bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergistic effect of the human GLP‐1 analogue liraglutide and a dual PPARα/γ agonist on glycaemic control in Zucker diabetic fatty rats
Authors: Brand C. L. , Galsgaard E. D. , Tornehave D. , Rømer J. , Gotfredsen C. F. , Wassermann K. , Knudsen L. B. , Vølund A. , Sturis J.
Published: June 2009

Aim/Hypothesis:  Combination therapies are increasingly common in the clinical management of type 2 diabetes. We investigated to what extent combined treatment with the human glucagon‐like peptide‐1 (GLP‐1) analogue liraglutide and the dual PPARα/γ agonist ragaglitazar would improve glycaemic control in overtly diabetic Zucker diabetic fatty (ZDF) rats.

Methods:  Ninety overtly diabetic male ZDF rats were stratified into groups with matched haemoglobin A1c (HbA1c) (9.0 ± 0.1%). Liraglutide (15 and 50 μg/kg subcutaneously twice daily), ragaglitazar (1 and 3 mg/kg perorally once daily) and their vehicles were studied as monotherapy and in combination in a 3 × 3 factorial design.

Results:  After 4‐week treatment, synergistic effects on HbA1c, non‐fasting morning blood glucose (BG) and/or 24‐h BG profiles were observed with three of the four combinations. The relationship between plasma insulin and BG in combination‐treated animals approached that of historical lean ZDF rats representing normal glucose homeostasis, suggesting that insulin secretion and insulin sensitivity were markedly improved. Increased insulin immunostaining in islets further supports the improved beta‐cell function and/or insulin sensitivity in combination‐treated animals. The synergistic effect on glycaemic control was found without a similar synergistic increase in beta‐cell mass in the combination groups.

Conclusions/Interpretation:  Our data demonstrate that combination treatment with a human GLP‐1 analogue and a dual PPARα/γ agonist through distinct mechanism of actions synergistically improves glycaemic control in the ZDF rat.
Organisational Justice and Citizenship Behaviors: A Study in the Portuguese Cultural Context
Authors: Rego Arménio , Cunha Miguel Pina e
Published: June 2009

Theoretical and empirical evidence suggests that justice and organisational citizenship behaviors (OCB), as well as the relationship between them, are not culture free. However, most studies have been carried out in parts of Asia and Northern Europe, and especially in the USA, shedding little understanding on the dynamics of justice and OCB in less‐studied contexts. We show how four dimensions of organisational justice predict four dimensions of OCB in an under‐studied context—Portugal, a feminine, collectivistic, high power distance and low performance‐oriented culture—a profile that is antipodal to that of US culture. A sample of 269 employees reported their justice perceptions, their OCBs being described by supervisors. The findings suggest that: (a) employees are more sensitive to the interactional dimensions of justice than to the procedural and distributive ones; (b) among the interactional dimensions, the interpersonal one is more predictive of some OCB dimensions than the informational one.

Des données théoriques et empiriques suggèrent que la justice et les comportements de citoyenneté organisationnelle (OCB), tout comme la relation entre eux, ne sont pas sans base culturelle. Toutefois, la plupart des études ont été menées dans certaines parties de l’Asie, de l’Europe du Nord, et plus particulièrement aux USA, ce qui restreint la compréhension des dynamiques de la justice et des OCB qui peuvent être appréhendés dans d’autres contextes. Nous montrons comment 4 dimensions de la justice organisationnelle prédisent 4 dimensions des OCB dans un contexte peu étudié—le Portugal, une culture féminine, orientée vers la collectivité, avec une forte distance au pouvoir et de faibles performances—, un profil aux antipodes de la culture américaine. Chacun des 269 employés de l’échantillon indique ses perceptions de la justice, ses OCB ont été décrits par ses supérieurs. Les résultats montrent que (a) les employés sont plus sensibles aux dimensions interactionnelles de la justice qu’à celles procédurales et distributives (b) parmi les dimensions interactionnelles, l’interpersonnelle est plus prédictive de certaines dimensions des OCB plutôt que l’informationnelle.
Inequality for Wage Earners and Self‐Employed: Evidence from Panel Data*
Authors: Albarran Pedro , Carrasco Raquel , Martinez‐Granado Maite
Published: June 2009

In this paper we highlight the importance of analysing the evolution of income inequality separately for employees and self‐employed workers. Using Spanish panel data on income and consumption for the period 1987–96, we find noticeable differences across these groups in the evolution of income inequality, and in the relative importance of the transitory and permanent components of income variance. The evolution of inequality is mainly explained by movements in the transitory component for the self‐employed and by the permanent component for the employees. Our results suggest that different policies should be implemented for each group.
Why a Victim's Age is Irrelevant When Assessing the Wrongness of Killing
Authors: COHEN DANIEL , LUCK MORGAN
Published: June 2009

abstract

Intuitively, all killings are equally wrong, no matter how old one's victim. In this paper we defend this claim — The Equal Wrongness of Killings Thesis — against a challenge presented by Kasper Lippert‐Rasmussen. Lippert‐Rasmussen shows The Equal Wrongness of Killings Thesis to be incompatible with two further theses: The Unequal Wrongness of Renderings Unconscious Thesis and The Equivalence Thesis. Lippert‐Rasmussen argues that, of the three, The Equal Wrongness of Killings Thesis is the least defensible. He suggests that the most convincing considerations apparently in favour of the Equal Wrongness thesis may be satisfied just as well if we adopt an alternative principle, a ‘Prioritarian View’ about the wrongness of killing. We argue that The Prioritarian View does not resolve the trilemma: it too is inconsistent with the other two theses. Instead, we argue, the most plausible resolution of the trilemma involves a rejection, rather, of The Unequal Wrongness of Renderings Unconscious Thesis. In its place, we offer an attractive principle that is compatible with both The Equal Wrongness of Killings Thesis as well as The Equivalence Thesis.
Avian eggshell thickness: scaling and maximum body mass in birds
Authors: Birchard G. F. , Deeming D. C.
Published: June 2009

The avian eggshell represents a highly evolved structure adapted to the physiological requirements of the embryo and the potential fracturing forces it is exposed to during incubation. Given its many roles, it is not surprising that the eggshell is also central to the current hypothesis about maximum avian body mass. Eggshell thickness (L) and strength has historically been scaled as a function of initial egg mass (IEM). However, maximum incubator mass (IM) is likely a better indicator of the forces the shell must be selected to withstand during incubation. We compare the results of analyses ofL2(an indicator of shell strength) as a function of IEM and IM. We conclude from IM scaling that megapode and kiwi eggshells are not thin but rather are thicker than expected and in general birds with a clutch size of 1 have thicker shells, and further, that reversed sexual dimorphism in the large, particularly extinct birds may be a strategy to avoid shell breakage during incubation of the largest eggs without creating a shell so thick as to inhibit hatching.
The University of Plymouth Sexual Health SIM experience in Second Life®: evaluation and reflections after 1 year
Authors: Kamel Boulos Maged N. , Toth‐Cohen Susan
Published: June 2009

Background and objectives:  Virtual environments such as Second Life are increasingly used as venues for public health education. This paper reports an evaluation of a sexual health project in Second Life, designed to provide education about sexually transmitted infections, prevention of unintended pregnancy and promotion of equalitarian sexual relationships.

Methods:  The University of Plymouth Sexual Health SIM provides a wide variety of educational experiences, including opportunities to test knowledge of sexual health through quizzes and games, web resources integrated within the virtual context and live seminars on sexual health topics. Primary methods of evaluation consisted of a survey (n = 135) and traffic statistics on the virtual programme.

Results:  Evaluation results indicated that the Sexual Health SIM was positively viewed by its audience and fostered development of a vibrant virtual community.

Conclusions:  While these results are promising, it is important to keep in mind the many challenges of delivering and evaluating the impact of educational programmes within 3‐D virtual environments.
State Power, Private Plots and the Greening of Havana's Urban Agriculture Movement
Authors: PREMAT ADRIANA
Published: June 2009

Drawing on ethnographic research conducted over a decade from 1997 to 2007 in Havana, Cuba, this paper applies Henri Lefebvre's insights on the social production of space to the processes involved in the creation of officially‐sanctioned sustainable urban agriculture sites. Without denying the important function of the state in these processes, this paper highlights the significant role played by a range of non‐state actors, and interests, largely left out from most scholarly accounts of Cuba's recent agricultural developments. In this manner, the paper offers a more refined understanding of the influence and the limits of the Cuban state at the current historical juncture.
Effect of Varying Displacement Rates on the Densification of Nanostructured Zirconia by Current Activation
Authors: Xu Jin , Casolco Said R. , Garay Javier E.
Published: June 2009

Nanostructured yttria‐stabilized zirconia powder (fully and partially stabilized) was densified using simultaneous applied current and pressure using varying displacement control rates for pressure application. The varying displacement rates were found to significantly affect densification rates as well as the final density of the products at all temperatures in the study. The densification rates were significantly higher than those previously reported without current application. In addition the effective densification activation energies are affected by the displacement control rates, highlighting the importance of pressure application method.
Low‐Temperature Densification of Lanthanum Strontium Manganite (La1−xSrxMnO3+δ), x=0.0–0.20
Authors: McCarthy Benjamin P. , Pederson Larry R. , Williford Ralph E. , Zhou Xiao‐Dong
Published: June 2009

Intermediate‐stage sintering of lanthanum strontium manganite (LSM, where Sr=0.00, 0.05, 0.10, 0.15, and 0.20) was shown in dilatometry studies to be accelerated when subjected to alternating flows of air and nitrogen. The extent of rate enhancement decreased with increased Sr content, and decreased with increased temperature, which coincides with diminished oxygen nonstoichiometry. Shrinkage rates were further shown to be sensitive to the difference in oxygen content in the alternating gas flows. Baseline air sintering rates were measured using stepwise isothermal dilatometry, from which kinetic parameters were calculated using the Makipirtti–Meng model. Activation energies for sintering in air were determined to be 255 ± 26, 258 ± 28, 308 ± 32, 373 ± 37, and 417 ± 41 kJ/mol for Sr=0.0, 0.05, 0.10, 0.15, and 0.20, respectively. A diffusion‐based model is proposed that is consistent with trends in accelerated shrinkage versus temperature. Transient cation vacancy gradients, which lead to higher cation mobility, were calculated from established oxygen diffusivities and oxygen nonstoichiometry as a function of temperature and time. A potential application of this approach is the processing of LSM‐based cathode‐side contact pastes in solid oxide fuel cells.
Fracture Toughness Analysis of Advanced Ceramic Composite for Hip Prosthesis
Authors: Pezzotti Giuseppe , Yamada Kiyotaka , Porporati Alessandro Alan , Kuntz Meinhard , Yamamoto Kengo
Published: June 2009

The fracture behavior of a zirconia‐toughened alumina‐matrix composite (added with small amounts of mixed oxides) for ceramic hip joint prostheses has been evaluated with emphasis placed on the effect of environmental surface degradation in moist environment. Accelerated aging tests were performed up to 300 h in an autoclave operating at 121°C (under 0.1 MPa pressure) in vapor environment, which represents a quite severe environmental testing condition. Besides conventional fracture mechanics characterizations, including different types of fracture toughness test, microscopic insight into the effect of environmental surface degradation on toughness could be obtained according to Raman and fluorescence microprobe spectroscopy. The main outcomes of this study were as follows: (i) after 10‐h autoclaving (according to ISO standard recommendation) no significant change of monoclinic volume fraction and fracture toughness could be detected; (ii) after very long exposure time (300 h) the monoclinic phase content increased and the surface fracture toughness decreased by approximately 30%, although it was still above the toughness level of pure alumina; and (iii) the bulk toughness was unaffected by autoclave exposure, independent of exposure time elongation.
Surface Chemistry, Dispersion Behavior, and Slip Casting of Ti3AlC2 Suspensions
Authors: Sun Ziqi , Li Meishuan , Hu Longfei , Lu Xinpo , Zhou Yanchun
Published: June 2009

The surface chemistry and dispersion properties of aqueous Ti3AlC2 suspension were studied in terms of hydrolysis, adsorption, electrokinetic, and rheological measurements. The Ti3AlC2 particle had complex surface hydroxyl groups, such as ≡Ti–OH,=Al–OH, and −OTi–(OH)2, etc. The surface charging of the Ti3AlC2 particle and the ion environment of suspensions were governed by these surface groups, which thus strongly influenced the stability of Ti3AlC2 suspensions. PAA dispersant was added into the Ti3AlC2 suspension to depress the hydrolysis of the surface groups by the adsorption protection mechanism and to increase the stability of the suspension by the steric effect. Ti3AlC2 suspensions with 2.0 dwb% PAA had an excellent stability at pH=∼5 and presented the characteristics of Newtonian fluid. Based on the well‐dispersed suspension, dense Ti3AlC2 materials were obtained by slip casting and after pressureless sintering. This work provides a feasible forming method for the engineering applications of MAX‐phase ceramics, wherein complex shapes, large dimensions, or controlled microstructures are needed.
Immediate efficacy of diode laser application in the treatment of dentine hypersensitivity in periodontal maintenance patients: a randomized clinical trial
Authors: Sicilia Alberto , Cuesta‐Frechoso Susana , Suárez Alfonso , Angulo Jorge , Pordomingo Armando , De Juan Pablo
Published: June 2009

Background: To evaluate the immediate efficacy in the reduction of dentine hypersensitivity (DH) when applying an 810 nm diode laser (DL), and a 10% potassium nitrate bioadhesive gel (NK10%).

Material and Methods: Forty‐five consecutive periodontal maintenance patients of both sexes, with a DH≥2 on the verbal rating scale (VRS) in one or more teeth, were randomly allocated into three equal groups: 15 patients received DL and placebo gel; 15 patients were tested with a placebo laser and NK10%; and the remaining 15 received a placebo laser and placebo gel. The DH was evaluated at the start of the study, 15 and 30 min. after the laser application, and on days 2, 4, 7, 14, 30 and 60 by a blind examiner.

Results: After 15 min., observations showed a reduction in DH after an evaporative stimulus (ES) of 36.9% (0.86), three times greater than that of the control group (0.23) (p=0.008). After 14 days, this effect was even greater [DL 71.7% (1.67)/NK10% 36.3% (1.73)/control 28.1% (0.73); p=0.004], and lasted until day 60 [65.7% (1.53)/30.4% (0.73)/25.8% (0.67); p=0.01].

Conclusions: The DL and NK10% gel were proven effective in the treatment of DH. A significantly greater immediate response was observed with DL.
Optical transfer diagnosis of pigmented lesions: a pilot study
Authors: Swanson David L. , Laman Susan D. , Biryulina Marina , Nielsen Kristian P. , Ryzhikov Gennady , Stamnes Jakob J. , Hamre Borge , Zhao Lu , Castellana Frank S. , Stamnes Knut
Published: June 2009

Objective: To evaluate the potential of a novel imaging technology, optical transfer diagnosis (OTD), for differentiation of benign from malignant pigmented melanocytic lesions.

Design: Patients with pigmented lesions suspicious for melanoma were referred for OTD. After scanning, lesions were biopsied for histopathologic examination, each by two separate dermatopathologists. To create morphologic–physiologic maps, the imaging system used the morphologic and physiologic parameters derived from prediction models of light absorption and scattering by chromophores such as hemoglobin, keratin, and melanin at different epidermal and dermal depths. The relative entropies were analyzed for output prediction of malignancy vs. nonmalignancy.

Setting: General dermatology clinic in a tertiary care academic medical center.

Patients: Fifty patients with suspected melanoma.

Intervention: OTD of pigmented lesions suspicious for melanoma, followed by biopsies for histopathologic examination.

Main outcome measures: Histopathologic confirmation of malignant lesions identified by OTD as melanoma.

Results: Sixty‐three pigmented suspicious lesions were scanned before being biopsied for histopathologic examination by the two dermatopathologists. Of the 63 lesions, five were identified as melanoma and 58 were found to be benign (including three seborrheic keratoses and 55 melanocytic nevi). OTD was able to identify the malignant lesions with 100% sensitivity and 94.8–96.6% specificity.

Conclusions: Further study is indicated, but this technology is a promising adjunct to clinical skin cancer screening. Additionally, if the physiologic prediction models can be validated, OTD may facilitate the noninvasive study of some aspects of cutaneous physiology.
Δ FosB overexpression in the nucleus accumbens enhances sexual reward in female Syrian hamsters
Authors: Hedges V. L. , Chakravarty S. , Nestler E. J. , Meisel R. L.
Published: June 2009

Repeated activation of the mesolimbic dopamine system results in persistent behavioral alterations accompanied by a pattern of neural plasticity in the nucleus accumbens (NAc). As the accumulation of the transcription factor Δ FosB may be an important component of this plasticity, the question addressed in our research is whether Δ FosB is regulated by sexual experience in females. We have shown that female Syrian hamsters, given sexual experience, exhibit several behavioral alterations including increased sexual efficiency with naïve male hamsters, sexual reward and enhanced responsiveness to psychomotor stimulants (e.g. amphetamine). We recently demonstrated that sexual experience increased the levels of Δ FosB in the NAc of female Syrian hamsters. The focus of this study was to explore the functional consequences of this induction by determining if the constitutive overexpression of Δ FosB by adeno‐associated virus (AAV) vectors in the NAc could mimic the behavioral effects of sexual experience. Animals with AAV‐mediated overexpression of Δ FosB in the NAc showed evidence of sexual reward in a conditioned place preference paradigm under conditions in which control animals receiving an injection of AAV‐green fluorescent protein (GFP) into the NAc did not. Sexual behavior tests further showed that males paired with the AAV‐Δ FosB females had increased copulatory efficiency as measured by the proportion of mounts that included intromission compared to males mated with the AAV‐GFP females. These results support a role for ΔFosB in mediating natural motivated behaviors, in this case female sexual behavior, and provide new insight into the possible endogenous actions of ΔFosB.
Crossing Over to Cross-Over Trials
Authors: Jones Byron , Haughie Scott
Published: June 2009

If you have never designed a cross-over trial before then Byron Jones and Scott Haughie give some helpful tips on how to do it.
Inhibition of Quorum Sensing in Vibrio harveyi by Boronic Acids
Authors: Ni Nanting , Choudhary Gaurav , Peng Hanjing , Li Minyong , Chou Han‐Ting , Lu Chung‐Dar , Gilbert Eric S. , Wang Binghe
Published: June 2009

Bacterial quorum sensing refers to the ability of bacteria to control gene expression through the detection of a threshold concentration of certain chemicals called autoinducer(s), which are secreted by self and/or other bacteria. Quorum sensing is implicated in the regulation of pathologically relevant events such as biofilm formation, virulence, conjugation, sporulation, and swarming mobility. Inhibitors of bacterial quorum sensing are valuable research tools and potential antimicrobial agents. In this paper, we describe the discovery of several boronic acid inhibitors of bacterial quorum sensing in Vibrio harveyi with IC50 values in the low to sub‐micromolar range in whole cell assays.
Microsatellite markers for the Common ringtail possum (Pseudocheirus peregrinus) and their amplification in other Pseudocheirids
Authors: LANCASTER MELANIE L. , COOPER STEVEN J. B. , CARTHEW SUE , TAYLOR ANDREA
Published: June 2009

Eleven microsatellite markers were developed for the Common ringtail possum, an arboreal marsupial abundant in fragmented forests of south‐eastern Australia. Loci were highly polymorphic (4–32 alleles per locus) and heterozygosity ranged from 0.66 to 1. Two loci deviated significantly from Hardy–Weinberg equilibrium proportions, possibly because of low‐frequency null alleles. These markers will be informative for examining patterns of gene flow, relatedness and mating systems within fragmented populations of the Common ringtail possum and have potential for use in other Pseudocheirids.
genhet: an easy‐to‐use R function to estimate individual heterozygosity
Authors: COULON A.
Published: June 2009

genhet is an R function which calculates the five most used estimates of individual heterozygosity. The advantage of this program is that it can be applied to any diploid genotype dataset, without any limitation in the number of individuals, loci or alleles. Its detailed manual should allow people who have never used R before to make the function work quite easily. The program is freely available at http://www.aureliecoulon.net/research/ac‐computer‐programs.html.
The global methane cycle: recent advances in understanding the microbial processes involved
Authors: Conrad Ralf
Published: June 2009

The global budget of atmospheric CH4, which is on the order of 500–600 Tg CH4 per year, is mainly the result of environmental microbial processes, such as archaeal methanogenesis in wetlands, rice fields, ruminant and termite digestive systems and of microbial methane oxidation under anoxic and oxic conditions. This review highlights recent progress in the research of anaerobic CH4 oxidation, of CH4 production in the plant rhizosphere, of CH4 serving as substrate for the aquatic trophic food chain and the discovery of novel aerobic methanotrophs. It also emphasizes progress and deficiencies in our knowledge of microbial utilization of low atmospheric CH4 concentrations in soil, CH4 production in the plant canopy, intestinal methanogenesis and CH4 production in pelagic water.
Combustion Simulation of an Exhaust Gas Recirculation Operated Micro-gas Turbine
Authors: Cameretti Maria Cristina , Piazzesi Renzo , Reale Fabrizio , Tuccillo Raffaele
Published: June 2009

Following their recent experiences in the search of methods for reducing the nitric oxide emissions from a micro-gas turbine, the authors discuss in this paper the results of the combustion simulation under different conditions induced by the activation of an exhaust recirculation system. The theoretical approach starts with a matching analysis of the exhaust gas recirculation equipped microturbine, and then proceeds with the computational fluid dynamics analysis of the combustor. Different combustion models are compared in order to validate the method for NOx reduction by the point of view of a correct development of the chemically reacting process.
Experimental Study of the Shaft Motion in the Journal Bearing of a Gear Pump
Authors: Castilla R. , Gutes M. , Gamez-Montero P. J. , Codina E.
Published: June 2009

The movement of the shaft of a driven gear in a gear pump is experimentally studied. Three different methods are considered, and the use of a laser micrometer measurement method is validated. In order to use the laser micrometer, some modifications are made to the gear pump. Experimental results for different working pressures and rotational velocities are shown. For a low nondimensional working pressure, defined in a similar way as the Sommerfeld load, experimental and numerical results agree very well for relative eccentricity. Nevertheless, experimental results made clear that the role of the lateral plate of the pump is very important for high nondimensional working pressure. A value of 100 is given for the critical nondimensional working pressure in order to avoid wear and slant in the lateral plate. Frequency analysis of the outlet pressure, as well as the precise measurement of the wear in the pump case, support experimental observation of the inability of the journal to retain the shaft for high nondimensional pressure.
A Stochastic Model for Piping Failure Frequency Analysis Using OPDE Data
Authors: Yuan X.-X. , Pandey M. D. , Riznic J.
Published: June 2009

The accurate estimation of piping failure frequency is an important task to support the probabilistic risk assessment and risk-informed in-service inspection of nuclear power plants. Although probabilistic models have been reported in the literature to analyze the piping failure frequency, this paper proposes a stochastic point process model that incorporates both a time dependent trend and plant-specific (or cohort) effects on the failure rate. A likelihood based statistical method is proposed for estimating the model parameters. A case study is presented to analyze the Class 1 pipe failure data given in the OPDE Database.
Are we asking the right questions? Validating clicker question sequences by student interviews
Authors: Ding Lin , Reay Neville W. , Lee Albert , Bao Lei
Published: June 2009

When answering physics questions, students often have different perspectives than do physics experts. Sometimes this difference does not mean students possess misconceptions, but might indicate that the questions need to be revised. We conducted student interviews to identify and resolve validity issues that stem from the different perspectives of students and question designers. After interviews with 35 student volunteers, we selected 14 verbal and detail-oriented individuals for repeated interviews. Instead of using interviews for soliciting and confirming students’ incorrect answers, we conducted interviews as a “student consultation” process that revealed validity issues missed by physics experts. A four-stage response model was used to examine student verbal reports, and validity issues corresponding to each of the response stages were uncovered.
Repurposing with a Difference
Authors: Boguski Mark S. , Mandl Kenneth D. , Sukhatme Vikas P.
Published: June 2009

Consumer activism, genetic information, and social networking technologies are creating many opportunities for drug repurposing.
Magnetic Fields in the Formation of Massive Stars
Authors: Girart Josep M. , Beltrán Maria T. , Zhang Qizhou , Rao Ramprasad , Estalella Robert
Published: June 2009

Stellar Hourglass Figure

Star-forming clouds are thought to be supported against gravity by ordered interstellar magnetic fields, which are strong enough to slow gravitation collapse but too weak to prevent it.

Girart
et al.

(p.
1408
) measured polarized radio waves from dust particles around a forming massive star, which reveal an hourglass shape. The data imply that a magnetic field strength dominates over turbulence—the telltale signs of magnetically controlled star formation. These conditions mimic those found in low-mass star-forming regions, suggesting that the magnetic field plays an important role in star formation, irrespective of differences in mass.
Genome-Wide Demethylation of
Arabidopsis
Endosperm
Authors: Hsieh Tzung-Fu , Ibarra Christian A. , Silva Pedro , Zemach Assaf , Eshed-Williams Leor , Fischer Robert L. , Zilberman Daniel
Published: June 2009

Dynamic Imprinting

Gene imprinting—the silencing of either a maternally derived or paternally derived gene allele—is controlled in large part by DNA methylation. In plants, imprinting occurs in the endosperm, which nourishes the embryonic plant.

Gehring
et al.

(p.
1447
) and

Hsieh
et al.

(p.
1451
) analyzed the dynamics of DNA methylation in the endosperm and embryo of
Arabidopsis
and found extensive demethylation in the endosperm, suggesting that many imprinted genes are likely to exist. Gehring
et al.
characterized five imprinted genes in detail. Four of the 10 known imprinted genes are related homeodomain transcription factors. Furthermore, 5′ sequences demethylated in several of the genes were found to be derived from transposable elements, which supports the idea that imprinting arose as a by-product of silencing invading DNA.
Extreme Spinning Tops
Authors: Kramer Michael
Published: June 2009

Observations of the same binary star system over 10 years confirm a scenario of how pulsars form and evolve.
Congress Takes First Step Toward One-Stop Shopping for Climate
Authors: Stokstad Erik
Published: June 2009

Congress is moving quickly to lay a framework for a new federal body that would generate scientifically credible predictions about the impact of global warming, for use by everyone from city planners to state wildlife managers.
U.S. Supreme Court Delves Into What Is and Isn't Patentable
Authors: Marshall Eliot
Published: June 2009

Last week, the U.S. Supreme Court agreed to hear a case that could clarify rules about what is, or is not, patentable.
Changing Epidemiology of
Streptococcus pyogenes emm
Types and Associated Invasive and Noninvasive Infections in Southern Taiwan
Authors: Su Yu-Fang , Wang Shih-Min , Lin Ya-Lan , Chuang Woei-Jer , Lin Yee-Shin , Wu Jiunn-Jong , Lin Ming T. , Liu Ching-Chuan
Published: June 2009

A total of 242 isolates were recovered from 76 patients with invasive diseases, 89 with scarlet fever, and 77 with pharyngitis. The most frequent
emm
types were types 12 (43.4%), 4 (18.2%), and 1 (16.9%).
emm
12 reemerged in 2005 and peaked in 2007.
emm
11 was recovered only from patients with invasive disease.
Role of Cholesterol Pathways in Norovirus Replication
Authors: Chang Kyeong-Ok
Published: June 2009

Norwalk virus (NV) is a prototype strain of the noroviruses (family
Caliciviridae
) that have emerged as major causes of acute gastroenteritis worldwide. I have developed NV replicon systems using reporter proteins such as a neomycin-resistant protein (NV replicon-bearing cells) and a green fluorescent protein (pNV-GFP) and demonstrated that these systems were excellent tools to study virus replication in cell culture. In the present study, I first performed DNA microarray analysis of the replicon-bearing cells to identify cellular factors associated with NV replication. The analysis demonstrated that genes in lipid (cholesterol) or carbohydrate metabolic pathways were significantly (
P
< 0.001) changed by the gene ontology analysis. Among genes in the cholesterol pathways, I found that mRNA levels of hydroxymethylglutaryl-coenzyme A (HMG-CoA) synthase, squalene epoxidase, and acyl-CoA:cholesterol acyltransferase (ACAT), ACAT2, small heterodimer partner, and low-density lipoprotein receptor (LDLR)-related proteins were significantly changed in the cells. I also found that the inhibition of cholesterol biosynthesis using statins (an HMG-CoA reductase inhibitor) significantly increased the levels of NV proteins and RNA, whereas inhibitors of ACAT significantly reduced the replication of NV in replicon-bearing cells. Up- or downregulation of virus replication with these agents significantly correlated with the mRNA level of LDLR in replicon-bearing cells. Finally, I found that the expression of LDLR promoted NV replication in
trans
by transfection study with pNV-GFP. I conclude that the cholesterol pathways such as LDLR expression and ACAT activity may be crucial in the replication of noroviruses in cells, which may provide potential therapeutic targets for viral infection.
Fate of Minus-Strand Templates and Replication Complexes Produced by a P23-Cleavage-Defective Mutant of Sindbis Virus
Authors: Mai Junbo , Sawicki Stanley G. , Sawicki Dorothea L.
Published: June 2009

SIN2V is an engineered mutant Sindbis virus (SIN) that is unable to process the P23 cleavage site in polyproteins P123 and P1234 that are translated from the genome after its entry into cells. Unlike wild-type (wt) SIN, it caused minus strands to be made continuously and replication-transcription complex (RTC) activity to be unstable (R. Gorchakov, E. Frolova, S. Sawicki, S. Atasheva, D. Sawicki, and I. Frolov, J. Virol.
82:
6218-6231, 2008). We examined further the effects of P23 on SIN RNA replication and RTC activity. Continuous minus-strand synthesis by SIN2V produced 250% of wt levels of minus strands but accumulated only 110% of wt levels (0.39 pg, or 2.7 × 10
4
molecules of double-stranded RNA per cell). Because SIN2V-infected cells accumulated only 40% of the minus strands that were made, cells must possess some process to limit RTC accumulation. The loss of activity by SIN2V RTC after translation was inhibited was stochastic and not due to their inherent instability, based on finding that activity was lost without the degradation of the minus-strand templates. In addition to their normal functions, P23 RTCs exhibited the novel phenotype of being unable to switch from making less to making more genomes than subgenomic 26S mRNA at late times during infections. Our results lend credence to the hypothesis that nsP2 (and possibly nsP3) possesses functions other than those needed solely for RTC activity and that it may also act with the host to regulate minus-strand synthesis and the stability of the RTC.
The First Virally Encoded Cytochrome P450
Authors: Lamb David C. , Lei Li , Warrilow Andrew G. S. , Lepesheva Galina I. , Mullins Jonathan G. L. , Waterman Michael R. , Kelly Steven L.
Published: June 2009

The genome sequence of the giant virus
Acanthamoeba polyphaga
mimivirus revealed the presence of two putative cytochrome P450 (
CYP
) genes. The product of one of the two predicted
CYP
genes (YP_143162) showed low-level homology to sterol 14-demethylase (CYP51) and contained a C-terminal polypeptide domain of unknown function. YP_143162 expression (without an N-terminal membrane binding domain) in
Escherichia coli
yields a CYP protein which gives a reduced CO difference maximum at 448 nm and was formally demonstrated as the first viral cytochrome P450. Analysis of binding of lipid and sterol substrates indicated no perturbation in CYP heme environment, and an absence of activity was seen when 14-methyl sterols were used as a substrate. The function of the CYP protein and its C-terminal domain remain unknown.
Four Conserved Cysteine Residues of the Hepatitis B Virus Polymerase Are Critical for RNA Pregenome Encapsidation
Authors: Kim Seahee , Lee Jehan , Ryu Wang-Shick
Published: June 2009

Hepadnaviruses replicate via reverse transcription of an RNA template, the pregenomic RNA (pgRNA). Although hepadnaviral polymerase (Pol) and retroviral reverse transcriptase are distantly related, some of their features are distinct. In particular, Pol contains two additional N-terminal subdomains, the terminal protein and spacer subdomains. Since much of the spacer subdomain can be deleted without detrimental effects to hepatitis B virus (HBV) replication, this subdomain was previously thought to serve only as a spacer that links the terminal protein and reverse transcriptase subdomains. Unexpectedly, we found that the C terminus of the spacer subdomain is indispensable for the encapsidation of pgRNA. Alanine-scanning mutagenesis revealed that four conserved cysteine residues, three at the C terminus of the spacer subdomain and one at the N terminus of the reverse transcriptase subdomain, are critical for encapsidation. The inability of the mutant Pol proteins to incorporate into nucleocapsid particles, together with other evidence, argued that the four conserved cysteine residues are critical for RNA binding. One implication is that these four cysteine residues might form a putative zinc finger motif. Based on these findings, we speculate that the RNA binding activity of HBV Pol may be mediated by this newly identified putative zinc finger motif.
Maternal Transmission of Human Immunodeficiency Virus Escape Mutations Subverts HLA-B57 Immunodominance but Facilitates Viral Control in the Haploidentical Infant
Authors: Schneidewind Arne , Tang Yanhua , Brockman Mark A. , Ryland Elizabeth G. , Dunkley-Thompson Jacqueline , Steel-Duncan Julianne C. , St. John M. Anne , Conrad Joseph A. , Kalams Spyros A. , Noel Francine , Allen Todd M. , Christie Celia D. , Feeney Margaret E.
Published: June 2009

Expression of HLA-B57 is associated with restricted replication of human immunodeficiency virus (HIV), but the mechanism for its protective effect remains unknown. If this advantage depends upon CD8 T-cell recognition of B57-restricted epitopes, mother-to-child transmission of escape mutations within these epitopes could nullify its protective effect. However, if the B57 advantage is largely mediated by selection for fitness-attenuating viral mutations within B57-restricted epitopes, such as T242N in TW10-Gag, then the transmission of such mutations could facilitate viral control in the haploidentical infant. We assessed the consequences of B57-associated mutations on replication capacity, viral control, and clinical outcome after vertical transmission in 13 mother-child pairs. We found that expression of HLA-B57 was associated with exceptional control of HIV during infancy, even when mutations within TW10 and most other B57-restricted epitopes were transmitted, subverting the natural immunodominance of HLA-B57. In contrast, most B57-negative infants born to B57-positive mothers progressed rapidly to AIDS. The presence of T242N led to a reproducible reduction in viral fitness, as demonstrated by in vitro assays using NL4-3 constructs encoding p24 sequences from individual mothers and infants. Associated compensatory mutations within p24-Gag were observed to reverse this impairment and to influence the propensity of T242N to revert after transmission to B57-negative hosts. Moreover, primary failure to control viremia was observed in one infant to whom multiple compensatory mutations were transmitted along with T242N. These parallel in vivo and in vitro data suggest that HLA-B57 confers its advantage primarily by driving and maintaining a fitness-attenuating mutation in p24-Gag.
Shedding of Vaccine Viruses with Increased Antigenic and Genetic Divergence after Vaccination of Newborns with Monovalent Type 1 Oral Poliovirus Vaccine
Authors: van der Sanden Sabine , Pallansch Mark A. , van de Kassteele Jan , El-Sayed Nasr , Sutter Roland W. , Koopmans Marion , van der Avoort Harrie
Published: June 2009

For the final stages in the eradication of poliovirus type 1 (P1), the World Health Organization advocates the selective use of monovalent type 1 oral poliovirus vaccine (mOPV1). To compare the immunogenicity of mOPV1 with that of trivalent OPV (tOPV) in infants, a study was performed in Egypt in 2005. Newborns were vaccinated with mOPV1 or tOPV immediately after birth and were challenged with mOPV1 after 1 month. Vaccination with mOPV1 at birth resulted in significantly higher seroconversion against P1 viruses and lower excretion of P1 viruses than vaccination with tOPV. Intratypic differentiation of the viruses shed by the newborns revealed the presence of remarkably high numbers of antigenically divergent (AD) P1 isolates, especially in the mOPV1 study group. The majority of these AD P1 isolates (71%) were mOPV1 challenge derived and were shed by newborns who did not seroconvert to P1 after the birth dose. Genetic characterization of the viruses revealed that amino acid 60 of the VP3 region was mutated in all AD P1 isolates. Isolates with substitution of residue 99 of the VP1 region had significantly higher numbers of nonsynonymous mutations in the VP1 region than isolates without this substitution and were preferentially shed in the mOPV1 study group. The widespread use of mOPV1 has proven to be a powerful tool for fighting poliovirus circulation in the remaining areas of endemicity. This study provides another justification for the need to achieve high vaccination coverage in order to prevent the circulation of AD strains.
Nipah Virus Sequesters Inactive STAT1 in the Nucleus via a P Gene-Encoded Mechanism
Authors: Ciancanelli Michael J. , Volchkova Valentina A. , Shaw Megan L. , Volchkov Viktor E. , Basler Christopher F.
Published: June 2009

The Nipah virus (NiV) phosphoprotein (P) gene encodes the C, P, V, and W proteins. P, V, and W, have in common an amino-terminal domain sufficient to bind STAT1, inhibiting its interferon (IFN)-induced tyrosine phosphorylation. P is also essential for RNA-dependent RNA polymerase function. C is encoded by an alternate open reading frame (ORF) within the common amino-terminal domain. Mutations within residues 81 to 113 of P impaired its polymerase cofactor function, as assessed by a minireplicon assay, but these mutants retained STAT1 inhibitory function. Mutations within the residue 114 to 140 region were identified that abrogated interaction with and inhibition of STAT1 by P, V, and W without disrupting P polymerase cofactor function. Recombinant NiVs were then generated. A G121E mutation, which abrogated inhibition of STAT1, was introduced into a C protein knockout background (C
ko
) because the mutation would otherwise also alter the overlapping C ORF. In cell culture, relative to the wild-type virus, the C
ko
mutation proved attenuating but the G121E mutant virus replicated identically to the C
ko
virus. In cells infected with the wild-type and C
ko
viruses, STAT1 was nuclear despite the absence of tyrosine phosphorylation. This latter observation mirrors what has been seen in cells expressing NiV W. In the G121E mutant virus-infected cells, STAT1 was not phosphorylated and was cytoplasmic in the absence of IFN stimulation but became tyrosine phosphorylated and nuclear following IFN addition. These data demonstrate that the gene for NiV P encodes functions that sequester inactive STAT1 in the nucleus, preventing its activation and suggest that the W protein is the dominant inhibitor of STAT1 in NiV-infected cells.
VOLCANIC ASH LAYERS OF RECENT AGE AT BANFF NATIONAL PARK, ALBERTA, CANADA
Authors: Westgate J. A. , Dreimanis A.
Published: June 2009

Three distinctive volcanic ash layers are present in the postglacial sediments at Banff National Park, Alberta. The chemical and mineralogical composition of the ash deposits, together with the radiocarbon age of associated charcoal, indicate the presence of Bridge River ash, whose source area is approximately located in the heart of the southern Coast Mountains, British Columbia, and Mazama ash, derived from Mount Mazama at Crater Lake, Oregon. A maximal age for Bridge River ash is 2 670 ± 140 years B.P. (GSC-531); a minimal age is 2 120 ± 150 years B.P, (G5C-577). Mazama ash is established as being about 6 600 years old, although a slightly younger date of 6 020 ± 90 years B.P. (S-191) was obtained on organic matter associated with this ash at Banff National Park. The source and age of the third ash deposit is not definitely known, but the presence of cummingtonite suggests that it might be St. Helens Y ash, derived from Mount St. Helens, Washington.
Stromatoporoid Assemblages, Ancient Wall Reef Complex (Devonian), Alberta
Authors: Stearn Colin W.
Published: June 2009

On the south margin of the reef complex, five assemblages of stromatoporoids are defined in the 500 m thick Frasnian succession. The first, in the lower part of the Flume unit, consists of five species that occupied a platform environment in the initial Devonian sea. The second assemblage, of the upper Flume and upper Cairn interval, contains the greatest number of species and represents a patch reef environment formed as relief between the reef complex and basin developed. The third assemblage, of the lower Pecchee Member, contains few species of dominamly tabular-encrusting stromatoporoids that occupied the complex margin at the time of maximum relief and is contained in a megabreccia bed derived from the edge of the complex. The fourth, in the upper part of the Peechee Member, is associated with the close of reef growth at the complex margin and is found in an upper megabreccia bed and bioherms that grew on its surface. The fifth assemblage, of the Arcs Member, represents the return to a patch reef environment that supplied carbonate sand to form this member. Stromatoporoid diversity is low in assemblage I, increases to a maximum at the bottom of assemblage II, and decreases through the upper parts of assemblages II, III, and IV. It is again high in assemblage V. Low values of diversity are interpreted as reflecting shallow water environments of high unpredictability.Twenty-two species of the stromatoporoid fauna are described or re viewed. The following new taxa are established: Sticlostroma jasperense, Taleastroma steleforme, Hermatostroma haultainense, Stachyodes jonelrayi.
Earthquake fault plane solutions near Vancouver Island
Authors: Rogers Garry C.
Published: June 2009

P nodal solutions for six earthquakes in the Vancouver Island region are consistent with a north–south orientation for the principal compressive stress. The predominant type of faulting is strike slip, either dextral slip on northwest striking faults or sinistral slip on northeast striking faults. The few aftershock sequences that can be documented for shallow earthquakes greater than magnitude 5 all contain very few aftershocks, which are small in size. This may indicate that higher than average stress drop is characteristic of large earthquakes in the Vancouver Island region.
Geophysical evidence for the extent of the Avalon zone in Atlantic Canada
Authors: Haworth Richard T. , Lefort Jean Pierre
Published: June 2009

Precambrian volcanic rocks exposed in structural highs of the Avalon zone of Newfoundland are marked by high magnetic anomalies whose continuity offshore permits recognition of the extent of the Avalon zone, particularly on the Grand Banks. South of Newfoundland and in the Gulf of St. Lawrence, where the magnetic pattern is less well defined, the Avalon platform can also be recognized by the existence of seismic velocities of the order of 6.6 km s−1, which are apparently associated with volcanic rocks. The magnetic Collector Anomaly running eastwards from Cape Breton across the southern Grand Banks is the southern limit of these Avalonian markers, while the northern boundary follows a serrated path (the offsets apparently caused by a series of northwest-trending faults) from the Belle Isle Fault in New Brunswick to the Hermitage and Dover Faults in Newfoundland, thence to the western end of the Charlie Fracture zone. These Avalonian boundaries provide markers for the constraint of pre-drift continental reconstructions.