bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuromuscular electrical stimulation (NMES) reduces structural and functional losses of quadriceps muscle and improves health status in patients with knee osteoarthritis
Authors: Vaz Marco Aurélio , Baroni Bruno Manfredini , Geremia Jeam Marcel , Lanferdini Fábio Juner , Mayer Alexandre , Arampatzis Adamantios , Herzog Walter
Published: November 2012

Knee osteoarthritis (OA) is associated with quadriceps atrophy and weakness, so muscle strengthening is an important point in the rehabilitation process. Since pain and joint stiffness make it often difficult to use conventional strength exercises, neuromuscular electrical stimulation (NMES) may be an alternative approach for these patients. This study was aimed at (1) identifying the associations of knee OA with quadriceps muscle architecture and strength, and (2) quantifying the effects of a NMES training program on these parameters. In phase 1, 20 women with knee OA were compared with 10 healthy female, asymptomatic, age‐matched control subjects. In phase 2, 12 OA patients performed an 8‐week NMES strength training program. OA patients presented smaller vastus lateralis thickness (11.9 mm) and fascicle length (20.5%) than healthy subjects (14.1 mm; 24.5%), and also had a 23% smaller knee extensor torque compared to the control group. NMES training increased vastus lateralis thickness (from 12.6 to 14.2 mm) and fascicle length (from 19.6% to 24.6%). Additionally, NMES training increased the knee extensor torque by 8% and reduced joint pain, stiffness, and functional limitation. In conclusion, OA patients have decreased strength, muscle thickness, and fascicle length in the knee extensor musculature compared to control subjects. NMES training appears to offset the changes in quadriceps structure and function, as well as improve the health status in patients with knee OA. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 511–516, 2013
Photo‐controlled Hierarchical Assembly and Fusion of Coumarin‐containing Polydiacetylene Vesicles
Authors: Li Jingguo , Jiang Hao , Hu Wenlong , Xia Hongyan , Zou Gang , Zhang Qijin
Published: November 2012

Herein, we synthesize a coumarin‐substituted diacetylene monomer (CODA) and report the novel photo‐controlled reversible assembly and disassembly behavior of the polymerized CODA (PCODA) vesicles. The photo‐triggered dimerization and cleavage reactions of the coumarin groups within the surface of the adjacent PCODA vesicles can be utilized as the driving force to induce assembly and disassembly of PCODA vesicles. Moreover, the boundary of PCODA vesicles in the aggregates becomes more obscure when the irradiation time exceeds 30 min. Fusion occurs upon close docking of target membranes, driven by sufficient dimerization of the coumarin groups within the surface of PCODA vesicles.
WYE‐120318, a ring contraction product of methylnaltrexone, and structure revision of coniothyrione
Authors: Kong Fangming , Zhu Tianmin , Pan Weitao , Tsao Russ , Pagano Thomas G. , Nguyen Bao , Marquez Brian
Published: November 2012

A contracted ring degradation product, WYE‐120318 (compound 2), was discovered during the development phase for methylnaltrexone bromide (compound 1) drug substance. The compound was isolated by high‐performance liquid chromatography fractionation, and its structure was determined by spectroscopic data analyses. WYE‐120318 is formed from methylnaltrexone through a benzyl‐benzilic acid type rearrangement reaction to yield an α‐hydroxy‐cyclopentanecarboxylic acid substructure. The proposed structure and the formation mechanism are confirmed by the synthesis of WYE‐120318 from methylnaltrexone (compound 1).

A similar benzyl‐benzilic acid type rearrangement reaction can be envisioned as the biological origin of remisporine A (compound 3), a naturally occurring cyclopentadienyl compound that autocatalytically dimerizes to remisporine B (compound 4). The structure of remisporine A was deduced from its dimer 4. Coniothyione (compound 5) can be considered as the first example of a stable natural product bearing the remisporine A skeleton. However, the regiochemistry of the chlorosubstitution in the coniothyrione structure needs to be revised to compound 6 on the basis of the nuclear magnetic resonance data and biogenesis analysis. Copyright © 2012 John Wiley & Sons, Ltd.
Kit ligand and glial‐derived neurotrophic factor as alternative supplements for activation and development of ovine preantral follicles in vitro
Authors: Esmaielzadeh F. , Hosseini S.M. , Nasiri Z. , Hajian M. , Chamani M. , Gourabi H. , Shahverdi A.H. , Vosough A.D. , Nasr‐Esfahani M.H.
Published: November 2012

In vitro growth of preantral follicles has the potential to produce considerable numbers of competent oocytes for use in medicine, agriculture, and even wildlife conservation. The critical regulatory role of growth factors and hormones in the development of preantral follicles has been established. This study investigated the effect of glial‐derived neurotropic factor (GDNF) and kit ligand (KL) on the in vitro development of ovine preantral follicles. Results indicated that both GDNF and KL significantly improved activation of primordial follicles, similar to co‐addition of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), which are commonly used for in vitro follicular development. Importantly, GDNF had a more profound effect on follicle health, development, and differentiation compared with KL alone. Furthermore, the combination of GDNF and KL in the presence of EGF and bFGF had a positive, synergic effect on health, development, and differentiation of preantral follicles, as determined by histological and hormonal assessments. The results of this study may provide a foundation for further studies that will unravel the molecular mechanisms of follicular development to further improve the current status of in vitro preantral follicle culture. Mol. Reprod. Dev. 80: 35–47, 2013. © 2012 Wiley Periodicals, Inc.
Safety of repetitive nerve stimulation in patients with cardiac implantable electronic devices
Authors: Cronin Edmond M. , Gray Jennifer , Abi‐Saleh Bernard , Wilkoff Bruce L. , Levin Kerry H.
Published: November 2012

Introduction: Pacemakers and implantable cardioverter‐defibrillators (ICDs) are vulnerable to inappropriate sensing of electromagnetic interference (EMI), such as from nerve conduction studies. We conducted a prospective study to assess the safety of repetitive nerve stimulation (RNS). Methods: Fourteen patients undergoing insertion of 10 ICDs and 4 pacemakers under general anesthesia received RNS of the median, axillary, and spinal accessory nerves at 2 HZ and 50 HZ. We recorded detection of EMI and whether or not this resulted in an arrhythmia diagnosis or change in pacing output. Results: EMI was visible in 2 ICDs, without spurious tachyarrhythmia detection. EMI was observed in 3 of the 4 pacemakers, which led to pacing inhibition and a pause in 2, both of which were programmed to a unipolar sensing configuration. Conclusions: RNS is safe in patients with ICDs. In pacemaker patients, RNS appears safe during bipolar sensing, but caution is recommended in pacemaker patients with unipolar sensing. Muscle Nerve 47: 840–844, 2013
Concentric needle jitter on voluntary activated frontalis in 20 healthy subjects
Authors: Kouyoumdjian João A. , Stålberg Erik V.
Published: November 2012

Introduction: Normative data for jitter parameters using a disposable concentric needle have been described in a few studies. Methods: Jitter, expressed as the mean consecutive difference (MCD), was measured in the frontalis muscle in 20 subjects by voluntary contraction. Results: Mean MCD for individual studies (20, Gaussian), all potentials (400, non‐Gaussian), and 18th highest value (20, Gaussian) were 19.9 ± 2.9 μs, 19.9 ± 6.6 μs, and 26.9 ± 4.4 μs, respectively. Conclusion: The suggested upper normal limit for mean MCD is 26 μs and for outliers is 36 μs. Muscle Nerve 47:440‐442, 2013
Gentherapie der Hämophilie B
Authors: Winckler Thomas
Published: November 2012

Die Bluterkrankheit (Hämophilie) ist eine typische Indikation für die Substitutionstherapie mit Blutgerinnungsfaktor‐Konzentraten oder Biopharmazeutika – und bald vielleicht auch für eine Gentherapie.
Alternative Wege zu “Multidrug”‐resistenten Bakterien via reaktiver Sauerstoffspezies
Authors: Holzgrabe Ulrike
Published: November 2012

Inzwischen kennen wir eine ganze Reihe von Mechanismen, wie Bakterien eine Antibiotika‐Resistenz entwickeln können, wie z.B. den horizontalen Transfer von Resistenz‐Genen, die Antibiotika‐selektive Selektion von natürlich vorkommenden, resistenten Stämmen einer Population oder die gesteigerte Mutagenese in sog. “Hypermutator”‐Stämmen. Kohanski et al. berichteten kürzlich über die Entwicklung von Multiresistenzen bei der Gabe von subletalen Antibiotikadosen verursacht durch reaktive Sauerstoffspezies wie Hydroxyl‐Radikale.
Dielectric and electric properties of plasticized PEO‐AgCF3SO3‐SiO2 nanocomposite polymer electrolyte system
Authors: Gondaliya Nirali , Kanchan D.K. , Sharma Poonam , Jayswal Manish S.
Published: November 2012

The effect of plasticizer poly(ethylene glycol) (PEG) on dielectric and electrical properties of an ionically conducting polymer nanocomposite electrolyte PEO: AgCF3SO3: SiO2: PEG has been investigated. The variation of relative dielectric constant and tangent loss peak with frequency have been discussed. The ionic and polymer segmental motions have been analyzed by electrical modulus and dielectric permittivity. The electrical modulus formalism is used to study the ionic relaxation process in these composites in terms of conductivity relaxation time. On addition of plasticizer, the modulus peak shifts toward higher frequency side suggesting the speeding up of the relaxation time. The frequency dependence of AC conductivity follows the universal power law. POLYM. COMPOS., 2012. © 2012 Society of Plastics Engineers
Haemolysis risk in methylene blue treatment of G6PD‐sufficient and G6PD‐deficient West‐African children with uncomplicated falciparum malaria: a synopsis of four RCTs
Authors: Müller Olaf , Mockenhaupt Frank P. , Marks Bernd , Meissner Peter , Coulibaly Boubacar , Kuhnert Ronny , Buchner Hannes , Schirmer R. Heiner , Walter‐Sack Ingeborg , Sié Ali , Mansmann Ulrich
Published: November 2012

Purpose

Methylene blue (MB), which was recently tested in a number of clinical malaria studies in Burkina Faso, is currently investigated for its benefit when added to artemisinin‐based combination therapy. Together with a number of other antimalarials, MB is on the list of drugs which potentially induce haemolysis in patients with G6PD deficiency. Ruling out safety concerns is of major importance during drug development.

Methods

A pooled analysis was performed with patient data from four clinical studies conducted in West African children with falciparum malaria between 2003 and 2007. The primary endpoints were haemoglobin levels over time as well as haemolysis in G6PD‐deficient (n = 199) and G6PD‐sufficient (n = 806) children treated with MB‐containing (n = 844) compared to children without MB‐containing (n = 161) drug regimens.

Results

In the chosen model, the haemoglobin time course was significantly influenced by the G6PD genotype and the MB dose. In children with hemi‐ or homozygous G6PD (A‐) deficiency, MB treatment with 15 mg/kg per day was associated with a significant reduction in Hb values which reached a minimum of 8.5 g/dl. Two episodes of haemolysis occurred (out of 1005 children); one in a girl heterozygous for G6PD deficiency and one in a hemizygous boy, both had received MB.

Conclusions

MB treatment of malaria in Africa is associated with slightly reduced haemoglobin values in children with a full G6PD defect compared to non‐G6PD deficient children. This effect appears to be of limited clinical relevance but needs to be monitored. Copyright © 2012 John Wiley & Sons, Ltd.
Conformational and thermal analyses of α‐methoxy‐poly(ethylene glycol)‐block‐poly[ϵ‐(benzyloxycarbonyl)‐l‐lysine] hybrid block copolymers
Authors: Izunobi Josephat U , Higginbotham Clement L
Published: November 2012

Hybrid block copolymers find applications in drug delivery, tissue engineering, biomimetics and bioimaging, amongst others, mainly due to their propensity to form phase‐separated microdomains as well as to the aggregation of their polypeptide segments. They not only enhance control over structure at the nanometre scale but also yield materials that can interface with various biosystems for different utilities. α‐Methoxy‐poly(ethylene glycol)‐block‐poly[ϵ‐(benzyloxycarbonyl)‐l‐lysine] hybrid block copolymers of varying degrees of polymerization, MPEGn‐b‐PLL(Z)m, were synthesized by N‐carboxyanhydride ring‐opening polymerization and characterized using infrared and NMR spectroscopy and gel permeation chromatography. Their secondary structures and bulk conformations were investigated using circular dichroism spectroscopy and wide‐angle X‐ray diffraction, respectively, whereas thermogravimetric analysis (TGA), derivative TGA and differential scanning calorimetry were employed for thermal analyses. The resulting block copolymers exhibited microphase separation and suppressed degrees of crystallinity with increasing l‐lysine content and adopted α‐helix and β‐sheet secondary structures in aqueous milieu. The copolymers were also more thermally stable than their constituent homopolymers. Interestingly, the effects of the retention of the Nϵ‐benzyloxycarbonyl moiety on polymer properties proved considerable. The hybrid block copolymers herein afforded hierarchical structures of potential utility in the biomedical and pharmaceutical fields. © 2012 Society of Chemical Industry
2D DIGE analysis of the bursa of Fabricius reveals characteristic proteome profiles for different stages of chicken B‐cell development
Authors: Korte Julia , Fröhlich Thomas , Kohn Marina , Kaspers Bernd , Arnold Georg J. , Härtle Sonja
Published: November 2012

Antibody producing B‐cells are an essential component of the immune system. In contrast to human and mice where B‐cells develop in the bone marrow, chicken B‐cells develop in defined stages in the bursa of Fabricius, a gut associated lymphoid tissue. In order to gain a better understanding of critical biological processes like immigration of B‐cell precursors into the bursa anlage, their differentiation and final emigration from the bursa we analyzed the proteome dynamics of this organ during embryonic and posthatch development. Samples were taken from four representative developmental stages (embryonic day (ED) 10, ED18, day 2, and day 28) and compared in an extensive 2D DIGE approach comprising six biological replicates per time point. Cluster analysis and PCA demonstrated high reliability and reproducibility of the obtained data set and revealed distinctive proteome profiles for the selected time points, which precisely reflect the differentiation processes. One hundred fifty three protein spots with significantly different intensities were identified by MS. We detected alterations in the abundance of several proteins assigned to retinoic acid metabolism (e.g. retinal‐binding protein 5) and the actin‐cytoskeleton (e.g. vinculin and gelsolin). By immunohistochemistry, desmin was identified as stromal cell protein associated with the maturation of B‐cell follicles. Strongest protein expression difference (10.8‐fold) was observed for chloride intracellular channel 2. This protein was thus far not associated with B‐cell biology but our data suggest an important function in bursa B‐cell development.
Recombinant reflectin‐based optical materials
Authors: Qin Guokui , Dennis Patrick B. , Zhang Yuji , Hu Xiao , Bressner Jason E. , Sun Zhongyuan , Crookes‐Goodson Wendy J. , Naik Rajesh R. , Omenetto Fiorenzo G. , Kaplan David L.
Published: November 2012

Reflectins are a unique group of structural proteins involved in dynamic optical systems in cephalopods that modulate incident light or bioluminescence. We describe cloning, structural characterization, and optical properties of a reflectin‐based domain, refCBA, from reflectin 1a of Hawaiian bobtail squid, Euprymna scolopes. Thin films created from the recombinant protein refCBA display interesting optical features when the recombinant protein is appropriately organized. RefCBA was cloned and expressed as a soluble protein enabling purification, with little structural organization found using Fourier transform infrared spectroscopy and circular dichroism. Single‐layer and multi‐layer thin films of refCBA were then produced by flow coating and spin coating, and displayed colors due to thin film interference. Diffraction experiments showed the assemblies were ordered enough to work as diffraction gratings to generate diffraction patterns. Nano‐spheres and lamellar microstructures of refCBA samples were observed by scanning electron microscopy and atomic force microscopy. Despite the reduced complexity of the refCBA protein compared to natural reflectins, unique biomaterials with similar properties to reflectins were generated by self‐assembled reflectin‐based refCBA molecules. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2013
Influence of thermal history on mesoscale ordering in polydomain smectic networks
Authors: Chen Huipeng , Yu Ziniu , Hedden Ronald C.
Published: November 2012

Dramatic changes in mesoscale ordering and macroscopic mechanical behavior are observed in smectic polydomain networks after annealing at a temperature well above the glass transition temperature but below the clearing temperature. Tensile testing reveals gradual stiffening and loss of extensibility, and X‐ray linewidth measurements confirm that stiffening is initially due to thickening of domains. At long annealing times, a more highly ordered smectic mesophase forms, further stiffening the networks and reducing their extensibility. Increasing the concentration of (flexible) crosslinkers hinders domain growth and suppresses formation of the higher order mesophase, a useful guideline for design of smectic networks that exhibit reduced sensitivity to thermal history. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2013
Prevalence and predictors of post‐traumatic stress symptoms in adolescent and young adult cancer survivors: a 1‐year follow‐up study
Authors: Kwak Minyoung , Zebrack Brad J. , Meeske Kathleen A. , Embry Leanne , Aguilar Christine , Block Rebecca , Hayes‐Lattin Brandon , Li Yun , Butler Melissa , Cole Steven
Published: November 2012

Objectives

Post‐traumatic stress symptoms (PTSS) have been identified as a meaningful indicator of distress in cancer survivors. Distinct from young adult survivors of childhood cancer, young people diagnosed with cancer as adolescents and young adults (AYAs) face unique psychosocial issues; however, there is little published research of PTSS in the AYA population. This study examines prevalence and predictors of PTSS among AYAs with cancer.

Methods

As part of a longitudinal study of AYAs with cancer, 151 patients aged 15–39 years completed mailed surveys at 6 and 12 months post‐diagnosis. Severity of PTSS was estimated at 6 and 12 months post‐diagnosis. Multiple regression analyses were conducted to investigate the predictive effects of socio‐demographic and clinical characteristics on changes in PTSS over time.

Results

At 6 and 12 months, respectively, 39% and 44% of participants reported moderate to severe levels of PTSS; 29% had PTSS levels suggestive of post‐traumatic stress disorder. No significant differences in severity of PTSS between 6 and 12 months were observed. Regression analyses suggested that a greater number of side effects were associated with higher levels of PTSS at 6 months. Currently receiving treatment, having surgical treatment, diagnosis of a cancer type with a 90–100% survival rate, remaining unemployed/not in school, and greater PTSS at 6 months were associated with higher levels of PTSS at 12 months.

Conclusions

Post‐traumatic stress symptoms were observed as early as 6 months following diagnosis and remained stable at 12‐month follow‐up. The development of early interventions for reducing distress among AYA patients in treatment is recommended.

Copyright © 2012 John Wiley & Sons, Ltd.
Palivizumab immunoprophylaxis effectiveness in children with cystic fibrosis
Authors: Winterstein Almut G. , Eworuke Efe , Xu Dandan , Schuler Pamela
Published: November 2012

Background

Evidence on the effectiveness of respiratory syncytial virus (RSV) immunoprophylaxis with palivizumab in children with cystic fibrosis (CF) is lacking.

Methods

We utilized Medicaid Extract files from 27 states from 1999 to 2006 linked to the National Cystic Fibrosis Registry to establish a cohort of children 0–2 years with CF diagnosis. Eligible children entered the cohort after CF diagnosis and after RSV season onset, and were followed until season end, second birthday, death, or hospitalizations for reasons other then the study outcome. Two outcomes were examined: hospitalization for RSV infections (RSV‐ha), or hospitalization for acute respiratory infections (ARI‐ha). Palivizumab exposure was defined based on pharmacy or procedure claims as current (claim date plus 30 days), former (day 31–60 after a claim), and no exposure (days before the first or >60 days after any claim). Both outcomes were examined in a Cox regression model, adjusting for RSV risk factors and CF severity via exposure propensity score.

Results

The matched cohort included 1,974 infants (2,875 infant seasons), who experienced 32 RSV‐ha and 212 ARI‐ha (3.9 and 26.2/1,000 season months, respectively). Compared to periods of no use, the adjusted hazard ratio for current use was 0.57 (95% confidence interval [CI]: 0.20–1.60) for RSV‐related hospitalization and 0.85 (95% CI: 0.59–1.21) for ARI‐related hospitalization. Each month of increasing age reduced the ARI‐ha by 5.8%.

Conclusion

RSV hospitalization incidence was low suggesting either little contribution of the virus to respiratory infections in patients with CF or lack of RSV testing. Unadjusted and adjusted RSV‐hospitalization incidence rates suggested potentially positive effects of palivizumab, but results were inconclusive due to small event rates. Hospitalizations for acute respiratory illness with possible RSV contribution showed no association with palivizumab use, suggesting limited overall effect of palivizumab. Younger age greatly increased infection risk. Pediatr Pulmonol. 2013; 48:874–884. © 2012 Wiley Periodicals, Inc.
The BMPR2 missense mutation p.K230N and pulmonary arterial hypertension
Authors: Hayes Don , Ramanathan Chandar , Kopp Benjamin T.
Published: November 2012

We present a patient that is the index case of pulmonary arterial hypertension (PAH) in a child due to the bone morphogenetic protein type II (BMPR2) missense mutation p.K230N, also known as c.690A>T. Missense mutations typically have earlier onset and more severe disease in PAH, so pulmonologists should be aware of this in the evaluation of PAH in children. Pediatr Pulmonol. 2014; 49:E5–E6. © 2013 Wiley Periodicals, Inc.
Structure and function of the SPRY/B30.2 domain proteins involved in innate immunity
Authors: D'Cruz Akshay A. , Babon Jeffrey J. , Norton Raymond S. , Nicola Nicos A. , Nicholson Sandra E.
Published: November 2012

The SPRY domain is a protein interaction module found in 77 murine and ∼100 human proteins, and is implicated in important biological pathways, including those that regulate innate and adaptive immunity. The current definition of the SPRY domain is based on a sequence repeat discovered in the splA kinase and ryanodine receptors. The greater SPRY family is divided into the B30.2 (which contains a PRY extension at the N‐terminus) and “SPRY‐only” sub‐families. In this brief review, we examine the current structural and biochemical literature on SPRY/B30.2 domain involvement in key immune processes and highlight a PRY‐like 60 amino acid region in the N‐terminus of “SPRY‐only” proteins. Phylogenetic, structural, and functional analyses suggest that this N‐terminal region is related to the PRY region of B30.2 and should be characterized as part of an extended SPRY domain. Greater understanding of the functional importance of the N‐terminal region in “SPRY only” proteins will enhance our ability to interrogate SPRY interactions with their respective binding partners.
Crystal structure of Jararacussin‐I: The highly negatively charged catalytic interface contributes to macromolecular selectivity in snake venom thrombin‐like enzymes
Authors: Ullah A. , Souza T. A. C. B. , Zanphorlin L. M. , Mariutti R. B. , Santana V. S. , Murakami M. T. , Arni R. K.
Published: November 2012

Snake venom serine proteinases (SVSPs) are hemostatically active toxins that perturb the maintenance and regulation of both the blood coagulation cascade and fibrinolytic feedback system at specific points, and hence, are widely used as tools in pharmacological and clinical diagnosis. The crystal structure of a thrombin‐like enzyme (TLE) from Bothrops jararacussu venom (Jararacussin‐I) was determined at 2.48 Å resolution. This is the first crystal structure of a TLE and allows structural comparisons with both the Agkistrodon contortrix contortrix Protein C Activator and the Trimeresurus stejnegeri plasminogen activator. Despite the highly conserved overall fold, significant differences in the amino acid compositions and three‐dimensional conformations of the loops surrounding the active site significantly alter the molecular topography and charge distribution profile of the catalytic interface. In contrast to other SVSPs, the catalytic interface of Jararacussin‐I is highly negatively charged, which contributes to its unique macromolecular selectivity.
Growth kinetics of CD133‐positive prostate cancer cells
Authors: Reyes Edwin E. , Kunovac Stefan K. , Duggan Ryan , Kregel Steven , Griend Donald J. Vander
Published: November 2012

BACKGROUND

In the adult human prostate CD133 expression is thought to mark rare prostate epithelial stem cells and malignant tumor stem/initiating cells. Such putative stem cell populations are thought to proliferate slowly, but possess unlimited proliferative potential. Based on this, we hypothesized that CD133pos prostate cancer cells proliferate slower than CD133neg cells.

METHODS

Human prostate cancer cell lines were analyzed for CD133 expression and DNA content using flow cytometry. Rates of cell division and DNA synthesis were determined using CFSE cell tracing and BrdU uptake, respectively. Changes in cell cycle distribution and the percentage of CD133pos cells were assayed under conditions of different cell density and AR‐pathway modulation. Lastly, we over‐expressed lentiviral CD133 to measure whether CD133 regulates the cell cycle.

RESULTS

The cell cycle distribution differs between CD133pos and CD133neg cells in all three human prostate cancer cell lines studied. CD133pos cells have a greater proportion of cells in G2 and proliferate faster than CD133neg cells. High cell density increases the percentage of CD133pos cells without changing CD133pos cell cycle progression. Treatment with the AR agonist R1881, or the anti‐androgen MDV3100, significantly changed the percentage and proliferation of CD133pos cells. Finally, ectopic over‐expression of CD133 had no effect on cell cycle progression.

CONCLUSIONS

Contrary to our hypothesis, we demonstrate that CD133pos cells proliferate faster than CD133neg cells. This association of CD133 expression with increased cell proliferation is not directly mediated by CD133, suggesting that surface CD133 is a downstream target gene of an undefined pathway controlling cell proliferation. Prostate 73: 724–733, 2013. © 2012 Wiley Periodicals, Inc.
Differentiation of isomeric pentose disaccharides by electrospray ionization tandem mass spectrometry and discriminant analysis
Authors: da Costa Elisabete V. , Moreira Ana S. P. , Nunes Fernando M. , Coimbra Manuel A. , Evtuguin Dmitry V. , Domingues M. Rosário M.
Published: November 2012

RATIONALE

The structural characterization of unknown oligosaccharides remains a big challenge since a large number of isomeric structures are possible even for disaccharides. In this work, electrospray ionization collision‐induced dissociation tandem mass spectrometry (ESI‐CID‐MS/MS) was used for the differentiation of isomeric pentose disaccharides, α‐(1 → 5)‐l‐arabinobiose (Ara2) and β‐(1 → 4)‐d‐xylobiose (Xyl2).

METHODS

ESI‐MS/MS spectra of [M + Li]+ and [M + Na]+ ions of Ara2 and Xyl2, as well as these precursor ions of 18O‐labelled disaccharides, were acquired using two mass spectrometers equipped with different analyzers: LIT (linear ion trap) and Q‐TOF (quadrupole time‐of‐flight).

RESULTS

Product ions observed in MS/MS spectra arise from the cleavage at the nonreducing side of the glycosidic bond (Y1+) and from cross‐ring cleavages 0,1A2+, 0,2A2+, and 0,3A2+ at the reducing residue. Statistically significant differences were observed between the relative abundance of specific product ions, when comparing both disaccharides. These differences allowed discriminant models to be built and to propose a criterion using the relative abundances of selected ions capable of discriminating between the isomers for both adduct ions and spectrometers.

CONCLUSIONS

Isomeric pentose disaccharides can be distinguished based on the fragmentation of both [M + Li]+ and [M + Na]+ ions and using different mass spectrometers. However, LIT instrument has a better discriminant power. Copyright © 2012 John Wiley & Sons, Ltd.
Simulated gastrointestinal digestion of Pru ar 3 apricot allergen: Assessment of allergen resistance and characterization of the peptides by ultra‐performance liquid chromatography/electrospray ionisation mass spectrometry
Authors: Prandi Barbara , Farioli Laura , Tedeschi Tullia , Pastorello Elide Anna , Sforza Stefano
Published: November 2012

RATIONALE

Non‐specific lipid transfer proteins (ns‐LTPs) are major food allergens of the Rosaceæ family. The severity of allergic reactions often relates to resistance of the allergen to digestion. Thus, it is important to evaluate the digestibility of these proteins and characterise the peptides generated in the gastrointestinal tract.

METHODS

Simulated gastrointestinal digestion of purified allergen Pru ar 3 was performed using pepsin for the gastric phase in aqueous HCl at pH = 2 and chymotrypsin and trypsin for the intestinal phase in aqueous NH4HCO3 at pH = 7.8. The peptide mixture obtained was analysed by ultra‐performance liquid chromatography/electrospray ionisation mass spectrometry (UPLC/ESI‐MS). Peptide sequences were identified by comparing their molecular mass to that obtained by in silico digestion, and were confirmed by the ions obtained by in‐source fragmentation. Semi‐quantification was performed for the intact protein by comparison with internal standards.

RESULTS

The resistance to gastrointestinal digestion of Pru ar 3 allergen was evaluated to be 9%. This value is consistent with that found for grape LTP, but much lower than the resistance found for peach LTP (35%). All the peptides generated were identified by ESI‐MS on the basis of their molecular mass and from the ions generated from in‐source fragmentation. Apart from low molecular mass peptides, five high molecular mass peptides (4500–7000 Da) containing disulphide bridges were identified. ESI‐MS of the intact protein indicated a less compact folded structure when compared to that of the homologous peach LTP.

CONCLUSIONS

An extensive characterisation of the peptides generated from the gastrointestinal digestion of Pru ar 3 allergen was performed here for the first time via UPLC/ESI‐MS analysis. The digestibility of the allergen was evaluated and compared with that of other LTPs, demonstrating that only a small amount of undigested protein remains, and that specific proteolytic action involves immunodominant epitopes. These data might explain the lower allergenicity of apricot LTP compared to peach LTP, despite their high sequence homology. Copyright © 2012 John Wiley & Sons, Ltd.
Pressure baseline correction and high‐precision CO2 clumped‐isotope (∆47) measurements in bellows and micro‐volume modes
Authors: He Bo , Olack Gerard A. , Colman Albert S.
Published: November 2012

RATIONALE

CO2 ‘clumped‐isotope’ measurements (tracking enrichment of 16O13C18O, reported as ∆47 values, on CO2 derived from carbonate minerals or the atmosphere) are becoming central to a wide range of geochemical investigations. We present a novel approach to address problems with instrument stability, external precision, and the analysis of small samples that have hampered the advancement of Δ47 measurements.

METHODS

We measured Δ47 values on CO2 gases introduced via dual inlet to an isotope ratio mass spectrometer. We developed a method for determining the 'pressure baseline' and integrating a correction to ion beam intensity measurements during analysis. We then tested this approach for both bellows and micro‐volume modes of sample introduction. Heated gas and equilibrated gas lines (Δ47 vs. δ47) established the effectiveness of this correction.

RESULTS

We have determined that drift in instrument calibration that compromises Δ47 measurements results from a shift in the baseline signal on sensitive collectors (m/z 47, 48, and 49) that occurs when gas is admitted to the ion source. Applying a 'pressure baseline' (PBL) correction significantly stabilizes ∆47 measurements and reduces the dependence of ∆47 values on δ47 values by up to an order of magnitude.

CONCLUSIONS

PBL‐corrected heated gas and equilibrated gas calibrations in bellows and micro‐volume modes are nearly identical and stable through time. Introduction of the PBL correction, a revision to the absolute reference frame approach to determining Δ47 values, dramatically improves the external precision of Δ47 measurements to near instrumental analytical uncertainty (6–8 ppm (1σ) in bellows mode; 10–12 ppm in micro‐volume mode). Copyright © 2012 John Wiley & Sons, Ltd.
Coke Reactivity under Blast Furnace Conditions and in the CSR/CRI Test
Authors: Lundgren Maria , Sundqvist Ökvist Lena , Björkman Bo
Published: November 2012

The present work aims to study the high‐temperature strength of coke. Mechanisms of disintegration were evaluated using basket samples charged into LKAB's experimental blast furnace prior to quenching and dissection. Coke charged into basket samples was analysed with CSR/CRI tests and compared with treated coke from the blast furnace. Results from tumbling tests, chemical analyses of coarse and fine material, as well as light optical microscopy studies of original and treated coke have been combined and evaluated. The results indicate a correlation between the ash composition and the CSR values. Differences in the texture of the coke were noted with light optical microscopy, and a significant change in the coke texture during the CSR/CRI test conditions was found. The results suggest that the main reaction between coke and CO2 took place in isotropic areas, which was especially pronounced in coke with a low CSR. Signs of degradation were apparent throughout the coke pieces that have undergone CSR/CRI testing, but were less observable in coke reacted in the blast furnace. The results indicate that reaction with CO2 is generally limited by the chemical reaction rate in the CSR/CRI test, while in the blast furnace the reaction is limited by the diffusion rate. Coke degradation is therefore mostly restricted to the coke surface in the blast furnace.
Local people's accounts of climate change: to what extent are they influenced by the media?
Authors: Marin Andrei , Berkes Fikret
Published: November 2012

Researchers using local and indigenous people's accounts of climate change in their scientific work often face scepticism regarding the value of such information. The critics' argument is that since local and indigenous people are often exposed to the global discourse on climate change, their observations and information may in fact be reproductions of science popularized through communication media. There are instances in which local people's accounts of climate change and impacts thereof may be influenced by how media frame and popularize scientific models and predictions. However, we propose several reasons why the influence of media reports and coverage of climate change is usually superficial. First, there are significant differences between the epistemologies employed by media and those of local people. Although media may be borrowing local environmental categories, they may be filling them with different content, leading to incoherence. Second, media accounts are often general and locally irrelevant, in contrast with the detailed local anchoring of the knowledge often held by people who rely on natural resources for their livelihoods. Their observations often rely on holistic ways of knowing their environments, integrating large numbers of variables, and the relationships between these. We propose that accounts based on such observations are probably not influenced by media framings and that uncovering their underlying ‘ways of knowing’ would provide valuable additional evidence in interdisciplinary studies of climate change. WIREs Clim Change 2013, 4:1–8. doi: 10.1002/wcc.199

This article is categorized under:

Social Status of Climate Change Knowledge > Sociology/Anthropology of Climate Knowledge
Transfer RNA modifications: nature's combinatorial chemistry playground
Authors: Jackman Jane E. , Alfonzo Juan D.
Published: November 2012

Following synthesis, tRNAs are peppered by numerous chemical modifications which may differentially affect a tRNA's structure and function. Although modifications affecting the business ends of a tRNA are predictably important for cell viability, a majority of modifications play more subtle structural roles that can affect tRNA stability and folding. The current trend is that modifications act in concert and it is in the context of the specific sequence of a given tRNA that they impart their differing effects. Recent developments in the modification field have highlighted the diversity of modifications in tRNA. From these, the combinatorial nature of modifications in explaining previously described phenotypes derived from their absence has emerged as a growing theme. WIREs RNA 2013, 4:35–48. doi: 10.1002/wrna.1144

This article is categorized under:

RNA Processing > RNA Editing and Modification

RNA Processing > tRNA Processing
Inflammation‐based prognostic score is a useful predictor of postoperative outcome in patients with extrahepatic cholangiocarcinoma
Authors: Oshiro Yukio , Sasaki Ryoko , Fukunaga Kiyoshi , Kondo Tadashi , Oda Tatsuya , Takahashi Hideto , Ohkohchi Nobuhiro
Published: November 2012

Background/purpose

Recent studies have revealed that the Glasgow prognostic score (GPS), an inflammation‐based prognostic score, is useful for predicting outcome in a variety of cancers. This study sought to investigate the significance of GPS for prognostication of patients who underwent surgery with extrahepatic cholangiocarcinoma.

Methods

We retrospectively analyzed a total of 62 patients who underwent resection for extrahepatic cholangiocarcinoma. We calculated the GPS as follows: patients with both an elevated C‐reactive protein (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a score of 2; patients with one or none of these abnormalities were allocated a score of 1 or 0, respectively. Prognostic significance was analyzed by the log‐rank test and a Cox proportional hazards model.

Results

Overall survival rate was 25.5 % at 5 years for all 62 patients. Venous invasion (p = 0.01), pathological primary tumor category (p = 0.013), lymph node metastasis category (p < 0.001), TNM stage (p < 0.001), and GPS (p = 0.008) were significantly associated with survival by univariate analysis. A Cox model demonstrated that increased GPS was an independent predictive factor with poor prognosis.

Conclusions

The preoperative GPS is a useful predictor of postoperative outcome in patients with extrahepatic cholangiocarcinoma.
Virtual liver resection: computer‐assisted operation planning using a three‐dimensional liver representation
Authors: Mise Yoshihiro , Tani Keigo , Aoki Taku , Sakamoto Yoshihiro , Hasegawa Kiyoshi , Sugawara Yasuhiko , Kokudo Norihiro
Published: November 2012

In liver surgery, understanding the complicated liver structures and a detailed evaluation of the functional liver remnant volume are essential to perform safe surgical procedures. Recent advances in imaging technology have enabled operation planning using three‐dimensional (3D) image—processing software. Virtual liver resection systems provide (1) 3D imaging of liver structures, (2) detailed volumetric analyses based on portal perfusion, and (3) quantitative estimates of the venous drainage area, enabling the investigation of uncharted fields that cannot be examined using a conventional two‐dimensional modality. The next step in computer‐assisted liver surgery is the application of a virtual hepatectomy to real‐time operations. However, the need for a precise alignment between the preoperative imaging data and the intraoperative situation remains to be adequately addressed, since the liver is subject to deformation and respiratory movements during the surgical procedures. We expect that the practical application of a navigation system for transferring the preoperative planning to real‐time operations could make liver surgery safer and more standardized in the near future.
Chronic kidney disease in adolescent and adult patients with phenylketonuria
Authors: Hennermann Julia B. , Roloff Sylvia , Gellermann Jutta , Vollmer Ilka , Windt Elke , Vetter Barbara , Plöckinger Ursula , Mönch Eberhard , Querfeld Uwe
Published: November 2012

Objectives

A lifelong phenylalanine‐restricted diet with supplementation of a phenylalanine‐free amino acid formula is recommended in patients with phenylketonuria (PKU). The effect of a long‐term PKU diet on renal function and blood pressure has not been investigated yet.

Design

We analyzed renal function in 67 patients with PKU, aged 15–43 years, by measuring glomerular filtration rate (GFR) and effective renal plasma flow by isotope clearance (51Cr‐EDTA, 123J‐Hippuran), estimated GFR, blood retention parameters, urinary protein and electrolyte excretion. Renal ultrasound and 24 h ambulatory blood pressure monitoring were performed additionally. Patients were divided into three groups according to their: 1) current diet (CD), i.e., daily protein intake: ICD <0.8 g/kg, IICD 0.8–1.04 g/kg, IIICD >1.04 g/kg; 2) life‐long diet time (LDT), i.e., cumulative years of life in which daily protein intake exceeded dietary recommendations: ILDT <15 years, IILDT 15–19 years, IIILDT >19 years.

Results

GFR was decreased in 19 % of the patients. With increasing protein intake, GFR decreased significantly (ICD 111 ml/min; IICD 105 ml/min; IIICD 99 ml/min. ILDT 112 ml/min; IILDT 103 ml/min; IIILDT 99 ml/min). Proteinuria was detected in 31 %, microalbuminuria in 7 %, and hypercalciuria in 23 % of the patients. 23 % of the patients had arterial hypertension, and 41 % revealed a nocturnal non‐dipping status.

Conclusions

In patients with PKU on a lifelong diet we could detect impaired renal function in 19 %, proteinuria in 31 %, and arterial hypertension in 23 %. Thus, chronic kidney disease may develop in PKU patients, and routine renal function tests should be performed during long‐term follow‐up.
Demographics, diagnosis and treatment of 256 patients with tetrahydrobiopterin deficiency in mainland China: results of a retrospective, multicentre study
Authors: Ye Jun , Yang Yanling , Yu Weimin , Zou Hui , Jiang Jianhui , Yang Rulai , Shang Sunny , Gu Xuefan
Published: November 2012

Background

National coverage of neonatal screening for hyperphenylalaninaemia (HPA) in China is still low and tests to differentiate causes of HPA are not performed in many centres. This study aimed to describe the demographics, geographic distribution, diagnosis, treatment and clinical outcomes of treatment, including intellectual development, in patients with tetrahydrobiopterin (BH4) deficiency in mainland China.

Methods

This was a retrospective, multicentre, chart review in patients with BH4 deficiency across mainland China born 1985–2010.

Results

Two hundred fifty six patients were included; 59.9 % (267/446) of parents were from eastern China. Median (interquartile range) age at diagnosis decreased from 12.0 (5.5, 102.0) months to 2.0 (1.0, 3.5) months in patients born 1985–1999 (n = 28) and 2005–2010 (n = 152), respectively. 6‐Pyruvoyl‐tetrahydropterin synthase (PTPS) deficiency was the primary cause of BH4 deficiency (96.0 %); four hotspot mutations accounted for 76.6 % of PTS gene mutations; two novel variants in the QDPR gene were identified. Most patients (83.6 %) received treatment with BH4, l‐dopa, 5‐hydroxytryptophan and/or diet therapy. Target blood Phe concentration was confirmed at 88.9 % of visits; median (Q1, Q3) blood Phe concentration was 106.8 (73.0, 120.0) μmol/L during therapy and 117.0 (67.1, 120.0) μmol/L at last visit. Median (Q1, Q3) WISC IQ score was 80.0 (69.0, 90.0) in 33 patients. DQ scores were within normal range (≥85) for 37/59 (62.7 %) patients. Physical development indicators were within normal ranges. Treatment‐related adverse events, reported in 20/256 (7.8 %) patients, were mild‐to‐moderate in severity.

Conclusion

This study provides valuable information on the current and historical situation of BH4 deficiency in mainland China.
A Coupled Thermal/Material Flow Model of Friction Stir Welding Applied to Sc-Modified Aluminum Alloys
Authors: Hamilton Carter , Kopyściański Mateusz , Senkov Oleg , Dymek Stanislaw
Published: November 2012

A coupled thermal/material flow model of friction stir welding was developed and applied to the joining of Sc-modified aluminum alloy (7042-T6) extrusions. The model reveals that surface material is pulled from the retreating side into the weld zone where it is interleaved with in situ material. Due to frictional contact with the shoulder, the surface material is hotter than the in situ material, so that the final weld microstructure is composed of bands of material with different temperature histories. For this alloy and the associated FSW heating rates, secondary phase dissolution/precipitation temperatures are in proximity to the welding temperatures. Therefore, depending on the surface and in situ material temperatures in relation to these transformation temperatures, disparate precipitate distributions can develop in the bands of material comprising the weld nugget. Based on the numerical simulation and on thermal analysis data from differential scanning calorimetry, a mechanism for the formation of onion rings within the weld zone is presented.
Some Sugar Fatty Ester Ethoxylates as Demulsifiers for Petroleum Sludge
Authors: Abdul‐Raheim Mahmoud A. , Abdel‐Raouf Manar El‐Sayed , Maysour Nermine El‐Sayed , El‐Kafrawy Ahmed Fawzy , Mehany Ahmed Zaher , Abdel‐Azim Ahmed
Published: November 2012

Several ethoxylated sugar fatty ester surfactants were prepared by the reaction of glucose with three fatty acids, namely, adipic, stearic and palmitic acids to produce GA, GS and GP esters. These glucose esters were then ethoxylated by four different molecular weight polyethylene glycols, namely, 400, 1,000, 2,000 and 4,000 mol L−1. The prepared ethoxylated esters (12 compounds) were characterized by IR and 1H‐NMR spectroscopy. The surface activity of the prepared compounds was thoroughly studied by measuring the surface tension of different solutions of these compounds at three temperatures, namely 298, 308 and 318 K. From the surface tension‐concentration plots of these compounds some surface properties, such as CMC (critical micelle concentration), Γmax (maximum surface excess concentration) and Amin (area occupied per molecule) were calculated. The surface properties of the prepared surfactants were correlated to their chemical structure. It was found that the CMC decreases when increasing the molecular weight of polyethylene glycols, whereas Amin increases. Furthermore, the demulsification test was carried out and the results of demulsification efficiency were correlated to the chemical composition of the investigated compounds. Some factors that affect the demulsification efficiency were also considered. The oil phase recovered from the treated sludge was characterized and mixed with fresh crude to improve its API.