bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systems Biology Approach to the Evolution of Codon Use Pattern
Authors: Thiele Ines , Fleming Ronan , Que Richard , Bordbar Aarash , Palsson Bernhard
Published: August 2011

The genetic code is redundant as amino acids are encoded by synonymous codons that are unequally used.This codon usage bias (CUB) affects gene expression and cellular functions yet the underlying mechanisms have not been elucidated. We used a sequence-specific, stoichiometric model of metabolism and macromolecular synthesis for Escherichia coli K12 MG1655 to test the effect of randomly changed CUB on growth maximization under various environmental conditions. Amongst CUB mutant strains, we identified reduced growth phenotypes, which were caused by tRNA supply shortage. We propose, supported by computations and bibliomic data, that expansion of tRNA gene content or tRNA reading is a mechanism to respond to changes in CUB. Our systems biology modelling framework suggests that in order to maximize growth and to adapt to new environmental niches, CUB and tRNA content must co-evolve and provides further evidence for the mutation-selection-drift balance theory of CUB.
Pressure enhancement in carbon nanopores: a major confinement effect
Authors: Long Yun , Palmer Jeremy C. , Coasne Benoit , Śliwinska-Bartkowiak Małgorzata , Gubbins Keith E.
Published: August 2011

Phenomena that only occur at high pressures in bulk phases are observed in nanopores because of a pressure enhancement effect.
Impact of histamine on dendritic cell functions
Authors: Simon Tünde , László Valéria , Falus András
Published: August 2011

A rapidly growing body of evidence highlighted that histamine, a small biogenic amine, is implicated in the regulation of DC (dendritic cell) functions. It is well established that DCs represent the most potent antigen‐presenting cells of the body, linking innate and acquired immunity and regulating the outcome of immune responses. Signals, associated with ongoing inflammation and uptake of foreign antigens, promote maturation of DCs and activation of T‐cell responses in secondary lymphatic organs. These bone marrow‐derived cells patrol continuously all over the body. During their persistent migration, several mediators may influence the behaviour and functions of DCs. Histamine, produced by mast cells, basophils or DCs themselves, may have an important role in the life cycle of DCs. From the differentiation, through their never‐ending circulation, until the induction of T‐cell response, histamine is present and influences the life cycle of DCs. Here, we summarize recent progress in histamine research with respect to DC functions. We also point out some controversial aspects of histamine action on DCs.
Improved vascular organization enhances functional integration of engineered skeletal muscle grafts
Authors: Koffler Jacob , Kaufman-Francis Keren , Shandalov Yulia , Egozi Dana , Amiad Pavlov Daria , Landesberg Amir , Levenberg Shulamit
Published: August 2011

Severe traumatic events such as burns, and cancer therapy, often involve a significant loss of tissue, requiring surgical reconstruction by means of autologous muscle flaps. The scant availability of quality vascularized flaps and donor site morbidity often limit their use. Engineered vascularized grafts provide an alternative for this need. This work describes a first-time analysis, of the degree of in vitro vascularization and tissue organization, required to enhance the pace and efficacy of vascularized muscle graft integration in vivo. While one-day in vitro was sufficient for graft integration, a three-week culturing period, yielding semiorganized vessel structures and muscle fibers, significantly improved grafting efficacy. Implanted vessel networks were gradually replaced by host vessels, coupled with enhanced perfusion and capillary density. Upregulation of key graft angiogenic factors suggest its active role in promoting the angiogenic response. Transition from satellite cells to mature fibers was indicated by increased gene expression, increased capillary to fiber ratio, and similar morphology to normal muscle. We suggest a “relay” approach in which extended in vitro incubation, enabling the formation of a more structured vascular bed, allows for graft-host angiogenic collaboration that promotes anastomosis and vascular integration. The enhanced angiogenic response supports enhanced muscle regeneration, maturation, and integration.
Stereotyped fetal brain disorganization is induced by hypoxia and requires lysophosphatidic acid receptor 1 (LPA
1
) signaling
Authors: Herr Keira Joann , Herr Deron R. , Lee Chang-Wook , Noguchi Kyoko , Chun Jerold
Published: August 2011

Fetal hypoxia is a common risk factor that has been associated with a range of CNS disorders including epilepsy, schizophrenia, and autism. Cellular and molecular mechanisms through which hypoxia may damage the developing brain are incompletely understood but are likely to involve disruption of the laminar organization of the cerebral cortex. Lysophosphatidic acid (LPA) is a bioactive lipid capable of cortical influences via one or more of six cognate G protein-coupled receptors, LPA
1–6
, several of which are enriched in fetal neural progenitor cells (NPCs). Here we report that fetal hypoxia induces cortical disruption via increased LPA
1
signaling involving stereotyped effects on NPCs:
N
-cadherin disruption, displacement of mitotic NPCs, and impaired neuronal migration, as assessed both ex vivo and in vivo. Importantly, genetic removal or pharmacological inhibition of LPA
1
prevented the occurrence of these hypoxia-induced phenomena. Hypoxia resulted in overactivation of LPA
1
through selective inhibition of G protein-coupled receptor kinase 2 expression and activation of downstream pathways including G
αi
and Ras-related C3 botulinum toxin substrate 1. These data identify stereotyped and selective hypoxia-induced cerebral cortical disruption requiring LPA
1
signaling, inhibition of which can reduce or prevent disease-associated sequelae, and may take us closer to therapeutic treatment of fetal hypoxia-induced CNS disorders and possibly other forms of hypoxic injury.
The classification of torsion-free abelian groups of finite rank up to isomorphism and up to quasi-isomorphism
Authors: Coskey Samuel
Published: August 2011

The isomorphism and quasi-isomorphism relations on the

p
p

-local torsion-free abelian groups of rank

n
≥
3

n\geq 3

are incomparable with respect to Borel reducibility.
A Role for Bradyrhizobium japonicum ECF16 Sigma Factor EcfS in the Formation of a Functional Symbiosis with Soybean
Authors: Stockwell S. B. , Reutimann L. , Guerinot M. L.
Published: August 2011

Alternative sigma (σ) factors, proteins that recruit RNA polymerase core enzyme to target promoters, are one mechanism by which bacteria transcriptionally regulate groups of genes in response to environmental stimuli. A class of σ70 proteins, termed extracytoplasmic function (ECF) σ factors, are involved in cellular processes such as bacterial stress responses and virulence. Here, we describe an ECF16 σ factor, EcfS (Blr4928) from the gram-negative soil bacterium Bradyrhizobium japonicum USDA110, that plays a critical role in the establishment of a functional symbiosis with soybean. Nonpolar insertional mutants of ecfS form immature nodules that do not fix nitrogen, a defect that can be successfully complemented by expression of ecfS. Overexpression of the cocistronic gene, tmrS (blr4929), phenocopies the ecfS mutant in planta and, therefore, we propose that TmrS is a negative regulator of EcfS, a determination consistent with the prediction that it encodes an anti-σ factor. Microarray analysis of the ecfS mutant and tmrS overexpressor was used to identify 40 transcripts misregulated in both strains. These transcripts primarily encode proteins of unknown and transport-related functions and may provide insights into the symbiotic defect in these strains.
Role of Polyphenol Oxidase, Peroxidase, Phenylalanine Ammonia Lyase, Chlorogenic Acid, and Total Soluble Phenols in Resistance of Potatoes to Soft Rot
Authors: Ngadze Elizabeth , Icishahayo David , Coutinho Teresa A. , van der Waals Jacquie E.
Published: August 2011

Pectobacterium atrosepticum, P. carotovorum subsp. brasiliensis, and Dickeya spp. cause soft rot of potato (Solanum tuberosum) worldwide. Plants respond to bacterial invasion by activating defense responses associated with accumulation of several enzymes and inhibitors, which prevent pathogen infection. This study focused on the role of polyphenol oxidase (PPO), peroxidase (POD), phenylalanine ammonia lyase (PAL), chlorogenic acid, and total soluble phenols in imparting resistance to soft rot pathogens. Seven and 11 varieties grown by farmers in South Africa and Zimbabwe, respectively, were used in the study. The results showed significantly higher (P < 0.001) enzyme activity of PPO and PAL as well as higher concentrations of chlorogenic acid and total soluble phenols in Vanderplank, Pentland Dell, M69/11, Romano, M59/20, and MondialZw. PAL activity increased significantly with time in all varieties, and the highest activity was recorded 8 h after cutting. The resistance of the varieties was correlated with high PPO and PAL enzyme activity as well as increased concentrations of chlorogenic acid and total soluble phenols. PPO, POD, and PAL activities increased significantly in wounded and inoculated tubers. These findings show that PAL, PPO, POD, chlorogenic acid, and total soluble phenols play a role in imparting resistance to potato soft rot infection.
Evaluation of a Warning System for Early-Season Control of Grapevine Powdery Mildew
Authors: Caffi Tito , Legler Sara E. , Rossi Vittorio , Bugiani Riccardo
Published: August 2011

In several grape-growing areas of the world, including northern Italy, powdery mildew epidemics, caused by Erysiphe necator, are mainly triggered by the ascospores produced in overwintered chasmothecia. Growers in northern Italy usually control the disease with fixed-interval fungicide applications. A warning system was developed for early-season powdery mildew control based on (i) short-term weather forecasts, (ii) a model that simulates the severity of each E. necator ascosporic infection, and (iii) a mobile phone short-message system. This warning system was evaluated in six vineyards in northern Italy from 2006 to 2008, between bud break of vines and early berry development; an unsprayed control was compared with “low-risk” and “high-risk” model-driven sprays and a calendar-based “grower” spray program. Use of the warning system reduced disease severity on leaves and bunches compared with the unsprayed control and resulted in the same level of control of powdery mildew as the grower's spray program, with reduced fungicide applications and costs. On average, 5.7 sprays were applied following the grower's spray program (with an average cost of 221 €/ha/year); use of the warning system reduced fungicide applications by 36% (low-risk program, saving of 56 €/ha/year) or 75% (high-risk program, saving of 161 €/ha/year).
Colonization and Movement of GFP-Labeled Clavibacter michiganensis subsp. michiganensis During Tomato Infection
Authors: Chalupowicz L. , Zellermann E.-M. , Fluegel M. , Dror O. , Eichenlaub R. , Gartemann K.-H. , Savidor A. , Sessa G. , Iraki N. , Barash I. , Manulis-Sasson S.
Published: August 2011

The vascular pathogen Clavibacter michiganensis subsp. michiganensis is responsible for bacterial wilt and canker of tomato. Pathogenicity of this bacterium is dependent on plasmid-borne virulence factors and serine proteases located on the chromosomal chp/tomA pathogenicity island (PAI). In this study, colonization patterns and movement of C. michiganensis subsp. michiganensis during tomato infection was examined using a green fluorescent protein (GFP)-labeled strain. A plasmid expressing GFP in C. michiganensis subsp. michiganensis was constructed and found to be stable in planta for at least 1 month. Confocal laser-scanning microscopy (CLSM) of inoculated stems showed that the pathogen extensively colonizes the lumen of xylem vessels and preferentially attaches to spiral secondary wall thickening of the protoxylem. Acropetal movement of the wild-type strain C. michiganensis subsp. michiganensis NCPPB382 (Cmm382) in tomato resulted in an extensive systemic colonization of the whole plant reaching the apical region after 15 days, whereas Cmm100 (lacking the plasmids pCM1 and pCM2) or Cmm27 (lacking the chp/tomA PAI) remained confined to the area surrounding of the inoculation site. Cmm382 formed biofilm-like structures composed of large bacterial aggregates on the interior of xylem walls as observed by CLSM and scanning electron microscopy. These findings suggest that virulence factors located on the chp/tomA PAI or the plasmids are required for effective movement of the pathogen in tomato and for the formation of cellular aggregates.
Calculation of Diagnostic Parameters of Advanced Serological and Molecular Tissue-Print Methods for Detection of Citrus tristeza virus: A Model for Other Plant Pathogens
Authors: Vidal E. , Yokomi R. K. , Moreno A. , Bertolini E. , Cambra M.
Published: August 2011

Citrus tristeza virus (CTV) is one of the most important virus diseases that affect citrus. Control of CTV is achieved by grafting selected virus-free citrus scions onto CTV-tolerant or -resistant rootstocks. Quarantine and certification programs are essential for avoiding the entry and propagation of severe strains of CTV. Citrus nurseries in Spain and central California (United States) maintain zero-tolerance policies for CTV that require sensitive, specific, and reliable pathogen-detection methods. Tissue-print (TP) real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay was compared with the validated TP enzyme-linked immunosorbent assay (ELISA), using the CTV-specific monoclonal antibodies 3DF1 and 3CA5, for CTV detection. In total, 1,395 samples from healthy and CTV-infected nursery and mature tree plants were analyzed with both methods. The total agreement between both detection methods was substantial (Cohen's kappa index of 0.77 ± 0.03). The diagnostic parameters of each technique (i.e., the sensitivity, specificity, and likelihood ratios) were evaluated in a second test involving 658 Citrus macrophylla nursery plants. Mexican lime indexing was used to evaluate samples with discrepant results in the analysis. For TP-ELISA, a sensitivity of 0.8015, a specificity of 0.9963, and a positive and negative likelihood ratio of 216.42 and 0.199, respectively, were estimated. For TP real-time RT-PCR, a sensitivity of 0.9820, a specificity of 0.8519, and a positive and negative likelihood ratio of 6.63 and 0.021, respectively, were estimated. These diagnostic parameters show that TP real-time RT-PCR was the most sensitive technique, whereas TP-ELISA showed the highest specificity, validating the use of the molecular technique for routine CTV-detection purposes. In addition, our results show that the combination of both techniques can accurately substitute for the conventional biological Mexican lime index for the detection of CTV. The calculation of diagnostic parameters is discussed, as a necessary tool, to validate detection or diagnostic methods in plant pathology. Furthermore, assessment of the post-test probability of disease after a diagnostic result and CTV prevalence allows selection of the best method for accurate and reliable diagnosis.
Sequence and Simple-Sequence Repeat Analyses of the Fungal PathogenSeiridium cardinaleIndicate California Is the Most Likely Source of the Cypress Canker Epidemic for the Mediterranean Region
Authors: Della Rocca G. , Eyre C. A. , Danti R. , Garbelotto M.
Published: August 2011

Seiridium cardinale is the pathogenic fungus of unknown origin responsible for a world pandemic known as cypress canker affecting several species of Cupressaceae in both the Northern and Southern Hemisphere. In this study, a comparative genetic analysis of worldwide populations was performed using sequence analysis of a portion of the β-tubulin locus and seven polymorphic simple-sequence repeat (SSR) loci on 96 isolates. Sequence analysis identified two distinct β-tubulin alleles, both present in California. Only one of the two alleles was detected in the Mediterranean basin, while two isolates from the Southern Hemisphere were characterized by the presence of the allele absent from the Mediterranean. SSRs identified a total of 46 multilocus genotypes (MGs): genotypic diversity was always higher in the California population, and calculations of the index of association (IA) determined the presence of linkage disequilibrium associated with the absence of sexual reproduction only in the Mediterranean population but not in California. In 50 instances, the same MG was found at great geographic distances, implying a role played by humans in spreading the disease. Network analysis performed on SSR data identified three clusters of MGs: California, Morocco, and the rest of the Mediterranean. Both the Morocco and the Mediterranean clusters were linked to the California cluster. Coalescent analysis identified insignificant migration between California and Italy, as expected in the presence of a single introduction event, and very high migration from Italy into Greece, as expected of an outbreak still in exponential growth phase and starting from an Italian source.
Alec Douglas Bangham. 10 November 1921 — 9 March 2010
Authors: Heap Sir Brian , Gregoriadis Gregory
Published: August 2011

A first meeting with Alec Bangham would leave an impression of a larger-than-life scientist with a penetrating curiosity and formidable features characteristically portrayed in the dramatic portrait painted by his nephew, Humphrey Bangham, which currently hangs in one of the Royal Society’s rooms. Or, as Jeffrey Watkins (FRS) experienced on reaching the Institute of Animal Physiology at Babraham in September 1963, ‘at the moment of my arrival he was avidly peering down a microscope and excitedly proclaiming the wonders of myelin figures as viewed through crossed polaroids … [and that] they might prove useful as model systems for the study of structure and function in biological membranes. It was decided that I should work immediately along these lines.’ So what were the formative events that led to these first impressions? What had contributed to the formation of a scientist who became known worldwide as the father of liposomes, the inventor of Artificial Lung Expanding Compound (ALEC)—and someone who never stopped thinking about membranes, surfactant, anaesthetics, cricket, vegetables, family and friends?
Peter Neville Robson OBE FREng. 23 November 1930 — 10 January 2010
Authors: Houston Peter A. , Jackson Roy
Published: August 2011

Peter Robson was a distinguished scientist/engineer, internationally renowned for his pioneering work in the field of II–V semiconductor materials and devices. His early research was on the theory and experimentation of guided microwaves, and he was able to apply this expertise directly to semiconductors when his work moved from vacuum devices to the solid state. A further move occurred when his semiconductor research shifted from microwaves to the optical part of the electromagnetic spectrum. Peter made significant contributions to the then new field of optoelectronics and produced a lasting legacy. Much of his research on semiconductors sowed the seeds for many technological developments that have an enormous impact on our lives today, such as the Internet and mobile phones.
Preparation of Simian Foamy Virus Type-1 Vectors
Authors: Park Jeonghae , Mergia Ayalew
Published: August 2011

INTRODUCTION

Foamy viruses (FVs) are nonpathogenic retroviruses that offer opportunities for efficient and safe gene transfer in various cell types from different species. These viruses have unique replication mechanisms that are distinct from other retroviruses, which may give an advantage to FV-mediated gene transfer. This protocol describes a method for simian foamy virus type-1 (SFV-1) vector preparation and concentration. A transient transfection of vector and packaging constructs allows generation of the SFV-1 vector with titers of 107/mL. The vectors can be further concentrated by 100–200-fold without significant loss of vector titer.
Immunostaining of Mitotic Chromosomes from Drosophila Larval Brain: Figure 1.
Authors: Pimpinelli Sergio , Bonaccorsi Silvia , Fanti Laura , Gatti Maurizio
Published: August 2011

INTRODUCTION

Good mitotic chromosome preparations are essential for the immunolocalization of chromosomal proteins. Although methanol/acetic acid fixation techniques preserve chromosome morphology very well, they remove a substantial fraction of chromosomal proteins. We have developed fixation/immunostaining procedures, described here, that are suitable for the immunolocalization of proteinaceous components of metaphase chromosomes from larval Drosophila brain cells. These procedures result in good chromosomal quality with minimal removal of proteins.
Mounting Caenorhabditis elegans Embryos for Live Imaging of Embryogenesis: Figure 1.
Authors: Bao Zhirong , Murray John I.
Published: August 2011

INTRODUCTION

Caenorhabditis elegans has been a key model organism for biomedical research. Light microscopy has played a central role in C. elegans biology. C. elegans is transparent throughout its life cycle, and its physical size, from 50 µm (embryos) to 1 mm (adults), is well suited for light microscopy. Furthermore, it has an invariant body plan that arises from an invariant cell lineage. A wide range of biological processes, from patterns of gene expression to cell migration to neuronal activity, can be readily observed in single cells with a well-defined developmental context. This protocol describes how to collect and mount young C. elegans embryos for live imaging throughout embryogenesis.
Dissection of Third-Instar Drosophila Larvae for Electrophysiological Recording from Neurons
Authors: Marley Richard , Baines Richard A.
Published: August 2011

INTRODUCTION

The fruit fly Drosophila melanogaster has been instrumental in expanding our understanding of early aspects of neural development. The use of this model system has greatly added to our knowledge of neural cell-fate determination, axon guidance, and synapse formation. It has also become possible to access and make electrophysiological recordings directly from neurons in situ in an intact central nervous system (CNS), which has facilitated studies of the development and regulation of neuronal signaling. It is possible to obtain electrophysiological recordings from all stages of Drosophila. Exposure of the intact Drosophila CNS is a prerequisite for such electrophysiological recordings. The dissection procedure described here is suitable for third-instar larvae. The dissection should take ∼5 min to complete if all preparation work has been completed in advance. Owing to the short life span of the dissected larva, it is not recommended that the procedure be stopped or the preparation stored for later use.
Whole-Cell Patch Recording from Drosophila Larval Neurons
Authors: Marley Richard , Baines Richard A.
Published: August 2011

INTRODUCTION

The fruit fly Drosophila melanogaster has been instrumental in expanding our understanding of early aspects of neural development. The use of this model system has greatly added to our knowledge of neural cell-fate determination, axon guidance, and synapse formation. It has also become possible to access and make electrophysiological recordings directly from neurons in situ in an intact central nervous system (CNS), which has facilitated studies of the development and regulation of neuronal signaling. This protocol describes a procedure for revealing larval motor neurons and applying whole-cell patch recording techniques to these cells. The useful lifetime of first-instar larval preparations is ∼30 min, and that of third-instar CNS preparations is up to 1 h. It is therefore recommended that fresh preparations are used and that no breaks are taken during the procedure, although there may be time to pull and polish a patch pipette.
Soybean Homologs of MPK4 Negatively Regulate Defense Responses and Positively Regulate Growth and Development
Authors: Liu Jian-Zhong , Horstman Heidi D. , Braun Edward , Graham Michelle A. , Zhang Chunquan , Navarre Duroy , Qiu Wen-Li , Lee Yeunsook , Nettleton Dan , Hill John H. , Whitham Steven A.
Published: August 2011

Mitogen-activated protein kinase (MAPK) cascades play important roles in disease resistance in model plant species such as Arabidopsis (Arabidopsis thaliana) and tobacco (Nicotiana tabacum). However, the importance of MAPK signaling pathways in the disease resistance of crops is still largely uninvestigated. To better understand the role of MAPK signaling pathways in disease resistance in soybean (Glycine max), 13, nine, and 10 genes encoding distinct MAPKs, MAPKKs, and MAPKKKs, respectively, were silenced using virus-induced gene silencing mediated by Bean pod mottle virus. Among the plants silenced for various MAPKs, MAPKKs, and MAPKKKs, those in which GmMAPK4 homologs (GmMPK4s) were silenced displayed strong phenotypes including stunted stature and spontaneous cell death on the leaves and stems, the characteristic hallmarks of activated defense responses. Microarray analysis showed that genes involved in defense responses, such as those in salicylic acid (SA) signaling pathways, were significantly up-regulated in GmMPK4-silenced plants, whereas genes involved in growth and development, such as those in auxin signaling pathways and in cell cycle and proliferation, were significantly down-regulated. As expected, SA and hydrogen peroxide accumulation was significantly increased in GmMPK4-silenced plants. Accordingly, GmMPK4-silenced plants were more resistant to downy mildew and Soybean mosaic virus compared with vector control plants. Using bimolecular fluorescence complementation analysis and in vitro kinase assays, we determined that GmMKK1 and GmMKK2 might function upstream of GmMPK4. Taken together, our results indicate that GmMPK4s negatively regulate SA accumulation and defense response but positively regulate plant growth and development, and their functions are conserved across plant species.
Cost‐effectiveness of tobacco control policies in Vietnam: the case of personal smoking cessation support
Authors: Higashi Hideki , Barendregt Jan J.
Published: August 2011

Aims  To examine the cost‐effectiveness of personal smoking cessation support in Vietnam.

Design, setting and participants  We followed‐up the population aged 15 years and over in 2006 to model the costs and health gains associated with five interventions: physician brief advice; nicotine replacement therapy (patch and gum); bupropion; and varenicline. Threshold analysis was undertaken to determine the price levels of pharmaceuticals for the interventions to be cost‐effective. A multi‐state life table model was constructed such that the interventions affect the smoking cessation behaviour of the age cohorts, and the resulting smoking prevalence defines their health outcomes. A health‐care perspective was employed.

Measurements  Cost‐effectiveness is measured in 2006 Vietnamese Dong (VND) per disability‐adjusted life year (DALY) averted. We adopted the World Health Organization thresholds of being ‘cost‐effective’ if less than three times gross domestic product (GDP) per capita (VND 34 600 000) and ‘very cost‐effective’ if less than GDP per capita (VND 11 500 000).

Findings  The cost‐effectiveness result of physician brief advice was VND 1 742 000 per DALY averted (international dollars 543), which was ‘very cost‐effective’. Varenicline dominated bupropion and nicotine‐replacement therapies, although it did not fall within the range of being ‘cost‐effective’ under different scenarios. The threshold analysis revealed that prices of pharmaceuticals must be substantially lower than the levels from other countries if pharmacological therapies are to be cost‐effective in Vietnam.

Conclusions  Physician brief advice is a cost‐effective intervention and should be included in the priority list of tobacco control policy in Vietnam. Pharmacological therapies are not cost‐effective, and so they are not recommended in Vietnam at this time unless pharmaceuticals could be produced locally at substantially lower costs in the future.
Rhinitis symptoms caused by grass pollen are associated with elevated basophile allergen sensitivity and a larger grass‐specific immunoglobulin E fraction
Authors: Zidarn M. , Košnik M. , Šilar M. , Grahek A. , Korošec P.
Published: August 2011

Background

The mechanisms responsible for the difference between clinically irrelevant IgE‐sensitization and allergic rhinitis are not fully understood.

Objective

We evaluated the humoral and cellular mechanisms that may be associated with the presence of allergic rhinitis symptoms.

Methods

We selected 26 subjects with positive grass pollen skin tests and IgE antibodies to Timothy (g6) and the major grass allergens rPhl p 1, 5b. Fourteen of those patients reported a history of allergic rhinitis. During winter, we performed a grass pollen CD63 basophile activation test using four log allergen concentrations, followed by a grass nasal provocation test (NPT). We obtained symptom scores in the subsequent pollination season.

Results

We showed that subjects with a positive NPT have significantly higher CD63 basophile grass pollen responsiveness than NPT‐negative subjects, preferably at submaximal allergen concentrations, which represent cellular sensitivity. Moreover, basophile sensitivity positively correlated with the size of the grass‐specific IgE fraction in relation to total IgE, and it was highly predictive of allergic rhinitis symptoms in the following pollination season.

Conclusion and Clinical Relevance

Allergic rhinitis symptoms are significantly associated with allergen‐specific basophile sensitivity. In vitro evaluation of basophile sensitivity should prove useful for distinguishing clinical phenotype of allergic sensitization.
Histological and molecular features of lipomatous and nonlipomatous adipose tissue in familial partial lipodystrophy caused by LMNA mutations
Authors: Araújo‐Vilar D. , Victoria B. , González‐Méndez B. , Barreiro F. , Fernández‐Rodríguez B. , Cereijo R. , Gallego‐Escuredo J.M. , Villarroya F. , Pañeda‐Menéndez A.
Published: August 2011

Objectives  Type 2 familial partial lipodystrophy (FPLD2) is a rare adipose tissue (AT) disease caused by mutations in LMNA, in which lipomas appear occasionally. In this study, we aimed to histologically characterize FPLD2‐associated lipomatosis and study the expression of genes and proteins involved in cell cycle control, mitochondrial function, inflammation and adipogenesis.

Design and patients  One lipoma and perilipoma fat from each of four subjects with FPLD2 and 10 control subjects were analysed by optical microscopy. The presence of inflammatory cells was evaluated by immunohistochemistry. Real‐time RT‐PCR and Western blot were used to evaluate gene and protein levels.

Results  Adipocytes from lipodystrophic patients were significantly larger than those of controls, in both the lipomas and perilipoma fat. Lipodystrophic AT exhibited CD68+ macrophages and CD3+ lymphocytes infiltration. TP53 expression was reduced in all types of lipomas. At protein level, C/EBPβ, p53 and pRb were severely disturbed in both lipodystrophic lipomas and perilipoma fat coming from lipoatrophic areas, whereas the expression of CEBPα was normal. Mitochondrial function genes were less expressed in lipoatrophic fat. In both lipomas and perilipoma fat from lipoatrophic areas, the expression of adipogenes was lower than controls.

Conclusions  Even in lipomas, the adipogenic machinery is impaired in lipodystrophic fat coming from lipoatrophic regions in FPLD2, although the histological phenotype is near‐normal, exhibiting low‐grade inflammatory features. Our results suggest that the p53 pathway and some adipogenic proteins, such as CEBPα, could contribute to the maintenance of this near normal phenotype in the remnant AT present in these patients.
Functional and structural evaluation of hearing in acromegaly
Authors: Aydin Kadriye , Ozturk Burak , Turkyilmaz Meral Didem , Dagdelen Selcuk , Ozgen Burce , Unal Faruk , Erbas Tomris
Published: August 2011

Context  The impact of acromegaly on the auditory system remains unknown.

Objective  This study aimed to examine audiological symptoms and the structure and function of the auditory system in patients with acromegaly.

Design/Setting and Patients  The study included 44 patients with acromegaly. Pure tone audiometry, speech audiometry, tympanometry, otoacoustic emissions testing, computerized tomography of the temporal bone and magnetic resonance imaging of the ear were performed in all patients. The study also included 36 age‐ and sex‐matched healthy controls. The patients with acromegaly were divided into three subgroups, as follows: controlled disease (n = 13); partially controlled disease (n = 16); uncontrolled disease (n = 15).

Results  In all, 43% of the patients with acromegaly had hearing loss, and 20% had had an episode of otitis in at least one ear. Median pure tone average (PTA) in the patients with acromegaly was 12.5 dB (range: 2–72 dB), vs 8.3 dB (range: 0–20 dB) in the control group (P < 0.001). PTA did not differ significantly between the three patient subgroups. Audiometric tests showed various degrees of hearing loss in at least one ear in 21 patients (48%). Conductive, sensorineural and mixed type hearing loss in at least one ear was noted in 9%, 30% and 18% of the patients, respectively. Auditory imaging showed that 50% of the patients had temporomandibular joint degeneration (TMJD).

Conclusions  Hearing loss is quite common in patients with acromegaly. Contrary to common belief, in this study, conductive hearing loss did not occur more frequently than other types. Based on PTA findings in the controls and patients with acromegaly, acromegaly caused hearing loss, but the level of disease activity had no effect on hearing. Middle ear pressure problems might be caused by increased perilymph because of growth hormone (GH)‐related volume overload.
Coral reefs modify their seawater carbon chemistry – case study from a barrier reef (Moorea, French Polynesia)
Authors: Kleypas Joan A. , Anthony Kenneth R. N. , Gattuso Jean‐Pierre
Published: August 2011

Changes in the carbonate chemistry of coral reef waters are driven by carbon fluxes from two sources: concentrations of CO2 in the atmospheric and source water, and the primary production/respiration and calcification/dissolution of the benthic community. Recent model analyses have shown that, depending on the composition of the reef community, the air‐sea flux of CO2 driven by benthic community processes can exceed that due to increases in atmospheric CO2 (ocean acidification). We field test this model and examine the role of three key members of benthic reef communities in modifying the chemistry of the ocean source water: corals, macroalgae, and sand. Building on data from previous carbon flux studies along a reef‐flat transect in Moorea (French Polynesia), we illustrate that the drawdown of total dissolved inorganic carbon (CT) due to photosynthesis and calcification of reef communities can exceed the draw down of total alkalinity (AT) due to calcification of corals and calcifying algae, leading to a net increase in aragonite saturation state (Ωa). We use the model to test how changes in atmospheric CO2 forcing and benthic community structure affect the overall calcification rates on the reef flat. Results show that between the preindustrial period and 1992, ocean acidification caused reef flat calcification rates to decline by an estimated 15%, but loss of coral cover caused calcification rates to decline by at least three times that amount. The results also show that the upstream–downstream patterns of carbonate chemistry were affected by the spatial patterns of benthic community structure. Changes in the ratio of photosynthesis to calcification can thus partially compensate for ocean acidification, at least on shallow reef flats. With no change in benthic community structure, however, ocean acidification depressed net calcification of the reef flat consistent with findings of previous studies.
Quantitative approaches in climate change ecology
Authors: Brown Christopher J. , Schoeman David S. , Sydeman William J. , Brander Keith , Buckley Lauren B. , Burrows Michael , Duarte Carlos M. , Moore Pippa J. , Pandolfi John M. , Poloczanska Elvira , Venables William , Richardson Anthony J.
Published: August 2011

Contemporary impacts of anthropogenic climate change on ecosystems are increasingly being recognized. Documenting the extent of these impacts requires quantitative tools for analyses of ecological observations to distinguish climate impacts in noisy data and to understand interactions between climate variability and other drivers of change. To assist the development of reliable statistical approaches, we review the marine climate change literature and provide suggestions for quantitative approaches in climate change ecology. We compiled 267 peer‐reviewed articles that examined relationships between climate change and marine ecological variables. Of the articles with time series data (n = 186), 75% used statistics to test for a dependency of ecological variables on climate variables. We identified several common weaknesses in statistical approaches, including marginalizing other important non‐climate drivers of change, ignoring temporal and spatial autocorrelation, averaging across spatial patterns and not reporting key metrics. We provide a list of issues that need to be addressed to make inferences more defensible, including the consideration of (i) data limitations and the comparability of data sets; (ii) alternative mechanisms for change; (iii) appropriate response variables; (iv) a suitable model for the process under study; (v) temporal autocorrelation; (vi) spatial autocorrelation and patterns; and (vii) the reporting of rates of change. While the focus of our review was marine studies, these suggestions are equally applicable to terrestrial studies. Consideration of these suggestions will help advance global knowledge of climate impacts and understanding of the processes driving ecological change.
Retrospective analysis of differences in annual factor VIII utilization among haemophilia A patients
Authors: EPSTEIN J. , XIONG Y. , WOO P. , LI‐McLEOD J. , SPOTTS G.
Published: August 2011

Summary.  Finding differences in drug utilization patterns within rare patient populations is challenging without access to a large sample. Our objective was to identify patient and treatment‐related factors associated with differences in annual recombinant factor VIII (rFVIII) utilization in a large cohort of haemophilia A patients. This retrospective analysis utilized a large, US specialty pharmacy dispensing database from January 2006 to September 2009. Differences in median annual FVIII utilization (IU kg−1year−1) by age, severity, treatment regimen, rFVIII product type and health insurance plan were tested using non‐parametric statistics and regression analysis. A total of 1011 haemophilia A patients were included in the overall analysis. Severe haemophilia patients had higher median annual FVIII utilization than mild/moderate patients (P < 0.0001). Median annual FVIII utilization was also significantly different between treatment regimens (episodic = 1429 IU kg−1year−1 vs. prophylaxis = 3993 IU kg−1year−1 for severe patients, P < 0.0001). Children (0–12 years old), adolescents (13–18 years old) and adults (19+ years old) with severe haemophilia A receiving prophylaxis utilized 4588, 4082 and 3223 IU kg−1year−1 (P < 0.0001). After controlling for age, severity, treatment regimen and insurance type, regression analysis revealed B domain‐deleted recombinant FVIII (BDD‐rFVIII) was associated with 33% higher FVIII consumption compared with full‐length recombinant FVIII (FL‐rFVIII) (P = 0.0172). Similar results were also seen when matching BDD‐rFVIII and FL‐rFVIII patients. Health insurance type was not associated with annual FVIII utilization. As expected, age, severity and treatment regimen were significantly associated with FVIII utilization. After controlling for confounders, patients receiving FL‐rFVIII prophylactically were associated with lower annual FVIII utilization compared with patients receiving BDD‐rFVIII prophylactically.
Could our fisheries be more productive? Indirect negative effects of bottom trawl fisheries on fish condition
Authors: Hiddink Jan G. , Johnson Andrew F. , Kingham Rachel , Hinz Hilmar
Published: August 2011

1. The nets used in bottom trawl fisheries cause mortality of benthic invertebrates and this can decrease the long‐term availability of prey to exploited fish species by reducing the abundance of benthic invertebrates. This may have consequences for the sustainability of fisheries.

2. We assessed the impact of bottom trawling on the food availability of fish by comparing the condition of fish (as weight‐at‐length) in an area that had a steep commercial bottom‐trawling gradient in the Irish Sea but otherwise homogeneous environmental conditions.

3. We found that the condition of the important commercial flatfish plaice Pleuronectes platessa was negatively related to trawling frequency, and this could be explained by a reduced production of the infaunal invertebrates they feed on. Density‐dependent changes in competition over food could not explain this difference. No effect of trawling on the condition of the flatfish dab Limanda limanda was detected. Whiting Merlangius merlangus feeds primarily on fish, and therefore, no effect of bottom trawling on its condition was expected or detected.

4. This study therefore indicates that bottom trawl fisheries may have a negative effect on the condition of some of their target species, but not others, by reducing the abundance of their benthic prey.

5. Synthesis and application. Bottom trawls may indirectly affect the population size and growth rate of the target fish species and result in lower fishing yields. Such reductions in the yield and sustainability of fisheries are highly undesirable. The effects of bottom trawls may be mitigated by the modification of fishing gears or by minimizing the area of the seabed fished by bottom trawls.
Observation of health technologies after their introduction into clinical practice: a systematic review on data collection instruments
Authors: Varela‐Lema Leonor , Ruano‐Ravina Alberto , Cerdá Mota Teresa
Published: August 2011

Rationale, aims and objectives  Early assessment of health technologies after they are covered by the health system is deemed crucial to promptly identify and analyse unforeseen problems that may arise when these are used in real world settings. This paper aims to describe the various instruments which could be used for collecting information intended for prospective observation of health technologies, so as to choose the specific instrument best suited to each context.

Methods  Systematic review of the medical literature aimed at retrieving general reference documents on data collection instruments for post‐introduction observation of health technologies. A purpose‐designed systematic bibliographic search was elaborated for the main three data collection instruments identified.

Results  The three instruments are briefly described along with the main results of the studies retrieved, in terms of the advantages, drawbacks and considerations to be borne in mind when it comes to use these tools in post‐introduction observation of new technologies.

Conclusions  At present, the most appropriate data collection method for conducting post‐introduction observation of new technologies is the use of prospective clinical registries. Electronic clinical records may replace clinical registries in the near future, but currently there are still many doubts as to the quality of the information retrieved.
Satisfaction after the transition between electronic health record systems at six ambulatory practices
Authors: Pfoh Elizabeth R. , Abramson Erika , Zandieh Stephanie , Edwards Alison , Kaushal Rainu
Published: August 2011

Rationale, aims and objectives  Early adopters of electronic health records (EHRs) are transitioning from older to newer EHRs to satisfy meaningful use requirements. Facilitators and barriers to satisfaction after transitioning are important to understand as provider satisfaction is linked with improvement in health care.

Method  We conducted a cross‐sectional survey of providers who transitioned from an older to a newer EHR at six academic, urban ambulatory medical practices. A novel survey was developed to assess: (1) satisfaction with the EHR implementation; (2) patterns of information technology use; (3) work perceptions; (4) methods for completing clinical tasks; and (5) demographic characteristics. We analysed the results using bivariate and multivariate analyses.

Results  The response rate was 64% (n = 197). A small majority were satisfied with the new EHR (64%, n = 120). Providers who reported satisfaction with overall quality of work life, their workload and the transition were more likely to be satisfied with the new EHR (P < 0.01). Providers who reported using the Internet at least daily were also more likely to be satisfied with the new EHR (P < 0.05). In a multivariate model, satisfaction with the transition was a strong predictor of satisfaction with the new EHR (P < 0.01). Barriers to satisfaction include dissatisfaction with: maintaining problem and medication lists, tracking health maintenance information, referring to clinical practice guidelines and ordering laboratory and radiology tests (P < 0.01).

Conclusion  This study provides groundwork for understanding the facilitators and barriers to provider satisfaction after the transition between EHRs and provides insight into areas requiring attention by entities undergoing similar transitions.
A naïve Bayes classifier for planning transfusion requirements in heart surgery
Authors: Cevenini Gabriele , Barbini Emanuela , Massai Maria R. , Barbini Paolo
Published: August 2011

Rationale, aims and objectives  Transfusion of allogeneic blood products is a key issue in cardiac surgery. Although blood conservation and standard transfusion guidelines have been published by different medical groups, actual transfusion practices after cardiac surgery vary widely among institutions. Models can be a useful support for decision making and may reduce the total cost of care. The objective of this study was to propose and evaluate a procedure to develop a simple locally customized decision‐support system.

Methods  We analysed 3182 consecutive patients undergoing cardiac surgery at the University Hospital of Siena, Italy. Univariate statistical tests were performed to identify a set of preoperative and intraoperative variables as likely independent features for planning transfusion quantities. These features were utilized to design a naïve Bayes classifier. Model performance was evaluated using the leave‐one‐out cross‐validation approach. All computations were done using spss and matlab code.

Results  The overall correct classification percentage was not particularly high if several classes of patients were to be identified. Model performance improved appreciably when the patient sample was divided into two classes (transfused and non‐transfused patients). In this case the naïve Bayes model correctly classified about three quarters of patients with 71.2% sensitivity and 78.4% specificity, thus providing useful information for recognizing patients with transfusion requirements in the specific scenario considered.

Conclusions  Although the classifier is customized to a particular setting and cannot be generalized to other scenarios, the simplicity of its development and the results obtained make it a promising approach for designing a simple model for different heart surgery centres needing a customized decision‐support system for planning transfusion requirements in intensive care unit.