bluuebunny/crossref_metadata_2025 huggingface dataset:
Free polyamine and polyamine regulation during pre‐penetration and penetration resistance events in oat against crown rust (Puccinia coronata f. sp. avenae)
Authors: Montilla‐Bascón G. , Rubiales D. , Altabella T. , Prats E.
Published: June 2015

During recent years a wealth of studies has focused on the role of polyamines in plant–environment stress interaction. However, less is known about the role of these compounds in plant disease resistance, and most of this knowledge is related to the hypersensitive response. Here the involvement of polyamines in the oat–crown rust interaction is examined, focusing on the mesophyll cell pre‐penetration and penetration resistance mechanisms. Two different oat cultivars were used, one resistant (Saia) and the other susceptible (Araceli) to crown rust (Puccinia coronata f. sp. avenae). Differential increases in polyamines between oat cultivars upon rust inoculation were observed and associated with increased pre‐penetration and penetration resistance. Elevated levels of spermidine and spermine, together with increases in the cell wall‐bound diamine‐ and polyamine oxidase activities, and concomitant increases in the polyamine oxidation product 1,3‐diaminopropane, were observed in the resistant cultivar at early stages of the infection process. This suggests an involvement of polyamines and derived H2O2 during penetration resistance. The putative role of polyamines in oat resistance to crown rust is supported by the increased resistance observed in the susceptible cultivar Araceli, as a result of reduced appressorium formation, after treatment with exogenous polyamines. Because arginine decarboxylase (ADC) has been reported as a key polyamine biosynthesis enzyme in plants exposed to stress, ADC transcript levels and enzyme activity were also evaluated, revealing an increase in ADC activity in cv. Saia at the key time points for the pre‐penetration and penetration resistance responses, which suggest an involvement of this enzyme in the resistance response.
‘Un étrange moyen de séduction’: Anne de Graville's Chaldean Histories and her role in literary culture at the French court in the early sixteenth century
Authors: L'Estrange Elizabeth
Published: June 2015

This article considers a little‐known manuscript – the Chaldean Histories – that was offered to Anne de Graville, author, bibliophile, and lady‐in‐waiting to Claude of France, by her husband Pierre de Balsac around 1507–10. The manuscript contains a partial translation into French of Annius of Viterbo's Antiquities, first published in Rome in 1498 and purporting to be ancient texts relating the history of the world around the time of the Flood. Although previous scholars have noted the close reliance on the Antiquities by Jean Lemaire des Belges in his Illustrations de Gaule et singularités de Troyes (1511–13), the translation offered to Anne is unknown. Here I argue that Anne's personalized manuscript and translation predates Lemaire des Belges’ work, indicating that she and Pierre were early players in an emerging courtly interest in translated works relating to antiquity. In addition, I suggest that the choice of text and the manuscript's frontispiece by a leading court artist showing Anne receiving the book meant that it was designed to appeal to, and likely shaped, Anne's interests in literature and translation which are later evident in her own library and writings for the French queen, Claude.
Exposure to Mixtures of Metals and Neurodevelopmental Outcomes: A Multidisciplinary Review Using an Adverse Outcome Pathway Framework
Authors: von Stackelberg Katherine , Guzy Elizabeth , Chu Tian , Henn Birgit Claus
Published: June 2015

Current risk assessment guidance calls for an individual chemical‐by‐chemical approach that fails to capture potential interactive effects of exposure to environmental mixtures and genetic variability. We conducted a review of the literature on relationships between prenatal and early life exposure to mixtures of lead (Pb), arsenic (As), cadmium (Cd), and manganese (Mn) with neurodevelopmental outcomes. We then used an adverse outcome pathway (AOP) framework to integrate lines of evidence from multiple disciplines based on evolving guidance developed by the Organization for Economic Cooperation and Development (OECD). Toxicological evidence suggests a greater than additive effect of combined exposures to As–Pb–Cd and to Mn with any other metal, and several epidemiologic studies also suggest synergistic effects from binary combinations of Pb–As, Pb–Cd, and Pb–Mn. The exposure levels reported in these epidemiologic studies largely fall at the high‐end (e.g., 95th percentile) of biomonitoring data from the National Health and Nutrition Examination Survey (NHANES), suggesting a small but significant potential for high‐end exposures. This review integrates multiple data sources using an AOP framework and provides an initial application of the OECD guidance in the context of potential neurodevelopmental toxicity of several metals, recognizing the evolving nature of regulatory interpretation and acceptance.
Objective Bayesian Estimation of the Probability of Default
Authors: Kazianka Hannes
Published: June 2015

Reliable estimation of the probability of default (PD) of a customer is one of the most important tasks in credit risk modelling for banks applying the internal ratings-based approach under the Basel II–III framework. Motivated by the desire to analyse reliably a low default portfolio of non-profit housing companies, we consider PD estimation within a Bayesian framework and develop objective priors for the parameter θ representing the PD in the Gaussian and the Student t single-factor models. A marginal reference prior and limiting versions of it are presented and their posterior propriety is studied. The priors are shown to be direct generalizations of the Jeffreys prior in the binomial model. We use Markov chain Monte Carlo strategies to sample efficiently from the posterior distributions and compare the developed priors on the grounds of the frequentist properties of the resulting Bayesian inferences with subjective priors previously proposed in the literature. Finally, the analysis of the non-profit housing companies portfolio highlights the ultility of the methodological developments.
A Localized Masculine Crisis: Local Men's Subordination within theMarcellusShale Region's Masculine Structure
Authors: Filteau Matthew R.
Published: June 2015

Rural economic decline in theUnitedStates has contributed to new situational conditions under which men construct masculinity. Under these conditions, men define jobs and activities that were feminized during periods of economic stability as masculine. One exception to rural economic decline for men is economic growth associated with oil and natural gas development in geographical hot spots throughout theUnitedStates and around the world. Employment opportunities in the oil and gas industry largely favor men; however, it is unclear what effect this development has on local men because itinerant extralocal male workers complete most of the labor. This article conceptualizes masculinity as a social structure, and uses economic reports and theoretically distinct literatures on natural‐resource‐based masculinities and energy boomtowns to illuminate how multinational energy companies and a predominantly extralocal, male itinerant workforce in Pennsylvania'sMarcellusShale region cause adverse situational conditions for local men's constructions of masculinity. Within the new masculine structure, extralocal men's constructions of hegemonic masculinity become more important for defining the local socially dominant masculinity, which subordinates local men's constructions of nonhegemonic masculinities in their own communities. The article concludes with a discussion of how the oil and gas industry's hegemonic masculinity impedes sustainable economic development and community well‐being.
A Closer Examination of Sexual Trauma During Deployment: Not all Sexual Traumas are Associated with Suicidal Ideation
Authors: Monteith Lindsey L. , Menefee Deleene S. , Forster Jeri E. , Bahraini Nazanin H.
Published: June 2015

Military personnel can be exposed to a wide range of sexual trauma while deployed, including sexual harassment and sexual assault. We examined whether different types of sexual trauma during deployment associated with recent suicidal ideation among previously deployed OEF/OIF/OND veterans admitted to trauma‐focused treatment (n = 199). More severe forms of sexual trauma (e.g., sexual assault) were significantly and positively associated with suicidal ideation. In contrast, sexual trauma involving verbal remarks (e.g., sexual harassment) was not associated with suicidal ideation. Our findings suggest that sexual harassment and sexual assault during deployment may be differentially associated with suicidal ideation.
A phytochrome/phototropin chimeric photoreceptor of fern functions as a blue/far‐red light‐dependent photoreceptor for phototropism in Arabidopsis
Authors: Kanegae Takeshi , Kimura Izumi
Published: June 2015

In the fern Adiantum capillus‐veneris, the phototropic response of the protonemal cells is induced by blue light and partially inhibited by subsequent irradiation with far‐red light. This observation strongly suggests the existence of a phytochrome that mediates this blue/far‐red reversible response; however, the phytochrome responsible for this response has not been identified. PHY3/NEO1, one of the three phytochrome genes identified in Adiantum, encodes a chimeric photoreceptor composed of both a phytochrome and a phototropin domain. It was demonstrated that phy3 mediates the red light‐dependent phototropic response of Adiantum, and that phy3 potentially functions as a phototropin. These findings suggest that phy3 is the phytochrome that mediates the blue/far‐red response in Adiantum protonemata. In the present study, we expressed Adiantum phy3 in a phot1 phot2 phototropin‐deficient Arabidopsis line, and investigated the ability of phy3 to induce phototropic responses under various light conditions. Blue light irradiation clearly induced a phototropic response in the phy3‐expressing transgenic seedlings, and this effect was fully inhibited by simultaneous irradiation with far‐red light. In addition, experiments using amino acid‐substituted phy3 indicated that FMN‐cysteinyl adduct formation in the light, oxygen, voltage (LOV) domain was not necessary for the induction of blue light‐dependent phototropism by phy3. We thus demonstrate that phy3 is the phytochrome that mediates the blue/far‐red reversible phototropic response in Adiantum. Furthermore, our results imply that phy3 can function as a phototropin, but that it acts principally as a phytochrome that mediates both the red/far‐red and blue/far‐red light responses.
Ectopic expression of snapdragon transcription factors facilitates the identification of genes encoding enzymes of anthocyanin decoration in tomato
Authors: Tohge Takayuki , Zhang Yang , Peterek Silke , Matros Andrea , Rallapalli Ghanasyam , Tandrón Yudelsy A. , Butelli Eugenio , Kallam Kalyani , Hertkorn Norbert , Mock Hans‐Peter , Martin Cathie , Fernie Alisdair R.
Published: June 2015

Given the potential health benefits of polyphenolic compounds in the diet, there is a growing interest in the generation of food crops enriched with health‐protective flavonoids. We undertook a series of metabolite analyses of tomatoes ectopically expressing the Delila and Rosea1 transcription factor genes from snapdragon (Antirrhinum majus), paying particular attention to changes in phenylpropanoids compared to controls. These analyses revealed multiple changes, including depletion of rutin and naringenin chalcone, and enhanced levels of anthocyanins and phenylacylated flavonol derivatives. We isolated and characterized the chemical structures of the two most abundant anthocyanins, which were shown by NMR spectroscopy to be delphinidin‐3–(4′′′–O‐trans‐p–coumaroyl)‐rutinoside‐5–O–glucoside and petunidin‐3–(4′′′–O‐trans‐p‐coumaroyl)‐rutinoside‐5–O–glucoside. By performing RNA sequencing on both purple fruit and wild‐type fruit, we obtained important information concerning the relative expression of both structural and transcription factor genes. Integrative analysis of the transcript and metabolite datasets provided compelling evidence of the nature of all anthocyanin biosynthetic genes, including those encoding species‐specific anthocyanin decoration enzymes. One gene, SlFdAT1 (Solyc12g088170), predicted to encode a flavonoid‐3–O‐rutinoside‐4′′′–phenylacyltransferase, was characterized by assays of recombinant protein and over‐expression assays in tobacco. The combined data are discussed in the context of both our current understanding of phenylpropanoid metabolism in Solanaceous species, and evolution of flavonoid decorating enzymes and their transcriptional networks in various plant species.
How we use WinRho in patients with idiopathic thrombocytopenic purpura
Authors: Stotler Brie A. , Schwartz Joseph
Published: June 2015

Primary immune thrombocytopenia (ITP) is an autoimmune disease that affects children and adults. WinRho SDF is a D immune globulin product that is Food and Drug Administration approved for the treatment of ITP in D+ pediatric and adult patients. WinRho is a plasma‐derived biologic product dispensed from blood banks. Transfusion medicine physicians serve as a resource to health care providers regarding blood component and derivative usage and, as such, should be familiar with the use of WinRho for ITP, including the dosage, administration, and contraindications. This report details the transfusion medicine consultation practice and guidelines at a tertiary care academic medical center for the usage of WinRho SDF in patients with ITP.
Mucocutaneous lupus erythematosus in dogs (21 cases)
Authors: Olivry Thierry , Rossi Michael A. , Banovic Frane , Linder Keith E.
Published: June 2015

Background

The diagnosis of dogs with chronic juxtamucosal erosive lesions and histopathology typical of cutaneous lupus erythematosus (CLE) is unclear.

Hypothesis/Objectives

We report herein 21 dogs with mucocutaneous erosive lesions and lupus‐specific histopathology that we propose to be affected with mucocutaneous lupus erythematosus (MCLE), another variant of chronic CLE.

Methods

Inclusion criteria were the presence of the following: (i) a >2 month history of chronic or recurrent skin lesions; (ii) erosions or ulcers predominating at mucosae or mucocutaneous junctions; (iii) microscopic lesions of CLE (i.e. a lymphocyte‐rich interface dermatitis with basal keratinocyte damage); and (iv) a lack of complete remission following antimicrobials. Clinical questionnaires and skin biopsies were reviewed. Direct immunofluorescence and antinuclear antibody serology were performed whenever possible.

Results

More than half of the 21 dogs were German shepherds or their crosses. The disease affected mostly dogs in their mid‐adulthood and there was an over‐representation of females. Erosions and ulcers predominated at genital/perigenital and anal/perianal areas, with a lower frequency of involvement of periocular, perioral and perinasal regions. In these dogs, there were no clinical signs suggestive of an associated systemic lupus erythematosus. Microscopic lesions were specific for CLE, but they were patchy and often infected with bacteria. The most common immunological finding was focal IgG deposition at the basement membrane zone. Lesions responded to varying interventions, but oral glucocorticoids led to a shorter time to complete remission. Relapses were common upon treatment tapering.

Conclusions and clinical importance

These observations support MCLE being another variant of canine CLE.
Generalized severe junctional epidermolysis bullosa with congenital absence of skin in churra lambs
Authors: Benavides Julio , Suárez‐Vega Aroa , Gutiérrez Jorge , de la Hera Sandra , Fuertes Miguel , Delgado Laetitia , Fernández Miguel , Ferreras María del Carmen , Arranz Juan José , Pérez Valentín
Published: June 2015

Background

Up to 0.5% of churra lambs from two genetically related flocks showed congenital skin lesions of variable severity, jeopardizing the life of the lambs in the most severe cases.

Hypothesis/Objectives

The primary objective of this study was to classify the type of congenital epithelial disease suffered by these animals, based on the description of the macroscopic skin defects, the histological and ultrastructural changes and the hereditary nature of the condition.

Animals

Thirty affected newborn lambs from two genetically related flocks were studied. Three additional lambs acquired from two other flocks, which had no grossly apparent skin lesions and had died of infectious diseases, were studied as unaffected control animals.

Methods

Histological and ultrastructural examinations of skin and oral mucosa samples were performed. Pedigree analyses were used to investigate genealogical relationships.

Results

Generalized severe junctional epidermolysis bullosa with congenital absence of skin was described in all lambs studied and an autosomal recessive mode of inheritance was identified.

Conclusions and clinical importance

The pathological findings and mode of inheritance in these lambs are similar to an inherited epidermolysis bullosa subtype of humans, which has not been reported previously in veterinary medicine.
IMAGING DIAGNOSIS–SCLEROSING ENCAPSULATING PERITONITIS IN A DOG
Authors: Veiga‐Parga Tamara , Hecht Silke , Craig Linden
Published: June 2015

An approximately 5‐month‐old American Staffordshire terrier was presented with a history of recurrent peritoneal effusion. Abdominal radiographs and ultrasound showed a loculated effusion in the ventral abdomen with dorsal displacement of abdominal organs, hepatomegaly and rounding of liver and splenic margins. Computed tomography demonstrated centrally located gastrointestinal segments surrounded by a thin soft tissue band and a thickened peritoneal lining. At necropsy a fibrous membrane continuous with liver and splenic capsules encapsulated all abdominal organs. Microscopically the abdominal wall and fibrous capsule consisted of an irregular thick layer of hypocellular connective tissue. The final diagnosis was sclerosing encapsulating peritonitis.
Development and Validation of Finite Element Structure-Tuned Liquid Damper System Models
Authors: Soliman Islam M. , Tait Michael J. , El Damatty Ashraf A.
Published: June 2015

Implementation of supplemental damping systems (e.g., the dynamic vibration absorbers (DVAs)) to mitigate excessive tall building vibrations induced by external dynamic loads (wind storms or earthquakes) has increased over the last several decades. A tuned liquid damper (TLD) is a specific type of the DVAs that consists of a rigid tank which is partially filled with a liquid, usually water. The sloshing liquid inside the tank provides inertia forces that counteract the forces acting on the structure, thus reducing the building motion. A single sway mode of vibration is usually targeted, however, for certain structures multiple modes may need to be suppressed. Moreover, the location of the TLD on the floor plate is important for certain modes, such as a torsionally dominate mode. In this paper, a three-dimensional (3D) finite element (FE) structure-TLD system model (3D-structure-TLD) is proposed where the TLDs can be positioned at any location on the structure allowing the most effective positions in reducing the structure's dynamic response to be determined. Therefore, the response of a 3D structure (tower, high-rise building, bridge, etc.) fitted with single or multiple TLD(s) and subjected to dynamic excitation can be predicted using the proposed FE model. For torsionally sensitive structure (eccentric/irregular structures), this type of 3D numerical analysis is highly recommended. Two nonlinear TLD models are employed to simulate the TLD and implemented in the FE model. The 3D-structure-TLD system model is validated for the cases of sinusoidal and random excitation forces using existing experimental test values. Results from the 3D-structure-TLD system model are found to be in excellent agreement with values obtained from experimental tests.
Tracking Controller Design for MIMO Nonlinear Systems With Application to Automotive Cold Start Emission Reduction
Authors: Pan Selina , Karl Hedrick J.
Published: June 2015

The main contribution of this paper is the development of a nonlinear multiple-input, multiple-output (MIMO) tracking controller design using a discrete time sliding control approach. A Lyapunov stability analysis is used to prove the asymptotic stability of both the output errors as well as the parameter estimation errors. The application of the “New Invariance Principle” is key to the proof of the parameter error convergence. The developed approach is applied to the cold start emissions problem. The software design process for automotive powertrains on vehicles is growing increasingly complex. Verification and validation provides a systematic procedure to follow for the implementation of control algorithms on physical systems. However, errors can arise that prove costly if not mitigated early on in the verification and validation process. Therefore, the detection and mitigation of potential uncertainties early on in the design process is vital. In this work, the determination of the system model uncertainty is the focus of an adaptation algorithm designed in parallel with a discrete time, MIMO sliding controller. The unknown parameter representing the model uncertainty is updated online in order to decrease tracking error and control effort. The MIMO formulation allows for implementation of both coupled and decoupled frameworks, thus providing a basis for the algorithm to be utilized on a variety of complex vehicle systems. The control algorithms are implemented on a cold start emissions engine model as a case study. A matlab simulink environment is used for simulation results, and an engine test cell is used for experimental validation. Simulation results demonstrate that the algorithm drives tracking error to zero in a fraction of the run time and that the algorithm may be applied with equal efficacy to coupled and decoupled systems. Experimental results demonstrate the ability of the adaptation algorithm to estimate uncertainty in the engine and decrease tracking error.
Shape Bifurcation of a Spherical Dielectric Elastomer Balloon Under the Actions of Internal Pressure and Electric Voltage
Authors: Liang Xudong , Cai Shengqiang
Published: June 2015

Under the actions of internal pressure and electric voltage, a spherical dielectric elastomer balloon usually keeps a sphere during its deformation, which has also been assumed in many previous studies. In this article, using linear perturbation analysis, we demonstrate that a spherical dielectric elastomer balloon may bifurcate to a nonspherical shape under certain electromechanical loading conditions. We also show that with a nonspherical shape, the dielectric elastomer balloon may have highly inhomogeneous electric field and stress/stretch distributions, which can lead to the failure of the system. In addition, we conduct stability analysis of the dielectric elastomer balloon in different equilibrium configurations by evaluating its second variation of free energy under arbitrary perturbations. Our analyses indicate that under pressure-control and voltage-control modes, nonspherical deformation of the dielectric elastomer balloon is energetically unstable. However, under charge-control or ideal gas mass-control mode, nonspherical deformation of the balloon is energetically stable.
An Efficient Wiener Path Integral Technique Formulation for Stochastic Response Determination of Nonlinear MDOF Systems
Authors: Kougioumtzoglou Ioannis A. , Di Matteo Alberto , Spanos Pol D. , Pirrotta Antonina , Di Paola Mario
Published: June 2015

The recently developed approximate Wiener path integral (WPI) technique for determining the stochastic response of nonlinear/hysteretic multi-degree-of-freedom (MDOF) systems has proven to be reliable and significantly more efficient than a Monte Carlo simulation (MCS) treatment of the problem for low-dimensional systems. Nevertheless, the standard implementation of the WPI technique can be computationally cumbersome for relatively high-dimensional MDOF systems. In this paper, a novel WPI technique formulation/implementation is developed by combining the “localization” capabilities of the WPI solution framework with an appropriately chosen expansion for approximating the system response PDF. It is shown that, for the case of relatively high-dimensional systems, the herein proposed implementation can drastically decrease the associated computational cost by several orders of magnitude, as compared to both the standard WPI technique and an MCS approach. Several numerical examples are included, whereas comparisons with pertinent MCS data demonstrate the efficiency and reliability of the technique.
Analysis of the Be KLL Auger Transition of Beryllium Nitride and Beryllium Carbide by AES
Authors: Mallinson Christopher F. , Castle James E. , Watts John F.
Published: June 2015

Secondary phase particles of beryllium nitride and beryllium carbide in beryllium were analyzed by Auger Electron Spectroscopy. Survey spectra as well as high resolution Be KLL, N KLL and C KLL transitions were collected and are presented. The primary beryllium KLL Auger transitions for the nitride and carbide were recorded at 96.7 and 100.4 eV respectively. The homogeneity and composition of the secondary phase particles was confirmed by energy dispersive x-ray spectroscopy.
Study on spatial distribution of plasma parameters in a magnetized inductively coupled plasma
Authors: Cheong Hee-Woon , Lee Woohyun , Kim Ji-Won , Whang Ki-Woong , Kim Hyuk , Park Wanjae
Published: June 2015

Spatial distributions of various plasma parameters such as plasma density, electron temperature, and radical density in an inductively coupled plasma (ICP) and a magnetized inductively coupled plasma (M-ICP) were investigated and compared. Electron temperature in between the rf window and the substrate holder of M-ICP was higher than that of ICP, whereas the one just above the substrate holder of M-ICP was similar to that of ICP when a weak (<8 G) magnetic field was employed. As a result, radical densities in M-ICP were higher than those in ICP and the etch rate of oxide in M-ICP was faster than that in ICP without severe electron charging in 90 nm high aspect ratio contact hole etch.
The 2D surfaces that generate Newtonian and general relativistic orbits with small eccentricities
Authors: Middleton Chad A.
Published: June 2015

Embedding diagrams prove to be quite useful when learning general relativity as they offer a way of visualizing spacetime curvature through warped two dimensional (2D) surfaces. In this manuscript, we present a different 2D construct that also serves as a useful conceptual tool for gaining insight into gravitation: orbital dynamics—namely, the cylindrically symmetric surfaces that generate Newtonian and general relativistic orbits with small eccentricities. Although we first show that no such surface exists that can exactly reproduce the arbitrary bound orbits of Newtonian gravitation or of general relativity (or, more generally, of any spherically symmetric potential), surfaces do exist that closely approximate the resulting orbital motion for small eccentricities (exactly the regime that describes the motion of the solar system planets). These surfaces help to illustrate the similarities and differences between the two theories of gravitation (i.e., stationary elliptical orbits in Newtonian gravitation and precessing elliptical-like orbits in general relativity) and offer, in this age of 3D printing, an opportunity for students and instructors to experimentally explore the predictions made by each.
The Short Questionnaire to Assess Health-Enhancing (SQUASH) Physical Activity in Adolescents: A Validation Using Doubly Labeled Water
Authors: Campbell Nerissa , Gaston Anca , Gray Casey , Rush Elaine , Maddison Ralph , Prapavessis Harry
Published: June 2015

Background:

Accurate assessment of physical activity energy expenditure (PAEE) among adolescents is important for surveillance, evaluating interventions, and understanding the relation between energy balance and normal physiological and behavioral growth and development. The purpose of this study was to examine the validity of the Short Questionnaire to Assess Health-Enhancing Physical Activity (SQUASH)13 for measuring PAEE among adolescents.

Methods:

The participants were seventeen adolescents (9 females; Mean age = 17.53; SD = 0.62). Energy expenditure was measured during a 9-day period with doubly labeled water (DLW). The SQUASH was self-administered on the morning of the 10th day and assessed commuting activities, leisure time activities, household activities, and activities at work and school over the previous 9 days.

Results:

A Bland-Altman plot indicated that the SQUASH underestimated PAEE compared with DLW by a mean difference of 126 kcal·d−1 (95% limits of agreement: –1,207 to 1,459 kcal·d−1), representative of a 10% underestimation. The Spearman rank order correlation coefficient showed there was a significant association between the SQUASH and DLW (r = .50, P = .04), for estimating PAEE.

Conclusion:

When using a sample of highly active adolescents, the SQUASH is a valid self-report tool for measuring PAEE at the group and individual rank order level.
Can DNA foil the poachers?
Authors: Hoelzel A. Rus
Published: June 2015

Forensic data help to identify elephant poaching hotspots

[Also see Report by

Wasser
et al.

]
DNA methylation regulates neuronal glutamatergic synaptic scaling
Authors: Meadows Jarrod P. , Guzman-Karlsson Mikael C. , Phillips Scott , Holleman Cassie , Posey Jessica L. , Day Jeremy J. , Hablitz John J. , Sweatt J. David
Published: June 2015

Epigenetically mediated changes in postsynaptic glutamate receptor expression enable neurons to adjust responsiveness to their environment.
A degrading game plan for cancer therapy
Authors: Kiberstis Paula A.
Published: June 2015

A chemical strategy that leads to selective destruction of proteins of interest may be a valuable tool for drug development.
Transcription Factor ADS-4 Regulates Adaptive Responses and Resistance to Antifungal Azole Stress
Authors: Wang Kangji , Zhang Zhenying , Chen Xi , Sun Xianyun , Jin Cheng , Liu Hongwei , Li Shaojie
Published: June 2015

Azoles are commonly used as antifungal drugs or pesticides to control fungal infections in medicine and agriculture. Fungi adapt to azole stress by rapidly activating the transcription of a number of genes, and transcriptional increases in some azole-responsive genes can elevate azole resistance. The regulatory mechanisms that control transcriptional responses to azole stress in filamentous fungi are not well understood. This study identified a bZIP transcription factor, ADS-4 (
a
ntifungal
d
rug
s
ensitive-4), as a new regulator of adaptive responses and resistance to antifungal azoles. Transcription of
ads-4
in
Neurospora crassa
cells increased when they were subjected to ketoconazole treatment, whereas the deletion of
ads-4
resulted in hypersensitivity to ketoconazole and fluconazole. In contrast, the overexpression of
ads-4
increased resistance to fluconazole and ketoconazole in
N. crassa
. Transcriptome sequencing (RNA-seq) analysis, followed by quantitative reverse transcription (qRT)-PCR confirmation, showed that ADS-4 positively regulated the transcriptional responses of at least six genes to ketoconazole stress in
N. crassa
. The gene products of four ADS-4-regulated genes are known contributors to azole resistance, including the major efflux pump CDR4 (Pdr5p ortholog), an ABC multidrug transporter (NcAbcB), sterol C-22 desaturase (ERG5), and a lipid transporter (NcRTA2) that is involved in calcineurin-mediated azole resistance. Deletion of the
ads-4
-homologous gene Af
ads-4
in
Aspergillus fumigatus
caused hypersensitivity to itraconazole and ketoconazole, which suggested that ADS-4 is a functionally conserved regulator of adaptive responses to azoles. This study provides important information on a new azole resistance factor that could be targeted by a new range of antifungal pesticides and drugs.
A Novel Point Mutation Promotes Growth Phase-Dependent Daptomycin Tolerance in Staphylococcus aureus
Authors: Mechler Lukas , Herbig Alexander , Paprotka Kerstin , Fraunholz Martin , Nieselt Kay , Bertram Ralph
Published: June 2015

Recalcitrance of genetically susceptible bacteria to antibiotic killing is a hallmark of bacterial drug tolerance. This phenomenon is prevalent in biofilms, persisters, and also planktonic cells and is associated with chronic or relapsing infections with pathogens such as
Staphylococcus aureus
. Here we report the
in vitro
evolution of an
S. aureus
strain that exhibits a high degree of nonsusceptibility to daptomycin as a result of cyclic challenges with bactericidal concentrations of the drug. This phenotype was attributed to stationary growth phase-dependent drug tolerance and was clearly distinguished from resistance. The underlying genetic basis was revealed to be an adaptive point mutation in the putative inorganic phosphate (P
i
) transporter gene
pitA
. Drug tolerance caused by this allele, termed
pitA6
, was abrogated when the upstream gene
pitR
was inactivated. Enhanced tolerance toward daptomycin, as well as the acyldepsipeptide antibiotic ADEP4 and various combinations of other drugs, was accompanied by elevated intracellular concentrations of P
i
and polyphosphate, which may reversibly interfere with critical cellular functions. The evolved strain displayed increased rates of survival within human endothelial cells, demonstrating the correlation of intracellular persistence and drug tolerance. These findings will be useful for further investigations of
S. aureus
drug tolerance, toward the development of additional antipersister compounds and strategies.
In Vitro
Selection of Ceftazidime-Avibactam Resistance in Enterobacteriaceae with KPC-3 Carbapenemase
Authors: Livermore David M. , Warner Marina , Jamrozy Dorota , Mushtaq Shazad , Nichols Wright W. , Mustafa Nazim , Woodford Neil
Published: June 2015

Ceftazidime-avibactam is active against most
Enterobacteriaceae
isolates with KPC carbapenemases. We investigated whether this activity could be compromised by mutation. Single-step and multistep selections were attempted using ceftazidime-avibactam (avibactam fixed at 1 or 4 μg/ml)
versus
two strains each of
Enterobacter cloacae
and
Klebsiella pneumoniae
, all with the KPC-3 enzyme. Mutant
bla
KPC
alleles were sequenced, and their parentage was confirmed by typing. Ceftazidime-avibactam selected mutants at up to 16× MIC, with frequencies of ca. 10
−9
. This contrasted with previous experience for ceftaroline-avibactam, where mutant frequencies under similar conditions were <10
−9
. The MICs of ceftazidime with 1 μg/ml avibactam for the ceftazidime-avibactam-selected mutants rose from 1 to 8 μg/ml to 16 to >256 μg/ml and those of ceftazidime with 4 μg/ml avibactam from 0.25 to 1 μg/ml to 4 to 128 μg/ml; ceftaroline-avibactam MICs rose less, typically from 0.5 to 1 μg/ml to 1 to 8 μg/ml. The MICs of carbapenems and cephalosporins except ceftazidime and piperacillin-tazobactam were reduced for many mutants. Sequencing of

bla
KPC

revealed point and insertion changes in 12/13 mutants investigated, representing all four parents; one mutant lacked
bla
KPC
changes and possibly had reduced permeability. Amino acid changes commonly involved Ω loop alterations or 1 to 6 amino acid insertions immediately C-terminal to this loop. The most frequent change, seen in four mutants from three strains, was Asp179Tyr, replacing a residue that ordinarily forms a salt bridge to stabilize the Ω loop. Since ceftaroline-avibactam was less affected than ceftazidime-avibactam, we postulate that these mutations increase ceftazidimase specificity rather than conferring avibactam resistance. The clinical relevance remains uncertain.
In Vitro
Activities of a Wide Panel of Antifungal Drugs against Various Scopulariopsis and Microascus Species
Authors: Skóra Magdalena , Bulanda Małgorzata , Jagielski Tomasz
Published: June 2015

The
in vitro
activities of 11 antifungal drugs against 68
Scopulariopsis
and
Microascus
strains were investigated. Amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, voriconazole, and ciclopirox showed no or poor antifungal effect. The best activities were exhibited by terbinafine and caspofungin, where the MIC and MEC (minimal effective concentration) ranges were 0.0313 to >16 μg/ml and 0.125 to 16 μg/ml, respectively. The MIC and MEC modes were both 1 µg/ml for terbinafine and caspofungin; the MIC
50
and MEC
50
were 1 µg/ml for both drugs, whereas the MIC
90
and MEC
90
were 4 µg/ml and 16 µg/ml, respectively.
Genome Sequences of Mycobacteriophages Luchador and Nerujay
Authors: Pope Welkin H. , Ahmed Taha , Drobitch Marissa K. , Early David R. , Eljamri Soukaina , Kasturiarachi Naomi S. , Klonicki Emily F. , Manjooran Daniel T. , Ní Chochlain Aífe N. , Puglionesi Andrew O. , Rajakumar Vinod , Shindle Katherine A. , Tran Mai T. , Brown Bryony R. , Churilla Bryce M. , Cohen Karen L. , Wilkes Kellyn E. , Grubb Sarah R. , Warner Marcie H. , Bowman Charles A. , Russell Daniel A. , Hatfull Graham F.
Published: June 2015

Luchador and Nerujay are two newly isolated mycobacteriophages recovered from soil samples using
Mycobacterium smegmatis
. Their genomes are 53,387 bp and 53,455 bp long and have 96 and 97 predicted open reading frames, respectively. Nerujay is related to subcluster A1 phages, and Luchador represents a new subcluster, A14.
Genome Sequence of Mycobacteriophage Momo
Authors: Pope Welkin H. , Bina Elizabeth A. , Brahme Indraneel S. , Hill Amy B. , Himmelstein Philip H. , Hunsicker Sara M. , Ish Amanda R. , Le Tinh S. , Martin Mary M. , Moscinski Catherine N. , Shetty Sameer A. , Swierzewski Tomasz , Iyengar Varun B. , Kim Hannah , Schafer Claire E. , Grubb Sarah R. , Warner Marcie H. , Bowman Charles A. , Russell Daniel A. , Hatfull Graham F.
Published: June 2015

Momo is a newly discovered phage of
Mycobacterium smegmatis
mc
2
155. Momo has a double-stranded DNA genome 154,553 bp in length, with 233 predicted protein-encoding genes, 34 tRNA genes, and one transfer-messenger RNA (tmRNA) gene. Momo has a myoviral morphology and shares extensive nucleotide sequence similarity with subcluster C1 mycobacteriophages.
Draft Genome Sequences of Bacillus anthracis Strains Stored for Several Decades in Japan
Authors: Okutani Akiko , Osaki Makoto , Takamatsu Daisuke , Kaku Yoshihiro , Inoue Satoshi , Morikawa Shigeru
Published: June 2015

We report the draft genome sequences ofBacillus anthracisstrains Shikan-NIID, 52-40-NIAH, and 44-NIAH stored in Japan and belonging to the A3 cluster.
Molecular Characterization of the First Ebola Virus Isolated in Italy, from a Health Care Worker Repatriated from Sierra Leone
Authors: Castilletti Concetta , Carletti Fabrizio , Gruber Cesare E. M. , Bordi Licia , Lalle Eleonora , Quartu Serena , Meschi Silvia , Lapa Daniele , Colavita Francesca , Chiappini Roberta , Mazzarelli Antonio , Marsella Patrizia , Petrosillo Nicola , Nicastri Emanuele , Chillemi Giovanni , Valentini Alessio , Desideri Alessandro , Di Caro Antonino , Ippolito Giuseppe , Capobianchi Maria R.
Published: June 2015

Here, we report the complete genome sequence of an Ebola virus (EBOV) isolated from a health worker repatriated from Sierra Leone to Italy in November 2014. The sequence, clustering in clade 3 of the Sierra Leone sequences, was analyzed with respect to mutations possibly affecting diagnostic and therapeutic targets as well as virulence.
Complete Genome Sequence of a Recent Panzootic Virulent Newcastle Disease Virus from Pakistan
Authors: Wajid Abdul , Wasim Muhammad , Rehmani Shafqat F. , Bibi Tasra , Ahmed Nazir , Afonso Claudio L.
Published: June 2015

The genome sequence of a new strain of Newcastle disease virus (NDV) (chicken/Pak/Quality Operations Lab/SFR-611/13) is reported here. The strain was isolated from a vaccinated chicken flock in Pakistan in 2013 and has panzootic features. The genome is 15,192 nucleotides in length and is classified in subgenotype VIIi of genotype VII, class II.
Manipulation of Autophagy in Phagocytes Facilitates Staphylococcus aureus Bloodstream Infection
Authors: O'Keeffe Kate M. , Wilk Mieszko M. , Leech John M. , Murphy Alison G. , Laabei Maisem , Monk Ian R. , Massey Ruth C. , Lindsay Jodi A. , Foster Timothy J. , Geoghegan Joan A. , McLoughlin Rachel M.
Published: June 2015

The capacity for intracellular survival within phagocytes is likely a critical factor facilitating the dissemination of
Staphylococcus aureus
in the host. To date, the majority of work on
S. aureus
-phagocyte interactions has focused on neutrophils and, to a lesser extent, macrophages, yet we understand little about the role played by dendritic cells (DCs) in the direct killing of this bacterium. Using bone marrow-derived DCs (BMDCs), we demonstrate for the first time that DCs can effectively kill
S. aureus
but that certain strains of
S. aureus
have the capacity to evade DC (and macrophage) killing by manipulation of autophagic pathways. Strains with high levels of Agr activity were capable of causing autophagosome accumulation, were not killed by BMDCs, and subsequently escaped from the phagocyte, exerting significant cytotoxic effects. Conversely, strains that exhibited low levels of Agr activity failed to accumulate autophagosomes and were killed by BMDCs. Inhibition of the autophagic pathway by treatment with 3-methyladenine restored the bactericidal effects of BMDCs. Using an
in vivo
model of systemic infection, we demonstrated that the ability of
S. aureus
strains to evade phagocytic cell killing and to survive temporarily within phagocytes correlated with persistence in the periphery and that this effect is critically Agr dependent. Taken together, our data suggest that strains of
S. aureus
exhibiting high levels of Agr activity are capable of blocking autophagic flux, leading to the accumulation of autophagosomes. Within these autophagosomes, the bacteria are protected from phagocytic killing, thus providing an intracellular survival niche within professional phagocytes, which ultimately facilitates dissemination.
Protection against Shiga-Toxigenic Escherichia coli by Non-Genetically Modified Organism Receptor Mimic Bacterial Ghosts
Authors: Paton Adrienne W. , Chen Austen Y. , Wang Hui , McAllister Lauren J. , Höggerl Florian , Mayr Ulrike Beate , Shewell Lucy K. , Jennings Michael P. , Morona Renato , Lubitz Werner , Paton James C.
Published: June 2015

Shiga-toxigenic
Escherichia coli
(STEC) causes severe gastrointestinal infections in humans that may lead to life-threatening systemic sequelae, such as the hemolytic uremic syndrome (HUS). Rapid diagnosis of STEC infection early in the course of disease opens a window of opportunity for therapeutic intervention, for example, by administration of agents that neutralize Shiga toxin (Stx) in the gut lumen. We previously developed a recombinant bacterium that expresses a mimic of the Stx receptor globotriaosyl ceramide (Gb3) on its surface through modification of the lipopolysaccharide (A. W. Paton, R. Morona, and J. C. Paton, Nat Med
6:
265–270, 2000,
http://dx.doi.org/10.1038/73111
). This construct was highly efficacious
in vivo
, protecting mice from otherwise fatal STEC disease, but the fact that it is a genetically modified organism (GMO) has been a barrier to clinical development. In the present study, we have overcome this issue by development of Gb3 receptor mimic bacterial ghosts (BGs) that are not classified as GMOs. Gb3-BGs neutralized Stx1 and Stx2
in vitro
with high efficiency, whereas alternative Gb3-expressing non-GMO subbacterial particles (minicells and outer membrane blebs) were ineffective. Gb3-BGs were highly efficacious in a murine model of STEC disease. All mice (10/10) treated with Gb3-BGs survived challenge with a highly virulent O113:H21 STEC strain and showed no pathological signs of renal injury. In contrast, 6/10 mice treated with control BGs succumbed to STEC challenge, and survivors exhibited significant weight loss, neutrophilia, and histopathological evidence of renal damage. Thus, Gb3-BGs offer a non-GMO approach to treatment of STEC infection in humans, particularly in an outbreak setting.
Post-transfusion breathlessness in a patient with acute myeloid leukaemia
Authors: Gupta Arjun , Parikh Kisan , Pandey Ambarish
Published: June 2015

We present a case of a 38-year-old man with acute myeloid leukaemia (AML) in remission who developed sudden-onset chest pain and shortness of breath 30 min after receiving a blood transfusion. His condition deteriorated and required transferring him to the intensive care unit. The initial differential diagnosis was wide given his immunosuppression, recent chemotherapy, hospitalised status and receipt of blood products. Extensive work up concluded Coxsackie virus-induced myopericarditis as the cause of his symptoms. He was treated with colchicine monotherapy for 3 months and remained without recurrence of pericarditis at 3 months of follow-up.
Associations between objectively assessed and questionnaire-based sedentary behaviour with BMI-defined obesity among general population children and adolescents living in England
Authors: Coombs Ngaire A , Stamatakis Emmanuel
Published: June 2015

Objectives

Sedentary behaviour (SB) is an emerging candidate risk factor for obesity in young people. Evidence to date is conflicting and it is unclear how different SB types are associated with obesity independently of physical activity. The objective of this study was to examine associations between a range of objectively measured and questionnaire-based SB indicators with obesity and body mass index (BMI) to assess whether these associations were independent of physical activity.

Participants

4469 (705 with accelerometer data) children aged 5–15 years from the 2008 Health Survey for England.

Outcomes

The outcome was adiposity, classified using age-specific and sex-specific BMI SD scores (continuous) and obesity cut-offs (binary). Questionnaire-based measures comprised TV time, non-TV sitting time (such as homework, drawing, time at a computer or playing video games), total sitting time (TV time+non-TV sitting time) and average daily MVPA time. Objective SB and moderate to vigorous physical activity (MVPA) time were measured using an Actigraph GT1M accelerometer, with cut-offs of 100 and 200 counts per minute for SB, and 2802 counts per minute for MVPA. Multiple logistic and multiple linear regression models examined associations between each indicator of sedentary time with obesity and BMI SD scores.

Results

TV time (but not non-TV sitting or objectively-measured SB) was consistently associated with higher levels of obesity and BMI SD score, even after adjusting for MVPA and other potential confounders. Weaker associations were observed for total sitting time.

Conclusions

TV viewing (but not other forms of objectively-measured or questionnaire-based sedentary time) was associated with obesity in children and adolescents. Although a causal relationship cannot be established, TV time may be a reasonable target for obesity prevention in young populations.