bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of 3T MR scanners in regional cartilage-thickness analysis in osteoarthritis: a cross-sectional multicenter, multivendor study
Authors: Balamoody Sharon , Williams Tomos G , Waterton John C , Bowes Michael , Hodgson Richard , Taylor Chris J , Hutchinson Charles E
Published: October 2010

Introduction

Cartilage thickness from MR images has been identified as a possible biomarker in knee osteoarthritis (OA) research. The ability to acquire MR data at multiple centers by using different vendors' scanners would facilitate patient recruitment and shorten the duration of OA trials. Several vendors manufacture 3T MR scanners, including Siemens, Philips Medical Systems, and GE Healthcare. This study investigates whether quantitative MR assessments of cartilage morphology are comparable between scanners of three different vendors.

Methods

Twelve subjects with symptoms of knee OA and one or more risk factors had their symptomatic knee scanned on each of the three vendor's scanners located in three sites in the UK: Manchester (Philips), York (GE), and Liverpool (Siemens). The NIH OAI study protocol was used for the Siemens scanner, and equivalent protocols were developed for the Philips and GE scanners with vendors' advice. Cartilage was segmented manually from sagittal 3D images. By using recently described techniques for Anatomically Corresponded Regional Analysis of Cartilage (ACRAC), a statistical model was used anatomically to align all the images and to produce detailed maps of mean differences in cartilage-thickness measures between scanners. Measures of cartilage mean thickness were computed in anatomically equivalent regions for each subject and scanner image.

Results

The ranges of mean cartilage-thickness measures for this cohort were similar for all regions and across all scanners. Philips intrascanner root-mean-square coefficients of variation were low in the range from 2.6% to 4.6%. No significant differences were found for thickness measures of the weight-bearing femorotibial regions from the Philips and Siemens images except for the central medial femur compartment (P = 0.04). Compared with the other two scanners, the GE scanner provided consistently lower mean thickness measures in the central femoral regions (mean difference, -0.16 mm) and higher measures in the tibial compartments (mean difference, +0.19 mm).

Conclusions

The OAI knee-imaging protocol, developed on the Siemens platform, can be applied to research and trials by using other vendors' 3T scanners giving comparable morphologic results. Accurate sequence optimization, differences in image postprocessing, and extremity coil type are critical factors for interscanner precision of quantitative analysis of cartilage morphology. It is still recommended that longitudinal observations on individuals should be performed on the same scanner and that assessment of intra- and interscanner precision errors is undertaken before commencement of the main study.
Resistin is associated with mortality in patients with traumatic brain injury
Authors: Dong Xiao-Qiao , Yang Song-Bin , Zhu Fang-Long , Lv Qing-Wei , Zhang Guo-Hai , Huang Hang-Bin
Published: October 2010

Introduction

Recently, we reported that high levels of resistin are present in the peripheral blood of patients with intracerebral hemorrhage and are associated with a poor outcome. However, not much is known regarding the change in plasma resistin and its relation with mortality after traumatic brain injury (TBI). Thus, we sought to investigate change in plasma resistin level after TBI and to evaluate its relation with disease outcome.

Methods

Fifty healthy controls and 94 patients with acute severe TBI were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5 and 7 after TBI. Its concentration was measured by enzyme-linked immunosorbent assay.

Results

Twenty-six patients (27.7%) died from TBI within 1 month. After TBI, plasma resistin level in patients increased during the 6-hour period immediately after TBI, peaked within 24 hours, plateaued at day 2, decreased gradually thereafter and was substantially higher than that in healthy controls during the 7-day period. A forward stepwise logistic regression selected plasma resistin level (odds ratio, 1.107; 95% confidence interval, 1.014-1.208; P = 0.023) as an independent predictor for 1-month mortality of patients. A multivariate linear regression showed that plasma resistin level was negatively associated with Glasgow Coma Scale score (t = -6.567, P < 0.001). A receiver operating characteristic curve identified plasma resistin cutoff level (30.8 ng/mL) that predicted 1-month mortality with the optimal sensitivity (84.6%) and specificity (75.0%) values (area under curve, 0.854; 95% confidence interval, 0.766-0.918; P < 0.001).

Conclusions

Increased plasma resistin level is found and associated with Glasgow Coma Scale score and mortality after TBI.
Hyperoncotic colloids and acute kidney injury: a meta-analysis of randomized trials
Authors: Wiedermann Christian J , Dunzendorfer Stefan , Gaioni Luigi U , Zaraca Francesco , Joannidis Michael
Published: October 2010

Introduction

It has been hypothesized that hyperoncotic colloids might contribute to acute kidney injury (AKI). However, the validity of this hypothesis remains unclear.

Methods

A meta-analysis was conducted of randomized controlled trials evaluating AKI after infusion of hyperoncotic albumin and hydroxyethyl starch (HES) solutions. Mortality was a secondary endpoint. Eligible trials were sought by multiple methods, and the pooled odds ratios (OR) for AKI and death and 95% confidence intervals (CI) were computed under a random effects model.

Results

Eleven randomized trials with a total of 1220 patients were included: 7 evaluating hyperoncotic albumin and 4 hyperoncotic HES. Clinical indications were ascites, surgery, sepsis and spontaneous bacterial peritonitis. Hyperoncotic albumin decreased the odds of AKI by 76% (OR, 0.24; CI, 0.12-0.48;P< 0.0001), while hyperoncotic HES increased those odds by 92% (OR, 1.92; CI, 1.31-2.81;P= 0.0008). Parallel effects on mortality were observed, with hyperoncotic albumin reducing the odds of death by 48% (OR, 0.52; CI, 0.28-0.95;P= 0.035) and hyperoncotic HES raising those odds by 41% (OR, 1.41; CI, 1.01-1.96;P= 0.043).

Conclusions

This meta-analysis does not support the hypothesis that hyperoncotic colloid solutionsper seinjure the kidney. Renal effects appear instead to be colloid-specific, with albumin displaying renoprotection and HES showing nephrotoxicity.
Normal Cortisol Response to High-Dose Synacthen and Insulin Tolerance Test in Children and Adults with Prader-Willi Syndrome
Authors: Farholt Stense , Sode-Carlsen Rasmus , Christiansen Jens Sandahl , Østergaard John R. , Høybye Charlotte
Published: October 2010

Context: Prader-Willi syndrome (PWS) is a genetic disease associated with hypogonadism and partial GH insufficiency, possibly explained in part by a hypothalamic dysfunction. Partial insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis has recently been suggested.

Objective: The objective of the study was to further explore the HPA axis in PWS by use of routine tests.

Design: Nonselected PWS patients were examined with a standard high-dose synacthen test or the insulin tolerance test (ITT). A random serum (s) cortisol was measured in case of acute illness.

Setting: The study was conducted at university hospitals in Denmark and Sweden.

Patients: Sixty-five PWS patients with a confirmed genetic diagnosis participated in the study.

Main Outcome Measures: A s-cortisol value above 500 nmol/liter as well as an increase of 250 nmol/liter or greater was considered a normal response.

Results: Fifty-seven PWS patients (median age 22 yr, total range 0.5–48 yr) were examined with the high-dose synacthen test. The median s-cortisol at the time of 30 min was 699 (474–1578) nmol/liter. Only one patient had a s-cortisol level below 500 nmol/liter but an increase of 359 nmol/liter. This patient subsequently showed a normal ITT response. Two patients had increases less than 250 nmol/liter but a time of 30-min s-cortisol values of 600 nmol/liter or greater. These three patients were interpreted as normal responders. Eight patients [aged 26 (16–36) yr] examined with the ITT had a median peak s-cortisol of 668 (502–822) nmol/liter. Four children admitted for acute illnesses had s-cortisol values ranging from 680 to 1372 nmol/liter.

Conclusion: In this PWS cohort, the function of the HPA axis was normal, suggesting that clinically significant adrenal insufficiency in PWS is rare.
Association of 25(OH)D and PTH with Metabolic Syndrome and Its Traditional and Nontraditional Components
Authors: Kayaniyil Sheena , Vieth Reinhold , Harris Stewart B. , Retnakaran Ravi , Knight Julia A. , Gerstein Hertzel C. , Perkins Bruce A. , Zinman Bernard , Hanley Anthony J.
Published: October 2010

Context: Emerging evidence suggests that 25-hydroxy vitamin D [25(OH)D] and PTH may play a role in the etiology of the metabolic syndrome (MetS). However, evidence to date is limited and inconsistent, and few studies have examined associations with nontraditional MetS components.

Objective: The objective of the study was to examine the association of vitamin D and PTH with MetS and its traditional and nontraditional components in a large multiethnic sample.

Design, Setting, and Participants: In this cross-sectional study, we examined 654 participants from London and Toronto, Ontario, Canada, aged 30 yr and older with risk factors for type 2 diabetes.

Main Outcome Measures: Presence of MetS and its traditional and nontraditional components was measured.

Results: Approximately 43% of the study participants were classified as having MetS. Higher 25(OH)D was significantly associated with a reduced presence of MetS after adjustment for age, sex, season, ethnicity, supplement use, physical activity, and PTH (odds ratio 0.76, 95% confidence interval 0.62–0.93). PTH was not associated with the presence of MetS after multivariate adjustment. Multivariate linear regression analyses indicated significant adjusted inverse associations of 25(OH)D with waist circumference, triglyceride level, fasting insulin, and alanine transaminase (P < 0.041). Elevated PTH was positively associated with waist circumference and high-density lipoprotein cholesterol (P < 0.04). Other associations between PTH and MetS components were attenuated after adjustment for adiposity.

Conclusions: Serum 25(OH)D, but not PTH, was significantly associated with MetS as well as a number of MetS components after multivariate adjustment. These results suggest that low 25(OH)D may play a role in the etiology of the MetS.
Klf5 regulates lineage formation in the pre-implantation mouse embryo
Authors: Lin Suh-Chin J. , Wani Maqsood A. , Whitsett Jeffrey A. , Wells James M.
Published: October 2010

Kruppel-like transcription factors (Klfs) are essential for the induction and maintenance of pluripotency of embryonic stem cells (ESCs), yet little is known about their roles in establishing the three lineages of the pre-implantation embryo. Here, we show that Klf5 is required for the formation of the trophectoderm (TE) and the inner cell mass (ICM), and for repressing primitive endoderm (PE) development. Although cell polarity appeared normal, Klf5 mutant embryos arrested at the blastocyst stage and failed to hatch due to defective TE development. Klf5 acted cell-autonomously in the TE, downstream of Fgf4 and upstream of Cdx2, Eomes and Krt8. In the ICM, loss of Klf5 resulted in reduced expression of pluripotency markers Oct4 and Nanog, but led to increased Sox17 expression in the PE, suggesting that Klf5 suppresses the PE lineage. Consistent with this, overexpression of Klf5 in transgenic embryos was sufficient to suppress the Sox17+ PE lineage in the ICM. Klf5 overexpression led to a dose-dependent decrease in Sox17 promoter activity in reporter assays in cultured cells. Moreover, in chimeric embryos, Klf5–/– cells preferentially contributed to the Sox17+ PE lineage and Cdx2 expression was not rescued in Klf5–/– outer cells. Finally, outgrowths from Klf5–/– embryos failed to form an ICM/pluripotent colony, had very few Oct4+ or Cdx2+ cells, but showed an increase in the percentage of Sox17+ PE cells. These findings demonstrate that Klf5 is a dynamic regulator of all three lineages in the pre-implantation embryo by promoting the TE and epiblast lineages while suppressing the PE lineage.
Role of canonical Wnt signaling/β-catenin viaDermo1in cranial dermal cell development
Authors: Tran Thu H. , Jarrell Andrew , Zentner Gabriel E. , Welsh Adrienne , Brownell Isaac , Scacheri Peter C. , Atit Radhika
Published: October 2010

Cranial dermis develops from cephalic mesoderm and neural crest cells, but what signal(s) specifies the dermal lineage is unclear. Using genetic tools to fate map and manipulate a cranial mesenchymal progenitor population in the supraorbital region, we show that the dermal progenitor cells beneath the surface ectoderm process canonical Wnt signaling at the time of specification. We show that Wnt signaling/β-catenin is absolutely required and sufficient for Dermo1 expression and dermal cell identity in the cranium. The absence of the Wnt signaling cue leads to formation of cartilage in craniofacial and ventral trunk regions at the expense of dermal and bone lineages. Dermo1 can be a direct transcription target and may mediate the functional role of Wnt signaling in dermal precursors. This study reveals a lineage-specific role of canonical Wnt signaling/β-catenin in promoting dermal cell fate in distinct precursor populations.
Defective granulation tissue formation in mice with specific ablation of integrin-linked kinase in fibroblasts – role of TGFβ1 levels and RhoA activity
Authors: Blumbach Katrin , Zweers Manon C. , Brunner Georg , Peters Andreas S. , Schmitz Markus , Schulz Jan-Niklas , Schild Alexander , Denton Christopher P. , Sakai Takao , Fässler Reinhard , Krieg Thomas , Eckes Beate
Published: October 2010

Wound healing crucially relies on the mechanical activity of fibroblasts responding to TGFβ1 and to forces transmitted across focal adhesions. Integrin-linked kinase (ILK) is a central adapter recruited to integrin β1 tails in focal adhesions mediating the communication between cells and extracellular matrix. Here, we show that fibroblast-restricted inactivation of ILK in mice leads to impaired healing due to a severe reduction in the number of myofibroblasts, whereas inflammatory infiltrate and vascularization of the granulation tissue are unaffected. Primary ILK-deficient fibroblasts exhibit severely reduced levels of extracellular TGFβ1, α-smooth muscle actin (αSMA) production and myofibroblast conversion, which are rescued by exogenous TGFβ1. They are further characterized by elevated RhoA and low Rac1 activities, resulting in abnormal shape and reduced directional migration. Interference with RhoA–ROCK signaling largely restores morphology, migration and TGFβ1 levels. We conclude that, in fibroblasts, ILK is crucial for limiting RhoA activity, thus promoting TGFβ1 production, which is essential for dermal repair following injury.
Dynamic instability of the intracellular pressure drives bleb-based motility
Authors: Maugis Benoît , Brugués Jan , Nassoy Pierre , Guillen Nancy , Sens Pierre , Amblard François
Published: October 2010

We have demonstrated that the two- and three-dimensional motility of the human pathogenic parasite Entamoeba histolytica (Eh) depends on sustained instability of the intracellular hydrostatic pressure. This instability drives the cyclic generation and healing of membrane blebs, with typical protrusion velocities of 10–20 μm/second over a few hundred milliseconds and healing times of 10 seconds. The use of a novel micro-electroporation method to control the intracellular pressure enabled us to develop a qualitative model with three parameters: the rate of the myosin-driven internal pressure increase; the critical disjunction stress of membrane–cytoskeleton bonds; and the turnover time of the F-actin cortex. Although blebs occur randomly in space and irregularly time, they can be forced to occur with a defined periodicity in confined geometries, thus confirming our model. Given the highly efficient bleb-based motility of Eh in vitro and in vivo, Eh cells represent a unique model for studying the physical and biological aspects of amoeboid versus mesenchymal motility in two- and three-dimensional environments.
Kinectin-mediated endoplasmic reticulum dynamics supports focal adhesion growth in the cellular lamella
Authors: Zhang Xin , Tee Yee Han , Heng Justin K. , Zhu Yajuan , Hu Xian , Margadant Felix , Ballestrem Christoph , Bershadsky Alexander , Griffiths Gareth , Yu Hanry
Published: October 2010

Focal adhesions (FAs) control cell shape and motility, which are important processes that underlie a wide range of physiological functions. FA dynamics is regulated by cytoskeleton, motor proteins and small GTPases. Kinectin is an integral endoplasmic reticulum (ER) membrane protein that extends the ER along microtubules. Here, we investigated the influence of the ER on FA dynamics within the cellular lamella by disrupting the kinectin–kinesin interaction by overexpressing the minimal kinectin–kinesin interaction domain on kinectin in cells. This perturbation resulted in a morphological change to a rounded cell shape and reduced cell spreading and migration. Immunofluorescence and live-cell imaging demonstrated a kinectin-dependent ER extension into the cellular lamella and ER colocalisation with FAs within the cellular lamella. FRAP experiments showed that ER contact with FAs was accompanied with an increase in FA protein recruitment to FAs. Disruption of the kinectin–kinesin interaction caused a reduction in FA protein recruitment to FAs. This suggests that the ER supports FA growth within the cellular lamella. Microtubule targeting to FAs is known to promote adhesion disassembly; however, ER contact increased FA size even in the presence of microtubules. Our results suggest a scenario whereby kinectin–kinesin interaction facilitates ER transport along microtubules to support FA growth.
ADAM17 is regulated by a rapid and reversible mechanism that controls access to its catalytic site
Authors: Le Gall Sylvain M. , Maretzky Thorsten , Issuree Priya D. A. , Niu Xiao-Da , Reiss Karina , Saftig Paul , Khokha Rama , Lundell Daniel , Blobel Carl P.
Published: October 2010

Protein ectodomain shedding is crucial for cell–cell interactions because it controls the bioavailability of soluble tumor necrosis factor-α (TNFα) and ligands of the epidermal growth factor (EGF) receptor, and the release of many other membrane proteins. Various stimuli can rapidly trigger ectodomain shedding, yet much remains to be learned about the identity of the enzymes that respond to these stimuli and the mechanisms underlying their activation. Here, we demonstrate that the membrane-anchored metalloproteinase ADAM17, but not ADAM10, is the sheddase that rapidly responds to the physiological signaling pathways stimulated by thrombin, EGF, lysophosphatidic acid and TNFα. Stimulation of ADAM17 is swift and quickly reversible, and does not depend on removal of its inhibitory pro-domain by pro-protein convertases, or on dissociation of an endogenous inhibitor, TIMP3. Moreover, activation of ADAM17 by physiological stimuli requires its transmembrane domain, but not its cytoplasmic domain, arguing against inside–out signaling via cytoplasmic phosphorylation as the underlying mechanism. Finally, experiments with the tight binding hydroxamate inhibitor DPC333, used here to probe the accessibility of the active site of ADAM17, demonstrate that this inhibitor can quickly bind to ADAM17 in stimulated, but not quiescent cells. These findings support the concept that activation of ADAM17 involves a rapid and reversible exposure of its catalytic site.
Autocrine fibronectin directs matrix assembly and crosstalk between cell–matrix and cell–cell adhesion in vascular endothelial cells
Authors: Cseh Botond , Fernandez-Sauze Samantha , Grall Dominique , Schaub Sébastien , Doma Eszter , Van Obberghen-Schilling Ellen
Published: October 2010

Cellular fibronectin (cFN) variants harboring extra FN type 3 repeats, namely extra domains B and A, are major constituents of the extracellular matrix around newly forming blood vessels during development and angiogenesis. Their expression is induced by angiogenic stimuli and their assembly into fibrillar arrays is driven by cell-generated tension at α5β1 integrin-based adhesions. Here, we examined the role and functional redundancy of cFN variants in cultured endothelial cells by isoform-selective RNA interference. We show that FN fibrillogenesis is a cell-autonomous process whereby basally directed secretion and assembly of cellular FN are tightly coupled events that play an important role not only in signaling at cell–matrix adhesions but also at cell–cell contacts. Silencing of cFN variants differentially affects integrin usage, cell spreading, motility and capillary morphogenesis in vitro. cFN-deficient cells undergo a switch from α5β1- to αvβ3-based adhesion, accompanied by a Src-regulated disruption of adherens junctions. These studies identify a crucial role for autocrine FN in subendothelial matrix assembly and junctional integrity that provides spatially and temporally restricted control of endothelial plasticity during angiogenic blood vessel remodeling.
Oncogenic Src requires a wild-type counterpart to regulate invadopodia maturation
Authors: Kelley Laura C. , Ammer Amanda Gatesman , Hayes Karen E. , Martin Karen H. , Machida Kazuya , Jia Lin , Mayer Bruce J. , Weed Scott A.
Published: October 2010

The proto-oncogene Src tyrosine kinase (Src) is overexpressed in human cancers and is currently a target of anti-invasive therapies. Activation of Src is an essential catalyst of invadopodia production. Invadopodia are cellular structures that mediate extracellular matrix (ECM) proteolysis, allowing invasive cell types to breach confining tissue barriers. Invadopodia assembly and maturation is a multistep process, first requiring the targeting of actin-associated proteins to form pre-invadopodia, which subsequently mature by recruitment and activation of matrix metalloproteases (MMPs) that facilitate ECM degradation. We demonstrate that active, oncogenic Src alleles require the presence of a wild-type counterpart to induce ECM degradation at invadopodia sites. In addition, we identify the phosphorylation of the invadopodia regulatory protein cortactin as an important mediator of invadopodia maturation downstream of wild-type Src. Distinct phosphotyrosine-based protein-binding profiles in cells forming pre-invadopodia and mature invadopodia were identified by SH2-domain array analysis. These results indicate that although elevated Src kinase activity is required to target actin-associated proteins to pre-invadopodia, regulated Src activity is required for invadopodia maturation and matrix degradation activity. Our findings describe a previously unappreciated role for proto-oncogenic Src in enabling the invasive activity of constitutively active Src alleles.
Biogenesis pathways of piRNAs loaded onto AGO3 in the Drosophila testis
Authors: Nagao Akihiro , Mituyama Toutai , Huang Haidong , Chen Dahua , Siomi Mikiko C. , Siomi Haruhiko
Published: October 2010

PIWI-interacting RNAs (piRNAs) silence transposable elements in animal germ cells. In Drosophila ovaries, piRNAs are produced by two distinct pathways: the “ping-pong” amplification cycle that operates in germ cells and a ping-pong-independent pathway termed the primary pathway that mainly operates in somatic cells. AGO3, one of three PIWI proteins in flies, is involved in the ping-pong cycle in ovaries. We characterized AGO3-associated piRNAs in fly testes and found that like in ovaries, AGO3 functions in the ping-pong cycle with Aubergine (Aub) for piRNA production from transposon transcripts. In contrast, most AGO3-associated piRNAs corresponding to Suppressor of Stellate [Su(Ste)] genes are antisense-oriented and bound to Aub. In addition, the vast majority of AGO3-bound piRNAs derived from the AT-chX locus on chromosome X are antisense-oriented and are also found among Aub-associated piRNAs. The presence of very few sense Su(Ste) and AT-chX piRNAs suggests that biogenesis of both Su(Ste) and AT-chX piRNAs by a ping-pong mechanism only is highly unlikely. Nevertheless, the mutual interdependence of AGO3 and Aub for the accumulation of these piRNAs shows that their production relies on both AGO3 and Aub. Analysis of piRNA pathway mutants revealed that although the requirements for piRNA factors for Su(Ste)- and AT-chX-piRNA levels mostly overlap and resemble those for the ping-pong mechanism in the ovaries, Armitage (armi) is not required for the accumulation of AT-chX-1 piRNA. These findings suggest that the impacts of armi mutants on the operation of the piRNA pathway are variable in germ cells of fly testes.
Modified least-variant set normalization for miRNA microarray
Authors: Suo Chen , Salim Agus , Chia Kee-Seng , Pawitan Yudi , Calza Stefano
Published: October 2010

MicroRNAs (miRNAs) are short noncoding RNAs that are involved in post-transcriptional regulation of mRNAs. Microarrays have been employed to measure global miRNA expressions; however, because the number of miRNAs is much smaller than the number of mRNAs, it is not clear whether traditional normalization methods developed for mRNA arrays are suitable for miRNA. This is an important question, since normalization affects downstream analyses of the data. In this paper we develop a least-variant set (LVS) normalization method, which was previously shown to outperform other methods in mRNA analysis when standard assumptions are violated. The selection of the LVS miRNAs is based on a robust linear model fit of the probe-level data that takes into account the considerable differences in variances between probes. In a spike-in study, we show that the LVS has similar operating characteristics, in terms of sensitivity and specificity, compared with the ideal normalization, and it is better than no normalization, 75th percentile-shift, quantile, global median, VSN, and lowess normalization methods. We evaluate four expression-summary measures using a tissue data set; summarization from the robust model performs as well as the others. Finally, comparisons using expression data from two dissimilar tissues and two similar ones show that LVS normalization has better operating characteristics than other normalizations.
Conformational distributions at the N-peptide/boxB RNA interface studied using site-directed spin labeling
Authors: Zhang Xiaojun , Lee Sang Won , Zhao Liang , Xia Tianbing , Qin Peter Z.
Published: October 2010

In bacteriophage λ, interactions between a 22-amino acid peptide (called the N-peptide) and a stem–loop RNA element (called boxB) play a critical role in transcription anti-termination. The N-peptide/boxB complex has been extensively studied, and serves as a paradigm for understanding mechanisms of protein/RNA recognition. Particularly, ultrafast spectroscopy techniques have been applied to monitor picosecond fluorescence decay behaviors of 2-aminopurines embedded at various positions of the boxB RNA. The studies have led to a model in which the bound N-peptide exists in dynamic equilibrium between two states, with peptide C-terminal fragment either stacking on (i.e., the stacked state) or peeling away from (i.e., the unstacked state) the RNA loop. The function of the N-peptide/boxB complex seems to correlate with the fraction of the stacked state. Here, the N-peptide/boxB system is studied using the site-directed spin labeling technique, in which X-band electron paramagnetic resonance spectroscopy is applied to monitor nanosecond rotational behaviors of stable nitroxide radicals covalently attached to different positions of the N-peptide. The data reveal that in the nanosecond regime the C-terminal fragment of bound N-peptide adopts multiple discrete conformations within the complex. The characteristics of these conformations are consistent with the proposed stacked and unstacked states, and their distributions vary upon mutations within the N-peptide. These results suggest that the dynamic two-state model remains valid in the nanosecond regime, and represents a unique mode of function in the N-peptide/boxB RNA complex. It also demonstrates a connection between picosecond and nanosecond dynamics in a biological complex.
The contribution of free dailies and news on the web: implications of media structural changes for the Swedish newspaper readership market
Authors: Bergstrm Annika , Wadbring Ingela
Published: October 2010

The decline in reading the morning papers has been considered a problem in modern countries in recent decades. In particular, it is young people who are abandoning the paid morning paper. During the same period, new forms of newspapers such as free dailies and online news have developed.
The purpose of this article, in which we take different types of newspapers into consideration, is to analyse the development of readership among Swedes in the first decade of the twenty-first century. The data analysed have been collected through postal surveys of 6000 people each year since
2000. When we add new forms of newspapers to the traditional ones, the readership level is very stable even among young people. Readership is still decreasing, but not to the same extent as when only traditional papers are measured. It can be difficult to determine, however, what should be
considered a newspaper in the twenty-first century. Evening tabloids online are not the same with regard to content and function as local morning papers.
The reading of cultural and lifestyle journalism
Authors: From Unni
Published: October 2010

Based on analyses of 25 qualitative individual interviews with readers from different demographic backgrounds, this article investigates how readers experience and use journalism on culture in both online and print press. I argue that the use of journalism on culture is constituted
within different reading positions. These reading positions are characterized not only as objectively and ideologically determined categories (Hall 1973), but also as subjectively constituted (Schrder 2000) ways for audiences to negotiate personal and professional interests related to their
engagement in the (cultural) public sphere (Couldry et al 2007) and the media they choose to use. Different reading patterns result from the ways in which readers negotiate and use different texts and textual elements (e.g. critical debate in a review) for different purposes (e.g. relaxation,
entertainment, information, education etc.). Thus, the article explores whether and how the use of journalism on culture is interrelated with more universal processes of meaning production, and therefore it draws on a socio-cognitive perspective, especially in regard to schemes of expectation
and experience (e.g. Bruun 2004; Waldahl 1998; Engebretsen 1998).
Audience views on user-generated content: exploring the value of news from the bottom up
Authors: Wahl-Jorgensen Karin , Williams Andrew , Wardle Claire
Published: October 2010

News organizations increasingly view user-generated content (UGC) as a vital resource for audience engagement and empowerment. Researchers have investigated the production practices and journalistic cultures surrounding UGC, but have paid less attention to the audiences who produce and consume the content. This article seeks to fill this gap in knowledge, drawing on a series of focus groups to understand why audiences value particular forms of UGC and renounce others. Further, by comparing focus group findings to data from in-depth interviews with BBC producers and journalists, it explores how audience perceptions differ from those of producers. In particular, the article focuses on why and how audiences value news-based UGC (in the form of images, footages and eyewitness accounts), which is perceived as authentic, immediate and real. This is contrasted with a dislike for audience comment, or opinion-based contributions, seen as ill-informed, repetitive and extremist. By contrast, BBC producers and journalists are more concerned with UGC as a tool to supplement traditional news-gathering practices.
From party agitators to independent pundits The changed historical roles of newspaper and television journalists in Norwegian election campaigns
Authors: Allern Sigurd
Published: October 2010

The focus of this article is the changing roles of the pundits of the press during national election campaigns and the consequences for the political role of television news and newspapers. Three election campaigns 1965, 1989 and 2009 are compared, mainly through content analyses. In
1965 most political commentators in the national and regional newspapers were leading party members, the members of the press lobby even meeting regularly in the party's groups in Stortinget (the Norwegian parliament). Their role as interpreters and agitators was on behalf of their party and
its ideology. In 1989 the party press was nearly abolished and the National Broadcasting Company had for long exercised full control over their election debates. The questioning programmes had been developed into tough interrogations, nicknamed as grilling of the politicians. Most of the political
commentators of the press were now formally independent, however often with strong political and ideological roots in the old party system. During the national election campaign in 2009 the political commentators had a new and far more visible role than in the public debate, compared with
1965 and 1989. The leading commentators are published more prominently than before, and are used as trademark for their own newspapers. The pundit elite has also been elevated to the role of chief experts on the political horse race in television news and debates.
The historical transformation of cultural journalism
Authors: Kristensen Nete Nrgaard
Published: October 2010

This article is based on the first content analysis of the coverage of culture, lifestyle and consumption or journalism on culture in the Danish printed press during the twentieth century. It argues that cultural journalism has expanded and developed its focus, interpretation and presentation
of culture concurrently with a changing culture and consumer industry and especially as part of, and a result of, an increasingly competitive and professionalized media landscape. This should be seen in the light of a culturalized and mediatized society: the media (in this case the newspapers
analysed and their coverage of journalism on culture) have developed from cultural institutions with a primary focus on the common public interest, towards media institutions whose primary focus is commercial and media-professional. More specifically, contemporary cultural journalism in a
continuum between culture, lifestyle and consumption is of considerable value and importance to the newspapers as media institutions. The individual newspapers, however, manage the form and content of their coverage of these subjects quite differently, according to their existing editorial
profiles. Thus, cultural journalism is a subject of both shared editorial priority and differentiation.
Constructing the audience: a study of segmentation in the Danish press
Authors: Willig Ida
Published: October 2010

No more than twenty years ago, the doors between the newsrooms and the marketing departments of Danish newspapers were tightly shut. Today, all major Danish newspapers work with reader profiles using marketing data to create journalistic concepts. This article identifies two dominant
reader constructions in policy papers of Danish newspapers: the reader-as-citizen, which can be traced back to the late 1940s, and the reader-as-consumer, visible in the historically new reader profiles, where we also find a third reader construction, the reader-as-commodity. The development
indicates a transformation from an Omnibus press system with a publicist logic of practice to a Segment press system with a commercial logic of practice.
Dialogical ambiguities: journalism, professionalism and flattery
Authors: Eide Martin
Published: October 2010

Journalism, as a soft profession, is facing severe challenges these days, and a need arises for professional maintenance work. Efforts to renegotiate the social contract of journalism reflect an expanding need for justification of journalism as a social institution. This position paper
asks what challenges are facing journalistic expertise. What kind of professional competences are at stake? And how does the drawing of boundaries and cooperation take place when journalists confront digital competitors and/or partners? The article addresses the professional interest in audience
participation and teamwork in current journalism, and discusses the problem of a flattering approach towards the audience.
Inhibition of interferon-α-induced signaling by hyperosmolarity and hydrophobic bile acids
Authors: Graf Dirk , Haselow Katrin , Münks Ivo , Bode Johannes G. , Häussinger Dieter
Published: October 2010

Apart from viral conditions, host factors such as elevated bile acid concentrations are determinants of successful interferon-α (IFN-α) treatment in patients with chronic hepatitis C or B. The present study demonstrates that hydrophobic bile acids inhibit Jak1- and Tyk2-phosphorylation, which lead to blockade of STAT1-mediated IFN-α-signaling in the sodium-taurocholate cotransporting peptide (NTCP)-transfected human hepatoma cell line HepG2, resulting in a decreased mRNA and protein expression of IFN-stimulated genes such as myxovirus resistance protein A (MxA) or dsRNA-activated protein kinase (PKR). In addition, hyperosmotic stress leads to an inhibition of IFN-α-induced Jak1- and Tyk2-phosphorylation, and STAT1/STAT2-phosphorylation and gene expression. This inhibitory effect of hydrophobic bile acids or hyperosmolarity is not due to caspase-mediated cleavage or lysosomal degradation of the cognate receptors or to the generation of oxidative stress, activation of p38- or Erk-mediated MAPK pathways or phosphatase activity. Preincubation with the organic osmolyte betaine blocked the inhibitory effect of bile acids or hyperosmolarity on MxA protein expression, but had no effect on transcript levels or activation of STAT1, suggesting that betaine mediates its effects on MxA expression at a translational or post-translational level. Our findings could provide a rationale for betaine use in cholestatic HBV/HCV patients undergoing interferon therapy.
Highlight: The Biology of Aging: Mechanisms and Intervention
Authors: Brüning Jens , Langer Thomas , Trifunovic Aleksandra
Published: October 2010

No abstract available
Plastic Tubing Prospect to Replace Cast Iron Conduit in Steam Heating Systems
Authors: Zhadanovsky Igor
Published: October 2010

Steam heating systems become obsolete because of water hammering, noise, high heat loss, installation cost, and poor control. The replacement of metal piping by a coaxial two tube thermoplastic conduit resolves all issues of current steam heating systems along with improvements in heating comfort level, energy efficiency, and maintenance and equipment durability. Polysulfone materials are proposed for the plastic conduit and fluoropolymers for the end connections to the radiators.
Measurement Method for the Assessment of the Energy Consumption of Cooking Setups
Authors: Grossmann Günter , Weiss Claudio
Published: October 2010

Energy efficiency in household appliances is a concern in energy saving scenarios. Especially, the equipment for cooking is very likely for energy waste since a lot of energy is used to produce steam, where simmering the goods to be cooked is sufficient. The reduction of this loss is the main goal of the energy optimization of cooking equipment. In standardization, only the measurement of the energy consumption of the heat up of water is regulated, not the cooking procedure itself, since the standard is dedicated to assess the heat transfer from the cooking zone to the water in a pan. However, it is the cooking phase after heat up that accounts for the largest part of energy waste. Thus, a comparison of the energy consumption between different cooking setups is difficult. In the work presented, a measurement procedure has been worked out to measure the energy needed for a cooking cycle with a cooking setup, which consists of the cooking zone, the cookware, and the regulating equipment, as well as to determine the influence of the behaviour of the user.
Kinetic Analysis of Thermally Simulated Processes in Biopolymer Poly(3-Hydroxybutyrate)
Authors: Yang Mu-Hoe
Published: October 2010

The thermal degradation of poly(3-hydroxybutyrate) (PHB) under a nitrogen atmosphere was studied by using various analytical models of thermogravimetric data in the dynamic conditions of temperatures ranging from 250 to 650 K. The activation energy of the thermal degradation for PHB was based on the variation of the analytical model. The influence of the testing analytical model on the thermal degradation characteristics of PHB has been discussed. The thermal degradation of PHB could be optimally corrected and calculated on the basis of kinetic parameters determined through the multiple regression method. Under these experimental conditions, the reaction was found to be of a 0.94-order with activation energy of 276 kJ/mol and a pre-exponential factor of 4.31×1026 s−1.
The Crystal Palace Concerts: Canon Formation and the English Musical Renaissance
Authors: Eatock Colin
Published: October 2010

This article examines the role of London's Crystal Palace in the popularization of “classical music” in Victorian Britain, and in the creation of the orchestral canon in the nineteenth century. The Crystal Palace was originally built in Hyde Park for the Great Exhibition of 1851 and was reconstructed in the London suburb of Sydenham in 1854. This popular attraction assumed a musical prominence in British culture when the ambitious conductor Augustus Manns established an orchestra there in 1855, and presented a series of Saturday Concerts until 1900.

Central to this discussion of the significance of the Crystal Palace concerts are two audience plebiscites that Manns conducted, in 1880 and 1887, which shed much light on Victorian popular taste and musical values. As well, particular attention is given to his involvement in the “English Musical Renaissance” in both of its aspects: as a campaign to raise British composers to canonic stature (to construct a “British Beethoven”); and as an effort to securely embed classical music within British culture.
Drosophila Mis12 Complex Acts as a Single Functional Unit Essential for Anaphase Chromosome Movement and a Robust Spindle Assembly Checkpoint
Authors: Venkei Zsolt , Przewloka Marcin R , Glover David M
Published: October 2010

The kinetochore is a dynamic multiprotein complex assembled at the centromere in mitosis. Exactly how the structure of the kinetochore changes during mitosis and how its individual components contribute to chromosome segregation is largely unknown. Here we have focused on the contribution of the Mis12 complex to kinetochore assembly and function throughout mitosis in Drosophila. We show that despite the sequential kinetochore recruitment of Mis12 complex subunits Mis12 and Nsl1, the complex acts as a single functional unit. mis12 and nsl1 mutants show strikingly similar developmental and mitotic defects in which chromosomes are able to congress at metaphase, but their anaphase movement is strongly affected. While kinetochore association of Ndc80 absolutely depends on both Mis12 and Nsl1, BubR1 localization shows only partial dependency. In the presence of residual centromeric BubR1 the checkpoint still responds to microtubule depolymerization but is significantly weaker. These observations point to a complexity of the checkpoint response that may reflect subpopulations of BubR1 associated with residual kinetochore components, the core centromere, or elsewhere in the cell. Importantly our results indicate that core structural elements of the inner plate of the kinetochore have a greater contribution to faithful chromosome segregation in anaphase than in earlier stages of mitosis.
Escherichia coli rnlA and rnlB Compose a Novel Toxin–Antitoxin System
Authors: Koga Mitsunori , Otsuka Yuichi , Lemire Sébastien , Yonesaki Tetsuro
Published: October 2010

RNase LS was originally identified as a potential antagonist of bacteriophage T4 infection. When T4 dmd is defective, RNase LS activity rapidly increases after T4 infection and cleaves T4 mRNAs to antagonize T4 reproduction. Here we show that rnlA, a structural gene of RNase LS, encodes a novel toxin, and that rnlB (formally yfjO), located immediately downstream of rnlA, encodes an antitoxin against RnlA. Ectopic expression of RnlA caused inhibition of cell growth and rapid degradation of mRNAs in ΔrnlAB cells. On the other hand, RnlB neutralized these RnlA effects. Furthermore, overexpression of RnlB in wild-type cells could completely suppress the growth defect of a T4 dmd mutant, that is, excess RnlB inhibited RNase LS activity. Pull-down analysis showed a specific interaction between RnlA and RnlB. Compared to RnlA, RnlB was extremely unstable, being degraded by ClpXP and Lon proteases, and this instability may increase RNase LS activity after T4 infection. All of these results suggested that rnlA–rnlB define a new toxin–antitoxin (TA) system.
Guanine Nucleotide Pool Imbalance Impairs Multiple Steps of Protein Synthesis and Disrupts GCN4 Translational Control in Saccharomyces cerevisiae
Authors: Iglesias-Gato Diego , Martín-Marcos Pilar , Santos María A , Hinnebusch Alan G , Tamame Mercedes
Published: October 2010

Purine nucleotides are structural components of the genetic material, function as phosphate donors, participate in cellular signaling, are cofactors in enzymatic reactions, and constitute the main carriers of cellular energy. Thus, imbalances in A/G nucleotide biosynthesis affect nearly the whole cellular metabolism and must be tightly regulated. We have identified a substitution mutation (G388D) that reduces the activity of the GMP synthase Gua1 in budding yeast and the total G-nucleotide pool, leading to precipitous reductions in the GDP/GTP ratio and ATP level in vivo. gua1–G388D strongly reduces the rate of growth, impairs general protein synthesis, and derepresses translation of GCN4 mRNA, encoding a transcriptional activator of diverse amino acid biosynthetic enzymes. Although processing of pre-tRNAiMet and other tRNA precursors, and the aminoacylation of tRNAiMet are also strongly impaired in gua1–G388D cells, tRNAiMet-containing complexes with the macromolecular composition of the eIF2·tRNAiMet.GTP complex (TC) and the multifactor complex (MFC) required for translation initiation accumulate ∼10-fold in gua1–G388D cells and, to a lesser extent, in wild-type (WT) cells treated with 6-azauracil (6AU). Consistently, addition of an external supply of guanine reverts all the phenotypes of gua1–G388D cells, but not those of gua1–G388D Δhpt1 mutants unable to refill the internal GMP pool through the salvage pathway. These and other findings suggest that a defect in guanine nucleotide biosynthesis evokes a reduction in the rate of general protein synthesis by impairing multiple steps of the process, disrupts the gene-specific reinitiation mechanism for translation of GCN4 mRNA and has far-reaching effects in cell biology and metabolism.