bluuebunny/crossref_metadata_2025_split huggingface dataset:
CGHnormaliter: an iterative strategy to enhance normalization of array CGH data with imbalanced aberrations
Authors: van Houte Bart PP , Binsl Thomas W , Hettling Hannes , Pirovano Walter , Heringa Jaap 
Published: August 2009

Abstract

Background
Array comparative genomic hybridization (aCGH) is a popular technique for detection of genomic copy number imbalances. These play a critical role in the onset of various types of cancer. In the analysis of aCGH data, normalization is deemed a critical pre-processing step. In general, aCGH normalization approaches are similar to those used for gene expression data, albeit both data-types differ inherently. A particular problem with aCGH data is that imbalanced copy numbers lead to improper normalization using conventional methods.

Results
In this study we present a novel method, called CGHnormaliter, which addresses this issue by means of an iterative normalization procedure. First, provisory balanced copy numbers are identified and subsequently used for normalization. These two steps are then iterated to refine the normalization. We tested our method on three well-studied tumor-related aCGH datasets with experimentally confirmed copy numbers. Results were compared to a conventional normalization approach and two more recent state-of-the-art aCGH normalization strategies. Our findings show that, compared to these three methods, CGHnormaliter yields a higher specificity and precision in terms of identifying the 'true' copy numbers.

Conclusion
We demonstrate that the normalization of aCGH data can be significantly enhanced using an iterative procedure that effectively eliminates the effect of imbalanced copy numbers. This also leads to a more reliable assessment of aberrations. An R-package containing the implementation of CGHnormaliter is available at http://www.ibi.vu.nl/programs/cghnormaliterwww.
Two distinct groups of porcine enteropathogenic Escherichia coli strains of serogroup O45 are revealed by comparative genomic hybridization and virulence gene microarray
Authors: Bruant Guillaume , Zhang Yongxiang , Garneau Philippe , Wong Justin , Laing Chad , Fairbrother John M , Gannon Victor PJ , Harel Josée 
Published: August 2009

Abstract

Background
Porcine enteropathogenic Escherichia coli (PEPEC) strains of serogroup O45 cause post-weaning diarrhea and produce characteristic attaching and effacing (A/E) lesions. Most O45 PEPEC strains possess the locus of enterocyte effacement (LEE), encoding the virulence factors required for production of A/E lesions, and often possess the paa gene, which is thought to contribute to the early stages of PEPEC pathogenicity. In this study, nine O45 PEPEC strains and a rabbit enteropathogenic (REPEC) strain, known to produce A/E lesions in vivo, were characterized using an E. coli O157-E. coli K12 whole genome microarray and a virulence gene-specific microarray, and by PCR experiments.

Results
Based on their virulence gene profiles, the 10 strains were considered to be atypical EPEC. The differences in their genomes pointed to the identification of two distinct evolutionary groups of O45 PEPEC, Groups I and II, and provided evidence for a contribution of these genetic differences to their virulence in pigs. Group I included the REPEC strain and four O45 PEPEC strains known to induce severe A/E lesions in challenged pigs whereas Group II was composed of the five other O45 PEPEC strains, which induced less severe or no A/E lesions in challenged pigs. Significant differences between Groups I and II were found with respect to the presence or absence of 50 O-Islands (OIs) or S-loops and 13 K-islands (KIs) or K-loops, including the virulence-associated islands OI#1 (S-loop#1), OI#47 (S-loop#71), OI#57 (S-loop#85), OI#71 (S-loop#108), OI#115, OI#122, and OI#154 (S-loop#253).

Conclusion
We have genetically characterized a collection of O45 PEPEC strains and classified them into two distinct groups. The differences in their virulence gene and genomic island content may influence the pathogenicity of O45 PEPEC strains, and explain why Group I O45 PEPEC strains induced more severe A/E lesions in explants and challenged pigs than Group II strains.
Transduction of the MPG-tagged fusion protein into mammalian cells and oocytes depends on amiloride-sensitive endocytic pathway
Authors: Kwon So-Jung , Han Kyuyong , Jung Suhyun , Lee Jong-Eun , Park Seongsoon , Cheon Yong-Pil , Lim Hyunjung Jade 
Published: August 2009

Abstract

Background
MPG is a cell-permeable peptide with proven efficiency to deliver macromolecular cargoes into cells. In this work, we examined the efficacy of MPG as an N-terminal tag in a fusion protein to deliver a protein cargo and its mechanism of transduction.

Results
We examined transduction of MPG-EGFP fusion protein by live imaging, flow cytometry, along with combination of cell biological and pharmacological methods. We show that MPG-EGFP fusion proteins efficiently enter various mammalian cells within a few minutes and are co-localized with FM4-64, a general marker of endosomes. The transduction of MPG-EGFP occurs rapidly and is inhibited at a low temperature. The entry of MPG-EGFP is inhibited by amiloride, but cytochalasin D and methyl-β-cyclodextrin did not inhibit the entry, suggesting that macropinocytosis is not involved in the transduction. Overexpression of a mutant form of dynamin partially reduced the transduction of MPG-EGFP. The partial blockade of MPG-EGFP transduction by a dynamin mutant is abolished by the treatment of amiloride. MPG-EGFP transduction is also observed in the mammalian oocytes.

Conclusion
The results show that the transduction of MPG fusion protein utilizes endocytic pathway(s) which is amiloride-sensitive and partially dynamin-dependent. Collectively, the MPG fusion protein could be further developed as a novel tool of "protein therapeutics", with potentials to be used in various cell systems including mammalian oocytes.
Measuring adolescents' HRQoL via self reports and parent proxy reports: an evaluation of the psychometric properties of both versions of the KINDL-R instrument
Authors: Erhart Michael , Ellert Ute , Kurth Bärbel-Maria , Ravens-Sieberer Ulrike 
Published: August 2009

Abstract

Background
Several instruments are available to assess children's health-related quality of life (HRQoL) based on self reports as well as proxy reports from parents. Previous studies have found only low-to-moderate agreement between self and proxy reports, but few studies have explicitly compared the psychometric qualities of both. This study compares the reliability, factorial validity and convergent and known group validity of the self-report and parent-report versions of the HRQoL KINDL-R questionnaire for children and adolescents.

Methods
Within the nationally representative cross-sectional German Health Interview and Examination Survey for Children and Adolescents (KiGGS), 6,813 children and adolescents aged 11 to 17 years completed the KINDL-R generic HRQoL instrument while their parents answered the KINDL proxy version (both in paper-and-pencil versions). Cronbach's alpha and confirmatory factor-analysis models (linear structural equation model) were obtained. Convergent and discriminant validity were assessed by calculating the Pearson's correlation coefficient for the Strengths and Difficulties Questionnaire. Known-groups differences were examined (ANOVA) for obese children and children with a lower familial socio-economic status.

Results
The parent reports achieved slightly higher Cronbach's alpha values for the total score (0.86 vs. 0.83) and most sub-scores. Confirmatory factor analysis revealed an acceptable fit of the six-dimensional measurement model of the KINDL for the parent (RMSEA = 0.07) and child reports (RMSEA = 0.06). Factorial invariance across the two versions did not hold with regards to the pattern of loadings, the item errors and the covariation between latent concepts. However the magnitude of the differences was rather small. The parent report version achieved slightly higher convergent validity (r = 0.44 – 0.63 vs. r = 0.33 – 0.59) in the Strengths and Difficulties Questionnaire. No clear differences were observed for known-groups validity.

Conclusion
Our study showed that parent proxy reports and child self reports on the child's HRQoL slightly differ with regards to how the perceptions, evaluations and possibly the affective resonance of each group are structured and internally consistent. Overall, the parent reports achieved slightly higher reliability and thus are favoured for the examination of small samples. No version was universally superior with regards to the validity of the measurements. Whenever possible, children's HRQoL should be measured via both sources of information.
Botulinum toxin type A injections for the management of muscle tightness following total hip arthroplasty: a case series
Authors: Bhave Anil , Zywiel Michael G , Ulrich Slif D , McGrath Mike S , Seyler Thorsten M , Marker David R , Delanois Ronald E , Mont Michael A 
Published: August 2009

Abstract

Background
Development of hip adductor, tensor fascia lata, and rectus femoris muscle contractures following total hip arthroplasties are quite common, with some patients failing to improve despite treatment with a variety of non-operative modalities. The purpose of the present study was to describe the use of and patient outcomes of botulinum toxin injections as an adjunctive treatment for muscle tightness following total hip arthroplasty.

Methods
Ten patients (14 hips) who had hip adductor, abductor, and/or flexor muscle contractures following total arthroplasty and had been refractory to physical therapeutic efforts were treated with injection of botulinum toxin A. Eight limbs received injections into the adductor muscle, 8 limbs received injections into the tensor fascia lata muscle, and 2 limbs received injection into the rectus femoris muscle, followed by intensive physical therapy for 6 weeks.

Results
At a mean final follow-up of 20 months, all 14 hips had increased range in the affected arc of motion, with a mean improvement of 23 degrees (range, 10 to 45 degrees). Additionally all hips had an improvement in hip scores, with a significant increase in mean score from 74 points (range, 57 to 91 points) prior to injection to a mean of 96 points (range, 93 to 98) at final follow-up. There were no serious treatment-related adverse events.

Conclusion
Botulinum toxin A injections combined with intensive physical therapy may be considered as a potential treatment modality, especially in difficult cases of muscle tightness that are refractory to standard therapy.
Watermelon juice: a promising feedstock supplement, diluent, and nitrogen supplement for ethanol biofuel production
Authors: Fish Wayne W , Bruton Benny D , Russo Vincent M 
Published: August 2009

Abstract

Background
Two economic factors make watermelon worthy of consideration as a feedstock for ethanol biofuel production. First, about 20% of each annual watermelon crop is left in the field because of surface blemishes or because they are misshapen; currently these are lost to growers as a source of revenue. Second, the neutraceutical value of lycopene and L-citrulline obtained from watermelon is at a threshold whereby watermelon could serve as starting material to extract and manufacture these products. Processing of watermelons to produce lycopene and L-citrulline, yields a waste stream of watermelon juice at the rate of over 500 L/t of watermelons. Since watermelon juice contains 7 to 10% (w/v) directly fermentable sugars and 15 to 35 μmol/ml of free amino acids, its potential as feedstock, diluent, and nitrogen supplement was investigated in fermentations to produce bioethanol.

Results
Complete watermelon juice and that which did not contain the chromoplasts (lycopene), but did contain free amino acids, were readily fermentable as the sole feedstock or as diluent, feedstock supplement, and nitrogen supplement to granulated sugar or molasses. A minimum level of ~400 mg N/L (~15 μmol/ml amino nitrogen) in watermelon juice was required to achieve maximal fermentation rates when it was employed as the sole nitrogen source for the fermentation. Fermentation at pH 5 produced the highest rate of fermentation for the yeast system that was employed. Utilizing watermelon juice as diluent, supplemental feedstock, and nitrogen source for fermentation of processed sugar or molasses allowed complete fermentation of up to 25% (w/v) sugar concentration at pH 3 (0.41 to 0.46 g ethanol per g sugar) or up to 35% (w/v) sugar concentration at pH 5 with a conversion to 0.36 to 0.41 g ethanol per g sugar.

Conclusion
Although watermelon juice would have to be concentrated 2.5- to 3-fold to serve as the sole feedstock for ethanol biofuel production, the results of this investigation indicate that watermelon juice, either as whole juice fermented on-site or as a waste stream from neutraceutical production, could easily integrate with other more concentrated feedstocks where it could serve as diluent, supplemental feedstock, and nitrogen supplement.
Disparity in health care: HIV, stigma, and marginalization in Nepal
Authors: Jha Chandra K , Madison Jeanne 
Published: August 2009

BackgroundThe provision of effective health care to people with HIV and those from usually marginalised backgrounds, such as drug users and sex workers is a growing concern in Nepal, because these populations often do not seek health care, as willingly as the general population. Exploration of the factors, which hinder them seeking health care is crucial. The ‘lived' experiences of the usually marginalized participants in this research will reflect on the constraining factors, and contribute to the development of appropriate strategies, which will facilitate people with HIV and other marginal populations to seek more readily appropriate health services.MethodsThis study explored the healthcare‐seeking experiences of 20 HIV‐positive participants in Nepal, as well as 10 drug‐using participants who had never had an HIV test and did not know their HIV status. Using grounded theory, this study investigated the perceptions and experiences of HIV‐positive persons, or those perceived to be at risk for HIV, as they sought health care services in locations around Kathmandu Valley.ResultsHealth professionals were perceived to lack knowledge and sensitivity in providing health care to often marginalized and stigmatized injecting drug users, sex workers and HIV‐positive people. Stigma and marginalization seem to interfere with doctors' and other health professionals' decisions to voluntarily treat persons who they perceive to be at high risk for HIV infections. Doctors and other health professionals appear suspicious, even unaware, of contemporary biomedical knowledge as it relates to HIV. The fear that certain marginalized groups, such as injecting drug users and sex workers, would be infected with HIV has further intensified stigma against these groups.ConclusionThe study identified the beginning of a change in the experiences of HIV‐positive people, or those at risk of HIV, in their seeking of health care. With focused, contemporary HIV education and training, the beginning of positive changes in the knowledge base and attitude of health providers seemed to be apparent to some participants of this study.
'Diabetology & Metabolic Syndrome: providing an open access future for diabetes research'
Authors: Giannella-Neto Daniel , de Brito Gomes Marília 
Published: August 2009

Abstract

Diabetology & Metabolic Syndrome (D&MS), the official journal of the Brazilian Diabetes Society (SBD), is a new open access, peer reviewed journal publishing research on all aspects of the pathophysiology of diabetes and metabolic syndrome. With the many ongoing and upcoming challenges for diabetes diagnosis, treatment and care, a dedicated journal providing unrestricted access for researchers and health care professionals working in the field of diabetes is needed. Diabetology & Metabolic Syndrome aims to fulfil this need.
Resident macrophages influence stem cell activity in the mammary gland
Authors: Gyorki David E , Asselin-Labat Marie-Liesse , van Rooijen Nico , Lindeman Geoffrey J , Visvader Jane E 
Published: August 2009

Abstract
Introduction
Macrophages in the mammary gland are essential for morphogenesis of the ductal epithelial tree and have been implicated in promoting breast tumor metastasis. Although it is well established that macrophages influence normal mammopoiesis, the mammary cell types that these accessory cells influence have not been determined. Here we have explored a role for macrophages in regulating mammary stem cell (MaSC) activity, by assessing the ability of MaSCs to reconstitute a mammary gland in a macrophage-depleted fat pad.

Methods
Two different in vivo models were used to deplete macrophages from the mouse mammary fat pad, allowing us to examine the effect of macrophage deficiency on the mammary repopulating activity of MaSCs. Both the Csf1
op/op
mice and clodronate liposome-mediated ablation models entailed transplantation studies using the MaSC-enriched population.

Results
We show that mammary repopulating ability is severely compromised when the wild-type MaSC-enriched subpopulation is transplanted into Csf1
op/op
fat pads. In reciprocal experiments, the MaSC-enriched subpopulation from Csf1
op/op
glands had reduced regenerative capacity in a wild-type environment. Utilizing an alternative strategy for selective depletion of macrophages from the mammary gland, we demonstrate that co-implantation of the MaSC-enriched subpopulation with clodronate-liposomes leads to a marked decrease in repopulating frequency and outgrowth potential.

Conclusions
Our data reveal a key role for mammary gland macrophages in supporting stem/progenitor cell function and suggest that MaSCs require macrophage-derived factors to be fully functional. Macrophages may therefore constitute part of the mammary stem cell niche.
BRCA1-deficient mammary tumor cells are dependent on EZH2 expression and sensitive to Polycomb Repressive Complex 2-inhibitor 3-deazaneplanocin A
Authors: Puppe Julian , Drost Rinske , Liu Xiaoling , Joosse Simon A , Evers Bastiaan , Cornelissen-Steijger Paulien , Nederlof Petra , Yu Qiang , Jonkers Jos , van Lohuizen Maarten , Pietersen Alexandra M 
Published: August 2009

Abstract
Introduction
Treatment of breast cancer is becoming more individualized with the recognition of tumor subgroups that respond differently to available therapies. Breast cancer 1 gene (BRCA1)-deficient tumors are usually of the basal subtype and associated with poor survival rates, highlighting the need for more effective therapy.

Methods
We investigated a mouse model that closely mimics breast cancer arising in BRCA1-mutation carriers to better understand the molecular mechanism of tumor progression and tested whether targeting of the Polycomb-group protein EZH2 would be a putative therapy for BRCA1-deficient tumors.

Results
Gene expression analysis demonstrated that EZH2 is overexpressed in BRCA1-deficient mouse mammary tumors. By immunohistochemistry we show that an increase in EZH2 protein levels is also evident in tumors from BRCA1-mutation carriers. EZH2 is responsible for repression of genes driving differentiation and could thus be involved in the undifferentiated phenotype of these tumors. Importantly, we show that BRCA1-deficient cancer cells are selectively dependent on their elevated EZH2 levels. In addition, a chemical inhibitor of EZH2, 3-deazaneplanocin A (DZNep), is about 20-fold more effective in killing BRCA1-deficient cells compared to BRCA1-proficient mammary tumor cells.

Conclusions
We demonstrate by specific knock-down experiments that EZH2 overexpression is functionally relevant in BRCA1-deficient breast cancer cells. The effectiveness of a small molecule inhibitor indicates that EZH2 is a druggable target. The overexpression of EZH2 in all basal-like breast cancers warrants further investigation of the potential for targeting the genetic make-up of this particular breast cancer type.
Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model
Authors: Rosengarten Bernhard , Wolff Stephanie , Klatt Sabine , Schermuly Ralf T 
Published: August 2009

Abstract
Introduction
The inducible nitric oxide synthase (iNOS) plays a crucial role in early sepsis-related microcirculatory dysfunction. Compared to a catecholamine therapy we tested effects of a specific iNOS-inhibitor (1400W) on the microcirculatory function in the brain.

Methods
Seventy SD-rats (280-310 g) were divided into 1 control and 6 sepsis groups. Sepsis groups received 1 or 5 mg/kg lipopolysaccharide (LPS) intravenously to induce a moderate or severe sepsis syndrome. Thirty minutes later rats were further randomized into subgroups receiving moderate volume therapy alone or additionally continuous norepinephrine (NE) or 1400W infusion. Separately, effects of 1400W on neurofunctional parameters were investigated in 3 rats without sepsis induction. Performing electric forepaw-stimulation evoked potentials (N2-P1 amplitude, P1-latency) and local hemodynamic responses were recorded with surface electrodes and laser Doppler over the somatosensory cortex at baseline and repeatedly after LPS administration. Cytokine levels (tumor necrosis factor-alpha (TNFα), interleukin-6 (IL6), interferon-gamma (IFNγ)) and cell destruction markers (neuron-specific enolase (NSE), S-100 calcium binding protein B (S100B)) were obtained at the end of experiments.

Results
During sepsis progression resting cerebral blood flow increased and functionally activated hemodynamic responses decreased in a dose-dependent manner. Whereas 1400W and NE improved blood pressure, only 1400W stabilized resting flow levels. However, both regimens were ineffective on the functionally coupled flow responses and destruction markers were similar between groups.

Conclusions
NE and 1400W appeared to be ineffective in mitigating the effects of sepsis on the neurovascular coupling. Other regimens are needed to protect the cerebral microcirculation under septic conditions.
Depletion of T-cell intracellular antigen proteins promotes cell proliferation
Authors: Reyes Raquel , Alcalde José , Izquierdo José M 
Published: August 2009

Abstract
Background
T-cell intracellular antigen-1 (TIA-1) and TIA-1 related/like protein (TIAR/TIAL1), two DNA/RNA binding proteins broadly expressed in eukaryotic cells, participate in the regulation of gene expression through RNA metabolism. Despite the biological relevance of these regulators, there are no genome-wide studies assessing global transcriptomic and phenotypic impacts after changes in the expression and/or function of these proteins.

Results
Using high-throughput gene expression profiling, we found that the TIA-1/TIAR-depleted cell phenotype is linked to a transcriptome involved in the control of inflammation, cell-cell signaling, immune-suppression, angiogenesis, metabolism and cell proliferation. Induced genes included pro-inflammatory cytokines, inflammatory chemokines, growth-stimulating factors and pro-angiogenic inducers. Repressed genes involved the RAS oncogene family member RAB40B, regulators of cytoskeleton organization and biogenesis and a mitochondrial modulator. Consistent with these observations, depletion of TIA proteins in HeLa cells results in increased cell proliferation, altered cell-cycle and anchorage-independent growth. Mechanistically, the changes associated with the steady-state target mRNA levels regulated by TIA proteins are consistent with overlapping effects on gene basal transcription rate and mRNA turnover.

Conclusions
Collectively, our findings suggest a role for TIA proteins as cellular sensors that modulate gene expression control at the transcriptional and post-transcriptional levels, coupling cell proliferation responses and metabolic homeostasis to cell survival and growth.