculated, based on the dimensions of the sampling unit, the position of the ‘primary’ infestation within the sampling unit and the size of the infestation focus. It is concluded that a demarcation of 90% of possible foci positions and dimension, analogous to the specified detection probability of the EU sampling method, provides sufficient security to demarcate any infestation. With the preferred sampling unit of 11 m width and 300 m length (1/3 ha sampled), used in The Netherlands, only 0.61% of the cyst numbers will be situated outside the demarcated unit. These cyst numbers compare to 0.17% of total amount of cysts in the EU infestation model: 1 focus with a CPD of 100 cysts kg−1 and three foci with CPDs of 50 cysts kg−1. The required demarcation area has a width of 36 m and a (maximum) length of 402 m and covers an unit of 1.5 ha. The methodology described can be applied to all proposed sampling methods and sampling unit dimensions.
First record of Rhagoletis cingulata (Loew) (Dipt., Tephritidae) in Austria
Authors: Egartner A. , Zeisner N. , Hausdorf H. , Blümel S.
Published: March 2010

The Nearctic eastern cherry fruit fly species Rhagoletis cingulata (Loew) (Dipt., Tephritidae) has been detected several times in different European countries during the last decades. This species as well as Rhagoletis indifferens (Curran) are major pests of cultivated cherries in North America and are classified as quarantine pests in Europe. The introduction and establishment of both species could result in severe problems for Austrian cherry production due to additional infestation pressure caused by overlapping developmental cycles of American and native cherry fruit flies. A survey of both non‐European cherry fruit fly species was carried out during the growing seasons of 2007 and 2008 at eleven sampling sites in the eastern part of Austria. Pherocon® AM yellow sticky traps were installed in cherry trees and replaced at weekly or fortnightly intervals. Identification of the cherry fruit flies caught was based on morphological characteristics. Two specimens of R. cingulata were caught in 2007 in different weeks and at different locations while none were caught in 2008. R. indifferens was not detected at all. While it is possible that these specimens originate from established populations with low densities, it is more likely that the catches derived from accidental introductions.
Current status of the tomato leafminer Tuta absoluta in Greece
Authors: Roditakis E. , Papachristos D. , Roditakis N. E.
Published: March 2010

The tomato leafminer, Tuta absoluta (Meyrick), was recorded in Crete (Greece) for the first time in June 2009. The species was subsequently identified in various geographically distant regions in Crete, Peloponnesus and Western Greece. Damage has been reported in tomato and aubergine greenhouse crops as well as in open field tomato crops. In two cases, infestations of the indigenous lepidopteran species Phthorimaea operculella (Zeller) erroneously alarmed farmers and local agronomists, as symptoms caused by the two species on tomato leaves and fruits are identical macroscopically. In collaboration with the Ministry of Rural Development and Food an official survey is under way to accurately define the extent of the T. absoluta distribution in the country, while constructing the basis for integrated management of the pest.
Snail and millipede complementarity in decomposing Mediterranean forest leaf litter mixtures
Authors: De Oliveira Tatiana , Hättenschwiler Stephan , Tanya Handa Ira
Published: March 2010

1. The projected increase in loss of biodiversity worldwide has prompted the need to understand the role that diversity plays in key ecosystem functions such as litter decomposition and nutrient cycling. Here we asked how two contrasting species of saprophagous macrofauna and four Mediterranean forest leaf litter species interactively affect decomposition in a 6‐week microcosm study.

2. Litter mass loss and macrofauna relative consumption rates (RCR) were measured on treatments with freshly fallen or partially decomposed leaf litter ofAlnus glutinosa,Fraxinus angustifolia,Pistacia terebinthusandQuercus ilexas single‐species or mixtures in absence and presence of the gastropod,Pomatias elegans,the diplopod,Glomeris marginata, or both macrofauna species.

3. Macrofauna consumed all litter substrates except freshly fallenP. terebinthusas a single‐species litter that was fatal to both animals, although its presence in litter mixtures increased overall RCR. Consumption was higher in partially decomposed than freshly fallen litter, and higher in litter mixtures than in single‐species litter. Both litter state and mixing interacted significantly with macrofauna treatment where generally, RCR byP. elegansalone was inferior to that ofG. marginataalone or in combination withP. elegans.

4. An overall positive complementarity effect on litter RCR betweenG. marginataandP. eleganswas observed in freshly fallen litter. Particularly strong complementarity was observed in two mixtures of freshly fallen litter and also in one mixture of partially decomposed litter.

5. There were no non‐additive effects of litter mixing on litter mass loss in the absence of animals, indicating no interactions among litter substrates during decomposition. However, in the presence of eitherG. marginataand/orP. elegans, positive and negative interactions among litter substrates occurred and were enhanced or reversed by the addition of the second macrofauna species.

6. We conclude that saprophagous macrofauna play a critical role in the decomposition dynamics of Mediterranean forest litter by interacting with each other and by driving interactions among litter substrates.
Interactions among patch area, forest structure and water fluxes in a fog‐inundated forest ecosystem in semi‐arid Chile
Authors: Barbosa Olga , Marquet Pablo A. , Bacigalupe Leonardo D. , Christie Duncan A. , Del‐Val Ek , Gutierrez Alvaro G. , Jones Clive G. , Weathers Kathleen C. , Armesto Juan J.
Published: March 2010

1. The area or size of an ecosystem affects the acquisition, storage and redistribution of energy and matter. Patch size reduction due to natural or anthropogenic habitat loss will not only modify species distribution and patch structure but also affect the ecosystem processes that are, in part, responsible for patch persistence.

2. In a fog‐dependent forest ecosystem, trees and their architectures play essential roles in capturing and redistributing water from collection surfaces. In this paper, we address the question of how forest patch size and structure interact to determine fog water inputs and storage in a fog‐inundated, coastal ecosystem in semi‐arid Chile (30°S).

3. Six forest patches ranging in area from 0·2 to 36 ha on a coastal mountaintop of Fray Jorge National Park were characterized using 0·1 ha plots laid down at the centre of each forest patch. In each patch, we assessed tree basal area as a measure of forest structure, recorded daily air temperature and humidity, measured water influx from stemflow and throughfall (water that has passed through the forest canopy). Soil and litter gravimetric water contents were used as a measure of storage.

4. Total tree basal area per hectare was positively related to patch area, despite some variation at the species level. Mean and maximum air temperatures inside the patches were inversely related to patch size, with maximum temperatures differing by 2 °C on average. Annual fog water capture by trees within forest patches (net throughfall) was estimated in 296·1 mm after rain flux (about 122 mm) was subtracted. Throughfall volume and patch area were uncorrelated, but stemflow volume, soil and litter water contents scaled positively with patch area, showing a functional link between water interception and ecosystem retention.

5. Our study shows that ecosystem area in this mosaic of fog‐dependent temperate forest patches can modify water fluxes and storage capacity of the ecosystem. This finding has important consequences for fragmented landscapes, where large continuous forests are fragmented into smaller patches, affecting not only the persistence of species but also the continuity of critical ecosystem processes.
Clinical reasoning: concept analysis
Authors: Simmons Barbara
Published: March 2010

simmons b. (2010)  Clinical reasoning: concept analysis. Journal of Advanced Nursing 66(5), 1151–1158.

Title.  Clinical reasoning: concept analysis.

Aim.  This paper is a report of a concept analysis of clinical reasoning in nursing.

Background.  Clinical reasoning is an ambiguous term that is often used synonymously with decision‐making and clinical judgment. Clinical reasoning has not been clearly defined in the literature. Healthcare settings are increasingly filled with uncertainty, risk and complexity due to increased patient acuity, multiple comorbidities, and enhanced use of technology, all of which require clinical reasoning.

Data sources.  Literature for this concept analysis was retrieved from several databases, including CINAHL, PubMed, PsycINFO, ERIC and OvidMEDLINE, for the years 1980 to 2008.

Review methods.  Rodgers’s evolutionary method of concept analysis was used because of its applicability to concepts that are still evolving.

Results.  Multiple terms have been used synonymously to describe the thinking skills that nurses use. Research in the past 20 years has elucidated differences among these terms and identified the cognitive processes that precede judgment and decision‐making. Our concept analysis defines one of these terms, ‘clinical reasoning,’ as a complex process that uses cognition, metacognition, and discipline‐specific knowledge to gather and analyse patient information, evaluate its significance, and weigh alternative actions.

Conclusion.  This concept analysis provides a middle‐range descriptive theory of clinical reasoning in nursing that helps clarify meaning and gives direction for future research. Appropriate instruments to operationalize the concept need to be developed. Research is needed to identify additional variables that have an impact on clinical reasoning and what are the consequences of clinical reasoning in specific situations.