bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between brachial artery flow-mediated dilatation, hyperemic shear stress, and the metabolic syndrome
Authors: Title Lawrence M , Lonn Evan , Charbonneau Francois , Fung Marinda , Mather Kieren J , Verma Subodh , Anderson Todd J 
Published: October 2008

Abstract Metabolic syndrome (MetSyn) may predispose to cardiovascular disease (CVD) by causing vascular dysfunction. This study aimed to determine the association of MetSyn with vascular function, as assessed by brachial artery flow-mediated dilatation (FMD) and hyperemic shear stress (HSS). A total of 1,417 male firefighters without established diabetes and CVD were classified for MetSyn, according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP) definition. MetSyn was present in 267 individuals (19%). Although FMD was lower in those with versus without MetSyn (8.1 ± 4.1 vs 8.7 ± 4.0%; p = 0.02), this was not significant after adjusting for baseline differences (age, smoking, and brachial artery diameter) ( p = 0.2). However, HSS was significantly lower in those with versus without MetSyn (72.0 ± 27.8 vs 80.9 ± 24.8 dyne/cm2; p < 0.001), and there was a significant inverse graded relationship with the number of NCEP criteria present (mean HSS for those with 0, 1, 2, 3, 4, and 5 criteria: 83.2 ± 22.5, 82.2 ± 24.7, 76.5 ± 27.2, 74.3 ± 27.4, 66.5 ± 28.4, 67.1 ± 27.6 dyne/cm2; p < 0.001 for trend). The individual NCEP criteria of abdominal obesity, systolic hypertension, and impaired fasting glucose were independent predictors for HSS. In conclusion, MetSyn was not associated with impaired FMD. Alternatively, HSS, a measure of microvascular function, was significantly lower in those with MetSyn. Thus, MetSyn may contribute to CVD by causing microvascular dysfunction.
miR-34a as part of the resistance network in chronic lymphocytic leukemia
Authors: Zenz Thorsten , Mohr Julia , Eldering Eric , Kater Arnon P. , Bühler Andreas , Kienle Dirk , Winkler Dirk , Dürig Jan , van Oers Marinus H. J. , Mertens Daniel , Döhner Hartmut , Stilgenbauer Stephan 
Published: October 2008

Abstract
17p (TP53) deletion identifies patients with chronic lymphocytic leukemia (CLL) who are resistant to chemotherapy. The members of the miR-34 family have been discovered to be direct p53 targets and mediate some of the p53-dependent effects. We studied miR-34a and miR-34b/c expression in a large cohort to define their potential role in refractory CLL. While no expression of miR-34b/c could be detected, we found variable expression levels of miR-34a. miR-34a levels were up-regulated after DNA damage in the presence of functional p53, but not in cases with 17p deletion (P < .001). We found a strong correlation of low miR-34a levels with impaired DNA damage response, TP53 mutations (without 17p deletion), and fludarabine-refractory disease (also in the absence of 17p deletion). Up-regulation of miR-34a after irradiation was associated with induction of Bax and p21, but not Puma. CLL cells with reduced miR-34a expression showed increased viability after DNA damage independently of 17p status. Therefore, low expression of miR-34a in CLL is associated with p53 inactivation but also chemotherapy-refractory disease, impaired DNA damage response, and apoptosis resistance irrespective of 17p deletion/TP53 mutation. The elucidation of mechanisms underlying miR-34a regulation and overcoming its role in chemotherapy resistance warrant further study.
The UPS: a promising target for breast cancer treatment
Authors: Sato Ko , Rajendra Eeson , Ohta Tomohiko 
Published: October 2008

AbstractAbstractDuring the past decade, progress in endocrine therapy and the use of trastuzumab has significantly contributed to the decline in breast cancer mortality for hormone receptor-positive and ERBB2 (HER2)-positive cases, respectively. As a result of these advances, a breast cancer cluster with poor prognosis that is negative for the estrogen receptor (ESR1), the progesterone receptor (PRGR) and ERBB2 (triple negative) has come to the forefront of medical therapeutic attention. DNA microarray analyses have revealed that this cluster is phenotypically most like the basal-like breast cancer that is caused by deficiencies in the BRCA1 pathways. To gain further improvements in breast cancer survival, new types of drugs might be required, and small molecules targeting the ubiquitin proteasome system have moved into the spotlight. The success of bortezomib in the treatment of multiple myeloma has sent encouraging signals that proteasome inhibitors could be used to treat other types of cancers. In addition, ubiquitin E3s involved in ESR1, ERBB2 or BRCA1 pathways could be ideal targets for therapeutic intervention. This review summarizes the ubiquitin proteasome pathways related to these proteins and discusses the possibility of new drugs for the treatment of breast cancers.Publication historyRepublished from Current BioData's Targeted Proteins database (TPdb;http://www.targetedproteinsdb.com).
Deubiquitylating enzymes and disease
Authors: Singhal Shweta , Taylor Matthew C , Baker Rohan T 
Published: October 2008

Abstract

Abstract
Deubiquitylating enzymes (DUBs) can hydrolyze a peptide, amide, ester or thiolester bond at the C-terminus of UBIQ (ubiquitin), including the post-translationally formed branched peptide bonds in mono- or multi-ubiquitylated conjugates. DUBs thus have the potential to regulate any UBIQ-mediated cellular process, the two best characterized being proteolysis and protein trafficking. Mammals contain some 80–90 DUBs in five different subfamilies, only a handful of which have been characterized with respect to the proteins that they interact with and deubiquitylate. Several other DUBs have been implicated in various disease processes in which they are changed by mutation, have altered expression levels, and/or form part of regulatory complexes. Specific examples of DUB involvement in various diseases are presented. While no specific drugs targeting DUBs have yet been described, sufficient functional and structural information has accumulated in some cases to allow their rapid development.

Publication history
Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).
A machine vision system for automated non-invasive assessment of cell viability via dark field microscopy, wavelet feature selection and classification
Authors: Wei Ning , Flaschel Erwin , Friehs Karl , Nattkemper Tim Wilhelm 
Published: October 2008

Abstract

Background
Cell viability is one of the basic properties indicating the physiological state of the cell, thus, it has long been one of the major considerations in biotechnological applications. Conventional methods for extracting information about cell viability usually need reagents to be applied on the targeted cells. These reagent-based techniques are reliable and versatile, however, some of them might be invasive and even toxic to the target cells. In support of automated noninvasive assessment of cell viability, a machine vision system has been developed.

Results
This system is based on supervised learning technique. It learns from images of certain kinds of cell populations and trains some classifiers. These trained classifiers are then employed to evaluate the images of given cell populations obtained via dark field microscopy. Wavelet decomposition is performed on the cell images. Energy and entropy are computed for each wavelet subimage as features. A feature selection algorithm is implemented to achieve better performance. Correlation between the results from the machine vision system and commonly accepted gold standards becomes stronger if wavelet features are utilized. The best performance is achieved with a selected subset of wavelet features.

Conclusion
The machine vision system based on dark field microscopy in conjugation with supervised machine learning and wavelet feature selection automates the cell viability assessment, and yields comparable results to commonly accepted methods. Wavelet features are found to be suitable to describe the discriminative properties of the live and dead cells in viability classification. According to the analysis, live cells exhibit morphologically more details and are intracellularly more organized than dead ones, which display more homogeneous and diffuse gray values throughout the cells. Feature selection increases the system's performance. The reason lies in the fact that feature selection plays a role of excluding redundant or misleading information that may be contained in the raw data, and leads to better results.
Aggresomes do not represent a general cellular response to protein misfolding in mammalian cells
Authors: Beaudoin Simon , Goggin Kevin , Bissonnette Cyntia , Grenier Catherine , Roucou Xavier 
Published: October 2008

Abstract

Background
Aggresomes are juxtanuclear inclusion bodies that have been proposed to represent a general cellular response to misfolded proteins in mammalian cells. Yet, why aggresomes are not a pathological characteristic of protein misfolding diseases is unclear. Here, we investigate if a misfolded protein inevitably forms aggresomes in mammalian cells.

Results
We show that a cytoplasmic form of the prion protein may form aggresomes or dispersed aggregates in different cell lines. In contrast to aggresomes, the formation of dispersed aggregates is insensitive to histone deacetylase 6 inhibitors and does not result in cytoskeleton rearrangements. Modulation of expression levels or proteasome inhibitors does not alter the formation of dispersed aggregates.

Conclusion
Our results establish that aggresomes are not obligatory products of protein misfolding in vivo.
Empirical Bayes accomodation of batch-effects in microarray data using identical replicate reference samples: application to RNA expression profiling of blood from Duchenne muscular dystrophy patients
Authors: Walker Wynn L , Liao Isaac H , Gilbert Donald L , Wong Brenda , Pollard Katherine S , McCulloch Charles E , Lit Lisa , Sharp Frank R 
Published: October 2008

Abstract

Background
Non-biological experimental error routinely occurs in microarray data collected in different batches. It is often impossible to compare groups of samples from independent experiments because batch effects confound true gene expression differences. Existing methods can correct for batch effects only when samples from all biological groups are represented in every batch.

Results
In this report we describe a generalized empirical Bayes approach to correct for cross-experimental batch effects, allowing direct comparisons of gene expression between biological groups from independent experiments. The proposed experimental design uses identical reference samples in each batch in every experiment. These reference samples are from the same tissue as the experimental samples. This design with tissue matched reference samples allows a gene-by-gene correction to be performed using fewer arrays than currently available methods. We examine the effects of non-biological variation within a single experiment and between experiments.

Conclusion
Batch correction has a significant impact on which genes are identified as differentially regulated. Using this method, gene expression in the blood of patients with Duchenne Muscular Dystrophy is shown to differ for hundreds of genes when compared to controls. The numbers of specific genes differ depending upon whether between experiment and/or between batch corrections are performed.
PrimerSNP: a web tool for whole-genome selection of allele-specific and common primers of phylogenetically-related bacterial genomic sequences
Authors: Yao Jiqiang , Lin Hong , Van Deynze Allen , Doddapaneni Harshavardhan , Francis Martha , Lemos Eliana Gertrudes Macedo , Civerolo Edwin L 
Published: October 2008

Abstract

Background
The increasing number of genomic sequences of bacteria makes it possible to select unique SNPs of a particular strain/species at the whole genome level and thus design specific primers based on the SNPs. The high similarity of genomic sequences among phylogenetically-related bacteria requires the identification of the few loci in the genome that can serve as unique markers for strain differentiation. PrimerSNP attempts to identify reliable strain-specific markers, on which specific primers are designed for pathogen detection purpose.

Results
PrimerSNP is an online tool to design primers based on strain specific SNPs for multiple strains/species of microorganisms at the whole genome level. The allele-specific primers could distinguish query sequences of one strain from other homologous sequences by standard PCR reaction. Additionally, PrimerSNP provides a feature for designing common primers that can amplify all the homologous sequences of multiple strains/species of microorganisms. PrimerSNP is freely available at http://cropdisease.ars.usda.gov/~primer.

Conclusion
PrimerSNP is a high-throughput specific primer generation tool for the differentiation of phylogenetically-related strains/species. Experimental validation showed that this software had a successful prediction rate of 80.4 – 100% for strain specific primer design.
Role of protease activated receptor-2 in lymph node metastasis of uterine cervical cancers
Authors: Jahan Israt , Fujimoto Jiro , Alam Syed Mahfuzul , Sato Eriko , Tamaya Teruhiko 
Published: October 2008

AbstractBackgroundProtease activated receptor-2 (PAR-2) has been implicated in cellular proliferation, invasion and metastasis in various tumors. Lymph node metastasis is an important patient prognostic factor for uterine cervical cancers. This prompted us to study the role of PAR-2 in lymph node metastasis of uterine cervical cancers.MethodsThirty patients underwent surgery for uterine cervical cancers. PAR-2 histoscores and mRNA levels were determined by immunohistochemistry and real-time reverse transcription-polymerase chain reaction, respectively. Patient prognosis was analyzed with a 48-month survival rate.ResultsPAR-2 histoscores and mRNA levels significantly (P< 0.05) increased in 12 of 30 metastatic lymph node lesions from the corresponding primary tumor. The 48-month survival rate of the 12 patients with increased PAR-2 levels in metastatic lymph nodes was 42%, while the rate of the other 18 patients with no change in PAR-2 levels was 82%, regardless of histopathological type.ConclusionPAR-2 might work on lymph node metastasis of uterine cervical cancers, and is considered to be a novel prognostic indicator for uterine cervical cancers.
STAT3 can be activated through paracrine signaling in breast epithelial cells
Authors: Lieblein Jacqueline C , Ball Sarah , Hutzen Brian , Sasser A Kate , Lin Huey-Jen , Huang Tim HM , Hall Brett M , Lin Jiayuh 
Published: October 2008

Abstract

Background
Many cancers, including breast cancer, have been identified with increased levels of phosphorylated or the active form of Signal Transducers and Activators of Transcription 3 (STAT3) protein. However, whether the tumor microenvironment plays a role in this activation is still poorly understood.

Methods
Conditioned media, which contains soluble factors from MDA-MB-231 and MDA-MB-468 breast cancer cells and breast cancer associated fibroblasts, was added to MCF-10A breast epithelial and MDA-MB-453 breast cancer cells. The stimulation of phosphorylated STAT3 (p-STAT3) levels by conditioned media was assayed by Western blot in the presence or absence of neutralized IL-6 antibody, or a JAK/STAT3 inhibitor, JSI-124. The stimulation of cell proliferation in MCF-10A cells by conditioned media in the presence or absence of JSI-124 was subjected to MTT analysis. IL-6, IL-10, and VEGF levels were determined by ELISA analysis.

Results
Our results demonstrated that conditioned media from cell lines with constitutively active STAT3 are sufficient to induce p-STAT3 levels in various recipients that do not possess elevated p-STAT3 levels. This signaling occurs through the JAK/STAT3 pathway, leading to STAT3 phosphorylation as early as 30 minutes and is persistent for at least 24 hours. ELISA analysis confirmed a correlation between elevated levels of IL-6 production and p-STAT3. Neutralization of the IL-6 ligand or gp130 was sufficient to block increased levels of p-STAT3 (Y705) in treated cells. Furthermore, soluble factors within the MDA-MB-231 conditioned media were also sufficient to stimulate an increase in IL-6 production from MCF-10A cells.

Conclusion
These results demonstrate STAT3 phosphorylation in breast epithelial cells can be stimulated by paracrine signaling through soluble factors from both breast cancer cells and breast cancer associated fibroblasts with elevated STAT3 phosphorylation. The induction of STAT3 phosphorylation is through the IL-6/JAK pathway and appears to be associated with cell proliferation. Understanding how IL-6 and other soluble factors may lead to STAT3 activation via the tumor microenvironment will provide new therapeutic regimens for breast carcinomas and other cancers with elevated p-STAT3 levels.
Implementation of Home based management of malaria in children reduces the work load for peripheral health facilities in a rural district of Burkina Faso
Authors: Tiono Alfred B , Kaboré Youssouf , Traoré Abdoulaye , Convelbo Nathalie , Pagnoni Franco , Sirima Sodiomon B 
Published: October 2008

Abstract

Background
Home Management of Malaria (HMM) is one of the key strategies to reduce the burden of malaria for vulnerable population in endemic countries. It is based on the evidence that well-trained communities health workers can provide prompt and adequate care to patients close to their homes. The strategy has been shown to reduce malaria mortality and severe morbidity and has been adopted by the World Health Organization as a cornerstone of malaria control in Africa. However, the potential fall-out of this community-based strategy on the work burden at the peripheral health facilities level has never been investigated.

Methods
A two-arm interventional study was conducted in a rural health district of Burkina Faso. The HMM strategy has been implemented in seven community clinics catchment's area (intervention arm). For the other seven community clinics in the control arm, no HMM intervention was implemented. In each of the study arms, presumptive treatment was provided for episodes of fevers/malaria (defined operationally as malaria).
The study drug was artemether-lumefantrine, which was sold at a subsidized price by community health workers/Key opinion leaders at the community level and by the pharmacists at the health facility level.
The outcome measured was the proportion of malaria cases among all health facility attendance (all causes diseases) in both arms throughout the high transmission season.

Results
A total of 7,621 children were enrolled in the intervention arm and 7,605 in the control arm. During the study period, the proportions of malaria cases among all health facility attendance (all causes diseases) were 21.0%, (445/2,111, 95% CI [19.3%–22.7%]) and 70.7% (2,595/3,671, 95% CI 68.5%–71.5%), respectively in the intervention and control arms (p << 0.0001). The relative risk ratio for a fever/malaria episode to be treated at the HF level was 30% (0.30 < RR < 0.32).
The number of malaria episodes treated in the intervention arm was much higher than in the control arm (6,661 vs. 2,595), with malaria accounting for 87.4% of all disease episodes recorded in the intervention area and for 34.1% in the control area (P < 0.0001). Of all the malaria cases treated in the intervention arm, only 6.7% were treated at the health facility level.

Conclusion
These findings suggest that implementation of HMM, by reducing the workload in health facilities, might contributes to an overall increase of the performance of the peripheral health facilities.
Interaction of an atypical Plasmodium falciparum ETRAMP with human apolipoproteins
Authors: Vignali Marissa , McKinlay Anastasia , LaCount Douglas J , Chettier Rakesh , Bell Russell , Sahasrabudhe Sudhir , Hughes Robert E , Fields Stanley 
Published: October 2008

Abstract

Background
In order to establish a successful infection in the human host, the malaria parasite Plasmodium falciparum must establish interactions with a variety of human proteins on the surface of different cell types, as well as with proteins inside the host cells. To better understand this aspect of malaria pathogenesis, a study was conducted with the goal of identifying interactions between proteins of the parasite and those of its human host.

Methods
A modified yeast two-hybrid methodology that preferentially selects protein fragments that can be expressed in yeast was used to conduct high-throughput screens with P. falciparum protein fragments against human liver and cerebellum libraries. The resulting dataset was analyzed to exclude interactions that are not likely to occur in the human host during infection.

Results
An initial set of 2,200 interactions was curated to remove proteins that are unlikely to play a role in pathogenesis based on their annotation or localization, and proteins that behave promiscuously in the two-hybrid assay, resulting in a final dataset of 456 interactions. A cluster that implicates binding between P. falciparum PFE1590w/ETRAMP5, a putative parasitophorous vacuole membrane protein, and human apolipoproteins ApoA, ApoB and ApoE was selected for further analysis. Different isoforms of ApoE, which are associated with different outcomes of malaria infection, were shown to display differential interactions with PFE1590w.

Conclusion
A dataset of interactions between proteins of P. falciparum and those of its human host was generated. The preferential interaction of the P. falciparum PFE1590w protein with the human ApoE ε3 and ApoE ε4 isoforms, but not the ApoE ε2 isoform, supports the hypothesis that ApoE genotype affects risk of malaria infection. The dataset contains other interactions of potential relevance to disease that may identify possible vaccine candidates and drug targets.
Differences in genetic population structures of Plasmodium falciparum isolates from patients along Thai-Myanmar border with severe or uncomplicated malaria
Authors: Susomboon Pannapa , Iwagami Moritoshi , Tangpukdee Noppadon , Krusood Srivicha , Looareesuwan Sornchai , Kano Shigeyuki 
Published: October 2008

AbstractBackgroundThere have been many reports on the population genetic structures ofPlasmodium falciparumfrom different endemic regions, but few studies have examined the characteristics of isolates from patients with different clinical outcomes. The population genetic structures ofP. falciparumisolates from patients with either severe or uncomplicated malaria were examined.MethodsTwelve microsatellite DNA loci fromP. falciparumwere used to assess the population genetic structures of 50 isolates (i.e., 25 isolates from patients with severe malaria and 25 from patients with uncomplicated malaria) collected in the Thai-Myanmar border area between 2002 and 2005.ResultsGenetic diversity and effective population sizes were greater in the uncomplicated malaria group than in the severe malaria group. Evidence of genetic bottlenecks was not observed in either group. Strong linkage disequilibrium was observed in the uncomplicated malaria group. The groups demonstrated significant genetic differentiation (P< 0.05), and allele frequencies for 3 of the 12 microsatellite loci differed significantly between the two groups.ConclusionThese findings suggest that the genetic structure ofP. falciparumpopulations in patients with severe malaria differs from that in patients with uncomplicated malaria. The microsatellite loci used in this study were presumably unrelated to antigenic features of the parasites, but, these findings suggest that some loci may influence the clinical outcome of malaria.