bluuebunny/crossref_metadata_2025 huggingface dataset:
2-Deoxy d-Glucose Prevents Cell Surface Expression of NKG2D Ligands through Inhibition of N-Linked Glycosylation
Authors: Andresen Lars , Skovbakke Sarah Line , Persson Gry , Hagemann-Jensen Michael , Hansen Karen Aagaard , Jensen Helle , Skov Søren
Published: January 2012

NKG2D ligand surface expression is important for immune recognition of stressed and neotransformed cells. In this study, we show that surface expression of MICA/B and other NKG2D ligands is dependent on N-linked glycosylation. The inhibitor of glycolysis and N-linked glycosylation, 2-deoxy-d-glucose (2DG), potently inhibited surface expression of MICA/B after histone deacetylase inhibitor treatment; the inhibition occurred posttranscriptionally without affecting MICA promoter activity. Transient overexpression of MICA surface expression was also inhibited by 2DG. 2DG blocks N-linked glycosylation of MICA/B by a reversible mechanism that can be alleviated by addition of d-mannose; this does not, however, affect the inhibition of glycolysis. Addition of d-mannose restored MICA/B surface expression after 2DG treatment. In addition, specific pharmacological or small interfering RNA-mediated targeting of glycolytic enzymes did not affect MICA/B surface expression, strongly suggesting that N-linked glycosylation, and not glycolysis, is essential for MICA/B surface expression. Corroborating this, tunicamycin, a selective inhibitor of N-linked glycosylation, abolished MICA/B surface expression without compromising activation of MICA promoter activity. NK cell-mediated killing assay and staining with a recombinant NKG2D–Fc fusion protein showed that all functional NKG2D ligands induced by histone deacetylase inhibitor treatment were abolished by 2DG treatment and fully reconstituted by further addition of d-mannose. Our data suggest that posttranslational N-linked glycosylation is strictly required for NKG2D ligand surface expression. Cancer and infection often result in aberrant glycosylation, which could likely be involved in modulation of NKG2D ligand expression. Our data further imply that chemotherapeutic use of 2DG may restrict NKG2D ligand surface expression and inhibit secretion of immunoinhibitory soluble NKG2D ligands.
Linagliptin–-A Novel Dipeptidyl Peptidase Inhibitor for Type 2 Diabetes Therapy
Authors: Gallwitz Baptist
Published: January 2012

Incretin based therapies have been introduced into the treatment options of type 2 diabetes a few years ago. Among them, the orally active DPP-4 inhibitors have established themselves as insulinotropic agents. Their advantage is the glucose-dependent insulinotropic action without an intrinsic risk for causing hypoglycemia. Additionally DPP-4 inhibitors have a glucose dependent glucagonostatic action contributing to improved glucose control. They are weight neutral and show a good safety and tolerability profile with comparable efficacy to sulfonylureas. Linagliptin is a novel DPP-4 inhibitor with a distinct pharmacological profile. In contrast to the other approved DPP-4 inhibitors it is eliminated by a hepatic/biliary route rather than a renal route. Therefore no dose adjustment is recommended in patients with type 2 diabetes and renal impairment. In clinical studies, it has been shown to be non-inferior to sulfonylurea treatment regarding glycemic parameters, but to possess favourable safety advantages regarding hypoglycemia frequency, body weight development and effects on cardioavascular parameters. This article gives an overview on the pharmacology of linagliptin as well as on the clinical data available.
Gas-particle partitioning of atmospheric Hg(II) and its effect on global mercury deposition
Authors: Amos H. M. , Jacob D. J. , Holmes C. D. , Fisher J. A. , Wang Q. , Yantosca R. M. , Corbitt E. S. , Galarneau E. , Rutter A. P. , Gustin M. S. , Steffen A. , Schauer J. J. , Graydon J. A. , Louis V. L. St. , Talbot R. W. , Edgerton E. S. , Zhang Y. , Sunderland E. M.
Published: January 2012

Abstract. Atmospheric deposition of Hg(II) represents a major input of mercury to surface environments. The phase of Hg(II) (gas or particle) has important implications for deposition. We use long-term observations of reactive gaseous mercury (RGM, the gaseous component of Hg(II)), particle-bound mercury (PBM, the particulate component of Hg(II)), fine particulate matter (PM2.5), and temperature (T) at five sites in North America to derive an empirical gas-particle partitioning relationship log10(K−1) = (10±1)–(2500±300)/T where K = (PBM/PM2.5)/RGM with PBM and RGM in common mixing ratio units, PM2.5 in μg m−3, and T in K. This relationship is within the range of previous work but is based on far more extensive data from multiple sites. We implement this empirical relationship in the GEOS-Chem global 3-D Hg model to partition Hg(II) between the gas and particle phases. The resulting gas-phase fraction of Hg(II) ranges from over 90 % in warm air with little aerosol to less than 10 % in cold air with high aerosol. Hg deposition to high latitudes increases because of more efficient scavenging of particulate Hg(II) by precipitating snow. Model comparison to Hg observations at the North American surface sites suggests that subsidence from the free troposphere (warm air, low aerosol) is a major factor driving the seasonality of RGM, while elevated PBM is mostly associated with high aerosol loads. Simulation of RGM and PBM at these sites is improved by including fast in-plume reduction of Hg(II) emitted from coal combustion and by assuming that anthropogenic particulate Hg(p) behaves as semi-volatile Hg(II) rather than as a refractory particulate component. We improve the simulation of Hg wet deposition fluxes in the US relative to a previous version of GEOS-Chem; this largely reflects independent improvement of the washout algorithm. The observed wintertime minimum in wet deposition fluxes is attributed to inefficient snow scavenging of gas-phase Hg(II).
Adaptive correction of deterministic models to produce accurate probabilistic forecasts
Authors: Smith P. J. , Beven K. , Weerts A. , Leedal D.
Published: January 2012

Abstract. This paper considers the correction of deterministic forecasts given by a flood forecasting model. A stochastic correction based on the evolution of an adaptive, multiplicative, gain is presented. A number of models for the evolution of the gain are considered and the quality of the resulting probabilistic forecasts assessed. The techniques presented offer, in certain situations, an effective and computationally efficient method for providing probabilistic forecasts based on existing flood forecasting system output.
Early use of Brachial-Basilic Arteriovenous Fistula
Authors: Matsumoto Harunobu , Yamamoto Eisuke , Kamiya Chiaki , Miura Emi , Kitaoka Tadashi , Suzuki Jun , Deguchi Juno , Ogawa Tomonari , Matsuda Akihiko , Sato Osamu
Published: January 2012

Purpose

The aim of this study was to evaluate the long-term patency rate and complications associated with the use of the BBAVF in the early period.

Methods

The records of all patients undergoing BBAVFs for hemodialysis access between June 2001 and June 2011 were retrospectively evaluated. We allowed the use of the BBAVF beginning two weeks after the fistula creation. The primary and secondary patencies were estimated using the Kaplan-Meier method.

Results

A total of 44 BBAVFs were created for 41 patients. Most (73.2%) of the patients had previously been on hemodialysis. A previous history of AVG creation was noted in 36.6% and previous insertion of a catheter was reported for 72.7% of the patients, respectively. The mean time to the first cannulation of the BBAVF was 18.8 days (13–42 days). In two cases, the BBAVFs were not used. Postoperative complications were noted in 2 cases, and included prolonged arm edema and thrombosis. There was no infection of the wound or steal syndrome. The primary and secondary patency rates were 68.1% and 84.2% at 1 year, 55.0% and 80.7% at 2 years, and 38.1% and 70.1% at 5 years, respectively.

Conclusions

In this study, the patency rates following the early use of the BBAVFs were not inferior to the previously reported patency rates in the literature. In cases where the patients already have an inserted central catheter, the early use of the BBAVFs decreases the complications associated with catheters.
Do Other Components of Bedding Dust Affect Sensitisation to House Dust Mites?
Authors: Smith Claire , Stanley Thorsten , Crane Julian , Siebers Robert
Published: January 2012

Bedding dust is a mixture of many components, of which the house dust mite (HDM) allergen, Der p 1, is the most allergenic. There has been little work to investigate the effect of other bedding dust components on HDM sensitisation. The objective of the study was to determine the effect of endotoxin in bedding dust on the allergic response in HDM-sensitised individuals. Twenty-nine house dust mite-sensitised adults were skin prick and allergen patch tested against a sterile solution of their own bedding dust and against a solution containing the same concentration of Der p 1 as the bedding solution for comparison. There was no significant difference in wheal size between the diluted house dust mite solution and the bedding dust in spite of their high levels of endotoxin. Symptomatic subjects had larger, but not statistically significant, responses to commercial house dust mite solution than asymptomatic subjects. Allergen patch test responses were negative in 22/29 of subjects using either bedding dust solutions or comparable diluted house dust mite solutions. An individual's own bedding dust does not appear to contain factors that enhance skin prick test or atopy patch test responses to house dust mites.
Artifact versus reality—How astrocytes contribute to synaptic events
Authors: Nedergaard Maiken , Verkhratsky Alexei
Published: January 2012

The neuronal doctrine, developed a century ago regards neuronal networks as the sole substrate of higher brain function. Recent advances in glial physiology have promoted an alternative hypothesis, which places information processing in the brain into integrated neuronal‐glial networks utilizing both binary (neuronal action potentials) and analogue (diffusional propagation of second messengers/metabolites through gap junctions or transmitters through the interstitial space) signal encoding. It has been proposed that the feed‐forward and feed‐back communication between these two types of neural cells, which underlies information transfer and processing, is accomplished by the release of neurotransmitters from neuronal terminals as well as from astroglial processes. Understanding of this subject, however, remains incomplete and important questions and controversies require resolution. Here we propose that the primary function of perisynaptic glial processes is to create an “astroglial cradle” that shields the synapse from a multitude of extrasynaptic signaling events and provides for multifaceted support and long‐term plasticity of synaptic contacts through variety of mechanisms, which may not necessarily involve the release of “glio” transmitters. © 2012 Wiley Periodicals, Inc.
Assessment of enveloping distribution sampling to calculate relative free enthalpies of binding for eight netropsin–DNA duplex complexes in aqueous solution
Authors: Hansen Niels , Dolenc Jožica , Knecht Matthias , Riniker Sereina , van Gunsteren Wilfred F.
Published: January 2012

The performance of enveloping distribution sampling (EDS) simulations to estimate free enthalpy differences associated with seven alchemical transformations of A‐T into G‐C base pairs at the netropsin binding site in the minor groove of a 13‐base pair DNA duplex in aqueous solution is evaluated. It is demonstrated that sufficient sampling can be achieved with a two‐state EDS Hamiltonian even for large perturbations such as the simultaneous transformation of up to three A‐T into three G‐C base pairs. The two parameters required to define the EDS reference state Hamiltonian are obtained automatically using a modified version of a scheme presented in earlier work. The sensitivity of the configurational sampling to a variation of these parameters is investigated in detail. Although for relatively small perturbations, that is, one base pair, the free enthalpy estimate depends only weakly on the EDS parameters, the sensitivity is stronger for the largest perturbation. Yet, EDS offers various convenient measures to evaluate the degree of sampling and thus the reliability of the free enthalpy estimate and appears to be an efficient alternative to the conventional thermodynamic integration methodology to obtain free energy differences for molecular systems. © 2012 Wiley Periodicals, Inc. J Comput Chem, 2012
Lennard‐Jones parameters for small diameter carbon nanotubes and water for molecular mechanics simulations from van der Waals density functional calculations
Authors: Kaukonen M. , Gulans A. , Havu P. , Kauppinen E.
Published: January 2012

Lennard‐Jones (LJ) parameters are derived for classical nonpolarizable force fields for carbon nanotubes (CNTs) and for CNT–water interaction from van der Waals (vdW) enhanced density functional calculations. The new LJ parameters for carbon–carbon interactions are of the same order as those previously used in the literature but differ significantly for CNT–water interactions. This may partially originate from the fact that in addition to pure vdW interactions the polarization and other quantum mechanics effects are embedded into the LJ‐potential. © 2012 Wiley Periodicals, Inc. J Comput Chem, 2012
Seminumerical calculation of the Hartree–Fock exchange matrix: Application to two‐component procedures and efficient evaluation of local hybrid density functionals
Authors: Plessow Philipp , Weigend Florian
Published: January 2012

A two‐component extension of the seminumerical procedure for the calculation of the Hartree–Fock (HF) exchange matrix recently presented by Neese et al. (Chem Phys 2009, 356, 98) was implemented into the program system TURBOMOLE. It is demonstrated that this allows for efficient self‐consistent treatment of spin–orbit coupling at HF and hybrid density functional theory level. One‐component HF calculations were performed to study the accuracy of integration grids and the exploitation of the molecular point group symmetry. The efficiency was tested, and for one‐component calculations compared to the implementation realized by Neese. It was further demonstrated that local hybrid density functionals can be evaluated with this technique. The “prototype” of this class of functionals, Lh‐BLYP, was applied to an organic molecule with more than 150 atoms. © 2012 Wiley Periodicals, Inc. J Comput Chem, 2012
Interactive quantum chemistry: A divide‐and‐conquer ASED‐MO method
Authors: Bosson Mäel , Richard Caroline , Plet Antoine , Grudinin Sergei , Redon Stephane
Published: January 2012

We present interactive quantum chemistry simulation at the atom superposition and electron delocalization molecular orbital (ASED‐MO) level of theory. Our method is based on the divide‐and‐conquer (D&C) approach, which we show is accurate and efficient for this non‐self‐consistent semiempirical theory. The method has a linear complexity in the number of atoms, scales well with the number of cores, and has a small prefactor. The time cost is completely controllable, as all steps are performed with direct algorithms, i.e., no iterative schemes are used. We discuss the errors induced by the D&C approach, first empirically on a few examples, and then via a theoretical study of two toy models that can be analytically solved for any number of atoms. Thanks to the precision and speed of the D&C approach, we are able to demonstrate interactive quantum chemistry simulations for systems up to a few hundred atoms on a current multicore desktop computer. When drawing and editing molecular systems, interactive simulations provide immediate, intuitive feedback on chemical structures. As the number of cores on personal computers increases, and larger and larger systems can be dealt with, we believe such interactive simulations—even at lower levels of theory—should thus prove most useful to effectively understand, design and prototype molecules, devices and materials. © 2012 Wiley Periodicals, Inc.
Oligonucleotide‐mediated gene editing is underestimated in cells expressing mutated green fluorescent protein and is positively associated with target protein expression
Authors: Disterer Petra , Papaioannou Ioannis , Evans Vanessa C. , Paul Simons J. , Owen James S.
Published: January 2012

Background

Single‐stranded DNA oligonucleotides (ssODNs) can introduce small, specific sequence alterations into genomes. Potential applications include creating disease‐associated mutations in cell lines or animals, functional studies of single nucleotide polymorphisms and, ultimately, clinical therapy by correcting genetic point mutations. Here, we report feasibility studies into realizing this potential by targeting a reporter gene, mutated enhanced green fluorescent protein (mEGFP).

Methods

Three mammalian cell lines, CHO, HEK293T and HepG2, expressing multiple copies of mEGFP were transfected with a 27‐mer ssODN capable of restoring fluorescence. Successful cell correction was quantified by flow cytometry.

Results

Gene editing in each isogenic cell line, as measured by percentage of green cells, correlated tightly with target protein levels, and thus gene expression. In the total population, 2.5% of CHO‐mEGFP cells were successfully edited, although, remarkably, in the highest decile producing mEGFP protein, over 20% of the cells had restored green fluorescence. Gene‐edited clones initially selected for green fluorescence lost EGFP expression during cell passaging, which partly reflected G2‐phase cycle arrest and perhaps eventual cell death. The major cause, however, was epigenetic down‐regulation; incubation with sodium butyrate or 5‐aza‐2′‐deoxycytidine reactivated fluorescent EGFP expression and hence established that the repaired genotype was stable.

Conclusions

Our data establish that ssODN‐mediated gene editing is underestimated in cultured mammalian cells expressing nonfluorescent mutated EGFP, because of variable expression of this mEGFP target gene in the cell population. This conclusion was endorsed by studies in HEK293T‐mEGFP and HepG2‐mEGFP cells. We infer that oligonucleotide‐directed editing of endogenous genes is feasible, particularly for those that are transcriptionally active. Copyright © 2012 John Wiley & Sons, Ltd.
Antitumor effect of chondroitin sulfate‐coated ternary granulocyte macrophage‐colony‐stimulating factor plasmid complex for ovarian cancer
Authors: Hamada Katsuyuki , Yoshihara Chieko , Ito Tomoko , Tani Kenzaburo , Tagawa Masatoshi , Sakuragawa Norio , Itoh Hiroshi , Koyama Yoshiyuki
Published: January 2012

Background

Although replication‐competent viruses have been developed for treating cancers, their cytotoxic effects are insufficient as a result of infection inhibited by the generation of neutralizing antibodies, and systemic administration is difficult as a result of the life‐threatening serious side‐effects of virus‐induced cytokine surge. To overcome these critical problems, we devised a plasmid/polycation/polyanion complex and assessed the potential of ternary plasmid complexes coated with chondroitin sulfate in gene therapy for ovarian cancer. The antitumor effects of chondroitin sulfate‐coated complex as an anionic component were compared with those of hyaluronic acid on ovarian cancer.

Methods

Plasmid harboring the gene of murine granulocyte macrophage‐colony‐stimulating factor (mGM‐CSF) was complexed with polyethyleneimine (PEI) and hyaluronic acid or chondroitin sulfate. Murine ovarian cancer cells were injected into (C57BL/6 × C3H/He) F1 mice to prepare a subcutaneous or intraperitoneal tumor model.

Results

DNA/PEI was charged positively and DNA/PEI/chondroitin sulfate or DNA/PEI/hyaluronic acid was charged negatively. Plasmid‐green fluorescent protein (GFP)/PEI coated with 10‐kilodalton (kDa) chondroitin sulfate increased transfection efficiency compared to coating with chondroitin sulfate of higher‐molecular‐weight or hyaluronic acid. The transfection efficiency of GFP/PEI/10‐kDa chondroitin sulfate in ovarian cancer cells was six‐fold higher than that in normal cells. Intraperitoneal injection of mGM‐CSF/PEI coated with 10‐kDa chondroitin sulfate prolonged survival compared to that coated with hyaluronic acid. Intratumoral injection of mGM‐CSF/PEI coated with 10‐kDa chondroitin sulfate achieved mouse survival rates of 100%, although that with hyaluronic acid did not.

Conclusions

These findings suggest that GM‐CSF/PEI coated with 10‐kDa chondroitin sulfate has the potential for use in gene therapy of ovarian cancer. Copyright © 2012 John Wiley & Sons, Ltd.
CD40‐targeted adenoviral cancer vaccines: the long and winding road to the clinic
Authors: Hangalapura Basav N. , Timares Laura , Oosterhoff Dinja , Scheper Rik J. , Curiel David T. , de Gruijl Tanja D.
Published: January 2012

The ability of dendritic cells (DCs) to orchestrate innate and adaptive immune responses has been exploited to develop potent anti‐cancer immunotherapies. Recent clinical trials exploring the efficacy of ex vivo modified autologous DC‐based vaccines have reported some promising results. However, in vitro generation of autologous DCs for clinical administration, their loading with tumor associated antigens (TAAs) and their activation, is laborious and expensive, and, as a result of inter‐individual variability in the personalized vaccines, remains poorly standardized. An attractive alternative approach is to load resident DCs in vivo by targeted delivery of TAAs, using viral vectors and activating them simultaneously. To this end, we have constructed genetically‐modified adenoviral (Ad) vectors and bispecific adaptor molecules to retarget Ad vectors encoding TAAs to the CD40 receptor on DCs. Pre‐clinical human and murine studies conducted so far have clearly demonstrated the suitability of a ‘two‐component’ (i.e. Ad and adaptor molecule) configuration for targeted modification of DCs in vivo for cancer immunotherapy. This review summarizes recent progress in the development of CD40‐targeted Ad‐based cancer vaccines and highlights pre‐clinical issues in the clinical translation of this approach. Copyright © 2012 John Wiley & Sons, Ltd.
EphrinA1–EphA2 interaction‐mediated apoptosis and FMS‐like tyrosine kinase 3 receptor ligand‐induced immunotherapy inhibit tumor growth in a breast cancer mouse model
Authors: Tandon Manish , Vemula Sai V. , Sharma Anurag , Ahi Yadvinder S. , Mittal Shalini , Bangari Dinesh S. , Mittal Suresh K.
Published: January 2012

Background

The receptor tyrosine kinase EphA2 is overexpressed in several types of cancers and is currently being pursued as a target for breast cancer therapeutics. The EphA2 ligand EphrinA1 induces EphA2 phosphorylation and intracellular internalization and degradation, thus inhibiting tumor progression. The hematopoietic growth factor, FMS‐like tyrosine kinase 3 receptor ligand (Flt3L), promotes expansion and mobilization of functional dendritic cells.

Methods

We tested the EphrinA1–EphA2 interaction in MDA‐MB‐231 breast cancer cells focusing on the receptor‐ligand‐mediated apoptosis of breast cancer cells. To determine whether EphrinA1–EphA2 interaction‐associated apoptosis and Flt3L‐mediated immunotherapy would have an additive effect in inhibiting tumor growth, we used an immunocompetent mouse model of breast cancer to evaluate intratumoral (i.t.) inoculation strategies with human adenovirus (HAd) vectors expressing either EphrinA1 (HAd‐EphrinA1‐Fc), Flt3L (HAd‐Flt3L) or a combination of EphrinA1‐Fc + Flt3L (HAd‐EphrinA1‐Fc + HAd‐Flt3L).

Results

In vitro analysis demonstrated that an EphrinA1–EphA2 interaction led to apoptosis‐related changes in breast cancer cells. In vivo, three i.t. inoculations of HAd‐EphrinA1‐Fc showed potent inhibition of tumor growth. Furthermore, increased inhibition in tumor growth was observed with the combination of HAd‐EphrinA1‐Fc and HAd‐Flt3L accompanied by the generation of an anti‐tumor adaptive immune response.

Conclusions

The results obtained in the present study, indicating the induction of apoptosis and inhibition of mammary tumor growth, show the potential therapeutic benefits of HAd‐EphrinA1‐Fc. In combination with HAd‐Flt3L, this represents a promising strategy for effectively inducing mammary tumor regression by HAd vector‐based therapy. Copyright © 2012 John Wiley & Sons, Ltd.
Lipid‐soluble Extracts from Salvia miltiorrhiza Inhibit Production of LPS‐induced Inflammatory Mediators via NF‐κB Modulation in RAW 264.7 Cells and Perform Antiinflammatory Effects In Vivo
Authors: Li Meng , Zhang Lei , Cai Run‐Lan , Gao Yuan , Qi Yun
Published: January 2012

Salvia miltiorrhiza, a traditional Chinese herbal medicine, is used to treat various inflammatory diseases. In the present study, the antiinflammatory effects of S. miltiorrhiza lipid‐soluble extracts (SMLE) were demonstrated in vitro and in vivo, along with its underlying mechanism of action. SMLE significantly inhibited the production of NO, TNF‐α, IL‐1β and IL‐6 in lipopolysaccharides (LPS)‐stimulated RAW 264.7 cells. SMLE also inhibited the LPS‐induced degradation of IκB‐α in the cytoplasm and the translocation of p65 to the nucleus in RAW 264.7 cells. In addition, SMLE inhibited the production of intracellular reactive oxygen species (ROS) and the surface expression of CD14 induced by LPS. In animal models, intraperitoneal administration of SMLE increased the survival rate of endotoxemia and sepsis in mice. The topical administration of SMLE significantly inhibited ear edema induced by PMA. It was found that SMLE inhibits the LPS‐induced gene and protein expression of iNOS, TNF‐α, IL‐1β and IL‐6 in macrophages by blocking NF‐κB activation, and these effects are mediated, at least in part, through the inhibition of intracellular ROS generation and the surface expression of CD14. The results suggest a possible therapeutic application of SMLE in inflammatory diseases and provide scientific evidence in support of the traditional Chinese medical practice of treatment with S. miltiorrhiza. Copyright © 2012 John Wiley & Sons, Ltd.
Preventive Effects of Hesperidin, Glucosyl Hesperidin and Naringin on Hypertension and Cerebral Thrombosis in Stroke‐prone Spontaneously Hypertensive Rats
Authors: Ikemura Miyako , Sasaki Yasuto , Giddings John C. , Yamamoto Junichiro
Published: January 2012

The effects of hesperidin, glucosyl hesperidin (G‐hesperidin), a water‐soluble derivative of hesperidin, and naringin on blood pressure and cerebral thrombosis were investigated using stroke‐prone spontaneously hypertensive rats (SHRSP). Hesperidin, G‐hesperidin and naringin were mixed with diet and fed to the animals for 4 weeks. No effect was evident on body weight, but the supplements significantly suppressed the age related increase in blood pressure. Thrombotic tendency, as assessed using a He‐Ne laser technique in the cerebral blood vessels, was significantly decreased in the treated animals compared with the control animals. Measurements of 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) demonstrated that the supplements had strong antioxidant activity. Furthermore, these supplements significantly increased the production of nitric oxide (NO) metabolites in urine measured with Griess reagent. Vasodilation induced by acetylcholine‐mediated NO production in the endothelium was assessed using thoracic aortic ring preparations and indicated that endothelial function was significantly improved by the administration of these supplements.

These findings suggest that the strong antioxidant properties of hesperidin, G‐hesperidin and naringin could modulate the inactivation of NO and protect endothelial function from reactive oxygen species (ROS). In this manner, the flavonoids could contribute beneficial effects on the mechanisms of hypertension and thrombosis by increasing the bioavailability of NO. Copyright © 2012 John Wiley & Sons, Ltd.
Antiobesity Effects of a Sulfur Compound Thiacremonone Mediated via Down‐regulation of Serum Triglyceride and Glucose Levels and Lipid Accumulation in the Liver of db/db Mice
Authors: Ban Jung Ok , Lee Dong Hun , Kim Eun Jin , Kang Jeong Woo , Kim Man Sub , Cho Min Chul , Jeong Heon Sang , Kim Jong Wan , Yang Young , Hong Jin Tae , Yoon Do Young
Published: January 2012

Garlic is widely used as a spice. Garlic extracts exert anticancer and antiinflammatory effects, but its antiobesity efficacy studies have produced conflicting results. The antiobesity effects of thiacremonone, a sulfur compound isolated from garlic, was evaluated in obese db/db mice. Thiacremonone was orally administrated to mice for 3 weeks. The thiacremonone‐treated db/db mice showed a loss of body weight and decrease in blood triglyceride and glucose levels compared with the control mice. Histological analysis further revealed that thiacremonone significantly decreased lipid accumulation in the fatty livers of treated db/db mice. It was observed that GLUT‐4 expression and glucose uptake were up‐regulated by thiacremonone in 3T3‐L1 adipocytes. Thiacremonone treatment also suppressed expression levels of acetyl‐CoA carboxylase (ACC) and fatty acid synthase (FAS), which are involved in lipid metabolism, in the liver of db/db mice. In addition, thiacremonone enhanced peroxisome proliferator‐activated receptor γ (PPARγ) expression in the fatty liver. Taken together, these results suggest that thiacremonone may play a vital role in improving the management of obesity and related metabolic syndromes via inhibition of lipid accumulation. Copyright © 2012 John Wiley & Sons, Ltd.
Extending science beyond the classroom door: Learning from students' experiences with the Choice, Control and Change (C3) curriculum
Authors: Mallya Aarti , Mensah Felicia Moore , Contento Isobel R. , Koch Pamela A. , Barton Angela Calabrese
Published: January 2012

This article describes the experiences of seventh‐grade students living in high poverty areas of New York City who participated in the Choice, Control and Change (C3) science curriculum. Data were collected from eight case study students in the form of individual interviews, classroom observations, and student artifacts. Analysis of these data revealed that students were able to extend their C3 science understandings beyond the classroom door by developing and expressing science agency in the following ways: (1) critically analyze the conditions of their food environment, (2) purposefully make healthier choices, and (3) expand the food and activity options available to themselves and others. Through participation in the C3 curriculum, and the science content and practices addressed therein, students began to view their worlds with a more critical mindset and to devise ways to transform themselves and the conditions of their own and others' lives. Based on the findings, we propose taking a closer look at how we might create meaningful and relevant learning opportunities for students through connecting school science with issues of personal and social significance in students' lives outside of school. © 2011 Wiley Periodicals, Inc. J Res Sci Teach 49: 244–269, 2012
Expression of Enzymes and Transcription Factors Involved in n‐3 Long Chain PUFA Biosynthesis in Limousin Bull Tissues
Authors: Cherfaoui Maya , Durand Denys , Bonnet Muriel , Cassar‐Malek Isabelle , Bauchart Dominique , Thomas Agnès , Gruffat Dominique
Published: January 2012

The current low consumption of n‐3 long chain polyunsaturated fatty acids (n‐3 LCPUFA) led scientists to wonder about the possible enrichment of human food, including meats such as beef, with n‐3 LCPUFA. However, their biosynthesis from dietary n‐3 PUFA seems limited in mammalian tissues implying that a better understanding of the molecular mechanisms responsible for this down regulation is needed. This study aimed at identifying and comparing the limiting steps of n‐3 LCPUFA synthesis in liver, intermuscular adipose tissue (IM‐AT) and semitendinosus muscle (ST) from six Limousin bulls. Tissue FA composition was analysed by GLC and mRNA abundance of enzymes and transcription factors involved in n‐3 LCPUFA synthesis was assessed by RT‐qPCR. In liver, mRNA encoding proteins involved in n‐3 LCPUFA synthesis were present in agreement with the significant high content of n‐3 LCPUFA (8.4 mol% of total FA, 257 mg/100 g of fresh tissue) in this organ. In IM‐AT, these mRNA were all present, but at a tenfold lower intensity than in liver in agreement with the low contents of n‐3 LCPUFA in this tissue. In ST muscle, these mRNA were all present except elongase 5 mRNA which was only present as trace, the corresponding protein being undetectable, probably inducing a break of n‐3 LCPUFA synthesis from 18:4n‐3. In conclusion, Limousin bull ST muscle seemed unable to synthesize n‐3 LCPUFA. However, the presence of 20:5n‐3 (EPA) and 22:5n‐3 (DPAn‐3) in muscle raised the question of the origin of these n‐3 LCPUFA.
Effect of Enzymatic Trans‐ and Interesterification on the Thermal Properties of Groundnut and Linseed Oils and Their Blends
Authors: Sharma Meesha , Lokesh Belur Ramaswamy
Published: January 2012

The present study was undertaken to compare the alterations observed in the triacylglycerol (TAG) molecular species of blended and interesterified oils containing groundnut oil (GNO) and linseed oil (LIN). The blended oil (BLE) was subjected to a lipase catalyzed reaction to prepare transesterified oil (TRA). A structured lipid (STR) was also prepared by a lipase catalyzed acidolysis reaction of GNO and free fatty acids concentrate from LIN. The changes in the molecular species of modified lipids were determined by high performance liquid chromatography. The thermal profiles were determined by differential scanning calorimetry. In comparison with GNO, the triunsaturated triacylglycerols were increased and the disaturated triacylglycerol molecular species were decreased in TRA and STR. Both BLE and TRA showed a decrease in the onset temperature for crystallization as compared to that observed with GNO. The total transitional enthalpy for crystallization was higher for BLE, TRA and STR as compared to GNO. The melting temperature of TRA and STR showed a decrease in comparison to GNO, reflecting on the changes in the TAG molecules species present in the oil. Thus, interesterification of oils introduced changes in the physical properties of oils, even though the overall fatty acid composition of blended and interesterified oils remained similar.
Are Virtues Shaped by National Cultures or Religions?
Authors: van Oudenhoven Jan Pieter , de Raad Boele , Carmona Carmen , Helbig Anne-Kathrin , van der Linden Meta
Published: January 2012

The present paper examines the relative influence of religion and nation on conceptions of virtues. In a first study, conducted in the Netherlands, 926 respondents of different profession, age, sex, and religious background rank ordered a list of 15 virtues. A comparison of Dutch Muslims and non-Muslims showed a remarkably high resemblance in their ratings of virtues. Only faith was rated as being much more important by Muslims than by non-Muslims. In the second study, the influence of national cultures was examined. Adults (N = 795) from two culturally relatively similar countries, Germany and the Netherlands, and from Spain rated the same list of virtues. Crossnational differences between the two Northern European countries and Spain by far exceeded the influence of religion on the importance ratings of virtues. The implications of the findings for the often-mentioned clash of religions are discussed. Currently, the influence of religion on the values of immigrants may be overemphasized and other important characteristics may be underestimated.
Personality and Culture
Authors: Allik Jüri , Massoudi Koorosh , Realo Anu , Rossier Jérôme
Published: January 2012

A review of nearly three decades of cross-cultural research shows that this domain still has to address several issues regarding the biases of data collection and sampling methods, the lack of clear and consensual definitions of constructs and variables, and measurement invariance issues that seriously limit the comparability of results across cultures. Indeed, a large majority of the existing studies are still based on the anthropological model, which compares two cultures and mainly uses convenience samples of university students. This paper stresses the need to incorporate a larger variety of regions and cultures in the research designs, the necessity to theorize and identify a larger set of variables in order to describe a human environment, and the importance of overcoming methodological weaknesses to improve the comparability of measurement results. Cross-cultural psychology is at the next crossroads in it’s development, and researchers can certainly make major contributions to this domain if they can address these weaknesses and challenges.
When Spandrels Become Arches: Neural crosstalk and the evolution of consciousness
Authors: Wallace Rodrick
Published: January 2012

Once cognition is recognized as having a 'dual' information source, the information theory chain rule implies that isolating coresident information sources from crosstalk requires more metabolic free energy than permitting correlation. This provides conditions for an evolutionary exaptation leading to the rapid, shifting global neural broadcasts of consciousness. The argument is quite analogous to the well-studied exaptation of noise to trigger stochastic resonance amplification in neurons and neuronal subsystems. Astrobiological implications are obvious.
Long double stranded RNA is present in scrapie infected cells and tissues
Authors: Karapetyan Yervand
Published: January 2012

The nature of the infectious agent causing scrapie and other Transmissible Spongiform Encephalopathies remains an enigma despite decades of research efforts. The protein-only prion hypothesis posits that abnormal conformer of a host protein is the infectious agent. Virus and virino theories include host-independent nucleic acid as the genome of the infectious agent in addition to protein component (in case of virino a host protein and in case of virus a viral protein). Viral or sub-viral nucleic acids have long been sought in scrapie to explain the existence of multiple agent strains. Many different approaches were undertaken to find such nucleic acid. Despite that no scrapie specific nucleic acid sequences have been found in infected cells or tissues. Most viruses induce synthesis of long double stranded RNA (dsRNA) during their replication in cells. Therefore the presence of long dsRNA would be an indication of viral infection in cells. J2 monoclonal antibody against long dsRNA is a great tool for easy screening of cells and tissues for the presence of suspected unknown viral infection. This antibody has not been used for testing of scrapie infected tissues.Evidence is presented here for long dsRNA in scrapie infected cells and tissues. Such dsRNA is also found in scrapie free tissue culture cells.
Retracted Article: A series of novel types of immobilized chiral salen Mn(iii) on different organic polymer-inorganic hybrid crystalline zinc phosphonate-phosphate act as catalysts for asymmetric epoxidation of unfunctionalized olefins
Authors: Huang Jing , Fu Xiangkai , Wang Gang , Ge Yaqin , Miao Qiang
Published: January 2012

The immobilized catalysts displayed superior catalytic ability both for experimental scale and for large-scale reactions.
Adiabatic nonlinear waves with trapped particles. II. Wave dispersion
Authors: Dodin I. Y. , Fisch N. J.
Published: January 2012

A general nonlinear dispersion relation is derived in a nondifferential form for an adiabatic sinusoidal Langmuir wave in collisionless plasma, allowing for an arbitrary distribution of trapped electrons. The linear dielectric function is generalized, and the nonlinear kinetic frequency shift ωNL is found analytically as a function of the wave amplitude a. Smooth distributions yield ωNL∝a, as usual. However, beam-like distributions of trapped electrons result in different power laws, or even a logarithmic nonlinearity, which are derived as asymptotic limits of the same dispersion relation. Such beams are formed whenever the phase velocity changes, because the trapped distribution is in autoresonance and thus evolves differently from the passing distribution. Hence, even adiabatic ωNL(a) is generally nonlocal.
Studies on room-temperature electric-field effect in ionic-liquid gated VO2 three-terminal devices
Authors: Yang Zheng , Zhou You , Ramanathan Shriram
Published: January 2012

We present a study of electrostatic gating of VO2 thin films in ionic-liquid-based electric double-layer transistor geometry. Devices were fabricated by lithographic patterning of VO2 thin films as channel on sapphire substrates, ionic liquid as gate dielectric, and Au as gate/source/drain electrode, respectively. A significant unipolar increase in channel conductance at room temperature is observed. The VO2 channel resistance decreases ∼50% at + 2 V gate bias, whereas it increases slightly under negative bias. The polarity dependence of resistance modulation suggests electrons to be a dominant carrier, which is consistent with Hall measurements. In the high-temperature metallic state of VO2, no gating effect is observed. The effect of multiple transition cycles on the channel resistance change under bias is discussed. The study contributes to on-going efforts to realize room-temperature field-effect switches with correlated oxides.
Nuclear magnetic resonance investigation of dynamics in poly(ethylene oxide)-based lithium polyether-ester-sulfonate ionomers
Authors: Roach David J. , Dou Shichen , Colby Ralph H. , Mueller Karl T.
Published: January 2012

Nuclear magnetic resonance spectroscopy has been utilized to investigate the dynamics of poly(ethylene oxide)-based lithium sulfonate ionomer samples that have low glass transition temperatures. 1H and 7Li spin-lattice relaxation times (T1) of the bulk polymer and lithium ions, respectively, were measured and analyzed in samples with a range of ion contents. The temperature dependence of T1 values along with the presence of minima in T1 as a function of temperature enabled correlation times and activation energies to be obtained for both the segmental motion of the polymer backbone and the hopping motion of lithium cations. Similar activation energies for motion of both the polymer and lithium ions in the samples with lower ion content indicate that the polymer segmental motion and lithium ion hopping motion are correlated in these samples, even though lithium hopping is about ten times slower than the segmental motion. A divergent trend is observed for correlation times and activation energies of the highest ion content sample with 100% lithium sulfonation due to the presence of ionic aggregation. Details of the polymer and cation dynamics on the nanosecond timescale are discussed and complement the findings of X-ray scattering and quasi-elastic neutron scattering experiments.
Optical feedback mechanisms in laser induced growth of carbon nanotube forests
Authors: Bock M. C. D. , Denk R. , Wirth C. T. , Goldberg-Oppenheimer P. , Hofmann S. , Baumberg J. J.
Published: January 2012

We study optical feedback mechanisms occurring during growth of multi-walled carbon nanotube forests on transparent substrates. Growth is realised via laser-induced chemical vapour deposition using iron nanoparticle catalysts. In situ Raman and reflection spectroscopy employed clearly distinguish three growth phases. In the initial seed phase, growth of carbon nanostructures increases the laser absorption and this feedback enables growth of radially orientated carbon nanotubes. Understanding the laser interaction with the growing nanostructure holds the key towards controlled growth and opens up new routes to nanostructure and nanodevice design and fabrication.
Fundamental limits on optical transparency of transparent conducting oxides: Free-carrier absorption in SnO2
Authors: Peelaers H. , Kioupakis E. , Van de Walle C. G.
Published: January 2012

Transparent conducting oxides combine high electrical conductivity with transparency to visible light. However, the large concentration of free electrons introduces a source of absorption that limits the transparency. Here, we evaluate the importance of phonon-assisted free-carrier absorption in SnO2 completely from first principles. Our results show that absorption is modest in the visible and much stronger in the UV and infrared. We also provide insight into the mechanisms that govern absorption in different wavelength regimes.
A density matrix renormalization group method study of optical properties of porphines and metalloporphines
Authors: Kumar Manoranjan , Pati Y. Anusooya , Ramasesha S.
Published: January 2012

The symmetrized density matrix renormalization group method is used to study linear and nonlinear optical properties of free base porphine and metalloporphine. Long-range interacting model, namely, Pariser-Parr-Pople model is employed to capture the quantum many-body effect in these systems. The nonlinear optical coefficients are computed within the correction vector method. The computed singlet and triplet low-lying excited state energies and their charge densities are in excellent agreement with experimental as well as many other theoretical results. The rearrangement of the charge density at carbon and nitrogen sites, on excitation, is discussed. From our bond order calculation, we conclude that porphine is well described by the 18-annulenic structure in the ground state and the molecule expands upon excitation. We have modeled the regular metalloporphine by taking an effective electric field due to the metal ion and computed the excitation spectrum. Metalloporphines have D4h symmetry and hence have more degenerate excited states. The ground state of metalloporphines shows 20-annulenic structure, as the charge on the metal ion increases. The linear polarizability seems to increase with the charge initially and then saturates. The same trend is observed in third order polarizability coefficients.