bluuebunny/crossref_metadata_2025 huggingface dataset:
Free Fatty Acids and Oxidative Changes of a Raw Goat Milk Cheese through Maturation
Authors: Delgado Francisco J. , González‐Crespo José , Cava Ramón , Ramírez Rosario
Published: April 2011

Abstract:  Free fatty acids (FFA) and lipid and protein oxidation changes were studied throughout maturation process of a raw goat milk cheese with protected designation of origin. Cheeses were analyzed at 4 different times of maturation, at 1, 30, 60, and 90 d. All FFA significantly increased during maturation and the relative increase was higher for long‐chain than medium‐ or short‐chain FFA. At the end of maturation, oleic (C18:1 n9), butyric (C4:0), and palmitic (C16:0) acids were the most abundant. The higher levels of short‐chain fatty acids (SCFA) regarding total FFA obtained at the end of Ibores cheese ripening compared with other raw goat milk cheeses, highlight the notable role of SCFA on the flavor of this cheese owing to their low‐odor thresholds. Lipid oxidation values significantly increased during maturation process but low levels of malondialdehyde were reported; however, protein oxidation did not significantly change during ripening.

Practical Application:  The knowledge of the lypolitic and oxidative changes of cheeses along maturation is essential for the optimization and standardization of cheese changes during manufacture processes. The lack of studies about the lypolitic and the oxidative processes during cheese maturation, and especially in raw goat milk cheeses, make these topics essential to go further in the characterization of cheese ripening processes. In addition, the control of lypolitic and oxidative changes (including lipid and protein oxidation) should be evaluated due to their effect on cheese quality and also for consumers’ health if they are produced in a great extent.
Phytochemicals Characterization of Solvent Extracts from Taro‐Scented Japonica Rice Bran
Authors: Chen Hua Han , Chiu Tsai Hsin
Published: April 2011

Abstract:  The major phytochemicals and antioxidant properties of taro‐scented rice bran (TaiNung 71; TN71) extracts using 3 different solvents are characterized. Some progress is realized in creating an economic value for rice bran that has long been considered an agricultural waste. Various solvent extracts reveal the presence of phenolic compounds, oryzanols, tocopherols, and tocotrienols. Ethyl acetate (EtOAc) can extract more oryzanols (1.55 ± 0.20 g/kg rice bran). Meanwhile, the methanol (MeOH) extract possesses a higher yield in total contents (15.42 ± 1.41 g/kg bran), which includes phenolic compounds (2.69 ± 0.29 g gallic acid equivalent/kg bran), tocopherols (251 ± 26 mg/kg bran) and tocotrienols (111 ± 4 mg/kg bran). The MeOH extract exhibits more effective antioxidant activity against various oxidative systems in vitro, including the inhibition of linoleic acid peroxidation (33.89%), scavenging of DPPH radicals (83.88%), and reducing power. It is found that the yield, total content in phenolic compounds and tocols of the extracts increase with increasing Synder's polarity value and viscosity, which can then be used as the indices in isolation of the desired rice bran phytochemicals extracts.

Practical Application:  The results from this study have provided essential information concerning the utilization of rice bran extracts in cosmetics or in nutritional medicine.
Chemical Composition and Antioxidant Properties of Candlenut Oil Extracted by Supercritical CO2
Authors: Siddique Bazlul Mobin , Ahmad Anees , Alkarkhi Abbas F.M. , Ibrahim Mahamad Hakimi , Omar A.K Mohd
Published: April 2011

Abstract:  Candlenut oil was extracted using supercritical CO2 (SC‐CO2) with an optimization of parameters, by the response surface methodology. The ground candlenut samples were treated in 2 different ways, that is, dried in either a heat oven (sample moisture content of 2.91%) or dried in a vacuum oven (sample moisture content of 1.98%), before extraction. An untreated sample (moisture content of 4.87%) was used as a control. The maximum percentage of oil was extracted from the heat‐oven‐dried sample (77.27%), followed by the vacuum‐oven‐dried sample (74.32%), and the untreated sample (70.12%). At an SC‐CO2 pressure of 48.26 Mpa and 60 min of extraction time, the optimal temperatures for extraction were found to be 76.4 °C, 73.9 °C, and 70.6 °C for the untreated, heat‐oven‐dried, and vacuum‐oven‐dried samples, respectively. The heat‐oven‐dried sample contains the highest percentage of linoleic acid, followed by the untreated and vacuum‐oven‐dried samples. The antiradical activity of candlenut oil corresponded to an IC50 value of 30.37 mg/mL.
Effect of Maturity, Processing, and Storage on the Furanocoumarin Composition of Grapefruit and Grapefruit Juice
Authors: Cancalon Paul F. , Barros Santiago M. , Haun Carl , Widmer Wilbur W.
Published: April 2011

Abstract:  Since the early 1990's, grapefruit juice has been implicated in drug interaction with various furanocoumarins (FCs) now associated with the effect. Although FCs are present in various fruits and vegetables, it is their presence in grapefruit that has attracted the most attention. Studies have shown that FCs in grapefruit juice can vary significantly and from multiple causes. Most of all, FCs are stress‐induced molecules, their levels affected by many factors ranging from UV exposure to insect infestation. There are also varietal and seasonal factors. In this study, juice processing and storage parameters were investigated. Prolonged fruit storage prior to processing and most steps involved in juice processing had little influence on the levels of 6′,7′‐dihydroxybergamottin (DHB), paradisin C, or bergamottin. However, products that were hot filled or stored at room temperature had lower amounts of DHB and paradisin C and higher amounts of bergaptol compared to juices that were not hot filled and stored at refrigerated temperatures. Both DHB and paradisin C are potent CYP3A4 inhibitors, while bergaptol is a very weak inhibitor. Bergamottin amounts decreased to a lesser extent. Therefore, grapefruit juice products that were hot filled or have been stored at room temperature for an extended period of time will have a reduced drug interaction potential.

Practical Application:  This research provides information on how grapefruit drug interaction potential of grapefruit juice products are affected by processing and storage of juice products. Shelf stable products stored at room temperature in cans and glass containers will have lower levels of FCs compared to fresh products made from the same juice. Those wishing to minimize drug interaction potential in grapefruit products may do so by heating to pasteurization temperatures for 30 to 60 min. However, this will only lower and not eliminate the drug interaction potential.
Differentiation between Aspergillus flavus and Aspergillus parasiticus from Pure Culture and Aflatoxin‐Contaminated Grapes Using PCR‐RFLP Analysis of aflR‐aflJ Intergenic Spacer
Authors: El Khoury André , Atoui Ali , Rizk Toufic , Lteif Roger , Kallassy Mireille , Lebrihi Ahmed
Published: April 2011

Abstract:  Aflatoxins (AFs) represent the most important single mycotoxin‐related food safety problem in developed and developing countries as they have adverse effects on human and animal health. They are produced mainly by Aspergillus flavus and A. parasiticus. Both species have different aflatoxinogenic profile. In order to distinguish between A. flavus and A. parasiticus, gene‐specific primers were designed to target the intergenic spacer (IGS) for the AF biosynthesis genes, aflJ and aflR. Polymerase chain reaction (PCR) products were subjected to restriction endonuclease analysis using BglII to look for restriction fragment length polymorphisms (RFLPs). Our result showed that both species displayed different PCR‐based RFLP (PCR‐RFLP) profile. PCR products from A. flavus cleaved into 3 fragments of 362, 210, and 102 bp. However, there is only one restriction site for this enzyme in the sequence of A. parasiticus that produced only 2 fragments of 363 and 311 bp. The method was successfully applied to contaminated grapes samples. This approach of differentiating these 2 species would be simpler, less costly, and quicker than conventional sequencing of PCR products and/or morphological identification.
A combined approach of bifocal distraction and autogenous iliac grafting for reconstructing large mandibular defect: a unique approach to reconstruction
Authors: Krishnan S. , Subramaniyam R.
Published: April 2011

Aim:  To reconstruct a mandibular continuity defect using a technique of bifocal distraction osteogenesis, causing minimal morbidity to the patient.

Materials and methods:  A forty five year old male with an incompletely reconstructed mandibular defect extending from the right subcodylar region to the symphysis region of the mandible for whom reconstruction of the defect was attempted using a custom made distractor device. The device was not able to achieve the planned target site of reconstruction. The device was removed and the remaining defect site was reconstructed autogenous anterior iliac block graft.

Results:  A significant portion of the large mandibular segmental defect was reconstructed using the bifocal distraction technique, with the residual defect being reconstructed using an anterior iliac block graft, hence avoiding a microvascular reconstructive procedure.

Discussion:  The procedure was planned to completely avoid a bone grafting or a microvascular procedure to reconstruct the lost mandible. However, complete regeneration was unable to be achieved due to various factors. A microvascular reconstruction was not attempted due to various known complications involving prolonged surgical procedure, donor site morbidity, failure of the uptake of graft, long term rehabilitation problem, and difficulty of dental rehabilitation.

Conclusion:  The patient obtained a satisfactory facial symmetry and a functionally continuous mandibular bone for daily function of speech, and once the dental rehabilitation is accomplished the chewing and swallowing functions, which were a tedious process for the patient before the procedure, would be re‐established.
A biophysical model of Sugarcane growth
Authors: CUADRA S. V. , COSTA M. H. , KUCHARIK C. J. , DA ROCHA H. R. , TATSCH J. D. , INMAN‐BAMBER G. , DA ROCHA R. P. , LEITE C. C. , CABRAL O. M. R.
Published: April 2011

Scientists predict that global agricultural lands will expand over the next few decades due to increasing demands for food production and an exponential increase in crop‐based biofuel production. These changes in land use will greatly impact biogeochemical and biogeophysical cycles across the globe. It is therefore important to develop models that can accurately simulate the interactions between the atmosphere and important crops. In this study, we develop and validate a new process‐based sugarcane model (included as a module within the Agro‐IBIS dynamic agro‐ecosystem model) which can be applied at multiple spatial scales. At site level, the model systematically under/overestimated the daily sensible/latent heat flux (by −10.5% and 14.8%,HandλE, respectively) when compared against the micrometeorological observations from southeast Brazil. The model underestimated ET (relative bias between −10.1% and –12.5%) when compared against an agro‐meteorological field experiment from northeast Australia. At the regional level, the model accurately simulated average yield for the four largest mesoregions (clusters of municipalities) in the state of São Paulo, Brazil, over a period of 16 years, with a yield relative bias of −0.68% to 1.08%. Finally, the simulated annual average sugarcane yield over 31 years for the state of Louisiana (US) had a low relative bias (−2.67%), but exhibited a lower interannual variability than the observed yields.
Astragaloside IV inhibits adenovirus replication and apoptosis in A549 cells in vitro
Authors: Shang Lei , Qu Zhangyi , Sun Lihua , Wang Yingchen , Liu Fenghai , Wang Shu , Gao Hong , Jiang Fuyang
Published: April 2011

Objectives

Astragaloside IV, purified from the Chinese medical herb Astragalus membranaceus (Fisch) Bge and Astragalus caspicus Bieb, is an important natural product with multiple pharmacological actions. This study investigated the anti-ADVs effect of astragaloside IV on HAdV-3 (human adenovirus type 3) in A549 cell.

Methods

CPE, MTT, quantitative real-time PCR (qPCR), flow cytometry (FCM) and Western blot were apply to detect the cytotoxicity, the inhibition and the mechanisms of astragaloside IV on HAdV-3.

Key findings

TC0 of astragaloside IV was 116.8 µm, the virus inhibition rate from 15.98% to 65.68% positively was correlated with the concentration of astragaloside IV from 1.25 µm to 80 µm, IC50 (the medium inhibitory concentration) was 23.85 µm, LC50 (lethal dose 50% concentration) was 865.26 µm and the TI (therapeutic index) was 36.28. qPCR result showed astragaloside IV inhibited the replication of HAdV-3. Flow FCM analysis demonstrated that the anti-HAdV-3 effect was associated with apoptosis. Astragaloside IV was further detected to reduce the protein expressions of Bax and Caspase-3 and increasing the protein expressions of Bcl-2 using western blotting, which improved the anti-apoptosis mechanism of astragaloside IV on HAdV-3.

Conclusions

Our findings suggested that astragaloside IV possessed anti-HAdV-3 capabilities and the underlying mechanisms might involve inhibiting HAdV-3 replication and HAdV-3-induced apoptosis.
Ganoderma lucidum polysaccharides antagonize the suppression on lymphocytes induced by culture supernatants of B16F10 melanoma cells
Authors: Sun Li-Xin , Lin Zhi-Bin , Duan Xin-Suo , Lu Jie , Ge Zhi-Hua , Li Xue-Jun , Li Min , Xing En-Hong , Jia Jing , Lan Tian-Fei , Li Wei-Dong
Published: April 2011

Objectives

Tumour cells produce factors such as interleukin 10 (IL-10), transforming growth factor β1 (TGF-β1) and vascular endothelial growth factor (VEGF) that suppress the function of immune cells or induce apoptosis of immune cells. One of the most important goals of tumour immunotherapy is to antagonize this suppression on immune cells. Ganoderma lucidum polysaccharides (Gl-PS) may have this potential. The purpose of this study was to determine the antagonistic effects of Gl-PS on the suppression induced by B16F10 melanoma cell culture supernatant (B16F10-CS) on lymphocytes.

Methods

Gl-PS was used on lymphocytes incubated with B16F10-CS. Enzyme-linked immunosorbent assay was used to determine the levels of IL-10, TGF-β1 and VEGF in B16F10-CS. The MTT assay was used to determine the proliferation of lymphocytes. Immunocytochemistry and Western blot assay were used to determine perforin and granzyme B production in lymphocytes.

Key findings

There were elevated levels of IL-10, TGF-β1 and VEGF in B16F10-CS. The lymphocyte proliferation, and perforin and granzyme B production in lymphocytes after induction with phytohemagglutinin, as well as lymphocyte proliferation in the mixed lymphocyte reaction, were suppressed by B16F10-CS. This suppression was fully or partially antagonized by Gl-PS.

Conclusions

B16F10-CS suppressed lymphocyte proliferation and perforin and granzyme B production in lymphocytes after induction with phytohemagglutinin, as well as lymphocyte proliferation in the mixed lymphocyte reaction. This suppression may be associated with elevated levels of immunosuppressive IL-10, TGF-β1 and VEGF in B16F10-CS. Gl-PS had antagonistic effects on the immunosuppression induced by B16F10-CS, suggesting the potential for Gl-PS in cancer immunotherapy.
Non-prescription medicines and Australian community pharmacy interventions: rates and clinical significance
Authors: Williams Kylie A , Emmerton Lynne M , Taylor Richard , Werner Joel , Benrimoj Shalom Isaac
Published: April 2011

Objective

To quantify pharmacy intervention rates for non-prescription medications (pharmacist-only and pharmacy medicines), to document the clinical significance of these interventions and to determine the adverse health consequences and subsequent health care avoided as a result of the interventions.

Methods

Non-prescription medicines interventions undertaken by community pharmacy staff were recorded in two field studies: a study of all Australian pharmacies to determine incidence rates for low-incidence, highly significant interventions, and a study of a sample of pharmacies to collect data on all non-prescription interventions. Recorded interventions were assessed by a clinical panel for clinical significance, potential adverse health consequence avoided, probability and likely duration of the adverse health consequence.

Key findings

The rate of professional intervention that occurs in Australia for pharmacist-only and pharmacy medicines is 5.66 per 1000 unit sales (95% confidence interval 4.79–6.64). Rates of intervention varied by clinical significance. When considering health care avoided, the main impact of the interventions was avoidance of urgent general practitioner (GP) visits, followed by avoidance of regular GP visits and accident and emergency treatment. The most common adverse health consequences avoided were exacerbations of an existing condition (e.g. hypertension, asthma) and adverse drug effects.

Conclusions

This study demonstrates the way in which community pharmacy encourages appropriate non-prescription medicine use and prevents harm through intervening at the point of supply. It was estimated that Australian pharmacies perform 485 912 interventions per annum when dealing with non-prescription medicines, with 101 324 per annum being interventions that avert emergency medical attention or serious harm, or which are potentially life saving.
Assessment of levels of moral reasoning in pharmacy students at different stages of the undergraduate curriculum
Authors: Gallagher Cathal T
Published: April 2011

Objectives

The principal aim of this study was to demonstrate the maturation of moral reasoning among pharmacy students as they progress through a 4-year degree programme at a school of pharmacy in the UK.

Methods

The moral reasoning of 332 students from across all 4 years of the Master of Pharmacy (M Pharm) degree, together with 13 faculty members, was assessed using Rest's Defining Issues Test over a 1-week period.

Key findings

The results demonstrate clear increase moral reasoning scores through all years of study and on into membership of the faculty. This trend was highly significant (t = 7.09; df = 1; P < 0.001). The coefficient of variability (R2) was calculated as 0.92 using linear least squares regression. There was a wide range of moral reasoning scores at each educational level: the top 18% of the Level 1 cohort achieved higher scores than the bottom 11% of faculty.

Conclusions

The students at a school of pharmacy at a UK university experienced significant moral growth throughout the course of their studies. A further, longitudinal study of the cohort, which attempts to correlate the moral development with age, sex, level of education and mode of delivery of moral education is warranted.
Laminar Flame Speed Measurements and Modeling of Pure Alkanes and Alkane Blends at Elevated Pressures
Authors: Lowry William , de Vries Jaap , Krejci Michael , Petersen Eric , Serinyel Zeynep , Metcalfe Wayne , Curran Henry , Bourque Gilles
Published: April 2011

Alkanes such as methane, ethane, and propane make up a large portion of most natural gas fuels. Natural gas is the primary fuel used in industrial gas turbines for power generation. Because of this, a fundamental understanding of the physical characteristics such as the laminar flame speed is necessary. Most importantly, this information is needed at elevated pressures to have the most relevance to the gas turbine industry for engine design. This study includes experiments performed at elevated pressures, up to 10 atm initial pressure, and investigates the fuels in a pure form as well as in binary blends. Flame speed modeling was done using an improved version of the kinetics model that the authors have been developing over the past few years. Modeling was performed for a wide range of conditions, including elevated pressures. Experimental conditions include pure methane, pure ethane, 80/20 mixtures of methane/ethane, and 60/40 mixtures of methane/ethane at initial pressures of 1 atm, 5 atm, and 10 atm. Also included in this study are pure propane and 80/20 methane/propane mixtures at 1 atm and 5 atm. The laminar flame speed and Markstein length measurements were obtained from a high-pressure flame speed facility using a constant-volume vessel. The facility includes optical access, a high-speed camera, a schlieren optical setup, a mixing manifold, and an isolated control room. The experiments were performed at room temperature, and the resulting images were analyzed using linear regression. The experimental and modeling results are presented and compared with previously published data. The data herein agree well with the published data. In addition, a hybrid correlation was created to perform a rigorous uncertainty analysis. This correlation gives the total uncertainty of the experiment with respect to the true value rather than reporting the standard deviation of a repeated experiment. Included in the data set are high-pressure results at conditions where in many cases for the single-component fuels few data existed and for the binary blends no data existed prior to this study. Overall, the agreement between the model and data is excellent.
Modeling of the Constitutive Behavior of Inconel 718 at Intermediate Temperatures
Authors: Gustafsson D. , Moverare J. J. , Simonsson K. , Sjöström S.
Published: April 2011

Turbine disks are of large importance to turbine designers as they are exposed to hot environment and subjected to high loads. In order to analyze such components with respect to fatigue crack initiation, the work generally starts with a rigorous analysis of the first few cycles, during which an important stress redistribution will always take place in an inelastic structure. In this work, the nonlinear kinematic hardening law by Ohno and Wang (1998, “Constitutive Modeling of Cyclic Plasticity With Emphasis on Ratchetting,” Int. J. Mech. Sci., 40, pp. 251–261) has been used in combination with an isotropic softening law for describing the initial stress-strain distribution for strain controlled uniaxial tests of the material Inconel 718. Focus has been placed on finding a simple model with few material parameters and to describe the initial softening and the comparatively small mean stress relaxation observed during the material testing. The simulation results obtained by using the model fit the experimental results well.
An Analytical Study on the Post-Peak Structural Response
Authors: Dai Hui-Hui , Zhu Xiaowu , Chen Zhen
Published: April 2011

An analytical study is taken to investigate the relationship between material softening and structural softening through the use of a model problem in one dimension. General nonlinear constitutive relations are used. Compared with the bilinear assumptions in previous literature, we find that the nonlinear assumptions herein capture more details in the post-peak structural response. We manage to derive necessary and sufficient conditions for the occurrence of four important post-peak cases, which are often observed in experiments. In particular, our analysis reveals that the mechanism of the snap-through phenomenon is due to the convexity change in the constitutive curve of the softening part.
Formation of single-orientation epitaxial islands of TiSi2 on Si(001) using Sr passivation
Authors: Posadas A. , Dargis R. , Choi M. R. , Slepko A. , Demkov A. A. , Kim J. J. , Smith D. J.
Published: April 2011

Epitaxial islands of C49-phase TiSi2 of up to 100 nm in size, and with a single crystallographic orientation, have been fabricated on Si(001) substrates. The growth process involves passivation of the Si surface using Sr, followed by deposition of Ti in the form of SrTiO3, which prevents the reaction between Ti and Si. Decomposition of SrTiO3 at temperatures above 800 °C drives off Sr and O completely, leaving epitaxial islands of TiSi2 dispersed on the Si surface. The TiSi2 islands have (010) orientation and an in-plane epitaxial relationship of Si[110]∥TiSi2[100]. Density functional calculations of the surface and interface energies show that the island sizes and contact angles are consistent with surface energy minimization.
Dark current mechanisms in stabilized amorphous selenium based n-i detectors for x-ray imaging applications
Authors: Mahmood S. A. , Kabir M. Z.
Published: April 2011

The dark current behavior under operating bias is one of the important selection criteria for an x-ray photoconductor to be usable in a practical x-ray image detector. The authors have developed an analytical model for describing the transient and steady-state behavior of dark current in n-i-type amorphous selenium (a-Se) detectors by considering carrier injections from the metal contacts and thermally generated carriers. It has been found that the thermal generation current is almost two orders of magnitude smaller than the total steady-state dark current in n-i-type a-Se detectors. The main source of dark current is the injection of holes from the metal/n-layer interface which is described by the diffusion theory. The hole injection from the metal depends on the blocking layer (n-layer) thickness, the concentration of trap centers in the blocking layer, the characteristic carrier release time, and the effective barrier height. The fitting of the first principles model with the experimental results estimates the concentration of deep hole trap center in the n-layer, the trap depth from the valence band edge, and the effective barrier heights for the injecting carriers. The electron injection varies with the work function of the contact metal.
Noncanonical TGFβ Signaling Contributes to Aortic Aneurysm Progression in Marfan Syndrome Mice
Authors: Holm Tammy M. , Habashi Jennifer P. , Doyle Jefferson J. , Bedja Djahida , Chen YiChun , van Erp Christel , Lindsay Mark E. , Kim David , Schoenhoff Florian , Cohn Ronald D. , Loeys Bart L. , Thomas Craig J. , Patnaik Samarjit , Marugan Juan J. , Judge Daniel P. , Dietz Harry C.
Published: April 2011

Transforming growth factor–β promotes aortic aneurysm formation through activation of its “noncanonical” signaling pathway.
Specificity of
Drosophila
Cytonemes for Distinct Signaling Pathways
Authors: Roy Sougata , Hsiung Frank , Kornberg Thomas B.
Published: April 2011

Signaling protein receptors are segregated into different cell protrusions in
Drosophila
cells.
A Frontal Challenge for Climate Models
Authors: Ferrari Raffaele
Published: April 2011

An unusually detailed portrait of an ocean front off Japan could help improve climate predictions.
Photosynthesis, Reorganized
Authors: West-Eberhard Mary Jane , Smith J. Andrew C. , Winter Klaus
Published: April 2011

Comparative physiology suggests that reorganization and co-option of ancestral traits drove diversification of C
4
and CAM photosynthesis.
The Young Academy Movement
Authors: Alberts Bruce
Published: April 2011

I have often argued on this page that scientists need to do more than simply advance their individual research projects. Maintaining excellence in the global scientific enterprise will require constant adjustments to policies and programs. In addition, much more outreach by scientists will be needed to make science better understood by the general public and by governments. Promising progress toward both of these goals comes from a movement that is forging new organizations of young scientists—the “young academies”—around the world. A few weeks ago, a new international organization, the Global Young Academy, held its initial meeting in Berlin to discuss spreading the idea to many more nations (
www.globalyoungacademy.org
). This effort deserves full support from of all of society.
Outlook Brightens for Plastic Solar Cells
Authors: Service Robert F.
Published: April 2011

In early April, Mitsubishi Chemical reportedly set a new efficiency record, producing organic solar cells with a 9.2% conversion efficiency. Many researchers in the field are confident that the figure could soon top 10% and possibly reach 15%.
Frightening Risk of Marfan Syndrome, and Potential Treatment, Elucidated
Authors: Couzin-Frankel Jennifer
Published: April 2011

In this week's issue of
Science
, researchers parse the molecular cascades that lead to aneurysms in Marfan syndrome, shedding light on why the blood pressure drug losartan looks so promising and potential avenues for the development of new treatments.
Snapshots From the Meeting
Authors: Kerr Richard A.
Published: April 2011

Snapshots from the Lunar and Planetary Science Conference include briny flows and new crater-forming meteorite hits on Mars.
Adenoviral Infection Presenting as an Isolated Central Nervous System Disease without Detectable Viremia in Two Children after Stem Cell Transplantation
Authors: Frange Pierre , Peffault de Latour Régis , Arnaud Cécile , Boddaert Nathalie , Oualha Mehdi , Avettand-Fenoel Véronique , Bernaudin Françoise , Aguilar Claire , Barnerias Christine , Leruez-Ville Marianne , Touzot Fabien , Lortholary Olivier , Fischer Alain , Blanche Stéphane
Published: April 2011

We report two cases of adenoviral meningoencephalitis in children following allogeneic stem cell transplantation. These cases showed four similarities: isolated neurological involvement, infiltrating hyperintensities next to the third ventricle on the cerebral magnetic resonance image, the absence of concomitant detectable adenoviral viremia, and a severe clinical outcome.
Development of Echinocandin Resistance in Clavispora lusitaniae during Caspofungin Treatment
Authors: Desnos-Ollivier Marie , Moquet Olivier , Chouaki Taieb , Guérin Anne-Marie , Dromer Françoise
Published: April 2011

Clavispora lusitaniae
is an opportunistic human pathogen responsible for 0.6 to 2% of candidemia. This species is intrinsically susceptible to echinocandins. Nevertheless, in this study, development of echinocandin resistance in
C. lusitaniae
isolates was observed during caspofungin treatment. This resistance resulted from missense mutation in the echinocandin target
Fks1
gene.
Demonstration of Cord Formation by Rough Mycobacterium abscessus Variants: Implications for the Clinical Microbiology Laboratory
Authors: Sánchez-Chardi Alejandro , Olivares Francesc , Byrd Thomas F. , Julián Esther , Brambilla Cecilia , Luquin Marina
Published: April 2011

In low-income countries some infections caused by nontuberculous mycobacteria are misdiagnosed as multidrug-resistant tuberculosis. In most of these settings the observation of microscopic cords is the only technique used to identify
Mycobacterium tuberculosis
in the laboratory. In this article we definitively demonstrate that
Mycobacterium abscessus
, an emerging pulmonary pathogen, also forms microscopic cords.
Feline Tetherin Efficiently Restricts Release of Feline Immunodeficiency Virus but Not Spreading of Infection
Authors: Dietrich Isabelle , McMonagle Elizabeth L. , Petit Sarah J. , Vijayakrishnan Swetha , Logan Nicola , Chan Chi N. , Towers Greg J. , Hosie Margaret J. , Willett Brian J.
Published: April 2011

Domestic cats endure infections by all three subfamilies of the retroviridae: lentiviruses (feline immunodeficiency virus [FIV]), gammaretroviruses (feline leukemia virus [FeLV]), and spumaretroviruses (feline foamy virus [FFV]). Thus, cats present an insight into the evolution of the host-retrovirus relationship and the development of intrinsic/innate immune mechanisms. Tetherin (BST-2) is an interferon-inducible transmembrane protein that inhibits the release of enveloped viruses from infected cells. Here, we characterize the feline homologue of tetherin and assess its effects on the replication of FIV. Tetherin was expressed in many feline cell lines, and expression was induced by interferons, including alpha interferon (IFN-α), IFN-ω, and IFN-γ. Like human tetherin, feline tetherin displayed potent inhibition of FIV and HIV-1 particle release; however, this activity resisted antagonism by either HIV-1 Vpu or the FIV Env and “OrfA” proteins. Further, as overexpression of complete FIV genomes in
trans
could not overcome feline tetherin, these data suggest that FIV lacks a functional tetherin antagonist. However, when expressed stably in feline cell lines, tetherin did not abrogate the replication of FIV; indeed, syncytium formation was significantly enhanced in tetherin-expressing cells infected with cell culture-adapted (CD134-independent) strains of FIV (FIV Fca-F14 and FIV Pco-CoLV). Thus, while tetherin may prevent the release of nascent viral particles, cell-to-cell spread remains efficient in the presence of abundant viral receptors and tetherin upregulation may enhance syncytium formation. Accordingly, tetherin expression
in vivo
may promote the selective expansion of viral variants capable of more efficient cell-to-cell spread.
An Exploratory Trial of Cyclooxygenase Type 2 Inhibitor in HIV-1 Infection: Downregulated Immune Activation and Improved T Cell-Dependent Vaccine Responses
Authors: Pettersen Frank O. , Torheim Eirik A. , Dahm Anders E. A. , Aaberge Ingeborg S. , Lind Andreas , Holm Malin , Aandahl Einar M. , Sandset Per M. , Taskén Kjetil , Kvale Dag
Published: April 2011

Chronic HIV infection is characterized by chronic immune activation and dysfunctional T cells with elevated intracellular cyclic AMP (cAMP), which inhibits the T cell activation capability. cAMP may be induced by prostaglandin E
2
following lipopolysaccharide (LPS)-induced upregulation of cyclooxygenase type 2 (COX-2) in monocytes due to the elevated LPS levels in patients with chronic HIV infection. This hypothesis was tested using celecoxib, a COX-2 inhibitor, for 12 weeks in HIV-infected patients without antiretroviral treatment in a prospective, open, randomized exploratory trial. Thirty-one patients were randomized in the trial; 27 completed the study, including 13 patients on celecoxib. Celecoxib reduced chronic immune activation in terms of CD38 density on CD8
+
T cells (−24%;
P
= 0.04), IgA levels (
P
= 0.04), and a combined score for inflammatory markers (
P
< 0.05). Celecoxib further reduced the inhibitory surface receptor programmed death 1 (PD-1) on CD8
+
T cells (
P
= 0.01), including PD-1 on the HIV Gag-specific subset (
P
= 0.02), enhanced the number of CD3
+
CD4
+
CD25
+
CD127
lo/−
Treg or activated cells (
P
= 0.02), and improved humoral memory recall responses to a T cell-dependent vaccine (
P
= 0.04). HIV RNA (
P
= 0.06) and D dimers (
P
= 0.07) tended to increase in the controls, whereas interleukin-6 (IL-6) possibly decreased in the treatment arm (
P
= 0.10). In conclusion, celecoxib downmodulated the immune activation related to clinical progression of chronic HIV infection and improved T cell-dependent functions
in vivo
.
Spatiotemporally Different DNA Repair Systems Participate in Epstein-Barr Virus Genome Maturation
Authors: Sugimoto Atsuko , Kanda Teru , Yamashita Yoriko , Murata Takayuki , Saito Shinichi , Kawashima Daisuke , Isomura Hiroki , Nishiyama Yukihiro , Tsurumi Tatsuya
Published: April 2011

Productive replication of Epstein-Barr virus occurs in discrete sites in nuclei, called replication compartments, where viral DNA replication proteins and host homologous recombinational repair (HRR) and mismatch repair (MMR) factors are recruited. Three-dimensional (3D) surface reconstruction imaging clarified the spatial arrangements of these factors within the replication compartments. Subnuclear domains, designated BMRF1 cores, which were highly enriched in viral polymerase processivity factor BMRF1 could be identified inside the replication compartments. Pulse-chase experiments revealed that newly synthesized viral genomes organized around the BMRF1 cores were transferred inward. HRR factors could be demonstrated mainly outside BMRF1 cores, where
de novo
synthesis of viral DNA was ongoing, whereas MMR factors were found predominantly inside. These results imply that
de novo
synthesis of viral DNA is coupled with HRR outside the cores, followed by MMR inside cores for quality control of replicated viral genomes. Thus, our approach unveiled a viral genome manufacturing plant.
From Resistance to Stimulation: the Evolution of a Virus in the Presence of a Dominant Lethal Inhibitory Scaffolding Protein
Authors: Cherwa James E. , Fane Bentley A.
Published: April 2011

By acquiring resistance to an inhibitor, viruses can become dependent on that inhibitor for optimal fitness. However, inhibitors rarely, if ever, stimulate resistant strain fitness to values that equal or exceed the uninhibited wild-type level. This would require an adaptive mechanism that converts the inhibitor into a beneficial replication factor. Using a plasmid-encoded inhibitory external scaffolding protein that blocks φX174 assembly, we previously demonstrated that such mechanisms are possible. The resistant strain, referred to as the evolved strain, contains four mutations contributing to the resistance phenotype. Three mutations confer substitutions in the coat protein, whereas the fourth mutation alters the virus-encoded external scaffolding protein. To determine whether stimulation by the inhibitory protein coevolved with resistance or whether it was acquired after resistance was firmly established, the strain temporally preceding the previously characterized mutant, referred to as the intermediary strain, was isolated and characterized. The results of the analysis indicated that the mutation in the virus-encoded external scaffolding protein was primarily responsible for stimulating strain fitness. When the mutation was placed in a wild-type background, it did not confer resistance. The mutation was also placed in
cis
with the plasmid-encoded dominant lethal mutation. In this configuration, the stimulating mutation exhibited no activity, regardless of the genotype (wild type, evolved, or intermediary) of the infecting virus. Thus, along with the coat protein mutations, stimulation required two external scaffolding protein genes: the once inhibitory gene and the mutant gene acquired during evolution.
Partial Functional Complementation between Human and Mouse Cytomegalovirus Chemokine Receptor Homologues
Authors: Farrell Helen E. , Abraham Alexander M. , Cardin Rhonda D. , Sparre-Ulrich Alexander H. , Rosenkilde Mette M. , Spiess Katja , Jensen Tine H. , Kledal Thomas N. , Davis-Poynter Nicholas
Published: April 2011

The human cytomegalovirus (CMV) proteins US28 and UL33 are homologous to chemokine receptors (CKRs). Knockout of the mouse CMV M33 protein (UL33 homologue) results in substantial attenuation of salivary gland infection/replication and reduced efficiency of reactivation from tissue explants. M33-mediated G protein-coupled signaling is critical for the salivary gland phenotype. In this report, we demonstrate that US28 and (to a lesser degree) UL33 restore reactivation from tissue explants and partially restore replication in salivary glands (compared to a signaling-deficient M33 mutant). These studies provide a novel small animal model for evaluation of therapies targeting the human CMV CKRs.
The Replisome Pausing Factor Timeless Is Required for Episomal Maintenance of Latent Epstein-Barr Virus
Authors: Dheekollu Jayaraju , Lieberman Paul M.
Published: April 2011

The Epstein-Barr virus (EBV) genome is maintained as an extrachromosomal episome during latent infection of B lymphocytes. Episomal maintenance is conferred by the interaction of the EBV-encoded nuclear antigen 1 (EBNA1) with a tandem array of high-affinity binding sites, referred to as the family of repeats (FR), located within the viral origin of plasmid replication (OriP). How this nucleoprotein array confers episomal maintenance is not completely understood. Previous studies have shown that DNA replication forks pause and terminate with high frequency at OriP. We now show that cellular DNA replication fork pausing and protection factors Timeless (Tim) and Tipin (Timeless-interacting protein) accumulate at OriP during S phase of the cell cycle. Depletion of Tim inhibits OriP-dependent DNA replication and causes a complete loss of the closed-circular form of EBV episomes in latently infected B lymphocytes. Tim depletion also led to the accumulation of double-strand breaks at the OriP region. These findings demonstrate that Tim is essential for sustaining the episomal forms of EBV DNA in latently infected cells and suggest that DNA replication fork protection is integrally linked to the mechanism of plasmid maintenance.
Analysis of Interferon Signaling by Infectious Hepatitis C Virus Clones with Substitutions of Core Amino Acids 70 and 91
Authors: Funaoka Yusuke , Sakamoto Naoya , Suda Goki , Itsui Yasuhiro , Nakagawa Mina , Kakinuma Sei , Watanabe Takako , Mishima Kako , Ueyama Mayumi , Onozuka Izumi , Nitta Sayuri , Kitazume Akiko , Kiyohashi Kei , Murakawa Miyako , Azuma Seishin , Tsuchiya Kiichiro , Watanabe Mamoru
Published: April 2011

Substitution of amino acids 70 and 91 in the hepatitis C virus (HCV) core region is a significant predictor of poor responses to peginterferon-plus-ribavirin therapy, while their molecular mechanisms remain unclear. Here we investigated these differences in the response to alpha interferon (IFN) by using HCV cell culture with R70Q, R70H, and L91M substitutions. IFN treatment of cells transfected or infected with the wild type or the mutant HCV clones showed that the R70Q, R70H, and L91M core mutants were significantly more resistant than the wild type. Among HCV-transfected cells, intracellular HCV RNA levels were significantly higher for the core mutants than for the wild type, while HCV RNA in culture supernatant was significantly lower for these mutants than for the wild type. IFN-induced phosphorylation of STAT1 and STAT2 and expression of the interferon-inducible genes were significantly lower for the core mutants than for the wild type, suggesting cellular unresponsiveness to IFN. The expression level of an interferon signal attenuator, SOCS3, was significantly higher for the R70Q, R70H, and L91M mutants than for the wild type. Interleukin 6 (IL-6), which upregulates SOCS3, was significantly higher for the R70Q, R70H, and L91M mutants than for the wild type, suggesting interferon resistance, possibly through IL-6-induced, SOCS3-mediated suppression of interferon signaling. Expression levels of endoplasmic reticulum (ER) stress proteins were significantly higher in cells transfected with a core mutant than in those transfected with the wild type. In conclusion, HCV R70 and L91 core mutants were resistant to interferonin vitro, and the resistance may be induced by IL-6-induced upregulation of SOCS3. Those mechanisms may explain clinical interferon resistance of HCV core mutants.
The Copenhagen Hip and Groin Outcome Score (HAGOS): development and validation according to the COSMIN checklist
Authors: Thorborg K , Hölmich P , Christensen R , Petersen J , Roos E M
Published: April 2011

Background

Valid, reliable and responsive Patient-Reported Outcome (PRO) questionnaires for young to middle-aged, physically active individuals with hip and groin pain are lacking.

Objective

To develop and validate a new PRO in accordance with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) recommendations for use in young to middle-aged, physically active patients with long-standing hip and/or groin pain.

Methods

Preliminary patient interviews (content validity) included 25 patients. Validity, reliability and responsiveness were evaluated in a clinical study including 101 physically active patients (50 women); mean age 36 years, range 18–63 years.

Results

The Copenhagen Hip and Groin Outcome Score (HAGOS) consists of six separate subscales assessing Pain, Symptoms, Physical function in daily living, Physical function in Sport and Recreation, Participation in Physical Activities and hip and/or groin-related Quality of Life (QOL). Test–retest reliability was substantial, with intraclass correlation coefficients ranging from 0.82 to 0.91 for the six subscales. The smallest detectable change ranged from 17.7 to 33.8 points at the individual level and from 2.7 to 5.2 points at the group level for the different subscales. Construct validity and responsiveness were confirmed with statistically significant correlation coefficients (0.37–0.73, p < 0.01) for convergent construct validity and for responsiveness from 0.56 to 0.69, p < 0.01.

Conclusion

HAGOS has adequate measurement qualities for the assessment of symptoms, activity limitations, participation restrictions and QOL in physically active, young to middle-aged patients with long-standing hip and/or groin pain and is recommended for use in interventions where the patient's perspective and health-related QOL are of primary interest.

Trial registration

ClinicalTrials.govNCT00716729
Risk factors for patellar tendinopathy in competitive volleyball players
Authors: De Ridder R , Mahieu N , Reynaert L , Poppe W , Strubbe K , Cools A , Roosen P
Published: April 2011

Background

Patellar tendinopathy (PT) is an important problem in a volleyball population. However, in order to optimize rehabilitation and prevention strategies, not all intrinsic risk factors are known. This study is the first study that takes the hip strength into account.

Objective

The objective is to identify some intrinsic risk factors of the lower limb for the development of PT in competitive volleyball players.

Design

Retrospective.

Setting

Eight male national volleyball teams participated in this study. Risk factors were assessed at the beginning of the season 2009–2010. By means of questionnaires, the participants injury history was documented.

Participants

A total of 71 male players (25.1±4.5 years) were included. Players with a history of surgery and pain on the moment of testing were excluded.

Assessment of risk factors

Muscle strength, muscle length and landing strategies were assessed.

Main outcome measurements

The strength of the hip muscles was measured with a hand-held dynamometer. Muscle length of gastrocnemius, soleus, hamstrings and quadriceps was determined by means of a plurimeter. A 2D video analyses was made of a vertical jump. Knee flexion angle, Q-angle and Ankle dorsiflexion angle during the landing were calculated.

Results

The players with a history of PT (>6 months ago) displayed a significant greater ankle dorsiflexion ROM, a significant lower hip flexion strength and a significant shorter quadriceps. A logistic regression model indicated that a greater ankle dorsiflexion ROM and a lower hip flexion strength are predictors for occurrence of PT.

Conclusions

It can be concluded that a greater dorsiflexion ankle during landing and a lower hip flexion strength are associated with the occurrence of a PT. Future prospective studies should include, not only the knee, but also the hip and the ankle in their assessment.