bluuebunny/crossref_metadata_2025 huggingface dataset:
Rescue, Amplification, and Large-Scale Production of Helper-Dependent Adenoviral Vectors
Authors: Palmer Donna J. , Ng Philip
Published: July 2011

INTRODUCTION

This protocol describes in detail the rescue, amplification, and large-scale production of helper-dependent adenoviral vectors (HDAds) for gene transfer and gene therapy.

Production of HDAd can be divided into three parts: (1) rescue, which involves converting pHDAd (plasmid form) to HDAd (viral form); (2) amplification, in which the amount of HDAd is increased by serial coinfections (passages) of the producer cells with the HDAd and the helper virus; and (3) large-scale production to generate large quantities of HDAd. HDAds (also referred to as gutless, gutted, mini, fully deleted, high-capacity, Δ, pseudo) are deleted of all virus-coding sequences. HDAds retain the advantages of early-generation Ad vectors including high-efficiency in vivo transduction and high-level transgene expression. However, the absence of viral gene expression in transduced cells permits long-term transgene expression in the absence of chronic toxicity. Moreover, the deletion of the viral sequences permits a cloning capacity of ∼37 kb. This allows for the delivery of whole-genomic loci, multiple transgenes, and large cis-acting elements to enhance, prolong, and regulate transgene expression. In addition, because the vector genome exists episomally in transduced cells, the risks of germ-line transmission and insertional mutagenesis leading to oncogenic transformation are negligible.
Electrophysiological Recording from Drosophila Taste Sensilla
Authors: Benton Richard , Dahanukar Anupama
Published: July 2011

INTRODUCTION

The chemical senses smell and taste, detect and discriminate an enormous diversity of environmental stimuli and provide fascinating but challenging models to investigate how sensory cues are represented in the brain. Important stimulus-coding events occur in peripheral sensory neurons, which express specific combinations of chemosensory receptors with defined ligand-response profiles. These receptors convert ligand recognition into spatial and temporal patterns of neural activity that are transmitted to and interpreted in central brain regions. Drosophila provides an attractive model to study chemosensory coding, because it possesses relatively simple peripheral olfactory and gustatory systems that display many organizational parallels to those of vertebrates. Moreover, virtually all of the peripheral chemosensory neurons are easily accessible for physiological analysis, as they are exposed on the surface of sensory organs in specialized sensory hairs called sensilla. In recent years, improvements in microscopy and instrumentation for electrode manipulation have opened up the much smaller Drosophila system to electrophysiological techniques, powerfully complementing many years of molecular genetic studies. As with most electrophysiological methods, there is probably no substitute for learning this technique directly from a laboratory in which it is already established. This protocol describes the basics of setting up the electrophysiology rig and stimulus delivery device, sample preparation, and performing and analyzing recordings of stimulus-evoked activity from Drosophila taste sensilla.
Setup and Demonstration of a Nanoelectrospray Ionization Source and Tandem Mass Spectrometry
Authors: Link Andrew J. , LaBaer Joshua
Published: July 2011

INTRODUCTION

In this protocol, an electrospray ionization source is assembled and an empty pulled microcapillary column is connected to the assembly for infusion of a peptide sample. The microcapillary column is positioned directly in front of the opening to the mass spectrometer. Angiotensin I peptide is infused using a nanoelectrospray ionization (nanoESI) source to demonstrate the fundamentals of electrospray ionization and tandem mass spectrometry (MS/MS). The setup can also be used to tune the mass spectrometer for liquid chromatography (LC)-MS/MS experiments. After being tuned, the ion trap mass spectrometer is operated manually so that precursor scans can be performed to detect and analyze precursor ions. A selected ion is trapped and fragmented to demonstrate the principles of MS/MS.
Facilitative and antagonistic interactions between plant viruses in mixed infections
Authors: SYLLER JERZY
Published: July 2011

Mixed infections of plant viruses are common in nature, and a number of important virus diseases of plants are the outcomes of interactions between causative agents. Multiple infections lead to a variety of intrahost virus–virus interactions, many of which may result in the generation of variants showing novel genetic features, and thus change the genetic structure of the viral population. Hence, virus–virus interactions in plants may be of crucial significance for the understanding of viral pathogenesis and evolution, and consequently for the development of efficient and stable control strategies. The interactions between plant viruses in mixed infections are generally categorized as synergistic or antagonistic. Moreover, mixtures of synergistic and antagonistic interactions, creating usually unpredictable biological and epidemiological consequences, are likely to occur in plants. The mechanisms of some of these are still unknown. This review aims to bring together the current knowledge on the most commonly occurring facilitative and antagonistic interactions between related or unrelated viruses infecting the same host plant. The best characterized implications of these interactions for virus–vector–host relationships are included. The terms ‘synergism’ and ‘helper dependence’ for facilitative virus–virus interactions, and ‘cross‐protection’ and ‘mutual exclusion’ for antagonistic interactions, are applied in this article.
The tomato UV‐damaged DNA‐binding protein‐1 (DDB1) is implicated in pathogenesis‐related (PR) gene expression and resistance to Agrobacterium tumefaciens
Authors: LIU JIKAI , LI HANJING , MIAO MIN , TANG XIAOFENG , GIOVANNONI JIM , XIAO FANGMING , LIU YONGSHENG
Published: July 2011

Plants defend themselves against potential pathogens via the recognition of pathogen‐associated molecular patterns (PAMPs). However, the molecular mechanisms underlying this PAMP‐triggered immunity (PTI) are largely unknown. In this study, we show that tomato HP1/DDB1, coding for a key component of the CUL4‐based ubiquitin E3 ligase complex, is required for resistance to Agrobacterium tumefaciens. We found that the DDB1‐deficient mutant (high pigment‐1, hp1) is susceptible to nontumorigenic A. tumefaciens. The efficiency of callus generation from the hp1 cotyledons was extremely low as a result of the necrosis caused by Agrobacterium infection. On infiltration of nontumorigenic A. tumefaciens into leaves, the hp1 mutant moderately supported Agrobacterium growth and developed disease symptoms, but the expression of the pathogenesis‐related gene SlPR1a1 and several PTI marker genes was compromised at different levels. Moreover, exogenous application of salicylic acid (SA) triggered SlPR1a1 gene expression and enhanced resistance to A. tumefaciens in wild‐type tomato plants, whereas these SA‐regulated defence responses were abolished in hp1 mutant plants. Thus, HP1/DDB1 may function through interaction with the SA‐regulated PTI pathway in resistance against Agrobacterium infection.
The challenge of haemoglobinopathies in resource‐poor countries
Authors: Weatherall David J.
Published: July 2011

The haemoglobinopathies, inherited disorders of the structure or synthesis of haemoglobin, are the commonest monogenic diseases. Approximately 80% of the annual births of babies with these conditions occur in low‐or middle‐income countries, many of which have extremely limited facilities for their control and management. Given that the population size of many of them is growing and, as social and public health facilities improve, increasing numbers of these babies will survive to present for diagnosis and treatment. Hence, the haemoglobinopathies will constitute an increasing global health burden. Hitherto, they have been largely ignored by governments of high‐frequency countries and by the international health agencies. However, a start has been made in developing control programmes in some low‐income countries and there is already considerable evidence that much can be done to improve the situation by the development of partnerships between groups in richer countries and centres in low‐income countries. The natural extension of this approach is the further development of partnerships between countries where expertise in this field has been developed and adjacent countries where no such expertise exists. It is vital that the haematology community of the richer countries becomes involved in programmes of this type while, at the same time, putting pressure on their governments and on international health agencies for support for this work.
Lack of responsiveness to 1‐desamino‐d arginin vasopressin (desmopressin) in male patients with nephrogenic syndrome of inappropriate antidiuresis: from bench to bedside
Authors: Vandergheynst Frederic , Pradier Olivier , Beukinga Ingrid , Kornreich Anne , Vassart Gilbert , Decaux Guy
Published: July 2011

Eur J Clin Invest 2012; 42 (3): 254–259

Background  Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a recently described entity, linked to gain‐of‐function mutations (R137C and R137L) in arginine vasopressin (AVP) gene leading to chronic activation of tubular V2 AVP receptor (V2R) and thus free water reabsorption. In addition to collecting duct cells, the V2R is also expressed in endothelial cells, where it mediates the rise in circulating levels of von Willebrand factor (vWF) and coagulation factor VIII (fVIII).

Recent in vitro data showed that these mutant receptors are resistant to vasopressin‐stimulated cAMP production. We aimed to explore by clinical observations the sensitivity to vasopressin of the R137C–V2R mutant in vivo.

Material and methods  We performed a stimulation test with 1‐desamino‐d arginin vasopressin (dDAVP) 0·3 μg/kg of bodyweight in three patients (two hemizygous male and one heterozygous female) with NSIAD with R137C mutation and measured on the one hand the levels of vWF and fVIII and the other hand urine osmolality and albumin excretion (UAE).

Results  Whereas the female heterozygous patient displayed normal response to simulation by dDAVP (except for UAE), no increase in vWF, fVIII, urinary osmolality and UAE was observed among hemizygous male patients.

Conclusions  Coherent with in vitro observation in transfected cells, our clinical observations demonstrate that the R137C–V2R mutant is resistant to vasopressin stimulation in its physiological sites of expression.
The application of spatial derivatives to non‐potential field data interpretation
Authors: Beamish David
Published: July 2011

Source/body edge detection is a common feature in the processing and interpretation of potential field data sets. A wide range of spatial derivatives is available to enhance the information contained in the basic data. Here the ability of these procedures to assist with the mapping interpretation of non‐potential field data is considered. The study uses airborne electromagnetic (conductivity) data but also provides a general context for other conductivity/resistivity data, provided the non‐potential field nature of active and thus spatially‐focused, measurements is acknowledged. The study discusses and demonstrates the application of a range of common spatial derivative procedures, including the analytic signal and upward continuation, to both magnetic and conductivity data. The ability of the tilt derivative to provide enhanced mapping of conductivity data is considered in detail. Tilt and its associated functions are formed by taking combinations of vertical and horizontal derivatives of the data set. Theoretical forward modelling studies are first carried out to assess the performance of the tilt derivative in relation to the detection and definition of concealed conductivity structure. The tilt derivative embodies automatic gain control that normalizes the detection and definition of both weak and strong conductivity gradients across an appropriate subsurface depth range. The use of high‐order spatial derivatives inevitably results in a degree of noise (cultural perturbation) amplification that is survey and technique specific. Both of these aspects are considered using practical case studies of jointly obtained magnetic and conductivity data at a variety of spatial scales.
Carbon (δ13C) and nitrogen (δ15N) stable isotope composition in plant and soil in Southern Patagonia's native forests
Authors: Peri Pablo L. , Ladd Brenton , Pepper David A. , Bonser Stephen P. , Laffan Shawn W. , Amelung Wulf
Published: July 2011

Stable isotope natural abundance measurements integrate across several biogeochemical processes in ecosystem N and C dynamics. Here, we report trends in natural isotope abundance (δ13C and δ15N in plant and soil) along a climosequence of 33 Nothofagus forest stands located within Patagonia, Southern Argentina. We measured 28 different abiotic variables (both climatic variables and soil properties) to characterize environmental conditions at each of the 33 sites. Foliar δ13C values ranged from −35.4‰ to −27.7‰, and correlated positively with foliar δ15N values, ranging from −3.7‰ to 5.2‰. Soil δ13C and δ15N values reflected the isotopic trends of the foliar tissues and ranged from −29.8‰ to −25.3‰, and −4.8‰ to 6.4‰, respectively, with no significant differences between Nothofagus species (Nothofagus pumilio, Nothofagus antarctica, Nothofagus betuloides). Principal component analysis and multiple regressions suggested that mainly water availability variables (mean annual precipitation), but not soil properties, explained between 42% and 79% of the variations in foliar and soil δ13C and δ15N natural abundance, which declined with increased moisture supply. We conclude that a decline in water use efficiency at wetter sites promotes both the depletion of heavy C and N isotopes in soil and plant biomass. Soil δ13C values were higher than those of the plant tissues and this difference increased as annual precipitation increased. No such differences were apparent when δ15N values in soil and plant were compared, which indicates that climatic differences contributed more to the overall C balance than to the overall N balance in these forest ecosystems.
Information security policies in the UK healthcare sector: a critical evaluation
Authors: Stahl Bernd Carsten , Doherty Neil F. , Shaw Mark
Published: July 2011

All organisations must take active steps to maintain the security and integrity of their information resources, and nowhere is this strategy more critical than in hospitals where issues of information accuracy and patient confidentiality are paramount. Of all the tools at the information security manager's disposal, none is more widely valued and used than the information security policy. Much research therefore concentrates on the way in which information security policies contribute to the protection of systems from internal and external threats. Such work is legitimate and important, but it often fails to explore alternative views of security and related policies. Against this backdrop, this paper seeks to provide novel insights into the role and purpose of information security policies by reviewing them through a critical theoretical lens. It presents the results of a critical discourse analysis which looked for evidence of ideology and hegemony within a sample of information security policies from the UK's National Health Service. The findings support the contention that an alternative description of information security policies from a critical perspective provides better insights into existing problems than most mainstream work. The paper concludes by discussing the implications of the findings and future research avenues.
Patterns of trait convergence and divergence among native and exotic species in herbaceous plant communities are not modified by nitrogen enrichment
Authors: Cleland Elsa E. , Clark Chris M. , Collins Scott L. , Fargione Joseph E. , Gough Laura , Gross Katherine L. , Pennings Steven C. , Suding Katharine N.
Published: July 2011

1. Community assembly theories predict that the success of invading species into a new community should be predictable by functional traits. Environmental filters could constrain the number of successful ecological strategies in a habitat, resulting in similar suites of traits between native and successfully invading species (convergence). Conversely, concepts of limiting similarity and competitive exclusion predict native species will prevent invasion by functionally similar exotic species, resulting in trait divergence between the two species pools. Nutrient availability may further alter the strength of convergent or divergent forces in community assembly, by relaxing environmental constraints and/or influencing competitive interactions.

2. To investigate how nutrient availability influences forces of divergence and convergence during the invasion of exotic species into native communities, we conducted multivariate analyses of community composition and functional traits from naturally assembled plant communities in long‐term nitrogen (N) addition experiments across North America.

3. Relative abundances of key functional traits differed between the native and exotic plant communities, consistent with limiting similarity or a trait bias in the exotic species pool. Environmental context also played an important role in invasion because sites varied in the identity of the traits that predicted dissimilarity between native and exotic communities. Nitrogen enrichment did not alter these patterns.

4. Nitrogen enrichment tended to increase exotic abundance, but this result was driven by a dramatic increase in exotics in only a few experiments. When similarity between native and exotic communities was included in the statistical model, N enrichment no longer predicted an increase in exotic relative abundance. Instead, sites with the highest abundance of exotic species were the ones where native and exotic communities had the highest trait similarity.

5. Synthesis. Our analysis of natural patterns of invasion across herbaceous communities in North America found evidence of both divergent and convergent forces on community assembly with exotic species. Together, these results suggest that while functionally dissimilar exotic species may be more likely to invade, they are unlikely to become abundant unless they have traits pre‐adapting them to environmental conditions in their invaded range. Contrary to prior studies, invasion was not consistently promoted by N enrichment.
Sexual differences in year‐to‐year flowering trends in the dioecious multi‐stemmed shrub Lindera triloba: effects of light and clonal integration
Authors: Matsushita Michinari , Nakagawa Michiko , Tomaru Nobuhiro
Published: July 2011

1. To obtain information on mechanisms underlying between‐sex differences in flowering patterns of dioecious plants, we tested two hypotheses: first, that sexual differences in year‐to‐year flowering variations result from differences in sensitivity to inter‐annual variations of environmental factors and second, that the degree to which physiological integration within genets controls the flowering of ramets differs between the sexes.

2. The flowering patterns of a dioecious multi‐stemmed understorey shrub, Lindera triloba, were monitored both at the ramet and genet levels over five consecutive years in a 4‐ha plot.

3. The numbers of flowering genets of both sexes fluctuated annually and were positively related to the hours of sunshine during July and August in the previous year. The number of flowering ramets within genets and inflorescence numbers within ramets or genets tended to be larger for male genets than for female genets. There was significant inter‐annual variation in the number of flowering ramets within male genets, but not within female genets. Although both sexes showed significant inter‐annual variation in inflorescence numbers, the extent of variation was larger for males than females. These between‐sex differences resulted from significant relationships for male genets between their number of flowering ramets and both their total number of ramets and the number of hours of sunshine they experienced, whereas there were no such relationships for female genets.

4. There were also between‐sex differences in the probability of flowering and inflorescence production of individual ramets within genets: male ramets exhibited a stronger sensitivity of flowering than females to the growth status of the genets to which they belonged. This suggests that individual ramets within genets bloom in an integrated manner rather than in an autonomous manner, and that the magnitude of integrated flowering of ramets differs between sexes.

5. Synthesis. This study not only measured flowering at the whole‐plant level but also showed that flowering patterns of the lower‐level module were controlled within the higher‐level module differently by male and female plants. Future studies should be designed to consider environmental variation between years and modular integrations, when investigating differences between the sexes during the reproduction of dioecious plants.
Working memory in Down syndrome: is there a dual task deficit?
Authors: Lanfranchi S. , Baddeley A. , Gathercole S. , Vianello R.
Published: July 2011

Background  Recent studies have shown that individuals with Down syndrome (DS) are poorer than controls in performing verbal and visuospatial dual tasks. The present study aims at better investigating the dual task deficit in working memory in individuals with DS.

Method  Forty‐five individuals with DS and 45 typically developing children matched for verbal mental age completed a series of verbal and visuospatial working memory tasks, involving conditions that either required the combination of two tasks in the same modality (verbal or visual) or of cross‐modality pairs of tasks.

Results and conclusions  Two distinct deficits were found in individuals with DS: impairment in verbal tasks and further impairment in all dual task conditions. The results confirm the hypothesis of a central executive impairment in individuals with DS.
Social integration of people with intellectual disability: insights from a social psychological research programme
Authors: Dijker A. , van Alphen L. , Bos A. , van den Borne B. , Curfs L.
Published: July 2011

Background  Social integration of people with intellectual disability (ID) moving into regular neighbourhoods tends to be studied and evaluated without detailed knowledge about the social psychological aspects of everyday interaction between neighbours with and without ID. The goal of the present paper is to show how the authors' social psychological research programme may contribute to this field of inquiry.

Methods  The different ways in which societies respond to features and behaviours that may be perceived as deviant are theoretically analysed. Results of empirical studies are reported to clarify how social responses to people with ID are special in terms of perceptions, emotions and interaction desires of people with and without ID during a pre‐contact and contact phase.

Results  On the basis of the theoretical analysis, it is concluded that regular neighbouring in modern Western society often takes the form of benevolent tolerance, rather than stigmatisation and prejudice. However, empirical studies reveal that, prior to getting people with ID as new neighbours, prospective neighbours without ID experience a specific pattern of emotions that are associated with specific desires (e.g. with respect to information supply or a caring relationship). These anticipatory reactions are dependent on the expected size of the group moving in and on the severity of ID. Furthermore, while actually engaging in neighbouring, neighbours with and without ID appear to have experiences related to behaviour of residents, staff and features of housing facilities that are perceived as (in)congruent with regular neighbouring.

Conclusions  It is concluded that interpersonal relationships between neighbours with and without ID should not be simplified in terms of attitudes that would be primarily prejudiced/stigmatising versus entirely accepting. Rather, our studies paint a more complex picture of sometimes ambivalent thoughts, feelings and interaction needs that all should be taken into account to make social integration a success.
Clients with intellectual disabilities on psychiatric units: care coordination for positive outcomes
Authors: KRCH‐COLE E. L. , LYNCH P. , AILEY S. H.
Published: July 2011

Accessible summary

Resources for treatment of clients with intellectual disabilities and a psychiatric illness are scarce in the USA.

This case study looks at a treatment approach which includes multidisciplinary as well as interagency cooperation and coordination to enhance the outcomes for a client in crisis.

This case study presents a Best Practice model for clients with intellectual disabilities who are treated for psychiatric illness and maladaptive or unsafe behaviours on a general adult psychiatric inpatient unit.

The transition from residential facilities to and from the psychiatric hospital setting is difficult for individuals with intellectual disabilities (ID). In the USA, specialized psychiatric units for individuals with ID are uncommon and this population is usually served in generalized services. Nevertheless, providers of mental health services in the USA receive little training in their specific needs. Best practices call for coordination of plans between psychiatric units and community agencies, multidisciplinary care plans, staff education and comprehensive discharge planning in order to improve outcomes of psychiatric hospitalization. An inner city psychiatric unit in a major academic medical centre and a community agency providing residential care for individuals with ID cooperated to provide a plan of care for a client with ID both for hospitalization and for discharge leading to improved outcomes.
Pudendal afferent innervation of the guinea pig external anal sphincter
Authors: Lynn P. A. , Brookes S. J. H.
Published: July 2011

Background  Sensory nerves to the external anal sphincter (EAS) contribute to mechanisms promoting continence and defecation, yet we know little about their function. We investigated the function of pudendal mechanoreceptors to the guinea pig EAS.

Methods  Extracellular recordings from pudendal nerve branches to 14 EAS preparations, in vitro, were used to characterize extrinsic primary afferent nerve endings activated by circumferential distension.

Key Results  All 42 pudendal nerve afferents were silent under non‐distended conditions. Thirty‐three of 42 afferents had slowly adapting, low‐threshold responses to circumferential stretch that correlated with stretch length (R2 = 0.40, P < 0.001). Twenty of 20 slowly adapting afferents reduced firing when stretch was maintained for 60 s (P < 0.0001). They had low thresholds to von Frey hairs (0.1–0.5 mN). Firing frequency correlated with degree of compression (R2 = 0.40, P < 0.0001). Nine of 42 afferents had rapidly adapting responses at the onset/offset of isometric stretch. During ramp stretch, small vibrations from the stepper motor evoked rapid bursts of firing at frequencies up to 200 Hz. Instantaneous frequency was unrelated to either the rate or degree of stretch. Rapidly adapting units had low thresholds (0.1–0.2 mN) to von Frey hairs and small punctate mechanotransduction sites. Responses to von Frey hair compression were also rapidly adapting, and instantaneous frequency was unrelated to the degree of compression.

Conclusions & Inferences  The EAS has two functional classes of mechanoreceptors: slowly adapting low‐threshold and rapidly adapting low‐threshold mechanoreceptors. These two classes of afferents are likely to be involved in the maintenance of continence, and the process of defecation.
Hirano body‐rich subtypes of Creutzfeldt–Jakob disease
Authors: Martinez‐Saez E. , Gelpi E. , Rey M. J. , Ferrer I. , Ribalta T. , Botta‐Orfila T. , Nos C. , Yagüe J. , Sanchez‐Valle R.
Published: July 2011

E. Martinez‐Saez, E. Gelpi, M. J. Rey, I. Ferrer, T. Ribalta, T. Botta‐Orfila, C. Nos, J. Yagüe and R. Sanchez‐Valle (2012) Neuropathology and Applied Neurobiology38, 153–161

Hirano body‐rich subtypes of Creutzfeldt–Jakob disease

Background: In definite Creutzfeldt–Jakob disease (CJD), morphological and immunohistochemical patterns are useful to identify molecular subtypes. Severe cerebellar pathology and hippocampal involvement helps to identify VV subtypes. The rare VV1 variant (<1%), more frequent in young individuals, is additionally characterized by the presence of ballooned neurones in affected areas. In 1985, Cartier et al. described a family cluster of three individuals with an ataxic CJD form, showing, in addition to severe cerebellar and hippocampal involvement, the presence of frequent Hirano bodies (HB) in CA1 pyramidal neurones. HB are frequently found in aged individuals with Alzheimer pathology although they are not a specific finding. Aims and methods: In this study, we evaluated the presence of HB in hippocampi of 54 genetically and molecularly characterized CJD cases, aiming to elucidate whether additional morphological features could be helpful to point to molecular subtypes. Results: We identified nine cases (four VV1, one out of three MV2K, three out of six MV2K+2C and one MV carrying a 96‐base pair insertion) with abundant, partly bizarre and clustered HB in CA1 sector, not observed in other subtypes. The presence of HB was independent of hippocampal involvement by the disease itself. Conclusions: Clusters of abundant HB might be found in rare CJD subtypes such as VV1, MV2K/MV2K+2C and some genetic cases. In addition to histopathological and PrP immunohistochemical deposition patterns, their presence might be a useful additional morphologic feature that could point to the molecular subtype, especially when genetic and/or Western blot analyses are not available.
Photosynthetic photon flux density and phytochrome B interact to regulate branching in Arabidopsis
Authors: SU HONGWEN , ABERNATHY SCOTT D. , WHITE RICHARD H. , FINLAYSON SCOTT A.
Published: July 2011

Branching is regulated by environmental signals including phytochrome B (phyB)‐mediated responses to the ratio of red to far red light. While the mechanisms associated with phytochrome regulation of branching are beginning to be elucidated, there is little information regarding other light signals, including photosynthetic photon flux density (PPFD) and how it influences phytochrome‐mediated responses. This study shows that Arabidopsis (Arabidopsis thaliana) branching is modified by both varying PPFD and phyB status and that significant interactions occur between these variables. While phyB deficiency decreased branching when the PPFD was low, the effect was suppressed by high PPFD and some branching aspects were actually promoted. Photosynthesis measurements showed that PPFD may influence branching in phyB‐deficient plants at least partially through a specific signalling pathway rather than directly through energy effects on the shoot. The expression of various genes in unelongated buds of phyB‐deficient and phyB‐sufficient plants grown under high and low PPFD demonstrated potential roles for several hormones, including auxin, cytokinins and ABA, and also showed imperfect correlation between expression of the branching regulators BRC1 and BRC2 and bud fate. These results may implicate additional undiscovered bud autonomous mechanisms and/or components contributing to bud outgrowth regulation by environmental signals.
Efficacy of a 0.0584% hydrocortisone aceponate spray in presumed feline allergic dermatitis: an open label pilot study
Authors: Schmidt Vanessa , Buckley Laura M. , McEwan Neil A. , Rème Christophe A. , Nuttall Tim J.
Published: July 2011

This study evaluated the efficacy of a 0.0584% hydrocortisone aceponate (HCA) spray (Cortavance®; Virbac SA) in 10 cats with presumed allergic dermatitis. The cats initially received two sprays/100 cm2of skin once daily. Clinical lesions (a Feline Dermatitis Extent and Severity Index; FeDESI), pruritus (10 cm visual analog scale with grade descriptors) and owner assessments of efficacy, tolerance and ease of use (from 1 = very poor to 5 = excellent) were assessed every 14 days. The frequency of treatment was reduced after day 28 in cats with a >50% reduction in FeDESI and pruritus scores. One cat was lost to follow up at day 28 and two at day 42. Intention‐to‐treat data were analysed. The FeDESI [mean (SD): day 0, 42.2 (15.7) and day 56, 9.9 (11.7);P < 0.0001] and pruritus scores [day 0, 61.2 mm (20.1) and day 56, 14.6 mm (16.1);P < 0.0001] significantly decreased throughout the trial. The owner scores for tolerance [median (range): day 14, 4 (1–5) and day 56, 4 (3–5);P = 0.003] and ease of administration [day 14, 3 (2–5) and day 56, 4 (2–5);P = 0.02] significantly increased during the trial, but there was no significant change in efficacy scores [day 14, 4 (3–5) and day 56, 4 (2–5);P = 0.5]. There were no adverse effects attributable to the HCA spray, no significant changes in weight [mean (SD): day 0, 5.0 kg (1.4) and day 56, 5.0 kg (1.6);P = 0.51] and no significant changes in haematology, biochemistry or urinalysis (n = 4). Six cats required every‐other‐day treatment and four required daily treatment. In conclusion, HCA spray appeared to be effective and safe in these cats, although it is not licensed for use in this species.
Primary brain tumours and specific serum immunoglobulin E: a case–control study nested in the European Prospective Investigation into Cancer and Nutrition cohort
Authors: Schlehofer B. , Siegmund B. , Linseisen J. , Schüz J. , Rohrmann S. , Becker S. , Michaud D. , Melin B. , Bas Bueno‐de‐Mesquita H. , Peeters P. H. M. , Vineis P. , Tjonneland A. , Olsen A. , Overvad K. , Romieu I. , Boeing H. , Aleksandrova K. , Trichopoulou A. , Bamia C. , Lagiou P. , Sacerdote C. , Palli D. , Panico S. , Sieri S. , Tumino R. , Sanchez M.‐J. , Rodriguez L. , Dorronsoro M. , Duell E. J. , Chirlaque M.‐D. , Barricarte A. , Borgquist S. , Manjer J. , Gallo V. , Allen N. E. , Key T. J. , Riboli E. , Kaaks R. , Wahrendorf J.
Published: July 2011

To cite this article: Schlehofer B, Siegmund B, Linseisen J, Schüz J, Rohrmann S, Becker S, Michaud D, Melin B, Bas Bueno‐de‐Mesquita H, Peeters PHM, Vineis P, Tjonneland A, Olsen A, Overvad K, Romieu I, Boeing H, Aleksandrova K, Trichopoulou A, Bamia C, Lagiou P, Sacerdote C, Palli D, Panico S, Sieri S, Tumino R, Sanchez M‐J, Rodriguez L, Dorronsoro M, Duell EJ, Chirlaque M‐D, Barricarte A, Borgquist S, Manjer J, Gallo V, Allen NE, Key TJ, Riboli E, Kaaks R, Wahrendorf J. Primary brain tumours and specific serum immunoglobulin E: a case–control study nested in the European Prospective Investigation into Cancer and Nutrition cohort. Allergy 2011; 66: 1434–1441.

Background:  Case–control studies suggest that patients with allergic diseases have a lower risk of developing glioma but not meningioma or schwannoma. However, those data can be differentially biased. Prospective studies with objective measurements of immunologic biomarkers, like immunoglobulin E (IgE), in blood obtained before cancer diagnosis could help to clarify whether an aetiological association exists.

Methods:  The present case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) measured specific serum IgE as a biomarker for the most common inhalant allergens in 275 glioma, 175 meningioma and 49 schwannoma cases and 963 matched controls using the ImmunoCAP specific IgE test. Subjects with an IgE level ≥0.35 kUA/l (kilo antibody units per litre) were classified as sensitized by allergens. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by adjusted conditional logistic regression models for each tumour subtype. The effect of dose–response relationship was assessed in five increasing IgE level categories to estimate P‐values for trend.

Results:  The risk of glioma was inversely related to allergic sensitization (OR = 0.73; 95% CI 0.51–1.06), especially pronounced in women (OR = 0.53; 95% CI 0.30–0.95). In dose–response analyses, for high‐grade glioma, the lowest OR was observed in sera with the highest IgE levels (P for trend = 0.04). No association was seen for meningioma and schwannoma.

Conclusion:  The results, based on serum samples prospectively collected in a cohort study, provide some support for the hypothesis that individuals with allergic sensitization are at reduced risk of glioma and confirm results from previous case–control studies.
Effects of GnRH or Progesterone Treatment on Day 5 Post‐AI on Plasma Progesterone, Luteal Blood Flow and Leucocyte Counts During the Luteal Phase in Dairy Cows
Authors: Garcia‐Ispierto I , López‐Gatius F
Published: July 2011

Contents

This study was designed to test the effects of progesterone or GnRH treatment on day 5 post‐AI on fertility and luteal function in dairy cows and heifers. Five days after AI, 32 animals were randomly assigned to a control, intravaginal progesterone for 14 days progesterone releasing intravaginal device (PRID) or GnRH treatment group. On days 5, 7, 12, 14, 17 and 19 post‐AI, each animal underwent colour Doppler ultrasonography of the corpus luteum and blood samples were collected for cell counts and plasma progesterone determination. Through general linear model repeated measures analysis of variance, significant effects were observed of treatment, parity, inseminating bull, reduced vascularization of the CL and pregnancy on plasma progesterone concentrations, whereas mean plasma progesterone and time luteal phase day, and treatment and plasma progesterone concentration on day 5 post‐AI were found to, respectively, affect neutrophil and lymphocyte counts throughout the luteal phase. Moreover, two binary logistic regression analyses were performed. Based on the odds ratio, the likelihood of pregnancy by days 26–32 post‐AI was 23.4 times higher in animals with high mean progesterone levels throughout the study period, compared with animals with low mean progesterone. The likelihood of reduced CL vascularization was 14 times higher in animals treated with PRID, compared with control and GnRH‐treated animals. In conclusion, our results indicate that treatment on day 5 post‐AI with PRID reduced subsequent CL vascularization, whereas GnRH treatment increased plasma progesterone concentrations on day 12 post‐AI, although an effect was identified of the inseminating bull on plasma progesterone levels. Pregnant animals showed higher mean plasma progesterone concentrations than in nonpregnant ones and heifers higher than in lactating cows, whereas blood cell counts differed depending on the treatment and on the mean plasma progesterone concentration on day 5 post‐AI.
Mitigating endoplasmic reticulum stress with revaprazan ameliorates stress‐related mucosal disease
Authors: Kim Jung Ho , Kim Eun Hee , Ock Chanyoung , Hong Hua , Kim Yoon Jae , Kwon Kwang An , Park Dong Kyun , Hahm Ki Baik
Published: July 2011

Background and Aim:  The term “stress‐related mucosal disease” (SRMD) represents conditions ranging from superficial mucosal damage to focal deep mucosal damage in the stomach, of which pathogenesis is deduced to be violent mucosal ischemia or excess oxidative stress, but not fully clarified yet. Under the hypothesis that mucosal cell apoptosis subsequent to endoplasmic reticulum (ER) stress might play a crucial role, we evaluated the efficacy and mechanism that novel acid pump antagonist (APA), revaprazan, alleviated water immersion restraint stress (WIRS) induced SRMD in rats.

Methods:  In order to define whether WIRS‐induced SRMD is associated with ER stress, we checked the alteration in the expression of ER stress markers including GRP78, CHOP, XBP‐1, BiP as well as apoptosis in WIRS‐induced SRMD. The efficacy of revaprazan on either alleviating ER stress or attenuating SRMD was compared with proton pump inhibitor (PPI) and gastroprotectant.

Results:  Ten hours of WIRS induced a severe degree of SRMD, in which ER stress markers including CHOP, XBP1, and BiP were significantly overexpressed in the gastric tissues. However, these markers of ER stress were significantly decreased in the group pretreated with revaprazan compared to PPI or gastroprotectant, accompanied with a significant reduction in apoptotic index. In addition to ER stress, revaprazan imposed anti‐inflammatory benefit to limit SRMD based on significant levels of inflammatory cell apoptosis.

Conclusion:  Endoplasmic reticulum stress accompanied with drastic apoptosis was implicated in the development of SRMD, but revaprazan could rescue the stomach from SRMD through alleviating ER stress in epithelial cells much better than either PPI or gastroprotectant.
Autoimmune pancreatitis and biliary intraepithelial neoplasia of the common bile duct: A case with diagnostically challenging but pathogenetically significant association
Authors: Ohtani Haruo , Ishida Hiroyasu , Ito Yuka , Yamaguchi Takashi , Koizumi Masanori
Published: July 2011

Autoimmune pancreatitis (AIP) (also called IgG4‐related sclerosing pancreatitis (IgG4‐SP)) and IgG4‐related sclerosing cholangitis (IgG4‐SC) are frequently associated with each other. It is generally believed that association of these diseases with pancreatobiliary malignancy is, however, rare. Here, we report on the case of a patient with AIP whose biliary cytology revealed severely atypical cells. Surgically resected specimens from this patient showed typical AIP with IgG4‐SC, as well as a mildly elevated lesion in the common bile duct with varying degrees of cellular atypia. In addition, the atypical cells tested positive for the mucin‐core protein, MUC5AC and p53 overexpression. These findings led us to diagnose the common bile duct lesion as biliary intraepithelial neoplasia (BilIN, mainly BilIN‐1/2). Recently, associations between K‐ras mutations and pancreatobiliary carcinoma have been reported in patients with AIP. This case, therefore, provides important new insight into the potential association of AIP and/or IgG4‐SC with malignancy (or precursor lesions) of the pancreatobiliary system.
Low‐dose hydrocortisone treatment for patients with septic shock: A pilot study comparing 3 days with 7 days
Authors: HUH JIN WON , CHOI HYE‐SOOK , LIM CHAE‐MAN , KOH YOUNSUCK , OH YEON MOK , SHIM TAE SUN , LEE SANG DO , KIM WOO SUNG , KIM DONG SOON , HONG SANG‐BUM
Published: July 2011

Background and objective:  Although there is controversy regarding the benefit of low‐dose corticosteroid therapy in patients with septic shock, the Surviving Sepsis Campaign has advocated that low‐dose intravenous hydrocortisone be used to treat adult septic shock patients. This study investigated the effect of the duration of a stress dose of hydrocortisone on survival of septic shock patients with relative adrenal insufficiency.

Methods:  One hundred and thirty consecutive patients who met the American College of Chest Physicians/Society of Critical Care Medicine criteria for septic shock were included in the study. An additional inclusion criterion was vasopressor support after fluid resuscitation. The primary end‐point was 28‐day mortality, and the secondary end‐points were shock reversal and mortality in the intensive care unit and hospital. All eligible patients were prospectively randomized to receive hydrocortisone treatment for 3 or 7 days. Hydrocortisone treatment was started at a dose of 50 mg every 6 h.

Results:  Baseline data at recruitment did not differ between the two groups. After 28 days, mortality did not differ between the 3‐ and 7‐day treatment groups (33.8% vs 36.9%, P = 0.629). Mortality rates in the intensive care unit and hospital did not differ significantly between the two groups. The median time to withdrawal of vasopressor therapy was 5.0 days in the 3‐day treatment group and 6.4 days in the 7‐day treatment group (P = 0.102).

Conclusions:  This pilot study showed that in patients with septic shock and relative adrenal insufficiency, 28‐day mortality did not differ between those treated with low‐dose hydrocortisone for 3 or 7 days.
Explaining the acetaminophen–ibuprofen analgesic interaction using a response surface model
Authors: Hannam Jacqueline , Anderson Brian J.
Published: July 2011

Background:  The value of acetaminophen–ibuprofen combination therapy over single therapy is uncertain in acute pediatric pain management. A model describing the interaction between these two drugs would be useful both for understanding current literature and for future study design.

Methods:  Published pooled time–effect profiles in adults given combination or single therapy after dental extraction were used to construct an interaction model. Pain was measured using pain intensity differences (PRID, 0–10) from zero to eight hours postoperatively. Pharmacodynamic parameter estimates were assumed the same in adults as children. Pediatric pharmacokinetic estimates were scaled using allometric theory. Curve fitting was performed using nonlinear mixed effects models.

Results:  Pooled data were available in adults given eight single and multiple dose combinations as well as placebo. The ibuprofen dose range was 100–400 mg, and acetaminophen dose range was 500–1000 mg. Pharmacodynamic parameter estimates, expressed using the Hill equation, were maximum effect (EMAX) 4.06 (95% CI: 3.24, 5.51), the concentration of acetaminophen associated with 50% of the maximal drug effect (EC50,ACET) 11.9 (95% CI: 6.0, 49.5) mg·l−1, the ibuprofen EC50 (EC50,IBU) 5.07 (95% CI: 3.50, 8.26) mg·l−1, and Hill coefficient 2 (95% CI: 1.3, 2.8). An interaction term was fixed at zero (additive interaction). Simulation showed that the addition of acetaminophen to ibuprofen when less than 5 mg·kg−1 was effective; acetaminophen had minimal effect when given with ibuprofen at doses greater than 5 mg·kg−1 in the immediate postoperative period. A more sustained analgesic effect was noted at 4–8 h after combination dosing.

Conclusions:  This drug interaction modeling example is useful to explain combination therapy nuances and impacts on study design. Differences in effect between single drug therapy and combination therapy should be sought at lower doses and beyond the immediate postoperative period. Combination therapy may prolong the duration of analgesia. The maximum effect (EMAX) limits the early additional analgesic gain from combination therapy beyond commonly used doses.
To boldly go: individual differences in boldness influence migratory tendency
Authors: Chapman Ben B. , Hulthén Kaj , Blomqvist David R. , Hansson Lars‐Anders , Nilsson Jan‐Åke , Brodersen Jakob , Anders Nilsson P. , Skov Christian , Brönmark Christer
Published: July 2011

Ecology Letters (2011) 14: 871–876

Partial migration, whereby only a fraction of the population migrates, is thought to be the most common type of migration in the animal kingdom, and can have important ecological and evolutionary consequences. Despite this, the factors that influence which individuals migrate and which remain resident are poorly understood. Recent work has shown that consistent individual differences in personality traits in animals can be ecologically important, but field studies integrating personality traits with migratory behaviour are extremely rare. In this study, we investigate the influence of individual boldness, an important personality trait, upon the migratory propensity of roach, a freshwater fish, over two consecutive migration seasons. We assay and individually tag 460 roach and show that boldness influences migratory propensity, with bold individuals being more likely to migrate than shy fish. Our data suggest that an extremely widespread personality trait in animals can have significant ecological consequences via influencing individual‐level migratory behaviour.