bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergistic effect of TGF‐β superfamily members on the induction of Foxp3+ Treg
Authors: Lu Ling , Ma Jilin , Wang Xuehao , Wang Julie , Zhang Feng , Yu Jiangning , He Ge , Xu Bing , Brand David D , Horwitz David A , Shi Wei , Zheng Song Guo
Published: November 2009

TGF‐β plays an important role in the induction of Treg and maintenance of immunologic tolerance, but whether other members of TGF‐β superfamily act together or independently to achieve this effect is poorly understood. Although others have reported that the bone morphogenetic proteins (BMP) and TGF‐β have similar effects on the development of thymocytes and T cells, in this study, we report that members of the BMP family, BMP‐2 and ‐4, are unable to induce non‐regulatory T cells to become Foxp3+ Treg. Neutralization studies with Noggin have revealed that BMP‐2/4 and the BMP receptor signaling pathway is not required for TGF‐β to induce naïve CD4+CD25− cells to express Foxp3; however, BMP‐2/4 and TGF‐β have a synergistic effect on the induction of Foxp3+ Treg. BMP‐2/4 affects non‐Smad signaling molecules including phosphorylated ERK and JNK, which could subsequently promote the differentiation of Foxp3+ Treg induced by TGF‐β. Data further advocate that TGF‐β is a key signaling factor for Foxp3+ Treg development. In addition, the synergistic effect of BMP‐2/4 and TGF‐β indicates that the simultaneous manipulation of TGF‐β and BMP signaling might have considerable effects in the clinical setting for the enhancement of Treg purity and yield.
CeO2 Buffer Layers for HTSC by an Aqueous Sol‐Gel Method – Chemistry and Microstructure
Authors: Van de Velde Nigel , Van de Vyver David , Brunkahl Oliver , Hoste Serge , Bruneel Els , Van Driessche Isabel
Published: November 2009

During the last decade the focus in superconductivity research has shifted towards the manufacturing of easy‐to‐handle superconductors, because of their high usability in electronic applications in comparison to bulky ceramics. This article reviews our recent progress made in the buffer‐layer architecture of such a coated conductor, focusing on CeO2 thin films prepared by an aqueous sol‐gel method and deposited by dip‐coating. Starting from water‐soluble cerium(III) nitrate precursors, we were able to deposit films showing a very high degree of [002] orientation depending on the film characteristics and synthesis conditions. The formation and stability of the chemical complexes in the solution was studied by potentiometric titrations. The main parameters influencing the texture seem to be the ambient Ar‐(5 %)H2 atmosphere and the thickness of the synthesized buffer layers. The microstructure of the thin films deposited on metallic tapes was controlled by the incorporation of doping elements. This research allowed us to achieve a 50 nm thick CeO2 film, showing a very high degree of [002] orientation and exhibiting a low surface roughness. SubsequentYBa2Cu3O7 synthesis by TFA‐MOD resulted in promising XRD and Jc measurements. Our easy‐to‐use, environmentally friendly strategy could contribute to the spreading of the use of coated conductors in everyday applications.
Preparation, Crystal Structures, and Spectroscopic and Redox Properties of Nickel(II) Complexes Containing Phosphane–(Amine or Quinoline)‐Type Hybrid Ligands and a Nickel(I) Complex Bearing 8‐(Diphenylphosphanyl)quinoline
Authors: Hashimoto Akira , Yamaguchi Hiroshi , Suzuki Takayoshi , Kashiwabara Kazuo , Kojima Masaaki , Takagi Hideo D.
Published: November 2009

Nickel(II) complexes containing P–N‐type bidentate hybrid ligands of 2‐aminoethylphosphanes (RR′Pea; RR′ = Ph2 or MePh) or 8‐quinolylphosphanes (RR′Pqn), namely [Ni(P–N)2](BF4)2 [P–N = Ph2Pea (1), MePhPea (2), Ph2Pqn (3), or MePhPqn (4)] have been prepared, and their structural, spectroscopic, and electrochemical properties determined. The crystal structure analysis indicates that the 2‐aminoethylphosphane complexes (1 and 2) have a square‐planar coordination geometry around the NiII center with a cis(P,P) configuration, whereas the 8‐quinolylphosphane complexes (3 and 4) exhibit a severe tetrahedral distortion because of the steric repulsion between the ortho‐H atoms in the mutually cis‐positioned quinolyl rings. Complexes 1 and 2 maintain their diamagnetic square‐planar four‐coordinate structure on acetonitrile solution, whereas complexes 3 and 4 show paramagnetic behavior. Spectroscopic and electrochemical measurements suggest that the ligand‐field strengths of these four P–N‐type ligands increase in the order Ph2Pqn (3) < MePhPqn (4) < Ph2Pea (1) < MePhPea (2). The Ph2Pqn complex 3 is readily reduced by Zn powder to afford the corresponding nickel(I) complex [Ni(Ph2Pqn)2]BF4 (5). The crystal structure of complex 5 reveals that the NiI ion adopts a distorted tetrahedral coordination geometry with slightly longer (≈ 0.05 Å) Ni–P and Ni–N bond lengths than those in the corresponding NiII complex 3.
A Radical Approach to Hydroxylaminotrichlorosilanes: Synthesis, Reactivity, and Crystal Structure of TEMPO‐SiCl3 (TEMPO = 2,2,6,6‐Tetramethylpiperidine‐N‐oxyl)
Authors: Stefan Spirk , Belaj Ferdinand , Madl Tobias , Pietschnig Rudolf
Published: November 2009

The reaction of the nitroxy radical 2,2,6,6‐tetramethylpiperidine‐N‐oxyl (TEMPO) with SiCl4 has been investigated in detail. One silicon‐containing product, TEMPO‐SiCl3 (1), could be isolated in crystalline form, and its crystal structure was determined. The structural parameters have been compared with the related hydroxylaminotrichlorosilane known from the literature and with DFT calculations. According to the calculations, the formation of 1 follows an SN2 mechanism, which is thermodynamically favored over an SN1 pathway. Upon hydrolysis, 1 decomposes and yields several TEMPO‐containing species. These were all characterized crystallographically.
A Short and Efficient Synthesis of Bridgehead Mono‐ and Dideuteriated Tropinones
Authors: Fournial Anaïs , Ranaivondrambola Tsiresy , Mathé‐Allainmat Monique , Robins Richard J. , Lebreton Jacques
Published: November 2009

Studies of the biosynthesis and degradation of alkaloids of the tropane class require substrates isotopically‐labelled at specific positions. To investigate the mechanism of the enzyme reactions involved in the hydroxylation of the bridgehead position(s), compounds deuteriated at this position are needed. An efficient synthesis of 1,5‐dideuterio‐ and racemic 1‐deuteriotropinone is described in which high levels of deuterium are incorporated from the corresponding di‐ and mono‐labelled 2,5‐dibutoxytetrahydrofuran.
Too late to coordinate: Contextual influences on behavioral synchrony
Authors: Miles Lynden K. , Griffiths Jordan L. , Richardson Michael J. , Macrae C. Neil
Published: November 2009

The temporal coupling of behavior serves as a foundation for effective social exchange with synchronized actions moderating core components of social‐cognitive functioning. Questions remain, however, regarding the precise conditions under which this form of behavioral coordination emerges. In particular, do social factors moderate the extent to which people synchronize their movements with others? Given that synchrony serves as an important non‐verbal route through which interpersonal connections can be forged, the current investigation considered whether contextual influences moderate the emergence of behavioral coupling. To explore this issue, movements were recorded while participants performed a repetitive activity (i.e., stepping) with an interaction partner who either turned up for the experiment on time or was 15 minutes late. Results revealed that coordination (i.e., in‐phase synchrony) was substantially reduced when participants interacted with a tardy partner, a finding that highlights the impact that social factors exert on the spontaneous emergence of behavioral synchrony. Copyright © 2009 John Wiley & Sons, Ltd.
A numerical modelling and experimental study of flow width dynamics on alluvial fans
Authors: Nicholas A. P. , Clarke L. , Quine T. A.
Published: November 2009

Alluvial fans are dynamic landforms, the evolution of which is controlled by both external environmental forcing (climate, tectonics and base level change) and internal process‐form feedbacks. The latter include changes in flow configuration (between sheetflow and channelized flow states), driven by aggradation and degradation, which may in turn promote changes in sediment transport capacity. Recent numerical modelling indicates that such feedbacks may lead to dramatic and persistent fan entrenchment in the absence of external forcing. However, the parameterization of flow width within such models is untested to date and is subject to considerable uncertainty. This paper presents results from an experimental study of flow width dynamics on an aggrading fan in which spatial and temporal patterns of fan inundation are monitored continuously using analysis of digital vertical photography. Observed flow widths are compared with results from a simple theoretical model developed for non‐equilibrium (aggradational) conditions. Results demonstrate that the theoretical model is capable of capturing the first‐order characteristics of width adjustment over the course of the experiment, and indicate that flow width is a function of fan aggradation rate. This illustrates that models of alluvial flow width derived for equilibrium conditions may have limited utility in non‐equilibrium situations, despite their widespread use to date. Copyright © 2009 John Wiley & Sons, Ltd.
Assessment and modification of sub‐cell‐fix method for re‐initialization of level‐set distance function
Authors: Sun M. B. , Wang Z. G. , Bai X. S.
Published: November 2009

Sub‐cell‐fix re‐initialization method was proposed by Russo and Smereka (J. Comput. Phys. 2000; 163: 51–67) as a modification to the re‐distancing algorithm of Sussman et al. (J. Comput. Phys. 1994; 114: 146–159) that determines the distance function from an interface known as the zero level‐set. The principal goal of sub‐cell‐fix method is to compute the distance function of the cells adjacent to the zero level‐set without disturbing the original zero level‐set. Following the original work of Russo and Smereka, several improved sub‐cell‐fix schemes were reported in the literature. In this paper, we show that in certain situations almost all the previous sub‐cell‐fix schemes can disturb the zero level‐set, and the accuracy would not improve when the CFL numbers are decreased. Based on the scheme of Hartmann et al. (J. Comput. Phys. 2008; 227:6821–6845), we propose an improved sub‐cell‐fix scheme that can significantly increase the accuracy of sub‐cell‐fix method on problems that are challenging. The scheme makes use of a combination of the points adjacent to zero level‐set surfaces and preserves the interface in a second‐order accuracy. The new sub‐cell‐fix scheme is capable of handling large local curvature, and as a result it demonstrates satisfactory performance on several challenging test cases. Limitations of the schemes on highly stretched grids are illustrated. Copyright © 2009 John Wiley & Sons, Ltd.
Plant mitochondrial RNA editing: The Strasbourg chapter
Authors: Grienenberger Jean Michel
Published: November 2009

For 8 years, it was not understood why certain genes of plant mitochondria contain CGG (arginine) codons at positions where tryptophan codons (UGG) are present in the corresponding genes of nonplant species. Identification and sequencing of a tRNATrp gene showed that it is not able to decode the CGG codon. Analysis of different discrepancies in the sequences of plant mitochondrial proteins prompted us to determine directly the corresponding RNA sequences. These experiments showed that plant mitochondrial transcripts are subject to RNA editing that changes C into U, resulting in a better phylogenetic conservation of protein sequences [Gualberto et al. (1989) Nature 341, 660–662]. © 2009 IUBMB IUBMB Life, 61: 1110–1113, 2009
Effect of chitosan‐alginate nanoparticles and ultrasound on the efficiency of gene transfection of human cancer cells
Authors: Yang Shu‐Jyuan , Chang Szu‐Min , Tsai Kun‐Che , Chen Wen‐Shiang , Lin Feng‐Huei , Shieh Ming‐Jium
Published: November 2009

Background

Gene therapy has been used to treat a variety of health problems, but transfection inefficiency and the lack of safe vectors have limited clinical progress. Fabrication of a vector that is safe and has high transfection efficiency is crucial for the development of successful gene therapy. The present study aimed to synthesize chitosan‐alginate nanoparticles that can be used as carriers of the pAcGFP1‐C1 plasmid and to use these nanoparticles with an ultrasound protocol to achieve high efficiency gene transfection.

Methods

Chitosan was complexed with alginate and the pAcGFP1‐C1 plasmid at different charge ratios to create chitosan‐alginate‐DNA nanoparticles (CADNs). The average particle size and loading efficiency were measured. Plasmid DNA retardation and integrity were analysed on 1% agarose gels. The effect of CADNs and ultrasound on the efficiency of transfection of cells and subcutaneous tumors was evaluated.

Results

In the CADNs, the average size of incorporated plasmid DNA was 600–650 nm and the loading efficiency was greater than 90%. On the basis of the results of the plasmid DNA protection test, CADNs could protect the transgene from DNase I degradation. The transgene product expression could be enhanced efficiently if cells or tumor tissues were first given CADNs and then treated with ultrasound.

Conclusions

The use of CADNs combined with an ultrasound regimen is a promising method for safe and effective gene therapy. Copyright © 2009 John Wiley & Sons, Ltd.
Quantitative reconstruction of palaeoclimate from pollen profiles in northeastern Japan and the timing of a cold reversal event during the Last Termination
Authors: Yoshida Akihiro , Takeuti Sadako
Published: November 2009

We reconstructed quantified palaeoclimate changes within two Japanese pollen profiles spanning the Last Termination (LT; 18–10 cal. ka) in an attempt to better understand past monsoon activity. The reconstructed winter climate at the Tashiro mire, which is strongly influenced by the Siberian air mass, showed a weak and a short‐lived cooling event at 11.8–10.6 cal. ka. This event spans part of the Younger Dryas (YD) cooling event in the North Atlantic region, suggesting the latter influenced the Siberian high‐pressure system. In contrast, the summer climate at the Komado mire, which is more influenced by the Pacific air mass, experienced a strong and a prolonged cooling event at 15.5–13.0 cal. ka. The latter event is broadly synchronous with the Antarctica Cold Reversal (ACR) event, and suggests that the Pacific high‐pressure system weakened during this period. The pattern of climate change across East Asia shows that the YD event did not extend beyond the East Asian monsoon front, while the ACR event strongly affected the Pacific high‐pressure system during the LT. We suggest the East Asian monsoon front is an important geo‐climatic boundary between YD‐like and ACR‐like deglacial climate changes. Copyright © 2009 John Wiley & Sons, Ltd.
Synergistic Reinforcement of Highly Oriented Poly(propylene) Tapes by Sepiolite Nanoclay
Authors: Bilotti Emiliano , Deng Hua , Zhang Rui , Lu Dun , Bras Wim , Fischer Hartmut R. , Peijs Ton
Published: November 2009

This paper reports the properties of highly oriented nanocomposite tapes based on isotactic PP and needle‐like sepiolite nanoclay, obtained by a solid state drawing process. The intrinsic 1D character of sepiolite allows its exploitation in 1D objects, such as oriented polymer fibres and tapes, where it can be uniaxially oriented upon drawing. A synergistic increase in mechanical properties is presented for highly drawn tapes (λ ≤ 20) and low filler loadings (≤2.5 wt.‐%), which can not be simply explained by micromechanical composite models. Instead, mechanical properties are intimately related to the dispersion state of the nanoclays in PP, the rheological properties of the nanocomposites and the polymer morphology.

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Lysosomal destabilization and cathepsin B contributes for cytochrome c release and caspase activation in embelin‐induced apoptosis
Authors: Joy Beena , Sivadasan Rajeeve , Emilia Abraham T. , John Mohan , Sobhan Praveen K. , Seervi Mahendra , T.R. Santhoshkumar
Published: November 2009

XIAP is an important antiapoptotic protein capable of conferring resistance to cancer cells. Embelin, the small molecular inhibitor of XIAP, possesses wide spectrum of biological activities with strong inhibition of nuclear factor kappa B and downstream antiapoptotic genes. However, the mechanism of its cell death induction is not known. Our studies using colon cancer cells lacking p53 and Bax suggest that both lysosomes and mitochondria are prominent targets of embelin‐induced cell death. Embelin induced cell‐cycle arrest in G1 phase through p21, downstream of p53. In the absence of p21, the cells are sensitized to death in a Bax‐dependent manner. The loss of mitochondrial membrane potential induced by embelin was independent of Bax and p53, but lysosomal integrity loss was strongly influenced by the presence of p53 but not by Bax. Lysosomal role was further substantiated by enhanced cathepsin B activity noticed in embelin‐treated cells. p53‐dependent lysosomal destabilization and cathepsin B activation contribute for increased sensitivity of p21‐deficient cells to embelin with enhanced caspase 9 and caspase 3 activation. Cathepsin B inhibitor reduced cell death and cytochrome c release in embelin‐treated cells indicating lysosomal pathway as the upstream of mitochondrial death signaling. Deficiency of cell‐cycle arrest machinery renders cells more sensitive to embelin with enhanced lysosomal destabilization and caspase processing emphasizing its potential therapeutic importance to address clinical drug resistance. © 2009 Wiley‐Liss, Inc.
A comparison of the in vitro biotransformation of (–)‐epicatechin and procyanidin B2 by human faecal microbiota
Authors: Stoupi Stavroula , Williamson Gary , Drynan J. Warren , Barron Denis , Clifford Michael N.
Published: November 2009

The catabolism by human faecal microbiota of (–)‐epicatechin (1) (2, 3‐cis stereochemistry) and its dimer pure procyanidin B2 (2), has been compared using a static in vitro culture model. The catabolites were characterised by LC‐MSn, UV absorption and relative retention time, and quantified relative to standards. No more than ∼10% of procyanidin B2 (2) was converted to epicatechin (1) by scission of the interflavan bond. Five phenolic acid catabolites (Mr<290) were unique to 2, and ten phenolic acid catabolites (Mr<290) were common to both substrates. The dominant catabolites (≥24 h incubation) were 5‐(3′‐hydroxy phenyl) valeric acid (9), 3‐(3′‐hydroxyphenyl) propionic acid (10) and phenyl acetic acid (12) (maximum yields 27.4±4.2, 38.2±4.2, 22.7±2.9%, respectively, from 1 and 9.4±1.2, 52.8±2.1, 28.8±1.6%, respectively, from 2). Substrate 2 was degraded twice as rapidly as 1. Evidence is presented for the production of previously unreported catabolites of 2 that retain the flavanol A‐ring and the C4→C8 interflavan bond. It was confirmed that catabolism favoured removal of the 4′‐hydroxyl rather than the 3′‐hydroxyl group and that both β‐oxidation and α‐oxidation occurred.
A possible case of Scheuermann's disease from Akarçay Höyük, Birecik (Şanlıurfa, Turkey)
Authors: Üstündağ H. , Deveci A.
Published: November 2009

During excavations in Akarçay Höyük, located in Birecik (Şanlıurfa, Turkey), a human and a horse skeleton were found together as a co‐burial. This burial was in an Islamic cemetery dated to 13th–14th century AD. The human skeleton was that of a young adult female with a distinct thoracic kyphosis. Three adjacent thoracic vertebral bodies, T4, T5 and T6, were wedge shaped and this wedging was also apparent in radiographs. There were Schmorl's nodes and anterior extensions on the same vertebral bodies. All these vertebral changes are typical signs of Scheuermann's disease (SD). Since she was buried with a horse, it is likely that she was a horse rider. Although she was young, the skeletal changes associated with horse riding like elongated acetabula and enthesopathies on the femora were evident. There was a compression fracture on T12, and irregularities on the upper and lower vertebral body rims due to traumatic anterior disc herniation. It is postulated that a trauma due to horse riding is responsible for the occurrence of SD in this case. Copyright © 2009 John Wiley & Sons, Ltd.
Possible cases of scalping from pre‐hispanic highland Peru
Authors: Toyne J. Marla
Published: November 2009

For years, the pre‐Hispanic Chachapoya of Northern Peru have been described as the ‘Warriors of the Clouds’. A more detailed look at newly excavated osteological samples from the highland site of Kuelap allows us to better examine the types of traumatic injuries among the Chachapoya. This paper describes an individual with evidence of a recent scalp removal including cut marks encircling the vault and a large area of active inflammatory response due to exposure of the outer table. The degree of osseous response and a small area of healing indicate short‐term survival. A second fragmentary skull demonstrates similar features but more advanced healing. The location and patterning of the cut marks are consistent with North American Indian pre‐historic and historic cases of scalping. The skulls of these two individuals provide the first osteological evidence of scalp removal from a pre‐Hispanic South American Andean context, although it is difficult to determine the motivation whether for therapeutic treatment or trophy taking. These cases, along with other evidence of interpersonal violence and cranial trauma, serve to elucidate the possible volatile nature of cultural contact between this region and lowland Amazonian tribes, where scalps and trophy heads were commonly taken in raids. Copyright © 2009 John Wiley & Sons, Ltd.
Proteomics reveal tissue‐specific features of the cress (Lepidium sativum L.) endosperm cap proteome and its hormone‐induced changes during seed germination
Authors: Müller Kerstin , Job Claudette , Belghazi Maya , Job Dominique , Leubner‐Metzger Gerhard
Published: November 2009

Mature angiosperm seeds consist of an embryo surrounded by the endosperm and the testa. The endosperm cap that covers the radicle plays a regulatory role during germination and is a major target of abscisic acidinduced inhibition of germination. Cress (Lepidium sativum) is a close relative of the model plant Arabidopsis thaliana (Arabidopsis). Cress seeds offer the unique possibility of performing tissue‐specific proteomics due to their larger size while benefiting the genomic tools available for Arabidopsis. This work provides the first description of endosperm cap proteomics during seed germination. An analysis of the proteome of the cress endosperm cap at key stages during germination and after radicle protrusion in the presence and absence of abscisic acid led to the identification of 144 proteins, which were clustered by the changes in their abundances and categorized by function. Proteins with a function in energy production, protein stability and stress response were overrepresented among the identified endosperm cap proteins. This strongly suggests that the cress endosperm cap is not a storage tissue as the cereal endosperm but a metabolically very active tissue regulating the rate of radicle protrusion.
Patterns in vegetation composition, surface height and thaw depth in polygon mires in the Yakutian Arctic (NE Siberia): a microtopographical characterisation of the active layer
Authors: Minke Merten , Donner Norman , Karpov Nikolay , de Klerk Pim , Joosten Hans
Published: November 2009

Mapping of two low‐centred ice‐wedge polygons in the Yakutian tundra (NE Siberia) along a regular grid with 1‐m spacing revealed large spatial variability in thaw depths and strong correlation with relief, water and vegetation. Average thaw depths in polygon ridges (23 cm and 31 cm) were smaller than in depressions (33 cm and 40 cm, respectively). The greatest thaw depths, however, were also found in the ridges and probably result from thermal erosion by water flow. Copyright © 2009 John Wiley & Sons, Ltd.
Rockfall activity in the Kangchenjunga area, Nepal Himalaya
Authors: Regmi Dhananjay , Watanabe Teiji
Published: November 2009

Rockfall activity and related environmental factors (i.e. bedrock thermal regime and precipitation) were monitored through most of one year at elevations between 4600 m and 6800 m in the Kangchenjunga valley of the Nepal Himalaya to identify rockfall dynamics, estimate rockfall frequency for different aspects, and assess temporal and spatial variations in rockfall activity. Rockfall activity on north‐facing slopes is mainly controlled by insolation relating to solar elevation and showed an abrupt increase in the pre‐monsoon season. Rockfall activity on east‐, west‐ and south‐facing slopes is controlled by the duration and effectiveness of sunshine and accumulation of snow. The north‐facing slope has a small diurnal range of rock surface temperatures and exhibits seasonal freeze‐thaw, whereas the other aspects show frequent diurnal freeze‐thaw. These differences result in seasonal rockfall activity on the north‐facing slope and the infrequent release of large debris and year‐round rockfall activity on the other aspects. Copyright © 2009 John Wiley & Sons, Ltd.
Using the MODIS land surface temperature product for mapping permafrost: an application to northern Québec and Labrador, Canada
Authors: Hachem Sonia , Allard Michel , Duguay Claude
Published: November 2009

The Land Surface Temperature (LST) products of the Moderate Resolution Imaging Spectroradiometers (MODIS) aboard NASA's Terra and Aqua satellites were used to develop maps of annual near‐surface temperatures for comparison with the spatial distribution of permafrost and boundaries of the permafrost zones. The methodological approach involved fitting a sinusoidal model over the daily LST readings to reproduce seasonal thermal variations near the ground for each 1‐km2 pixel. Calculations of mean annual surface temperatures and of thawing and freezing indices led to the development of regional maps, in this case for northern Québec and Labrador. The maps show the expected geographic distribution of near‐surface temperatures and acceptably represent known permafrost boundaries. Ongoing efforts to incorporate snow and vegetation cover from complementary remotely sensed data should improve the ground surface temperature mapping capability based on this approach. Copyright © 2009 John Wiley & Sons, Ltd.
Cellular uptake and biological activity of peptide nucleic acids conjugated with peptides with and without cell‐penetrating ability
Authors: Turner Yvonne , Wallukat Gerd , Säälik Pille , Wiesner Burkhard , Pritz Stephan , Oehlke Johannes
Published: November 2009

A 12‐mer peptide nucleic acid (PNA) directed against the nociceptin/orphanin FQ receptor mRNA was disulfide bridged with various peptides without and with cell‐penetrating features. The cellular uptake and the antisense activity of these conjugates were assessed in parallel. Quantitation of the internalized PNA was performed by using an approach based on capillary electrophoresis with laser‐induced fluorescence detection (CE‐LIF). This approach enabled a selective assessment of the PNA moiety liberated from the conjugate in the reducing intracellular environment, thus avoiding bias of the results by surface adsorption. The biological activity of the conjugates was studied by an assay based on the downregulation of the nociceptin/orphanin FQ receptor in neonatal rat cardiomyocytes (CM). Comparable cellular uptake was found for all conjugates and for the naked PNA, irrespective of the cell‐penetrating properties of the peptide components. All conjugates exhibited a comparable biological activity in the 100 nMrange. The naked PNA also exhibited extensive antisense activity, which, however, proved about five times lower than that of the conjugates. The found results suggest cellular uptake and the bioactivity of PNA‐peptide conjugates to be not primarily related to the cell‐penetrating ability of their peptide components. Likewise from these results it can be inferred that the superior bioactivity of the PNA‐peptide conjugates in comparison with that of naked PNA rely on as yet unknown factors rather than on higher membrane permeability. Several hints point to the resistance against cellular export and the aggregation propensity combined with the endocytosis rate to be candidates for such factors. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.
Blinded sample size recalculation for clinical trials with normal data and baseline adjusted analysis
Authors: Friede Tim , Kieser Meinhard
Published: November 2009

Baseline adjusted analyses are commonly encountered in practice, and regulatory guidelines endorse this practice. Sample size calculations for this kind of analyses require knowledge of the magnitude of nuisance parameters that are usually not given when the results of clinical trials are reported in the literature. It is therefore quite natural to start with a preliminary calculated sample size based on the sparse information available in the planning phase and to re‐estimate the value of the nuisance parameters (and with it the sample size) when a portion of the planned number of patients have completed the study. We investigate the characteristics of this internal pilot study design when an analysis of covariance with normally distributed outcome and one random covariate is applied. For this purpose we first assess the accuracy of four approximate sample size formulae within the fixed sample size design. Then the performance of the recalculation procedure with respect to its actual Type I error rate and power characteristics is examined. The results of simulation studies show that this approach has favorable properties with respect to the Type I error rate and power. Together with its simplicity, these features should make it attractive for practical application. Copyright © 2009 John Wiley & Sons, Ltd.
Inhibitory effect of the cree traditional medicine wiishichimanaanh (Vaccinium vitis‐idaea) on advanced glycation endproduct formation: identification of active principles
Authors: Beaulieu Louis‐Philippe , Harris Cory S. , Saleem Ammar , Cuerrier Alain , Haddad Pierre S. , Martineau Louis C. , Bennett Steffany A.L. , Arnason John T.
Published: November 2009

Like many aboriginal populations, First Nations communities such as the Cree of Eeyou Istchee are facing continuously increasing rates of diabetes and related complications. Advanced glycation endproducts (AGEs), which readily form and accumulate with sustained hyperglycemia, contribute to the development of diabetic complications and, as such, are considered a potential therapeutic target. In the present study, the inhibition of AGE formation by ethanolic extracts of the Cree medicinal plant Vaccinium vitis‐idaea L. was assessed by fluorometric detection of fluorescent AGEs and immunodetection of Nϵ‐(carboxymethyl)lysine adducts of albumin. Extracts from V. vitis‐idaea berries demonstrated a concentration‐dependent inhibition of AGE formation in both measures. High performance liquid chromatography mass spectrometry (HPLC/MS) identified nine main phenolic constituents. Four were selected for further testing, of which catechin, quercetin‐3‐O‐galactoside and cyanidin‐3‐O‐glucoside but not para‐coumaric acid displayed antiglycation activities. These results demonstrate that the flavonoid components of the berry extract are potent antiglycation agents and provide pharmacological validation for the traditional use of V. vitis‐idaea as an antidiabetic remedy. Copyright © 2009 John Wiley & Sons, Ltd.
Suppression of inducible nitric oxide synthase expression by furfuran lignans from flower buds of Magnolia fargesii in BV‐2 microglial cells
Authors: Kim Ji Sun , Kim Jae Yeon , Lee Hwa Jin , Lim Hyo Jin , Lee Da Yeon , Kim Do Hee , Ryu Jae‐Ha
Published: November 2009

Activated microglia produces diverse neurotoxic factors such as nitric oxide (NO) and tumor necrosis factor‐α that serve as apoptotic inducers resulting in various neurodegenerative diseases. The inhibition of microglia‐derived NO production by inducible nitric oxide synthase (iNOS) has been reported to be beneficial in retarding neurodegenerative disorders. Three active lignans have been isolated from the flower buds of Magnolia fargesii by the bioassay‐guided fractionation using lipopolysaccharide (LPS)‐activated BV‐2 microglial cell culture system. The structures of them were identified as kobusin (1), aschantin (2) and fargesin (3) by the analyses of spectroscopic data. They inhibited the production of NO by activated microglia. Their IC50 values were 21.8 ± 3.7, 14.8 ± 2.5 and 10.4 ± 2.8 μg/mL, respectively. They suppressed LPS‐induced NF‐κB activation and the expression of iNOS protein and mRNA. Furthermore, they showed scavenging activity of neurotoxic peroxynitrite that can be produced by NO and superoxide anion. These results imply that lignans from Magnolia fargesii might be beneficial for the treatment of neuro‐inflammatory diseases through the inhibition of iNOS expression and peroxynitrite scavenging potential. Copyright © 2009 John Wiley & Sons, Ltd.
Neuroprotective and neurochemical properties of mint extracts
Authors: López Víctor , Martín Sara , Gómez‐Serranillos Maria Pilar , Carretero Maria Emilia , Jäger Anna K. , Calvo Maria Isabel
Published: November 2009

Mints are aromatic plants with a tradition as medicinal remedies and culinary herbs. With the aim of investigating potential central nervous system (CNS) activities of traditional medicinal plants, four species and one hybrid of the genus Mentha (M. aquatica, M. longifolia, M. pulegium, M. suaveolens and M. × piperita) were selected. Methanolic extracts of the plants were tested for protective effects against hydrogen‐peroxide‐induced toxicity in PC12 cells, antioxidant activity (by ABTS and X/XO methods) and neurochemical properties (MAO‐A inhibition, AChE inhibition and affinity to the GABAA receptor). Mentha × piperita and Mentha aquatica produced significant (p < 0.05) protection of the PC12 cells against oxidative stress. All the plants exhibited antioxidant and MAO‐A inhibitory activities, M. × piperita being the most active. M. aquatica showed the highest affinity to the GABAA‐receptor assay. Results demonstrate that mints might have effect on the CNS. Copyright © 2009 John Wiley & Sons, Ltd.
Prophylaxis with Centella asiatica confers protection to prepubertal mice against 3‐nitropropionic‐acid‐induced oxidative stress in brain
Authors: Shinomol George K. , Ravikumar Hosamani , Muralidhara
Published: November 2009

While the usage of Centella asiatica (CA) is on the increase worldwide, evidence demonstrating its protective efficacy against neurotoxicants is scarce. Hence the present study aimed to understand the neuroprotective efficacy of a standardized aqueous extract of CA against 3‐nitropropionic‐acid(3‐NPA)‐induced oxidative stress in the brain of prepubertal mice. We assessed the degree of oxidative stress in cytoplasm of brain regions of male mice (4 wk‐ old) given CA prophylaxis (5 mg/kg bw) for 10 days followed by 3‐NPA administration (i.p.75 mg/kg bw) on the last 2 days. The neurotoxicant elicited marked oxidative stress in the brain of untreated mice as evident by enhanced malondialdehyde levels, reactive oxygen species (ROS) generation, hydroperoxides and protein carbonyls (a measure of protein oxidation) in striatum and other regions (cortex, cerebellum and hippocampus), while CA prophylaxis completely ameliorated the 3‐NPA‐ induced oxidative stress. Depletion of glutathione (GSH) levels, total thiols, perturbations in antioxidant enzymes and cholinergic enzymes in brain discernible among 3‐NPA‐treated mice were predominantly restored to normalcy with CA prophylaxis. It is hypothesized that the prophylactic protection offered by CA extract against neurotoxicant exposure may be largely due to its ability to enhance GSH, thiols and antioxidant defenses in the brain of prepubertal mice. Copyright © 2009 John Wiley & Sons, Ltd.
Increased vascular permeability, angiogenesis and wound healing induced by the serum of natural latex of the rubber tree Hevea brasiliensis
Authors: Mendonça Ricardo José , Maurício Vanessa Beatriz , de Bortolli Teixeira Larissa , Lachat João José , Coutinho‐Netto Joaquim
Published: November 2009

Increases in vascular permeability and angiogenesis are crucial events to wound repair, tumoral growth and revascularization of tissues submitted to ischemia. An increased vascular permeability allows a variety of cytokines and growth factors to reach the damaged tissue. Nevertheless, the angiogenesis supply tissues with a wide variety of nutrients and is also important to metabolites clearance. It has been suggested that the natural latex from Hevea brasiliensis showed wound healing properties and angiogenic activity. Thus, the purpose of this work was to characterize its angiogenic activity and its effects on vascular permeability and wound healing. The serum fraction of the latex was separated from the rubber with reduction of the pH. The activity of the dialyzed serum fraction on the vascular permeability injected in subcutaneous tissue was assayed according Mile's method. The angiogenic activity was determined using a chick embryo chorioallantoic membrane assay and its effects on the wound‐healing process was determined by the rabbit ear dermal ulcer model. The serum fraction showed evident angiogenic effect and it was effective in enhancing vascular permeability. In dermal ulcers, this material significantly accelerated wound healing. Moreover, the serum fraction boiled and treated with proteases lost these activities. These results are in accordance with the enhancement of wound healing observed in clinical trials carried out with a biomembrane prepared with the same natural latex. Copyright © 2009 John Wiley & Sons, Ltd.
Effects of the aqueous extract of Salvia Miltiorrhiza (danshen) and its magnesium tanshinoate B‐enriched form on blood pressure
Authors: Leung S.W.S. , Zhu D‐Y. , Man R.Y.K.
Published: November 2009

Danshen is the dried root and rhizome of the Chinese medicinal plant Salvia miltiorrhiza Bunge (Labiatae), which has been used to treat hypertension and myocardial infarction. One of its water‐soluble active components is magnesium tanshinoate B (MTB). The present study examined and compared the cardiovascular effects of the water‐soluble extract of danshen (SME) and its MTB‐enriched form (containing 70% of MTB (MTB70)). Anaesthetized rats were infused intravenously with saline or phenylephrine to achieve a normal or elevated blood pressure, respectively. Different doses of SME, MTB70 or vehicle were then injected intravenously and their effect on blood pressure was monitored. The results indicate that SME and MTB70 reduce blood pressure dose‐dependently. Independently of the initial blood pressure, SME caused a smaller reduction in blood pressure than MTB70. In rats infused with phenylephrine, MTB70 caused greater decreases in blood pressure than in rats infused with saline, while the responses to SME did not differ between the two groups. From these findings, it appears that MTB is one of the major components responsible for the cardiovascular effects of danshen, and that the beneficial cardiovascular effect of the extract is more prominent under conditions of elevated blood pressure. Copyright © 2009 John Wiley & Sons, Ltd.
Quantitative Structure‐Retention Relationship Study of Mercapto‐Compounds by the Method of Dividing the Molecular Structure into Substructure
Authors: Liu Fengping , Cao Chenzhong , Li Xun
Published: November 2009

In order to investigate the quantitative structure‐retention relationship in gas chromatography (GC) of mercapto‐esters, alcohols, aldehydes, and ketones, the molecular structure RX is divided into two parts, R and X to generate structural parameter. It was proposed that the retention index (RI) is affected by three main factors for mercapto‐compounds: alkyl group R, substituted group X, and interaction between R and X. On the basis of the PEI index previously developed by Cao, the novel total polarizability effect index (TPEI) combining with odd‐even index (OEI) previously developed in our team, were used to predict the RI of mercapto‐compounds. A high quality model (R2=0.9839, s=23.5, F=1432.2) was generated using only calculated descriptors and multiple linear regression techniques. Good results were also obtained for the external data set.
Statistical design for a small serial dilution series
Authors: Zelterman Daniel , Tulupyev Alexander , Heimer Robert , Abdala Nadia
Published: November 2009

We describe statistical plans for a serial dilution series designed to detect and estimate the number of viral particles in a solution. The design addresses a problem when a very limited number of aliquots are available for proliferation. A gamma prior distribution on the number of viral particles allows us to describe the marginal probability distribution of all experimental outcomes. We examine a design that minimizes the expected reciprocal information and compare this with the maximum entropy design. We argue that the maximum entropy design is more useful from the point of view of the laboratory technician. The problem and design are motivated by our study of the viability of human immunodeficiency virus in syringes and other equipment that might mediate blood‐borne viral transmission. Copyright © 2009 John Wiley & Sons, Ltd.
Assessing coping strategies by analysing expressive writing samples
Authors: Lee Hyoung S. , Cohn Lawrence D.
Published: November 2009

This study examined whether coping style can be assessed using a text analysis of expressive writing samples. Participants (n = 153) wrote about a stressful college experience and then completed a depression scale and three coping measures, including the COPE. Writing samples were analysed using Pennebaker's Linguistic Inquiry and Word Count computer programme. Depression scores were related to the use of words denoting negative emotions but were unrelated to the use of the pronoun ‘I’. Respondents who used more words denoting negative emotions in their essays obtained lower problem‐focused coping scores on the COPE. The use of insight‐related words was associated with lower scores on measures of emotion‐focused coping. Copyright © 2009 John Wiley & Sons, Ltd.
Surface Dependence of Protein Nanocrystal Formation
Authors: Lopez Aitziber Eleta , Moreno‐Flores Susana , Pum Dietmar , Sleytr Uwe B. , Toca‐Herrera José L.
Published: November 2009

The self‐assembly kinetics and nanocrystal formation of the bacterial surface‐layer‐protein SbpA are studied with a combination of quartz crystal microbalance with dissipation monitoring (QCM‐D) and atomic force microscopy (AFM). Silane coupling agents, aminopropyltriethoxysilane (APTS) and octadecyltrichlorosilane (OTS), are used to vary the protein–surface interaction in order to induce new recrystallization pathways. The results show that the final S‐layer crystal lattice parameters (a = b = 14 nm, γ = 90°), the layer thickness (15 nm), and the adsorbed mass density (1700 ng cm−2) are independent of the surface chemistry. Nevertheless, the adsorption rate is five times faster on APTS and OTS than on SiO2, strongly affecting protein nucleation and growth. As a consequence, protein crystalline domains of 0.02 µm2 for APTS and 0.05 µm2 for OTS are formed, while for silicon dioxide the protein domains have a typical size of about 32 µm2. In addition, more‐rigid crystalline protein layers are formed on hydrophobic substrates. In situ AFM experiments reveal three different kinetic steps: adsorption, self‐assembly, and crystalline‐domain reorganization. These steps are corroborated by frequency–dissipation curves. Finally, it is shown that protein adsorption is a diffusion‐driven process. Experiments at different protein concentrations demonstrate that protein adsorption saturates at 0.05 mg mL−1 on silane‐coated substrates and at 0.07 mg mL−1 on hydrophilic silicon dioxide.
Imaging Individual Proteins and Nanodomains on Intact Cell Membranes with a Probe‐Based Optical Antenna
Authors: van Zanten Thomas S. , Lopez‐Bosque Maria J. , Garcia‐Parajo Maria F.
Published: November 2009

Optical antennas that confine and enhance electromagnetic fields in a nanometric region hold great potential for nanobioimaging and biosensing. Probe‐based monopole optical antennas are fabricated to enhance fields localized to <30 nm near the antenna apex in aqueous conditions. These probes are used under appropriate excitation antenna conditions to image individual antibodies with an unprecedented resolution of 26 ± 4 nm and virtually no surrounding background. On intact cell membranes in physiological conditions, the obtained resolution is 30 ± 6 nm. Importantly, the method allows individual proteins to be distinguished from nanodomains and the degree of clustering to be quantified by directly measuring physical size and intensity of individual fluorescent spots. Improved antenna geometries should lead to true live cell imaging below 10‐nm resolution with position accuracy in the subnanometric range.
Rattle‐Type Fe3O4@SiO2 Hollow Mesoporous Spheres as Carriers for Drug Delivery
Authors: Zhu Yufang , Ikoma Toshiyuki , Hanagata Nobutaka , Kaskel Stefan
Published: November 2009

Rattle‐type Fe3O4@SiO2 hollow mesoporous spheres with different particle sizes, different mesoporous shell thicknesses, and different levels of Fe3O4 content are prepared by using carbon spheres as templates. The effects of particle size and concentration of Fe3O4@SiO2 hollow mesoporous spheres on cell uptake and their in vitro cytotoxicity to HeLa cells are evaluated. The spheres exhibit relatively fast cell uptake. Concentrations of up to 150 µg mL−1 show no cytotoxicity, whereas a concentration of 200 µg mL−1 shows a small amount of cytotoxicity after 48 h of incubation. Doxorubicin hydrochloride (DOX), an anticancer drug, is loaded into the Fe3O4@SiO2 hollow mesoporous spheres, and the DOX‐loaded spheres exhibit a somewhat higher cytotoxicity than free DOX. These results indicate the potential of Fe3O4@SiO2 hollow mesoporous spheres for drug loading and delivery into cancer cells to induce cell death.
Multifunctional Magnetic–Optical Nanoparticle Probes for Simultaneous Detection, Separation, and Thermal Ablation of Multiple Pathogens
Authors: Wang Chungang , Irudayaraj Joseph
Published: November 2009

Multifunctional nanoparticles possessing magnetization and near‐infrared (NIR) absorption have warranted interest due to their significant applications in magnetic resonance imaging, diagnosis, bioseparation, target delivery, and NIR photothermal ablation. Herein, the site‐selective assembly of magnetic nanoparticles onto the ends or ends and sides of gold nanorods with different aspect ratios (ARs) to create multifunctional nanorods decorated with varying numbers of magnetic particles is described for the first time. The resulting hybrid nanoparticles are designated as Fe3O4AurodFe3O4 nanodumbbells and Fe3O4Aurod necklacelike constructs with tunable optical and magnetic properties, respectively. These hybrid nanomaterials can be used for multiplex detection and separation because of their tunable magnetic and plasmonic functionality. More specifically, Fe3O4Aurod necklacelike probes of different ARs are utilized for simultaneous optical detection based on their plasmon properties, magnetic separation, and photokilling of multiple pathogens from a single sample at one time. The combined functionalities of the synthesized probes will open up many exciting opportunities in dual imaging for targeted delivery and photothermal therapy.