bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Oxidative Stress, Antioxidant and Thyroid Hormone Status in Patients with Diabetes Mellitus
Authors: Pasupathi P , Chandrasekar V , Kumar U Senthil
Published: July 2009

Oxidative stress is currently suggested as mechanism underlying diabetes and diabetic complications. The aim of the study was to evaluate the magnitude of oxidative stress in patients with diabetes by measuring the lipid peroxidation as well as the status of the antioxidant defense system, thyroid hormones status and other biochemical variables. The study population consisted of 100 subjects divided into two groups viz. diabetic (n=50) and healthy controls (n=50). Changes in the levels of lipid peroxidation and antioxidants and thyroid hormones status were determined in diabetic and non-diabetic subjects. The level of thiobarbituric acid reactive substances (TBARS) was found to be increased significantly in diabetic patients compared to healthy controls. On the other hand, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), reduced glutathione (GSH), vitamin A, vitamin E and vitamin C were found to be decreased significantly in diabetics when compared to control subjects. We also noticed a marked increase in serum total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and decrease in highdensity lipoprotein cholesterol (HDL-C), total protein and albumin in diabetic patients. The level of TSH was significantly decreased whereas the levels of T4 and FT4 were significantly increased in diabetic patients than the control subjects. However, the T3 and FT3 levels did not differ significantly between groups. Our findings indicate that changes in oxidant and antioxidant equilibrium will have biological and possibly pathological role in the development of secondary complications. It also demonstrate that detection of thyroid hormone status in the early stage of the disease will help the patients to improve quality of life and reduce the morbidity rate. Key Words: Diabetes mellitus, Oxidative stress, Lipid peroxidation, Antioxidant status, Thyroid hormones.   doi: 10.3329/jom.v10i2.2816 J MEDICINE 2009; 10 : 60-66
A Study on the Applicability of Kinetic Models for Shenfu Coal Char Gasification with CO2 at Elevated Temperatures
Authors: Wu Youqing , Wu Shiyong , Gao Jinsheng
Published: July 2009

In this paper, measurements of the CO2 gasification kinetics for two types of Shenfu coal chars, which were respectively prepared by slow and rapid pyrolysis at temperatures of 950 °C and 1,400 °C, were performed by an isothermal thermo-gravimetric analysis under ambient pressure and elevated temperature conditions. Simultaneously, the applicability of the kinetic model for the CO2 gasification reaction of Shenfu coal chars was discussed. The results showed: (i) the shrinking un-reacted core model was not appropriate to describe the gasification reaction process of Shenfu coal chars with CO2 in the whole experimental temperature range; (ii) at the relatively low temperatures, the modified volumetric model was as good as the random pore model to simulate the CO2 gasification reaction of Shenfu coal chars, while at the elevated temperatures, the modified volumetric model was superior to the random pore model for this process; (iii) the integral expression of the modified volumetric model was more favorable than the differential expression of that for fitting the experimental data. Moreover, by simply introducing a function: A = A★exp(ft), it was found that the extensive model of the modified volumetric model could make much better predictions than the modified volumetric model. It was recommended as a convenient empirical model for comprehensive simulation of Shenfu coal char gasification with under conditions close to those of entrained flow gasification.
Recent Development of Nano-Materials Used in DNA Biosensors
Authors: Xu Kai , Huang Junran , Ye Zunzhong , Ying Yibin , Li Yanbin
Published: July 2009

As knowledge of the structure and function of nucleic acid molecules has increased, sequence-specific DNA detection has gained increased importance. DNA biosensors based on nucleic acid hybridization have been actively developed because of their specificity, speed, portability, and low cost. Recently, there has been considerable interest in using nano-materials for DNA biosensors. Because of their high surface-to-volume ratios and excellent biological compatibilities, nano-materials could be used to increase the amount of DNA immobilization; moreover, DNA bound to nano-materials can maintain its biological activity. Alternatively, signal amplification by labeling a targeted analyte with nano-materials has also been reported for DNA biosensors in many papers. This review summarizes the applications of various nano-materials for DNA biosensors during past five years. We found that nano-materials of small sizes were advantageous as substrates for DNA attachment or as labels for signal amplification; and use of two or more types of nano-materials in the biosensors could improve their overall quality and to overcome the deficiencies of the individual nano-components. Most current DNA biosensors require the use of polymerase chain reaction (PCR) in their protocols. However, further development of nano-materials with smaller size and/or with improved biological and chemical properties would substantially enhance the accuracy, selectivity and sensitivity of DNA biosensors. Thus, DNA biosensors without PCR amplification may become a reality in the foreseeable future.
Taxonomical notes on the Sicilian populations of Asperula gussonei (Rubiaceae): A. peloritana sp. nov.
Authors: Brullo Cristian , Brullo Salvatore , Giusso del Galdo Gian Pietro , Scuderi Leonardo
Published: July 2009

Taxonomical investigation on Asperula gussonei, a rare Sicilian endemism, allowed us to verify that the Madonie population is well differentiated from the Mt. Scuderi one. These two populations are here treated as distinct species: A. gussonei Boiss. from Madonie and A. peloritana sp. nov. from Mt. Scuderi. The main morphological and ecological differences between the two species are pointed out. Their iconographies and relationships with the allied species are given too.
Taxonomic review of the genus Crambe sect. Crambe (Brassicaceae, Brassiceae)
Authors: Prina Aníbal Óscar
Published: July 2009

The systematics of the genus Crambe L. sect. Crambe is reviewed, within which 16 species and 5 infraspecific taxa are considered, which are distributed from E and N Europe to Central Asia. A key for their identification is provided, along with a brief description, synonyms, distribution and habitat of each taxon. The infrageneric systematics of Crambe is discussed briefly. The following new combinations are proposed: Crambe edentula var. glabrata (Freyn & Sintenis) Prina comb. nov. and C. orientalis subsp. sulphurea (Stapf ex O.E. Schulz) Prina stat. nov.
Vegetation of the gnamma of the Sierra de Guadarrama and La Serena (Spain)
Authors: Baonza Díaz Jorge
Published: July 2009

Weathering pits are wetlands of geomorphologic and biological interest, but this common fact is obscured by the different names used by biologists, such as the ambiguous name of rock pool. Aquatic or amphibious plant communities are known around the world, principally from SE North-America and Tropical Africa, but few are known from Spain. Here, I study the vegetation of weathering pits from two different localities: La Serena (Southweast Spain) and Sierra de Guadarrama (central Spain). Plant communities change with depth of water and depth of sediment in the weathering pits. Some of them are characterized by Crassula vaillantii or Isoetes velatum.
Mycobacterium abscessus Glycopeptidolipids Mask Underlying Cell Wall Phosphatidyl-myo-Inositol Mannosides Blocking Induction of Human Macrophage TNF-α by Preventing Interaction with TLR2
Authors: Rhoades Elizabeth R. , Archambault Angela S. , Greendyke Rebecca , Hsu Fong-Fu , Streeter Cassandra , Byrd Thomas F.
Published: July 2009

Mycobacterium abscessus causes disease in patients with structural abnormalities of the lung, and it is an emerging pathogen in patients with cystic fibrosis. Colonization of the airways by nontuberculous mycobacteria is a harbinger of invasive lung disease. Colonization is facilitated by biofilm formation, with M. abscessus glycopeptidolipids playing an important role. M. abscessus can transition between a noninvasive, biofilm-forming, smooth colony phenotype that expresses glycopeptidolipid, and an invasive rough colony phenotype that expresses minimal amounts of glycopeptidolipid and is unable to form biofilms. The ability of this pathogen to transition between these phenotypes may have particular relevance to lung infection in cystic fibrosis patients since the altered pulmonary physiology of these patients makes them particularly susceptible to colonization by biofilm-forming bacteria. In this study we demonstrate that rough variants of M. abscessus stimulate the human macrophage innate immune response through TLR2, while smooth variants do not. Temperature-dependent loss or physical removal of glycopeptidolipid from the cell wall of one of the smooth variants leads to TLR2 stimulation. This response is stimulated in part through phosphatidyl-myo-inositol mannosides that are present in the cell wall of both rough and smooth variants. Mannose-binding lectins bind to rough variants, but lectin binding to an isogenic smooth variant is markedly reduced. This suggests that glycopeptidolipid in the outermost portion of the M. abscessus cell wall masks underlying cell wall lipids involved in stimulating the innate immune response, thereby facilitating colonization. Conversely spontaneous “unmasking” of cell wall lipids may promote airway inflammation.
Flexible Stereospecific Interactions and Composition within Nucleoprotein Complexes Assembled on the TCRα Gene Enhancer
Authors: del Blanco Beatriz , Roberts Joseph L. , Zamarreño Noelia , Balmelle-Devaux Nadège , Hernández-Munain Cristina
Published: July 2009

During thymocyte maturation, enhancers of genes encoding for TCRδ (Tcrd) and TCRα (Tcra), Eδ8, and Eα, work as a developmental switch controlling transition from Tcrd to Tcra activity at the Tcrad locus. Previous experiments revealed that an Eα fragment, Tα1-Tα2, which constitutes a well-characterized compact nucleoprotein structure led to premature activation of V(D)J recombination compared with that observed for the entire Eα or Tα1-Tα4. These experiments indicated that Tα3-Tα4 collaborates with factors bound to Tα1-Tα2 for the strict developmental regulation of Tcra rearrangement. The compact enhanceosome created on Tα1-Tα2 explained the molecular basis for requirement of intact Tα2 TCF/LEF and ets sites for enhancer function. We have created a mutant version of Eα, EαMC, in which Eδ myb and runx sites have been substituted for Tα2 runx and ets sites, that argues against the notion of a requirement for strict Eα enhanceosome structure for function. EαMC resulted in a very potent enhancer indicating that stereospecific interactions among proteins that form an Eα enhanceosome are rather flexible. Activation of V(D)J recombination by EαMC during thymocyte development resulted, however, to be premature and indistinguishable from that of Tα1-Tα2. These results indicate that Tα3-Tα4 itself is not sufficient to impart a developmental delay to a chimeric “early” enhancer, and indicate the need for functional collaboration between Tα2 runx/ets sites binding proteins and proteins bound to Tα3-Tα4 for proper developmental activation. The possibility of assembly of distinct sets of proteins on Eα might represent a more flexible form of information processing during thymocyte development.
Glucocorticoids Induce Protein S-Dependent Phagocytosis of Apoptotic Neutrophils by Human Macrophages
Authors: McColl Aisleen , Bournazos Stylianos , Franz Sandra , Perretti Mauro , Morgan B. Paul , Haslett Christopher , Dransfield Ian
Published: July 2009

During resolution of an inflammatory response, recruited neutrophil granulocytes undergo apoptosis and are removed by tissue phagocytes before induction of secondary necrosis without provoking proinflammatory cytokine production and release. Promotion of physiological neutrophil clearance mechanisms may represent a viable therapeutic strategy for the treatment of inflammatory or autoimmune diseases in which removal of apoptotic cells is impaired. The mechanism underlying enhancement of macrophage capacity for phagocytosis of apoptotic cells by the powerful anti-inflammatory drugs of the glucocorticoid family has remained elusive. In this study, we report that human monocyte-derived macrophages cultured in the presence of dexamethasone exhibit augmented capacity for phagocytosis of membrane-intact, early apoptotic cells only in the presence of a serum factor. Our results eliminate a role for a number of potential opsonins, including complement, pentraxin-3, and fibronectin. Using ion-exchange and gel filtration chromatography, we identified a high molecular mass serum fraction containing C4-binding protein and protein S responsible for the augmentation of phagocytosis of apoptotic neutrophils. Because the apoptotic neutrophils used in this study specifically bind protein S, we suggest that glucocorticoid treatment of macrophages induces a switch to a protein S-dependent apoptotic cell recognition mechanism. Consistent with this suggestion, pretreatment of macrophages with Abs to Mer tyrosine kinase, a member of the Tyro3/Axl/Mer family of receptor tyrosine kinases, prevented glucocorticoid augmentation of phagocytosis. Induction of a protein S/Mer tyrosine kinase-dependent apoptotic cell clearance pathway may contribute to the potent anti-inflammatory effects of glucocorticoids, representing a potential target for promoting resolution of inflammatory responses.
Dying and Necrotic Neutrophils Are Anti-Inflammatory Secondary to the Release of α-Defensins
Authors: Miles Katherine , Clarke David J. , Lu Wuyuan , Sibinska Zaneta , Beaumont Paula E. , Davidson Donald J. , Barr Tom A. , Campopiano Dominic J. , Gray Mohini
Published: July 2009

Neutrophils are recruited to sites of injury but their timely removal is thought to be vital to prevent exacerbating inflammation. In addition, the recognition of apoptotic cells by cells of the innate immune system provides potent anti-inflammatory and anti-immunogenic signals. In this article, we describe how human neutrophils dying by apoptosis or necrosis release anti-inflammatory peptides, the α-defensins. This family of small cationic peptides effectively inhibits the secretion of multiple proinflammatory cytokines and NO from macrophages, the main innate immune cell found at sites of chronic inflammation. In addition, the systemic administration of necrotic neutrophil supernatants and α-defensins protects mice from a murine model of peritonitis. Hence. their effects may be far-reaching and serve to kill microbes while regulating a potentially tissue-destructive inflammatory response.
Cutting Edge: SWI/SNF Mediates Antisense Igh Transcription and Locus-Wide Accessibility in B Cell Precursors
Authors: Osipovich Oleg A. , Subrahmanyam Ramesh , Pierce Steven , Sen Ranjan , Oltz Eugene M.
Published: July 2009

The stepwise process of Ag receptor gene assembly, termed V(D)J recombination, is coordinated during lymphocyte development by sweeping changes in chromatin that permit or deny access to a single recombinase enzyme. We now show that switching/sucrose nonfermenting (SWI/SNF) chromatin remodeling complexes are recruited to the Igh locus by an enhancer-dependent process and that these complexes are essential for generating recombinase accessibility throughout the locus. Depletion of SWI/SNF in pro-B cells also inhibits antisense transcription through all clusters of Igh gene segments, a pioneering process that has been implicated in the initial opening of chromatin. We conclude that SWI/SNF complexes play multiple roles in Igh gene assembly, ranging from initial locus activation to the spreading and maintenance of chromatin accessibility over large VH, DH, and JH domains.
Cutting Edge: Necrosis Activates the NLRP3 Inflammasome
Authors: Li Hanfen , Ambade Aditya , Re Fabio
Published: July 2009

Cells undergoing necrosis release endogenous danger signals that possess proinflammatory potential. In this study we show that mature IL-1β and IL-18 are released by necrotic cells but not by apoptotic cells. We identify 7-bromoindirubin-3′-oxime, an indirubin oxime derivative that induces necrosis, as a potent inducer of caspase-1 activation and release of mature IL-1β and IL-18. Inflammasome activation was triggered by other necrosis-inducing treatments but was not observed in response to apoptosis-inducing stimuli. Necrosis-induced inflammasome activation was mediated by the NLRP3 and ASC molecules. Release of IL-18 and IL-1β in response to necrosis-inducing stimuli was observed in THP-1 macrophages and the MSTO-211H human mesothelioma cell line independently of LPS priming. Using the in vivo model of naphthalene-induced airway epithelial cell injury, we showed that necrosis activates the ASC inflammasome in vivo. Our study identifies a new mechanism through which necrosis generates proinflammatory molecules that contributes to the sterile inflammatory response.
Cutting Edge: Limiting MHC Class II Expression to Dendritic Cells Alters the Ability to Develop Th2- Dependent Allergic Airway Inflammation
Authors: Niu Naiqian , Laufer Terri , Homer Robert J. , Cohn Lauren
Published: July 2009

In allergic airway inflammation, dendritic cells (DCs) are required for Th2 generation, recruitment, and activation in the respiratory tract. DCs have been shown to be necessary and sufficient for the induction of Th1 immune responses. In Th2 immunity and allergic airway inflammation, the ability of a DC to function as the sole APC has not been tested. We show that CD11c/Aβb mice with MHC class II expression restricted to CD11c-expressing DCs develop airway neutrophilia rather than allergic airway inflammation. Although CD11c/Aβb mice are capable of Th2 recruitment and activation in the lung, Th2 priming in CD11c/Aβb mice results in IFN-γ production. Effective Th2 generation and allergic airway inflammation was achieved in CD11c/Aβb mice after treatment with anti-IFN-γ. These studies show that DCs alone cannot drive the development of Th2 cells but require an additional MHC class II signal to stimulate effective Th2 immunity.
K-12 Education in the United States: Should We Implement National Standards and Assessments?
Authors: McKinney Jessica
Published: July 2009

In the face of increasing technical demands from the international labor market, U.S. students' math and science scores indicate a competitive disadvantage. Presently, states and equivalent state-level units control content standards and assessments for all students, creating over 50 distinct systems of measuring student success. This paper examines the possible use of national-level standards and assessments and evaluates such a policy based on effectiveness, political feasibility, cost, and administrative feasibility. Instituting national standards and assessments for elementary and secondary students could improve the competitiveness of the workforce in the United States if the standards are set at rigorous levels.
Renewable Energy Policy and Politics: A Handbook for Decision-Making
Authors: Jones Derek
Published: July 2009

No abstract available.
The graphemic/motor frontal area Exner's area revisited
Authors: Roux Franck‐Emmanuel , Dufor Olivier , Giussani Carlo , Wamain Yannick , Draper Louisa , Longcamp Marieke , Démonet Jean‐François
Published: July 2009

Objective

In 1881, Exner first described a “graphic motor image center” in the middle frontal gyrus. Current psycholinguistic models of handwriting involve the conversion of abstract, orthographic representations into motor representations before a sequence of appropriate hand movements is produced. Direct cortical stimulation and functional magnetic resonance imaging (fMRI) were used to study the human frontal areas involved in writing.

Methods

Cortical electrical stimulation mapping was used intraoperatively in 12 patients during the removal of brain tumors to identify the areas involved in oral language (sentence reading and naming) and writing, and to spare them during surgery. The fMRI activation experiment involved 12 right‐handed and 12 left‐handed healthy volunteers using word dictation (without visual control) and 2 control tasks.

Results

Direct cortical electrical stimulation of restricted areas rostral to the primary motor hand area (Brodmann area [BA] 6) impaired handwriting in 6 patients, without disturbing hand movements or oral language tasks. In 6 other patients, stimulation of lower frontal regions showed deficits combining handwriting with other language tasks. fMRI also revealed selective activation during word handwriting in left versus right BA6 depending on handedness. This area was anatomically matched to those areas that affected handwriting on electrical stimulation.

Interpretation

An area in middle frontal gyrus (BA6) that we have termed the graphemic/motor frontal area supports bridging between orthography and motor programs specific to handwriting. Ann Neurol 2009;66:537–545
Back‐propagation artificial neural network and attenuated total reflectance‐Fourier transform infrared spectroscopy for diagnosis of basal cell carcinoma by blood sample analysis
Authors: Khanmohammadi Mohammadreza , Garmarudi Amir Bagheri , Ghasemi Keyvan
Published: July 2009

A diagnostic method for the cancer, based on investigation of infrared spectra of blood samples, has been developed. The two‐layer modified principal component feed forward back‐propagation artificial neural network (BP‐ANN) was used to classify the attenuated total reflectance‐Fourier transform infrared (ATR‐FTIR) spectra of blood samples obtained from healthy people and those with basal cell carcinoma (BCC). Results showed 98.33% of accuracy, in comparison with the current clinical methods. In the first step, 20 blood samples (10 normal and 10 cancer cases) were applied to construct the calibration model. Spectroscopic studies were performed in 900–1800 cm−1 spectral region with 3.85 cm−1 data space. In order to modify the capability of ANN in prediction of test samples, two different algorithms were applied. The obtained results confirmed the compatibility of the proposed network with the architecture of 20‐8‐2 (input‐hidden‐output) with the pattern model. It was concluded that analysis of blood samples by ATR‐FTIR spectroscopy and ANN chemometric technique would be a reliable approach for detection of BCC. Copyright © 2009 John Wiley & Sons, Ltd.
Functionalization of Dihalophenylboronic Acids by Deprotonation of Their N‐Butyldiethanolamine Esters
Authors: Durka Krzysztof , Kurach Paweł , Luliński Sergiusz , Serwatowski Janusz
Published: July 2009

Deprotonative lithiation of various 6‐butyl‐2‐(dihalophenyl)‐(N–B)‐1,3,6,2‐dioxazaborocanes (N‐butyldiethanolamine esters of dihalophenylboronic acids) was investigated. It was found that selective transformations can be best achieved by use of LDA as the lithiating reagent. The reactivities of these compounds vary significantly, depending on the natures and positions of the halogen atoms. The resultant boron‐lithium bimetallic intermediates were subjected to reactions with electrophiles to afford functionalized halogenated arylboronic acids. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Enantiomeric separation by MEKC using dodecyl thioglycoside surfactants: Importance of an equatorially oriented hydroxy group at C‐2 position in separation of dansylated amino acids
Authors: Tano Chiharu , Son Sang‐Hyun , Furukawa Jun‐ichi , Furuike Tetsuya , Sakairi Nobuo
Published: July 2009

To investigate the influence of stereogenic centers of sugar‐based surfactants for enantiomeric separation, four n‐dodecyl thioglycoside sulfates (CMC 1.5–3.6 mM) were chosen as micelle‐forming surfactants and five dansylated hydrophobic amino acids were used as test analytes. The analytes were mutually separated by these micelles exhibiting almost similar migration times independent of the used surfactant. Baseline separations of all enantiomers were achieved using both β‐D‐glucose and β‐D‐galactose derivates that have an equatorially oriented hydroxy group at C‐2 position. In contrast, the ability of enantioseparation was markedly decreased in the case of β‐D‐mannose and 2‐deoxy‐β‐D‐glucose derivatives. These results suggested that the structure of C‐2 position of the sugar unit, namely presence of an equatorially oriented hydroxy group, is highly important for the enantiomeric separation of the chosen hydrophobic dansylated amino acids.
CE‐MS method development for peptides analysis, especially hepcidin, an iron metabolism marker
Authors: Martin Gaëlle B. , Mansion François , Servais Anne‐Catherine , Debrus Benjamin , Rozet Eric , Hubert Philippe , Crommen Jacques , Fillet Marianne
Published: July 2009

A method for the resolution of a peptides mixture including hepcidin‐25, an iron metabolism marker, was developed by CE‐ESI‐MS. Several strategies were tested to optimize peptide separation, such as the addition of cyclodextrins or organic solvents in the BGE or the use of coated capillaries. Best results in terms of resolution, symmetry and efficiency were obtained with a BGE made of 500 mM ammonium acetate pH 4.5/ACN 70:30 v/v. Using the methodology of experimental design, BGE concentration, sheath liquid composition and MS‐coupling parameters were then optimized in order to obtain the best signal intensity for hepcidin. Finally, a 225 mM BGE and a sheath liquid composed of isopropanol/water 80:20 v/v containing 0.5% v/v formic acid were selected as it constitutes the best compromise for selectivity, peak shape and sensitivity.
Analysis of γ‐globulin mobility on routine clinical CE equipment: Exploring its molecular basis and potential clinical utility
Authors: Vanderschaeghe Dieter , Debruyne Evi , Van Vlierberghe Hans , Callewaert Nico , Delanghe Joris
Published: July 2009

A study was conducted on the variability of γ‐globulin mobility in serum protein electrophoresis and its molecular basis. We found that the migration time of γ‐globulins can be reproducibly determined (CV=1.1%) on clinical CE equipment. Moreover, we found a significant difference (p<0.001) in the migration of γ‐globulins between chronic liver disease patients (n=98) and a healthy reference group (n=47). Serum immunoglobulins were purified from these patients' sera using protein L‐agarose and their glycosylation was studied using CE on a DNA sequencer. This glycomics approach revealed that several non‐sialylated N‐glycans show a moderate Pearson correlation coefficient (r=0.2–0.4) with the migration time of γ‐globulins. Their sialylated structures correlate negatively (r=−0.2 to −0.3). Immunoglobulins are significantly more sialylated in the healthy reference group compared with the patients (p<0.001). We estimated that sialylation heterogeneity contributes about 36% to the molecular variance (carbohydrates and amino acid composition) that affects the electrophoretic mobility of immunoglobulins. This is the first report on the migration time of γ‐globulins on a clinical CE instrument and its potential clinical value to the routinely analyzed serum protein CE profiles.
Vorinostat increases carboplatin and paclitaxel activity in non‐small cell lung cancer cells
Authors: Owonikoko Taofeek K. , Ramalingam Suresh S. , Kanterewicz Beatriz , Balius Trent E. , Belani Chandra P. , Hershberger Pamela A.
Published: July 2009

We observed a 53% response rate in non‐small cell lung cancer (NSCLC) patients treated with vorinostat plus paclitaxel/carboplatin in a Phase I trial. Studies were undertaken to investigate the mechanism (s) underlying this activity. Growth inhibition was assessed in NSCLC cells by MTT assay after 72 hr of continuous drug exposure. Vorinostat (1 μM) inhibited growth by: 17% ± 7% in A549, 28% ± 6% in 128‐88T, 39% ± 8% in Calu1 and 41% ± 7% in 201T cells. Vorinostat addition to carboplatin or paclitaxel led to significantly greater growth inhibition than chemotherapy alone in all 4 cell lines. Vorinostat (1 μM) synergistically increased the growth inhibitory effects of carboplatin/paclitaxel in 128‐88T cells. When colony formation was measured after drug withdrawal, vorinostat significantly increased the effects of carboplatin but not paclitaxel. The % colony formation was control 100%; 1 μM vorinostat, 83% ± 10%; 5 μM carboplatin, 41% ± 11%; carboplatin/vorinostat, 8% ± 4%; 2 nM paclitaxel, 53% ± 11%; paclitaxel/vorinostat, 46% ± 21%. In A549 and 128‐88T, vorinostat potentiated carboplatin induction of gamma‐H2AX (a DNA damage marker) and increased α‐tubulin acetylation (a marker for stabilized mictrotubules). In A549, combination of vorinostat with paclitaxel resulted in a synergistic increase in α‐tubulin acetylation, which reversed upon drug washout. We conclude that vorinostat interacts favorably with carboplatin and paclitaxel in NSCLC cells, which may explain the provocative response observed in our clinical trial. This likely involves a vorinostat‐mediated irreversible increase in DNA damage in the case of carboplatin and a reversible increase in microtubule stability in the case of paclitaxel.
Organic dyes as small molecule protein–protein interaction inhibitors for the CD40–CD154 costimulatory interaction
Authors: Buchwald Peter , Margolles‐Clark Emilio , Kenyon Norma S. , Ricordi Camillo
Published: July 2009

It is becoming increasingly clear that small molecules can often act as effective protein–protein interaction (PPI) inhibitors, an area of increasing interest for its many possible therapeutic applications. We have identified several organic dyes and related small molecules that (i) concentration‐dependently inhibit the important CD40–CD154 costimulatory interaction with activities in the low micromolar (µM) range, (ii) show selectivity toward this particular PPI, (iii) seem to bind on the surface of CD154, and (iv) concentration‐dependently inhibit the CD154‐induced B cell proliferation. They were identified through an iterative activity screening/structural similarity search procedure starting with suramin as lead, and the best smaller compounds, the main focus of the present work, achieved an almost 3‐fold increase in ligand efficiency (ΔG0/nonhydrogen atom = 0.8 kJ/NnHa) approaching the average of known promising small‐molecule PPI inhibitors (∼1.0 kJ/NnHa). Since CD154 is a member of the tumor necrosis factor (TNF) superfamily of cell surface interaction molecules, inhibitory activities on the TNF‐R1–TNF‐α interactions were also determined to test for specificity, and the compounds selected here all showed more than 30‐fold selectivity toward the CD40–CD154 interaction. Because of their easy availability in various structural scaffolds and because of their good protein‐binding ability, often explored for tissue‐specific staining and other purposes, such organic dyes can provide a valuable addition to the chemical space searched to identify small molecule PPI inhibitors in general. Copyright © 2009 John Wiley & Sons, Ltd.
VEGF‐D deficiency in mice does not affect embryonic or postnatal lymphangiogenesis but reduces lymphatic metastasis
Authors: Koch Marta , Dettori Daniela , Van Nuffelen An , Souffreau Joris , Marconcini Lucia , Wallays Goedele , Moons Lieve , Bruyère Françoise , Oliviero Salvatore , Noel Agnes , Foidart Jean‐Michel , Carmeliet Peter , Dewerchin Mieke
Published: July 2009

Vascular endothelial growth factor‐D (VEGF‐D) is one of the two ligands of the VEGFR‐3 receptor on lymphatic endothelial cells. Gene‐silencing studies in mice and Xenopus tadpoles recently showed that the role of endogenous VEGF‐D in lymphatic development is moderate. By contrast, exogenous VEGF‐D is capable of stimulating lymphangiogenesis. Nonetheless, its endogenous role in pathological conditions remains largely unknown. Hence, we reassessed its role in disease, using Vegf‐dnull mice. Vegf‐dnull mice were generated that, under physiological conditions, displayed normal embryonic and postnatal lymphangiogenesis and lymphatic remodelling, efficient lymphatic functioning and normal health. Vegf‐dnull mice also reponded normally in models of skin wound healing and healing of infarcted myocardium, despite enhanced expression of VEGF‐D in these models in wild‐type mice. In contrast, Vegf‐dnull mice displayed reduced peritumoral lymphangiogenesis and lymph node metastasis in an orthotopic pancreatic tumour model. Together, our data indicate that endogenous VEGF‐D in mice is dispensible for lymphangiogenesis during development, in postnatal and adult physiology and in several pathological conditions, but significantly contributes to lymphatic metastasis. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Familial small cell carcinoma of the ovary
Authors: Martinez‐Borges Anibal R. , Petty John K. , Hurt Gail , Stribling Jennifer T. , Press Joshua Z. , Castellino Sharon M.
Published: July 2009

Ovarian tumors have a low incidence in childhood, accounting for 1% of malignancies within the ages of 0–17 years. Small cell carcinoma of the ovary is a rare histology and historically has a poor prognosis. We report a case of an 11‐year‐old female diagnosed with small cell carcinoma of the ovary and hypercalcemia (SCCOHT). There was a strong family history of the disease, a reduction in the age of onset in the proband, and the absence of BRCA mutations. This case suggests the phenomenon of genetic anticipation in an ovarian cancer. Pediatr Blood Cancer 2009; 53:1334–1336. © 2009 Wiley‐Liss, Inc.
Lymphocytic vasculitis involving the central nervous system occurs in patients with X‐linked lymphoproliferative disease in the absence of Epstein–Barr virus infection
Authors: Talaat Kawsar R. , Rothman Jennifer A. , Cohen Jeffrey I. , Santi Mariarita , Choi John K. , Guzman Miguel , Zimmerman Robert , Nallasamy Sudha , Brucker Alexander , Quezado Martha , Pittaluga Stefania , Patronas Nicholas J. , Klion Amy D. , Nichols Kim E.
Published: July 2009

X‐linked lymphoproliferative disease (XLP) is an immunodeficiency caused by defects in the adaptor molecule SAP. The manifestations of XLP generally occur following Epstein–Barr virus (EBV) infection and include fulminant mononucleosis, hypogammaglobulinemia and lymphoma. In this report, we describe two unrelated patients with fatal T‐cell‐mediated central nervous system vasculitis for whom repeated serologic and molecular testing for EBV was negative. In both patients, clonal T‐cell populations were observed, but neither demonstrated evidence of lymphoma. Thus, loss of SAP function can lead to dysregulated immune responses characterized by the uncontrolled expansion and activation of T cells independent of EBV infection. Pediatr Blood Cancer 2009;53:1120–1123. © 2009 Wiley‐Liss, Inc.
Natural history and outcome of optic pathway gliomas in children
Authors: Nicolin Gary , Parkin Patricia , Mabbott Donald , Hargrave Darren , Bartels Ute , Tabori Uri , Rutka James , Buncic J. Raymond , Bouffet Eric
Published: July 2009

Background

The optimal management of optic pathway gliomas (OPGs) is complicated by their variable natural history, the association with neurofibromatosis type 1 (NF1) and difficulties in defining progression and response to treatment.

Methods

This study is a retrospective review of all children presenting to a single institution with an OPG between 1990 and 2004.

Results

Of the 133 children included, 78 (59%) had NF1; 87 (71 NF1) were observed initially, of whom 23 (11 NF1) subsequently required treatment. Forty‐six patients received immediate treatment. Initial treatment, without or with an observation period, comprised chemotherapy alone (32, 11 NF1); debulking + chemotherapy (15, 4 NF1); gross total resection (6); radiotherapy (2); debulking + radiotherapy (3); and debulking only (12, 3 NF1). Overall, 16 patients were irradiated during the study period. Four children died (overall survival at 5 and 10 years was 97.6% and 94.6% for those who required treatment). Progression‐free survival (PFS) for the 69 patients who needed treatment was 48%. There was no difference in PFS between chemotherapy versus chemotherapy + debulking or debulking alone. PFS for the NF1 patients who required treatment was similar to that of non‐NF1 patients. Mean follow‐up time was 9.0 (range 0.6–18.0, median 8.6) years.

Conclusions

The study confirms the complexity of OPGs and that NF1 is a major determinant of the resultant behavior of the tumor. Pediatr Blood Cancer 2009; 53:1231–1237. © 2009 Wiley‐Liss, Inc.
Role of Wnt inhibitory factor‐1 and Wnt/wingless signaling in choroid plexus tumors
Authors: Tomm Manuel , Koch Arend , Mertsch Sonja , Wrede Brigitte , Jeibmann Astrid , Wolff Johannes , Paulus Werner , Hasselblatt Martin
Published: July 2009

Little is known on pathways involved in the pathogenesis of choroid plexus tumors (CPTs). The finding of overexpression of Wnt inhibitory factor‐1 (Wif‐1) prompted us to investigate the functional role of Wif‐1 as well as nuclear accumulation of beta‐catenin in CPT. In Z310 neoplastic choroid plexus epithelial cells, silencing of Wif1 expression increased proliferative activity not associated with increased canonical Wnt signaling. Nuclear beta‐catenin accumulation was also lacking in a series of 16 CPT. In conclusion, our data show that Wif‐1 inhibits proliferation of neoplastic choroid plexus epithelial cells, but argue against a role of canonical Wnt/wingless signaling in CPT. Pediatr Blood Cancer 2009;53:1152–1155. © 2009 Wiley‐Liss, Inc.
Trends in the prescription of anti‐diabetic medications in the United Kingdom: a population‐based analysis
Authors: Filion Kristian B. , Joseph Lawrence , Boivin Jean‐François , Suissa Samy , Brophy James M.
Published: July 2009

Purpose

Over the last decade, guidelines for the treatment of type 2 diabetes have increasingly favored tighter glycemic control, necessitating the use of more aggressive pharmacological therapy. The objective of this study was to describe trends in the prescription of anti‐diabetic medications among patients with type 2 diabetes in the United Kingdom (UK).

Methods

Using the General Practice Research Database, we constructed a cohort of patients with type 2 diabetes. Diabetes was defined as the presence of a diagnosis of diabetes, HbA1c ≥ 7%, or ≥ 2 prescriptions for anti‐diabetic medications. Analyses were conducted for the full cohort as well as a sub‐cohort with incident diabetes.

Results

Our full cohort involved 67 981 patients and a total of 320 089 patient‐years, and our sub‐cohort involved 30 234 patients with incident diabetes and 111 890 patient‐years. From 2000 to 2006, there was a substantial increase in the prescription rate of anti‐diabetic medications. Overall, there were 9.6 prescriptions/patient‐year in 2000, and this had increased to 14.8 prescriptions/patient‐year in 2006. The greatest relative increase occurred in the prescription of thiazolidinediones. The greatest absolute increase occurred in the prescription of metformin, which surpassed sulfonylureas as the most commonly prescribed anti‐diabetic medication among patients with type 2 diabetes in 2002. Among those with incident diabetes, overall prescription rates were 4.6 prescriptions/patient‐year in 2000 and 13.6 prescriptions/patient‐year in 2006.

Conclusions

There was a substantial increase between 2000 and 2006 in the UK in the prescription of anti‐diabetic medications. This increasingly aggressive pharmacological management is consistent with recent practice guidelines. Copyright © 2009 John Wiley & Sons, Ltd.
Accuracy analysis of multiple structure alignments
Authors: Berbalk Christoph , Schwaiger Christine S. , Lackner Peter
Published: July 2009

Protein structure alignment methods are essential for many different challenges in protein science, such as the determination of relations between proteins in the fold space or the analysis and prediction of their biological function. A number of different pairwise and multiple structure alignment (MStA) programs have been developed and provided to the community. Prior knowledge of the expected alignment accuracy is desirable for the user of such tools. To retrieve an estimate of the performance of current structure alignment methods, we compiled a test suite taken from literature and the SISYPHUS database consisting of proteins that are difficult to align. Subsequently, different MStA programs were evaluated regarding alignment correctness and general limitations. The analysis shows that there are large differences in the success between the methods in terms of applicability and correctness. The latter ranges from 44 to 75% correct core positions. Taking only the best method result per test case this number increases to 84%. We conclude that the methods available are applicable to difficult cases, but also that there is still room for improvements in both, practicability and alignment correctness. An approach that combines the currently available methods supported by a proper score would be useful. Until then, a user should not rely on just a single program.
A Quantitative Structure‐Activity Relationship Study of Some Commercially Available Cephalosporins
Authors: Luan Feng , Liu Huitao , Gao Yuan , Guo Li , Zhang Xiaoyun , Guo Yun
Published: July 2009

A quantitative structure‐activity relationship study of the binding of 28 commercially available cephalosporins to human serum proteins was performed with descriptors of molecular structure. Experimental data was the concentration of protein‐bound drug expressed as a percent of the total plasma concentration (percent fraction bound, PFB). A four parameter multiple linear correlation with squared correlation coefficients (R2) of 0.927 and root mean square error (RMS) of 8.67 is reported. The stability and predictive power of the models was verified by using the cross‐validation procedure. Polar interactions and the forming of hydrogen‐bonding properties are two major factors affecting the binding ability. The QSAR model presented is suitable for the rapid evaluation of PFB of cephalosporins.
Origins for epitaxial order of sexiphenyl crystals on muscovite(001)
Authors: Resel R. , Haber T. , Lengyel O. , Sitter H. , Balzer F. , Rubahn H.‐G.
Published: July 2009

The epitaxial order of sexiphenyl crystals on muscovite(001) is investigated by x‐ray diffraction, lattice misfit calculations and atomic force microscopy. Depending on the substrate temperature during the thin film growth process, different epitaxial orientations are formed. Sexiphenyl thin films prepared at 370 K preferentially form crystals with the crystallographic (11‐1) planes parallel to the substrate surface while at 434 K a strong fraction of crystals with (11‐2) orientations is grown. The epitaxial orders of sexiphenyl crystals are compared with lattice misfit calculations. The in‐plane order of the {11‐1} crystals can be explained by a point‐on‐line coincidence I, which reveals that the interface is formed by undisturbed crystal surfaces. The epitaxial order of the {11‐2} oriented crystals is characterised by the experimental observation that low indexed crystal directions in the sexiphenyl(11‐2) plane and the muscovite(001) surface coincide with each other, forming a near‐coincidence case. Corrugations of the substrate surface are responsible for this second type of epitaxial order. Characteristic features in the thin film morphology could be correlated to the two observed epitaxial orientations of the sexiphenyl crystals. Copyright © 2009 John Wiley & Sons, Ltd.
Super‐medium‐scale traveling ionospheric disturbance observed at midlatitude during the geomagnetic storm on 10 November 2004
Authors: Nishioka M. , Saito A. , Tsugawa T.
Published: July 2009

Medium‐scale traveling ionospheric disturbances (MSTIDs) whose peak‐to‐peak amplitude was larger than 20 TECU (=1016el/m2) were observed at midlatitude during the geomagnetic storm on 10 November 2004. This amplitude was more than 10 times larger than that of the average MSTID. High‐resolution data of the GPS Earth Observation Network (GEONET) clarified the characteristic of the total electron content (TEC) disturbances over Japan on 10 November 2004. The disturbances started around 1000 UT in the central part of Japan. The maximum of TEC temporal change was 7.2 TECU in 30 s. The disturbances had several wave fronts which extended from northwest to southeast and propagated from northeast to southwest. TEC data around Japan revealed that the disturbances were mainly observed from 18°N/S to 34°N/S of the geomagnetic latitude in the both hemispheres. Since those characteristics were similar to those of MSTIDs in spite of the unusual large amplitude, the MSTIDs are referred as “super‐MSTIDs” in this paper. TEC variations of the super‐MSTIDs were also observed at 460 km altitude by the GRACE satellite. The ion density fluctuations of the super‐MSTIDs were observed in situ by the CHAMP and DMSP‐F15 satellites, which flew at 360 km and 850 km, respectively. It is found that the plasma density variations of the super‐MSTIDs occurred mainly above 360 km altitude. The characteristics that distinguish the event from plasma bubbles are its successive wave fronts, constant northwest‐southeast direction along which the wave fronts stretched, and late local time of the occurrence. It is found that the uplift of the ionosphere around sunset excited the super‐MSTIDs at midlatitudes. The uplift was attributed to the strong eastward electric field during the geomagnetic storm.
Tracking Pyroclastic Flows at Soufrière Hills Volcano
Authors: Ripepe Maurizio , De Angelis Silvio , Lacanna Giorgio , Poggi Pasquale , Williams Carlisle , Marchetti Emanuele , Donne Dario Delle , Ulivieri Giacomo
Published: July 2009

Explosive volcanic eruptions typically show a huge column of ash and debris ejected into the stratosphere, crackling with lightning. Yet equally hazardous are the fast moving avalanches of hot gas and rock that can rush down the volcano's flanks at speeds approaching 280 kilometers per hour. Called pyroclastic flows, these surges can reach temperatures of 400°C. Fast currents and hot temperatures can quickly overwhelm communities living in the shadow of volcanoes, such as what happened to Pompeii and Herculaneum after the 79 C.E. eruption of Italy's Mount Vesuvius or to Saint‐Pierre after Martinique's Mount Pelée erupted in 1902.
A Global Ground‐Based Magnetometer Initiative
Authors: Gjerloev J. W.
Published: July 2009

With the motto “Knowledge is the common wealth of humanity,” the 2007–2008 Electronic Geophysical Year (eGY) advocated that scientists have the responsibility to create and implement strategies that utilize the full potential of digital capabilities in providing information for present and future generations.

Although eGY has officially ended, the geomagnetic research community continues to support the goals of eGY through a global ground‐based magnetometer initiative. This initiative, called SuperMAG, helps scientists have easy access to measurements of the Earth's magnetic field.
Kastens Receives 2009 Excellence in Geophysical Education Award
Authors: Manduca Cathryn A. , Kastens Kim Anne
Published: July 2009

Kim Anne Kastens received the Excellence in Geophysical Education Award at the Joint Assembly, held 26 May 2009 in Toronto, Ontario, Canada. The award honors “a sustained commitment to excellence in geophysical education by a team, individual, or group.”