bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concentration- and time-dependent effects of enoxaparin on human adenocarcinomic epithelial cell line A549 proliferation in vitro
Authors: Abu Arab Walid , Kotb Rami , Sirois Marco , Rousseau Éric 
Published: September 2011

Non-small cell lung cancer (NSCLC) is a major health problem. Surgery is the only potential curative treatment, in spite of the high recurrence and mortality rates. Low molecular weight heparins (LMWH) have been suggested to have a positive impact on the outcome of various cancers, mainly attributed to their anticoagulant properties; yet a direct antineoplastic effect has not been excluded. We thought to evaluate the direct effect of the LMWH enoxaparin on the human lung adenocarcinomic epithelial cell line A549 and to determine potential antiproliferative and antimetastatic effects that could guide future trials. A549 cells were cultured with different concentrations of enoxaparin (1–30 U/mL). Cell counting was performed at 24, 48, and 72 h. Detection of c-Myc protein and CD44 protein was performed by electrophoresis and Western blotting. Statistical analysis was performed using paired Student’s t tests. Cell counts were decreased with increasing concentrations and time of exposure to enoxaparin. This corresponds to decreased expression of c-Myc and CD44. In conclusion, enoxaparin displayed a direct dose and exposure duration dependent suppressor effect on A549 cell proliferation and the expression of both c-Myc and CD44 in vitro, suggesting reduced proliferative and metastatic potentials of these cells.
A Comprehensive View of Nuclear Receptor Cancer Cistromes
Authors: Tang Qianzi , Chen Yiwen , Meyer Clifford , Geistlinger Tim , Lupien Mathieu , Wang Qian , Liu Tao , Zhang Yong , Brown Myles , Liu Xiaole Shirley 
Published: September 2011

Abstract
Nuclear receptors comprise a superfamily of ligand-activated transcription factors that play important roles in both physiology and diseases including cancer. The technologies of chromatin immunoprecipitation followed by array hybridization (ChIP-chip) or massively parallel sequencing (ChIP-seq) has been used to map, at an unprecedented rate, the in vivo genome-wide binding (cistrome) of nuclear receptors in both normal and cancer cells. We developed a curated database of 88 nuclear receptor cistrome data sets and other associated high-throughput data sets including 121 collaborating factor cistromes, 94 epigenomes, and 319 transcriptomes. Through integrative analysis of the curated nuclear receptor ChIP-chip/seq data sets, we discovered novel factor-specific noncanonical motifs that may have important regulatory roles. We also revealed a common feature of nuclear receptor pioneering factors to recognize relatively short and AT-rich motifs. Most nuclear receptors bind predominantly to introns and distal intergenetic regions, and binding sites closer to transcription start sites were found to be neither stronger nor more evolutionarily conserved. Interestingly, while most nuclear receptors appear to be predominantly transcriptional activators, our analysis suggests that the binding of ESR1, RARA, and RARG has both activating and repressive effects. Through meta-analysis of different omic data of the same cancer cell line model from multiple studies, we generated consensus cistrome and expression profiles. We further made probabilistic predictions of the nuclear receptor target genes by integrating cistrome and transcriptome data and validated the predictions using expression data from tumor samples. The final database, with comprehensive cistrome, epigenome, and transcriptome data sets and downstream analysis results, constitutes a valuable resource for the nuclear receptor and cancer community. Cancer Res; 71(22); 6940–7. ©2011 AACR.
DNA Cytometry Testing for Cervical Cancer Screening: Approaches and Reporting Standards for New Technologies
Authors: Colditz Graham A. , Crowley John 
Published: September 2011

Abstract
Evaluation of new technologies requires rigorous methods to provide unbiased estimates of the performance and so inform future clinical practice. We review evidence on DNA cytometry reported earlier in this journal and point to the standards for reporting of diagnostic accuracy as a metric against which this article can be evaluated. The cross-sectional nature of the data and incomplete reporting limit the clinical utility of the study. With application of improved reporting standards for diagnostic tests and improved design and evaluation of new technologies for screening, we may better inform practices to improve clinical outcomes and population health. Clin Cancer Res; 17(22); 6971–2. ©2011 AACR.
Homozygosity for an Allele Encoding Deacetylated FoxO1 Protects Macrophages From Cholesterol-Induced Inflammation Without Increasing Apoptosis
Authors: Tsuchiya Kyoichiro , Banks Alexander S. , Liang Chien-Ping , Tabas Ira , Tall Alan R. , Accili Domenico 
Published: September 2011

Objective—
Insulin resistance renders macrophages more prone to cholesterol-induced apoptosis by promoting nuclear localization of transcription factor forkhead box transcription factor (Fox) O1. However, FoxO1 also decreases macrophage inflammation, raising the question of how the balance between proapoptotic and antiinflammatory effects is determined. We sought to identify the mechanism whereby FoxO1 dampens inflammation without promoting apoptosis. We hypothesized that nutrient-dependent FoxO1 acetylation plays a role in this process.

Methods and Results—
We generated knock-in mice bearing alleles that encode constitutively deacetylated FoxO1 and studied the ex vivo response of primary peritoneal macrophages. We show that macrophages derived from mice homozygous for constitutively deacetylated FoxO1 alleles retain antiinflammatory properties in response to free cholesterol loading, without increasing apoptosis. Deacetylated FoxO1 inhibits free cholesterol–induced Akt phosphorylation and increases levels of the nuclear factor-κB precursor p105, decreasing nuclear translocation of nuclear factor-κB p65 subunit and dampening mitogen-activated protein/extracellular signal-regulated kinase activation to prevent inflammation.

Conclusion—
Deacetylated FoxO1 regulates p105 to prevent macrophage inflammation without causing apoptosis, suggesting a potential novel therapeutic approach to atherosclerosis through FoxO1 deacetylation.
Protease-Activated Receptor-2 Modulates Protease-Activated Receptor-1–Driven Neointimal Hyperplasia
Authors: Sevigny Leila M. , Austin Karyn M. , Zhang Ping , Kasuda Shogo , Koukos Georgios , Sharifi Sheida , Covic Lidija , Kuliopulos Athan 
Published: September 2011

Objective—
Emerging evidence suggests that protease-activated receptors-1 and -2 (PAR1 and PAR2) can signal together in response to proteases found in the rapidly changing microenvironment of damaged blood vessels. However, it is unknown whether PAR1 and PAR2 promote or mitigate the hyperplastic response to arterial injury. Using cell-penetrating PAR1 pepducins and mice deficient in PAR1 or PAR2, we set out to determine the respective contributions of the receptors to hyperplasia and phenotypic modulation of smooth muscle cells (SMCs) in response to arterial injury.

Methods and Results—

SMCs were strongly activated by PAR1 stimulation, as evidenced by increased mitogenesis, mitochondrial activity, and calcium mobilization. The effects of chronic PAR1 stimulation following vascular injury were studied by performing carotid artery ligations in mice treated with the PAR1 agonist pepducin, P1pal-13. Histological analysis revealed that PAR1 stimulation caused striking hyperplasia, which was ablated in PAR1
−/−
and, surprisingly, PAR2
−/−
mice. P1pal-13 treatment yielded an expression pattern consistent with a dedifferentiated phenotype in carotid artery SMCs. Detection of PAR1-PAR2 complexes provided an explanation for the hyperplastic effects of the PAR1 agonist requiring the presence of both receptors.

Conclusion—
We conclude that PAR2 regulates the PAR1 hyperplastic response to arterial injury leading to stenosis.
Physical Activity and Functional Outcomes From Cerebral Vascular Events in Men
Authors: Rist Pamela M. , Lee I-Min , Kase Carlos S. , Gaziano J. Michael , Kurth Tobias 
Published: September 2011

Background and Purpose—
In studies enrolling patients with stroke, higher levels of prestroke physical activity are associated with better functional outcomes. However, prospective studies evaluating this association are sparse. Using a cohort of initially healthy men, we aimed to prospectively assess the association between physical activity and functional outcomes from cerebral vascular events.

Methods—
We conducted a prospective cohort study among 21 794 men enrolled in the Physician's Health Study who provided information on physical activity at baseline and who did not have a history of stroke or transient ischemic attack (TIA). Baseline levels of physical activity were categorized as: vigorous exercise <1, 1, 2 to 4, and ≥5 times/week. Possible functional outcomes included TIA and stroke with modified Rankin Scale score of 0 to 1, 2 to 3, or 5 to 6. Multinomial logistic regression was used to determine the association between physical activity and functional outcomes from cerebral vascular events.

Results—
After a mean of 20.2 years of follow-up, 761 TIAs, 1146 ischemic strokes, 221 hemorrhagic strokes, and 11 strokes of unknown type occurred. Compared with men who did not experience a stroke or TIA and who exercise vigorously <1 time/week, men who exercise vigorously ≥5 times/week had adjusted relative risk (95% CIs) of 0.67 (0.53–0.86) for TIA, 0.84 (0.61–1.14) for stroke with modified Rankin Scale score 0 to 1, 0.85 (0.67–1.08) for modified Rankin Scale score 2 to 3, and 1.12 (0.78–1.60) for modified Rankin Scale score 5 to 6 after total stroke. Other levels of physical activity did not have a significant impact on the risk of our outcomes.

Conclusions—
Physical activity before TIA or stroke does not appear to influence functional outcomes after cerebral vascular events.
Comprehensive Cardiac Rehabilitation for Secondary Prevention After Transient Ischemic Attack or Mild Stroke
Authors: Prior Peter L. , Hachinski Vladimir , Unsworth Karen , Chan Richard , Mytka Sharon , O'Callaghan Christina , Suskin Neville 
Published: September 2011

Background and Purpose—
Comprehensive cardiac rehabilitation (CCR), which integrates structured lifestyle interventions and medications, reduces morbidity and mortality among cardiac patients. CCR has not typically been used with cerebrovascular populations, despite important commonalities with heart patients. We tested feasibility and effectiveness of 6-month outpatient CCR for secondary prevention after transient ischemic attack or mild, nondisabling stroke. This article presents risk factors. A future article will discuss psychological outcomes.

Methods—
Consecutive consenting subjects having sustained a transient ischemic attack or mild, nondisabling stroke within the previous 12 months (mean, 11.5 weeks; event-to-CCR entry) with ≥1 vascular risk factor, were recruited from a stroke prevention clinic providing usual care. We measured 6-month CCR outcomes following a prospective cohort design.

Results—

Of 110 subjects recruited from January 2005 to April 2006, 100 subjects (mean age, 64.9 years; 46 women) entered and 80 subjects completed CCR. We obtained favorable, significant intake-to-exit changes in: aerobic capacity (+31.4%;
P
<0.001), total cholesterol (−0.30 mmol/L;
P
=0.008), total cholesterol/high-density lipoprotein (−11.6%;
P
<0.001), triglycerides (−0.27 mmol/L;
P
=0.003), waist circumference (−2.44 cm;
P
<0.001), body mass index (−0.53 kg/m
2
;
P
=0.003), and body weight (−1.43 kg;
P
=0.001). Low-density lipoprotein (−0.24 mmol/L), high-density lipoprotein (+0.06 mmol/L), systolic (−3.21 mm Hg) and diastolic (−2.34 mm Hg) blood pressure changed favorably, but nonsignificantly. A significant shift toward nonsmoking occurred (
P
=0.008). Compared with intake, 11 more individuals (25.6% increase) finished CCR in the lowest-mortality risk category of the Duke Treadmill Score (
P
<0.001).

Conclusions—
CCR is feasible and effective for secondary prevention after transient ischemic attack or mild, nondisabling stroke, offering a promising model for vascular protection across chronic disease entities. We know of no similar previous investigation, and are now conducting a randomized trial.
Lipoprotein (a) and Carotid Atherosclerosis in Young Patients With Stroke
Authors: Nasr Nathalie , Ruidavets Jean Bernard , Farghali Ahmed , Guidolin Brigitte , Perret Bertrand , Larrue Vincent 
Published: September 2011

Background and Purpose—
Elevated lipoprotein (a) concentration is associated with carotid atherosclerosis in middle-aged and older patients with ischemic stroke. This association has not been explored in young patients with stroke.

Methods—
A retrospective analysis of data from patients aged 16 to 54 years consecutively treated for acute ischemic stroke in a tertiary stroke unit during 4.5 years was performed. We graded carotid atherosclerosis using carotid duplex as: no atherosclerosis (A); plaque without stenosis (B); or stenosis ≥50% (C).

Results—

One hundred ninety-six patients were included (male/female: 119/77; mean age±SD: 44.3±8.6 years): 115 in Group A; 67 in Group B; and 14 in Group C. Multivariate analysis using polynomial logistic regression showed a graded association of lipoprotein (a) plasma concentration with carotid atherosclerosis (
P
<0.001).

Conclusions—
Our results showed a positive association of lipoprotein (a) plasma concentration with carotid atherosclerosis in young adults with ischemic stroke. This association was strong, graded, and independent of traditional risk factors including cholesterol.
Ethnic and Geographic Variation in Stroke Mortality Trends
Authors: Gillum Richard F. , Kwagyan John , Obisesan Thomas O. 
Published: September 2011

Background and Purpose—
Magnitude, geographic, and ethnic variation in trends in stroke within the United States require updating for health services and health disparities research.

Methods—
Data for stroke were analyzed from the US mortality files for 1999 to 2007. Age-adjusted death rates were computed for non-Hispanic African Americans and European Americans aged ≥45 years.

Results—
Between 1999 and 2007, the age-adjusted death rate per 100 000 for stroke declined both in African Americans and in European Americans of both genders. Among African American females, European American females, and European American males, rates declined by at least 2% annually in every division. Among African American males, rates declined little in the East and West South Central divisions where disparities in trends by urbanization level were found.

Conclusions—
Between 1999 and 2007, the rate of decline in stroke mortality varied by geographic region and ethnic group.
Atherosclerosis and Dementia
Authors: Suemoto Claudia K. , Nitrini Ricardo , Grinberg Lea T. , Ferretti Renata E.L. , Farfel José M. , Leite Renata E.P. , Menezes Paulo R. , Fregni Felipe , Jacob-Filho Wilson , Pasqualucci Carlos A. ,   Brazilian Aging Brain Study Group
Published: September 2011

Background and Purpose—
Previous ultrasound-based studies have shown an association between carotid artery atherosclerosis and dementia. Our aim was to investigate this association using postmortem examination.

Methods—
Postmortem morphometric measurements of carotid stenosis and intima-media thickness were performed in individuals with dementia (n=112) and control subjects (n=577). Multivariate logistic regression models were applied.

Results—

High-grade left internal carotid stenosis (≥70%) was associated with increased odds for dementia (OR, 2.30; 95% CI, 1.14–4.74;
P
=0.02). Intima-media thickness was not associated with dementia.

Conclusions—
The likelihood of dementia is increased with high-grade left internal carotid artery atherosclerosis after adjusting for demographic and cardiovascular risk factors.
Revision Stapes Surgery
Authors: Özüer Mehmet Ziya , Olgun Levent , Gültekin Gürol 
Published: September 2011

ObjectivesSurgery for otosclerosis has a highly satisfactory hearing outcome, for both the patient and the otologic surgeon. However, subsequent conductive hearing loss, dizziness/vertigo, or sound distortion could necessitate revision surgery. The aim of the present study is to evaluate the surgical findings and hearing outcomes of 84 revision stapes surgeries.Study DesignCase series with chart review.SettingTertiary referral center.Subjects and MethodsAt our institution, 84 revision cases were performed between 1998 and 2009. Conductive hearing loss was the revision indication in 69 cases, severe dizziness/vertigo in 8 patients, sound distortion in 5 cases, and progressive hearing loss with dizziness in 2 patients. Operative findings were noted in every case and evaluated separately.ResultsSurgical intervention revealed problems related to prosthesis in 51 cases, fibrotic bands in 26 cases, adhesions in 13 cases, incus necrosis in 15 cases, perilymphatic fistula in 3 cases, intact footplate in 5 cases, incus‐malleus fixation in 2 cases, and reobliteration in 2 cases. Mean follow‐up period was 19 months (range, 12‐53 months). Successful hearing results (air‐bone gap <10 dB) were reached in 58% of the cases, and satisfactory hearing results (air‐bone gap <20 dB) were reached in 71% of the cases.ConclusionsThe ideal patient for revision stapes surgery is one who benefits from the initial surgery but complained of conductive hearing loss. In the present study, improvement in pure‐tone average was 13.2 dB, and the mean air‐bone gap was 9.6 dB.
Regulation of macrophage migration by a novel plasminogen receptor Plg-RKT
Authors: Lighvani Shahrzad , Baik Nagyung , Diggs Jenna E. , Khaldoyanidi Sophia , Parmer Robert J. , Miles Lindsey A. 
Published: September 2011

AbstractLocalization of plasmin on macrophages and activation of pro–MMP-9 play key roles in macrophage recruitment in the inflammatory response. These functions are promoted by plasminogen receptors exposing C-terminal basic residues on the macrophage surface. Recently, we identified a novel transmembrane plasminogen receptor, Plg-RKT, which exposes a C-terminal lysine on the cell surface. In the present study, we investigated the role of Plg-RKT in macrophage invasion, chemotactic migration, and recruitment. Plg-RKT was prominently expressed in membranes of human peripheral blood monocytes and monocytoid cells. Plasminogen activation by urokinase-type plasminogen activator (uPA) was markedly inhibited (by 39%) by treatment with anti–Plg-RKT mAb. Treatment of monocytes with anti–Plg-RKT mAb substantially inhibited invasion through the representative matrix, Matrigel, in response to MCP-1 (by 54% compared with isotype control). Furthermore, chemotactic migration was also inhibited by treatment with anti–Plg-RKT mAb (by 64%). In a mouse model of thioglycollate-induced peritonitis, anti–Plg-RKT mAb markedly inhibited macrophage recruitment (by 58%), concomitant with a reduction in pro–MMP-9 activation in the inflamed peritoneum. Treatment with anti–Plg-RKT mAb did not further reduce the low level of macrophage recruitment in plasminogen-null mice. We conclude that Plg-RKT plays a key role in the plasminogen-dependent regulation of macrophage invasion, chemotactic migration, and recruitment in the inflammatory response.
Iron regulatory protein-1 and -2: transcriptome-wide definition of binding mRNAs and shaping of the cellular proteome by iron regulatory proteins
Authors: Sanchez Mayka , Galy Bruno , Schwanhaeusser Bjoern , Blake Jonathon , Bähr-Ivacevic Tomi , Benes Vladimir , Selbach Matthias , Muckenthaler Martina U. , Hentze Matthias W. 
Published: September 2011

AbstractIron regulatory proteins (IRPs) 1 and 2 are RNA-binding proteins that control cellular iron metabolism by binding to conserved RNA motifs called iron-responsive elements (IREs). The currently known IRP-binding mRNAs encode proteins involved in iron uptake, storage, and release as well as heme synthesis. To systematically define the IRE/IRP regulatory network on a transcriptome-wide scale, IRP1/IRE and IRP2/IRE messenger ribonucleoprotein complexes were immunoselected, and the mRNA composition was determined using microarrays. We identify 35 novel mRNAs that bind both IRP1 and IRP2, and we also report for the first time cellular mRNAs with exclusive specificity for IRP1 or IRP2. To further explore cellular iron metabolism at a system-wide level, we undertook proteomic analysis by pulsed stable isotope labeling by amino acids in cell culture in an iron-modulated mouse hepatic cell line and in bone marrow-derived macrophages from IRP1- and IRP2-deficient mice. This work investigates cellular iron metabolism in unprecedented depth and defines a wide network of mRNAs and proteins with iron-dependent regulation, IRP-dependent regulation, or both.
Coevolution of amino acid residues in the key photosynthetic enzyme Rubisco
Authors: Wang Mingcong , Kapralov Maxim V , Anisimova Maria 
Published: September 2011

Abstract

Background
One of the key forces shaping proteins is coevolution of amino acid residues. Knowing which residues coevolve in a particular protein may facilitate our understanding of protein evolution, structure and function, and help to identify substitutions that may lead to desired changes in enzyme kinetics. Rubisco, the most abundant enzyme in biosphere, plays an essential role in the process of carbon fixation through photosynthesis, thus facilitating life on Earth. This makes Rubisco an important model system for studying the dynamics of protein fitness optimization on the evolutionary landscape. In this study we investigated the selective and coevolutionary forces acting on large subunit of land plants Rubisco using Markov models of codon substitution and clustering approaches applied to amino acid substitution histories.

Results
We found that both selection and coevolution shape Rubisco, and that positively selected and coevolving residues have their specifically favored amino acid composition and pairing preference. The mapping of these residues on the known Rubisco tertiary structures showed that the coevolving residues tend to be in closer proximity with each other compared to the background, while positively selected residues tend to be further away from each other. This study also reveals that the residues under positive selection or coevolutionary force are located within functionally important regions and that some residues are targets of both positive selection and coevolution at the same time.

Conclusion
Our results demonstrate that coevolution of residues is common in Rubisco of land plants and that there is an overlap between coevolving and positively selected residues. Knowledge of which Rubisco residues are coevolving and positively selected could be used for further work on structural modeling and identification of substitutions that may be changed in order to improve efficiency of this important enzyme in crops.