bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNMT3b overexpression contributes to a hypermethylator phenotype in human breast cancer cell lines
Authors: Roll J Devon , Rivenbark Ashley G , Jones Wendell D , Coleman William B 
Published: January 2008

AbstractBackgroundDNA hypermethylation events and other epimutations occur in many neoplasms, producing gene expression changes that contribute to neoplastic transformation, tumorigenesis, and tumor behavior. Some human cancers exhibit a hypermethylator phenotype, characterized by concurrent DNA methylation-dependent silencing of multiple genes. To determine if a hypermethylation defect occurs in breast cancer, the expression profile and promoter methylation status of methylation-sensitive genes were evaluated among breast cancer cell lines.ResultsThe relationship between gene expression (assessed by RT-PCR and quantitative real-time PCR), promoter methylation (assessed by methylation-specific PCR, bisulfite sequencing, and 5-aza-2'deoxycytidine treatment), and the DNA methyltransferase machinery (total DNMT activity and expression of DNMT1, DNMT3a, and DNMT3b proteins) were examined in 12 breast cancer cell lines. Unsupervised cluster analysis of the expression of 64 methylation-sensitive genes revealed two groups of cell lines that possess distinct methylation signatures: (i) hypermethylator cell lines, and (ii) low-frequency methylator cell lines. The hypermethylator cell lines are characterized by high rates of concurrent methylation of six genes (CDH1, CEACAM6, CST6, ESR1, LCN2, SCNN1A), whereas the low-frequency methylator cell lines do not methylate these genes. Hypermethylator cell lines coordinately overexpress total DNMT activity and DNMT3b protein levels compared to normal breast epithelial cells. In contrast, most low-frequency methylator cell lines possess DNMT activity and protein levels that are indistinguishable from normal. Microarray data mining identified a strong cluster of primary breast tumors that express the hypermethylation signature defined byCDH1,CEACAM6, CST6, ESR1, LCN2, andSCNN1A. This subset of breast cancers represents 18/88 (20%) tumors in the dataset analyzed, and 100% of these tumors were classified as basal-like, suggesting that the hypermethylator defect cosegregates with poor prognosis breast cancers.ConclusionThese observations combine to strongly suggest that: (a) a subset of breast cancer cell lines express a hypermethylator phenotype, (b) the hypermethylation defect in these breast cancer cell lines is related to aberrant overexpression of DNMT activity, (c) overexpression of DNMT3b protein significantly contributes to the elevated DNMT activity observed in tumor cells expressing this phenotype, and (d) the six-gene hypermethylator signature characterized in breast cancer cell lines defines a distinct cluster of primary basal-like breast cancers.
Human endogenous retrovirus-FRD envelope protein (syncytin 2) expression in normal and trisomy 21-affected placenta
Authors: Malassiné André , Frendo Jean-Louis , Blaise Sandra , Handschuh Karen , Gerbaud Pascale , Tsatsaris Vassilis , Heidmann Thierry , Evain-Brion Danièle 
Published: January 2008

Abstract
Human trophoblast expresses two fusogenic retroviral envelope proteins, the widely studied syncytin 1, encoded by HERV-W and the recently characterized syncytin 2 encoded by HERV-FRD. Here we studied syncytin 2 in normal and Trisomy 21-affected placenta associated with abnormal trophoblast differentiation. Syncytin 2 immunolocalization was restricted throughout normal pregnancy to some villous cytotrophoblastic cells (CT). During the second trimester of pregnancy, syncytin 2 was immunolocalized in some cuboidal CT in T21 placentas, whereas in normal placentas it was observed in flat CT, extending into their cytoplasmic processes. In vitro, CT isolated from normal placenta fuse and differentiate into syncytiotrophoblast. At the same time, syncytin 2 transcript levels decreased significantly with syncytiotrophoblast formation. In contrast, CT isolated from T21-affected placentas fused and differentiated poorly and no variation in syncytin 2 transcript levels was observed. Syncytin 2 expression illustrates the abnormal trophoblast differentiation observed in placenta of fetal T21-affected pregnancies.
Primary monophasic synovial sarcoma presenting as a pulmonary mass: a case report
Authors: Mermigkis Charalampos M. , Kopanakis Antony , Patentalakis George , Polychronopoulos Vlassis , Patentalakis Michael 
Published: January 2008

Abstract

Introduction
Primary pulmonary synovial sarcoma is an extremely rare tumor with only few case reports in the literature.

Case presentation
A healthy 67-year-old woman was admitted for investigation of a pulmonary mass found on a routine X-ray. She had a history of breast cancer diagnosed and treated 13 years previously with left mastectomy followed by adjuvant endocrine therapy. No progression of the disease was reported. Thoracic computer tomography disclosed a soft-tissue mass in the lower lobe of the left lung arising in the vicinity of the pleura. No abnormal lymph nodes were noted. Further work-up for metastases was negative. Subsequently, the lower lobe of the left lung was removed and the diagnosis was a monophasic synovial sarcoma.

Conclusion
The diagnosis of monophasic primary pulmonary synovial sarcoma requires clinical, imaging and immunohistochemical investigation to exclude alternative primary sources. The treatment of choice is excision (lobectomy or pneumonectomy), which in most of cases is helpful for diagnosis. The prognosis is usually poor.
CD47 associates with alpha 5 integrin and regulates responses of human articular chondrocytes to mechanical stimulation in an in vitromodel
Authors: Orazizadeh Mahmoud , Lee Herng Sheng , Groenendijk Bianca , Sadler S Jane Millward , Wright Malcolm O , Lindberg Frederik P , Salter Donald M 
Published: January 2008

Abstract
Background
Recent studies provide evidence of roles for integrins in mechanical signalling in bone and cartilage. Integrin signalling is modulated by various mechanisms, including interaction with other transmembrane proteins. We aimed to identify whether one such protein, integrin-associated protein (CD47/IAP), is expressed by chondrocytes and whether it may regulate integrin-dependent mechanotransduction.

Methods
Chondrocytes, isolated from macroscopically normal and osteoarthritic articular cartilage of human knee joints, were studied in a resting state or following mechanical stimulation at 0.33 Hz. CD47/IAP expression and associations were confirmed by immunohistology, reverse transcription-polymerase chain reaction, Western blotting, and immunoprecipitation. Roles in mechanotransduction were studied by assessing effects of function-blocking antibodies on a range of electrophysiological, cellular, and molecular responses of primary chondrocytes and responses of CD47/IAP-null cell lines transfected with CD47/IAP.

Results
Human articular chondrocytes were shown to express CD47/IAP, predominantly the type 2 isoform. Immunoprecipitation showed association of CD47/IAP with α5 integrin and thrombospondin but not SIRPα (signal-regulatory protein-alpha). The function-blocking anti-CD47/IAP antibody Bric 126 inhibited changes in membrane potential, tyrosine phosphorylation, and elevation of relative levels of aggrecan mRNA induced by mechanical stimulation, whereas in the presence of B6H12, an antibody that has partial agonist activity, a membrane depolarisation rather than a membrane hyperpolarisation response was induced by mechanical stimulation. CD47-null cell lines did not show changes in cell membrane potential following mechanical stimulation. Changes in cell membrane potential following mechanical stimulation were seen when CD47-null cells were transfected with CD47/IAP expression vectors but were not seen following mechanical stimulation of cells transfected with vectors for the extracellular immunoglobulin variable (IgV) domain of CD47/IAP in the absence of the transmembrane and intracellular domains.

Conclusion
CD47/IAP is necessary for chondrocyte mechanotransduction. Through interactions with α5β1 integrin and thrombospondin, CD47/IAP may modulate chondrocyte responses to mechanical signals.
Three-dimensional and thermal surface imaging produces reliable measures of joint shape and temperature: a potential tool for quantifying arthritis
Authors: Spalding Steven J , Kwoh C Kent , Boudreau Robert , Enama Joseph , Lunich Julie , Huber Daniel , Denes Louis , Hirsch Raphael 
Published: January 2008

Abstract
Introduction
The assessment of joints with active arthritis is a core component of widely used outcome measures. However, substantial variability exists within and across examiners in assessment of these active joint counts. Swelling and temperature changes, two qualities estimated during active joint counts, are amenable to quantification using noncontact digital imaging technologies. We sought to explore the ability of three dimensional (3D) and thermal imaging to reliably measure joint shape and temperature.

Methods
A Minolta 910 Vivid non-contact 3D laser scanner and a Meditherm med2000 Pro Infrared camera were used to create digital representations of wrist and metacarpalphalangeal (MCP) joints. Specialized software generated 3 quantitative measures for each joint region: 1) Volume; 2) Surface Distribution Index (SDI), a marker of joint shape representing the standard deviation of vertical distances from points on the skin surface to a fixed reference plane; 3) Heat Distribution Index (HDI), representing the standard error of temperatures. Seven wrists and 6 MCP regions from 5 subjects with arthritis were used to develop and validate 3D image acquisition and processing techniques. HDI values from 18 wrist and 9 MCP regions were obtained from 17 patients with active arthritis and compared to data from 10 wrist and MCP regions from 5 controls. Standard deviation (SD), coefficient of variation (CV), and intraclass correlation coefficients (ICC) were calculated for each quantitative measure to establish their reliability. CVs for volume and SDI were <1.3% and ICCs were greater than 0.99.

Results
Thermal measures were less reliable than 3D measures. However, significant differences were observed between control and arthritis HDI values. Two case studies of arthritic joints demonstrated quantifiable changes in swelling and temperature corresponding with changes in symptoms and physical exam findings.

Conclusion
3D and thermal imaging provide reliable measures of joint volume, shape, and thermal patterns. Further refinement may lead to the use of these technologies to improve the assessment of disease activity in arthritis.
The role of diacylglyceride generation by phospholipase D and phosphatidic acid phosphatase in the activation of 5-lipoxygenase in polymorphonuclear leukocytes
Authors: Albert Dana , Pergola Carlo , Koeberle Andreas , Dodt Gabriele , Steinhilber Dieter , Werz Oliver 
Published: January 2008

AbstractDiacylglycerides (DAGs) such as 1-oleoyl-2-acetyl-sn-glycerol (OAG) stimulate 5-lipoxygenase (5-LO) enzyme activity and function as agonists for human polymorphonuclear leukocytes (PMNL) to induce 5-LO product synthesis. Here, we addressed the role of endogenous DAG generation in agonist-induced 5-LO activation in human PMNL. Preincubation of PMNL with the phospholipase D (PLD) inhibitor 1-butanol potently suppressed 5-LO product synthesis induced by the Ca2+ ionophore A23187 or thapsigargin (TG) and blocked A23187-evoked translocation of 5-LO from the cytosol to the nuclear membrane, analyzed by subcellular fractionation as well as by indirect immunofluorescence microscopy. Tertiary-butanol, a rather poor inhibitor of PLD, caused only moderate suppression of 5-LO and hardly inhibited 5-LO translocation. Interestingly, 1-butanol failed to inhibit 5-LO product formation when PMNL were stimulated with OAG (30 μM). Moreover, coincubation of A23187- or TG-stimulated PMNL with OAG reversed inhibition of 5-LO product formation by 1-butanol in a concentration-dependent manner (EC50, ∼1 μM) and also restored 5-LO translocation. In addition, inhibition of phosphatidic acid phosphatase (PA-P) by propranolol or bromoenol lactone caused suppression of 5-LO product formation and of translocation, which could be reversed by addition of exogenous OAG. Together, our data suggest that in agonist-stimulated PMNL, the endogenous formation of DAGs via the PLD/PA-P pathway determines 5-LO activation.
The Thyrotropin Receptor Hinge Region Is Not Simply a Scaffold for the Leucine-Rich Domain but Contributes to Ligand Binding and Signal Transduction
Authors: Mizutori Yumiko , Chen Chun-Rong , McLachlan Sandra M. , Rapoport Basil 
Published: January 2008

AbstractThe glycoprotein hormone receptor hinge region connects the leucine-rich and transmembrane domains. The prevalent concept is that the hinge does not play a significant role in ligand binding and signal transduction. Portions of the hinge are redundant and can be deleted by mutagenesis or are absent in certain species. A minimal hinge will be more amenable to future investigation of its structure and function. We, therefore, combined and progressively extended previous deletions (Δ) in the TSH receptor (TSHR) hinge region (residues 277–418). TSHRΔ287–366, Δ287–371, Δ287–376, and Δ287–384 progressively lost their response to TSH stimulation of cAMP generation in intact cells, consistent with a progressive loss of TSH binding. The longest deletion (TSHRΔ287–384), reducing the hinge region from 141 to 43 amino acids, totally lost both functions. Surprisingly, however, with deletions extending from residues 371–384, constitutive (ligand-independent) activity increased severalfold, reversing the suppressive (inverse agonist) effect of the TSHR extracellular domain. TSHR-activating point mutations I486F and I568T in the first and second extracellular loops (especially the former) had reduced activity on a background of TSHRΔ287–371. In summary, our data support the concept that the TSHR hinge contributes significantly to ligand binding affinity and signal transduction. Residues within the hinge, particularly between positions 371–384, appear involved in ectodomain inverse agonist activity. In addition, the hinge is necessary for functionality of activating mutations in the first and second extracellular loops. Rather than being an inert linker between the leucine-rich and transmembrane domains, the TSHR hinge is a signaling-specificity domain.
Nuclear Hormone Receptors for Heme: REV-ERBα and REV-ERBβ Are Ligand-Regulated Components of the Mammalian Clock
Authors: Burris Thomas P. 
Published: January 2008

AbstractThe nuclear hormone receptors (NHRs), REV-ERBα and REV-ERBβ, regulate a number of physiological functions including the circadian rhythm, lipid metabolism, and cellular differentiation. These two receptors lack the activation function-2 region that is associated with the ability of NHRs to recruit coactivators and activate target gene transcription. These NHRs have been characterized as constitutive repressors of transcription due to their lack of an identified ligand and their strong ability to recruit the corepressor, nuclear receptor corepressor. Recently, the porphyrin heme was demonstrated to function as a ligand for both REV-ERBs. Heme binds directly to the ligand-binding domain and regulates the ability of these NHRs to recruit nuclear receptor corepressor to target gene promoters. This review focuses on the physiological roles that these two receptors play and the implications of heme functioning as their ligand. The prospect that these NHRs, now known to be regulated by small molecule ligands, may be targets for development of drugs for treatment of diseases associated with aberrant circadian rhythms including metabolic and psychiatric disorders as well as cancer is also addressed.
Inverse problems of plane wave scattering by 1D inhomogeneous layers
Authors: Alekseev A. S. , Megrabov A. G. 
Published: January 2008

Inverse problems of the plane waves scattering of inclined incidence of the SH type by an inhomogeneous half-space (in particular, by a transition layer) or by an inhomogeneous layer with a free boundary are considered. The characteristics of an inhomogeneous elastic medium, i.e., the wave propagation velocity ν(z) and the density ρ(z), are functions of depth z and should be determined in the inverse problems. The following are considered: the inverse problems with data for a fixed angle of incidence θ0 of a plane wave (the angle between the vector of the normal to the plane wave front and z-axis) when the shape φ0(ξ, θ0) of an incident wave is known; the inverse problems with data for a family of angles θ0 both for known and unknown shapes of the incident wave. The functions φ0(ξ, θ0) and φ1(ξ, θ0) (the shapes of incident and reflected waves), the functions φ0(ξ, θ0) and u(H, ξ, θ0) (the shapes of the incident wave and the free boundary oscillation field), only the function u(H, ξ, θ0) (in the inverse problem with the unknown function φ0(ξ, θ0)), or other data are given as data corresponding to any fixed value of θ0. Possible application areas of the inverse problems under consideration are specified.
This paper is essentially a review. A new result presented here has been obtained for inverse problems with the data {φ0(ξ, θ0), φ1(ξ, θ0} or {φ(ξ, θ0), u(H, ξ, θ0)} for a set of angles θ0. The results [Mathematical Problems of Geophysics, V. 5, P. 2. Computer Center of Siberian Branch of USSR Academy of Sciences, Novosibirsk, 1974, 78–107] (the uniqueness theorem, the solution method) are extended to the case when the limiting point θ0 of this set is zero. Also, a new explicit formula (formula (5.3) from Section 5), which makes it possible to find the functions ν(z) and ρ(z) using the data of these inverse problems for θ0 = 0, has been obtained.
The Review on Sustainability of National Building Standard Design in China
Authors: Gang Liu 
Published: January 2008

Abstract
There are more than 40 billion square metres of buildings in China and the number is forecasted to grow by 1.6∼1.9 billion square metres year over year by 2020. China has been facing serious energy and environmental challenges to address sustainable development. The National Building Standard Design (NBSD) is a set of standard drawings, compiled according to Chinese building standards and codes by the Ministry of Construction (MOC), including construction details, building components, selection and installation of equipment, etc. The NBSD has been tested by real projects and market feedback. It’s crucial to implement it to increase the efficiency of the construction process. The paper describes the historical development of NBSD and the contribution to sustainable development in China’s construction sector. The paper also introduces the effects and new trends of standard designs on sustainability in China.
Dynamic Characteristics of Different Aspect Ratios of Small Hydraulic Orifices Using a Pressure Square Wave Generator
Authors: Wu Y. C. , Fan P. S. , Tsung T. T. 
Published: January 2008

Abstract
This study examines the dynamic characteristics of different aspect ratios (length/diameter, L/D) of small hydraulic orifices. A homemade pressure square wave generator (PSWG) was employed to excite inlet pressure square waves The responses of time-domain and frequency-domain were measured by piezoelectric pressure sensors and a Spectrum Analyzer. Experimental conditions: At a pressure of 2 MPa, frequency was adjusted by the frequency converter to 200 Hz, orifice diameters range from 0.5 to 2.0 mm and lengths are from 0.5 to 3 mm (aspect ratios from 0.25 to 6). In the wave form of the time-domain response, a square waveform at the inlet of the orifice becomes a triangular waveform after the hydraulic fluid flows through the orifice. The pressure-drop via the orifice results in a delay of pressure increase and decrease. Results show a considerable pressure decay of over 90 % on the large aspect ratio of small orifices. For characteristics of dynamic control, it is necessary to improve hydraulic technology to reach the high precision field.
Nonvirally Engineered Porcine Adipose Tissue-Derived Stem Cells: Use in Posterior Spinal Fusion
Authors: Sheyn Dima , Pelled Gadi , Zilberman Yoram , Talasazan Farahnaz , Frank Jonathan M. , Gazit Dan , Gazit Zulma 
Published: January 2008

Abstract
Multiple factors alter intervertebral disc volume, structure, shape, composition, and biomechanical properties, often leading to low back pain. Spinal fusion is frequently performed to treat this problem. We recently published results of our investigation of a novel system of in vivo bone formation, in which we used nonvirally nucleofected human mesenchymal stem cells that overexpress a bone morphogenetic protein gene. We hypothesized that primary porcine adipose tissue-derived stem cells (ASCs) nucleofected with plasmid containing recombinant human bone morphogenetic protein-6 (rhBMP-6) could induce bone formation and achieve spinal fusion in vivo. Primary ASCs were isolated from freshly harvested porcine adipose tissue. Overexpression of rhBMP-6 was achieved ex vivo by using a nucleofection technique. Transfection efficiency was monitored by assessing a parallel transfection involving an enhanced green fluorescent protein reporter gene and flow cytometry analysis. rhBMP-6 protein secreted by the cells was measured by performing an enzyme-linked immunosorbent assay. Genetically engineered cells were injected into the lumbar paravertebral muscle in immunodeficient mice. In vivo bone formation was monitored by a quantitative microcomputed tomography (μCT). The animals were euthanized 5 weeks postinjection, and spinal fusion was evaluated using in vitro μCT and histological analysis. We found formation of a large bone mass adjacent to the lumbar area, which produced posterior spinal fusion of two to four vertebrae. Our data demonstrate that efficient bone formation and spinal fusion can be achieved using ex vivo, nonvirally transfected primary ASCs. These results could pave the way to a novel biological solution for spine treatment.
Disclosure of potential conflicts of interest is found at the end of this article.