bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactadherin/MFG‐E8 is essential for microglia‐mediated neuronal loss and phagoptosis induced by amyloid β
Authors: Neniskyte Urte , Brown Guy C.
Published: May 2013

Nanomolar β‐amyloid peptide (Aβ) can induce neuronal loss in culture by activating microglia to phagocytose neurons. We report here that this neuronal loss is mediated by the bridging protein lactadherin/milk‐fat globule epidermal growth factor‐like factor 8 (MFG‐E8), which is released by Aβ‐activated microglia, binds to co‐cultured neurons and opsonizes neurons for phagocytosis by microglia. Aβ stimulated microglial phagocytosis, but did not opsonize neurons for phagocytosis. Aβ (250 nM) induced delayed neuronal loss in mixed glial‐neuronal mouse cultures that required microglia and occurred without increasing neuronal apoptosis or necrosis. This neuronal death/loss was prevented by antibodies to MFG‐E8 and was absent in cultures from Mfge8 knockout mice (leaving viable neurons), but was reconstituted by addition of recombinant MFG‐E8. Thus, nanomolar Aβ caused neuronal death by inducing microglia to phagocytose otherwise viable neurons via MFG‐E8. The direct neurotoxicity of micromolar Aβ was not affected by MFG‐E8. The essential role of MFG‐E8 in Aβ‐induced phagoptosis, suggests this bridging protein as a potential therapeutic target to prevent neuronal loss in Alzheimer's disease.
Dynamic Pricing, Advance Sales and Aggregate Demand Learning in Airlines
Authors: Escobari Diego
Published: May 2013

This paper uses a unique U.S. airlines panel data set to study empirically the dynamic pricing of inventories with uncertain demand over a finite horizon. I estimate a dynamic pricing equation and a dynamic demand equation that jointly characterize the adjustment process between prices and sales as the flight date nears. I find that the price increases as the inventory decreases, and decreases as there is less time to sell. Consistent with aggregate demand learning and price adjustment, demand shocks have a positive and much larger effect on prices than the positive effect of anticipated sales.
The Impact of Market Structure and Learning on the Tradeoff between R&D Competition and Cooperation
Authors: Besanko David , Wu Jianjun
Published: May 2013

This paper compares R&D competition and cooperation when firms can devote resources to a ‘safe’ investment or a risky R&D investment. When the discovery of a new product creates positive externalities on non‐discovering firms, equilibrium investment flow, ex ante investment, and welfare under R&D competition are less than or equal to what they are under research cooperation. With negative externalities, R&D cooperation results in the same or lower ex ante investment than under R&D competition, and social welfare may also be less. Our results have relevance for empirical studies of the impact of R&D cooperation on R&D outcomes.
Waterfall Versus Sprinkler Product Launch Strategy: Influencing the Herd
Authors: Bhalla Manaswini
Published: May 2013

A seller decides the price and sequence in which a product of unknown value is introduced to consumers. Consumers inspect the product before consumption and observe past prices and sales. Consumption at a high price is informative for later consumers as it indicates that the product is likely to be of high value. I show that on an average prices decrease over time. However, expected revenue on an average rises over time. For a high enough discount factor, I find that for extreme beliefs the firm introduces the product to all consumers but for intermediate values the product is introduced only to one consumer.
Re‐evaluation of common paradigms regarding the clinical appearance of oral mucosal malignancies
Authors: Allon Irit , Allon Dror M. , Gal Gavriel , Anavi Yakir , Chaushu Gavriel , Kaplan Ilana
Published: May 2013

Purpose

To evaluate the clinical appearance and rate of ulceration of oral mucosal malignancies, and to investigate the accuracy of clinical provisional diagnoses.

Methods

A 10‐year retrospective analysis, which included diagnostic biopsies of malignant tumors of the oral mucosa. The clinical provisional diagnoses were compared with final diagnoses.

Results

Two hundred and twenty‐seven oral mucosal malignant tumors were included. Squamous cell carcinoma and its variants accounted for the majority (78%) of all malignant tumors. The most common clinical presentations were non‐ulcerated (59.7%) and ulcerated masses (20.4%). Only 11.9% presented as indurate ulcers. The highest ulceration rate of all malignancies was recorded for SCC, with only about half of SCC and its variants ulcerated at the time of biopsy. 31.1% of all malignancies were not clinically suspected to be malignant and did not even include a request to rule out malignancy. There was a better agreement between the clinical provisional diagnoses and microscopic diagnoses in the SCC group than in other types of malignancy (P < 0.001).

Conclusion

Within this study sample, non‐ulcerated masses rather than indurate ulcers are the most common clinical appearance of oral mucosal malignancies, and even for SCC, that showed the highest ulceration rate at presentation, half were non‐ulcerated. Approximately, one‐third of oral mucosal malignancies were not suspected to be malignant prior to biopsy. Thus, the level of suspicion currently reserved for mucosal ulcers and ulcerated masses should also be applied to non‐ulcerated oral mucosal masses.
Usefulness of the fluid balance: A randomised controlled trial in neonates
Authors: Bekhof Jolita , van Asperen Yvette , Brand Paul LP
Published: May 2013

Aim

To assess the effects of fluid balance charts in neonates with moderate disease severity on duration of hospitalisation and medical interventions.

Methods

Randomised, controlled trial in a neonatal ward in a general teaching hospital in the Netherlands between June 2009 and March 2010.

One hundred seventy neonates with moderate disease severity, requiring continuous monitoring of vital parameters (mean gestational age 36+2 weeks (standard deviation 2+5 days), mean birthweight 2782 g (standard deviation 749 g)) participated. In the control group (n = 86), attending physicians could access all fluid balance data, whilst these data were blacked out in the intervention group (n = 84). Primary outcome was length of hospital stay. Secondary outcomes were percentage weight loss, interventions based on the fluid status, unblinding of fluid balance data and incident reporting.

Results

Length of hospital stay did not differ significantly between the intervention and the control group (median 9 vs. 8 days, with ratio of geometric mean 1.25, 95% confidence interval 0.99 to 1.57; P = 0.06). We found no significant differences in secondary outcomes.

Conclusions

Routinely keeping fluid balances in neonates with moderate disease severity does not affect duration of hospitalisation or medical treatment.
Enzyme effects on extruded diets for dogs with soybean meal as a substitute for poultry by‐product meal
Authors: Tortola L. , Souza N. G. , Zaine L. , Gomes M. O. S. , Matheus L. F. O. , Vasconcellos R. S. , Pereira G. T. , Carciofi A. C.
Published: May 2013

The effects of exogenous enzymes supplementation on kibble diets for dogs formulated with soybean meal (SBM) as a substitute for poultry by‐product meal (PM) was investigated on nutrient digestibility, fermentation products formation, post‐prandial urea response and selected faecal bacteria counts. Two kibble diets with similar compositions were used in two trials: PM‐based diet (28.9% of PM; soybean hulls as a fibre source) and SBM‐based diet (29.9% of SBM). In experiment 1, the SBM diet was divided into three diets: SBM‐0, without enzyme addition; SBM‐1, covered after extrusion with 7500 U protease/kg and 45 U cellulase/kg; and SBM‐2, covered with 15 000 U protease/kg and 90 U cellulase/kg. In experiment 2, the SBM diet was divided into three diets: SBM‐0; SBM‐1, covered with 140 U protease/kg; 8 U cellulase/kg, 800 U pectinase/kg, 60 U phytase/kg, 40 U betaglucanase/kg and 20 U xylanase/kg; and SMB‐2, covered with 700 U protease/kg, 40 U cellulase/kg, 4000 U pectinase/kg, 300 U phytase/kg, 200 U betaglucanase/kg and 100 U xylanase/kg. Each experiment followed a block design with six dogs per diet. Data were submitted to analysis of variance and means compared by orthogonal and polynomial contrasts (p < 0.05). In both experiments, nutrients and energy digestibility did not differ between diets (p > 0.05). SBM consumption resulted in increased faecal moisture and production (p < 0.05), without effect on faecal score. Higher concentration of propionate, acetate and lactate, and lower ammonia and pH were found in the faeces of dogs fed SBM (p < 0.05). Higher post‐prandial urea was verified in dogs fed SBM (p < 0.05). In experiment 2, the addition of enzymes increased faecal concentration of propionate, acetate and total short‐chain fatty acid (p < 0.05) and tended to reduce post‐prandial urea concentration (p = 0.06). Although with similar digestibility, SBM shows a worse utilization of absorbed amino acids than the PM. Soybean oligosaccharides can beneficially change gut fermentation product formation. Enzymes can increase the gut fermentation activity and improve the SBM proteic value.
Dietary effects of linseed on fatty acid composition of milk and on liver, adipose and mammary gland metabolism of periparturient dairy cows
Authors: Mach N. , Zom R. L. G. , Widjaja H. C. A. , van Wikselaar P. G. , Weurding R. E. , Goselink R. M. A. , van Baal J. , Smits M. A. , van Vuuren A. M.
Published: May 2013

During the transition period in dairy cows, drastic adaptations within and between key tissues and cell types occur in a coordinated manner to support late gestation, the synthesis of large quantities of milk and metabolic homoeostasis. The start of lactation coincides with an increase of triacylglycerols in the liver, which has been associated with several economically important diseases in dairy cows (i.e. hepatic lipidiosis, mastitis). The polyunsaturated fatty acids have been used to improve liver metabolism and immune function in the mammary gland. Therefore, the effects of dietary linseed supplementation on milk quality and liver, adipose and mammary gland metabolism of periparturient dairy cows were studied in 14 cows that were randomly assigned to control or linseed supplementation. Animals were treated from 3 weeks antepartum until 6 weeks post‐partum. Linseed did not modify dry matter intake, but increased milk yield and lactose yield, and decreased milk fat concentration, which coincided with lower proportion of C16 and higher proportions of stearic acid, conjugated linoleic acid and α‐linolenic acid in milk fat. Linseed supplementation did not significantly change the expression of key lipid metabolism genes in liver and adipose tissues, except of glucose transporter 2 (GLUT2) in liver, which was increased in cows supplemented with linseed, suggesting that more glucose was secreted and probably available for lactose synthesis compared with cows fed control diet. Large adaptations of transcription occurred in the mammary gland when dairy cows were supplemented with linseed. The main affected functional modules were related to energy metabolism, cell proliferation and remodelling, as well as the immune system response.
Effects of Saccharomyces cerevisiae supplementation on apparent total tract digestibility of nutrients and fermentation profile in healthy horses
Authors: Mackenthun E. , Coenen M. , Vervuert I.
Published: May 2013

Supplementation with Saccharomyces cerevisiae (SC) in horses may have some potential to modify microbial populations and thereby improve fibre digestibility. The aim of this study was to investigate the effects of SC on apparent total tract digestibility (ATTD) of nutrients, with a special focus on fibre digestion in healthy horses. The fermentation profile of microbial populations was another focus of interest. Twelve geldings were randomly assigned to three groups. The basal diet consisted of cracked corn (2 g starch/kg body weight [BW]) and hay (1.2 kg/100 kg BW). During adaptation (3 weeks) and the total faecal collection period (5 days), cracked corn was fed once daily either as control (0 g SC) or supplemented with 1 or 3 g SC (1 g SC = 2 × 1010 colony‐forming units [cfu]). There was a 4‐week wash‐out period between the different SC regimes. Faeces were sampled by rectal collection for the analysis of pH, nitrogen, lactic acid, short‐chain fatty acids (SCFA) and SC. In faeces, mean SC cfu was significantly lower than the quantity supplemented: 0 g SC, no detection; 1 g SC, 1.1 × 106 cfu; 3 g SC, 3.6 × 106 cfu. Apparent total tract digestibility of crude fibre varied approximately 40% without any treatment‐related effects. Short‐chain fatty acids, lactic acids and pH in faeces were not significantly affected by SC supplementation. Saccharomyces cerevisiae supplementation was not associated with any changes in the fermentation profiles, and fibre digestion accordingly remained unchanged in intact and healthy horses. Taking into account that fibre digestion remained unchanged and recovery rate of SC in faeces was mariginal, colonization and proliferation of SC in the healthy equine intestinal tract seems to be unlikely.
Raw hulled shredded acorns from Downy Oak (Quercus pubescens) in the diet of pigs: effects on digestibility and faeces characteristics
Authors: Cappai M. G. , Wolf P. , Rust P. , Pinna W. , Kamphues J.
Published: May 2013

Faeces quality and composition are both of interest to veterinary practitioners dealing with pigs’ health and disturbances in the alimentary tract, especially in free‐range situations. In the Mediterranean basin, acorns are used as a starch source for fattening pigs, yet little information is available on how that affects faecal quality and digestibility. Therefore, a combined diet containing ripe hulled shredded acorns vs. a pelleted complete diet for finishers was evaluated for the digestibility and faecal consistency. The trial involved eight crossbred pigs, and a matched‐pair approach was used to divide animals into two groups, which were fed with two different diets: acorns group (A): n = 4, 70% ripe hulled shredded acorns + 30% pelleted complete diet combined, as fed; control group (C): n = 4, 100% pelleted complete feed. The pigs were housed individually and fed the experimental diets for 8 days; daily feed intake and faeces amounts were recorded and faeces quality assessed. The digestibility of organic matter (OM) and starch of the two diets, as well as of pure acorns, were calculated and compared. Daily feed consumption was significantly higher in group A, but the mean dry matter intake (DMI) per pig was similar in both groups. Dark, firm and consistent faeces were reported for each pig from group A in comparison with group B, whose faeces were paler and softer. Digestibility of OM and starch were lower in group A than in group B (67.8 ± 3.4 vs. 83.9 ± 1.1 and 82.5 ± 3.4 vs. 92.3 ± 2.1 respectively): total tract digestibility of native starch from pure acorns was calculated at 77%. The peculiar consistency of faeces was related to macroscopic acorn hulls, constantly detected in the faeces of all animals sampled in group A.
Female Ejaculation Orgasm vs. Coital Incontinence: A Systematic Review
Authors: Pastor Zlatko
Published: May 2013

Introduction

Women may expel various kinds of fluids during sexual arousal and at orgasm. Their origins, quantity, compositions, and expulsion mechanisms depend on anatomical and pathophysiological dispositions and the degree of sexual arousal. These are natural sexual responses but may also represent symptoms of urinary incontinence.

Aim

The study aims to clarify the etiology of fluid leakage at orgasm, distinguish between associated physiological sexual responses, and differentiate these phenomena from symptoms of illness.

Methods

A systematic literature review was performed. EMBASE (OvidSP) and Web of Science databases were searched for the articles on various phenomena of fluid expulsions in women during sexual arousal and at orgasm.

Main Outcome Measures

Articles included focused on female ejaculation and its variations, coital incontinence (CI), and vaginal lubrication.

Results

Female ejaculation orgasm manifests as either a female ejaculation (FE) of a smaller quantity of whitish secretions from the female prostate or a squirting of a larger amount of diluted and changed urine. Both phenomena may occur simultaneously. The prevalence of FE is 10–54%. CI is divided into penetration and orgasmic forms. The prevalence of CI is 0.2–66%. Penetration incontinence occurs more frequently and is usually caused by stress urinary incontinence (SUI). Urodynamic diagnoses of detrusor overactivity (DOA) and SUI are observed in orgasmic incontinence.

Conclusions

Fluid expulsions are not typically a part of female orgasm. FE and squirting are two different physiological components of female sexuality. FE was objectively evidenced only in tens of cases but its reported high prevalence is based mostly on subjective questionnaire research. Pathophysiology of squirting is rarely documented. CI is a pathological sign caused by urethral disorder, DOA, or a combination of both, and requires treatment. An in-depth appreciation of these similar but pathophysiologically distinct phenomena is essential for distinguishing normal, physiological sexual responses from signs of illness.
Bolivia's Energy and Mineral Resources Trade and Investments with China: Potential Socioeconomic and Environmental Effects of Lithium Extraction
Authors: Valle Valeria Marina , Holmes Héctor Cueto
Published: May 2013

In recent years, relations between China and Bolivia have increased. On the one hand, China has scaled up positions as a Bolivian trading partner; in particular, the Asian giant has continued to be one of the major contributors to Bolivian mineral and energy industries. On the other hand, Bolivia has increased its exportations to China by selling products—mainly raw materials—including minerals such as raw tin ore, tin, silver, zinc, lead, and antimony and hydrocarbons and lithium carbonate, used to produce electric vehicle batteries. The fact that Bolivia is increasing its mineral sales to China could be considered good news; Bolivia is rich in natural mineral and energy resources, but it is a country with poorly distributed wealth, and most of its indigenous and poor population is located in the Potosí region, where lithium is being extracted. This article will shed light on the potential negative socioeconomic and environmental effects that lithium extraction may have on these communities.
Public Finance and Social Protection System Reforms in Mexico: Part II
Authors: Chávez Presa Jorge A. , Trillo Fausto Hernández , López‐Calva Luis Felipe ,   Centro de Estudios Espinosa Yglesias
Published: May 2013

Mexico needs a proposal to integrate reforms into the social protection system as an indispensable factor for social cohesion with holistic fiscal reforms that create and nurture viability in the long term and improve the country's competitiveness. There is also a need for reforms that seek to break through the prevailing economic stagnation and provide the nation with medium‐ and long‐term development opportunities. Specifically, it needs a proposal that addresses the overwhelming need to formalize a new social contract based on justice and sustained by economic growth that allows Mexico's democracy to work for all of its residents. This document seeks to conduct an exercise that is rarely attempted in Mexico: establish achievable short‐ and medium‐term goals for universal social protection tied to revenue sources that provide long‐term viability and sustainability.
Comply or explain in corporate governance codes: in need of greater regulatory oversight?
Authors: Keay Andrew
Published: May 2013

At the heart of the voluntary corporate governance code in the UK and elsewhere is the concept of ‘comply or explain’. It provides that a company is to comply with a code's provision; but if it does not do so, then it is to state that it does not and explain why it does not. There is no provision in the UK for any statements by companies to be assessed by any regulatory body. It is incumbent on the markets generally and the company's shareholders specifically to determine whether the response of the company to code provisions does enough, and then to take some action if they do not. The aim of comply or explain is to empower shareholders to make an informed evaluation as to whether non-compliance is justified, given the company's circumstances. This paper assesses whether the present scheme, which relies on the stewardship of shareholders and the efficiency of the markets, should continue, or whether a regulatory body should be empowered to determine whether companies are in fact complying with code provisions or, if not, whether they are providing adequate explanations for not complying.
Pepino mosaic virus triple gene block protein 1 (TGBp1) interacts with and increases tomato catalase 1 activity to enhance virus accumulation
Authors: Mathioudakis Matthaios M. , Veiga Rita S. L. , Canto Tomas , Medina Vicente , Mossialos Dimitris , Makris Antonios M. , Livieratos Ioannis
Published: May 2013

Various plant factors are co‐opted by virus elements (RNA, proteins) and have been shown to act in pathways affecting virus accumulation and plant defence. Here, an interaction between Pepino mosaic virus (PepMV) triple gene block protein 1 (TGBp1; p26) and tomato catalase 1 (CAT1), a crucial enzyme in the decomposition of toxic hydrogen peroxide (H2O2), was identified using the yeast two‐hybrid assay, and confirmed via an in vitro pull‐down assay and bimolecular fluorescent complementation (BiFC) in planta. Each protein was independently localized within loci in the cytoplasm and nuclei, sites at which their interaction had been visualized by BiFC. Following PepMV inoculation, CAT mRNA and protein levels in leaves were unaltered at 0, 3 and 6 days (locally) and 8 days (systemically) post‐inoculation; however, leaf extracts from the last two time points contained increased CAT activity and lower H2O2 levels. Overexpression of PepMV p26 in vitro and in planta conferred the same effect, suggesting an additional involvement of TGBp1 in potexvirus pathogenesis. The accumulation of PepMV genomic and subgenomic RNAs and the expression of viral coat protein in noninoculated (systemic) leaves were reduced significantly in CAT‐silenced plants. It is postulated that, during PepMV infection, a p26–CAT1 interaction increases H2O2 scavenging, thus acting as a negative regulator of plant defence mechanisms to promote PepMV infections.
COMPARING PROACTIVE AND REACTIVE MANAGEMENT: MANAGING A TRANSBOUNDARY FISH STOCK UNDER CHANGING ENVIRONMENT
Authors: LIU XIAOZI , HEINO MIKKO
Published: May 2013

Environmental change in general, and climate change in particular, can lead to changes in distribution of fish stocks. When such changes involve transboundary fish stocks, the countries sharing the stock need to reconsider their harvesting policies. We investigate the effects of changing stock distribution on the optimal fishing policies in a two players’ noncooperative game. We compare reactive management, under which the manager ignores future distributional shifts (knowingly or unknowingly), with proactive management where the manager considers such shifts in his decisions. A dynamic programming model is developed to identify closed‐loop Nash strategies. We show that the role of two players is symmetric under reactive management but asymmetric under proactive management where managers anticipate future changes in stock ownership. The player losing the stock tends to harvest more aggressively compared to the player gaining the stock who acts more conservatively. Strategic interactions show tendency for complementary actions that can change abruptly during the ownership transition. The differences between management regimes vary from quantitative to qualitative; differences are minimal for stocks with little or no schooling, whereas highly schooling stocks may avoid collapse only under proactive management.
Comparison of the Kinetics of Electron Transfer in the Diffusion Limit for the Singlet and Triplet Quenching of Eosin Y by Quinones
Authors: Bertolotti Sonia G. , Montejano Hernán A. , Previtali Carlos M.
Published: May 2013

Electron transfer (ET) rate constants were determined by means of lifetime measurements for the fluorescence quenching and by laser flash photolysis for the triplet quenching of the dye eosin Y by benzoquinones in acetonitrile. The results represent a new aspect of the dependence of the rate constants with the driving force in the diffusion limit region. That is, the rate constants for singlet quenching in the highly negative region of ΔGet do not decrease as predicted by Marcus theory, but rather show a small positive dependence on the driving force. However, it is found that, in the same free energy range, the triplet rate constants are lower than those for the singlet process. They also increase with the exergonicity of the reaction, but the dependence with ΔGet is less marked than that found for the singlet reaction. Even at a Gibbs energy change of −1.0 eV the triplet quenching rate constants do not reach the theoretical diffusion limit. The results are analyzed using the current theories for diffusion‐mediated ET reactions.
BiVO4‐Silica Composites Containing Cobalt Phthalocyanine Groups: Synthesis, Characterization and Application in Photodegradation of 2,4,6‐Trichlorophenol
Authors: Golmojdeh Hosein , Zanjanchi Mohammad A. , Arvand Majid
Published: May 2013

BiVO4‐Silica composites were prepared and grafted with sulfonated cobalt phthalocyanine. The structural and chemical properties including crystalline phase, specific surface area, UV–Visible diffuse reflectance behavior, morphology and photocatalytic activity were investigated. Depending on the silica content and subsequently amounts of loaded phthalocyanine, various catalytic activities were observed. The sample containing nominal 15% silica and grafted with phthalocyanine showed less aggregated form of this organic dye, smaller and nanometric particles, and higher photocatalytic activity in degradation of 2,4,6‐trichlorophenol.
Strategic Sourcing in the Presence of Uncertain Supply and Retail Competition
Authors: Chen Jianqing , Guo Zhiling
Published: May 2013

This study develops an analytical model to evaluate competing retail firms' sourcing strategies in the presence of supply uncertainty. We consider a common supplier that sells its uncertain supply to two downstream retail firms engaging in price competition in a horizontally differentiated product market. The focal firm has a dual‐sourcing option, while the rival firm can only source from the common supplier. We assess the system‐wide effects of supply uncertainty on the focal firm's incentive to pursue the dual‐sourcing strategy. We find that the focal firm's dual‐sourcing strategy can create a win–win situation that leads to increased retail prices and expected profits for both firms. Furthermore, under certain conditions, we show that it is beneficial for the focal firm to strategically source from the common supplier, even if its alternative supplier offers a lower wholesale price. Overall, we identify two types of incentives for adopting the dual‐sourcing strategy: the incentive of mitigating supply risk through supplier diversification and the incentive of strategic sourcing for more effective retail competition.
Flexible Capacity Investments and Product Mix: Optimal Decisions and Value of Postponement Options
Authors: Kouvelis Panos , Tian Zhongjun
Published: May 2013

In this article, we study a firm's interdependent decisions in investing in flexible capacity, capacity allocation to individual products, and eventual production quantities and pricing in meeting uncertain demand. We propose a three‐stage sequential decision model to analyze the firm's decisions, with the firm being a value maximizer owned by risk‐averse investors. At the beginning of the time horizon, the firm sets the flexible capacity level using an aggregate demand forecast on the envelope of products its flexible resources can accommodate. The aggregate demand forecast evolves as a Geometric Brownian Motion process. The potential market share of each product is determined by the Multinomial Logit model. At a later time and before the end of the time horizon, the firm makes a capacity commitment decision on the allocation of the flexible capacity to each product. Finally, at the end of the time horizon, the firm observes the demand and makes the production quantity and pricing decisions for end products. We obtain the optimal solutions at each decision stage and investigate their optimal properties. Our numerical study investigates the value of the postponed capacity commitment option in supplying uncertain operation environments.
Flavescence dorée phytoplasma titre in field‐infected Barbera and Nebbiolo grapevines
Authors: Roggia C. , Caciagli P. , Galetto L. , Pacifico D. , Veratti F. , Bosco D. , Marzachì C.
Published: May 2013

Flavescence dorée phytoplasma (FDP) titre in two red grapevine cultivars, Barbera and Nebbiolo, was measured over the vegetative seasons of two consecutive years in two vineyards of the Piemonte Region (northwestern Italy), with a double absolute quantification of FDP cells and grapevine DNA in real‐time PCR. The relationships of pathogen concentration to cultivar susceptibility and symptom severity were investigated. FDP titre was always higher in cv. Barbera than in cv. Nebbiolo infected vines, and this difference was significant at early and late summer samplings of 2008 and at early summer sampling of 2009. A seasonal trend in FDP concentration (low in spring, high in early summer and intermediate in late summer) was conserved for cvs Barbera and Nebbiolo in both years and vineyards. Considering both cultivars and years from both vineyards, a significant positive correlation between FDP concentration and symptom severity was found in the spring samples. Regarding the FDP strains (‐C or ‐D), no differences in pathogen titres were detected for either cultivar. Similarly, the presence of another grapevine yellows phytoplasma, bois noir, a subgroup 16SrXII‐A phytoplasma, in mixed infection with FDP strains had no effect on FDP concentration. These results demonstrate for the first time that grapevine cultivars with different susceptibility to FDP support different pathogen titres.
The transforming growth factor‐β–bone morphogenetic protein type signalling pathway in pulmonary vascular homeostasis and disease
Authors: Upton Paul D. , Morrell Nicholas W.
Published: May 2013

New Findings

What is the topic of this review?

This review summarises our current knowledge of dysregulated bone morphogenetic protein (BMP) and transforming growth factor‐β1 (TGFβ1) signalling in pulmonary arterial hypertension.

What advances does it highlight?

Reduced expression of the bone morphogenetic protein (BMP) type II receptor is common to the monocrotaline (MCT‐PAH) and hypoxic rat models of pulmonary hypertension (PH). However, reduced BMP signalling and enhanced transforming growth factor‐β1 (TGFβ1) signalling is observed only in MCT‐PAH. Furthermore, TGFβ1 receptor blockade blocks MCT‐PAH, but not hypoxic PH. Transforming growth factor‐β1 inhibits BMP signalling in pulmonary artery smooth muscle cells.

Germ‐line mutations in the bone morphogenetic protein type II receptor (BMPR2; BMPR‐II) gene, a transforming growth factor‐β (TGFβ) receptor superfamily member, cause the majority of cases of heritable pulmonary arterial hypertension (PAH). Pulmonary arterial hypertension is a subset of pulmonary hypertension (PH) disorders, which also encompass hypoxia‐related lung diseases. Bone morphogenetic proteins (BMPs), via BMPR‐II, activate the canonical Smad1/5/9 pathway, whereas TGFβs (TGFβ1–3) activate the Smad2/3 pathway via the ALK5 receptor. Dysregulated TGFβ1 signalling is pathogenic in fibrotic diseases. We compared two rat PH models, monocrotaline‐induced PAH (MCT‐PAH) and chronic normobaric hypoxia (fractional inspired O2 10%), to address whether BMPR‐II loss is common to PH and permits pathogenic TGFβ1 signalling. Both models exhibited reduced lung BMPR‐II expression, but increased TGFβ1 signalling and decreased BMP signalling were observed only in MCT‐PAH. Furthermore, a pharmacological ALK5 inhibitor prevented disease progression in the MCT‐PAH model, but not in hypoxia. In vitro studies using human pulmonary artery smooth muscle cells showed that TGFβ1 directly inhibits BMP–Smad signalling. In conclusion, BMPR‐II loss is common to the hypoxic and MCT‐PAH models, but systemic ALK5 inhibition is effective only in the MCT model, highlighting a specific role for TGFβ1 in vascular remodelling in MCT‐PAH, potentially via direct inhibition of BMP signalling.
Unconventional Secretion, Unconventional Solutions
Authors: Zhang Min , Schekman Randy
Published: May 2013

Cargoes may be secreted across the plasma membrane by diverse alternative pathways.
Recombinatorial Logic
Authors: Benenson Yaakov
Published: May 2013

The use of sequence inversions allows all 16 possible logic gates for two inputs to be realized in bacterial cells.

[Also see Report by

Bonnet
et al.

]
Bill Would Set New Rules for Choosing NSF Grants
Authors: Mervis Jeffrey
Published: May 2013

The new chair of the House of Representatives science committee has drafted a bill that would alter peer review at the National Science Foundation, angering many.
Taking the Pulse of a Ravaged Ocean
Authors: Normile Dennis
Published: May 2013

The 11 March 2011 earthquake and tsunami wreaked havoc on fisheries and the marine environment. Researchers want to document—and aid—the recovery.
Preconditioning with Cations Increases the Attachment of Anoxybacillus flavithermus and Geobacillus Species to Stainless Steel
Authors: Somerton Ben , Flint Steve , Palmer Jon , Brooks John , Lindsay Denise
Published: May 2013

Preconditioning of
Anoxybacillus flavithermus
E16 and
Geobacillus
sp. strain F75 with cations prior to attachment often significantly increased (
P
≤ 0.05) the number of viable cells that attached to stainless steel (by up to 1.5 log CFU/cm
2
) compared with unconditioned bacteria. It is proposed that the transition of
A. flavithermus
and
Geobacillus
spp. from milk formulations to stainless steel product contact surfaces in milk powder manufacturing plants is mediated predominantly by bacterial physiological factors (e.g., surface-exposed adhesins) rather than the concentrations of cations in milk formulations surrounding bacteria.
Uncovering the Lactobacillus plantarum WCFS1 Gallate Decarboxylase Involved in Tannin Degradation
Authors: Jimï¿½nez Natalia , Curiel Josï¿½ Antonio , Reverï¿½n Inï¿½s , de las Rivas Blanca , Muï¿½oz Rosario
Published: May 2013

Lactobacillus plantarum
is a lactic acid bacterium able to degrade tannins by the subsequent action of tannase and gallate decarboxylase enzymes. The gene encoding tannase had previously been identified, whereas the gene encoding gallate decarboxylase is unknown. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of gallic-acid induced
L. plantarum
extracts showed a 54-kDa protein which was absent in the uninduced cells. This protein was identified as Lp_2945, putatively annotated UbiD. Homology searches identified
ubiD
-like genes located within three-gene operons which encoded the three subunits of nonoxidative aromatic acid decarboxylases.
L. plantarum
is the only bacterium in which the
lpdC
(
lp_2945
) gene and the
lpdB
and
lpdD
(
lp_0271
and
lp_0272
) genes are separated in the chromosome. Combination of extracts from recombinant
Escherichia coli
cells expressing the
lpdB
,
lpdC
, and
lpdC
genes demonstrated that LpdC is the only protein required to yield gallate decarboxylase activity. However, the disruption of these genes in
L. plantarum
revealed that the
lpdB
and
lpdC
gene products are essential for gallate decarboxylase activity. Similar to
L. plantarum
tannase, which exhibited activity only in esters derived from gallic and protocatechuic acids, purified His6-LpdC protein from
E. coli
showed decarboxylase activity against gallic and protocatechuic acids. In contrast to the tannase activity, gallate decarboxylase activity is widely present among lactic acid bacteria. This study constitutes the first genetic characterization of a gallate decarboxylase enzyme and provides new insights into the role of the different subunits of bacterial nonoxidative aromatic acid decarboxylases.
Characterization of Escherichia coli O157:H7 Strains Isolated from Supershedding Cattle
Authors: Arthur Terrance M. , Ahmed Rafiq , Chase-Topping Margo , Kalchayanand Norasak , Schmidt John W. , Bono James L.
Published: May 2013

Previous reports have indicated that a small proportion of cattle shedding high levels of
Escherichia coli
O157:H7 is the main source for transmission of this organism between animals. Cattle achieving a fecal shedding status of 10
4
CFU of
E. coli
O157:H7/gram or greater are now referred to as supershedders. The aim of this study was to investigate the contribution of
E. coli
O157:H7 strain type to supershedding and to determine if supershedding was restricted to a specific set of
E. coli
O157:H7 strains. Fecal swabs (
n
= 5,086) were collected from cattle at feedlots or during harvest. Supershedders constituted 2.0% of the bovine population tested. Supershedder isolates were characterized by pulsed-field gel electrophoresis (PFGE), phage typing, lineage-specific polymorphism assay (LSPA), Stx-associated bacteriophage insertion (SBI) site determination, and variant analysis of Shiga toxin,
tir
, and antiterminator
Q
genes. Isolates representing 52 unique PFGE patterns, 19 phage types, and 12 SBI clusters were obtained from supershedding cattle, indicating that there is no clustering to
E. coli
O157:H7 genotypes responsible for supershedding. While being isolated directly from cattle, this strain set tended to have higher frequencies of traits associated with human clinical isolates than previously collected bovine isolates with respect to lineage and
tir
allele, but not for SBI cluster and
Q
type. We conclude that no exclusive genotype was identified that was common to all supershedder isolates.
Two Novel Class II Hydrophobins from Trichoderma spp. Stimulate Enzymatic Hydrolysis of Poly(Ethylene Terephthalate) when Expressed as Fusion Proteins
Authors: Espino-Rammer Liliana , Ribitsch Doris , Przylucka Agnieszka , Marold Annemarie , Greimel Katrin J. , Herrero Acero Enrique , Guebitz Georg M. , Kubicek Christian P. , Druzhinina Irina S.
Published: May 2013

Poly(ethylene terephthalate) (PET) can be functionalized and/or recycled via hydrolysis by microbial cutinases. The rate of hydrolysis is however low. Here, we tested whether hydrophobins (HFBs), small secreted fungal proteins containing eight positionally conserved cysteine residues, are able to enhance the rate of enzymatic hydrolysis of PET. Species of the fungal genus
Trichoderma
have the most proliferated arsenal of class II hydrophobin-encoding genes among fungi. To this end, we studied two novel class II HFBs (HFB4 and HFB7) of
Trichoderma
. HFB4 and HFB7, produced in
Escherichia coli
as fusions to the C terminus of glutathione
S
-transferase, exhibited subtle structural differences reflected in hydrophobicity plots that correlated with unequal hydrophobicity and hydrophily, respectively, of particular amino acid residues. Both proteins exhibited a dosage-dependent stimulation effect on PET hydrolysis by cutinase from
Humicola insolens
, with HFB4 displaying an adsorption isotherm-like behavior, whereas HFB7 was active only at very low concentrations and was inhibitory at higher concentrations. We conclude that class II HFBs can stimulate the activity of cutinases on PET, but individual HFBs can display different properties. The present findings suggest that hydrophobins can be used in the enzymatic hydrolysis of aromatic-aliphatic polyesters such as PET.
A Functional Approach To Uncover the Low-Temperature Adaptation Strategies of the Archaeon Methanosarcina barkeri
Authors: Gunnigle Eoin , McCay Paul , Fuszard Matthew , Botting Catherine H. , Abram Florence , O'Flaherty Vincent
Published: May 2013

Low-temperature anaerobic digestion (LTAD) technology is underpinned by a diverse microbial community. The methanogenic archaea represent a key functional group in these consortia, undertaking CO
2
reduction as well as acetate and methylated C
1
metabolism with subsequent biogas (40 to 60% CH
4
and 30 to 50% CO
2
) formation. However, the cold adaptation strategies, which allow methanogens to function efficiently in LTAD, remain unclear. Here, a pure-culture proteomic approach was employed to study the functional characteristics of
Methanosarcina barkeri
(optimum growth temperature, 37ï¿½C), which has been detected in LTAD bioreactors. Two experimental approaches were undertaken. The first approach aimed to characterize a low-temperature shock response (LTSR) of
M. barkeri
DSMZ 800
T
grown at 37ï¿½C with a temperature drop to 15ï¿½C, while the second experimental approach aimed to examine the low-temperature adaptation strategies (LTAS) of the same strain when it was grown at 15ï¿½C. The latter experiment employed cell viability and growth measurements (optical density at 600 nm [OD
600
]), which directly compared
M. barkeri
cells grown at 15ï¿½C with those grown at 37ï¿½C. During the LTSR experiment, a total of 127 proteins were detected in 37ï¿½C and 15ï¿½C samples, with 20 proteins differentially expressed with respect to temperature, while in the LTAS experiment 39% of proteins identified were differentially expressed between phases of growth. Functional categories included methanogenesis, cellular information processing, and chaperones. By applying a polyphasic approach (proteomics and growth studies), insights into the low-temperature adaptation capacity of this mesophilically characterized methanogen were obtained which suggest that the metabolically diverse
Methanosarcinaceae
could be functionally relevant for LTAD systems.
An MDCK Cell Culture-Derived Formalin-Inactivated Influenza Virus Whole-Virion Vaccine from an Influenza Virus Library Confers Cross-Protective Immunity by Intranasal Administration in Mice
Authors: Haredy Ahmad M. , Takenaka Nobuyuki , Yamada Hiroshi , Sakoda Yoshihiro , Okamatsu Masatoshi , Yamamoto Naoki , Omasa Takeshi , Ohtake Hisao , Mori Yasuko , Kida Hiroshi , Yamanishi Koichi , Okamoto Shigefumi
Published: May 2013

It is currently impossible to predict the next pandemic influenza virus strain. We have thus established a library of influenza viruses of all hemagglutinin and neuraminidase subtypes and their genes. In this article, we examine the applicability of a rapid production model for the preparation of vaccines against emerging pandemic influenza viruses. This procedure utilizes the influenza virus library, cell culture-based vaccine production, and intranasal administration to induce a cross-protective immune response. First, an influenza virus reassortant from the library, A/duck/Hokkaido/Vac-3/2007 (H5N1), was passaged 22 times (P22) in Madin-Darby canine kidney (MDCK) cells. The P22 virus had a titer of >2 ×108PFU/ml, which was 40 times that of the original strain, with 4 point mutations, which altered amino acids in the deduced protein sequences encoded by the PB2 and PA genes. We then produced a formalin-inactivated whole-virion vaccine from the MDCK cell-cultured A/duck/Hokkaido/Vac-3/2007 (H5N1) P22 virus. Intranasal immunization of mice with this vaccine protected them against challenges with lethal influenza viruses of homologous and heterologous subtypes. We further demonstrated that intranasal immunization with the vaccine induced cross-reactive neutralizing antibody responses against the homotypic H5N1 influenza virus and its antigenic variants and cross-reactive cell-mediated immune responses to the homologous virus, its variants within a subtype, and even an influenza virus of a different subtype. These results indicate that a rapid model for emergency vaccine production may be effective for producing the next generation of pandemic influenza virus vaccines.
Polyclonal Outbreak of KPC-3-Producing Enterobacter cloacae at a Single Hospital in Montréal, Québec, Canada
Authors: Haraoui Louis-Patrick , Lévesque Simon , Lefebvre Brigitte , Blanchette Ruth , Tomkinson Melissa , Mataseje Laura , Mulvey Michael R. , Miller Mark A.
Published: May 2013

From September 2010 to December 2011, 26 KPC-3-producing
Enterobacter cloacae
isolates were identified from 16 patients at a single hospital. Analyses revealed the
bla
KPC
gene to be localized on multiple plasmids in a diverse nonclonal
E. cloacae
genetic background. These findings highlight the potential complexity of a KPC outbreak at a single hospital.
Functional Similarity between E6 Proteins of Cutaneous Human Papillomaviruses and the Adenovirus E1A Tumor-Restraining Module
Authors: Kuppuswamy Mohan , Subramanian T. , Kostas-Polston Elizabeth , Vijayalingam S. , Zhao Ling-jun , Varvares Mark , Chinnadurai G.
Published: May 2013

The adenovirus E1A C-terminal region restrains oncogenic transformation through interaction with three distinct cellular protein complexes that include the DYRK1A/1B/HAN11 complex. The E6 proteins of beta-human papillomaviruses (beta-HPVs) also interact with the DYRK1/HAN11 complex. A variant of HPV5 E6 frequently found in epidermodysplasia verruciformis skin lesions interacted less efficiently with DYRK1A/HAN11. The E6 variant and E7 of HPV5 efficiently coimmortalized primary epithelial cells, suggesting that naturally arising variants may contribute potential oncogenic activities of beta-HPV E6 proteins.
Induction of an Antiviral State and Attenuated Coxsackievirus Replication in Type III Interferon-Treated Primary Human Pancreatic Islets
Authors: Lind Katharina , Richardson Sarah J. , Leete Pia , Morgan Noel G. , Korsgren Olle , Flodström-Tullberg Malin
Published: May 2013

Type III interferons (IFNs), also called lambda interferons (IFN-λ), comprise three isoforms, IFN-λ1 (interleukin-29 [IL-29]), IFN-λ2 (IL-28A), and IFN-λ3 (IL-28B). Only limited information is available on their expression and biological functions in humans. Type I and type II IFNs protect human pancreatic islets against coxsackievirus infection, and this is important since such viruses have been proposed to play a role in the development of human type 1 diabetes. Here we investigated whether type III IFN is expressed during infection of human islet cells with coxsackievirus and if type III IFN regulates permissiveness to such infections. We show that human islets respond to a coxsackievirus serotype B3 (CVB3) infection by inducing the expression of type III IFNs. We also demonstrate that islet endocrine cells from nondiabetic individuals express the type III IFN receptor subunits IFN-λR1 and IL-10R2. Pancreatic alpha cells express both receptor subunits, while pancreatic beta cells express only IL-10R2. Type III IFN stimulation elicited a biological response in human islets as indicated by the upregulated expression of antiviral genes as well as pattern recognition receptors. We also show that type III IFN significantly reduces CVB3 replication. Our studies reveal that type III IFNs are expressed during CVB3 infection and that the expression of the type III IFN receptor by the human pancreatic islet allows this group of IFNs to regulate the islets' permissiveness to infection. Our novel observations suggest that type III IFNs may regulate viral replication and thereby contribute to reduced tissue damage and promote islet cell survival during coxsackievirus infection.