bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor necrosis is associated with increased alphavbeta3integrin expression and poor prognosis in nodular cutaneous melanomas
Authors: Bachmann Ingeborg M , Ladstein Rita G , Straume Oddbjørn , Naumov George N , Akslen Lars A 
Published: December 2008

Abstract

Background
Tumor necrosis and apoptotic activity are considered important in cancer progression, but these features have not been much studied in melanomas. Our hypothesis was that rapid growth in cutaneous melanomas of the vertical growth phase might lead to tissue hypoxia, alterations in apoptotic activity and tumor necrosis. We proposed that these tumor characteristics might be associated with changes in expression of cell adhesion proteins leading to increased invasive capacity and reduced patient survival.

Methods
A well characterized series of nodular melanoma (originally 202 cases) and other benign and malignant melanocytic tumors (109 cases) were examined for the presence of necrosis, apoptotic activity (TUNEL assay), immunohistochemical expression of hypoxia markers (HIF-1 α, CAIX, TNF-α, Apaf-1) and cell adhesion proteins (αvβ3 integrin, CD44/HCAM and osteopontin). We hypothesized that tumor hypoxia and necrosis might be associated with increased invasiveness in melanoma through alterations of tumor cell adhesion proteins.

Results
Necrosis was present in 29% of nodular melanomas and was associated with increased tumor thickness, tumor ulceration, vascular invasion, higher tumor proliferation and apoptotic index, increased expression of αvβ3 integrin and poor patient outcome by multivariate analysis. Tumor cell apoptosis did also correlate with reduced patient survival. Expression of TNF-α and Apaf-1 was significantly associated with tumor thickness, and osteopontin expression correlated with increased tumor cell proliferation (Ki-67).

Conclusion
Tumor necrosis and apoptotic activity are important features of melanoma progression and prognosis, at least partly through alterations in cell adhesion molecules such as increased αvβ3 integrin expression, revealing potentially important targets for new therapeutic approaches to be further explored.
Down-regulation of PPARgamma1 suppresses cell growth and induces apoptosis in MCF-7 breast cancer cells
Authors: Zaytseva Yekaterina Y , Wang Xin , Southard R Chase , Wallis Natalie K , Kilgore Michael W 
Published: December 2008

Abstract

Background
Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear hormone receptor superfamily and is highly expressed in many human tumors including breast cancer. PPARγ has been identified as a potential target for breast cancer therapy based on the fact that its activation by synthetic ligands affects the differentiation, proliferation, and apoptosis of cancer cells. However, the controversial nature of current studies and disappointing results from clinical trials raise questions about the contribution of PPARγ signaling in breast cancer development in the absence of stimulation by exogenous ligands. Recent reports from both in vitro and in vivo studies are inconsistent and suggest that endogenous activation of PPARγ plays a much more complex role in initiation and progression of cancer than previously thought.

Results
We have previously demonstrated that an increase in expression of PPARγ1 in MCF-7 breast cancer cells is driven by a tumor-specific promoter. Myc-associated zinc finger protein (MAZ) was identified as a transcriptional mediator of PPARγ1 expression in these cells. In this study, using RNA interference (RNAi) to inhibit PPARγ1 expression directly or via down-regulation of MAZ, we report for the first time that a decrease in PPARγ1 expression results in reduced cellular proliferation in MCF-7 breast cancer cells. Furthermore, we demonstrate that these changes in proliferation are associated with a significant decrease in cell transition from G1 to the S phase. Using a dominant-negative mutant of PPARγ1, Δ462, we confirmed that PPARγ1 acts as a pro-survival factor and showed that this phenomenon is not limited to MCF-7 cells. Finally, we demonstrate that down-regulation of PPARγ1 expression leads to an induction of apoptosis in MCF-7 cells, confirmed by analyzing Bcl-2 expression and PARP-1 cleavage.

Conclusion
Thus, these findings suggest that an increase in PPARγ1 signaling observed in breast cancer contributes to an imbalance between proliferation and apoptosis, and may be an important hallmark of breast tumorigenesis. The results presented here also warrant further investigation regarding the use of PPARγ ligands in patients who are predisposed or already diagnosed with breast cancer.
Fatigue characteristics in multiple sclerosis: the North American Research Committee on Multiple Sclerosis (NARCOMS) survey
Authors: Hadjimichael Olympia , Vollmer Timothy , Oleen-Burkey MerriKay 
Published: December 2008

Abstract

Background
Fatigue is a common disabling symptom of multiple sclerosis (MS) and has a significantly negative impact on quality of life. Persons with MS enrolled in the North American Research Committee on Multiple Sclerosis (NARCOMS) Patient Registry are invited to complete follow-up surveys every six months to update their original registration information. One of these surveys was designed to focus on the severity and impact of fatigue, and its association with other clinical parameters of MS such as physical disability.

Methods
In addition to the usual data collected in Registry update surveys such as demographic characteristics, MS-related medical history, disability and handicap, immunomodulatory and symptomatic therapies taken, and healthcare services used, the survey for this study included two validated self-report fatigue scales, the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS) and questions about the use of symptomatic management for fatigue, both pharmacologic and non-pharmacologic treatments. This Registry update survey was mailed to all NARCOMS registrants (n = 18,595) in November 2002. Information provided by registry participants was approved for research purposes by the Yale University Institutional Review Board.

Results
The response rate for the survey was 49.5% (9205/18,595). Severe fatigue as measured with the FSS using the developer's recommended severity cutpoint of ≥ 36 was reported by 6691 (74%) of evaluable respondents (n = 9077). A higher prevalence of severe fatigue was observed in relapsing-worsening MS compared with relapsing-stable and primary progressive MS. A distinct pattern of fatigue was observed across the disability levels of the Patient-Determined Disease Steps (PDDS). Although there were no differences in the severity or impact of fatigue by immunomodulatory agents (IMA), respondents who recalled therapy changes in the prior six months reported different patterns of change in fatigue with lower fatigue levels reported after changing from interferon-β to glatiramer acetate than after changing from glatiramer acetate to interferon-β. Concomitant therapy for fatigue was used by 47.2% of the 5799 survey respondents receiving IMA.

Conclusion
Characterizing MS symptoms like fatigue can increase awareness about their impact on persons with MS and suggest recommendations for a care plan.
Modelling phagosomal lipid networks that regulate actin assembly
Authors: Kühnel Mark , Mayorga Luis S , Dandekar Thomas , Thakar Juilee , Schwarz Roland , Anes Elsa , Griffiths Gareth , Reich Jens 
Published: December 2008

Abstract

Background
When purified phagosomes are incubated in the presence of actin under appropriate conditions, microfilaments start growing from the membrane in a process that is affected by ATP and the lipid composition of the membrane. Isolated phagosomes are metabolically active organelles that contain enzymes and metabolites necessary for lipid interconversion. Hence, addition of ATP, lipids, and actin to the system alter the steady-state composition of the phagosomal membrane at the same time that the actin nucleation is initiated. Our aim was to model all these processes in parallel.

Results
We compiled detailed experimental data on the effects of different lipids and ATP on actin nucleation and we investigated experimentally lipid interconversion and ATP metabolism in phagosomes by using suitable radioactive compounds.
In a first step, a complex lipid network interconnected by chemical reactions catalyzed by known enzymes was modelled in COPASI (Complex Pathway Simulator). However, several lines of experimental evidence indicated that only the phosphatidylinositol branch of the network was active, an observation that dramatically reduced the number of parameters in the model. The results also indicated that a lipid network-independent ATP-consuming activity should be included in the model. When this activity was introduced, the set of differential equations satisfactorily reproduced the experimental data. On the other hand, a molecular mechanism connecting membrane lipids, ATP, and the actin nucleation process is still missing. We therefore adopted a phenomenological (black-box) approach to represent the empirical observations. We proposed that lipids and ATP influence the dynamic interconversion between active and inactive actin nucleation sites. With this simple model, all the experimental data were satisfactorily fitted with a single positive parameter per lipid and ATP.

Conclusion
By establishing an active 'dialogue' between an initial complex model and experimental observations, we could narrow the set of differential equations and parameters required to characterize the time-dependent changes of metabolites influencing actin nucleation on phagosomes. For this, the global model was dissected into three sub-models: ATP consumption, lipid interconversion, and nucleation of actin on phagosomal membranes. This scheme allowed us to describe this complex system with a relatively small set of differential equations and kinetic parameters that satisfactorily reproduced the experimental data.
FitSNPs: highly differentially expressed genes are more likely to have variants associated with disease
Authors: Chen Rong , Morgan Alex A , Dudley Joel , Deshpande Tarangini , Li Li , Kodama Keiichi , Chiang Annie P , Butte Atul J 
Published: December 2008

AbstractBackgroundCandidate single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWASs) were often selected for validation based on their functional annotation, which was inadequate and biased. We propose to use the more than 200,000 microarray studies in the Gene Expression Omnibus to systematically prioritize candidate SNPs from GWASs.ResultsWe analyzed all human microarray studies from the Gene Expression Omnibus, and calculated the observed frequency of differential expression, which we called differential expression ratio, for every human gene. Analysis conducted in a comprehensive list of curated disease genes revealed a positive association between differential expression ratio values and the likelihood of harboring disease-associated variants. By considering highly differentially expressed genes, we were able to rediscover disease genes with 79% specificity and 37% sensitivity. We successfully distinguished true disease genes from false positives in multiple GWASs for multiple diseases. We then derived a list of functionally interpolating SNPs (fitSNPs) to analyze the top seven loci of Wellcome Trust Case Control Consortium type 1 diabetes mellitus GWASs, rediscovered all type 1 diabetes mellitus genes, and predicted a novel gene (KIAA1109) for an unexplained locus 4q27. We suggest that fitSNPs would work equally well for both Mendelian and complex diseases (being more effective for cancer) and proposed candidate genes to sequence for their association with 597 syndromes with unknown molecular basis.ConclusionsOur study demonstrates that highly differentially expressed genes are more likely to harbor disease-associated DNA variants. FitSNPs can serve as an effective tool to systematically prioritize candidate SNPs from GWASs.
Adenosine A2A receptors play an active role in mouse bone marrow-derived mesenchymal stem cell development
Authors: Katebi Majid , Soleimani Mansooreh , Cronstein Bruce N 
Published: December 2008

AbstractBone marrow-derived mesenchymal stem cells (BM-MSCs) play a role in wound healing and tissue repair and may also be useful for organ regeneration. As we have demonstrated previously that A2A adenosine receptors (A2AR) promote tissue repair and wound healing by stimulating local repair mechanisms and enhancing accumulation of endothelial progenitor cells, we investigated whether A2AR activation modulates BM-MSC proliferation and differentiation. BM-MSCs were isolated and cultured from A2A-deficient and ecto-5′nucleotidase (CD73)-deficient female mice; the MSCs were identified and quantified by a CFU-fibroblast (CFU-F) assay. Procollagen α2 type I expression was determined by Western blotting and immunocytochemistry. MSC-specific markers were examined in primary cells and third-passage cells by cytofluorography. PCR and real time-PCR were used to quantitate adenosine receptor and CD73 expression. There were significantly fewer CFU-Fs in cultures of BM-MSCs from A2AR knockout (KO) mice or BM-MSCs treated with the A2AR antagonist ZM241385, 1 μM. Similarly, there were significantly fewer procollagen α2 type I-positive MSCs in cultures from A2AR KO and antagonist-treated cultures as well. In late passage cells, there were significantly fewer MSCs from A2A KO mice expressing CD90, CD105, and procollagen type I (P&lt;0.05 for all; n=3). These findings indicate that adenosine and adenosine A2AR play a critical role in promoting the proliferation and differentiation of mouse BM-MSCs.
Coprecipitated Gold–Tricobalt Tetraoxide Catalyst for Heterogeneous Hydroformylation of Olefins
Authors: Liu Xiaohao , Haruta Masatake , Tokunaga Makoto 
Published: December 2008

Abstract
The combination of gold (Au0) and tricobalt tetraoxide (Co3O4) prepared by coprecipitation gives high-performance heterogeneous catalysts for hydroformylation reaction with selectivity above 85% in desired aldehydes, although neither Au0 nor Co3O4 have been demonstrated in this reaction and show poor activities. The Au/Co3O4 catalysts can be recycled by simple decantation with slight decrease in catalytic activity along with recycle times. The role of Au may mainly promote in situ reduction of Co3O4 to Co0 catalyzing the hydroformylation reaction.
Amidocarbonylation of Aldehydes Utilizing Cobalt Oxide-supported Gold Nanoparticles as a Heterogeneous Catalyst
Authors: Hamasaki Akiyuki , Liu Xiaohao , Tokunaga Makoto 
Published: December 2008

Abstract
Cobalt oxide-supported gold-nanoparticles-catalyzed transformation of aldehydes and their equivalents to N-acyl-α-amino acids was achieved. The desired products were obtained in moderate to excellent yields under milder reaction conditions than previous reports employing octacarbonyldicobalt as a catalyst.
Aqua-aminoorganoboron Catalyst: Engineering Single Water Molecule to Act as an Acid Catalyst in Nitro Aldol Reaction
Authors: Yoshimoto Junichi , Sandoval Christian A , Saito Susumu 
Published: December 2008

Abstract
We have disclosed the catalytic potential hidden behind a series of aqua-aminoorganoboron compounds in the formation and reaction of nitronate species. The pivotal role of a single-coordinated water molecule in the catalyst was demonstrated by comparison with the D2O-analogue. The present results provide a new strategy for the design of metal-free catalysts which function via elaborative hydrogen-bonding networks involving water.
Neopentyl-substituted PNP-pincer Ligand: Complexation with Iridium to Form an Iridacycle via Alkyl C–H Activation
Authors: Yano Toshiyuki , Moroe Yoshiki , Yamashita Makoto , Nozaki Kyoko 
Published: December 2008

Abstract
A new PNP-pincer ligand 1 bearing neopentyl substituents reacted with [Ir(cod)2]BF4 to form hydridoiridacycle 3 via oxidative addition of a C–H bond of a neopentyl group to IrI. Addition of π-acceptor ligands induced C–H reductive elimination to form cationic iridium(I) complexes 5 ligated by the π-acceptor ligand. Although 3 did not give a benzene adduct, reaction of 3 with nitrobenzene or acetophenone afforded the C–H activated 7a or 8a.
The psychological mindedness assessment procedure – validation study of a Dutch version
Authors: Smith Annemarie J. M. , Kleijn Wim Chr. , Trijsburg Wim R. , Segaar Jaap A. , van der Staak Cees P. F. , Hutschemaekers Giel J. M. 
Published: December 2008

Objective The Psychological Mindedness Assessment Procedure [PMAP; McCallum, M. & Piper, W. E. (1990)] operationalizes psychological mindedness as a participant's understanding of the problem presented by two videotaped enacted patients. To possibly enhance predictive power for psychotherapy outcome, we added two video scenarios with emotionally high‐impact. This article describes psychometric properties of the Dutch translation of the PMAP and the extended version, the PMAP‐plus.Design A therapy‐analogue study with non‐clinical participants (N=100).Methods In individual sessions, participants watched the four video‐scenarios and responded to the PMAP‐question ‘What seems to be troubling this woman?’. Emotional reactions were measured using the Positive And Negative Affect Schedule [PANAS; Watson, D., Clark, L. E. & Tellegen, A. (1988)].Results The PMAP and the PMAP‐plus had good interrater reliability. As expected, PMAP‐levels were lower for the newly added high‐emotional scenarios. Validity was further supported by a negative relation of PMAP‐scores with the Negative Affect subscale.Conclusions The Dutch translation of the PMAP and the added scenarios of the PMAP‐plus are reliable instruments. The predictive power for psychotherapy outcome needs to be investigated in a patient group. The variation in presented clinical problems could also make it a useful instrument to assess psychological mindedness in psychotherapists.
Thirty years on – a large anti‐Flynn effect/ (II): 13‐ and 14‐year‐olds. Piagetian tests of formal operations norms 1976–2006/7
Authors: Shayer Michael , Ginsburg Denise 
Published: December 2008

Background Shayer, Ginsburg, and Coe (2007) showed that children leaving primary school in Y6 entered secondary school with much lower levels of understanding of the physical conservations than in 1976. It seemed desirable to investigate cognitive development in the first three years of secondary education.Aims By using two Piagetian tests of formal operations, one of which had been used in the 1976 CSMS survey, the performance of Y8 and Y9 pupils would be compared with the survey results published in 1978.Sample Eight schools were selected as willing to test their Y9 or Y8 classes on either the Pendulum (in 2007) or the Equilibrium in the Balance tests (in 2006), giving 39 classes on which to make the comparison with 1976 performance.Method Regression of the pupils' class mean on each formal test on either the class's 2004 MidYIS or nferCAT standardized scores, and computing the regression at IQ = 100 allows comparison with that found in 1976.Results On Equilibrium in the Balance the Y8 pupils were down on the proportion at the early formal level or above by −0.61 standard deviations (SD) for boys and −0.63 SD for girls on the 1976 results. On the Pendulum the Y9 boys were down by −0.49 SD and the girls by −0.48 SD on the proportion at the early formal level or above.Conclusion The negative Flynn‐effect found on Volume & Heaviness for Y7 pupils is paralleled by a similar negative effect on attainment of formal operations by Y8 and Y9, compared with 1976. Yet at the same time the proportion of pupils using the top level of concrete operational thinking has increased on both tests. It seems that there has been a change either in general societal pressures on the individual or in the style of teaching in schools – or both – favouring a lower level of processing of reality.
A Life in the Field: Henry Glassie and the Study of Material Culture
Authors: Glassie Henry , Truesdell Barbara 
Published: December 2008

Abstract
Henry Glassie discusses the early life influences that led him to folklore as his vocation. He describes his formal education; his mentoring by Fred B. Kniffen, whose training shaped Glassie's study of material culture; his job as the state folklorist of Pennsylvania; and his participation in the evolution of public sector folklore. Glassie also describes the centrality of fieldwork to his career, his writings, his teaching, his museum work, and to the folklore enterprise. Finally, he evaluates the earmarks of a successful public history venture and the influence of his work's intention to democratize history.
Differential Recovery of Neural Stem Cells in the Subventricular Zone and Dentate Gyrus After Ionizing Radiation
Authors: Hellström Nina A.K. , Björk-Eriksson Thomas , Blomgren Klas , Kuhn H. Georg 
Published: December 2008

Abstract
Radiation therapy is a widely used treatment for malignant central nervous system tumors. Mature neurons are terminally differentiated, whereas stem and progenitor cells have a prominent proliferative capacity and are therefore highly vulnerable to irradiation. Our aim was to investigate how cranial radiation in young rats would affect stem/progenitor cells in the two niches of adult neurogenesis, the subventricular zone (SVZ) and the dentate gyrus of the hippocampal formation. Nine weeks after irradiation we found that in irradiated animals, hippocampal neurogenesis was reduced to 5% of control levels. Similarly, the numbers of actively proliferating cells and radial glia-like stem cells (nestin+/glial fibrillary acidic protein [GFAP]+) in the dentate gyrus were reduced to 10% and 15% of control levels, respectively. In the irradiated olfactory bulb, neurogenesis was reduced to 40% of control levels, and the number of actively proliferating cells in the SVZ was reduced to 53% of control levels. However, the number of nestin+/GFAP+ cells in the SVZ was unchanged compared with controls. To evaluate the immediate response to the radiation injury, we quantified the amount of proliferation in the SVZ and dentate gyrus 1 day after irradiation. We found an equal reduction in proliferating cells both in dentate gyrus and SVZ. In summary, we show an initial response to radiation injury that is similar in both brain stem cell niches. However, the long-term effects on stem cells and neurogenesis in these two areas differ significantly: the dentate gyrus is severely affected long-term, whereas the SVZ appears to recover with time.
Prospective Isolation of Bronchiolar Stem Cells Based Upon Immunophenotypic and Autofluorescence Characteristics
Authors: Teisanu Roxana M. , Lagasse Eric , Whitesides John F. , Stripp Barry R. 
Published: December 2008

Abstract
Bronchiolar stem cells have been functionally defined in vivo on the basis of their resistance to chemical (naphthalene) injury, their infrequent proliferation relative to other progenitor cell types, and their coexpression of the airway and alveolar secretory cell markers Clara cell secretory protein and pro-surfactant protein C, respectively. Cell surface markers that have previously been used for their prospective isolation included Sca-1 and CD34. Using transgenic animal models associated with stem cell expansion, ablation, and lineage tracing, we demonstrate that CD34pos cells do not belong to the airway epithelial lineage and that cell surface Sca-1 immunoreactivity does not distinguish between bronchiolar stem and facultative transit-amplifying (Clara) cell populations. Furthermore, we show that high autofluorescence (AFhigh) is a distinguishing characteristic of Clara cells allowing for the fractionation of AFlow bronchiolar stem cells. On the basis of these data we show that the defining phenotype of the bronchiolar stem cell is CD45neg CD31neg CD34neg Sca-llow AFlow. This refinement in the definition of bronchiolar stem cells provides a critical tool by which to assess functional and molecular distinctions between bronchiolar stem cells and the more abundant pool of facultative transit-amplifying (Clara) cells.