bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of Fc receptors in HIV prevention and therapy
Authors: Boesch Austin W. , Brown Eric P. , Ackerman Margaret E.
Published: October 2015

Over the past decade, a wealth of experimental evidence has accumulated supporting the importance of Fc receptor (FcR) ligation in antibody‐mediated pathology and protection in many disease states. Here we present the diverse evidence base that has accumulated as to the importance of antibody effector functions in the setting of HIV prevention and therapy, including clinical correlates, genetic associations, viral evasion strategies, and a rapidly growing number of compelling animal model experiments. Collectively, this work identifies antibody interactions with FcR as important to both therapeutic and prophylactic strategies involving both passive and active immunity. These findings mirror those in other fields as investigators continue to work toward identifying the right antibodies and the right effectors to be present at the right sites at the right time.
Fcγ receptor pathways during active and passive immunization
Authors: Bournazos Stylianos , Ravetch Jeffrey V.
Published: October 2015

IgG antibodies are actively produced in response to antigenic challenge or passively administered as an effective form of immunotherapy to confer immunity against foreign antigens. Their protective activity is mediated through their bifunctional nature: a variable Fab domain mediates antigen‐binding specificity, whereas the constant Fc domain engages Fcγ receptors (FcγRs) expressed on the surface of leukocytes to mediate effector functions. While traditionally considered the invariant domain of an IgG molecule, the Fc domain displays remarkable structural heterogeneity determined primarily by differences in the amino acid sequence of the various IgG subclasses and by the composition of the complex, Fc‐associated biantennary N‐linked glycan. These structural determinants regulate the conformational flexibility of the IgG Fc domain and affect its capacity to interact with distinct types of FcγRs (type I or type II FcγRs). FcγR engagement activates diverse downstream immunomodulatory pathways with pleiotropic functional consequences including cytotoxicity and phagocytosis of IgG‐coated targets, differentiation and activation of antigen presenting cells, modulation of T‐cell activation, plasma cell survival, and regulation of antibody responses. These functions highlight the importance of FcγR‐mediated pathways in the modulation of adaptive immune responses and suggest a central role for IgG–FcγR interactions during active and passive immunization.
Human IgG4: a structural perspective
Authors: Davies Anna M. , Sutton Brian J.
Published: October 2015

IgG4, the least represented human IgG subclass in serum, is an intriguing antibody with unique biological properties, such as the ability to undergo Fab‐arm exchange and limit immune complex formation. The lack of effector functions, such as antibody‐dependent cell‐mediated cytotoxicity and complement‐dependent cytotoxicity, is desirable for therapeutic purposes. IgG4 plays a protective role in allergy by acting as a blocking antibody, and inhibiting mast cell degranulation, but a deleterious role in malignant melanoma, by impeding IgG1‐mediated anti‐tumor immunity. These findings highlight the importance of understanding the interaction between IgG4 and Fcγ receptors. Despite a wealth of structural information for the IgG1 subclass, including complexes with Fcγ receptors, and structures for intact antibodies, high‐resolution crystal structures were not reported for IgG4‐Fc until recently. Here, we highlight some of the biological properties of human IgG4, and review the recent crystal structures of IgG4‐Fc. We discuss the unexpected conformations adopted by functionally important Cγ2 domain loops, and speculate about potential implications for the interaction between IgG4 and FcγRs.
TRIM21: a cytosolic Fc receptor with broad antibody isotype specificity
Authors: Foss Stian , Watkinson Ruth , Sandlie Inger , James Leo C. , Andersen Jan Terje
Published: October 2015

Antibodies are key molecules in the fight against infections. Although previously thought to mediate protection solely in the extracellular environment, recent research has revealed that antibody‐mediated protection extends to the cytosolic compartment of cells. This postentry viral defense mechanism requires binding of the antibody to a cytosolic Fc receptor named tripartite motif containing 21 (TRIM21). In contrast to other Fc receptors, TRIM21 shows remarkably broad isotype specificity as it does not only bind IgG but also IgM and IgA. When viral pathogens coated with these antibody isotypes enter the cytosol, TRIM21 is rapidly recruited and efficient neutralization occurs before the virus has had the time to replicate. In addition, inflammatory signaling is induced. As such, TRIM21 acts as a cytosolic sensor that engages antibodies that have failed to protect against infection in the extracellular environment. Here, we summarize our current understanding of how TRIM21 orchestrates humoral immunity in the cytosolic environment.
Accelerating antibody discovery using transgenic animals overexpressing the neonatal Fc receptor as a result of augmented humoral immunity
Authors: Cervenak Judit , Kurrle Roland , Kacskovics Imre
Published: October 2015

In recent years, there has been an increasing demand for the development of faster and more efficient technologies for the generation of monoclonal antibodies against challenging targets that are weakly immunogenic or available only in limited amounts. Typical classes of such targets are cell surface antigens such as G‐protein related receptors (GPCRs) or ion channels. We have developed transgenic (Tg) mice and rabbits that overexpress the neonatal Fc receptor (FcRn), resulting in an augmented humoral immune response even if challenging antigens are used for immunization. The impressively enhanced FcRn‐mediated immune reactions are characterized by improved IgG protection and enhanced antigen presentation leading to greater number of antigen‐specific T‐helper and B‐cell activation in lymphoid organs. Notably, these animals do not show any sign of autoimmunity and can be efficiently bred. FcRn overexpression thus leads to a number of practical benefits for improved generation of monoclonal and polyclonal antibodies against multiple antigens, including weakly immunogenic epitopes or tiny amounts of proteins. This review summarizes our current understanding about the mechanisms by which FcRn overexpression leads to such a significantly enhanced humoral immune response.
The platelet Fc receptor, FcγRIIa
Authors: Qiao Jianlin , Al‐Tamimi Mohammad , Baker Ross I. , Andrews Robert K. , Gardiner Elizabeth E.
Published: October 2015

Human platelets express FcγRIIa, the low‐affinity receptor for the constant fragment (Fc) of immunoglobulin (Ig) G that is also found on neutrophils, monocytes, and macrophages. Engagement of this receptor on platelets by immune complexes triggers intracellular signaling events that lead to platelet activation and aggregation. Importantly these events occur in vivo, particularly in response to pathological immune complexes, and engagement of this receptor on platelets has been causally linked to disease pathology. In this review, we will highlight some of the key features of this receptor in the context of the platelet surface, and examine the functions of platelet FcγRIIa in normal hemostasis and in response to injury and infection. This review will also highlight pathological consequences of engagement of this receptor in platelet‐based autoimmune disorders. Finally, we present some new data investigating whether levels of the extracellular ligand‐binding region of platelet glycoprotein VI which is rapidly shed upon engagement of platelet FcγRIIa by autoantibodies, can report on the presence of pathological anti‐heparin/platelet factor 4 immune complexes and thus identify patients with pathological autoantibodies who are at the greatest risk of developing life‐threatening thrombosis in the setting of heparin‐induced thrombocytopenia.
The Meaning of ‘choice and control’ for People with Intellectual Disabilities who are Planning their Social Care and Support
Authors: Williams Val , Porter Sue
Published: October 2015

Background

This paper questions consumerist assumptions in current English social care policy and aims to look behind the processes of personalization to interrogate what ‘choice and control’ means in the lives of a diverse group of people with intellectual disabilities.

Methods

Data were from multiple interviews and direct practice recordings with nine people using personal budgets and were analysed using an interpretative approach.

Results

Identity, other people and personal budget processes were all important for choice and control. People needed to build confidence in themselves as decision‐makers, both through peer support and through joint decisions with trusted others.

Conclusions

Practitioners need to take into account the spectrum of ways in which people may make decisions. Action needs to be taken both at the micro level of support interactions and at the macro level, with a clearer articulation of independent living in policy and strategy for people with intellectual disabilities.
Effect of ICD Therapies on Mortality in the OMNI Trial
Authors: SUN SHINING , JOHNSON JAMES , DEGROOT PAUL , BROWN MARK L. , OBEL OWEN
Published: October 2015

ICD Therapies and Mortality in OMNI

Background

Analyses from primary prevention trials on implantable cardioverter defibrillator (ICD) therapy have shown an association between shocks and increased mortality. Recent data suggest a similar association with antitachycardia pacing (ATP).

Objective

The OMNI study is an observational study of pacemaker and ICD use. We aim to examine associations between ICD therapies and mortality in this setting.

Methods

A total of 2,255 OMNI patients with ICDs were included. Treated episodes were classified as appropriate or inappropriate. Patients were assigned into 1 of 3 groups depending on whether the episode required ATP only, single shock, or multiple shocks, and then followed for all‐cause mortality. Additionally, we aimed to determine the frequency with which inappropriate ATP precipitated ventricular arrhythmias that led to shock, since this has been suggested as a mechanism of harm.

Results

Over a mean follow‐up of 39 ± 19 months, there were a total of 470 deaths (21%). Compared to patients with no treated episodes, patients with appropriate therapy had greater risk of death. Hazard ratios were 1.46 (95% confidence interval [CI] 1.05–2.02; P = 0.023) for the ATP‐only group, 2.11 (95% CI 1.51–2.96; P < 0.001) for the single‐shock group, and 2.55 (95% CI 1.43–4.57; P = 0.002) for the multishock group. There was no significant association between any type of inappropriate therapy and increased mortality. We identified only 7 instances of inappropriate ATP precipitating ventricular arrhythmia resulting in shock.

Conclusions

Patients receiving appropriate therapy of all types had increased mortality compared to those with no episodes. Furthermore, inappropriate ATP rarely precipitates ventricular arrhythmias.
The Price Evolution in China's Automobile Market
Authors: Li Shanjun , Xiao Junji , Liu Yimin
Published: October 2015

The automobile market in China has seen unprecedented expansion during the past decade with rapid model turnover and dramatic price decline. This paper aims to document the evolution of price and investigate the sources of price decline, paying attention to both market structure and cost factors. We estimate a market equilibrium model with differentiated multiproduct oligopoly using market‐level sales data in China together with information from household surveys. Our counterfactual simulations show that (quality‐adjusted) vehicle prices have dropped by 33% from 2004 to 2009. The decrease in markup from intensified competition accounts for about one third of this change and the rest comes from cost reductions through learning by doing and other channels. In addition, our simulations show that the price decline would have been larger had it not been for the growth of household income during this period.
Rater Bias and Incentive Provision
Authors: Müller Daniel , Weinschenk Philipp
Published: October 2015

The tendency of supervisors to judge an employee as either good or bad and then to seek out evidence supporting that earlier established opinion is regarded as one of the major problems of performance appraisal. We investigate the implications of this rater bias in a dynamic moral hazard model with a wealth‐constrained agent. Although rater bias weakens the agent's incentives to exert effort in late periods, at the same time it strengthens implicit incentives in early periods. Under the optimal contract, as long as rater bias is not overly strong, its adverse effect on late‐period incentives is fully offset by exploitation of stronger early‐period incentives and thereby leaves the principal's profits unchanged.
Islands of Difference: Design, Urbanism, and Sustainable Tourism in the Anthropocene Caribbean
Authors: Moore Amelia
Published: October 2015

Este artículo introduce la idea del antropoceno como un espacio problema con importancia para la antropología del caribe y la industria turística de éste. Este término es utilizado por científicos para definir la era presente en la cual los procesos humanos operan al nivel de escala geológica y biológica en la tierra, y ha venido a justificar una gran cantidad de acciones en el nombre de la sostenibilidad. A través de la examinación de una zona dedicada a la construcción de segundos hogares en las Bahamas, identifico cambios en diseño turístico de la isla que va dejando atrás el modelo del resort como enclave del turismo en masa. Argumento que las nociones de sostenibilidad del antropoceno no sólo re‐articulan las prácticas de construcción y el “branding” del destino turístico, pero también las posibilidades analíticas para el estudio de fabricación de lugar y procesos transnacionales. Abogo por una mayor incorporación de la antropología del diseño y urbana en el estudio del turismo al caribe como una forma de mejor entender estos eventos emergentes.
Performing Participation: Mining, Power, and the Limits of Public Consultation in Bolivia
Authors: Perreault Tom
Published: October 2015

Los mecanismos de consulta, particularmente aquellos dirigidos a los pueblos indígenas y campesinos, han sido promovidos por instituciones internacionales e incorporados a la normativa legal a lo largo de América Latina. En Bolivia, la consulta ha sido codificada legalmente desde 1991 y ha sido integrada a la normativa que gobierna la extracción minera y de hidrocarburos, así como a la Constitución Nacional de 2009 sólo recientemente. A pesar de ser un requisito legal, la consulta no se implementa con regularidad y tampoco es vinculante en términos jurídicos. Como resultado, ni las empresas privadas ni el estado están obligadas a cumplir las recomendaciones comunitarias. Asimismo, las comunidades no tienen derecho a frenar los proyectos a los que se oponen. Este artículo examina la consulta pública comunitaria en el sector minero de Bolivia. Basado en investigación etnográfica en el departamento boliviano de Oruro, propongo que los procesos de consulta pública son gestionados con fruición y circunscribiendo las opiniones emitidas a nivel local. En vez de fomentar la participación en la gobernanza de recursos naturales por parte de las poblaciones afectadas por la minería, la consulta pública circunscribe y despolitiza las relaciones sociales desiguales e injustas, con el fin de legitimar actividades extractivas. [Bolivia, minería, consulta pública, consulta previa, desarrollo participativa]
Strain mapping accuracy improvement using super‐resolution techniques
Authors: BÁRCENA‐GONZÁLEZ G. , GUERRERO‐LEBRERO M.P. , GUERRERO E. , FERNÁNDEZ‐REYES D. , GONZÁLEZ D. , MAYORAL A. , UTRILLA A.D. , ULLOA J.M. , GALINDO P.L.
Published: October 2015

Super‐resolution (SR) software‐based techniques aim at generating a final image by combining several noisy frames with lower resolution from the same scene. A comparative study on high‐resolution high‐angle annular dark field images of InAs/GaAs QDs has been carried out in order to evaluate the performance of the SR technique. The obtained SR images present enhanced resolution and higher signal‐to‐noise (SNR) ratio and sharpness regarding the experimental images. In addition, SR is also applied in the field of strain analysis using digital image processing applications such as geometrical phase analysis and peak pairs analysis. The precision of the strain mappings can be improved when SR methodologies are applied to experimental images.
Tumour necrosis factor‐α‐mediated disruption of cerebrovascular endothelial barrier integrity in vitro involves the production of proinflammatory interleukin‐6
Authors: Rochfort Keith D. , Collins Laura E. , McLoughlin Alisha , Cummins Philip M.
Published: October 2015

The co‐involvement of tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) during blood‐brain barrier (BBB) injury has been reported in various models of neuroinflammation, although the precise functional interplay between these archetypal proinflammatory cytokines remains largely undefined within this context. In the current paper, we tested the hypothesis that TNF‐α‐mediated BBB disruption is measurably attributable in‐part to induction of microvascular endothelial IL‐6 production. In initial experiments, we observed that treatment of human brain microvascular endothelial cells (HBMvECs) with TNF‐α (0–100 ng/mL, 0–24 h) robustly elicited both time‐ and dose‐dependent induction of IL‐6 expression and release, as well as expression of the IL‐6 family receptor, GP130. Further experiments demonstrated that the TNF‐α‐dependent generation of reactive oxygen species, down‐regulation of adherens/tight junction proteins, and concomitant elevation of HBMvEC permeability, were all significantly attenuated by blockade of IL‐6 signalling using either an anti‐IL‐6 neutralizing antibody or an IL‐6 siRNA. Based on these observations, we conclude that TNF‐α treatment of HBMvECs in vitro activates IL‐6 production and signalling, events that were shown to synergize with TNF‐α actions to elicit HBMvEC permeabilization. These novel findings offer a constructive insight into the specific contribution of downstream cytokine induction to the injurious actions of TNF‐α at the BBB microvascular endothelium interface.

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The co‐involvement of tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) during blood–brain barrier (BBB) injury has been widely reported. Using human brain microvascular endothelial cells (HBMvEC), we show that TNF‐α‐mediated BBB disruption is measurably attributable in‐part to induction of endothelial IL‐6 production and signalling. We demonstrate that the TNF‐α‐dependent generation of reactive oxygen species (ROS), down‐regulation of interendothelial junctions, and concomitant elevation of HBMvEC permeability, could be significantly attenuated by using either an IL‐6 neutralizing antibody or an IL‐6‐specific siRNA. These findings provide insight into the complex nature of proinflammatory cytokine injury at the BBB microvascular endothelium interface.
Chronic and progressive Parkinson's disease MPTP model in adult and aged mice
Authors: Muñoz‐Manchado Ana B. , Villadiego Javier , Romo‐Madero Sonia , Suárez‐Luna Nela , Bermejo‐Navas Alfonso , Rodríguez‐Gómez José A. , Garrido‐Gil Pablo , Labandeira‐García José L. , Echevarría Miriam , López‐Barneo José , Toledo‐Aral Juan J.
Published: October 2015

Despite the different animal models of Parkinson's disease developed during the last years, they still present limitations modelling the slow and progressive process of neurodegeneration. Here, we undertook a histological, neurochemical and behavioural analysis of a new chronic parkinsonian mouse model generated by the subcutaneous administration of low doses of MPTP (20 mg/kg, 3 times per week) for 3 months, using both young adult and aged mice. The MPTP‐induced nigrostriatal neurodegeneration was progressive and was accompanied by a decrease in striatal dopamine levels and motor impairment. We also demonstrated the characteristic neuroinflammatory changes (microglial activation and astrogliosis) associated with the neurodegenerative process. Aged animals showed both a faster time course of neurodegeneration and an altered neuroinflammatory response. The long‐term systemic application of low MPTP doses did not induce any increase in mortality in either young adult or aged mice and better resembles the slow evolution of the neurodegenerative process. This treatment could be useful to model different stages of Parkinson's disease, providing a better understanding of the pathophysiology of the disease and facilitating the testing of both protective and restorative treatments.

image

Here, we show a new chronic and progressive parkinsonian mouse model, in young and aged mice. This model produces a stable degeneration of the dopaminergic nigrostriatal pathway, continuous neuroinflammatory reaction and motor deficits. Aged animals showed a faster neurodegeneration and an altered neuroinflammatory response. This treatment could be useful to model different stages of PD and to test both protective and restorative therapeutic approaches.
Evaluation of Different Thickness, Die Color, and Resin Cement Shade for Veneers of Multilayered CAD/CAM Blocks
Authors: Çömlekoğlu Muharrem Erhan , Paken Gamze , Tan Firuzan , Dündar‐Çömlekoğlu Mine , Özcan Mutlu , Akan Ender , Aladağ Akın
Published: October 2015

Purpose

To investigate the effect of resin cement color on the post‐cementation shade of thin laminate veneers milled from multilayered glass ceramic blocks for each layer.

Materials and Methods

Thin slices (N = 180) with two thicknesses (A: 8 × 8×0.55 mm and B: 8×8×0.8 mm; n = 90/group) were obtained from multilayered glass ceramic blocks using a diamond saw. Resin die specimens were prepared (8 × 8 × 4 mm) (n = 180) and divided into two resin cement colors (D: –3. L: +3) and one control group (C: translucent). Each slice was luted to the composite specimens using a dual‐curing resin cement under a constant load of 250 g and light‐polymerized for 120 seconds. Specimens were placed on a white background and CIELab values for each layer of the blank slices (incisal [In], body [Bo], and cervical [Ce]) were recorded using a dental contact spectrophotometer. The values were calculated as ΔE, and the data were statistically analyzed (one‐way ANOVA, Shapiro‐Wilk).

Results

Mean ΔE values for A and B were significant (p < 0.05) for In (A: 6.2 ± 1.1; B: 6.6 ± 1.2), Bo (A: 5.1 ± 2.6; B: 3.9 ± 1), and Ce (A: 5.3 ± 2.7; B: 3.8 ± 1.2). Mean ΔE values for In for D and L for A and B groups were significantly higher (6.3 ± 1.2; 6.6 ± 1.2) than Bo and Ce for D (4.4 ± 2.4; 4.6 ± 2.6) and L (4.6 ± 1.4; 4.5 ± 1.7) groups (p < 0.05), respectively. Mean differences between Bo and Ce for A and B groups were insignificant (p ≥ 0.05), while for In the differences were significant. Mean differences between Bo and Ce for A (5.1 ± 2.6; 5.3 ± 2.7) and for B (3.9 ± 1; 3.5 ± 1.2) groups were insignificant (p ≥ 0.05), while for In the differences were significant (6.2 ± 1.1 for A and 6.6 ± 1.2 for B).

Conclusion

The color changes for body and cervical regions of multilayered ceramic veneers were not affected by resin color or ceramic thickness, but the incisal area was affected. The translucency of each layer in ceramic veneer fabricated with multilayered blanks should be considered for clinical situations.
Influence of Poles on Results from Reference‐Based Sensory Characterization Methodologies: Case Study with Polarized Projective Mapping Consumers
Authors: de Saldamando Luis , Antúnez Lucía , Giménez Ana , Varela Paula , Ares Gastón
Published: October 2015

One of the main steps related to the implementation of reference‐based sensory characterization methodologies is the selection of the references, sometimes referred to as poles. However, research on the influence of the reference selection on the results from these methodologies is scarce. In this context, the aim of the present work was to evaluate the influence of the poles on results from Polarized projective mapping (PPM). Three groups of consumers evaluated two sets of six samples of powdered drinks using three different sets of poles. Results showed that the set of poles did not largely affect sample configurations and consumers' descriptions. However, some differences in sample configurations were identified when the poles did not represent the whole sensory space represented by the sample sets.

Practical Applications

Results of the present work bring light to researchers on how to select poles for a PPM or PSP task. Given the fact that conclusions from PPM with different sets of poles did not largely differ, pole selection seems to be quite flexible. However, it seems advisable to select poles that represent the whole sensory space defined by the samples to be evaluated and that have an intermediate degree of difference among them. Also, more research applications on different categories of samples would be advised, as well as further research on the influence of the poles on results from other approaches for measuring the degree of difference between samples and poles.
Rapid Detection of Tomato chlorosis virus from Infected Plant and Whitefly by One‐step Reverse Transcription Loop‐mediated Isothermal Amplification
Authors: Karwitha Miriam , Feng Zhi‐Ke , Shen Yan , Essendi Walter , Zhang Wen‐Na , Li Jin‐Yu , Tao Xiao‐Rong
Published: October 2015

Tomato chlorosis virus (ToCV) is the causal agent of an emerging virus disease of tomatoes which causes significant economic losses worldwide. The rapid spread of ToCV is associated with the increasing whitefly population in many countries. In this study, a highly efficient and practical one‐step reverse transcription loop‐mediated isothermal amplification (RT‐LAMP) was developed for the rapid detection of ToCV in infected plant or whitefly. This RT‐LAMP assay can detect ToCV either in total RNA or crude RNA extracted from infected plants using a water bath within 1 h. The presence of ToCV in RT‐LAMP products could be evaluated as ladder‐like bands in an agarose gel or visualized in‐tube with inclusion of a SYBR Green I dye under UV or daylight. RT‐LAMP was 100–1000 times more sensitive compared to conventional RT‐PCR for the detection of ToCV. RT‐LAMP amplification was specific to ToCV, and no false reactions were detected when other viruses were tested. The developed RT‐LAMP assay was also able to detect ToCV from purified RNA extracted from its vector whitefly. This is the first report of the application of the RT‐LAMP to detect ToCV. The RT‐LAMP assay developed in this study provides a rapid, sensitive and practical approach to facilitate the surveillance and management of ToCV.
Comparing and decomposing the determinants of multiple health outcomes in southern and northeastern US states using county data
Authors: Nianogo Thierry , Okunade Albert A
Published: October 2015

Objectives

To investigate whether regional health disparities could explain health outcome differences between US regions.

Methods

The 2010–2012 County Level Raking database, which contains measures on health outcomes and factors for the US states, are used in this study. First, a regional comparison of the determinants of various health outcome measures (premature death rates, low birth weight rate and mean unhealthy days) is undertaken. Next, using the Blinder–Oaxaca decomposition method, the differences in health outcomes are partitioned into the portion explained by regional health factor endowments and the portion unexplained.

Key findings

Obesity rate and access to care determinants impact strongly each region's health outcomes. Half of the differences in clinically assessed (premature death rates and low birth weight rates) measures are unexplained by health endowments. The explained portion for the self-assessed (unhealthy days) outcomes is small.

Conclusions

Study findings both justify the imperatives of accounting for regional variations in order to strengthen policy inferences of research findings and suggest the prevalence of regional disparities in health outcomes. It is important to focus on region-specific preventive care. More effective public education and information strategies raising population awareness to the health hazards of obesity are in order. Greater access to various health services personnel should be provided to the relevant population. Implications are discussed for pharmaceutical care.
Mobility of a small mammalian predator changes according to the activity patterns of potential intraguild predators
Authors: Koivisto E. , Hoset K. S. , Le Tortorec A. H. , Norrdahl K. , Korpimäki E.
Published: October 2015

Competition, habitat structure and predation risk may alter mobility and activity of animals. In particular, small predators need to weigh the positive and negative impacts of the presence of competing larger predator species. Other predators present a risk but may also enhance the predation efficiency of smaller predators if avoiding one predator species increases prey exposure to the other. We studied how habitat structure and the presence of avian predators affected the activity patterns of radio‐collared least weasels Mustela nivalis nivalis, small‐bodied predators highly specialized on hunting small rodents and subject to intraguild predation. Least weasels appeared to schedule their mobility according to the peak activity of the avian predator present in large outdoor enclosures. In the presence of diurnal European kestrels Falco tinnunculus, least weasels moved less during night compared with evening and day, whereas in the presence of nocturnal Tengmalm's owls Aegolius funereus, least weasels moved more during night than during other time periods. Least weasels almost exclusively used the tall grass habitat in all treatments, whereas owls used the short grass habitat most and kestrels used both habitats equally. Our results suggest that beneficial interactions play an important role in the interaction between least weasels, kestrels and owls, and that the avoidance of risky habitats by least weasels minimizes the risk of intraguild predation.
Dorsal fin function in spiny dogfish during steady swimming
Authors: Maia A. , Wilga C. A.
Published: October 2015

Dorsal fins of actinopterygian fishes are known to function to varying degrees as stabilizers and as propulsive elements that augment thrust from the caudal fin. However, little is known about the ability of elasmobranchs to control three‐dimensional conformation of the dorsal fins during swimming, which may alter the force balance during locomotion. In this study, dorsal fin function was investigated in spiny dogfish, Squalus acanthias, swimming steadily at 0.5 and 0.75 BL s−1, using three‐dimensional kinematics and electromyography. Points on the dorsal and caudal fins were tracked in dorsal and lateral views with dual high‐speed video at 125 f s−1. Electrodes were implanted in three points along each dorsal fin muscle and in the adjacent red epaxial muscle. Conformational changes were detected in both dorsal fins at both speeds. Speed was found to influence lateral displacement of the first dorsal fin relative to trunk undulation, with larger magnitudes at 0.5 BL s−1. The first dorsal fin oscillates at a different phase lag than predicted by position on the body, while the second dorsal fin moves in synchrony with the axial musculature. Muscles of the first dorsal fin show synchronous bilateral activation, while there is no clear pattern in the second dorsal fin. This study provides evidence that spiny dogfish control movements of the first dorsal fin during steady swimming to stabilize body position. In contrast, the second dorsal fin appears to be capable of thrust generation. Thus, there is a dual dorsal fin function in spiny dogfish during steady swimming.
How Do We Choose Among Strategies to Accomplish Cognitive Tasks? Evidence From Behavioral and Event‐Related Potential Data in Arithmetic Problem Solving
Authors: Taillan Julien , Dufau Stéphane , Lemaire Patrick
Published: October 2015

We used event‐related potentials (ERPs) to determine the time course of mechanisms underlying strategy selection. Participants had to select the better strategy on multiplication problems (i.e., 51 × 27) to find approximate products. They could choose between rounding up and rounding down both operands to their nearest decades. Two types of problems were tested, homogeneous problems (e.g., 34 × 61) and heterogeneous problems (e.g., 61 × 36). Homogeneous problems are easier to solve because both operands are close to the lowest or the upper decades. Behavioral data revealed that participants selected the better strategy more often on homogeneous problems. ERPs showed that homogeneous problems elicited more positive cerebral activities than heterogeneous problems in the 0–200 and 800–1,000 ms windows, and more negative cerebral activities than heterogeneous problems in the 400–600 ms window. These findings have important theoretical implications for our understanding of the mechanisms underlying strategy selection.
Genetic architecture of growth traits in Populus revealed by integrated quantitative trait locus (QTL) analysis and association studies
Authors: Du Qingzhang , Gong Chenrui , Wang Qingshi , Zhou Daling , Yang Haijiao , Pan Wei , Li Bailian , Zhang Deqiang
Published: October 2015

Deciphering the genetic architecture underlying polygenic traits in perennial species can inform molecular marker‐assisted breeding. Recent advances in high‐throughput sequencing have enabled strategies that integrate linkage–linkage disequilibrium (LD) mapping in Populus.

We used an integrated method of quantitative trait locus (QTL) dissection with a high‐resolution linkage map and multi‐gene association mapping to decipher the nature of genetic architecture (additive, dominant, and epistatic effects) of potential QTLs for growth traits in a Populus linkage population (1200 progeny) and a natural population (435 individuals).

Seventeen QTLs for tree height, diameter at breast height, and stem volume mapped to 11 linkage groups (logarithm of odds (LOD) ≥ 2.5), and explained 2.7–18.5% of the phenotypic variance. After comparative mapping and transcriptome analysis, 187 expressed genes (10 046 common single nucleotide polymorphisms (SNPs)) were selected from the segmental homology regions (SHRs) of 13 QTLs. Using multi‐gene association models, we observed 202 significant SNPs in 63 promising genes from 10 QTLs (P ≤ 0.0001; FDR ≤ 0.10) that exhibited reproducible associations with additive/dominant effects, and further determined 11 top‐ranked genes tightly linked to the QTLs. Epistasis analysis uncovered a uniquely interconnected gene–gene network for each trait.

This study opens up opportunities to uncover the causal networks of interacting genes in plants using an integrated linkage–LD mapping approach.
Prospective neonatal screening for severe T‐ and B‐lymphocyte deficiencies in Seville
Authors: de Felipe Beatriz , Olbrich Peter , Lucenas José Manuel , Delgado‐Pecellin Carmen , Pavon‐Delgado Antonio , Marquez Josefina , Salamanca Carmen , Soler‐Palacin Pere , Gonzalez‐Granado Luis Ignacio , Antolin Laura Ferreras , Borte Stephan , Neth Olaf
Published: October 2015

Background

Early diagnosis of primary immunodeficiency such as severe combined immunodeficiency (SCID) and X‐linked agammaglobulinemia (XLA) improves outcome of affected children. T‐cell‐receptor‐excision circles (TRECs) and kappa‐deleting‐recombination‐excision circles (KRECs) determination from dried blood spots (DBS) identify neonates with severe T‐ and/or B‐lymphopenia. No prospective data exist of the impact of gestational age (GA) and birth weight (BW) on TRECs and KRECs values.

Methods

TRECs and KRECs determination using triplex RT‐PCR (TRECS‐KRECS‐β‐actin‐Assay) from prospectively collected DBS between 02/2014 and 02/2015 in three hospitals in Seville, Spain. Cut‐off levels were TRECs < 6/punch, KRECs < 4/punch and ‐β‐actin>700/punch. Internal (SCID, XLA, ataxia telangiectasia) and external controls (NBS quality assurance program, CDC) were included.

Results

A total of 5160 DBS were tested. Re‐punch was needed in 77 samples (1.5%) due to insufficient β‐actin (<700 copies/punch). Pre‐term neonates (GA<37 weeks) and neonates with a BW<2500 g showed significantly lower TRECs and KRECs levels (p < 0.001). Due to repeat positive results five neonates were re‐called (<0.1%): Fatal chromosomopathy (n = 1; TRECs 1/KRECs 4); extreme pre‐maturity (n = 2; TRECs 0/KRECs 0 and TRECs 1/KRECs 20 copies/punch); neonates born to mothers receiving azathioprine during pregnancy (n = 2; TRECs 92/KRECs 1 and TRECs 154/KRECs 3 copies/punch). All internal and external controls were correctly identified.

Conclusions

TRECS‐KRECS–β‐actin‐Assay correctly identifies T‐ and B‐cell lymphopenias. Pre‐maturity and low BW is associated with lower TREC and KREC levels. Extreme pre‐maturity and maternal immune suppressive therapy may be a cause for false positive results of TRECs and KRECs values, respectively. To reduce the rate of insufficient samples, DBS extraction and storage need to be improved.
Wheat protein recognition pattern in tolerant and allergic children
Authors: Sievers Steven , Rawel Harshadrai M. , Ringel Karl Peter , Niggemann Bodo , Beyer Kirsten
Published: October 2015

Background

Wheat is one of the most common food allergens in early childhood. In contrast to other food allergies, wheat‐specific IgE correlates badly with clinical symptoms and relevant components have been identified mostly for wheat‐depended exercise‐induced anaphylaxis. Moreover, a high percentage of patients present with immediate type symptoms but wheat‐specific IgE cannot be detected with commercial available systems.

Objective

We addressed the question whether the IgE recognition pattern between wheat allergic (WA) and clinically tolerant (WT) children differs in order to identify individual proteins useful for component‐resolved diagnostics.

Methods

Sera of 106 children with suspected wheat allergy, of whom 44 children had clinical relevant wheat allergy and 62 were tolerant upon oral food challenge, were analyzed for wheat‐specific IgE using the ImmunoCap system as well as immunoblots against water and salt soluble, and water‐insoluble protein fractions. 40 randomly selected sera were analyzed for specific IgE to ω5‐gliadin.

Results

Sixty‐three percent of the WT and 86% of the WA children were sensitized to wheat with >0.35 kUA/l in ImmunoCAP analysis. We could confirm the role of α‐, ß‐, γ‐, and ω‐gliadins, and LMW glutenin subunits as major allergens and found also IgE binding to a broad spectrum of water‐ and salt‐soluble protein bands. It is of great importance that wheat allergic and tolerant patients showed IgE binding to the same protein bands. WT and WA did not significantly differ in levels of ω5‐gliadin‐specific IgE.

Conclusions & Clinical Relevance

Children with challenge proven clinical relevant food allergy and tolerant ones had a similar spectrum of IgE binding to the same protein bands. These findings imply that component‐resolved diagnostics might not be helpful in the diagnostic work‐up of wheat allergy.
Transition from brand to generic tacrolimus is associated with a decrease in trough blood concentration in pediatric heart transplant recipients
Authors: Duong Son Q. , Lal Ashwin K. , Joshi Rujuta , Feingold Brian , Venkataramanan Raman
Published: October 2015

There are limited data available on the bioequivalence of generic and brand‐name tacrolimus in pediatric and heart transplant patients. We characterized changes in 12‐hour trough concentrations and clinical outcomes after transition from brand to generic tacrolimus in pediatric thoracic organ transplant recipients. Patients with a pharmacy‐confirmed date of switch between generic and brand tacrolimus were identified, as well as a matched control group that did not switch for comparison. We identified 18 patients with a confirmed date of switch, and in 12 patients that remained on the same dose, trough concentrations were 14% less than when they were on brand (p = 0.037). The average change was −1.15 ± 1.76 ng/mL (p = 0.045). The control group did not experience a change in trough concentration and was different than the switched group (p = 0.005). There were no differences in dosage changes or kidney or liver function. In the year after switch, 24% of patients who were switched to generic experienced a rejection event vs. 18% in the patients on brand. We suggest a strategy of monitoring around the time of transition, and education of the patient/family to notify the care team when changes from brand to generic or between generics occur.
Risks of overharvesting seed from native tallgrass prairies
Authors: Meissen Justin C. , Galatowitsch Susan M. , Cornett Meredith W.
Published: October 2015

Seed supply often limits the size and scope of restoration projects that require active revegetation. To meet demand from more and larger tallgrass prairie restoration projects in the Great Plains, U.S.A., seed is wild‐harvested—collected from remnant habitats—using agricultural combine harvesters. We investigated the potential impacts of wild‐harvest by comparing prairie remnants of northwestern Minnesota that varied in their histories of harvest frequency but were otherwise similar. We asked: (1) Do wild‐harvested prairies differ in species composition from unharvested prairies? (2) If so, can life history traits be used to predict the response of prairie communities to wild‐harvest? We conducted a retrospective study of 17 prairies harvested for seed frequently (annually/biennially), infrequently (2–3 times), or not at all. We sampled vegetation at 45 points within each site, recording all species present within 0.25 m2 quadrats. To address the first question, we used non‐metric multidimensional scaling and Mantel tests, followed by analysis of variance contrasts to identify any species less likely to occur on frequently harvested sites (“harvest‐negative”). For the second question, we used logistic regression to test whether lifespan, clonality, and seed production predicted harvest‐negative species. Plant community composition in frequently harvested prairies differed from that of infrequently or unharvested prairies. Fourteen species, generally short‐lived and non‐clonal, were classified as harvest‐negative. Our results suggest that frequent wild‐harvest disrupts reproduction of species relying on seed, and that life history traits may provide a basis for predicting a species' response to wild‐harvest.
Diversifying Nature Protection: Evaluating the Changing Tools for Forest Protection in Canada and Norway
Authors: Auld Graeme , Gulbrandsen Lars H.
Published: October 2015

Governments increasingly struggle to protect representative nature types and ecological diversity within their territories only via the instrument of publicly designated protected areas. This article examines the rise of voluntary conservation and certification (i.e., private conservation) as tools for forest protection in Norway and Canada. We contrast the differing potential of these private conservation tools with protection through government legislation and regulation using four evaluative criteria: the representativeness of protected areas, the strength of protection, the longevity of protection, and the information generated through protection. We find that private conservation tools can match the strength of legal protection and help to dispel conflict, but that private tools create protection that is more likely to be reversed in the future. However, we also show that voluntary private conservation can become public protection, which highlights the importance of examining different paths toward secure and long‐lasting protection.
How Self‐Image and Compassionate Goals Shape Intrapsychic Experiences
Authors: Canevello Amy , Crocker Jennifer
Published: October 2015

Self‐image goals focus on constructing, maintaining, and defending desired public and private images of the self, whereas compassionate goals focus on being supportive and not harming others. We suggest that these goals shape construals of others in relation to the self, which in turn, shape affective experiences. We review research showing that when people have self‐image goals, they construe others as competitors, which leads to feeling uneasy with others (i.e., conflicted, confused, and fearful), and that when they have compassionate goals, they construe others as collaborators and have more constructive approaches to interpersonal problems, which leads to feeling at ease with others (i.e., peaceful, clear, and loving) and less upset with them. Thus, interpersonal goals shape construals of others, which in turn shape intrapsychic experiences of the world and of the self.
The Tripartite Foundations of Temporal Psychological Distance: Metaphors, Ecology, and Teleology
Authors: Van Boven Leaf , Caruso Eugene M.
Published: October 2015

What is psychological distance? Why do events sometimes seem “close” yet other times seem “ages away?” We propose a tripartite model of the foundations of psychological distance in which: (a) people use spatial distance as a metaphor for psychological distance; (b) the ecology of subjective experiences that coincide with changes in objective distance define, and hence, influence psychological distance; (c) psychological distance is shaped in the service of people's ultimate goals, or teleological considerations, of successfully navigating through time. This model implies that the subjective experiences that are typically associated with reductions in objective temporal distance should reduce temporal psychological distance–the subjective sense of how close or far away events are. We review evidence indicating that emotional arousal, attention, fluency, and motivational considerations all reduce psychological distance. This model also implies a temporal asymmetry in which people prioritize thinking about the future, which approaches in time, over thinking about the past, which recedes in time. Consequently, the future is psychologically closer than the past, people attend more to the future than to the past, and people feel more emotionally aroused about the future than about the past. These findings help advance understanding of psychological distance as a distinct psychological construct.
Experimental Investigations of Fracture Process in Concrete by Means of X‐ray Micro‐computed Tomography
Authors: Skarżyński Ł. , Tejchman J.
Published: October 2015

The paper describes investigation results on fracture in notched concrete beams under quasi‐static three‐point bending by the X‐ray micro‐computed tomography. The two‐dimensional (2D) and three‐dimensional image procedures were used. Attention was paid to width, length, height and shape of cracks along beam depth. In addition, the displacements on the surface of concrete beams during the deformation process were measured with the 2D digital image correlation technique in order to detect strain localisation before a discrete crack occurred. The 2D fracture patterns in beams were numerically simulated with the finite‐element method using an isotropic damage constitutive model enhanced by a characteristic length of micro‐structure. Concrete was modelled as a random heterogeneous four‐phase material composed of aggregate, cement matrix, interfacial transitional zones and air voids. The advantages of the X‐ray micro‐computed tomography were outlined.
Measuring Connectivity in a Globally Networked Industry: The Case of Air Transport
Authors: Arvis Jean‐François , Shepherd Ben
Published: October 2015

We develop a new method for measuring air transport connectivity and apply it to data for 211 countries and territories for the year 2007. Our approach is grounded both in network analysis and in gravity modelling. It produces a global measure of connectivity, which captures the full range of interactions among all network nodes, even when there is no direct flight between them. Connectivity follows a power‐law distribution that is fully consistent with a hub‐and‐spoke network. Our approach provides a new basis for future research in related areas.