bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative therapeutic exercise in frail elderly scheduled for total hip replacement: a randomized pilot trial
Authors: Hoogeboom Thomas J , Dronkers Jaap J , van den Ende Cornelia HM , Oosting Ellen , van Meeteren Nico LU 
Published: June 2010

Objective: To evaluate the feasibility and preliminary effectiveness of therapeutic exercise before total hip replacement in frail elderly. Design: A single-blind, randomized clinical pilot trial. Setting: Outpatient physiotherapy department. Subjects: Frail elderly with hip osteoarthritis awaiting total hip replacement. Interventions: A short (3—6 weeks) tailor-made, therapeutic exercise programme was compared with usual care. Main measures: Feasibility was assessed through patient satisfaction, adherence, occurrence of adverse events and the number of eligible non-volunteers. Preliminary preoperative effectiveness was assessed with performance and self-reported measures of pain, functioning, physical activity and quality of life. Postoperatively we measured functional recovery and length of hospital stay. Results: Sixty-two eligible patients were approached of whom 21 (mean age 76 years) agreed to participate. Exercisers (n = 10), rated the intervention as very good 8.9 (8—10) (10-point rating scale). No serious adverse events occurred. Forty-one (66%) eligible patients did not participate, mainly because of logistic considerations, resulting in selection bias. The intervention group (trainings sessions participated 91%) showed relevant preoperative improvements on the chair-rise time (delta —2.9 seconds; 95% confidence interval (CI) —6.2 to 0.4) and timed-up-and-go (delta —4.4 seconds; 95% CI —9.3 to 0.5). Postoperatively, no significant differences were seen. Conclusions: A short, tailor-made, exercise programme is well tolerated and appreciated in elderly patients awaiting total hip replacement. However, a larger randomized clinical trial in the same setting is not warranted, because of the high number of eligible non-volunteers.
Psychometric properties of the Fatigue Severity Scale: Rasch analyses of responses in a Norwegian and a Swedish MS cohort
Authors: Lerdal A. , Johansson S. , Kottorp A. , von Koch L. 
Published: June 2010

Background: Rigorous testing of the original Fatigue Severity Scale (FSS—9) with modern psychometric methods is warranted. Objective: To determine the psychometric properties of the FSS—9 in multiple sclerosis (MS): internal scale validity; person response validity; unidimensionality; uniform differential item functioning; temporal stability of response patterns; and ability to separate people into distinct groups of fatigue. Methods: Rasch analyses were conducted on data from a Norwegian and a Swedish MS cohort followed for two years. Results: Item estimations in the FSS—9 did not differ between sex or levels of education but between the cohorts with regard to disability, disease course and time for evaluation, however, items 1 and 2 demonstrated unacceptable high outfit mean-square values in both cohorts. In an FSS—7 item version, items 3 and 4 in the Norwegian and 4 in the Swedish cohort demonstrated unacceptable goodness of fit but high separation indexes. In the FSS—7, the first unidimensional factor explained 87.5% (Norwegian cohort) and 86.4% (Swedish cohort) of the total variation. Conclusions: In MS, the FSS—7 demonstrates better psychometric properties than the FSS—9; items 1 and 2 neither empirically nor conceptually fit with the other seven items.
Modeling the human 8p11-myeloproliferative syndrome in immunodeficient mice
Authors: Ågerstam Helena , Järås Marcus , Andersson Anna , Johnels Petra , Hansen Nils , Lassen Carin , Rissler Marianne , Gisselsson David , Olofsson Tor , Richter Johan , Fan Xiaolong , Ehinger Mats , Fioretos Thoas 
Published: June 2010

AbstractThe 8p11 myeloproliferative syndrome (EMS), also referred to as stem cell leukemia/lymphoma, is a chronic myeloproliferative disorder that rapidly progresses into acute leukemia. Molecularly, EMS is characterized by fusion of various partner genes to the FGFR1 gene, resulting in constitutive activation of the tyrosine kinases in FGFR1. To date, no previous study has addressed the functional consequences of ectopic FGFR1 expression in the potentially most relevant cellular context, that of normal primary human hematopoietic cells. Herein, we report that expression of ZMYM2/FGFR1 (previously known as ZNF198/FGFR1) or BCR/FGFR1 in normal human CD34+ cells from umbilical-cord blood leads to increased cellular proliferation and differentiation toward the erythroid lineage in vitro. In immunodeficient mice, expression of ZMYM2/FGFR1 or BCR/FGFR1 in human cells induces several features of human EMS, including expansion of several myeloid cell lineages and accumulation of blasts in bone marrow. Moreover, bone marrow fibrosis together with increased extramedullary hematopoiesis is observed. This study suggests that FGFR1 fusion oncogenes, by themselves, are capable of initiating an EMS-like disorder, and provides the first humanized model of a myeloproliferative disorder transforming into acute leukemia in mice. The established in vivo EMS model should provide a valuable tool for future studies of this disorder.
Human FANCC is hypomorphic in murine Fancc-deficient cells
Authors: Hays Laura E. , Keeble Winifred W. , Yates Jane E. , Rathbun R. K. , Koretsky Tara , Olson Susan B. , Sun Zejin , Clapp D. Wade , Bagby Grover C. 
Published: June 2010

AbstractFancc suppresses cross-linker–induced genotoxicity, modulates growth-inhibitory cytokine responses, and modulates endotoxin responses. Although loss of the latter function is known to account for endotoxin-induced marrow failure in murine Fancc (mFancc)–deficient mice, some argue that cytokine and endotoxin hypersensitivities devolve simply from genomic instability. Seeking to resolve this question, we planned to ectopically express instructive human FANCC (hFANCC) mutants in murine Fancc-deficient hematopoietic stem cells. To first assure that hFANCC cDNA was competent in murine cells, we compared hFANCC and mFancc in complementation assays for cross-linking agent hypersensitivity and endotoxin hypersensitivity. We found that mFancc complemented murine Fancc-deficient cells in both assays, but that hFANCC fully suppressed only endotoxin hypersensitivity, not cross-linking agent hypersensitivity. These results support the notions that Fancc is multifunctional and that structural prerequisites for its genoprotective functions differ from those required to constrain endotoxin responses known to lead to marrow failure in Fancc-deficient mice.
Calcium-sensing receptors regulate cardiomyocyte Ca2+ signaling via the sarcoplasmic reticulum-mitochondrion interface during hypoxia/reoxygenation
Authors: Lu Fang-hao , Tian Zhiliang , Zhang Wei-hua , Zhao Ya-jun , Li Hu-lun , Ren Huan , Zheng Hui-shuang , Liu Chong , Hu Guang-xia , Tian Ye , Yang Bao-feng , Wang Rui , Xu Chang-qing 
Published: June 2010

Abstract
Communication between the SR (sarcoplasmic reticulum, SR) and mitochondria is important for cell survival and apoptosis. The SR supplies Ca2+ directly to mitochondria via inositol 1,4,5-trisphosphate receptors (IP3Rs) at close contacts between the two organelles referred to as mitochondrion-associated ER membrane (MAM). Although it has been demonstrated that CaR (calcium sensing receptor) activation is involved in intracellular calcium overload during hypoxia/reoxygenation (H/Re), the role of CaR activation in the cardiomyocyte apoptotic pathway remains unclear. We postulated that CaR activation plays a role in the regulation of SR-mitochondrial inter-organelle Ca2+ signaling, causing apoptosis during H/Re. To investigate the above hypothesis, cultured cardiomyocytes were subjected to H/Re. We examined the distribution of IP3Rs in cardiomyocytes via immunofluorescence and Western blotting and found that type 3 IP3Rs were located in the SR. [Ca2+]i, [Ca2+]m and [Ca2+]SR were determined using Fluo-4, x-rhod-1 and Fluo 5N, respectively, and the mitochondrial membrane potential was detected with JC-1 during reoxygenation using laser confocal microscopy. We found that activation of CaR reduced [Ca2+]SR, increased [Ca2+]i and [Ca2+]m and decreased the mitochondrial membrane potential during reoxygenation. We found that the activation of CaR caused the cleavage of BAP31, thus generating the pro-apoptotic p20 fragment, which induced the release of cytochrome c from mitochondria and the translocation of bak/bax to mitochondria. Taken together, these results reveal that CaR activation causes Ca2+ release from the SR into the mitochondria through IP3Rs and induces cardiomyocyte apoptosis during hypoxia/reoxygenation.
permGPU: Using graphics processing units in RNA microarray association studies
Authors: Shterev Ivo D , Jung Sin-Ho , George Stephen L , Owzar Kouros 
Published: June 2010

AbstractBackgroundMany analyses of microarray association studies involve permutation, bootstrap resampling and cross-validation, that are ideally formulated as embarrassingly parallel computing problems. Given that these analyses are computationally intensive, scalable approaches that can take advantage of multi-core processor systems need to be developed.ResultsWe have developed a CUDA based implementation, , that employs graphics processing units in microarray association studies. We illustrate the performance and applicability of within the context of permutation resampling for a number of test statistics. An extensive simulation study demonstrates a dramatic increase in performance when using on an NVIDIA GTX 280 card compared to an optimized C/C++ solution running on a conventional Linux server.Conclusionsis available as an open-source stand-alone application and as an extension package for the statistical environment. It provides a dramatic increase in performance for permutation resampling analysis in the context of microarray association studies. The current version offers six test statistics for carrying out permutation resampling analyses for binary, quantitative and censored time-to-event traits.
CGHpower: exploring sample size calculations for chromosomal copy number experiments
Authors: Scheinin Ilari , Ferreira José A , Knuutila Sakari , Meijer Gerrit A , van de Wiel Mark A , Ylstra Bauke 
Published: June 2010

AbstractBackgroundDetermining a suitable sample size is an important step in the planning of microarray experiments. Increasing the number of arrays gives more statistical power, but adds to the total cost of the experiment. Several approaches for sample size determination have been developed for expression array studies, but so far none has been proposed for array comparative genomic hybridization (aCGH).ResultsHere we explore power calculations for aCGH experiments comparing two groups. In a pilot experiment CGHpower estimates the biological diversity between groups and provides a statistical framework for estimating average power as a function of sample size. As the method requires pilot data, it can be used either in the planning stage of larger studies or in estimating the power achieved in past experiments.ConclusionsThe proposed method relies on certain assumptions. According to our evaluation with public and simulated data sets, they do not always hold true. Violation of the assumptions typically leads to unreliable sample size estimates. Despite its limitations, this method is, at least to our knowledge, the only one currently available for performing sample size calculations in the context of aCGH. Moreover, the implementation of the method provides diagnostic plots that allow critical assessment of the assumptions on which it is based and hence on the feasibility and reliability of the sample size calculations in each case.The CGHpower web application and the program outputs from evaluation data sets can be freely accessed athttp://www.cangem.org/cghpower/
C. elegans ten-1 is synthetic lethal with mutations in cytoskeleton regulators, and enhances many axon guidance defective mutants
Authors: Mörck Catarina , Vivekanand Vivekanand , Jafari Gholamali , Pilon Marc 
Published: June 2010

Abstract

Background
Teneurins are transmembrane proteins that assist morphogenetic processes in many organisms. ten-1 is the C. elegans teneurin homolog with two transcripts, ten-1a and ten-1b, that respectively encode a long (TEN-1L) and short (TEN-1S) form of the protein. We previously isolated a C. elegans mutant where one pharyngeal neuron was frequently misplaced, and now show that it corresponds to a novel allele of ten-1.

Results
The novel ten-1(et5) allele is a hypomorph since its post-embryonic phenotype is weaker than the null alleles ten-1(ok641) and ten-1(tm651). ten-1 mutants have defects in all pharyngeal neurons that we examined, and in vivo reporters show that only the long form of the ten-1 gene is expressed in the pharynx, specifically in six marginal cells and the M2 neurons. Defects in the pharyngeal M2 neurons were enhanced when the ten-1(ok641) mutation was combined with mutations in the following genes: mig-14, unc-5, unc-51, unc-52 and unc-129. None of the body neurons examined show any defects in the ten-1(ok641) mutant, but genetic interaction studies reveal that ten-1(ok641) is synthetic lethal with sax-3, unc-34 and unc-73, and examination of the hypodermal cells in embryos of the ten-1(ok641) mutant point to a role of ten-1 during hypodermal cell morphogenesis.

Conclusions
Our results are consistent with ten-1 normally providing a function complementary to the cytoskeletal remodeling processes that occur in migrating cells or cells undergoing morphogenesis. It is possible that ten-1 influences the composition/distribution of extracellular matrix.
Overexpression of CDC25B, CDC25C and phospho-CDC25C (Ser216) in vulvar squamous cell carcinomas are associated with malignant features and aggressive cancer phenotypes
Authors: Wang Zhihui , Trope Claes G , Flørenes Vivi Ann , Suo Zhenhe , Nesland Jahn M , Holm Ruth 
Published: June 2010

Abstract

Background
CDC25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of CDC25s in vulvar cancer is still unknown. To shed light on their roles in the pathogenesis and to clarify their prognostic values, expression of CDC25A, CDC25B and CDC25C in a large series of vulvar squamous cell carcinomas were examined.

Methods
Expression of CDC25A, CDC25B, CDC25C and phosphorylated (phospho)-CDC25C (Ser216) were examined in 300 vulvar carcinomas using immunohistochemistry. Western blot analysis was utilized to demonstrate CDC25s expression in vulvar cancer cell lines. Kinase and phosphatase assays were performed to exclude cross reactivity among CDC25s isoform antibodies.

Results
High nuclear CDC25A and CDC25B expression were observed in 51% and 16% of the vulvar carcinomas, respectively, whereas high cytoplasmic CDC25C expression was seen in 63% of the cases. In cytoplasm, nucleus and cytoplasm/nucleus high phospho-CDC25C (Ser216) expression was identified in 50%, 70% and 77% of the carcinomas, respectively. High expression of CDC25s correlated significantly with malignant features, including poor differentiation and infiltration of vessel for CDC25B, high FIGO stage, presence of lymph node metastases, large tumor diameter, poor differentiation for CDC25C and high FIGO stage, large tumor diameter, deep invasion and poor differentiation for phospho-CDC25C (Ser216). In univariate analysis, high expression of phospho-CDC25C (Ser216) was correlated with poor disease-specific survival (p = 0.04). However, such an association was annulled in multivariate analysis.

Conclusions
Our results suggest that CDC25C and phospho-CDC25C (Ser216) play a crucial role and CDC25B a minor role in the pathogenesis and/or progression of vulvar carcinomas. CDC25B, CDC25C and phospho-CDC25C (Ser216) were associated with malignant features and aggressive cancer phenotypes. However, the CDC25s isoforms were not independently correlated to prognosis.
Promoter- and cell-specific epigenetic regulation of CD44, Cyclin D2, GLIPR1 and PTEN by Methyl-CpG binding proteins and histone modifications
Authors: Müller Imke , Wischnewski Frank , Pantel Klaus , Schwarzenbach Heidi 
Published: June 2010

Abstract

Background
The aim of the current study was to analyze the involvement of methyl-CpG binding proteins (MBDs) and histone modifications on the regulation of CD44, Cyclin D2, GLIPR1 and PTEN in different cellular contexts such as the prostate cancer cells DU145 and LNCaP, and the breast cancer cells MCF-7. Since global chromatin changes have been shown to occur in tumours and regions of tumour-associated genes are affected by epigenetic modifications, these may constitute important regulatory mechanisms for the pathogenesis of malignant transformation.

Methods
In DU145, LNCaP and MCF-7 cells mRNA expression levels of CD44, Cyclin D2, GLIPR1 and PTEN were determined by quantitative RT-PCR at the basal status as well as after treatment with demethylating agent 5-aza-2'-deoxycytidine and/or histone deacetylase inhibitor Trichostatin A. Furthermore, genomic DNA was bisulfite-converted and sequenced. Chromatin immunoprecipitation was performed with the stimulated and unstimulated cells using antibodies for MBD1, MBD2 and MeCP2 as well as 17 different histone antibodies.

Results
Comparison of the different promoters showed that MeCP2 and MBD2a repressed promoter-specifically Cyclin D2 in all cell lines, whereas in MCF-7 cells MeCP2 repressed cell-specifically all methylated promoters. Chromatin immunoprecipitation showed that all methylated promoters associated with at least one MBD. Treatment of the cells by the demethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR) caused dissociation of the MBDs from the promoters. Only MBD1v1 bound and repressed methylation-independently all promoters. Real-time amplification of DNA immunoprecipitated by 17 different antibodies showed a preferential enrichment for methylated lysine of histone H3 (H3K4me1, H3K4me2 and H3K4me3) at the particular promoters. Notably, the silent promoters were associated with unmodified histones which were acetylated following treatment by 5-aza-CdR.

Conclusions
This study is one of the first to reveal the histone code and MBD profile at the promoters of CD44, Cyclin D2, GLIPR1 and PTEN in different tumour cells and associated changes after stimulation with methylation inhibitor 5-aza-CdR.
Toll-like receptor 9 polymorphisms influence mother-to-child transmission of human immunodeficiency virus type 1
Authors: Ricci Elisabetta , Malacrida Sandro , Zanchetta Marisa , Mosconi Ilaria , Montagna Marco , Giaquinto Carlo , De Rossi Anita 
Published: June 2010

Abstract

Background
Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and play a crucial role in the host's innate immune response. Genetic variations in TLR genes may influence host-viral interactions and might impact upon the risk of mother-to-child transmission (MTCT) of Human Immunodeficiency Virus type 1 (HIV-1). The aim of this study was to investigate the influence of genetic variants of TLR 9 gene on MTCT.

Methods
Three hundred children (118 HIV-1-infected and 182 HIV-1-uninfected) born to HIV-1-infected mothers were studied. Single nucleotide polymorphisms (SNPs) NM_017442.2: c.4-44G > A (rs352139) and c.1635A > G (rs352140) of the TLR9 gene were genotyped by TaqMan allelic discrimination assay. Statistical analyses were performed using SNPStats program.

Results
When considered separately, neither of the two SNPs was significantly associated with risk of HIV-1 infection. However, the [A;A] and [G;G] haplotypes were associated with a higher risk of HIV-1 infection compared to the prevalent [G;A] haplotype [odds ratio (OR) = 3.16, 95% confidence interval (CI) 1.24-8.03, p = 0.016, and OR = 5.54, 95% CI 1.76-17.50, p = 0.004, respectively].

Conclusions
Overall, results demonstrate a significant correlation between specific genetic variants of the TLR9 gene and risk of MTCT of HIV-1, thus confirming a critical role of innate immunity in perinatal HIV-1 infection. Strategies aimed at modulating innate immunity might be useful for future treatment of pediatric HIV-1 infection and AIDS.
Fusion to chicken C3d enhances the immunogenicity of the M2 protein of avian influenza virus
Authors: Zhang Zhenhua , Li Yongqing , Xu Shufang , Chen Fuyong , Zhang Li , Jiang Beiyu , Chen Xiaoling 
Published: June 2010

AbstractBackgroundCurrent vaccines to avian influenzae virus (AIV), a highly contagious disease of birds, need to be constantly updated due to the high level of variation in the target antigens. Therefore, a vaccine that could induce broad cross protection against AIV is required. The M2 membrane protein is structurally conserved amongst AIV subtypes but tends in induce a poor immune response, whereas C3d has been shown in many species to enhance immunogenicity. In this study, we investigated the potential of M2-avian C3d fusion proteins to provide effective immunity.ResultsWe fused chicken complement C3d to sM2 (M2 protein with the transmembrane region deleted) of AIV and expressed four fusion proteins, GST (Glutathione S-transferase tagged proteins in pGEX expression vector) -C3d-sM2, GST-C3d-L2-sM2, GST-C3d-L1-C3d-sM2 and GST-C3d-L1-C3d-L2-sM2 were used to immunize mice. In addition, Specific pathogen free (SPF) chickens were inoculated with the plasmids pcDNA-sM2, pcDNA-C3d-L1-C3d-L2-sM2, GST-sM2 and GST-C3d-L1-C3d-L2-sM2. The immune response was monitored by an enzyme-linked immunosorbent assay (ELISA) for sM2 antibody, and all the test animals were challenged with A/chicken/Bei Jing/WD9/98 (H9N2) virus. Results revealed that the anti-sM2 antibody in mice and chickens vaccinated with these proteins was higher than the nonfused forms of sM2, the GST-C3d-L1-C3d-L2-sM2 groups have conferred the highest 30% and 20% protection ratio in mice and chickens respectively. In addition, the pcDNA-C3d-L1-C3d-L2-sM2 also enhances the antibody responses to sM2 compared to pcDNA-sM2 in chickens, and acquired 13.3% protection ratio.ConclusionThese results indicated that chicken C3d enhanced the humoral immunity against AIV M2 protein either fused proteins expressed by the prokaryotic system or with the DNA vaccine. Nevertheless, in view of the poor protection ratio for these animals, we speculated that this is not a worthy developing of vaccine in these constructs.
Co-lethality studied as an asset against viral drug escape: the HIV protease case
Authors: Brouillet Sophie , Valere Thomas , Ollivier Emmanuelle , Marsan Laurent , Vanet Anne 
Published: June 2010

AbstractBackgroundCo-lethality, or synthetic lethality is the documented genetic situation where two, separately non-lethal mutations, become lethal when combined in one genome. Each mutation is called a "synthetic lethal" (SL) or a co-lethal. Like invariant positions, SL sets (SL linked couples) are choice targets for drug design against fast-escaping RNA viruses: mutational viral escape by loss of affinity to the drug may induce (synthetic) lethality.ResultsFrom an amino acid sequence alignment of the HIV protease, we detected the potential SL couples, potential SL sets, and invariant positions. From the 3D structure of the same protein we focused on the ones that were close to each other and accessible on the protein surface, to possibly bind putative drugs. We aligned 24,155 HIV protease amino acid sequences and identified 290 potential SL couples and 25 invariant positions. After applying the distance and accessibility filter, three candidate drug design targets of respectively 7 (under the flap), 4 (in the cantilever) and 5 (in the fulcrum) amino acid positions were found.ConclusionsThese three replication-critical targets, located outside of the active site, are key to our anti-escape strategy. Indeed, biological evidence shows that 2/3 of those target positions perform essential biological functions. Their mutational variations to escape antiviral medication could be lethal, thus limiting the apparition of drug-resistant strains.ReviewersThis article was reviewed by Arcady Mushegian, Shamil Sunyaev and Claus Wilke.