bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of nuclear factor-κB by 6-O-acetyl shanzhiside methyl ester protects brain against injury in a rat model of ischemia and reperfusion
Authors: Jiang Wanglin , Zhang Shuping , Fu Fenghua , Zhu Haibo , Hou Jian 
Published: September 2010

Abstract

Background
Recent studies have demonstrated an inflammatory response associated with the pathophysiology of cerebral ischemia. The beneficial effects of anti-inflammatory drugs in cerebral ischemia have been documented. When screening natural compounds for drug candidates in this category, we isolated 6-O-acetyl shanzhiside methyl ester (ND02), an iridoid glucoside compound, from the leaves of Lamiophlomis rotata (Benth.) Kudo. The objectives of this study were to determine the effects of ND02 on a cultured neuronal cell line, SH-SY5Y, in vitro, and on experimental ischemic stroke in vivo.

Methods
For TNF-α-stimulated SH-SY5Y cell line experiments in vitro, SH-SY5Y cells were pre-incubated with ND02 (20 μM or 40 μM) for 30 min and then incubated with TNF-α (20 ng/ml) for 15 min. For in vivo experiments, rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h followed by reperfusion for 23 h.

Results
ND02 treatment of SH-SY5Y cell lines blocked TNF-α-induced nuclear factor-κB (NF-κB) and IκB-α phosphorylation and increased Akt phosphorylation. LY294002 blocked TNF-α-induced phosphorylation of Akt and reduced the phosphorylation of both IκB-α and NF-κB. At doses higher than 10 mg/kg, ND02 had a significant neuroprotective effect in rats with cerebral ischemia and reperfusion (I/R). ND02 (25 mg/kg) demonstrated significant neuroprotective activity even after delayed administration 1 h, 3 h and 5 h after I/R. ND02, 25 mg/kg, attenuated histopathological damage, decreased cerebral Evans blue extravasation, inhibited NF-κB activation, and enhanced Akt phosphorylation.

Conclusion
These data show that ND02 protects brain against I/R injury with a favorable therapeutic time-window by alleviating cerebral I/R injury and attenuating blood-brain barrier (BBB) breakdown, and that these protective effects may be due to blocking of neuronal inflammatory cascades through an Akt-dependent NF-κB signaling pathway.
Isolation and characterization of a virus (CvV-BW1) that infects symbiotic algae of Paramecium bursaria in Lake Biwa, Japan
Authors: Hoshina Ryo , Shimizu Mayumi , Makino Yoichi , Haruyama Yoshihiro , Ueda Shin-ichiro , Kato Yutaka , Kasahara Masahiro , Ono Bun-ichiro , Imamura Nobutaka 
Published: September 2010

Abstract

Background
We performed an environmental study of viruses infecting the symbiotic single-celled algae of Paramecium bursaria (Paramecium bursaria Chlorella virus, PBCV) in Lake Biwa, the largest lake in Japan. The viruses detected were all Chlorella variabilis virus (CvV = NC64A virus). One of them, designated CvV-BW1, was subjected to further characterization.

Results
CvV-BW1 formed small plaques and had a linear DNA genome of 370 kb, as judged by pulsed-field gel electrophoresis. Restriction analysis indicated that CvV-BW1 DNA belongs to group H, one of the most resistant groups among CvV DNAs. Based on a phylogenetic tree constructed using the dnapol gene, CvV was classified into two clades, A and B. CvV-BW1 belonged to clade B, in contrast to all previously identified virus strains of group H that belonged to clade A.

Conclusions
We conclude that CvV-BW1 composes a distinct species within C. variabilis virus.
Differential Expression of ATP7A, ATP7B and CTR1 in Adult Rat Dorsal Root Ganglion Tissue
Authors: Ip Virginia , Liu Johnson J , Mercer Julian FB , McKeage Mark J 
Published: September 2010

Background: ATP7A, ATP7B and CTR1 are metal transporting proteins that control the cellular disposition of copper and platinum drugs, but their expression in dorsal root ganglion (DRG) tissue and their role in platinum-induced neurotoxicity are unknown. To investigate the DRG expression of ATP7A, ATP7B and CTR1, lumbar DRG and reference tissues were collected for real time quantitative PCR, RT-PCR, immunohistochemistry and Western blot analysis from healthy control adult rats or from animals treated with intraperitoneal oxaliplatin (1.85 mg/kg) or drug vehicle twice weekly for 8 weeks. Results: In DRG tissue from healthy control animals, ATP7A mRNA was clearly detectable at levels similar to those found in the brain and spinal cord, and intense ATP7A immunoreactivity was localised to the cytoplasm of cell bodies of smaller DRG neurons without staining of satellite cells, nerve fibres or co-localisation with phosphorylated heavy neurofilament subunit (pNF-H). High levels of CTR1 mRNA were detected in all tissues from healthy control animals, and strong CTR1 immunoreactivity was associated with plasma membranes and vesicular cytoplasmic structures of the cell bodies of larger-sized DRG neurons without co-localization with ATP7A. DRG neurons with strong expression of ATP7A or CTR1 had distinct cell body size profiles with minimal overlap between them. Oxaliplatin treatment did not alter the size profile of strongly ATP7A-immunoreactive neurons but significantly reduced the size profile of strongly CTR1-immunoreactive neurons. ATP7B mRNA was barely detectable, and no specific immunoreactivity for ATP7B was found, in DRG tissue from healthy control animals. Conclusions: In conclusion, adult rat DRG tissue exhibits a specific pattern of expression of copper transporters with distinct subsets of peripheral sensory neurons intensely expressing either ATP7A or CTR1, but not both or ATP7B. The neuron subtype-specific and largely non-overlapping distribution of ATP7A and CTR1 within rat DRG tissue may be required to support the potentially differing cuproenzyme requirements of distinct subsets of sensory neurons, and could influence the transport and neurotoxicity of oxaliplatin.
Meis1 specifies positional information in the retina and tectum to organize the zebrafish visual system
Authors: Erickson Timothy , French Curtis R , Waskiewicz Andrew J 
Published: September 2010

Abstract
Background
During visual system development, multiple signalling pathways cooperate to specify axial polarity within the retina and optic tectum. This information is required for the topographic mapping of retinal ganglion cell axons on the tectum. Meis1 is a TALE-class homeodomain transcription factor known to specify anterior-posterior identity in the hindbrain, but its role in visual system patterning has not been investigated.

Results
meis1 is expressed in both the presumptive retina and tectum. An analysis of retinal patterning reveals that Meis1 is required to correctly specify both dorsal-ventral and nasal-temporal identity in the zebrafish retina. Meis1-knockdown results in a loss of smad1 expression and an upregulation in follistatin expression, thereby causing lower levels of Bmp signalling and a partial ventralization of the retina. Additionally, Meis1-deficient embryos exhibit ectopic Fgf signalling in the developing retina and a corresponding loss of temporal identity. Meis1 also positively regulates ephrin gene expression in the tectum. Consistent with these patterning phenotypes, a knockdown of Meis1 ultimately results in retinotectal mapping defects.

Conclusions
In this work we describe a novel role for Meis1 in regulating Bmp signalling and in specifying temporal identity in the retina. By patterning both the retina and tectum, Meis1 plays an important role in establishing the retinotectal map and organizing the visual system.
Intronic motif pairs cooperate across exons to promote pre-mRNA splicing
Authors: Ke Shengdong , Chasin Lawrence A 
Published: September 2010

Abstract
Background
A very early step in splice site recognition is exon definition, a process that is as yet poorly understood. Communication between the two ends of an exon is thought to be required for this step. We report genome-wide evidence for exons being defined through the combinatorial activity of motifs located in flanking intronic regions.

Results
Strongly co-occurring motifs were found to specifically reside in four intronic regions surrounding a large number of human exons. These paired motifs occur around constitutive and alternative exons but not pseudo exons. Most co-occurring motifs are limited to intronic regions within 100 nucleotides of the exon. They are preferentially associated with weaker exons. Their pairing is conserved in evolution and they exhibit a lower frequency of single nucleotide polymorphism when paired. Paired motifs display specificity with respect to distance from the exon borders and in constitutive versus alternative splicing. Many resemble binding sites for heterogeneous nuclear ribonucleoproteins. Specific pairs are associated with tissue-specific genes, the higher expression of which coincides with that of the pertinent RNA binding proteins. Tested pairs acted synergistically to enhance exon inclusion, and this enhancement was found to be exon-specific.

Conclusions
The exon-flanking sequence pairs identified here by genomic analysis promote exon inclusion and may play a role in the exon definition step in pre-mRNA splicing. We propose a model in which multiple concerted interactions are required between exonic sequences and flanking intronic sequences to effect exon definition.
A novel MEK2/PI3Kδ pathway controls the expression of IL-1 receptor antagonist in IFN-β-activated human monocytes
Authors: Brandt Karim J , Carpintero Rakel , Gruaz Lyssia , Molnarfi Nicolas , Burger Danielle 
Published: September 2010

Abstract
sIL-1Ra production induced by IFN-β in human monocytes requires the activation of MEK2 upstream of PI3Kδ, MEK1, and ERK1/2 activation being dispensable.
IFN-β and sIL-1Ra play crucial roles in the regulation of innate immunity and inflammation. IFN-β, which is widely used to improve the course of relapsing, remitting multiple sclerosis, induces the production of sIL-1Ra in human monocytes through mechanisms that remain largely unknown. In this study, we identified PI3Kδ and MEK2 as key elements that control sIL-1Ra production in isolated human monocytes activated by IFN-β. Blockade of MEK2, but not of MEK1, by inhibitors and siRNA prevented IFN-β-induced PI3Kδ recruitment to the membrane, Akt phosphorylation, and sIL-1Ra production, suggesting that MEK2 acted upstream of PI3Kδ. Furthermore, ERK1/2, the only identified substrates of MEK1/2 to date, are dispensable for sIL-1Ra production in response to IFN-β stimulation. Upon IFN-β activation, MEK2 and PI3Kδ are translocated to monocyte membranes. These data suggest that MEK1 and MEK2 display different, nonredundant functions in IFN-β signaling. That neither MEK1 nor ERK1/2 play a part in this mechanism is also an unexpected finding that gives rise to a better understanding of the MAPK signaling network. Together, these findings demonstrate that IFN-β triggers an atypical MEK2/PI3Kδ signaling cascade to regulate sIL-1Ra expression in monocytes. The premise that MEK1 and MEK2 play a part in the induction of the proinflammatory cytokine, IL-1β in human monocytes provides a rationale for an alternative, IFN-β-mediated pathway to induce/enhance sIL-1Ra production and thus, to dampen inflammation.
Temsirolimus Has Activity in Non–Mantle Cell Non-Hodgkin's Lymphoma Subtypes: The University of Chicago Phase II Consortium
Authors: Smith Sonali M. , van Besien Koen , Karrison Theodore , Dancey Janet , McLaughlin Peter , Younes Anas , Smith Scott , Stiff Patrick , Lester Eric , Modi Sanjiv , Doyle L. Austin , Vokes Everett E. , Pro Barbara 
Published: September 2010

Purpose Despite high initial remission rates, most lymphomas relapse and require further therapy. The mammalian target of rapamycin (mTOR) pathway is a validated target in mantle cell lymphoma, but has not been extensively evaluated in other lymphomas. Patients and Methods We performed a phase II trial of single-agent temsirolimus 25-mg weekly in patients with relapsed aggressive and indolent lymphomas. The primary objective was overall and complete response rate. Patients were stratified by histology: group A (diffuse large B-cell lymphoma, transformed follicular lymphoma), group B (follicular lymphoma), and group C (chronic lymphocytic leukemia/small lymphocytic lymphoma, and other indolent lymphomas). Results Eighty-nine patients were treated, with outcome strongly dependent on histology. Group A had an overall and complete response rate of 28.1% and 12.5%, respectively, and median progression-free survival (PFS) of 2.6 months and median overall survival (OS) of 7.2 months. Group B had overall and complete response rates of 53.8% and 25.6%, respectively, and median PFS of 12.7 months; median OS has not yet been reached. Group C had a partial response rate of 11% with no complete responders. Toxicity was mainly mild and/or reversible myelosuppression and mucositis; however, four patients developed pneumonitis. Conclusions Single-agent temsirolimus has significant activity in both diffuse large B-cell lymphoma and follicular lymphoma, although the durability of responses and PFS are longer for patients with follicular lymphoma. This is the first report of substantial activity of temsirolimus in lymphomas other than mantle cell lymphoma, and supports further evaluation of mTOR as a target in these diseases.
Changes in Children's Physical Activity Over 12 Months: Longitudinal Results From the SPEEDY Study
Authors: Corder Kirsten , van Sluijs Esther M. F. , Ekelund Ulf , Jones Andrew P. , Griffin Simon J. 
Published: September 2010

OBJECTIVE:
We measured physical activity changes among 10-year-old British children over 12 months and assessed biological and demographic determinants.

METHODS:
Physical activity was measured with accelerometers (counts per minute) over ≥3 days at baseline and 1 year later in a prospective study of 844 children (41.6% male; mean ± SD baseline age: 10.2 ± 0.3 years) from 92 schools. Meeting physical activity recommendations was defined as ≥60 minutes/day at ≥2000 counts per minute. Biological (height, weight, and fat percentage) and demographic factors (gender, rural/urban home location, and socioeconomic status) were assessed at baseline. Associations between physical activity changes and multiple factors were studied.

RESULTS:
Physical activity decreased over 1 year (baseline: 665.7 ± 209.8 counts per minute; follow-up: 623.2 ± 179.2 counts per minute; P &lt; .001), with 70.4% of children meeting physical activity recommendations at the baseline evaluation and 65.8% at the follow-up evaluation (P &lt; .001). The decrease occurred mainly on weekends (−47.2 ± 395.8 counts per minute; P = .002), with no significant change on weekdays (8.0 ± 201.6 counts per minute; P = .20). Girls (P &lt; .001), participants with greater body fat percentage (P = .001), and participants of higher socioeconomic status (P = .008) were more likely to exhibit physical activity decreases.

CONCLUSIONS:
Physical activity decreased over 1 year among children in primary school, predominantly during the weekend. Because these children were relatively active at baseline, prevention of physical activity decreases in childhood, particularly among girls and on weekends, may be a suitable health promotion target.
Heritability of Apnea of Prematurity: A Retrospective Twin Study
Authors: Bloch-Salisbury Elisabeth , Hall Mei Hua , Sharma Priya , Boyd Theonia , Bednarek Francis , Paydarfar David 
Published: September 2010

BACKGROUND:
Apnea of prematurity (AOP) is a disturbance in respiratory rhythm defined by idiopathic pauses in breathing that reduce blood oxygen levels and/or heart rate. It is a major clinical problem among preterm infants.

OBJECTIVES:
The primary goal of this study was to estimate the genetic susceptibility to AOP in a cohort of preterm twins. A secondary aim was to identify risk factors associated with AOP in this cohort.

METHODS:
A single-center, retrospective study (2000–2008) was performed by using data from 317 premature twin pairs (&lt;36 weeks' gestational age). Heritability estimates were determined by comparing intrapair AOP concordance between 56 monozygotic and 161 dizygotic twin pairs by using structural equation modeling. Risk factors of AOP among a cohort of 543 premature twins were assessed by using mixed-effects logistic regression.

RESULTS:
The heritability of AOP was 87% (95% confidence interval [CI]: 0.64–0.97) among same-gender twins. A gender-dependent model revealed that genetic factors accounted for 99% of the variance in male twins (95% CI: 0.89–1.00) and 78% of the variance in female twins (95% CI: 0.49–0.94). Significant risk factors for AOP were low gestational age (P &lt; .001), cesarean delivery (P = .017), and conception through assisted reproductive technologies (P = .008).

CONCLUSIONS:
These findings suggest that AOP has an important genetic basis underlying this developmental-related disorder of respiratory control. Future genomic studies may provide information on pathophysiological mechanisms that underlie AOP.
Retinol Status of Newborn Infants Is Associated With Congenital Diaphragmatic Hernia
Authors: Beurskens Leonardus W. J. E. , Tibboel Dick , Lindemans Jan , Duvekot Johannes J. , Cohen-Overbeek Titia E. , Veenma Danielle C. M. , de Klein Annelies , Greer John J. , Steegers-Theunissen Régine P. M. 
Published: September 2010

OBJECTIVE:
Genetic analyses in humans suggest a role for retinoid-related genes in the pathogenesis of congenital diaphragmatic hernia (CDH). The goal of this study was to investigate the vitamin A status of mothers and their newborns in association with CDH.

METHODS:
We conducted a hospital-based, case-control study with 22 case and 34 control mothers and their newborns. In maternal and cord blood samples, retinol and retinol-binding protein (RBP) levels were measured with high-performance liquid chromatography and an enzyme-linked immunosorbent assay, respectively. Univariate and multivariate logistic regression analyses were performed to determine crude and adjusted risk estimates.

RESULTS:
Case newborns had significantly lower levels of retinol (0.60 vs 0.76 μmol/L; P = .003) and RBP (5.42 vs 7.11 mg/L; P = .02) than did control newborns. The multivariate logistic regression analysis showed lower levels of retinol and RBP in association with CDH risk; the odds ratio for retinol levels of &lt;15th percentile (&lt;0.61 μmol/L) was 11.11 (95% confidence interval: 2.54–48.66; P = .001), and that for RBP levels of &lt;15th percentile (&lt;4.54 mg/L) was 4.00 (95% confidence interval: 1.00–15.99; P = .05). Retinol and RBP levels were not different between case and control mothers.

CONCLUSIONS:
CDH is strongly associated with low retinol and RBP levels in newborns, independent of maternal retinol status. This is an important finding supporting the idea that human CDH is linked with abnormal retinoid homeostasis.
Application of systematic reviews in speech‐and‐language therapy
Authors: Marshall Julie , Goldbart Juliet , Pickstone Caroline , Roulstone Susan 
Published: September 2010

Background: Systematic reviews are increasingly being carried out in speech‐and‐language therapy and are used by practitioners, service commissioners, policy‐makers and researchers to inform decision‐making, as the body of evidence available about speech‐and‐language therapy grows. Although systematic reviewing is developing to incorporate new methods of review and synthesis, there are currently limitations in the use of some types of systematic reviews within speech‐and‐language therapy. Aims: The purpose of this paper is to provide an overview of the steps involved in the systematic review process and the range of options available. It highlights some challenges to using this process in speech‐and‐language therapy, with examples based in part on the authors' experiences of involvement in two systematic reviews. A number of developments in systematic review methodology will be outlined and several new approaches to reviewing, both within and outside of speech‐and‐language therapy, are introduced. These include realist synthesis, evidence‐based practice briefs, speech BITE™ and the journal Evidence‐Based Communication Assessment and Intervention. Main contribution: This paper highlights some of the current benefits and limitations of systematic reviews in speech‐and‐language therapy. It will facilitate readers to use and carry out systematic reviews in the speech‐and‐language therapy field. Conclusions: Systematic reviews are useful in speech‐and‐language therapy, but awareness of their limitations is important to practitioners, commissioners, policy‐makers and researchers. New developments may further increase the benefits of systematic reviews.
Influence of stacking fault energy and alloying on stage V hardening of HPT-deformed materials
Authors: Hafok Martin , Pippan Reinhard 
Published: September 2010

Abstract
The grain refinement after high pressure torsion of pure metals and alloys exhibiting fcc crystal structure was examined. The aim was to characterise the influence of the stacking fault energy and the alloying on the grain size in the saturation regime. In this regime no further hardening of the material is observed and a constant mean grain size is obtained. Pure metals such as silver, copper and nickel and different brass alloys were severely deformed using high pressure torsion. During the severe deformation the torque curves were recorded for the different metals at different hydrostatic pressures. Due to the different deformation conditions, the influence of friction on the torque in the saturation regime can be estimated. In addition tensile tests were performed and the results were compared with flow stresses determined in the high pressure torsion experiments. A clear influence of the alloying on the flow stresses and the grain sizes of the materials was found, the stacking fault energy has a significant effect on the refinement, but only a minor effect on the saturation grain size.
Cemented Versus Cementless Stems: A Verdict Is In
Authors: Bourne Robert B. , Corten Kristoff 
Published: September 2010

The purpose of this randomized clinical trial was to compare the >20-year outcomes of cemented (n=124) versus cementless (n=126) total hip replacements (THRs) in patients with end-stage, unilateral hip osteoarthritis. At 20 years, 168 patients (67%) were available for follow-up, 78 (31%) had died, and 4 (2%) were lost.
A power analysis was performed to determine the number of patients needed in each study cohort. Patients were assessed pre- and postoperatively by validated disease-specific Western Ontario McMaster Osteoarthritis Score, patient-specific McMaster Arthritis Score, global health (sickness impact profile), functional capacity (6-minute walk), and cost utility (cost-to-quality adjusted life years). Patients were followed every 2 years clinically and radiographically.

The cementless THR outperformed its cemented counterpart in terms of overall (
P
=.01), socket (
P
=.009), and stem (
P
<.0001) Kaplan-Meier survivorships. Patients younger than 65 years had significantly poorer cemented and cementless socket survivorships, and male sex adversely affected cementless socket survivorship. The cementless tapered stem had 100% survivorship with aseptic loosening as the endpoint at 20 years. Although this study has demonstrated the superiority of the cementless THR over its cemented counterpart, care must be taken in generalizing these results to other cemented and cementless THRs.
Case series: Congenital left ventricular diverticulum
Authors: Shah Dharita , Kumar C Kumar , Shah Mukesh S , Baraiya Mihir 
Published: September 2010

AbstractCongenital left ventricular diverticulum is a rare cardiac malformation characterized by a localized outpouching from the cardiac chamber. The patient is usually asymptomatic. However, complications like embolism, infective endocarditis, arrhythmia and, rarely, rupture can be the initial presentation. Diagnosis can be established by USG, echocardiography, CT angiography, and MRI. We report here two neonates with congenital left ventricular apical diverticulum associated with epigastric hernia.