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Sample records for factor analysis derived

  1. The Behaviour of Small Investors in the Hong Kong Derivatives Markets: A Factor Analysis

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    Tai-Yuen Hon

    2012-12-01

    Full Text Available This paper investigates the behaviour of small investors in Hong Kong’s derivatives markets. The study period covers the global economic crisis of 2011- 2012, and we focus on small investors’ behaviour during and after the crisis. We attempt to identify and analyse the key factors that capture their behaviour in derivatives markets in Hong Kong. The data were collected from 524 respondents via a questionnaire survey. Exploratory factor analysis was employed to analyse the data, and some interesting findings were obtained. Our study enhances our understanding of behavioural finance in the setting of an Asian financial centre, namely Hong Kong.

  2. Brain derived neurotrophic factor

    DEFF Research Database (Denmark)

    Mitchelmore, Cathy; Gede, Lene

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies are curre......Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies...

  3. Statistical Analysis of Instantaneous Frequency Scaling Factor as Derived From Optical Disdrometer Measurements At KQ Bands

    Science.gov (United States)

    Zemba, Michael; Nessel, James; Houts, Jacquelynne; Luini, Lorenzo; Riva, Carlo

    2016-01-01

    The rain rate data and statistics of a location are often used in conjunction with models to predict rain attenuation. However, the true attenuation is a function not only of rain rate, but also of the drop size distribution (DSD). Generally, models utilize an average drop size distribution (Laws and Parsons or Marshall and Palmer. However, individual rain events may deviate from these models significantly if their DSD is not well approximated by the average. Therefore, characterizing the relationship between the DSD and attenuation is valuable in improving modeled predictions of rain attenuation statistics. The DSD may also be used to derive the instantaneous frequency scaling factor and thus validate frequency scaling models. Since June of 2014, NASA Glenn Research Center (GRC) and the Politecnico di Milano (POLIMI) have jointly conducted a propagation study in Milan, Italy utilizing the 20 and 40 GHz beacon signals of the Alphasat TDP#5 Aldo Paraboni payload. The Ka- and Q-band beacon receivers provide a direct measurement of the signal attenuation while concurrent weather instrumentation provides measurements of the atmospheric conditions at the receiver. Among these instruments is a Thies Clima Laser Precipitation Monitor (optical disdrometer) which yields droplet size distributions (DSD); this DSD information can be used to derive a scaling factor that scales the measured 20 GHz data to expected 40 GHz attenuation. Given the capability to both predict and directly observe 40 GHz attenuation, this site is uniquely situated to assess and characterize such predictions. Previous work using this data has examined the relationship between the measured drop-size distribution and the measured attenuation of the link]. The focus of this paper now turns to a deeper analysis of the scaling factor, including the prediction error as a function of attenuation level, correlation between the scaling factor and the rain rate, and the temporal variability of the drop size

  4. Surface proteome analysis identifies platelet derived growth factor receptor-alpha as a critical mediator of transforming growth factor-beta-induced collagen secretion.

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    Heinzelmann, Katharina; Noskovičová, Nina; Merl-Pham, Juliane; Preissler, Gerhard; Winter, Hauke; Lindner, Michael; Hatz, Rudolf; Hauck, Stefanie M; Behr, Jürgen; Eickelberg, Oliver

    2016-05-01

    Fibroblasts are extracellular matrix-producing cells in the lung. Fibroblast activation by transforming growth factor-beta leads to myofibroblast-differentiation and increased extracellular matrix deposition, a hallmark of pulmonary fibrosis. While fibroblast function with respect to migration, invasion, and extracellular matrix deposition has been well-explored, little is known about the surface proteome of lung fibroblasts in general and its specific response to fibrogenic growth factors, in particular transforming growth factor-beta. We thus performed a cell-surface proteome analysis of primary human lung fibroblasts in presence/absence of transforming growth factor-beta, followed by characterization of our findings using FACS analysis, Western blot, and siRNA-mediated knockdown experiments. We identified 213 surface proteins significantly regulated by transforming growth factor-beta, platelet derived growth factor receptor-alpha being one of the top down-regulated proteins. Transforming growth factor beta-induced downregulation of platelet derived growth factor receptor-alpha induced upregulation of platelet derived growth factor receptor-beta expression and phosphorylation of Akt, a downstream target of platelet derived growth factor signaling. Importantly, collagen type V expression and secretion was strongly increased after forced knockdown of platelet derived growth factor receptor-alpha, an effect that was potentiated by transforming growth factor-beta. We therefore show previously underappreciated cross-talk of transforming growth factor-beta and platelet derived growth factor signaling in human lung fibroblasts, resulting in increased extracellular matrix deposition in a platelet derived growth factor receptor-alpha dependent manner. These findings are of particular importance for the treatment of lung fibrosis patients with high pulmonary transforming growth factor-beta activity.

  5. Analysis of spatio-temporal variability of C-factor derived from remote sensing data

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    Pechanec, Vilem; Benc, Antonin; Purkyt, Jan; Cudlin, Pavel

    2016-04-01

    In some risk areas water erosion as the present task has got the strong influence on agriculture and can threaten inhabitants. In our country combination of USLE and RUSLE models has been used for water erosion assessment (Krása et al., 2013). Role of vegetation cover is characterized by the help of vegetation protection factor, so-called C- factor. Value of C-factor is given by the ratio of washing-off on a plot with arable crops to standard plot which is kept as fallow regularly spud after any rain (Janeček et al., 2012). Under conditions we cannot identify crop structure and its turn, determination of C-factor can be problem in large areas. In such case we only determine C-factor according to the average crop representation. New technologies open possibilities for acceleration and specification of the approach. Present-day approach for the C-factor determination is based on the analysis of multispectral image data. Red and infrared spectrum is extracted and these parts of image are used for computation of vegetation index series (NDVI, TSAVI). Acquired values for fractional time sections (during vegetation period) are averaged out. At the same time values of vegetation indices for a forest and cleared area are determined. Also regressive coefficients are computed. Final calculation is done by the help of regressive equations expressing relation between values of NDVI and C-factor (De Jong, 1994; Van der Knijff, 1999; Karaburun, 2010). Up-to-date land use layer is used for the determination of erosion threatened areas on the base of selection of individual landscape segments of erosion susceptible categories of land use. By means of Landsat 7 data C-factor has been determined for the whole area of the Czech Republic in every month of the year of 2014. At the model area in a small watershed C-factor has been determined by the conventional (tabular) procedure. Analysis was focused on: i) variability assessment of C-factor values while using the conventional

  6. Quantitative analysis of cerebrospinal fluid brain derived neurotrophic factor in the patients with multiple sclerosis.

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    Mashayekhi, Farhad; Salehi, Zivar; Jamalzadeh, Hamid Reza

    2012-01-01

    Multiple sclerosis (MS) is the most common cause ofnontraumatic neurological disability in Europe and North America. Growth factor expression could participate in the repair process of the demyelinating disease. Among growth factors, brain derived neurotrophic factors (BDNF) has been demonstrated to play an important role in neuronal and axonal survival. In the central nervous system (CNS), neurons are the main source of BDNF. Another potential source are activated astrocytes, which are present in inflamed areas in the CNS as shown in MS. In this study, total protein concentration (TPC) and BDNF levels in the cerebrospinal fluid (CSF) samples from the patients with MS (n = 48) and control subjects (n = 53) were measured using a Bio-Rad protein assay and enzyme linked immunosorbent assay (ELISA). No significant change in the CSF TPC of patients with MS was seen as compared to normal CSF. The presence of BDNF in the CSF samples was shown by Western blot. Using ELISA, it was shown that the level of BDNF in the MS CSF is higher than in normal CSF. It is concluded that BDNF is a constant component of human CSF. Moreover, it could be implicated in the pathophysiology of MS.

  7. Meta-analysis and association of brain-derived neurotrophic factor (BDNF) gene with obsessive-compulsive disorder.

    Science.gov (United States)

    Zai, Gwyneth; Zai, Clement C; Arnold, Paul D; Freeman, Natalie; Burroughs, Eliza; Kennedy, James L; Richter, Margaret A

    2015-04-01

    Obsessive-compulsive disorder (OCD) is a severe psychiatric condition with a clear genetic component (Nicolini et al., 2009) in which neurodevelopmental mechanisms may be etiologically important. Brain-derived neurotrophic factor (BDNF) is an interesting candidate for molecular analysis in OCD on the basis of potential functional relevance, positive association studies, and reported interaction between this gene and other neurotransmitters implicated in this disorder.

  8. Growth factor expression in degenerated intervertebral disc tissue. An immunohistochemical analysis of transforming growth factor beta, fibroblast growth factor and platelet-derived growth factor.

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    Tolonen, Jukka; Grönblad, Mats; Vanharanta, Heikki; Virri, Johanna; Guyer, Richard D; Rytömaa, Tapio; Karaharju, Erkki O

    2006-05-01

    Degenerated intervertebral disc has lost its normal architecture, and there are changes both in the nuclear and annular parts of the disc. Changes in cell shape, especially in the annulus fibrosus, have been reported. During degeneration the cells become more rounded, chondrocyte-like, whereas in the normal condition annular cells are more spindle shaped. These chondrocyte-like cells, often forming clusters, affect extracellular matrix turnover. In previous studies transforming growth factor beta (TGFbeta) -1 and -2, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) have been highlighted in herniated intervertebral disc tissue. In the present study the same growth factors are analysed immunohistochemically in degenerated intervertebral disc tissue. Disc material was obtained from 16 discs operated for painful degenerative disc disease. Discs were classified according to the Dallas Discogram Description. Different disc regions were analysed in parallel. As normal control disc tissue material from eight organ donors was used. Polyclonal antibodies against different growth factors and TGFbeta receptor type II were used, and the immunoreaction was detected by the avidin biotin complex method. All studied degenerated discs showed immunoreactivity for TGFbeta receptor type II and bFGF. Fifteen of 16 discs were immunopositive for TGFbeta-1 and -2, respectively, and none showed immunoreaction for PDGF. Immunopositivity was located in blood vessels and in disc cells. In the nucleus pulposus the immunoreaction was located almost exclusively in chondrocyte-like disc cells, whereas in the annular region this reaction was either in chondrocyte-like disc cells, often forming clusters, or in fibroblast-like disc cells. Chondrocyte-like disc cells were especially prevalent in the posterior disrupted area. In the anterior area of the annulus fibrosus the distribution was more even between these two cell types. bFGF was expressed in the anterior annulus

  9. Purified protein derivative skin testing on HIV/AIDS patients and logistic regression analysis of its risk factors

    Institute of Scientific and Technical Information of China (English)

    Fengren Liu; Jianjun Ye; Changfu Xiong; Jiguo Yin; Weihua He; Gaobo Li; Dingyuan Zhao; Linxiang Ye

    2007-01-01

    Objective: To understand the reactivity of purified protein derivative skin test(PPD test) in HIV-infected persons and to determine the influential factors associated with PPD. Methods: 174 HIV/AIDS patients registered in the local center for disease control and prevention(CDC) participated this study from April to June in 2006. Questionnaire, CD4 count and thoracic roentgenogram were performed for all participants. Results: In this study, response rate of questionnaires was 83.65%. The majority of these participants had a different degree of immunodeficiency that accounted for 93.64%. Female patients had a higher CD4 count than that of males. The total positive rate of PPD was 38.15%. Analysis of single factor in our study indicated that CD4 count, previous tuberculosis history, tuberculosis contact history and thoracic roentgenogram manifestation of patients were related to their PPD diameters. Further analysis of multiple factors also supports the previous conclusion that CD4 count and previous tuberculosis history of patients were risk factors in the PPD test. Conclusion: The PPD test of HIV/AIDS patients could be affected by several factors. For persons infected with HIV, the confirmation of latent tuberculosis infection (LTBI) should be considered the combination effect of previous MTB infection and body cellular immune function.

  10. Risk Factors in Derivatives Markets

    Directory of Open Access Journals (Sweden)

    Raimonda Martinkutė-Kaulienė

    2015-02-01

    Full Text Available The objective of the article is to analyse and present the classification of risks actual to derivative securities. The analysis is based on classical and modern literature findings and analysis of newest statistical data. The analysis led to the conclusion, that the main risks typical for derivatives contracts and their traders are market risk, liquidity risk, credit and counterparty risk, legal risk and transactions risk. Pricing risk and systemic risk is also quite important. The analysis showed that market risk is the most important kind of risk that in many situations influences the level of remaining risks.

  11. Co-morbidity and factor analysis on attention deficit hyperactivity disorder and autism spectrum disorder DSM-IV-derived items

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    Ahmad Ghanizadeh

    2012-01-01

    Full Text Available Background: There is a gap in the literature regarding the extent of possible co-occurrence of attention deficit hyperactivity disorder (ADHD and pervasive developmental disorders (PDD. This study aimed to investigate co-occurring of ADHD in children with PDD. Methods: A clinical sample of 68 children with PDD was assessed according to DSM-IV criteria to make ADHD and/ or PDD diagnoses. All the different types of PDD were included. DSM-IV derived criteria for ADHD and PDD were analyzed. An exploratory factor analysis was conducted. Results: the rate of autism, Asperger syndrome, Rett′s disorder, childhood disintegrative disorder and PDD-NOS (not otherwise specified was 55.4%, 16.9%, 3.1%, 3.1%, 21.5%, respectively. 53.8% of the sample was with ADHD co-morbidity. The rate of ADHD subtypes was 37.1%, 22.9%, and 40.0% for inattentive type, hyperactivity/impulsivity type and combined type, respectively. Conclusion: ADHD and its symptoms highly co-occur with PDD. Meanwhile, the result of factor analysis supports the independence of ADHD and PDD diagnostic criteria.

  12. Co-morbidity and factor analysis on attention deficit hyperactivity disorder and autism spectrum disorder DSM-IV-derived items.

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    Ghanizadeh, Ahmad

    2012-04-01

    There is a gap in the literature regarding the extent of possible co-occurrence of attention deficit hyperactivity disorder (ADHD) and pervasive developmental disorders (PDD). This study aimed to investigate co-occurring of ADHD in children with PDD. A clinical sample of 68 children with PDD was assessed according to DSM-IV criteria to make ADHD and/ or PDD diagnoses. All the different types of PDD were included. DSM-IV derived criteria for ADHD and PDD were analyzed. An exploratory factor analysis was conducted. the rate of autism, Asperger syndrome, Rett's disorder, childhood disintegrative disorder and PDD-NOS (not otherwise specified) was 55.4%, 16.9%, 3.1%, 3.1%, 21.5%, respectively. 53.8% of the sample was with ADHD co-morbidity. The rate of ADHD subtypes was 37.1%, 22.9%, and 40.0% for inattentive type, hyperactivity/impulsivity type and combined type, respectively. ADHD and its symptoms highly co-occur with PDD. Meanwhile, the result of factor analysis supports the independence of ADHD and PDD diagnostic criteria.

  13. Meta-coexpression conservation analysis of microarray data: a "subset" approach provides insight into brain-derived neurotrophic factor regulation

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    Timmusk Tõnis

    2009-09-01

    Full Text Available Abstract Background Alterations in brain-derived neurotrophic factor (BDNF gene expression contribute to serious pathologies such as depression, epilepsy, cancer, Alzheimer's, Huntington and Parkinson's disease. Therefore, exploring the mechanisms of BDNF regulation represents a great clinical importance. Studying BDNF expression remains difficult due to its multiple neural activity-dependent and tissue-specific promoters. Thus, microarray data could provide insight into the regulation of this complex gene. Conventional microarray co-expression analysis is usually carried out by merging the datasets or by confirming the re-occurrence of significant correlations across datasets. However, co-expression patterns can be different under various conditions that are represented by subsets in a dataset. Therefore, assessing co-expression by measuring correlation coefficient across merged samples of a dataset or by merging datasets might not capture all correlation patterns. Results In our study, we performed meta-coexpression analysis of publicly available microarray data using BDNF as a "guide-gene" introducing a "subset" approach. The key steps of the analysis included: dividing datasets into subsets with biologically meaningful sample content (e.g. tissue, gender or disease state subsets; analyzing co-expression with the BDNF gene in each subset separately; and confirming co- expression links across subsets. Finally, we analyzed conservation in co-expression with BDNF between human, mouse and rat, and sought for conserved over-represented TFBSs in BDNF and BDNF-correlated genes. Correlated genes discovered in this study regulate nervous system development, and are associated with various types of cancer and neurological disorders. Also, several transcription factor identified here have been reported to regulate BDNF expression in vitro and in vivo. Conclusion The study demonstrates the potential of the "subset" approach in co-expression conservation

  14. Factor analysis

    CERN Document Server

    Gorsuch, Richard L

    2013-01-01

    Comprehensive and comprehensible, this classic covers the basic and advanced topics essential for using factor analysis as a scientific tool in psychology, education, sociology, and related areas. Emphasizing the usefulness of the techniques, it presents sufficient mathematical background for understanding and sufficient discussion of applications for effective use. This includes not only theory but also the empirical evaluations of the importance of mathematical distinctions for applied scientific analysis.

  15. Association analysis of the brain-derived neurotrophic factor gene polymorphisms with early-onset schizophrenia in the Chinese population

    Institute of Scientific and Technical Information of China (English)

    易正辉

    2012-01-01

    Objective To investigate the relationship between the brain-derived neurotrophic factor (BDNF) gene Tag SNPs(rs 11030101 and rs6265) and early-onset schizophrenia in the Chinese Han population. Methods The tag single nucleotide polymorphisms (tag SNPs) rs11030101 and rs6265 in the BDNF gene were genotyped

  16. Brain-Derived Neurotrophic Factor (BDNF protein levels in anxiety disorders: systematic review and meta-regression analysis

    Directory of Open Access Journals (Sweden)

    Sharain eSuliman

    2013-07-01

    Full Text Available Background: Brain-Derived Neurotrophic Factor (BDNF is a neurotrophin that is involved in the synaptic plasticity and survival of neurons. BDNF is believed to be involved in the pathogenesis of several neuropsychiatric disorders. As findings of BDNF levels in the anxiety disorders have been inconsistent, we undertook to conduct a systematic review and meta-analysis of studies that assessed BDNF protein levels in anxiety disorders. Methods: We conducted the review using electronic databases and searched reference lists of relevant articles for any further studies. Studies that measured BDNF protein levels in any anxiety disorder and compared these to a control group were included. Effect sizes of the differences in BDNF levels between anxiety disorder and control groups were calculated. Results: Eight studies with a total of 1179 participants were included. Initial findings suggested that BDNF levels were lower in individuals with any anxiety disorder compared to those without (Standard Mean Difference [SMD]=-0.94 [-1.75, -0.12], p≤0.05. This, however, differed with regards to source of BDNF protein (plasma: SMD=-1.31 [-1.69, -0.92], p≤0.01; serum: SMD=-1.06 [-2.27, 0.16], p≥0.01 and type of anxiety disorder (PTSD: SMD=-0.05 [-1.66, 1.75], p≥0.01; OCD: SMD=-2.33 [-4.21, -0.45], p≤0.01. Conclusion: Although BDNF levels appear to be reduced in individuals with an anxiety disorder, this is not consistent across the various anxiety disorders and may largely be explained by the significantly lowered BDNF levels found in OCD. Results further appear to be mediated by differences in sampling methods. Findings are, however, limited by the lack of research in this area, and given the potential for BDNF as a biomarker of anxiety disorders it would be useful to clarify the relationship further.

  17. [Analysis of factors related to the number of mesenchymal stem cells derived from synovial fluid of the temporomandibular joint].

    Science.gov (United States)

    Sun, Y P; Zheng, Y H; Zhang, Z G

    2017-06-09

    Objective: To analyze related factors on the number of mesenchymal stem cells in the synovial fluid of the temporomandibular joint (TMJ) and provide an research basis for understanding of the source and biological role of mesenchymal stem cells derived from synovial fluid in TMJ. Methods: One hundred and twenty-two synovial fluid samples from 91 temporomandibular disorders (TMD) patients who visited in Department of TMJ Center, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University from March 2013 to December 2013 were collected in this study, and 6 TMJ synovial fluid samples from 6 normal volunteers who were studying in the North Campus of Sun Yat-sen University were also collected, so did their clinical information. Then the relation between the number of mesenchymal stem cells derived from synovial fluid and the health status of the joints, age of donor, disc perforation, condylar bony destruction, blood containing and visual analogue scale score of pain were investigated using Mann-Whitney U test and Spearman rank correlation test. Results: The number of mesenchymal stem cells derived from synovial fluid had no significant relation with visual analogue scale score of pain (r=0.041, P=0.672), blood containing (P=0.063), condylar bony destruction (P= 0.371). Linear correlation between the number of mesenchymal stem cells derived from synovial fluid and age of donor was very week (r=0.186, P=0.043). The number of mesenchymal stem cells up-regulated when the joint was in a disease state (P=0.001). The disc perforation group had more mesenchymal stem cells in synovial fluid than without disc perforation group (P=0.042). Conclusions: The number of mesenchymal stem cells derived from synovial fluid in TMJ has no correlation with peripheral blood circulation and condylar bony destruction, while has close relation with soft tissue structure damage of the joint.

  18. LncRNA analysis of mouse spermatogonial stem cells following glial cell-derived neurotrophic factor treatment

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    Lufan Li

    2015-09-01

    Full Text Available Spermatonial stem cells (SSCs are the foundation of spermatogenesis. Long non-coding RNAs (lncRNAs are a class of non-coding RNAs with at least 200 bp in length, which play important roles in various biological processes. Growth factor glial cell line-derived neurotrophic factor (GDNF, secreted from testis niches, is critical for self-renewal of SSCs in vitro and in vivo. Using Illumina HiSeq™ 2000 high throughput sequencing, we found 55924 lncRNAs which were regulated by GDNF in SSCs in vitro; these included 21,929 known lncRNAs from NONCODE library (version 3.0 and 33,975 predicted lncRNAs which were identified using Coding Potential Calculator. Analyses of these data should provide new insights into regulated mechanism in SSC self-renewal and proliferation. The data have been deposited in the Gene Expression Omnibus (series GSE66998.

  19. Analysis of Activated Platelet-Derived Growth Factor β Receptor and Ras-MAP Kinase Pathway in Equine Sarcoid Fibroblasts

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    Gennaro Altamura

    2013-01-01

    Full Text Available Equine sarcoids are skin tumours of fibroblastic origin affecting equids worldwide. Bovine papillomavirus type-1 (BPV-1 and, less commonly, type-2 are recognized as etiological factors of sarcoids. The transforming activity of BPV is related to the functions of its major oncoprotein E5 which binds to the platelet-derived growth factor β receptor (PDGFβR causing its phosphorylation and activation. In this study, we demonstrate, by coimmunoprecipitation and immunoblotting, that in equine sarcoid derived cell lines PDGFβR is phosphorylated and binds downstream molecules related to Ras-mitogen-activated protein kinase-ERK pathway thus resulting in Ras activation. Imatinib mesylate is a tyrosine kinase receptors inhibitor which selectively inhibits the activation of PDGFβR in the treatment of several human and animal cancers. Here we show that imatinib inhibits receptor phosphorylation, and cell viability assays demonstrate that this drug decreases sarcoid fibroblasts viability in a dose-dependent manner. This study contributes to a better understanding of the molecular mechanisms involved in the pathology of sarcoids and paves the way to a new therapeutic approach for the treatment of this common equine skin neoplasm.

  20. Statistical Analysis of Instantaneous Frequency Scaling Factor as Derived from Optical Disdrometer Measurements at V/W Bands

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    Zemba, Michael; Nessel, James; Tarasenko, Nicholas; Lane, Steven

    2017-01-01

    Since October 2015, NASA Glenn Research Center (GRC) and the Air Force Research Laboratory (AFRL) have collaboratively operated an RF terrestrial link in Albuquerque, New Mexico to characterize atmospheric propagation phenomena at 72 and 84 GHz. The W/V-band Terrestrial Link Experiment (WTLE) consists of coherent transmitters at each frequency on the crest of the Sandia Mountains and a corresponding pair of receivers in south Albuquerque. The beacon receivers provide a direct measurement of the link attenuation, while concurrent weather instrumentation provides a measurement of the atmospheric conditions. Among the available weather instruments is an optical disdrometer which yields an optical measurement of rain rate, as well as droplet size and velocity distributions (DSD, DVD). In particular, the DSD can be used to derive an instantaneous scaling factor (ISF) by which the measured data at one frequency can be scaled to another - for example, scaling the 72 GHz to an expected 84 GHz timeseries. Given the availability of both the DSD prediction and the directly observed 84 GHz attenuation, WTLE is thus uniquely able assess DSD-derived instantaneous frequency scaling at the V/W-bands. Previous work along these lines has investigated the DSD-derived ISF at Ka and Q-band (20 GHz to 40 GHz) using a satellite beacon receiver experiment in Milan, Italy. This work will expand the investigation to terrestrial links in the V/W-bands, where the frequency scaling factor is lower and where the link is also much more sensitive to attenuation by rain, clouds, and other atmospheric effects.

  1. Plasma level of brain-derived neurotrophic factor and the related analysis in depressive patients with suicide attempt

    Institute of Scientific and Technical Information of China (English)

    操军

    2014-01-01

    Objective To explore the association between brainderived neurotrophic factor(BDNF)and suicidal behavior through analyzing and detecting the alteration of plasma BDNF level in depressive patients with suicide attempt.Methods Using enzyme-linked immunosorbent analysis(ELISA)to test the plasma level of BDNF in 27suicidal depressed patients,33 non-suicidal depressed patients and 30 normal controls.Meanwhile,the Hamilton Depression Scale(HAMD)and Beck

  2. Sequence analysis and functional study of the Han Nationality glial cell line-derived neurotrophic factor transcript

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhe-yu; HUANG Ai-jun; LU Chang-lin; WU Xiang-fu; HE Cheng

    2001-01-01

    To study the sequence and function of the glial cell line-derived neurotrophic factor (GDNF) transcript in subjects of Han nationality. Methods: The Han nationality GDNF transcript was amplified by RT-PCR and expressed by baculovirus expression system. Biological activity of the expressed product was measured by the primary culture of midbrain dopaminergic neurons. Results: There only existed the shorter GDNF transcript of 555 bp in the Han nationality. The secretory expression product of the shorter transcript in insect cells promoted the survival and differentiation of dopaminergic neurons. Conclusion: It is found that there is a 78 bp deletion in the Han nationality GDNF transcript compared with the reported 633 bp GDNF transcript. The 78 bp deletion does not affect the secretory expression and biological activity of GDNF mature protein.

  3. The Efficacy of Non-Pharmacological Interventions on Brain-Derived Neurotrophic Factor in Schizophrenia: A Systematic Review and Meta-Analysis

    OpenAIRE

    Kenji Sanada; Iñaki Zorrilla; Yusuke Iwata; Cristina Bermúdez-Ampudia; Ariel Graff-Guerrero; Mónica Martínez-Cengotitabengoa; Ana González-Pinto

    2016-01-01

    Several studies have investigated the relationship between non-pharmacological interventions (NPIs) and peripheral brain-derived neurotrophic factor (BDNF) in schizophrenia patients. We conducted a systematic review and meta-analysis to review the efficacy of NPIs on peripheral serum and plasma BDNF in subjects with schizophrenia (including schizoaffective disorder). Meta-analyses were conducted to examine the effects of NPIs on blood BDNF levels by using the standardized mean differences (SM...

  4. An expression analysis of 57 transcription factors derived from ESTs of developing seeds in Maize (Zea mays).

    Science.gov (United States)

    Wang, Guifeng; Wang, Hui; Zhu, Jia; Zhang, Jing; Zhang, Xiaowei; Wang, Fei; Tang, Yuanping; Mei, Bing; Xu, Zhengkai; Song, Rentao

    2010-06-01

    Maize seeds are an important source of food, animal feed, and industrial raw materials. To understand global gene expression and regulation during maize seed development, a normalized cDNA library, covering most of the developmental stages of maize seeds, was constructed. Sequencing analysis of 10,848 randomly selected clones identified 6,630 unique ESTs. Among them, 57 putative transcription factors (TFs) were identified. The TFs belong to seven different super-families, specifically 17 Zinc-finger, 13 bZIP, 8 bHLH, 6 MADS, 7 MYB, 3 Homedomain, and 3 AP2/EREBP. The spatial and temporal expression of the TFs was analyzed by semi-quantitative RT-PCR with representative tissue types and seeds at different developmental stages, revealing their diverse expression patterns and expression levels. One-third (19) of the maize TFs was found their putative orthologs in Arabidopsis. Similar expression patterns were observed in both maize and Arabidopsis for the majority of orthologous pairs (15 out of 19), suggesting their conserved functions during seed development. In conclusion, the systematic analysis of maize seed TFs has provided valuable insight into transcriptional regulation during maize seed development.

  5. Familiality of factor analysis-derived YBOCS dimensions in OCD-affected sibling pairs from the OCD Collaborative Genetics Study.

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    Hasler, Gregor; Pinto, Anthony; Greenberg, Benjamin D; Samuels, Jack; Fyer, Abby J; Pauls, David; Knowles, James A; McCracken, James T; Piacentini, John; Riddle, Mark A; Rauch, Scott L; Rasmussen, Steven A; Willour, Virginia L; Grados, Marco A; Cullen, Bernadette; Bienvenu, O Joseph; Shugart, Yin-Yao; Liang, Kung-Yee; Hoehn-Saric, Rudolf; Wang, Ying; Ronquillo, Jonne; Nestadt, Gerald; Murphy, Dennis L

    2007-03-01

    Identification of familial, more homogenous characteristics of obsessive-compulsive disorder (OCD) may help to define relevant subtypes and increase the power of genetic and neurobiological studies of OCD. While factor-analytic studies have found consistent, clinically meaningful OCD symptom dimensions, there have been only limited attempts to evaluate the familiality and potential genetic basis of such dimensions. Four hundred eighteen sibling pairs with OCD were evaluated using the Structured Clinical Interview for DSM-IV and the Yale-Brown Obsessive Compulsive Scale (YBOCS) Symptom Checklist and Severity scales. After controlling for sex, age, and age of onset, robust sib-sib intraclass correlations were found for two of the four YBOCS factors: Factor IV (hoarding obsessions and compulsions (p = .001) and Factor I (aggressive, sexual, and religious obsessions, and checking compulsions; p = .002). Smaller, but still significant, familiality was found for Factor III (contamination/cleaning; p = .02) and Factor II (symmetry/ordering/arranging; p = .04). Limiting the sample to female subjects more than doubled the familiality estimates for Factor II (p = .003). Among potentially relevant comorbid conditions for genetic studies, bipolar I/II and major depressive disorder were strongly associated with Factor I (p < .001), whereas ADHD, alcohol dependence, and bulimia were associated with Factor II (p < .01). Factor-analyzed OCD symptom dimensions in sibling pairs with OCD are familial with some gender-dependence, exhibit relatively specific relationships to comorbid psychiatric disorders and thus may be useful as refined phenotypes for molecular genetic studies of OCD.

  6. Foundations of factor analysis

    CERN Document Server

    Mulaik, Stanley A

    2009-01-01

    Introduction Factor Analysis and Structural Theories Brief History of Factor Analysis as a Linear Model Example of Factor AnalysisMathematical Foundations for Factor Analysis Introduction Scalar AlgebraVectorsMatrix AlgebraDeterminants Treatment of Variables as Vectors Maxima and Minima of FunctionsComposite Variables and Linear Transformations Introduction Composite Variables Unweighted Composite VariablesDifferentially Weighted Composites Matrix EquationsMulti

  7. Dietary Patterns Derived Using Exploratory and Confirmatory Factor Analysis are Stable and Generalizable Across Race, Region, and Gender Subgroups in the REGARDS Study

    Science.gov (United States)

    Judd, Suzanne E.; Letter, Abraham J.; Shikany, James M.; Roth, David L.; Newby, P. K.

    2015-01-01

    Background: Examining diet as a whole using dietary patterns as exposures is a complementary method to using single food or nutrients in studies of diet and disease, but the generalizability of intake patterns across race, region, and gender in the United States has not been established. Objective: To employ rigorous statistical analysis to empirically derive dietary patterns in a large bi-racial, geographically diverse population and examine whether results are stable across population subgroups. Design: The present analysis utilized data from 21,636 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who completed the Block 98 food frequency questionnaire. We employed exploratory factor analysis and confirmatory factor analyses on 56 different food groups iteratively and examined differences by race, region, and sex to determine the optimal factor solution in our sample. Results: Five dietary patterns emerged: the “Convenience” pattern was characterized by mixed dishes; the “Plant-based” pattern by fruits, vegetables, and fish; the “Sweets/Fats” pattern by sweet snacks, desserts, and fats and oils; the “Southern” pattern by fried foods, organ meat, and sweetened beverages; and the “Alcohol/Salads” pattern by beer, wine, liquor, and salads. Differences were most pronounced in the Southern pattern with black participants, those residing in the Southeast, and participants not completing high school having the highest scores. Conclusion: Five meaningful dietary patterns emerged in the REGARDS study and showed strong congruence across race, sex, and region. Future research will examine associations between these patterns and health outcomes to better understand racial disparities in disease and inform prevention efforts. PMID:25988129

  8. Brain-derived neurotrophic factor (BDNF) and neurocognitive deficits in people with schizophrenia: a meta-analysis.

    Science.gov (United States)

    Ahmed, Anthony O; Mantini, Andrew M; Fridberg, Daniel J; Buckley, Peter F

    2015-03-30

    Studies suggest that the BDNF Val66Met (rs6265) polymorphism is associated with the incidence of schizophrenia and neurocognitive functioning. These associations appear to be however somewhat mixed. We conducted two separate meta-analyses to investigate (1) the association between the Val66Met polymorphism and neurocognition in people with schizophrenia and (2) the association between peripheral expression of BDNF and neurocognitive phenotypes. For the first aim, we identified 12 studies and 67 comparisons of Met allele carriers and Val homozygotes. These comparisons included 1890 people with schizophrenia (men=1465, women=553), of whom 972 were Met allele carriers and 918 were Val homozygotes. For the second aim, we identified five studies and 25 correlations of peripheral BDNF and neurocognitive scores. The meta-analysis for the second aim included 414 people with schizophrenia (men=292, women=170). First, we found non-significant difference between the genotype groups on most neurocognitive domains. Second, correlations between peripheral BDNF and neurocognitive phenotypes were minimal but we obtained significant effects for the reasoning and problem-solving domains; thus, higher levels of BDNF expression corresponded to better performance on reasoning/problem-solving tasks. The meta-analyses did not robustly establish an association between BDNF Val66Met polymorphism and neurocognition in schizophrenia.

  9. The Brain Derived Neurotrophic Factor and Personality

    OpenAIRE

    Christian Montag

    2014-01-01

    The study of the biological basis of personality is a timely research endeavor, with the aim of deepening our understanding of human nature. In recent years, a growing body of research has investigated the role of the brain derived neurotrophic factor (BDNF) in the context of individual differences across human beings, with a focus on personality traits. A large number of different approaches have been chosen to illuminate the role of BDNF for personality, ranging from the measurement of BDNF...

  10. Measurements of brain-derived neurotrophic factor

    DEFF Research Database (Denmark)

    Trajkovska, Viktorija; Klein, Anders Bue; Vinberg, Maj;

    2007-01-01

    Although numerous studies have dealt with changes in blood brain-derived neurotrophic factor (BDNF), methodological issues about BDNF measurements have only been incompletely resolved. We validated BDNF ELISA with respect to accuracy, reproducibility and the effect of storage and repeated freezing...... reproducibility. Female gender is associated with higher whole blood BDNF concentrations whereas age, thrombocyte count and BDNF Val66Met polymorphism were un-associated....

  11. The Effect of Aerobic Exercise on Brain-Derived Neurotrophic Factor in People with Neurological Disorders: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Christopher P. Mackay

    2017-01-01

    Full Text Available Objective. To determine the effect of aerobic exercise on brain-derived neurotrophic factor (BDNF levels in people with neurological disorders. Data Sources. Six electronic databases (CINAHL, PubMed, Cochrane, PsycINFO, SportDiscus, and Web of Science were searched until the end of December 2016. Study Selection. Experimental or observational studies of people with neurological disorders who undertook an exercise intervention with BDNF as an outcome measure. The search strategy yielded 984 articles. Data Extraction. Study data were independently extracted from each article. Methodological quality of studies was assessed using the Physiotherapy Evidence Database (PEDro scale. A meta-analysis was planned based on the assessment of predetermined criteria. Data Synthesis. Eleven articles were included. Studies employed either a program of aerobic exercise, a single bout of aerobic exercise, or both. A meta-analysis of studies comparing a program of aerobic exercise against usual care/nil therapy showed a large effect (SMD: 0.84, 95% CI 0.47–1.20, p<0.001 in favour of aerobic exercise to increase levels of BDNF. Findings for a single bout of aerobic exercise were mixed. Quality of studies was low (PEDro average score 4.3/10. Conclusions. A program of aerobic exercise may contribute to increased levels of BDNF in neurological populations.

  12. The Efficacy of Non-Pharmacological Interventions on Brain-Derived Neurotrophic Factor in Schizophrenia: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Sanada, Kenji; Zorrilla, Iñaki; Iwata, Yusuke; Bermúdez-Ampudia, Cristina; Graff-Guerrero, Ariel; Martínez-Cengotitabengoa, Mónica; González-Pinto, Ana

    2016-10-24

    Several studies have investigated the relationship between non-pharmacological interventions (NPIs) and peripheral brain-derived neurotrophic factor (BDNF) in schizophrenia patients. We conducted a systematic review and meta-analysis to review the efficacy of NPIs on peripheral serum and plasma BDNF in subjects with schizophrenia (including schizoaffective disorder). Meta-analyses were conducted to examine the effects of NPIs on blood BDNF levels by using the standardized mean differences (SMDs) between the intervention groups and controls. In total, six randomized controlled trials with 289 participants were included. Of them, five studies used exercise, physical training or diet products. One study used cognitive training. Overall, the BDNF levels in the NPI group increased significantly compared with the control groups (SMD = 0.95, 95% confidence interval (CI) = 0.07 to 1.83, p = 0.03). Subgroup analyses indicated beneficial effects of a non-exercise intervention on peripheral BDNF levels (SMD = 0.41, 95% CI = 0.08 to 0.74, p = 0.01). Meta-regression analyses showed that the completion rate influenced the variation in SMD (p = 0.01). Despite insufficient evidence to draw a conclusion, our results suggest that use of NPIs as adjunctive treatments, specifically non-exercise interventions, may affect positively serum or plasma BDNF in patients with schizophrenia.

  13. The Efficacy of Non-Pharmacological Interventions on Brain-Derived Neurotrophic Factor in Schizophrenia: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Kenji Sanada

    2016-10-01

    Full Text Available Several studies have investigated the relationship between non-pharmacological interventions (NPIs and peripheral brain-derived neurotrophic factor (BDNF in schizophrenia patients. We conducted a systematic review and meta-analysis to review the efficacy of NPIs on peripheral serum and plasma BDNF in subjects with schizophrenia (including schizoaffective disorder. Meta-analyses were conducted to examine the effects of NPIs on blood BDNF levels by using the standardized mean differences (SMDs between the intervention groups and controls. In total, six randomized controlled trials with 289 participants were included. Of them, five studies used exercise, physical training or diet products. One study used cognitive training. Overall, the BDNF levels in the NPI group increased significantly compared with the control groups (SMD = 0.95, 95% confidence interval (CI = 0.07 to 1.83, p = 0.03. Subgroup analyses indicated beneficial effects of a non-exercise intervention on peripheral BDNF levels (SMD = 0.41, 95% CI = 0.08 to 0.74, p = 0.01. Meta-regression analyses showed that the completion rate influenced the variation in SMD (p = 0.01. Despite insufficient evidence to draw a conclusion, our results suggest that use of NPIs as adjunctive treatments, specifically non-exercise interventions, may affect positively serum or plasma BDNF in patients with schizophrenia.

  14. The Brain Derived Neurotrophic Factor and Personality

    Directory of Open Access Journals (Sweden)

    Christian Montag

    2014-01-01

    Full Text Available The study of the biological basis of personality is a timely research endeavor, with the aim of deepening our understanding of human nature. In recent years, a growing body of research has investigated the role of the brain derived neurotrophic factor (BDNF in the context of individual differences across human beings, with a focus on personality traits. A large number of different approaches have been chosen to illuminate the role of BDNF for personality, ranging from the measurement of BDNF in the serum/plasma to molecular genetics to (genetic brain imaging. The present review provides the reader with an overview of the current state of affairs in the context of BDNF and personality.

  15. Association of rs6265 and rs2030324 polymorphisms in brain-derived neurotrophic factor gene with Alzheimer's disease: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yan Lin

    Full Text Available BACKGROUND: The association between polymorphisms rs6265 and rs2030324 in brain-derived neurotrophic factor (BDNF and Alzheimer's disease (AD has been widely reported, but the results remain controversial. METHODS: A comprehensive search of Pubmed, Web of Science, China National Knowledge Infrastructure (CNKI, Wanfang Med Online and China Biology Medical literature database (CBM was performed. Pooled odds ratios (ORs with 95% confidence intervals (CIs were calculated using fixed or random-effects models. We excluded the studies with OR>3.0 or OR<0.3 for sensitive analysis. Subgroup analysis by ethnicity, form of AD and gender was carried out. Meta-regression was conducted to explore the potential sources of between-study heterogeneity. RESULTS: 29 articles with 7548 cases and 7334 controls concerning rs6265 and 22 articles with 5796 cases and 5706 controls concerning rs2030324 were included in this meta-analysis. The combined evidence suggested rs6265 contributing significantly to the increased risk of AD in females (codominant: fixed-effects model (FEM: OR = 1.13, 95% CI = 1.04-1.23; dominant: FEM: OR = 1.17, 95% CI = 1.05-1.31, especially for Caucasian females (codominant: FEM: OR = 1.18, 95% CI = 1.03-1.34; dominant: FEM: OR = 1.18, 95% CI = 1.01-1.37 and female late-onset Alzheimer's disease (LOAD patients (codominant: FEM: OR = 1.22, 95% CI = 1.05-1.41; dominant: FEM: OR = 1.23, 95% CI = 1.03-1.46. No evidence indicated an association between rs2030324 with AD in codominant (random-effects model (REM: OR = 1.06, 95% CI = 0.89-1.26 and dominant (REM: OR = 1.05, 95% CI = 0.86-1.27 models. CONCLUSION: This meta-analysis suggested A allele of rs6265 might increase the risk of AD in Caucasian females and female LOAD patients. In addition, no evidence indicated an association between rs2030324 with AD. Further studies are needed to confirm these results.

  16. Brain-derived Neurotrophic Factor in Megakaryocytes.

    Science.gov (United States)

    Chacón-Fernández, Pedro; Säuberli, Katharina; Colzani, Maria; Moreau, Thomas; Ghevaert, Cedric; Barde, Yves-Alain

    2016-05-06

    The biosynthesis of endogenous brain-derived neurotrophic factor (BDNF) has thus far been examined in neurons where it is expressed at very low levels, in an activity-dependent fashion. In humans, BDNF has long been known to accumulate in circulating platelets, at levels far higher than in the brain. During the process of blood coagulation, BDNF is released from platelets, which has led to its extensive use as a readily accessible biomarker, under the assumption that serum levels may somehow reflect brain levels. To identify the cellular origin of BDNF in platelets, we established primary cultures of megakaryocytes, the progenitors of platelets, and we found that human and rat megakaryocytes express the BDNF gene. Surprisingly, the pattern of mRNA transcripts is similar to neurons. In the presence of thapsigargin and external calcium, the levels of the mRNA species leading to efficient BDNF translation rapidly increase. Under these conditions, pro-BDNF, the obligatory precursor of biologically active BDNF, becomes readily detectable. Megakaryocytes store BDNF in α-granules, with more than 80% of them also containing platelet factor 4. By contrast, BDNF is undetectable in mouse megakaryocytes, in line with the absence of BDNF in mouse serum. These findings suggest that alterations of BDNF levels in human serum as reported in studies dealing with depression or physical exercise may primarily reflect changes occurring in megakaryocytes and platelets, including the ability of the latter to retain and release BDNF.

  17. Bayesian Exploratory Factor Analysis

    DEFF Research Database (Denmark)

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.;

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corr......This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor......, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates...

  18. Bayesian Exploratory Factor Analysis

    DEFF Research Database (Denmark)

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor......, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates...

  19. Epidermal Growth Factor Receptor in Prostate Cancer Derived Exosomes.

    Directory of Open Access Journals (Sweden)

    Geetanjali Kharmate

    Full Text Available Exosomes proteins and microRNAs have gained much attention as diagnostic tools and biomarker potential in various malignancies including prostate cancer (PCa. However, the role of exosomes and membrane-associated receptors, particularly epidermal growth factor receptor (EGFR as mediators of cell proliferation and invasion in PCa progression remains unexplored. EGFR is frequently overexpressed and has been associated with aggressive forms of PCa. While PCa cells and tissues express EGFR, it is unknown whether exosomes derived from PCa cells or PCa patient serum contains EGFR. The aim of this study was to detect and characterize EGFR in exosomes derived from PCa cells, LNCaP xenograft and PCa patient serum. Exosomes were isolated from conditioned media of different PCa cell lines; LNCaP xenograft serum as well as patient plasma/serum by differential centrifugation and ultracentrifugation on a sucrose density gradient. Exosomes were confirmed by electron microscopy, expression of exosomal markers and NanoSight™ analysis. EGFR expression was determined by western blot analysis and ELISA. This study demonstrates that exosomes may easily be derived from PCa cell lines, serum obtained from PCa xenograft bearing mice and clinical samples derived from PCa patients. Presence of exosomal EGFR in PCa patient exosomes may present a novel approach for measuring of the disease state. Our work will allow to build on this finding for future understanding of PCa exosomes and their potential role in PCa progression and as minimal invasive biomarkers for PCa.

  20. Nerve Growth Factor, Brain-derived Neurotrophic Factor and Osteocalcin gene relationship in energy regulation, bone homeostasis and reproductive organs analyzed by mRNA quantitative evaluation and linear correlation analysis

    OpenAIRE

    Claudia Camerino; Elena Conte; Maria Cannone; Roberta Caloiero; Adriano Fonzino; Domenico Tricarico

    2016-01-01

    Nerve Growth Factor (NGF) / Brain-derived Neurotrophic Factor (BDNF) and osteocalcin share common effects regulating energy, bone mass, reproduction and neuronal functions. To investigate on the gene-relationship between NGF, BDNF and Osteocalcin we compared by RT-PCR the transcript levels of Ngf, Bdnf and Osteocalcin as well as of their receptors p75NTR/NTRK1, NTRK2 and Gprc6a in brain, bone, white/brown adipose tissue (WAT/BAT) and reproductive organs of 3 months old female and male mice. B...

  1. Analysis of mutant platelet-derived growth factor receptors expressed in PC12 cells identifies signals governing sodium channel induction during neuronal differentiation.

    Science.gov (United States)

    Fanger, G R; Vaillancourt, R R; Heasley, L E; Montmayeur, J P; Johnson, G L; Maue, R A

    1997-01-01

    The mechanisms governing neuronal differentiation, including the signals underlying the induction of voltage-dependent sodium (Na+) channel expression by neurotrophic factors, which occurs independent of Ras activity, are not well understood. Therefore, Na+ channel induction was analyzed in sublines of PC12 cells stably expressing platelet-derived growth factor (PDGF) beta receptors with mutations that eliminate activation of specific signalling molecules. Mutations eliminating activation of phosphatidylinositol 3-kinase (PI3K), phospholipase C gamma (PLC gamma), the GTPase-activating protein (GAP), and Syp phosphatase failed to diminish the induction of type II Na+ channel alpha-subunit mRNA and functional Na+ channel expression by PDGF, as determined by RNase protection assays and whole-cell patch clamp recording. However, mutation of juxtamembrane tyrosines that bind members of the Src family of kinases upon receptor activation inhibited the induction of functional Na+ channels while leaving the induction of type II alpha-subunit mRNA intact. Mutation of juxtamembrane tyrosines in combination with mutations eliminating activation of PI3K, PLC gamma, GAP, and Syp abolished the induction of type II alpha-subunit mRNA, suggesting that at least partially redundant signaling mechanisms mediate this induction. The differential effects of the receptor mutations on Na+ channel expression did not reflect global changes in receptor signaling capabilities, as in all of the mutant receptors analyzed, the induction of c-fos and transin mRNAs still occurred. The results reveal an important role for the Src family in the induction of Na+ channel expression and highlight the multiplicity and combinatorial nature of the signaling mechanisms governing neuronal differentiation.

  2. Factor Analysis and AIC.

    Science.gov (United States)

    Akaike, Hirotugu

    1987-01-01

    The Akaike Information Criterion (AIC) was introduced to extend the method of maximum likelihood to the multimodel situation. Use of the AIC in factor analysis is interesting when it is viewed as the choice of a Bayesian model; thus, wider applications of AIC are possible. (Author/GDC)

  3. HBpF-proBDNF: A New Tool for the Analysis of Pro-Brain Derived Neurotrophic Factor Receptor Signaling and Cell Biology

    Science.gov (United States)

    Gaub, Perrine; de Léon, Andrès; Gibon, Julien; Soubannier, Vincent; Dorval, Geneviève; Séguéla, Philippe; Barker, Philip A.

    2016-01-01

    Neurotrophins activate intracellular signaling pathways necessary for neuronal survival, growth and apoptosis. The most abundant neurotrophin in the adult brain, brain-derived neurotrophic factor (BDNF), is first synthesized as a proBDNF precursor and recent studies have demonstrated that proBDNF can be secreted and that it functions as a ligand for a receptor complex containing p75NTR and sortilin. Activation of proBDNF receptors mediates growth cone collapse, reduces synaptic activity, and facilitates developmental apoptosis of motoneurons but the precise signaling cascades have been difficult to discern. To address this, we have engineered, expressed and purified HBpF-proBDNF, an expression construct containing a 6X-HIS tag, a biotin acceptor peptide (BAP) sequence, a PreScission™ Protease cleavage site and a FLAG-tag attached to the N-terminal part of murine proBDNF. Intact HBpF-proBDNF has activities indistinguishable from its wild-type counterpart and can be used to purify proBDNF signaling complexes or to monitor proBDNF endocytosis and retrograde transport. HBpF-proBDNF will be useful for characterizing proBDNF signaling complexes and for deciphering the role of proBDNF in neuronal development, synapse function and neurodegenerative disease. PMID:26950209

  4. Gene and protein analysis of brain derived neurotrophic factor expression in relation to neurological recovery induced by an enriched environment in a rat stroke model.

    Science.gov (United States)

    Hirata, Kenji; Kuge, Yuji; Yokota, Chiaki; Harada, Akina; Kokame, Koichi; Inoue, Hiroyasu; Kawashima, Hidekazu; Hanzawa, Hiroko; Shono, Yuji; Saji, Hideo; Minematsu, Kazuo; Tamaki, Nagara

    2011-05-20

    Although an enriched environment enhances functional recovery after ischemic stroke, the mechanism underlying this effect remains unclear. We previously reported that brain derived neurotrophic factor (BDNF) gene expression decreased in rats housed in an enriched environment for 4 weeks compared to those housed in a standard cage for the same period. To further clarify the relationship between the decrease in BDNF and functional recovery, we investigated the effects of differential 2-week housing conditions on the mRNA of BDNF and protein levels of proBDNF and mature BDNF (matBDNF). After transient occlusion of the right middle cerebral artery of male Sprague-Dawley rats, we divided the rats into two groups: (1) an enriched group housed multiply in large cages equipped with toys, and (2) a standard group housed alone in small cages without toys. Behavioral tests before and after 2-week differential housing showed better neurological recovery in the enriched group than in the standard group. Synaptophysin immunostaining demonstrated that the density of synapses in the peri-infarct area was increased in the enriched group compared to the standard group, while infarct volumes were not significantly different. Real-time reverse transcription polymerase chain reaction, Western blotting and immunostaining all revealed no significant difference between the groups. The present results suggest that functional recovery cannot be ascribed to an increase in matBDNF or a decrease in proBDNF but rather to other underlying mechanisms.

  5. Analysis of genetic polymorphisms of brain-derived neurotrophic factor and methylenetetrahydrofolate reductase in depressed patients in a Slovak (Caucasian) population.

    Science.gov (United States)

    Evinova, Andrea; Babusikova, Eva; Straka, Stanislav; Ondrejka, Igor; Lehotsky, Jan

    2012-12-01

    Major depressive disorder (MDD) is a complex neuropsychiatric disorder where both gene-gene and gene-environment interactions play an important role, but the clues are still not fully understood. One carbon metabolism in the CNS plays a critical role in the synthesis and release of neurotransmitters which are relevant to depressive disorder. We studied genetic polymorphisms of the brain derived neurotrophic factor (BDNF) and the methylenetetrahydrofolate reductase (MTHFR) in association with major depressive disorder. We genotyped the BDNF G196A, the MTHFR C677T, and A1298C polymorphisms in 134 patients diagnosed with major depression and 143 control subjects in Slovak (Caucasian) cohort of patients and probands. We found no significant association of either the BDNF G196A or MTHFR C677T polymorphisms with major depressive disorder neither in female nor male group of patients. However, the MTHFR A1298C genotype distribution was 36.6% (for AA genotype), 48.5% (AC) and 14.9% (CC) for the depressed patients, and 48.9% (AA), 42.7% (AC) and 8.4% (CC), respectively, for the control subjects. Patients with MDD had a higher prevalence of the CC genotype (OR = 2.38; 95% CI = 1.07-5.32; p = 0.032) and the AC + CC genotype (OR = 1.67; 95% CI = 1.03-2.69; p = 0.037) in comparison with the control subjects. This study shows that CC genotype of the MTHFR A1298C is associated with higher risk of MDD in Slovak population.

  6. Some Comments on Egghe’s Derivation of the Impact Factor Distribution

    NARCIS (Netherlands)

    L. Waltman (Ludo); N.J.P. van Eck (Nees Jan)

    2009-01-01

    textabstractIn a recent paper, Egghe [Egghe, L. (in press). Mathematical derivation of the impact factor distribution. Journal of Informetrics] provides a mathematical analysis of the rank-order distribution of journal impact factors. We point out that Egghe’s analysis relies on an unrealistic assum

  7. Ginsenoside Rg1 changes brain-derived neurotrophic factor expression in the facial nucleus of rats after ovariectomy:A semiquantitative analysis

    Institute of Scientific and Technical Information of China (English)

    Cuiying Zhou; Wenlong Luo; Dong Wang

    2009-01-01

    BACKGROUND: Estrogen is neuroprotective, but long-term estrogen treatment can induce side effects such as breast carcinoma, endometrial cancer, and stroke. However, phytoestrogen is neuroprotective without these side effects.OBJECTIVE: To study the effects of Ginsenoside Rg1 on facial neurons and brain-derived neurotrophic factor (BDNF) expression in the facial nucleus in ovariectomized rats.DESIGN, TIME AND SETTING: The randomized, controlled animal experiments were performed at the Ultrasonic Institute, Second Affiliated Hospital, Chongqing Medical University, China, from September 2007 to September 2008.MATERIALS: Ginsenoside Rg1 (Sigma, USA), rabbit anti-rat BDNF, Bcl-2, Bax antibodies, biotin-labeled goat anti-rabbit IgG (Boster, China), and a TUNEL kit (Roche, Germany) were used in this study.METHODS: A total of 48 adult Sprague Dawley rats undergoing ovariectomy were randomly assigned into sham operation (n=8), model (n=20), and Ginsenoside Rg1 (n=20) groups. Facial nerve damage was induced by bilateral clamping of the facial nerve trunk. The bilateral facial nerve trunk was exposed in the sham operation group, with no clamping. Rats in the Ginsenoside Rg1 group were intraperitoneally injected with 10 mg/kg per day Ginsenoside Rg1; other groups received 2 mL saline, once a day, for 14 days.MAIN OUTCOME MEASURES: Morphologic changes in neurons of the facial nucleus were observed following hematoxylin-eosin staining. Neuronal apoptosis was detected by TUNEL. Changes in ultrastructure of the facial nerve fibers were observed with a transmission electron microscope. Expression of BDNF, Bcl-2, and Bax protein was quantified by semiquantitative immunohistochemistry.RESULTS: At 3-14 days following facial nerve damage, Ginsenoside Rg1 increased BDNF expression and the number of regenerated nerve fibers, and produced thicker myelin sheaths (P< 0.05). Ginsenoside Rg1 also gradually increased Bcl-2 protein expression and decreased Bax protein expression (P < 0.05). By

  8. Identification of a potent endothelium-derived angiogenic factor.

    Directory of Open Access Journals (Sweden)

    Vera Jankowski

    Full Text Available The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U from the secretome of human endothelial cells. The angiogenic effect of the endothelial secretome was partially reduced after incubation with alkaline phosphatase and abolished in the presence of suramin. In one fraction, purified to homogeneity by reversed phase and affinity chromatography, Up4U was identified by MALDI-LIFT-fragment-mass-spectrometry, enzymatic cleavage analysis and retention-time comparison. Beside a strong angiogenic effect on the yolk sac membrane and the developing rat embryo itself, Up4U increased the proliferation rate of endothelial cells and, in the presence of PDGF, of vascular smooth muscle cells. Up4U stimulated the migration rate of endothelial cells via P2Y2-receptors, increased the ability of endothelial cells to form capillary-like tubes and acts as a potent inducer of sprouting angiogenesis originating from gel-embedded EC spheroids. Endothelial cells released Up4U after stimulation with shear stress. Mean total plasma Up4U concentrations of healthy subjects (N=6 were sufficient to induce angiogenic and proliferative effects (1.34 ± 0.26 nmol L(-1. In conclusion, Up4U is a novel strong human endothelium-derived angiogenic factor.

  9. Determinants of serum brain-derived neurotrophic factor

    NARCIS (Netherlands)

    Bus, B. A. A.; Molendijk, M. L.; Penninx, B. J. W. H.; Buitelaar, J. K.; Kenis, G.; Prickaerts, J.; Elzinga, B. M.; Voshaar, R. C. Oude

    2011-01-01

    Background: Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of growth factors and affects the survival and plasticity of neurons in the adult central nervous system. The high correlation between cortical and serum BDNF levels has led to many human studies on BDNF levels i

  10. Determinants of serum brain-derived neurotrophic factor

    NARCIS (Netherlands)

    Bus, B.A.A.; Molendijk, M.L.; Penninx, B.J.; Buitelaar, J.K.; Kenis, G.; Prickaerts, J.; Elzinga, B.M.; Oude Voshaar, R.C.

    2011-01-01

    BACKGROUND: Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of growth factors and affects the survival and plasticity of neurons in the adult central nervous system. The high correlation between cortical and serum BDNF levels has led to many human studies on BDNF levels i

  11. Method of thermal derivative gradient analysis (TDGA

    Directory of Open Access Journals (Sweden)

    M. Cholewa

    2009-07-01

    Full Text Available In this work a concept of thermal analysis was shown, using for crystallization kinetics description the temperature derivatives after time and direction. Method of thermal derivative gradient analysis (TDGA is assigned for alloys and metals investigation as well as cast composites in range of solidification. The construction and operation characteristics were presented for the test stand including processing modules and probes together with thermocouples location. Authors presented examples of results interpretation for AlSi11 alloy castings with diversified wall thickness and at different pouring temperature.

  12. Brain-Derived Neurotrophic Factor and Neuropsychiatric Disorders

    OpenAIRE

    Anita E Autry; Monteggia, Lisa M.

    2012-01-01

    Brain derived neurotrophic factor (BDNF) is the most prevalent growth factor in the central nervous system (CNS). It is essential for the development of the CNS and for neuronal plasticity. Because BDNF plays a crucial role in development and plasticity of the brain, it is widely implicated in psychiatric diseases. This review provides a summary of clinical and preclinical evidence for the involvement of this ubiquitous growth factor in major depressive disorder, schizophrenia, addiction, Ret...

  13. Pigment epithelium-derived factor (PEDF): a novel trophoblast-derived factor limiting feto-placental angiogenesis in late pregnancy.

    Science.gov (United States)

    Loegl, Jelena; Nussbaumer, Erika; Hiden, Ursula; Majali-Martinez, Alejandro; Ghaffari-Tabrizi-Wizy, Nassim; Cvitic, Silvija; Lang, Ingrid; Desoye, Gernot; Huppertz, Berthold

    2016-07-01

    The rapidly expanding feto-placental vasculature needs tight control by paracrine and endocrine mechanisms. Here, we focused on paracrine influence by trophoblast, the placental epithelium. We aimed to identify differences in regulation of feto-placental angiogenesis in early versus late pregnancy. To this end, the effect of conditioned media (CM) from early and late pregnancy human trophoblast was tested on network formation, migration and proliferation of human feto-placental endothelial cells. Only CM of late pregnancy trophoblast reduced network formation and migration. Screening of trophoblast transcriptome for anti-angiogenic candidates identified pigment epithelium-derived factor (PEDF) with higher expression and protein secretion in late pregnancy trophoblast. Addition of a PEDF-neutralizing antibody restored the anti-angiogenic effect of CM from late pregnancy trophoblast. Notably, human recombinant PEDF reduced network formation only in combination with VEGF. Also in the CAM assay, the combination of PEDF with VEGF reduced branching of vessels below control levels. Analysis of phosphorylation of ERK1/2 and FAK, two key players in VEGF-induced proliferation and migration, revealed that PEDF altered VEGF signaling, while PEDF alone did not affect phosphorylation of ERK1/2 and FAK. These data suggest that the trophoblast-derived anti-angiogenic molecule PEDF is involved in restricting growth and expansion of the feto-placental endothelium predominantly in late pregnancy and targets to modulate the intracellular effect of VEGF.

  14. Brain-Derived Neurotrophic Factor in Chronic Periodontitis

    Directory of Open Access Journals (Sweden)

    Jôice Dias Corrêa

    2014-01-01

    Full Text Available Brain-derived neurotrophic factor (BDNF is a member of the neurotrophic factor family. Outside the nervous system, BDNF has been shown to be expressed in various nonneural tissues, such as periodontal ligament, dental pulp, and odontoblasts. Although a role for BDNF in periodontal regeneration has been suggested, a function for BDNF in periodontal disease has not yet been studied. The aim of this study was to analyze the BDNF levels in periodontal tissues of patients with chronic periodontitis (CP and periodontally healthy controls (HC. All subjects were genotyped for the rs4923463 and rs6265 BDNF polymorphisms. Periodontal tissues were collected for ELISA, myeloperoxidase (MPO, and microscopic analysis from 28 CP patients and 29 HC subjects. BDNF levels were increased in CP patients compared to HC subjects. A negative correlation was observed when analyzing concentration of BDNF and IL-10 in inflamed periodontium. No differences in frequencies of BDNF genotypes between CP and HC subjects were observed. However, BDNF genotype GG was associated with increased levels of BDNF, TNF-α, and CXCL10 in CP patients. In conclusion, BDNF seems to be associated with periodontal disease process, but the specific role of BDNF still needs to be clarified.

  15. Econometric Analysis of Financial Derivatives : An overview

    NARCIS (Netherlands)

    C-L. Chang (Chia-Lin); M.J. McAleer (Michael)

    2014-01-01

    markdownabstract__Abstract__ One of the fastest growing areas in empirical finance, and also one of the least rigorously analyzed, especially from a financial econometrics perspective, is the econometric analysis of financial derivatives, which are typically complicated and difficult to analyze. Th

  16. Econometric Analysis of Financial Derivatives : An overview

    NARCIS (Netherlands)

    C-L. Chang (Chia-Lin); M.J. McAleer (Michael)

    2014-01-01

    markdownabstract__Abstract__ One of the fastest growing areas in empirical finance, and also one of the least rigorously analyzed, especially from a financial econometrics perspective, is the econometric analysis of financial derivatives, which are typically complicated and difficult to analyze.

  17. Econometric Analysis of Financial Derivatives: An Overview

    NARCIS (Netherlands)

    C-L. Chang (Chia-Lin); M.J. McAleer (Michael)

    2014-01-01

    markdownabstract__Abstract__ One of the fastest growing areas in empirical finance, and also one of the least rigorously analyzed, especially from a financial econometrics perspective, is the econometric analysis of financial derivatives, which are typically complicated and difficult to analyze.

  18. Adenovirally Delivered Brain-derived Neurotrophic Factor to Rat Retina

    Institute of Scientific and Technical Information of China (English)

    Xu Hou; Dan Hu; Yannian Hui

    2004-01-01

    Purpose: To study the expression of brain-derived neurotrophic factor (BDNF) in the rat retina delivered by adenovirus.Methods: Adenovirus with BDNF gene was injected into the vitreous. Gene expression was detected by immunofluorescence staining, and quantitative analysis was performed after injury and transfection by Enzyme-linked immunosorbent assay (ELISA).Results: The positive cells can be seen on the 3rd day and last 4 weeks by immunofluorescence staining. Positive cells in the control group were fewer than those in the transfection group or the fluorescence intensity was lower at every time point. Quantitative analysis showed that the expression of BDNF groups was higher than that of the control group at every time point(P < 0.01 ), and that of the injured group without transfection was higher than that of the control group on the 3rd day and the 7th day (P < 0.01 ).Conclusion: Efficient and stable transfer of BDNF gene could be achieved by adenovirus delivery into the retina of rats. Injury can promote the expression of BDNF in early period.

  19. Serum brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 levels in children with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Bilgiç, Ayhan; Toker, Aysun; Işık, Ümit; Kılınç, İbrahim

    2017-03-01

    It has been suggested that neurotrophins are involved in the etiopathogenesis of attention-deficit/hyperactivity disorder (ADHD). This study aimed to investigate whether there are differences in serum brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and neurotrophin-3 (NTF3) levels between children with ADHD and healthy controls. A total of 110 treatment-naive children with the combined presentation of ADHD and 44 healthy controls aged 8-18 years were enrolled in this study. The severity of ADHD symptoms was determined by scores on the Conners' Parent Rating Scale-Revised Short and Conners' Teacher Rating Scale-Revised Short. The severity of depression and anxiety symptoms of the children were evaluated by the self-report inventories. Serum levels of neurotrophins were measured using commercial enzyme-linked immunosorbent assay kits. The multivariate analysis of covariance (MANCOVA) revealed a significant main effect of groups in the levels of serum neurotrophins, an effect that was independent of age, sex, and the severity of the depression and anxiety. The analysis of covariance (ANCOVA) indicated that the mean serum GDNF and NTF3 levels of ADHD patients were significantly higher than that of controls. However, serum BDNF and NGF levels did not show any significant differences between groups. No correlations between the levels of serum neurotrophins and the severity of ADHD were observed. These results suggest that elevated serum GDNF and NTF3 levels may be related to ADHD in children.

  20. Analysis of receptor signaling pathways by mass spectrometry: identification of vav-2 as a substrate of the epidermal and platelet-derived growth factor receptors

    DEFF Research Database (Denmark)

    Pandey, A; Podtelejnikov, A V; Blagoev, B;

    2000-01-01

    Oligomerization of receptor protein tyrosine kinases such as the epidermal growth factor receptor (EGFR) by their cognate ligands leads to activation of the receptor. Transphosphorylation of the receptor subunits is followed by the recruitment of signaling molecules containing src homology 2 (SH2...

  1. [The research advance of brain derived neurotrophic factor].

    Science.gov (United States)

    Liu, Z; Chen, J

    2000-12-01

    Recent research advances in neuroscience show that neurotrophic factors are proteins that affect selectively various kinds of neurons of CNS and PNS. Brain derived neurotrophic factor (BDNF) is another neurotrophic factor that was first reported by Barde, a German chemist, thirty years later after the nerve growth factor had been found out. BDNF plays an important role in the growth, development, differentiation, maintenance and regeneration of various types of neurons in the CNS and has potential application to the treatment of brain injury and neurodegenerative diseases such as Alzheimer's disease, Parkinson's syndrome, Huntington's chorea and amyotrophic lateral sclerosis. In this paper, the structure, function and potential clinical application of BDNF were reviewed.

  2. Multiscale analysis of the CMB temperature derivatives

    Science.gov (United States)

    Marcos-Caballero, A.; Martínez-González, E.; Vielva, P.

    2017-02-01

    We study the Planck CMB temperature at different scales through its derivatives up to second order, which allows one to characterize the local shape and isotropy of the field. The problem of having an incomplete sky in the calculation and statistical characterization of the derivatives is addressed in the paper. The analysis confirms the existence of a low variance in the CMB at large scales, which is also noticeable in the derivatives. Moreover, deviations from the standard model in the gradient, curvature and the eccentricity tensor are studied in terms of extreme values on the data. As it is expected, the Cold Spot is detected as one of the most prominent peaks in terms of curvature, but additionally, when the information of the temperature and its Laplacian are combined, another feature with similar probability at the scale of 10o is also observed. However, the p-value of these two deviations increase above the 6% when they are referred to the variance calculated from the theoretical fiducial model, indicating that these deviations can be associated to the low variance anomaly. Finally, an estimator of the directional anisotropy for spinorial quantities is introduced, which is applied to the spinors derived from the field derivatives. An anisotropic direction whose probability is <1% is detected in the eccentricity tensor.

  3. Nerve Growth Factor, Brain-derived Neurotrophic Factor and Osteocalcin gene relationship in energy regulation, bone homeostasis and reproductive organs analyzed by mRNA quantitative evaluation and linear correlation analysis

    Directory of Open Access Journals (Sweden)

    Claudia Camerino

    2016-10-01

    Full Text Available Nerve Growth Factor (NGF / Brain-derived Neurotrophic Factor (BDNF and osteocalcin share common effects regulating energy, bone mass, reproduction and neuronal functions. To investigate on the gene-relationship between NGF, BDNF and Osteocalcin we compared by RT-PCR the transcript levels of Ngf, Bdnf and Osteocalcin as well as of their receptors p75NTR/NTRK1, NTRK2 and Gprc6a in brain, bone, white/brown adipose tissue (WAT/BAT and reproductive organs of 3 months old female and male mice. Brain and bone were used as positive controls for NGF/BDNF and Osteocalcin respectively. The role of oxitocin(Oxt and its receptor(Oxtr was also investigated. Ngf expression shows an opposite trend compared to Bdnf. Ngf/p75NTR expression is 50% higher in BAT than brain, in both genders, but lower in bone. In contrast, Bdnf expression in bone is higher than in brain, but low in BAT/WAT. We found Osteocalcin gene expressed in brain in both genders, but Gprc6a expression is low in brain and BAT/WAT. As expected, Gprc6a gene is expressed in bone. Oxt gene was markedly expressed in brain, Oxtr in the ovaries and in fat and bone in both genders. Ngf is highly expressed in reproductive tissues and p75NTR mRNA levels are respectively 300%, 100% and 50% higher in testis/ovaries/uterus than in brain. In contrast, BDNF genes are not expressed in reproductive tissues. As expected, Gprc6a is expressed in testis but not in the ovaries/uterus. A significant correlation was found between the expression levels of the gene ligands and their receptors in brain, BAT and testis suggesting a common pathway of different genes in these tissues in either male and female. Changes in the expression levels of osteocalcin, Ngf or Bdnf genes may mutually affect the expression levels of the others. Moreover, it may be possible that different ligands may operate through different receptor subtypes. Oxt and Oxtr failed to show significant correlation. The up-regulation of Ngf/p75NTR in BAT is

  4. Nerve Growth Factor, Brain-Derived Neurotrophic Factor and Osteocalcin Gene Relationship in Energy Regulation, Bone Homeostasis and Reproductive Organs Analyzed by mRNA Quantitative Evaluation and Linear Correlation Analysis

    Science.gov (United States)

    Camerino, Claudia; Conte, Elena; Cannone, Maria; Caloiero, Roberta; Fonzino, Adriano; Tricarico, Domenico

    2016-01-01

    Nerve Growth Factor (NGF)/Brain-derived Neurotrophic Factor (BDNF) and osteocalcin share common effects regulating energy, bone mass, reproduction and neuronal functions. To investigate on the gene-relationship between NGF, BDNF, and Osteocalcin we compared by RT-PCR the transcript levels of Ngf, Bdnf and Osteocalcin as well as of their receptors p75NTR/NTRK1, NTRK2, and Gprc6a in brain, bone, white/brown adipose tissue (WAT/BAT) and reproductive organs of 3 months old female and male mice. Brain and bone were used as positive controls for NGF/BDNF and Osteocalcin respectively. The role of oxitocin(Oxt) and its receptor(Oxtr) was also investigated. Ngf expression shows an opposite trend compared to Bdnf. Ngf /p75NTR expression is 50% higher in BAT than brain, in both genders, but lower in bone. In contrast, Bdnf expression in bone is higher than in brain, but low in BAT/WAT. We found Osteocalcin gene expressed in brain in both genders, but Gprc6a expression is low in brain and BAT/WAT. As expected, Gprc6a gene is expressed in bone. Oxt gene was markedly expressed in brain, Oxtr in the ovaries and in fat and bone in both genders. Ngf is highly expressed in reproductive tissues and p75NTR mRNA levels are respectively 300, 100, and 50% higher in testis/ovaries/uterus than in brain. In contrast, BDNF genes are not expressed in reproductive tissues. As expected, Gprc6a is expressed in testis but not in the ovaries/uterus. A significant correlation was found between the expression levels of the gene ligands and their receptors in brain, BAT and testis suggesting a common pathway of different genes in these tissues in either male and female. Changes in the expression levels of osteocalcin, Ngf, or Bdnf genes may mutually affect the expression levels of the others. Moreover, it may be possible that different ligands may operate through different receptor subtypes. Oxt and Oxtr failed to show significant correlation. The up-regulation of Ngf /p75NTR in BAT is consistent

  5. Nerve Growth Factor, Brain-Derived Neurotrophic Factor and Osteocalcin Gene Relationship in Energy Regulation, Bone Homeostasis and Reproductive Organs Analyzed by mRNA Quantitative Evaluation and Linear Correlation Analysis.

    Science.gov (United States)

    Camerino, Claudia; Conte, Elena; Cannone, Maria; Caloiero, Roberta; Fonzino, Adriano; Tricarico, Domenico

    2016-01-01

    Nerve Growth Factor (NGF)/Brain-derived Neurotrophic Factor (BDNF) and osteocalcin share common effects regulating energy, bone mass, reproduction and neuronal functions. To investigate on the gene-relationship between NGF, BDNF, and Osteocalcin we compared by RT-PCR the transcript levels of Ngf, Bdnf and Osteocalcin as well as of their receptors p75NTR/NTRK1, NTRK2, and Gprc6a in brain, bone, white/brown adipose tissue (WAT/BAT) and reproductive organs of 3 months old female and male mice. Brain and bone were used as positive controls for NGF/BDNF and Osteocalcin respectively. The role of oxitocin(Oxt) and its receptor(Oxtr) was also investigated. Ngf expression shows an opposite trend compared to Bdnf. Ngf /p75NTR expression is 50% higher in BAT than brain, in both genders, but lower in bone. In contrast, Bdnf expression in bone is higher than in brain, but low in BAT/WAT. We found Osteocalcin gene expressed in brain in both genders, but Gprc6a expression is low in brain and BAT/WAT. As expected, Gprc6a gene is expressed in bone. Oxt gene was markedly expressed in brain, Oxtr in the ovaries and in fat and bone in both genders. Ngf is highly expressed in reproductive tissues and p75NTR mRNA levels are respectively 300, 100, and 50% higher in testis/ovaries/uterus than in brain. In contrast, BDNF genes are not expressed in reproductive tissues. As expected, Gprc6a is expressed in testis but not in the ovaries/uterus. A significant correlation was found between the expression levels of the gene ligands and their receptors in brain, BAT and testis suggesting a common pathway of different genes in these tissues in either male and female. Changes in the expression levels of osteocalcin, Ngf, or Bdnf genes may mutually affect the expression levels of the others. Moreover, it may be possible that different ligands may operate through different receptor subtypes. Oxt and Oxtr failed to show significant correlation. The up-regulation of Ngf /p75NTR in BAT is consistent

  6. Empirically derived dietary patterns: interpretability and construct validity according to different factor rotation methods

    Directory of Open Access Journals (Sweden)

    Michelle Alessandra de Castro

    2015-02-01

    Full Text Available This study aimed to investigate the effects of factor rotation methods on interpretability and construct validity of dietary patterns derived in a representative sample of 1,102 Brazilian adults. Dietary patterns were derived from exploratory factor analysis. Orthogonal (varimax and oblique rotations (promax, direct oblimin were applied. Confirmatory factor analysis assessed construct validity of the dietary patterns derived according to two factor loading cut-offs (≥ |0.20| and ≥ |0.25|. Goodness-of-fit indexes assessed the model fit. Differences in composition and in interpretability of the first pattern were observed between varimax and promax/oblimin at cut-off ≥ |0.20|. At cut-off ≥ |0.25|, these differences were no longer observed. None of the patterns derived at cut-off ≥ |0.20| showed acceptable model fit. At cut-off ≥ |0.25|, the promax rotation produced the best model fit. The effects of factor rotation on dietary patterns differed according to the factor loading cut-off used in exploratory factor analysis.

  7. Differential activation of dendritic cells by nerve growth factor and brain-derived neurotrophic factor.

    Science.gov (United States)

    Noga, O; Peiser, M; Altenähr, M; Knieling, H; Wanner, R; Hanf, G; Grosse, R; Suttorp, N

    2007-11-01

    Neurotrophins are involved in inflammatory reactions influencing several cells in health and disease including allergy and asthma. Dendritic cells (DCs) play a major role in the induction of inflammatory processes with an increasing role in allergic diseases as well. The aim of this study was to investigate the influence of neurotrophins on DC function. Monocyte-derived dendritic cells were generated from allergic and non-allergic donors. Neurotrophin receptors were demonstrated by western blotting, flow cytometry and fluorescence microscopy. Activation of small GTPases was evaluated by pull-down assays. DCs were incubated with nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and supernatants were collected for measurement of IL-4, IL-6, IL-10, IL-12p70, TNF-alpha and TGF-beta. Receptor proteins were detectable by western blot, fluorescence activated cell sorting analysis and fluorescence microscopy. Signalling after neurotrophin stimulation occurred in a ligand-specific pattern. NGF led to decreased RhoA and increased Rac activation, while BDNF affected RhoA and Rac activity in a reciprocal fashion. Cells of allergics released a significantly increased amount of IL-6, while for healthy subjects a significantly higher amount of IL-10 was found. These data indicate that DCs are activated by the neurotrophins NGF and BDNF by different pathways in a receptor-dependant manner. These cells then may initiate inflammatory responses based on allergic sensitization releasing preferred cytokines inducing tolerance or a T-helper type 2 response.

  8. Factors influencing fluffy layer suspended matter (FLSM properties in the Odra River - Pomeranian Bay - Arkona Deep System (Baltic Sea as derived by principal components analysis (PCA, and cluster analysis (CA

    Directory of Open Access Journals (Sweden)

    J. Pempkowiak

    2005-01-01

    Full Text Available Factors conditioning formation and properties of suspended matter resting on the sea floor (Fluffy Layer Suspended Matter - FLSM in the Odra river mouth - Arkona Deep system (southern Baltic Sea were investigated. Thirty FLSM samples were collected from four sampling stations, during nine cruises, in the period 1996-1998. Twenty six chemical properties of the fluffy material were measured (organic matter-total, humic substances, a variety of fatty acids fractions, P, N, δ13C, δ15N; Li; heavy metals- Co, Cd, Pb, Ni, Zn, Fe, Al, Mn, Cu, Cr. The so obtained data set was subjected to statistical evaluation. Comparison of mean values of the measured properties led to conclusion that both seasonal and spatial differences of the fluffy material collected at the stations occured. Application of Principal Component Analysis, and Cluster Analysis, to the data set amended with environmental characteristics (depth, salinity, chlorophyll a, distance from the river mouth, led to quantification of factors conditioning the FLSM formation. The five most important factors were: contribution of the lithogenic component (responsible for 25% of the data set variability, time dependent factors (including primary productivity, mass exchange with fine sediment fraction, atmospheric deposition, contribution of material originating from abrasion-altogether 21%, contribution of fresh autochtonous organic matter (9%, influence of microbial activity (8%, seasonality (8%.

  9. Vancouver Experience of Recombinant Human Platelet-Derived Growth Factor.

    Science.gov (United States)

    Younger, Alistair; Penner, Murray; Montijo, Harvey E

    2016-12-01

    Joint arthrodesis utilizing autogenous bone graft remains the gold standard of treatment in fusion procedures of the foot and ankle. Graft harvest, however, has been associated with increased morbidity to patients as well as increased costs. With this in mind, multiple clinical studies have evaluated the efficacy of recombinant human platelet-derived growth factor (rh-PDGF-BB) with beta-tricalcium phosphate (B-TCP) to augment in foot and ankle arthrodesis with favorable results. These factors have led to the increased use of rh-PDGF-BB with B-TCP in Vancouver with good clinical results. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Purification of human platelet-derived growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Raines, E.W.; Ross, R.

    1985-01-01

    The paper describes a method for purification of human platelet-derived growth factor (PDGF) from outdated platelet-rich plasma (PRP) using commonly available laboratory reagents and yielding a mitogen purified 800,000-fold over the starting material. (/sup 3/H)thymidine incorporation into DNA of cultured cells responsive to PDGF represents the most readily available method to follow its purification and define the biological activity of a purified preparation. Other assays to quantitate PDGF include radioreceptor assay and radioimmunoassay.

  11. A Brief History of the Philosophical Foundations of Exploratory Factor Analysis.

    Science.gov (United States)

    Mulaik, Stanley A.

    1987-01-01

    Exploratory factor analysis derives its key ideas from many sources, including Aristotle, Francis Bacon, Descartes, Pearson and Yule, and Kant. The conclusions of exploratory factor analysis are never complete without subsequent confirmatory factor analysis. (Author/GDC)

  12. Factor analysis of multivariate data

    Digital Repository Service at National Institute of Oceanography (India)

    Fernandes, A.A.; Mahadevan, R.

    A brief introduction to factor analysis is presented. A FORTRAN program, which can perform the Q-mode and R-mode factor analysis and the singular value decomposition of a given data matrix is presented in Appendix B. This computer program, uses...

  13. Factor Analysis of Intern Effectiveness

    Science.gov (United States)

    Womack, Sid T.; Hannah, Shellie Louise; Bell, Columbus David

    2012-01-01

    Four factors in teaching intern effectiveness, as measured by a Praxis III-similar instrument, were found among observational data of teaching interns during the 2010 spring semester. Those factors were lesson planning, teacher/student reflection, fairness & safe environment, and professionalism/efficacy. This factor analysis was as much of a…

  14. Factor analysis and missing data

    NARCIS (Netherlands)

    Kamakura, WA; Wedel, M

    2000-01-01

    The authors study the estimation of factor models and the imputation of missing data and propose an approach that provides direct estimates of factor weights without the replacement of missing data with imputed values. First, the approach is useful in applications of factor analysis in the presence

  15. Signatures of prostate-derived Ets factor (PDEF) in cancer.

    Science.gov (United States)

    Mahajan, Nitin

    2016-11-01

    The Ets proteins are a family of transcription factors characterized by an evolutionarily conserved DNA-binding domain and have diverse biological functions including tumor suppressor as well as tumor promoter functions. They are regulated via a complex and diverse number of mechanisms and control key cellular processes. Prostate-derived Ets transcription factor (PDEF), a unique member of the ETS family, is present in tissues with high epithelial content are hormone-regulated, such as prostate, breast, salivary glands, ovaries, colon, airways, and stomach tissues. PDEF (prostate-derived Ets factor) is also referred to as SPDEF (SAM pointed domain containing Ets transcription factor), PSE (mouse homolog), or hPSE (human PSE) in the literature and is the sole member of the PDEF ETS sub-family. The role of PDEF in cancer development is still not fully elucidated though. The present article focuses on the key findings about the PDEF's biological functions, interacting proteins, and its target genes. There is a strong urge to focus on the clinical studies in larger cohort, which elucidate the regulation of PDEF and its target genes, to determine the potential of PDEF as biomarker. Based on the studies discussed in the present article, one can anticipate that PDEF offers a great potential for developing therapeutics against cancer.

  16. Brain-derived neurotrophic factor and neuropsychiatric disorders.

    Science.gov (United States)

    Autry, Anita E; Monteggia, Lisa M

    2012-04-01

    Brain derived neurotrophic factor (BDNF) is the most prevalent growth factor in the central nervous system (CNS). It is essential for the development of the CNS and for neuronal plasticity. Because BDNF plays a crucial role in development and plasticity of the brain, it is widely implicated in psychiatric diseases. This review provides a summary of clinical and preclinical evidence for the involvement of this ubiquitous growth factor in major depressive disorder, schizophrenia, addiction, Rett syndrome, as well as other psychiatric and neurodevelopmental diseases. In addition, the review includes a discussion of the role of BDNF in the mechanism of action of pharmacological therapies currently used to treat these diseases, such antidepressants and antipsychotics. The review also covers a critique of experimental therapies such as BDNF mimetics and discusses the value of BDNF as a target for future drug development.

  17. Derivation of Sky-View Factors from LIDAR Data

    Science.gov (United States)

    Kidd, Christopher; Chapman, Lee

    2013-01-01

    The use of Lidar (Light Detection and Ranging), an active light-emitting instrument, is becoming increasingly common for a range of potential applications. Its ability to provide fine resolution spatial and vertical resolution elevation data makes it ideal for a wide range of studies. This paper demonstrates the capability of Lidar data to measure sky view factors (SVF). The Lidar data is used to generate a spatial map of SVFs which are then compared against photographically-derived SVF at selected point locations. At each location three near-surface elevations measurements were taken and compared with collocated Lidar-derived estimated. It was found that there was generally good agreement between the two methodologies, although with decreasing SVF the Lidar-derived technique tended to overestimate the SVF: this can be attributed in part to the spatial resolution of the Lidar sampling. Nevertheless, airborne Lidar systems can map sky view factors over a large area easily, improving the utility of such data in atmospheric and meteorological models.

  18. ADAMTS13 content in plasma-derived factor VIII/von Willebrand factor concentrates.

    Science.gov (United States)

    Peyvandi, Flora; Mannucci, Pier M; Valsecchi, Carla; Pontiggia, Silvia; Farina, Claudio; Retzios, Anastassios D

    2013-10-01

    Thrombotic thrombocytopenic purpura (TTP) is a microangiopathy syndrome caused by a congenital or acquired deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor (VWF) and thus prevents the formation of platelet-rich thrombi in the microcirculation. TTP can be fatal if not appropriately and timely treated with the infusion of fresh frozen plasma (FFP) or exchange plasmapheresis, that reverse the process of microangiopathy by removing anti-ADAMTS13 autoantibodies and replacing functional ADAMTS13. The treatment of TTP with FFP is not free from risks and must be administered in hospitals or clinics, owing to the substantial amount of plasma volume infused or exchanged and the frequent need of catheter application. Moreover, most FFPs are not subjected to treatments to remove or inactivate blood-borne infectious agents. A number of recent reports indicate that certain plasma-derived VWF-factor VIII (FVIII) concentrates are clinically effective in the treatment of congenital TTP. In this study, we measured ADAMTS13 levels in various plasma-derived VWF-FVIII concentrates, showing that Koate(®) -DVI (Grifols), contained relatively high amounts of ADAMTS13 and that Alphanate(®) (Grifols) was the closest other product in terms of protease content. Koate(®) -DVI contains, on average (five lots tested), 0.091 ± 0.007 Units of ADAMTS13 activity per IU of FVIII. On the basis of this analysis and other reports of VWF-FVIII concentrate utilization in congenital TTP, potential dosing, and future clinical developments are discussed.

  19. Brain-derived neurotrophic factor and its clinical implications.

    Science.gov (United States)

    Bathina, Siresha; Das, Undurti N

    2015-12-10

    Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. It is widely expressed in the CNS, gut and other tissues. BDNF binds to its high affinity receptor TrkB (tyrosine kinase B) and activates signal transduction cascades (IRS1/2, PI3K, Akt), crucial for CREB and CBP production, that encode proteins involved in β cell survival. BDNF and insulin-like growth factor-1 have similar downstream signaling mechanisms incorporating both p-CAMK and MAPK that increase the expression of pro-survival genes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents exhaustion of β cells. Decreased levels of BDNF are associated with neurodegenerative diseases with neuronal loss, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Thus, BDNF may be useful in the prevention and management of several diseases including diabetes mellitus.

  20. A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor

    OpenAIRE

    Szuhany, Kristin L.; Bugatti, Matteo; Otto, Michael W

    2014-01-01

    Consistent evidence indicates that exercise improves cognition and mood, with preliminary evidence suggesting that brain-derived neurotrophic factor (BDNF) may mediate these effects. The aim of the current meta-analysis was to provide an estimate of the strength of the association between exercise and increased BDNF levels in humans across multiple exercise paradigms. We conducted a meta-analysis of 29 studies (N = 1,111 participants) examining the effect of exercise on BDNF levels in three e...

  1. The Effect of Brain-derived Neurotrophic Factor on Angiogenesis

    Institute of Scientific and Technical Information of China (English)

    Chunyan SUN; Yu HU; Zhangbo CHU; Jing HUANG; Lu ZHANG

    2009-01-01

    To investigate the in vitro and in vivo proangiogenic effects of brain-derived ncurotrophic factor (BDNF),human umbilical vein endothelial cells (HUVECs) were isolated and cultured in primary culture.The effect of BDNF on the proliferation of HUVECs was examined by MTT assay.The effects of BDNF on HUVEC migration and tube formation were studied by modified Boyden chamber assay and tube formation assay,respectively.Matrigel plug assay and chorioaUantoic membrane assay were used to evaluate the effects of BDNF on angiogencsis in vivo.Our results showed that BDNF substantially stimulated the migration and tube formation of HUVECs in vitro,although it did not induce HUVEC proliferation.BDNF also induced angiogenesis both in matrigcl plug of mouse model and in chick chorioallantoic membrane.In conclusion,BDNF can promote angiogenesis both in vitro and in vivo,and may be a proangiogenic factor.

  2. Brain-Derived Neurotrophic Factor: Three Ligands, Many Actions.

    Science.gov (United States)

    Hempstead, Barbara L

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) is a member of a family of neurotrophins which include nerve growth factor, neurotrophin 3, and neurotrophin 4. Studies over the last three decades have identified mature BDNF as a key regulator of neuronal differentiation, structure, and function; actions mediated by the TrkB receptor. More recently identified isoforms which are translated from the bdnf gene, including the uncleaved precursor, pro-BDNF, and the cleaved prodomain, have been found to elicit opposing functions in neurons through the activation of distinct receptors. This work emphasizes the critical roles for all three isoforms of BDNF in modulating neuronal activity that impact complex human behaviors including memory, anxiety, depression, and hyperphagia.

  3. Progesterone, brain-derived neurotrophic factor and neuroprotection.

    Science.gov (United States)

    Singh, M; Su, C

    2013-06-03

    While the effects of progesterone in the CNS, like those of estrogen, have generally been considered within the context of reproductive function, growing evidence supports its importance in regulating non-reproductive functions including cognition and affect. In addition, progesterone has well-described protective effects against numerous insults in a variety of cell models, animal models and in humans. While ongoing research in several laboratories continues to shed light on the mechanism(s) by which progesterone and its related progestins exert their effects in the CNS, our understanding is still incomplete. Among the key mediators of progesterone's beneficial effects is the family of growth factors called neurotrophins. Here, we review the mechanisms by which progesterone regulates one important member of the neurotrophin family, brain-derived neurotrophic factor (BDNF), and provides support for its pivotal role in the protective program elicited by progesterone in the brain.

  4. Endothelium-Derived Hyperpolarizing Factor and Vascular Function

    Directory of Open Access Journals (Sweden)

    Muhiddin A. Ozkor

    2011-01-01

    Full Text Available Endothelial function refers to a multitude of physiological processes that maintain healthy homeostasis of the vascular wall. Exposure of the endothelium to cardiac risk factors results in endothelial dysfunction and is associated with an alteration in the balance of vasoactive substances produced by endothelial cells. These include a reduction in nitric oxide (NO, an increase in generation of potential vasoconstrictor substances and a potential compensatory increase in other mediators of vasodilation. The latter has been surmised from data demonstrating persistent endothelium-dependent vasodilatation despite complete inhibition of NO and prostaglandins. This remaining non-NO, non-prostaglandin mediated endothelium-dependent vasodilator response has been attributed to endothelium-derived hyperpolarizing factor/s (EDHF. Endothelial hyperpolarization is likely due to several factors that appear to be site and species specific. Experimental studies suggest that the contribution of the EDHFs increase as the vessel size decreases, with a predominance of EDHF activity in the resistance vessels, and a compensatory up-regulation of hyperpolarization in states characterized by reduced NO availability. Since endothelial dysfunction is a precursor for atherosclerosis development and its magnitude is a reflection of future risk, then the mechanisms underlying endothelial dysfunction need to be fully understood, so that adequate therapeutic interventions can be designed.

  5. First course in factor analysis

    CERN Document Server

    Comrey, Andrew L

    2013-01-01

    The goal of this book is to foster a basic understanding of factor analytic techniques so that readers can use them in their own research and critically evaluate their use by other researchers. Both the underlying theory and correct application are emphasized. The theory is presented through the mathematical basis of the most common factor analytic models and several methods used in factor analysis. On the application side, considerable attention is given to the extraction problem, the rotation problem, and the interpretation of factor analytic results. Hence, readers are given a background of

  6. Exploring Serum Levels of Brain Derived Neurotrophic Factor and Nerve Growth Factor Across Glaucoma Stages

    Science.gov (United States)

    Busanello, Anna; Bonini, Stefano; Quaranta, Luciano; Agnifili, Luca; Manni, Gianluca

    2017-01-01

    Purpose To investigate the serum levels of Brain Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in patients affected by primary open angle glaucoma with a wide spectrum of disease severity compared to healthy controls and to explore their relationship with morphological and functional glaucoma parameters. Materials and Methods 45 patients affected by glaucoma at different stages and 15 age-matched healthy control subjects underwent visual field testing, peripapillary retinal nerve fibre layer thickness measurement using Spectral Domain Optical Coherence Tomography and blood collection for both neurotrophins detection by Enzyme-Linked Immunosorbent Assay. Statistical analysis and association between biostrumental and biochemical data were investigated. Results Serum levels of BDNF in glaucoma patients were significantly lower than those measured in healthy controls (261.2±75.0 pg/ml vs 313.6±79.6 pg/ml, p = 0.03). Subgroups analysis showed that serum levels of BDNF were significantly lower in early (253.8±40.7 pg/ml, p = 0.019) and moderate glaucoma (231.3±54.3 pg/ml, p = 0.04) but not in advanced glaucoma (296.2±103.1 pg/ml, p = 0.06) compared to healthy controls. Serum levels of NGF in glaucoma patients were significantly lower than those measured in the healthy controls (4.1±1 pg/mL vs 5.5±1.2 pg/mL, p = 0.01). Subgroups analysis showed that serum levels of NGF were significantly lower in early (3.5±0.9 pg/mL, p = 0.0008) and moderate glaucoma (3.8±0.7 pg/ml, p<0.0001) but not in advanced glaucoma (5.0±0.7 pg/ml, p = 0.32) compared to healthy controls. BDNF serum levels were not related to age, visual field mean deviation or retinal nerve fibre layer thickness either in glaucoma or in controls while NGF levels were significantly related to visual field mean deviation in the glaucoma group (r2 = 0.26, p = 0.004). Conclusions BDNF and NGF serum levels are reduced in the early and moderate glaucoma stages, suggesting the possibility that

  7. Correlation between Nerve Growth Factor (NGF) with Brain Derived Neurotropic Factor (BDNF) in Ischemic Stroke Patient

    OpenAIRE

    Islam, Andi Asadul

    2016-01-01

    - The neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) is a family of polypeptides that play critical role during neuronal development, appear to mediate protective role on neurorepair in ischemic stroke. Naturally in adult brain neurorepair process consist of: angiogenesis, neurogenesis, and neuronal plasticity, it can also be stimulated by endogenous neurorepair. In this study we observed correlation between NGF and BDNF ischemic stroke patient's onset...

  8. DYNAMIC PLASTICITY: THE ROLE OF GLUCOCORTICOIDS, BRAIN-DERIVED NEUROTROPHIC FACTOR AND OTHER TROPHIC FACTORS

    OpenAIRE

    Gray, J. D.; MILNER, T. A.; MCEWEN, B. S.

    2012-01-01

    Brain-derived neurotrophic factor (BDNF) is a secreted protein that has been linked to numerous aspects of plasticity in the central nervous system (CNS). Stress-induced remodeling of the hippocampus, prefrontal cortex and amygdala is coincident with changes in the levels of BDNF, which has been shown to act as a trophic factor facilitating the survival of existing and newly born neurons. Initially, hippocampal atrophy after chronic stress was associated with reduced BDNF, leading to the hypo...

  9. Brain-derived neurotrophic factor, food intake regulation, and obesity.

    Science.gov (United States)

    Rosas-Vargas, Haydeé; Martínez-Ezquerro, José Darío; Bienvenu, Thierry

    2011-08-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a fundamental role in development and plasticity of the central nervous system (CNS). It is currently recognized as a major participant in the regulation of food intake. Multiple studies have shown that different regulators of appetite such as leptin, insulin and pancreatic polypeptide (PP) potentially exert anorexigenic effects through BDNF. Low circulating levels of BDNF are associated with a higher risk of eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Strict food restriction reduces BDNF and may trigger binge-eating episodes and weight gain. The existence of mutations that cause haploinsufficiency of BDNF as well as some genetic variants, notably the BDNF p.Val66Met polymorphism, are also associated with the development of obese phenotypes and hyperphagia. However, association of the Met allele with AN and BN, which have different phenotypic characteristics, shows clearly the existence of other relevant factors that regulate eating behavior. This may, in part, be explained by the epigenetic regulation of BDNF through mechanisms like DNA methylation and histone acetylation. Environmental factors, primarily during early development, are crucial to the establishment of these stable but reversible changes that alter the transcriptional expression and are transgenerationally heritable, with potential concomitant effects on the development of eating disorders and body weight control.

  10. Evidence for a unique species-specific hypersensitive epitope in Mycobacterium tuberculosis derived cord factor.

    Science.gov (United States)

    McMullen, Ashley M; Hwang, Shen-An; O'Shea, Kelly; Aliru, Maureen L; Actor, Jeffrey K

    2013-12-01

    Presensitization with Mtb-derived trehalose 6,6'-dimycolate (TDM; cord factor) followed by challenge with the same glycolipid species resulted in elicitation of stronger inflammatory responses than when mice were similarly challenged with M. bovis-derived TDM. Mice presensitized to the homologous Mtb-derived TDM demonstrated cachexic over a 6 day period, whereas similarly presensitized mice challenged with the M. bovis-derived TDM, or with emulsion control, did not experience weight loss. Examination of inflammatory responses demonstrated increased lung histopathology in the Mtb-derived TDM challenged group, evidenced by severe tissue disruption, cellular influx, vascular occlusion and lymphocytic cuffing, and endothelial cell damage. Histological analysis demonstrated that lung pathology in the M. bovis challenged group was strikingly similar to that of the acute model challenge. Examination of proinflammatory mediators also showed findings consistent with histological manifestation, with significantly elevated TNF-α and IL-1β, as well as IFN-γ, in the homologous TDM challenged group relative to all other groups. Overall, these findings indicate a difference in hypersensitive immune responses to TDM derived from different mycobacterial strains. Development of specific adaptive immune responses to the Mtb-derived TDM were demonstrated that had limited cross-reactivity to that of M. bovis, thus strongly suggesting the presence of hypersensitive epitopes exclusive to Mtb TDM not present on M. bovis-derived TDM.

  11. Meta-analysis of the C270T polymorphism of brain-derived neurotrophic factor gene in schizophrenia%精神分裂症患者BDNF基因C270T多态性Meta分析

    Institute of Scientific and Technical Information of China (English)

    韩书贤; 钟衔江; 张丽丽; 罗晓; 安治国; 伊琦忠

    2014-01-01

    Objective To evaluate the relationship between the C270T polymorphism brain-derived neurotrophic factor and susceptibility of schizophrenia using meta-analysis. Methods A retrieval was performed on the case control study on the C270T polymorphism of the patients with schizophrenia. The meta-analysis was applied for investigating and summarizing the relationship between C270T polymorphism and schizophrenia. Subgroups were divided according to races. Results A total of 16 studies with 3874 patients and 4309 controls were included. The frequencies of C/T allele and genotype CC/(CT+TT) were associated with schizophrenia (all P<0.01) with OR 1.65 [95%CI (1.26, 2.16)] and 1.71 [95%CI (1.27, 2.30)], respectively. The association of C/T allele and genotype CC/(CT+TT) with schizophrenia was signif-icant in Asian subgroup (P<0.01), with OR 1.89 [95%CI (1.30, 2.75)] and 1.97 [95%CI (1.29, 3.03)], but not in Cauca-sian subgroup (all P=0.05). Conclusion The C270T polymorphism of brain-derived neurotrophic factor gene might con-tribute to the genetic susceptibility of schizophrenia in Asian population.%目的:评价脑源性神经营养因子基因C270T多态性与精神分裂症的关系。方法检索国内外公开发表的关于精神分裂症患者C270T位点多态性病例对照研究的文献,对C270T位点C/T等位基因和CC/(CT+TT)基因型进行Meta分析,计算OR值,并按人种因素分亚组分析。结果共纳入16篇文献,包括3874例患者与4309名对照。C/T等位基因和CC/(CT+TT)基因型均与精神分裂症有关(均P<0.01),OR值分别为1.65[95%CI(1.26,2.16)]和1.71[95%CI(1.27,2.30)]。亚组分析中,高加索人群等位基因和基因型与精神分裂症无统计学关联(均P=0.05);亚洲人群等位基因和基因型与发病风险有关(均P<0.01),OR值分别为1.89[95%CI(1.30,2.75)]和1.97[95%CI(1.29,3.03)]。结论脑源性神经营养因子基因C270T位点多态性可能增加

  12. Stromal cell-derived factor 1α (SDF-1α)

    DEFF Research Database (Denmark)

    Li, Dana; Bjørnager, Louise; Langkilde, Anne

    2016-01-01

    OBJECTIVES: Stromal cell-derived factor 1a (SDF-1α), is a chemokine and is able to home hematopoietic progenitor cells to injured areas of heart tissue for structural repair. Previous studies have found increased levels of SDF-1α in several cardiac diseases, but only few studies have investigated...... SDF-1α in patients with atrial fibrillation (AF). We aimed to test SDF-1α in a large cohort of patients with AF and its role as a prognostic marker. DESIGN: Between January 1st 2008 to December 1st 2012, 290 patients with ECG documented AF were enrolled from the in- and outpatient clinics...... at the Department of Cardiology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark. Plasma levels of SDF-1α were measured using ELISA technique. Clinical data were registered and patient follow-up was conducted. RESULTS: Patients with permanent AF had significantly higher SDF-1α levels (2199.5 pg...

  13. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes

    DEFF Research Database (Denmark)

    Krabbe, K. S.; Nielsen, A. R.; Krogh-Madsen, R.;

    2006-01-01

    Aims/hypothesis  Decreased levels of brain-derived neurotrophic factor (BDNF) have been implicated in the pathogenesis of Alzheimer's disease and depression. These disorders are associated with type 2 diabetes, and animal models suggest that BDNF plays a role in insulin resistance. We therefore...... explored whether BDNF plays a role in human glucose metabolism. Subjects and methods  We included (Study 1) 233 humans divided into four groups depending on presence or absence of type 2 diabetes and presence or absence of obesity; and (Study 2) seven healthy volunteers who underwent both a hyperglycaemic...... and a hyperinsulinaemic-euglycaemic clamp. Results  Plasma levels of BDNF in Study 1 were decreased in humans with type 2 diabetes independently of obesity. Plasma BDNF was inversely associated with fasting plasma glucose, but not with insulin. No association was found between the BDNF G196A (Val66Met) polymorphism...

  14. Glycosylation analysis and protein structure determination of murine fetal antigen 1 (mFA1)--the circulating gene product of the delta-like protein (dlk), preadipocyte factor 1 (Pref-1) and stromal-cell-derived protein 1 (SCP-1) cDNAs

    DEFF Research Database (Denmark)

    Krogh, T N; Bachmann, E; Teisner, B

    1997-01-01

    By means of sequence analysis, murine fetal antigen 1 (mFA1) isolated from Mus musculus amniotic fluid was shown to be the circulating protein of the delta-like protein, stromal-cell-derived protein 1 (SCP-1) and preadipocyte factor 1 (Pref-1) gene products. The protein contains 36 cysteine resid...

  15. Release kinetics of platelet-derived and plasma-derived growth factors from autologous plasma rich in growth factors.

    Science.gov (United States)

    Anitua, Eduardo; Zalduendo, Mari Mar; Alkhraisat, Mohammad Hamdan; Orive, Gorka

    2013-10-01

    Many studies have evaluated the biological effects of platelet rich plasma reporting the final outcomes on cell and tissues. However, few studies have dealt with the kinetics of growth factor delivery by plasma rich in growth factors. Venous blood was obtained from three healthy volunteers and processed with PRGF-Endoret technology to prepare autologous plasma rich in growth factors. The gel-like fibrin scaffolds were then incubated in triplicate, in a cell culture medium to monitor the release of PDGF-AB, VEGF, HGF and IGF-I during 8 days of incubation. A leukocyte-platelet rich plasma was prepared employing the same technology and the concentrations of growth factors and interleukin-1β were determined after 24h of incubation. After each period, the medium was collected, fibrin clot was destroyed and the supernatants were stored at -80°C until analysis. The growth factor delivery is diffusion controlled with a rapid initial release by 30% of the bioactive content after 1h of incubation and a steady state release when almost 70% of the growth factor content has been delivered. Autologous fibrin matrix retained almost 30% of the amount of the growth factors after 8 days of incubation. The addition of leukocytes to the formula of platelet rich plasma did not increase the concentration of the growth factors, while it drastically increased the presence of pro-inflammatory IL-1β. Further studies employing an in vitro inflammatory model would be interesting to study the difference in growth factors and pro-inflammatory cytokines between leukocyte-free and leukocyte-rich platelet rich plasma.

  16. S100B protein, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor in human milk.

    Directory of Open Access Journals (Sweden)

    Ruisong Li

    Full Text Available BACKGROUND: Human milk contains a wide variety of nutrients that contribute to the fulfillment of its functions, which include the regulation of newborn development. However, few studies have investigated the concentrations of S100B protein, brain-derived neurotrophic factor (BDNF, and glial cell line-derived neurotrophic factor (GDNF in human milk. The associations of the concentrations of S100B protein, BDNF, and GDNF with maternal factors are not well explored. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the concentrations of S100B protein, BDNF, and GDNF in human milk and characterize the maternal factors associated with their levels in human milk, human milk samples were collected at days 3, 10, 30, and 90 after parturition. Levels of S100B protein, BDNF, and GDNF, and their mRNAs in the samples were detected. Then, these concentrations were compared with lactation and other maternal factors. S100B protein levels in human milk samples collected at 3, 10, 30, and 90 d after parturition were 1249.79±398.10, 1345.05±539.16, 1481.83±573.30, and 1414.39±621.31 ng/L, respectively. On the other hand, the BDNF concentrations in human milk samples were 10.99±4.55, 13.01±5.88, 13.35±6.43, and 2.83±5.47 µg/L, while those of GDNF were 10.90±1.65, 11.38±1., 11.29±3.10, and 11.40±2.21 g/L for the same time periods. Maternal post-pregnancy body mass index was positively associated with S100B levels in human milk (r = 0.335, P = 0.030<0.05. In addition, there was a significant correlation between the levels of S100B protein and BDNF (z = 2.09, P = 0.037<0.05. Delivery modes were negatively associated with the concentration of GDNF in human milk. CONCLUSIONS: S100B protein, BDNF, and GDNF are present in all samples of human milk, and they may be responsible for the long term effects of breast feeding.

  17. Identification and proteomic analysis of osteoblast-derived exosomes

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Min; Ke, Ronghu; Cai, Tianyi; Yang, Junyi; Mu, Xiongzheng, E-mail: cranio@vip.163.com

    2015-11-06

    Exosomes are nanometer-sized vesicles with the function of intercellular communication, and they are released by various cell types. To reveal the knowledge about the exosomes from osteoblast, and explore the potential functions of osteogenesis, we isolated microvesicles from supernatants of mouse Mc3t3 by ultracentrifugation, characterized exosomes by electron microscopy and immunoblotting and presented the protein profile by proteomic analysis. The result demonstrated that microvesicles were between 30 and 100 nm in diameter, round shape with cup-like concavity and expressed exosomal marker tumor susceptibility gene (TSG) 101 and flotillin (Flot) 1. We identified a total number of 1069 proteins among which 786 proteins overlap with ExoCarta database. Gene Oncology analysis indicated that exosomes mostly derived from plasma membrane and mainly involved in protein localization and intracellular signaling. The Ingenuity Pathway Analysis showed pathways are mostly involved in exosome biogenesis, formation, uptake and osteogenesis. Among the pathways, eukaryotic initiation factor 2 pathways played an important role in osteogenesis. Our study identified osteoblast-derived exosomes, unveiled the content of them, presented potential osteogenesis-related proteins and pathways and provided a rich proteomics data resource that will be valuable for further studies of the functions of individual proteins in bone diseases. - Highlights: • We for the first time identified exosomes from mouse osteoblast. • Osteoblasts-derived exosomes contain osteoblast peculiar proteins. • Proteins from osteoblasts-derived exosomes are intently involved in EIF2 pathway. • EIF2α from the EIF2 pathway plays an important role in osteogenesis.

  18. Deriving time discounting correction factors for TTO tariffs.

    Science.gov (United States)

    Attema, Arthur E; Brouwer, Werner B F

    2014-04-01

    The Time Trade-off (TTO) method is a popular method for valuing health state utilities and is frequently used in economic evaluations. However, this method produces utilities that are distorted by several biases. One important bias entails the failure to incorporate time discounting. This paper aims to measure time discounting for health outcomes in a sample representative for the general population. In particular, we estimate TTO scores alongside time discounting in order to derive a set of correction factors that can be employed to correct raw TTO scores for the downward bias caused by time discounting. We find substantial positive correction factors, which are increasing with the severity of the health state. Furthermore, higher discounting is found when using more severe health states in the discounting elicitation task. More research is needed to further develop discount rate elicitation procedures and test their validity, especially in general public samples. Moreover, future research should investigate the correction of TTO values for other biases as well, such as loss aversion, and to develop a criterion to test the external validity of TTO scores.

  19. Transforming Rubrics Using Factor Analysis

    Science.gov (United States)

    Baryla, Ed; Shelley, Gary; Trainor, William

    2012-01-01

    Student learning and program effectiveness is often assessed using rubrics. While much time and effort may go into their creation, it is equally important to assess how effective and efficient the rubrics actually are in terms of measuring competencies over a number of criteria. This study demonstrates the use of common factor analysis to identify…

  20. Truncation Analysis for the Derivative Schrodinger Equation

    Institute of Scientific and Technical Information of China (English)

    XU Peng Cheng; CHANG Qian Shun; GUO Bo Ling

    2002-01-01

    The truncation equation for the derivative nonlinear Schrodinger equation has been dis-cussed in this paper. The existence of a special heteroclinic orbit has been found by using geometricalsingular perturbation theory together with Melnikov's technique.

  1. Diameter of basalt columns derived from fracture mechanics bifurcation analysis.

    Science.gov (United States)

    Bahr, H-A; Hofmann, M; Weiss, H-J; Bahr, U; Fischer, G; Balke, H

    2009-05-01

    The diameter of columnar joints forming in cooling basalt and drying starch increases with decreasing growth rate. This observation can be reproduced with a linear-elastic three-dimensional fracture mechanics bifurcation analysis, which has been done for a periodic array of hexagonal columnar joints by considering a bifurcation mode compatible with observations on drying starch. In order to be applicable to basalt columns, the analysis has been carried out with simplified stationary temperature fields. The critical diameter differs from the one derived with a two-dimensional model by a mere factor of 1/2. By taking into account the latent heat released at the solidification front, the results agree fairly well with observed column diameters.

  2. Identification and proteomic analysis of osteoblast-derived exosomes.

    Science.gov (United States)

    Ge, Min; Ke, Ronghu; Cai, Tianyi; Yang, Junyi; Mu, Xiongzheng

    2015-11-01

    Exosomes are nanometer-sized vesicles with the function of intercellular communication, and they are released by various cell types. To reveal the knowledge about the exosomes from osteoblast, and explore the potential functions of osteogenesis, we isolated microvesicles from supernatants of mouse Mc3t3 by ultracentrifugation, characterized exosomes by electron microscopy and immunoblotting and presented the protein profile by proteomic analysis. The result demonstrated that microvesicles were between 30 and 100 nm in diameter, round shape with cup-like concavity and expressed exosomal marker tumor susceptibility gene (TSG) 101 and flotillin (Flot) 1. We identified a total number of 1069 proteins among which 786 proteins overlap with ExoCarta database. Gene Oncology analysis indicated that exosomes mostly derived from plasma membrane and mainly involved in protein localization and intracellular signaling. The Ingenuity Pathway Analysis showed pathways are mostly involved in exosome biogenesis, formation, uptake and osteogenesis. Among the pathways, eukaryotic initiation factor 2 pathways played an important role in osteogenesis. Our study identified osteoblast-derived exosomes, unveiled the content of them, presented potential osteogenesis-related proteins and pathways and provided a rich proteomics data resource that will be valuable for further studies of the functions of individual proteins in bone diseases.

  3. Brain-derived neurotrophic factor: role in depression and suicide

    Directory of Open Access Journals (Sweden)

    Yogesh Dwivedi

    2009-08-01

    Full Text Available Yogesh DwivediPsychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USAAbstract: Depression and suicidal behavior have recently been shown to be associated with disturbances in structural and synaptic plasticity. Brain-derived neurotrophic factor (BDNF, one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons and in synaptic plasticity. Several lines of evidence suggest that BDNF is involved in depression, such that the expression of BDNF is decreased in depressed patients. In addition, antidepressants up-regulate the expression of BDNF. This has led to the proposal of the “neurotrophin hypothesis of depression”. Increasing evidence demonstrates that suicidal behavior is also associated with lower expression of BDNF, which may be independent from depression. Recent genetic studies also support a link of BDNF to depression/suicidal behavior. Not only BDNF, but abnormalities in its cognate receptor tropomycin receptor kinase B (TrkB and its splice variant (TrkB.T1 have also been reported in depressed/suicidal patients. It has been suggested that epigenetic modulation of the Bdnf and Trkb genes may contribute to their altered expression and functioning. More recently, impairment in the functioning of pan75 neurotrophin receptor has been reported in suicide brain specimens. pan75 neurotrophin receptor is a low-affinity neurotrophin receptor that, when expressed in conjunction with low availability of neurotropins/Trks, induces apoptosis. Overall, these studies suggest the possibility that BDNF and its mediated signaling may participate in the pathophysiology of depression and suicidal behavior. This review focuses on the critical evidence demonstrating the involvement of BDNF in depression and suicide.Keywords: BDNF, neurotrophins, p75NTR, Trk receptor, depression, antidepressants, suicide, genetics, epigenetics

  4. Role of brain-derived neurotrophic factor in Huntington's disease.

    Science.gov (United States)

    Zuccato, Chiara; Cattaneo, Elena

    2007-04-01

    Neurotrophic factors are essential contributors to the survival of peripheral and central nervous system (CNS) neurons, and demonstration of their reduced availability in diseased brains indicates that they play a role in various neurological disorders. This paper will concentrate on the role of brain-derived neurotrophic factor (BDNF) in the survival and activity of the neurons that die in Huntington's disease (HD) by reviewing the evidence indicating that it involves profound changes in BDNF levels and that attempts to restore these levels are therapeutically interesting. BDNF is a small dimeric protein that is widely expressed in adult mammalian brain and has been shown to promote the survival of all major neuronal types affected in Alzheimer's disease (AD) and Parkinson's disease (PD). Furthermore, cortical BDNF production is required for the correct activity of the corticostriatal synapse and the survival of the GABA-ergic medium-sized spiny striatal neurons that die in HD. We will highlight the available data concerning changes in BDNF levels in HD cells, mice and human postmortem samples, describe the molecular evidence underlying this alteration, and review the data concerning the impact of the experimental manipulation of BDNF levels on HD progression. Such studies have revealed a major loss of BDNF protein in the striatum of HD patients which may contribute to the clinical manifestations of the disease. They have also opened up a molecular window into the underlying pathogenic mechanism and new therapeutic perspectives by raising the possibility that one of the mechanisms triggering the reduction in BDNF in HD may also affect the activity of many other neuronal proteins.

  5. Biological characterization of purified macrophage-derived neutrophil chemotactic factor

    Directory of Open Access Journals (Sweden)

    M. Dias-Baruffi

    1995-01-01

    Full Text Available We have recently described the purification of a 54 kDa acidic protein, identified as macrophage-derived neutrophil chemotactic factor (MNCF. This protein causes in vitro chemotaxis as well as in vivo neutrophil migration even in animals treated with dexamethasone. This in vivo chemotactic activity of MNCF in animals pretreated with dexamethasone is an uncommon characteristic which discriminates MNCF from known chemotactic cytokines. MNCF is released in the supernatant by macrophage monolayers stimulated with lipopolysaccharide (LPS. In the present study, we describe some biological characteristics of homogenous purified MNCF. When assayed in vitro, MNCF gave a bell-shaped dose–response curve. This in vitro activity was shown to be caused by haptotaxis. Unlike N-formyl-methionylleucyl- phenylalanine (FMLP or interleukin 8 (IL-8, the chemotactic activity of MNCF in vivo and in vitro, was inhibited by preincubation with D-galactose but not with D-mannose. In contrast with IL-8, MNCF did not bind to heparin and antiserum against IL-8 was ineffective in inhibiting its chemotactic activity. These data indicate that MNCF induces neutrophil migration through a carbohydrate recognition property, but by a mechanism different from that of the known chemokines. It is suggested that MNCF may be an important mediator in the recruitment of neutrophils via the formation of a substrate bound chemotactic gradient (haptotaxis in the inflamed tissues.

  6. Aquifer test interpretation using derivative analysis and diagnostic plots

    Science.gov (United States)

    Hernández-Espriú, Antonio; Real-Rangel, Roberto; Cortés-Salazar, Iván; Castro-Herrera, Israel; Luna-Izazaga, Gabriela; Sánchez-León, Emilio

    2017-04-01

    Pumping tests remain a method of choice to deduce fundamental aquifer properties and to assess well condition. In the oil and gas (O&G) industry, well testing has been the core technique in examining reservoir behavior over the last 50 years. The pressure derivative by Bourdet, it is perhaps, the most significant single development in the history of well test analysis. Recently, the so-called diagnostics plots (e.g. drawdown and drawdown derivative in a log-log plot) have been successfully tested in aquifers. However, this procedure is still underutilized by groundwater professionals. This research illustrates the applicability range, advantages and drawbacks (e.g. smoothing procedures) of diagnostic plots using field examples from a wide spectrum of tests (short/long tests, constant/variable flow rates, drawdown/buildup stages, pumping well/observation well) in dissimilar geological conditions. We analyze new and pre-existent aquifer tests in Mexico, USA, Canada, Germany, France and Saudi Arabia. In constant flow rate tests, our results show that derivative analysis is an easy, robust and powerful tool to assess near-borehole damage effects, formation heterogeneity, boundaries, flow regimes, infinite-acting radial stages, i.e., valid Theisian framework, and fracture-driven flow. In step tests, the effectiveness relies on high-frequency drawdown measurements. Moreover, we adapt O&G analytical solutions to cater for the conditions in groundwater systems. In this context, further parameters can be computed analytically from the plots, such as skin factor, head losses, wellbore storage, distance to the boundary, channel-aquifer and/or fracture zone width, among others. Therefore, diagnostic plots should be considered a mandatory tool for pumping tests analysis among hydrogeologists. This project has been supported by DGAPA (UNAM) under the research project PAPIIT IN-112815.

  7. Identification of hypothalamic neuron-derived neurotrophic factor as a novel factor modulating appetite.

    Science.gov (United States)

    Byerly, Mardi S; Swanson, Roy D; Semsarzadeh, Nina N; McCulloh, Patrick S; Kwon, Kiwook; Aja, Susan; Moran, Timothy H; Wong, G William; Blackshaw, Seth

    2013-06-15

    Disruption of finely coordinated neuropeptide signals in the hypothalamus can result in altered food intake and body weight. We identified neuron-derived neurotrophic factor (NENF) as a novel secreted protein through a large-scale screen aimed at identifying novel secreted hypothalamic proteins that regulate food intake. We observed robust Nenf expression in hypothalamic nuclei known to regulate food intake, and its expression was altered under the diet-induced obese (DIO) condition relative to the fed state. Hypothalamic Nenf mRNA was regulated by brain-derived neurotrophic factor (BDNF) signaling, itself an important regulator of appetite. Delivery of purified recombinant BDNF into the lateral cerebral ventricle decreased hypothalamic Nenf expression, while pharmacological inhibition of trkB signaling increased Nenf mRNA expression. Furthermore, recombinant NENF administered via an intracerebroventricular cannula decreased food intake and body weight and increased hypothalamic Pomc and Mc4r mRNA expression. Importantly, the appetite-suppressing effect of NENF was abrogated in obese mice fed a high-fat diet, demonstrating a diet-dependent modulation of NENF function. We propose the existence of a regulatory circuit involving BDNF, NENF, and melanocortin signaling. Our study validates the power of using an integrated experimental and bioinformatic approach to identify novel CNS-derived proteins with appetite-modulating function and reveals NENF as an important central modulator of food intake.

  8. Deriving directions through procedural task analysis.

    Science.gov (United States)

    Yuen, H K; D'Amico, M

    1998-01-01

    Task analysis is one of the essential components of activity analysis. Procedural task analysis involves breaking down an activity into a sequence of steps. Directions are the sequence of steps resulting from the task analysis (i.e., the product of the task analysis). Directions become a guide for caregivers or trainers use in teaching clients a specific skill. However, occupational therapy students often have difficulty in writing directions that are clear enough for caregivers or trainers to carry out. Books on activity analysis only provide examples of directions without giving guidelines on how to perform the writing process. The purposes of this paper are to describe the process of procedural task analysis and to provide a guideline for writing steps of directions.

  9. Serum platelet-derived growth factor and fibroblast growth factor in patients with benign and malignant ovarian tumors

    DEFF Research Database (Denmark)

    Madsen, Christine Vestergaard; Steffensen, Karina Dahl; Olsen, Dorte Aalund

    2012-01-01

    New biological markers with predictive or prognostic value are highly warranted in the treatment of ovarian cancer. The platelet-derived growth factor (PDGF) system and fibroblast growth factor (FGF) system are important components in tumor growth and angiogenesis.......New biological markers with predictive or prognostic value are highly warranted in the treatment of ovarian cancer. The platelet-derived growth factor (PDGF) system and fibroblast growth factor (FGF) system are important components in tumor growth and angiogenesis....

  10. Platelet-derived stromal cell-derived factor-1 is required for the transformation of circulating monocytes into multipotential cells.

    Directory of Open Access Journals (Sweden)

    Noriyuki Seta

    Full Text Available BACKGROUND: We previously described a primitive cell population derived from human circulating CD14(+ monocytes, named monocyte-derived multipotential cells (MOMCs, which are capable of differentiating into mesenchymal and endothelial lineages. To generate MOMCs in vitro, monocytes are required to bind to fibronectin and be exposed to soluble factor(s derived from circulating CD14(- cells. The present study was conducted to identify factors that induce MOMC differentiation. METHODS: We cultured CD14(+ monocytes on fibronectin in the presence or absence of platelets, CD14(- peripheral blood mononuclear cells, platelet-conditioned medium, or candidate MOMC differentiation factors. The transformation of monocytes into MOMCs was assessed by the presence of spindle-shaped adherent cells, CD34 expression, and the potential to differentiate in vitro into mesenchymal and endothelial lineages. RESULTS: The presence of platelets or platelet-conditioned medium was required to generate MOMCs from monocytes. A screening of candidate platelet-derived soluble factors identified stromal cell-derived factor (SDF-1 as a requirement for generating MOMCs. Blocking an interaction between SDF-1 and its receptor CXCR4 inhibited MOMC generation, further confirming SDF-1's critical role in this process. Finally, circulating MOMC precursors were found to reside in the CD14(+CXCR4(high cell population. CONCLUSION: The interaction of SDF-1 with CXCR4 is essential for the transformation of circulating monocytes into MOMCs.

  11. Correspondence factor analysis of steroid libraries.

    Science.gov (United States)

    Ojasoo, T; Raynaud, J P; Doré, J C

    1995-06-01

    The receptor binding of a library of 187 steroids to five steroid hormone receptors (estrogen, progestin, androgen, mineralocorticoid, and glucocorticoid) has been analyzed by correspondence factor analysis (CFA) in order to illustrate how the method could be used to derive structure-activity-relationships from much larger libraries. CFA is a cartographic multivariate technique that provides objective distribution maps of the data after reduction and filtering of redundant information and noise. The key to the analysis of very complex data tables is the formation of barycenters (steroids with one or more common structural fragments) that can be introduced into CFA analyses used as mathematical models. This is possible in CFA because the method uses X2-metrics and is based on the distributional equivalence of the rows and columns of the transformed data matrix. We have thus demonstrated, in purely objective statistical terms, the general conclusions on the specificity of various functional and other groups derived from prior analyses by expert intuition and reasoning. A finer analysis was made of a series of A-ring phenols showing the high degree of glucocorticoid receptor and progesterone receptor binding that can be generated by certain C-11-substitutions despite the presence of the phenolic A-ring characteristic of estrogen receptor-specific binding.

  12. Action mechanisms of a new erythrocyte-derived depressing factor

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To investigate the action mechanisms of a new erythrocyte-derived depressing factor (EDDF), the focus is placed on the effect of EDDF on both cytosolic and nuclear free calcium (Ca2+) transportation in vascular smooth muscle cell (VSMC), as well as the apoptosis and cell cycle of VSMC of rats. EDDF has been extracted from human erythrocytes. The changes of Ca2+ levels in cytoplasm ([Ca2+]i) and nucleus ([Ca2+]n) have been observed using a laser scanning confocal microscope together with fluo-3/AM as a calcium indicator. Flow cytometric technique was used to study the effect of EDDF on cell cycle and apoptosis of VSMC. [Ca2+]i and [Ca2+]n were significantly decreased through several different pathways: (ⅰ) it reduced the Ca2+ influx by blocking L-type voltage-dependent calcium channel (L-VDC) and R-type voltage-dependent calcium channel (R-VDC); (ⅱ) it inhibited the Ca2+ release from inositol 1, 4, 5-trisphosphate (IP3) sensitive calcium store; and (ⅲ) activated Ca2+-ATPase of sarcoplasmic reticulum (SR) and promoted the transportation of Ca2+ from cytoplasm to SR. However, EDDF seemed to have little inhibitory effect on the Ca2+ release from ryonodine sensitive calcium pool. It was also found that EDDF (104 g/mL) significantly decreased the proportion of S phase of human umbilical vein (HUV) and inhibited the proliferation of VSMC induced by angiotensin Ⅱ (AngⅡ, 105 mol/L). The apopotosis did not occur when VSMC was cultured under normal condition. While VSMC apoptosis was induced by AngII (10-5 mol/L) and EDDF (104 g/mL) seemed to have little effect on it. The inhibitory effect of EDDF on the elevation of [Ca2+]i and [Ca2+]n of VSMC might play an essential role in its action mechanisms and the ways it affects the Ca2+ handling of VSMC demonstrate that EDDF was different from other endogenous blood pressure regulators and some known antihypertensive drugs. EDDF could inhibit the proliferation of VSMC, which indicated that it might be beneficial to the

  13. An easy guide to factor analysis

    CERN Document Server

    Kline, Paul

    2014-01-01

    Factor analysis is a statistical technique widely used in psychology and the social sciences. With the advent of powerful computers, factor analysis and other multivariate methods are now available to many more people. An Easy Guide to Factor Analysis presents and explains factor analysis as clearly and simply as possible. The author, Paul Kline, carefully defines all statistical terms and demonstrates step-by-step how to work out a simple example of principal components analysis and rotation. He further explains other methods of factor analysis, including confirmatory and path analysis, a

  14. Alterations in BDNF (brain derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) serum levels in bipolar disorder: The role of lithium.

    Science.gov (United States)

    Tunca, Zeliha; Ozerdem, Aysegul; Ceylan, Deniz; Yalçın, Yaprak; Can, Güneş; Resmi, Halil; Akan, Pınar; Ergör, Gül; Aydemir, Omer; Cengisiz, Cengiz; Kerim, Doyuran

    2014-09-01

    Brain-derived neurotrophic factor (BDNF) has been consistently reported to be decreased in mania or depression in bipolar disorders. Evidence suggests that Glial cell line-derived neurotrophic factor (GDNF) has a role in the pathogenesis of mood disorders. Whether GDNF and BDNF act in the same way across different episodes in bipolar disorders is unclear. BDNF and GDNF serum levels were measured simultaneously by enzyme-linked immunosorbent assay (ELISA) method in 96 patients diagnosed with bipolar disorder according to DSM-IV (37 euthymic, 33 manic, 26 depressed) in comparison to 61 healthy volunteers. SCID- I and SCID-non patient version were used for clinical evaluation of the patients and healthy volunteers respectively. Correlations between the two trophic factor levels, and medication dose, duration and serum levels of lithium or valproate were studied across different episodes of illness. Patients had significantly lower BDNF levels during mania and depression compared to euthymic patients and healthy controls. GDNF levels were not distinctive. However GDNF/BDNF ratio was higher in manic state compared to euthymia and healthy controls. Significant negative correlation was observed between BDNF and GDNF levels in euthymic patients. While BDNF levels correlated positively, GDNF levels correlated negatively with lithium levels. Regression analysis confirmed that lithium levels predicted only GDNF levels positively in mania, and negatively in euthymia. Small sample size in different episodes and drug-free patients was the limitation of thestudy. Current data suggests that lithium exerts its therapeutic action by an inverse effect on BDNF and GDNF levels, possibly by up-regulating BDNF and down-regulating GDNF to achieve euthymia. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. [Brain-derived neurotrophic factor gene (BDNF) polymorphism among Moscow citizens].

    Science.gov (United States)

    Kokaeva, Z G; Kochetkova, T O; Afonchikova, E V; Kondratyeva, N S; Klimov, E A

    2013-12-01

    Recent studies showed that brain-derived neurotrophic factor (BDNF) can participate in pathogenesis of various CNS disorders, being connected with proliferation, differentiation, and survival of neurons. In present study, analysis of occurrence rate was performed for three single nucleotide polymorphisms (SNPs) located in BDNF gene (rs6267 (A/G) allele A-0.265; rs2049046 (A/T) allele A-0.407; rs11030107 (A/G) allele A-0.872) in randomized selection of Moscow citizens. Linkage disequilibrium of rs6165 and rs2049046 loci was shown. Differences in allele frequencies in studied selection and populations of other re- gions were discovered.

  16. [Effect of cryotherapy over the expression of vascular endothelial growth factor and pigment epithelium-derived factor].

    Science.gov (United States)

    Toscano-Garibay, Julia Dolores; Quiroz-Mercado, Hugo; Espitia-Pinzón, Clara; Gil-Carrasco, Félix; Flores-Estrada, José Javier

    2014-01-01

    Cryotherapy is a no invasive technique that uses intense cold to freeze and destroy cancer tissues. There are no descriptions of its effects over the expression of vascular endothelial growth factor and pigment epithelium-derived factor. Experimental study in cryogenic spot were applied in the right sclera of twelve pigs for ten minutes. Other 3 pigs were used as normal controls. Animals were sacrificed at 7, 14 and 21 and the tissues of choriodes and retina were dissected in areas of approximately 1 cm2 surrounding cryogenic spots. Expression levels of vascular endothelial growth factor and pigment epithelium-derived factor were determined analyzed using polymerase chain reaction coupled to reverse-transcription. Vascular endothelial growth factor was significantly downregulated (24%, p< 0.05) seven days post-treatment meanwhile pigment epithelium-derived factor levels increased 44.8% (p< 0.05) as compared to normal controls (untreated). Both vascular endothelial growth factor and pigment epithelium-derived factor levels remain the same until day 14 but returned to basal expression at day 21. This work expose the relation of cryotherapy with the expression of two factors related to angiogenesis. RESULTS showed significant changes on the expression of vascular endothelial growth factor and pigment epithelium-derived factor illustrating that both proteins are regulated in response to cryogenic treatment in relatively short periods (21 days).

  17. Transfection of the glial cell line-derived neurotrophic factor gene promotes neuronal differentiation

    Institute of Scientific and Technical Information of China (English)

    Jie Du; Xiaoqing Gao; Li Deng; Nengbin Chang; Huailin Xiong; Yu Zheng

    2014-01-01

    Glial cell line-derived neurotrophic factor recombinant adenovirus vector-transfected bone marrow mesenchymal stem cells were induced to differentiate into neuron-like cells using inductive medium containing retinoic acid and epidermal growth factor. Cell viability, micro-tubule-associated protein 2-positive cell ratio, and the expression levels of glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43 protein in the su-pernatant were signiifcantly higher in glial cell line-derived neurotrophic factor/bone marrow mesenchymal stem cells compared with empty virus plasmid-transfected bone marrow mes-enchymal stem cells. Furthermore, microtubule-associated protein 2, glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43 mRNA levels in cell pellets were statistically higher in glial cell line-derived neurotrophic factor/bone marrow mesen-chymal stem cells compared with empty virus plasmid-transfected bone marrow mesenchymal stem cells. These results suggest that glial cell line-derived neurotrophic factor/bone marrow mesenchymal stem cells have a higher rate of induction into neuron-like cells, and this enhanced differentiation into neuron-like cells may be associated with up-regulated expression of glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43.

  18. Regulatory Mechanisms Involved in the Expression of Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor

    Science.gov (United States)

    1996-03-01

    Growth Factor Nerve growth factor (NGF), the prototypical neurotrophin, originally isolated by Levi -Montalcini and colleagues ( Levi -Montalcini, 1987; see...inclusion of NGF antibodies ( Levi -Montalcini, 1987). In addition, these neurons exhibit enhanced differentiation, as evidenced by extensive neurite...the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron 6: 845-858, 1991. Hefti, F. Nerve growth factor

  19. Identification of a potent endothelium-derived angiogenic factor

    DEFF Research Database (Denmark)

    Jankowski, Vera; Tölle, Markus; Tran, Thi Nguyet Anh

    2013-01-01

    The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U) from the secretome of human endothelial cells. The angiogenic effect of the endothelia...

  20. Secretion of nerve growth factor, brain-derived neurotrophic factor, and glial cell-line derived neurotrophic factor in co-culture of four cell types in cerebrospinal fluid-containing medium

    Institute of Scientific and Technical Information of China (English)

    Sanjiang Feng; Minghua Zhuang; Rui Wu

    2012-01-01

    The present study co-cultured human embryonic olfactory ensheathing cells, human Schwann cells, human amniotic epithelial cells and human vascular endothelial cells in complete culture medium- containing cerebrospinal fluid. Enzyme linked immunosorbent assay was used to detect nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor secretion in the supernatant of co-cultured cells. Results showed that the number of all cell types reached a peak at 7–10 days, and the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor peaked at 9 days. Levels of secreted nerve growth factor were four-fold higher than brain-derived neurotrophic factor, which was three-fold higher than glial cell line-derived neurotrophic factor. Increasing concentrations of cerebrospinal fluid (10%, 20% and 30%) in the growth medium caused a decrease of neurotrophic factor secretion. Results indicated co-culture of human embryonic olfactory ensheathing cells, human Schwann cells, human amniotic epithelial cells and human vascular endothelial cells improved the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor. The reduction of cerebrospinal fluid extravasation at the transplant site after spinal cord injury is beneficial for the survival and secretion of neurotrophic factors from transplanted cells.

  1. The effect of choosing three different C factor formulae derived from NDVI on a fully raster-based erosion modelling

    Science.gov (United States)

    Sulistyo, Bambang

    2016-11-01

    The research was aimed at studying the efect of choosing three different C factor formulae derived from NDVI on a fully raster-based erosion modelling of The USLE using remote sensing data and GIS technique. Methods applied was by analysing all factors affecting erosion such that all data were in the form of raster. Those data were R, K, LS, C and P factors. Monthly R factor was evaluated based on formula developed by Abdurachman. K factor was determined using modified formula used by Ministry of Forestry based on soil samples taken in the field. LS factor was derived from Digital Elevation Model. Three C factors used were all derived from NDVI and developed by Suriyaprasit (non-linear) and by Sulistyo (linear and non-linear). P factor was derived from the combination between slope data and landcover classification interpreted from Landsat 7 ETM+. Another analysis was the creation of map of Bulk Density used to convert erosion unit. To know the model accuracy, model validation was done by applying statistical analysis and by comparing Emodel with Eactual. A threshold value of ≥ 0.80 or ≥ 80% was chosen to justify. The research result showed that all Emodel using three formulae of C factors have coeeficient of correlation value of > 0.8. The results of analysis of variance showed that there was significantly difference between Emodel and Eactual when using C factor formula developed by Suriyaprasit and Sulistyo (non-linear). Among the three formulae, only Emodel using C factor formula developed by Sulistyo (linear) reached the accuracy of 81.13% while the other only 56.02% as developed by Sulistyo (nonlinear) and 4.70% as developed by Suriyaprasit, respectively.

  2. Brain-derived neurotrophic factor from bone marrow-derived cells promotes post-injury repair of peripheral nerve.

    Directory of Open Access Journals (Sweden)

    Yoshinori Takemura

    Full Text Available Brain-derived neurotrophic factor (BDNF stimulates peripheral nerve regeneration. However, the origin of BNDF and its precise effect on nerve repair have not been clarified. In this study, we examined the role of BDNF from bone marrow-derived cells (BMDCs in post-injury nerve repair. Control and heterozygote BDNF knockout mice (BDNF+/- received a left sciatic nerve crush using a cerebral blood clip. Especially, for the evaluation of BDNF from BMDCs, studies with bone marrow transplantation (BMT were performed before the injury. We evaluated nerve function using a rotarod test, sciatic function index (SFI, and motor nerve conduction velocity (MNCV simultaneously with histological nerve analyses by immunohistochemistry before and after the nerve injury until 8 weeks. BDNF production was examined by immunohistochemistry and mRNA analyses. After the nerve crush, the controls showed severe nerve dysfunction evaluated at 1 week. However, nerve function was gradually restored and reached normal levels by 8 weeks. By immunohistochemistry, BDNF expression was very faint before injury, but was dramatically increased after injury at 1 week in the distal segment from the crush site. BDNF expression was mainly co-localized with CD45 in BMDCs, which was further confirmed by the appearance of GFP-positive cells in the BMT study. Variant analysis of BDNF mRNA also confirmed this finding. BDNF+/- mice showed a loss of function with delayed histological recovery and BDNF+/+→BDNF+/- BMT mice showed complete recovery both functionally and histologically. These results suggested that the attenuated recovery of the BDNF+/- mice was rescued by the transplantation of BMCs and that BDNF from BMDCs has an essential role in nerve repair.

  3. Dynamic plasticity: the role of glucocorticoids, brain-derived neurotrophic factor and other trophic factors.

    Science.gov (United States)

    Gray, J D; Milner, T A; McEwen, B S

    2013-06-03

    Brain-derived neurotrophic factor (BDNF) is a secreted protein that has been linked to numerous aspects of plasticity in the central nervous system (CNS). Stress-induced remodeling of the hippocampus, prefrontal cortex and amygdala is coincident with changes in the levels of BDNF, which has been shown to act as a trophic factor facilitating the survival of existing and newly born neurons. Initially, hippocampal atrophy after chronic stress was associated with reduced BDNF, leading to the hypothesis that stress-related learning deficits resulted from suppressed hippocampal neurogenesis. However, recent evidence suggests that BDNF also plays a rapid and essential role in regulating synaptic plasticity, providing another mechanism through which BDNF can modulate learning and memory after a stressful event. Numerous reports have shown BDNF levels are highly dynamic in response to stress, and not only vary across brain regions but also fluctuate rapidly, both immediately after a stressor and over the course of a chronic stress paradigm. Yet, BDNF alone is not sufficient to effect many of the changes observed after stress. Glucocorticoids and other molecules have been shown to act in conjunction with BDNF to facilitate both the morphological and molecular changes that occur, particularly changes in spine density and gene expression. This review briefly summarizes the evidence supporting BDNF's role as a trophic factor modulating neuronal survival, and will primarily focus on the interactions between BDNF and other systems within the brain to facilitate synaptic plasticity. This growing body of evidence suggests a more nuanced role for BDNF in stress-related learning and memory, where it acts primarily as a facilitator of plasticity and is dependent upon the coactivation of glucocorticoids and other factors as the determinants of the final cellular response.

  4. A Hierarchical Three-Factor Model of Inattention-Hyperactivity-Impulsivity Derived from the Attention Problems Syndrome of the Teacher's Report Form

    Science.gov (United States)

    Dumenci, Levent; McConaughy, Stephanie H.; Achenbach, Thomas M.

    2005-01-01

    Confirmatory factor analysis was used to test three plausible conceptualizations of Inattention-Hyperactivity-Impulsivity (Ina-H-I) derived from the Attention Problems syndrome of the Teacher's Report Form (TRF): (a) a one factor model representing a general Ina-H-I factor; (b) a correlated two-factor model representing the Inattention (Ina) and…

  5. [Complaint analysis derived from surgical practice].

    Science.gov (United States)

    Fajardo-Dolci, Germán; Rodríguez-Suárez, Francisco Javier; Campos-Castolo, Esther Mahuina; Carrillo-Jaimes, Arturo; Zavala-Suárez, Etelvina; Aguirre-Gas, Héctor Gerardo

    2009-01-01

    This study reports on the analysis of medical complaints presented to the National Commission on Medical Arbitration (Comisión Nacional de Arbitraje Médico, CONAMED) between June 1996 and December 2007 to determine its magnitude and to identify the causes of safety problems in medical care. Out of 182,407 complaints presented to CONAMED, 87% were resolved by the Office of Orientation and Management. The remaining 18,443 complaints were presented to the Council Directorate. Of those cases, 48% were resolved by an agreement between the complainants and the physicians, 31% were not resolved by this method, and 3% were irresolute complaints. The highest frequency of complaints was registered in the Federal District (Distrito Federal) and the State of México (Estado de México), mainly corresponding to social security institutions and private hospitals. Among the nine most frequently involved specialties, six were surgical specialties. Malpractice was identified in 25% of all cases. The principal demands of those making complaints were the refunding of expenses in patient medical care (51%) and indemnification (40%) and, in those, the average amount of payments was 4.6 times greater. Due to the incidence of medical complaints, it was reasonable to investigate the causes and to take preventive and corrective actions required for its decrease. It was proposed to the Mexican Academy of Surgery that this organization should use their educational leadership and assume the vanguard in the dissemination and promotion of the WHO plan "Safe Surgery Saves Lives" and the implementation in Mexico of the "Surgical Safety Checklist."

  6. Glial cell derived neurotrophic factor induces spermatogonial stem cell marker genes in chicken mesenchymal stem cells.

    Science.gov (United States)

    Boozarpour, Sohrab; Matin, Maryam M; Momeni-Moghaddam, Madjid; Dehghani, Hesam; Mahdavi-Shahri, Naser; Sisakhtnezhad, Sajjad; Heirani-Tabasi, Asieh; Irfan-Maqsood, Muhammad; Bahrami, Ahmad Reza

    2016-06-01

    Mesenchymal stem cells (MSCs) are known with the potential of multi-lineage differentiation. Advances in differentiation technology have also resulted in the conversion of MSCs to other kinds of stem cells. MSCs are considered as a suitable source of cells for biotechnology purposes because they are abundant, easily accessible and well characterized cells. Nowadays small molecules are introduced as novel and efficient factors to differentiate stem cells. In this work, we examined the potential of glial cell derived neurotrophic factor (GDNF) for differentiating chicken MSCs toward spermatogonial stem cells. MSCs were isolated and characterized from chicken and cultured under treatment with all-trans retinoic acid (RA) or glial cell derived neurotrophic factor. Expression analysis of specific genes after 7days of RA treatment, as examined by RT-PCR, proved positive for some germ cell markers such as CVH, STRA8, PLZF and some genes involved in spermatogonial stem cell maintenance like BCL6b and c-KIT. On the other hand, GDNF could additionally induce expression of POU5F1, and NANOG as well as other genes which were induced after RA treatment. These data illustrated that GDNF is relatively more effective in diverting chicken MSCs towards Spermatogonial stem cell -like cells in chickens and suggests GDNF as a new agent to obtain transgenic poultry, nevertheless, exploitability of these cells should be verified by more experiments.

  7. Adenoviral E4 Gene Stimulates Secretion of Pigmental Epithelium Derived Factor (PEDF) that Maintains Long-term Survival of Human Glomerulus-derived Endothelial Cells*

    Science.gov (United States)

    Jerebtsova, Marina; Kumari, Namita; Obuhkov, Yuri; Nekhai, Sergei

    2012-01-01

    Renal glomerular endothelial cells are specialized cells with an important role in physiological filtration and glomerular disease. However, maintenance of human primary endothelial cells requires stimulation with serum and growth factors that often results in modification of the cells properties. Previously, expression of early adenovirus region E4 was shown to help maintaining long-term survival of human endothelial cells in serum free media without addition of growth factors. In the current study, we showed that media conditioned with human epithelial cells stably transfected with Ad E4 region also supported survival of human glomerulus-derived endothelial cells in serum-free media. Mass-spectrometry analysis of the conditioned media identified pigmental epithelium derived factor (PEDF) as a major component of the conditioned media. PEDF expression in 293-E4 cells was validated by RT-PCR, Western blot and ELISA analysis. PEDF expression was detected in mouse glomeruli. Supplementation with recombinant PEDF supported survival of primary endothelial cells and the cells transformed with SV40 large T antigen in serum-free media, and extended the life-span of both cell cultures. PEDF did not inhibit FGF-2 stimulated growth and tubulogenesis of endothelial cells. Thus we demonstrated that adenoviral E4 region stimulated expression and secretion of PEDF by human renal epithelial cells that acted as a survival factor for glomerulus-derived endothelial cells. PMID:22915824

  8. Decreased plasma brain-derived neurotrophic factor and vascular endothelial growth factor concentrations during military training.

    Directory of Open Access Journals (Sweden)

    Go Suzuki

    Full Text Available Decreased concentrations of plasma brain-derived neurotrophic factor (BDNF and serum BDNF have been proposed to be a state marker of depression and a biological indicator of loaded psychosocial stress. Stress evaluations of participants in military mission are critically important and appropriate objective biological parameters that evaluate stress are needed. In military circumstances, there are several problems to adopt plasma BDNF concentration as a stress biomarker. First, in addition to psychosocial stress, military missions inevitably involve physical exercise that increases plasma BDNF concentrations. Second, most participants in the mission do not have adequate quality or quantity of sleep, and sleep deprivation has also been reported to increase plasma BDNF concentration. We evaluated plasma BDNF concentrations in 52 participants on a 9-week military mission. The present study revealed that plasma BDNF concentration significantly decreased despite elevated serum enzymes that escaped from muscle and decreased quantity and quality of sleep, as detected by a wearable watch-type sensor. In addition, we observed a significant decrease in plasma vascular endothelial growth factor (VEGF during the mission. VEGF is also neurotrophic and its expression in the brain has been reported to be up-regulated by antidepressive treatments and down-regulated by stress. This is the first report of decreased plasma VEGF concentrations by stress. We conclude that decreased plasma concentrations of neurotrophins can be candidates for mental stress indicators in actual stressful environments that include physical exercise and limited sleep.

  9. A new FACS approach isolates hESC derived endoderm using transcription factors.

    Directory of Open Access Journals (Sweden)

    Yuqiong Pan

    Full Text Available We show that high quality microarray gene expression profiles can be obtained following FACS sorting of cells using combinations of transcription factors. We use this transcription factor FACS (tfFACS methodology to perform a genomic analysis of hESC-derived endodermal lineages marked by combinations of SOX17, GATA4, and CXCR4, and find that triple positive cells have a much stronger definitive endoderm signature than other combinations of these markers. Additionally, SOX17(+ GATA4(+ cells can be obtained at a much earlier stage of differentiation, prior to expression of CXCR4(+ cells, providing an important new tool to isolate this earlier definitive endoderm subtype. Overall, tfFACS represents an advancement in FACS technology which broadly crosses multiple disciplines, most notably in regenerative medicine to redefine cellular populations.

  10. Human Factors Analysis in Software Engineering

    Institute of Scientific and Technical Information of China (English)

    Xu Ren-zuo; Ma Ruo-feng; Liu Li-na; Xiong Zhong-wei

    2004-01-01

    The general human factors analysis analyzes human functions, effects and influence in a system. But in a narrow sense, it analyzes human influence upon the reliability of a system, it includes traditional human reliability analysis, human error analysis, man-machine interface analysis, human character analysis, and others. A software development project in software engineering is successful or not to be completely determined by human factors. In this paper, we discuss the human factors intensions, declare the importance of human factors analysis for software engineering by listed some instances. At last, we probe preliminarily into the mentality that a practitioner in software engineering should possess.

  11. Correlation between Nerve Growth Factor (NGF with Brain Derived Neurotropic Factor (BDNF in Ischemic Stroke Patient

    Directory of Open Access Journals (Sweden)

    Joko Widodo

    2016-05-01

    Full Text Available Background: The neurotrophins nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF is a family of polypeptides that play critical role during neuronal development, appear to mediate protective role on neurorepair in ischemic stroke. Naturally in adult brain neurorepair process consist of: angiogenesis, neurogenesis, and neuronal plasticity, it can also be stimulated by endogenous neurorepair. In this study we observed correlation between NGF and BDNF ischemic stroke patient’s onset: 7-30 and over 30 days. Methods: This is cross sectional study on 46 subjects aged 38 – 74 years old with ischemic stroke from The Indonesian Central Hospital of Army Gatot Subroto Jakarta. Diagnosis of ischemic stroke was made using clinical examination and magnetic resonance imaging (MRI by neurologist. Subjects were divided into 2 groups based on stroke onset: 7 – 30 days (Group A: 19 subjects and > 30 days (Group B: 27 Subjects. Serum NGF levels were measured with ELISA method and BDNF levels were measured using multiplex method with Luminex Magpix. Results: Levels of NGF and BDNF were significantly different between onset group A and B (NGF p= 0.022, and BDNF p=0.008, with mean levels NGF in group A higher than group B, indicating that BDNF levels is lower in group A than group B. There was no significant correlation between NGF and BDNF levels in all groups. Conclusion: The variations in neurotrophic factor levels reflect an endogenous attempt at neuroprotection against biochemical and molecular changes after ischemic stroke. NGF represents an early marker of brain injury while BDNF recovery is most prominent during the first 14 days after onsite but continuous for more than 30 days. There is no significant correlation between NGF and BDNF in each group.  

  12. Factors Involved in Extracellular Matrix Turnover in Human Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Gregori Casals

    2013-11-01

    Full Text Available Background: The molecular mechanisms by which myocardial ischemia translates into ventricular remodeling remain unclear. Methods: We investigated whether hypoxia and proinflammatory cytokines are specific inducers of remodeling signals in an in vitro model of cultured adult human ventricular myocytes (AC16 cells. Results:Hypoxia modified the ratio of matrix remodeling factors by increasing the aminoterminal propeptide of type III procollagen (PIIINP and reducing tissue inhibitor of matrix metalloproteinase type 1 (TIMP-1 secretion in AC16 cells. These effects, however, were not associated with either modifications in expression of matrix metalloproteinase type 2, collagen-I or metalloproteinase activity. Hypoxia does, actually increase the production of the cardiac antifibrogenic growth factors, Apelin and VEGF, through an Hypoxia Inducible Factor type 1-dependent mechanism. Concerning proinflammatory signaling pathways, IL1β emerged as a powerful inducer of matrix turnover, since it significantly enhanced PIIINP, TIMP-1 and hyaluronic acid production and increased metalloproteinase activity. In contrast, TNFα did not modify matrix turnover but markedly induced the production of Apelin and VEGF. Conclusion: Hypoxia and increased TNFα activity likely exert cardioprotective actions by activating the cardiac antifibrogenic factors Apelin and VEGF. In contrast, IL1β is a strong promoter of interstitial collagen remodeling that may contribute to ventricular dilation and heart failure in the ischemic myocardium.

  13. Distinctive diet-tissue isotopic discrimination factors derived from the exclusive bamboo-eating giant panda.

    Science.gov (United States)

    Han, Han; Wei, Wei; Nie, Yonggang; Zhou, Wenliang; Hu, Yibo; Wu, Qi; Wei, Fuwen

    2016-11-01

    Stable isotope analysis is very useful in animal ecology, especially in diet reconstruction and trophic studies. Differences in isotope ratios between consumers and their diet, termed discrimination factors, are essential for studies of stable isotope ecology and are species-specific and tissue-specific. Given the specialized bamboo diet and clear foraging behavior, here, we calculated discrimination factors for carbon and nitrogen isotopes from diet to tissues (tooth enamel, hair keratin and bone collagen) for the giant panda (Ailuropoda melanoleuca), a species derived from meat-eating ancestors. Our results showed that carbon discrimination factor obtained from giant panda tooth enamel (ε (13) Cdiet-enamel = 10.0‰) and nitrogen discrimination factors from hair keratin (Δ(15) Ndiet-hair = 2.2‰) and bone collagen (Δ(15) Ndiet-collagen = 2.3‰) were lower, and carbon discrimination factors from hair keratin (Δ(13) Cdiet-hair = 5.0‰) and bone collagen (Δ(13) Cdiet-collagen = 6.1‰) were higher than those of other mammalian carnivores, omnivores and herbivores. Such distinctive values are likely the result of a low-nutrient and specialized bamboo diet, carnivore-like digestive system and exceptionally low metabolism in giant pandas. © 2016 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  14. A factor analysis to detect factors influencing building national brand

    Directory of Open Access Journals (Sweden)

    Naser Azad

    Full Text Available Developing a national brand is one of the most important issues for development of a brand. In this study, we present factor analysis to detect the most important factors in building a national brand. The proposed study uses factor analysis to extract the most influencing factors and the sample size has been chosen from two major auto makers in Iran called Iran Khodro and Saipa. The questionnaire was designed in Likert scale and distributed among 235 experts. Cronbach alpha is calculated as 84%, which is well above the minimum desirable limit of 0.70. The implementation of factor analysis provides six factors including “cultural image of customers”, “exciting characteristics”, “competitive pricing strategies”, “perception image” and “previous perceptions”.

  15. Measurement Bias Detection through Factor Analysis

    Science.gov (United States)

    Barendse, M. T.; Oort, F. J.; Werner, C. S.; Ligtvoet, R.; Schermelleh-Engel, K.

    2012-01-01

    Measurement bias is defined as a violation of measurement invariance, which can be investigated through multigroup factor analysis (MGFA), by testing across-group differences in intercepts (uniform bias) and factor loadings (nonuniform bias). Restricted factor analysis (RFA) can also be used to detect measurement bias. To also enable nonuniform…

  16. Factorized molecular wave functions: Analysis of the nuclear factor

    Energy Technology Data Exchange (ETDEWEB)

    Lefebvre, R., E-mail: roland.lefebvre@u-psud.fr [Institut des Sciences Moléculaires d’ Orsay, Bâtiment 350, UMR8214, CNRS- Université. Paris-Sud, 91405 Orsay, France and Sorbonne Universités, UPMC Univ Paris 06, UFR925, F-75005 Paris (France)

    2015-06-07

    The exact factorization of molecular wave functions leads to nuclear factors which should be nodeless functions. We reconsider the case of vibrational perturbations in a diatomic species, a situation usually treated by combining Born-Oppenheimer products. It was shown [R. Lefebvre, J. Chem. Phys. 142, 074106 (2015)] that it is possible to derive, from the solutions of coupled equations, the form of the factorized function. By increasing artificially the interstate coupling in the usual approach, the adiabatic regime can be reached, whereby the wave function can be reduced to a single product. The nuclear factor of this product is determined by the lowest of the two potentials obtained by diagonalization of the potential matrix. By comparison with the nuclear wave function of the factorized scheme, it is shown that by a simple rectification, an agreement is obtained between the modified nodeless function and that of the adiabatic scheme.

  17. Hepatoma-derived growth factor predicts unfavorable prognosis of epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Liu XJ

    2015-08-01

    Full Text Available Xue-jun Liu,1 Wen-lian Liu,1 Fang-mei Yang,1 Xiao-qing Yang,2 Xiao-fei Lu3 1Department of Obstetrics, Linyi Hospital Affiliated to Shandong University, Linyi City, 2Department of Pathology, Qianfoshan Hospital Affiliated to Shandong University, Jinan City, 3Department of General Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan City, People’s Republic of China Aim: To evaluate the expression and clinical significance of hepatoma-derived growth factor (HDGF in epithelial ovarian cancer (EOC. Background: Recent studies have demonstrated that HDGF overexpression correlates to the progression and poor prognosis in several kinds of cancers. However, the clinical significance and prognostic value of HDGF in EOC have not been investigated. Methods: Expression of HDGF was visualized by immunohistology and then the cohort was divided into higher- and lower-expression groups. The correlation between HDGF and clinicopathologic factors was analyzed by χ2 test. The prognostic value of HDGF was assessed by univariate analysis with Kaplan–Meier method, and by multivariate analysis with Cox-regression model. With experiments in vitro, HDGF expression in ovarian cancer cell lines was detected by immunoblotting. Results: Higher HDGF expression rate was 52.76% in EOC. HDGF expression was significantly associated with lymphatic metastasis (P=0.006. Higher HDGF expression was closely correlated to poorer 5-year overall survival rate with univariate analysis (P=0.003, and was identified as an independent prognostic factor with multivariate analysis (P=0.007. With experiments in vitro, HDGF was proved to exist in all ovarian cancer cell lines with different expression levels. Conclusion: HDGF expression correlates to unfavorable prognosis and can be considered as an independent prognostic factor, indicating that HDGF may be a promising potential molecular drug target. Keywords: biomarker, HDGF, knockdown, invasion

  18. Regulatory and Functional Connection of Microphthalmia-Associated Transcription Factor and Anti-Metastatic Pigment Epithelium Derived Factor in Melanoma

    Directory of Open Access Journals (Sweden)

    Asunción Fernández-Barral

    2014-06-01

    Full Text Available Pigment epithelium-derived factor (PEDF, a member of the serine protease inhibitor superfamily, has potent anti-metastatic effects in cutaneous melanoma through its direct actions on endothelial and melanoma cells. Here we show that PEDF expression positively correlates with microphthalmia-associated transcription factor (MITF in melanoma cell lines and human samples. High PEDF and MITF expression is characteristic of low aggressive melanomas classified according to molecular and pathological criteria, whereas both factors are decreased in senescent melanocytes and naevi. Importantly, MITF silencing down-regulates PEDF expression in melanoma cell lines and primary melanocytes, suggesting that the correlation in the expression reflects a causal relationship. In agreement, analysis of Chromatin immunoprecipitation coupled to high throughput sequencing (ChIP-seq data sets revealed three MITF binding regions within the first intron of SERPINF1, and reporter assays demonstrated that the binding of MITF to these regions is sufficient to drive transcription. Finally, we demonstrate that exogenous PEDF expression efficiently halts in vitro migration and invasion, as well as in vivo dissemination of melanoma cells induced by MITF silencing. In summary, these results identify PEDF as a novel transcriptional target of MITF and support a relevant functional role for the MITF-PEDF axis in the biology of melanoma.

  19. Vascular Endothelial Growth Factor and Brain-Derived Neurotropic Factor Levels in Ischemic Stroke Subject

    Directory of Open Access Journals (Sweden)

    Andri Hidayat

    2016-08-01

    Full Text Available BACKGROUND: Vascular endothelial growth factor (VEGF and brain-derived neurotropic factor (BDNF present during early neuronal development and play important roles in the process of neurorepairing includes angiogenesis, neurogenesis and neuronal plasticity after ischemic stroke. In this study, we observed VEGF and BDNF levels of subjects with ischemic stroke in different onset time. METHODS: A cross sectional study was designed. Study subjects were 51 ischemic stroke subjects, aged 30-80 years old, recruited from Gatot Subroto Army Central Hospital, Jakarta, Indonesia. Ischemic stroke was diagnosed by neurologist, based on clinical examination and magnetic resonance imaging (MRI result. Subjects were divided into 3 groups based on onset time of stroke: 30 days (Group C. VEGF and BDNF levels from serum were measured using lumine Magpix. The data was analyzed for comparison and correlation. RESULTS: VEGF and BDNF levels of group B and C were significantly different with p=0.034 and p=0.007, respectively. Group B had the highest VEGF levels, whereas Group C had the highest BDNF level. VEGF and BDNF levels in each group were not significantly correlated. CONCLUSION: Each stage of time after ischemic stroke has different recovery activities like angiogenesis, neurogenesis and plasticity. Angiogenesis process was optimum in 7-30 days after onset. in more than 30 days onset, Low VEGF with high BDNF have important role in a long period of time after the onset of stroke in the regeneration and repair, such as maintaining neuronal survival and plasticity. KEYWORDS: ischemic stroke, VEGF, BDNF

  20. The Effect of Secretory Factors of Adipose-Derived Stem Cells on Human Keratinocytes

    Directory of Open Access Journals (Sweden)

    Soo-Wan Nam

    2012-01-01

    Full Text Available The beneficial effects of adipose-derived stem cell conditioned medium (ADSC-CM on skin regeneration have been reported. Although the mechanism of how ADSC-CM promotes skin regeneration is unclear, ADSC-CM contained various growth factors and it is an excellent raw material for skin treatment. ADSC-CM produced in a hypoxia condition of ADSC—in other words, Advanced Adipose-Derived Stem cell Protein Extract (AAPE—has great merits for skin regeneration. In this study, human primary keratinocytes (HKs, which play fundamental roles in skin tissue, was used to examine how AAPE affects HK. HK proliferation was significantly higher in the experimental group (1.22 μg/mL than in the control group. DNA gene chip demonstrated that AAPE in keratinocytes (p < 0.05 notably affected expression of 290 identified transcripts, which were associated with cell proliferation, cycle and migration. More keratinocyte wound healing and migration was shown in the experimental group (1.22 μg/mL. AAPE treatment significantly stimulated stress fiber formation, which was linked to the RhoA-ROCK pathway. We identified 48 protein spots in 2-D gel analysis and selected proteins were divided into 64% collagen components and 30% non-collagen components as shown by the MALDI-TOF analysis. Antibody array results contained growth factor/cytokine such as HGF, FGF-1, G-CSF, GM-CSF, IL-6, VEGF, and TGF-β3 differing from that shown by 2-D analysis. Conclusion: AAPE activates HK proliferation and migration. These results highlight the potential of the topical application of AAPE in the treatment of skin regeneration.

  1. Glycosylation analysis and protein structure determination of murine fetal antigen 1 (mFA1)--the circulating gene product of the delta-like protein (dlk), preadipocyte factor 1 (Pref-1) and stromal-cell-derived protein 1 (SCP-1) cDNAs

    DEFF Research Database (Denmark)

    Krogh, T N; Bachmann, E; Teisner, B

    1997-01-01

    By means of sequence analysis, murine fetal antigen 1 (mFA1) isolated from Mus musculus amniotic fluid was shown to be the circulating protein of the delta-like protein, stromal-cell-derived protein 1 (SCP-1) and preadipocyte factor 1 (Pref-1) gene products. The protein contains 36 cysteine resid......, Ser193 and fucose at Thr201) was tentatively ascertained by combining Edman degradation and MALDI-MS. The results presented shows mFA1 to be the circulating heterogeneous cleavage products of the membrane-bound protein encoded by the murine cDNAs dlk, pref-1 and SCP-1....

  2. Physical (in)activity and endothelium-derived constricting factors: overlooked adaptations

    National Research Council Canada - National Science Library

    D. H. J. Thijssen; G. A. Rongen; P. Smits; M. T. E. Hopman

    2008-01-01

    .... In response to physical stimuli, the endothelium varies its release of circulating vasoactive substances and serves as a source of local and systemic endothelium-derived dilator and vasoconstrictor factors...

  3. Serum brain-derived neurotrophic factor (BDNF) levels in schizophrenia: A systematic review

    National Research Council Canada - National Science Library

    Cui, Huiru; Jin, Yi; Wang, Jijun; Weng, Xuchu; Li, Chunbo

    2012-01-01

    There is increasing interest in the role of brain-derived neurotrophic factor (BDNF) in the onset and course of schizophrenia, but there are conflicting reports about serum levels of BDNF in patients with schizophrenia...

  4. Gene Transfer and Expression of Platelet-derived Growth Factors Modulate Periodontal Cellular Activity

    OpenAIRE

    Zhu, Z.; Lee, C. S.; Tejeda, K.M.; Giannobile, W.V.

    2001-01-01

    Platelet-derived growth factor (PDGF) is a potent stimulator of wound healing. PDGF gene therapy may promote greater periodontal regeneration than local protein application, due to sustained growth factor delivery to the target tissue. This investigation tested the ability of recombinant adenoviruses (rAds) encoding PDGF-A or PDGF-1308 (a PDGF-A dominant-negative mutant that disrupts endogenous PDGF bioactivity) to affect cells derived from the periodontium. Osteoblasts, periodontal ligament ...

  5. Statistical inference of Minimum Rank Factor Analysis

    NARCIS (Netherlands)

    Shapiro, A; Ten Berge, JMF

    2002-01-01

    For any given number of factors, Minimum Rank Factor Analysis yields optimal communalities for an observed covariance matrix in the sense that the unexplained common variance with that number of factors is minimized, subject to the constraint that both the diagonal matrix of unique variances and the

  6. Statistical inference of Minimum Rank Factor Analysis

    NARCIS (Netherlands)

    Shapiro, A; Ten Berge, JMF

    For any given number of factors, Minimum Rank Factor Analysis yields optimal communalities for an observed covariance matrix in the sense that the unexplained common variance with that number of factors is minimized, subject to the constraint that both the diagonal matrix of unique variances and the

  7. PROGNOSTIC FACTORS ANALYSIS FOR STAGEⅠ RECTAL CANCER

    Institute of Scientific and Technical Information of China (English)

    武爱文; 顾晋; 薛钟麒; 王怡; 徐光炜

    2001-01-01

    To explore the death-related factors of stageⅠrectal cancer patients. Methods: 89 cases of stage I rectal cancer patients between 1985 and 2000 were retrospectively studied for prognostic factors. Factors including age, gender, tumor size, circumferential occupation, gross type, pathological type, depth of tumor invasion, surgical procedure, adjuvant chemotherapy and postoperative complication were chosen for cox multivariate analysis (forward procedure) using Spss software (10.0 version). Results: multivariate analysis demonstrated that muscular invasion was an independent negative prognostic factor for stageⅠrectal cancer patients (P=0.003). Conclusion: Muscular invasion is a negative prognostic factor for stage I rectal cancer patients.

  8. Factors derived from the intrahospitable laboratories that cause stress in nursing students.

    Science.gov (United States)

    Basso Musso, Liliana; Ardiles Vargas, Bárbara; Bernal Torres, Milenca; Canovas Del Canto, María José; González Meléndez, Catherin; Kroff Balloqui, María Francisca; Soto Cornejo, Angélica

    2008-01-01

    Quantitative, correlation cross-sectional study with descriptive analysis, whose objective was to assess the factors derived from the intra-hospitable laboratories that affect the stress appearance in Infirmary students. The sample consisted of 129 students, which voluntarily acceded to answer questionnaires Evaluative Scale de Hamilton for the Anxiety, validated in 2003, and Questionnaire KEZKAK, both adapted by the investigating group. The obtained data was processed through Microsoft Excel program, appearing: the 100% of the students presented Stress. From the manifestations of Stress, the tensional anxiety and insomnia appear with the biggest percentages. From the Stress producing Factors, in Student's competitions: "having errors on its work and harming the patient", and in the Educational "receiving contradictory orders" are the ones that present greater frequency of intensity, being the Educational factor the preponderant in the appearance of stress. One concludes that is necessary to adapt the educational positions of a guardian in the clinical practices given greater emphasis to the support that will have to be lend to student, with the purpose of diminishing stress an favoring the learning.

  9. Kernel Factor Analysis Algorithm with Varimax

    Institute of Scientific and Technical Information of China (English)

    Xia Guoen; Jin Weidong; Zhang Gexiang

    2006-01-01

    Kernal factor analysis (KFA) with varimax was proposed by using Mercer kernel function which can map the data in the original space to a high-dimensional feature space, and was compared with the kernel principle component analysis (KPCA). The results show that the best error rate in handwritten digit recognition by kernel factor analysis with varimax (4.2%) was superior to KPCA (4.4%). The KFA with varimax could more accurately image handwritten digit recognition.

  10. Stromal derived factor-1 exerts differential regulation on distinct cortical cell populations in vitro

    Directory of Open Access Journals (Sweden)

    Zeef Leo

    2007-04-01

    Full Text Available Abstract Background Stromal derived factor (SDF-1, an alpha chemokine, is a widely known chemoattractant in the immune system. A growing body of evidence now suggests multiple regulatory roles for SDF-1 in the developing nervous system. Results To investigate the role of SDF-1 signaling in the growth and differentiation of cortical cells, we performed numerous in vitro experiments, including gene chip and quantitative RT-PCR analysis. Using SDF-1 medium and AMD3100, a receptor antagonist, we demonstrate that the chemokine signaling regulates key events during early cortical development. First, SDF-1 signaling maintains cortical progenitors in proliferation, possibly through a mechanism involving connexin 43 mediated intercellular coupling. Second, SDF-1 signaling upregulates the differentiation of cortical GABAergic neurons, independent of sonic signaling pathway. Third, SDF-1 enables the elongation and branching of axons of cortical glutamatergic neurons. Finally, cortical cultures derived from CXCR4-/- mutants show a close parallel to AMD3100 treatment with reduced cell proliferation and differentiation of GABAergic neurons. Conclusion Results from this study show that SDF-1 regulates distinct cortical cell populations in vitro.

  11. The role of dorsal root ganglia activation and brain-derived neurotrophic factor in multiple sclerosis.

    Science.gov (United States)

    Zhu, Wenjun; Frost, Emma E; Begum, Farhana; Vora, Parvez; Au, Kelvin; Gong, Yuewen; MacNeil, Brian; Pillai, Prakash; Namaka, Mike

    2012-08-01

    Multiple sclerosis (MS) is characterized by focal destruction of the white matter of the brain and spinal cord. The exact mechanisms underlying the pathophysiology of the disease are unknown. Many studies have shown that MS is predominantly an autoimmune disease with an inflammatory phase followed by a demyelinating phase. Recent studies alongside current treatment strategies, including glatiramer acetate, have revealed a potential role for brain-derived neurotrophic factor (BDNF) in MS. However, the exact role of BDNF is not fully understood. We used the experimental autoimmune encephalomyelitis (EAE) model of MS in adolescent female Lewis rats to identify the role of BDNF in disease progression. Dorsal root ganglia (DRG) and spinal cords were harvested for protein and gene expression analysis every 3 days post-disease induction (pdi) up to 15 days. We show significant increases in BDNF protein and gene expression in the DRG of EAE animals at 12 dpi, which correlates with peak neurological disability. BDNF protein expression in the spinal cord was significantly increased at 12 dpi, and maintained at 15 dpi. However, there was no significant change in mRNA levels. We show evidence for the anterograde transport of BDNF protein from the DRG to the dorsal horn of the spinal cord via the dorsal roots. Increased levels of BDNF within the DRG and spinal cord in EAE may facilitate myelin repair and neuroprotection in the CNS. The anterograde transport of DRG-derived BDNF to the spinal cord may have potential implications in facilitating central myelin repair and neuroprotection.

  12. Effect of platelet-derived growth factor on rabbit corneal wound healing.

    Science.gov (United States)

    Stern, M E; Waltz, K M; Beurerman, R W; Ghosn, C R; Mantras, C E; Nicolson, M; Assouline, M; Stern, K L; Wheeler, L A

    1995-01-01

    Human recombinant platelet-derived growth factor was evaluated with the use of wound healing models in New Zealand albino rabbits. The efficacy of the platelet-derived growth factor dimers, AA, AB, and BB, was determined in corneal reepithelialization and anterior keratectomy models which examined the healing response in the presence or absence of the basement membrane. All dimers increased the rate of wound healing in both models at 100 microg/ml when compared with control; however, the platelet-derived growth factor-BB isoform showed the most dramatic increase in both studies. The strength of the healing stroma after incision was evaluated by means of a tensile strength model. Histologic evaluation of the stromal wound area after 9 days of healing showed a marked increase in the number of keratocytes within the wound bed of the corneas treated with platelet-derived growth factor-BB when compared with control corneas. In addition, at 9 days, the epithelial plug was still present in the control corneas but had been extruded to the surface by the granulation tissue in the platelet-derived growth factor-BB-treated corneas. These results are indicative of a more advanced stage of healing in treated versus control wounds at 9 days after the operation. A 30% increase in corneal tensile strength versus control was noted after 21 days of healing. Finally, in an in vitro gel contraction assay, platelet-derived growth factor exhibited a dose-dependent effect on the contraction of fibroblasts for doses ranging from 0.01 to 10 ng/ml. These results indicate that platelet-derived growth factor is active in the corneal wound healing process.

  13. A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor.

    Science.gov (United States)

    Szuhany, Kristin L; Bugatti, Matteo; Otto, Michael W

    2015-01-01

    Consistent evidence indicates that exercise improves cognition and mood, with preliminary evidence suggesting that brain-derived neurotrophic factor (BDNF) may mediate these effects. The aim of the current meta-analysis was to provide an estimate of the strength of the association between exercise and increased BDNF levels in humans across multiple exercise paradigms. We conducted a meta-analysis of 29 studies (N = 1111 participants) examining the effect of exercise on BDNF levels in three exercise paradigms: (1) a single session of exercise, (2) a session of exercise following a program of regular exercise, and (3) resting BDNF levels following a program of regular exercise. Moderators of this effect were also examined. Results demonstrated a moderate effect size for increases in BDNF following a single session of exercise (Hedges' g = 0.46, p exercise intensified the effect of a session of exercise on BDNF levels (Hedges' g = 0.59, p = 0.02). Finally, results indicated a small effect of regular exercise on resting BDNF levels (Hedges' g = 0.27, p = 0.005). When analyzing results across paradigms, sex significantly moderated the effect of exercise on BDNF levels, such that studies with more women showed less BDNF change resulting from exercise. Effect size analysis supports the role of exercise as a strategy for enhancing BDNF activity in humans, but indicates that the magnitude of these effects may be lower in females relative to males.

  14. Multiple factor analysis by example using R

    CERN Document Server

    Pagès, Jérôme

    2014-01-01

    Multiple factor analysis (MFA) enables users to analyze tables of individuals and variables in which the variables are structured into quantitative, qualitative, or mixed groups. Written by the co-developer of this methodology, Multiple Factor Analysis by Example Using R brings together the theoretical and methodological aspects of MFA. It also includes examples of applications and details of how to implement MFA using an R package (FactoMineR).The first two chapters cover the basic factorial analysis methods of principal component analysis (PCA) and multiple correspondence analysis (MCA). The

  15. Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury:a biomechanical evaluation

    Institute of Scientific and Technical Information of China (English)

    Zhong-jun Zhang; Ya-jun Li; Xiao-guang Liu; Feng-xiao Huang; Tie-jun Liu; Dong-mei Jiang; Xue-man Lv; Min Luo

    2015-01-01

    Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood stem cells. After 30 days, the maximum load, max-imum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neu-rotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These ifndings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, im-prove biomechanical properties, and contribute to the recovery after injury.

  16. Expression of brain derived-neurotrophic factor and granulocyte-colony stimulating factor in the urothelium: relation with voiding function

    OpenAIRE

    Yuk, Seung Mo; Shin, Ju Hyun; Song, Ki Hak; Na, Yong Gil; Lim, Jae Sung; Sul, Chong Koo

    2015-01-01

    Background We designed this experiment to elucidate the relationship between the expression of brain derived-neurotrophic factor (BDNF), the expression of granulocyte-colony stimulating factor (G-CSF), and the development of overactive bladder (OAB). In our previous study, the urothelium was observed to be more than a simple mechanosensory receptor and was found to be a potential therapeutic target for OAB. Moreover, neuregulin-1 and BDNF were found to be potential new biomarkers of OAB. Here...

  17. Electrodynamic Analysis of Dissipative Electromagnetic Materials Based on Fractional Derivative

    Institute of Scientific and Technical Information of China (English)

    TAN Kang-Bo; LIANG Chang-Hong; DANG Xiao-Jie

    2007-01-01

    The generalized Lagrangian is defined in a dissipative electromagnetic medium on the basis of the combination of dynamical analysis and fractional derivative.Lorentz medium models are obtained by formulating relevant EulerLagrange equations.The invariance is obtained subsequently by investigating the invariance of time variation in the system,and then the relation between the related Hamiltonian and electromagnetic energy density is investigated.Canonical equations are obtained eventually.The electrodynamic interpretation on dissipative electromagnetic systems is revesled.

  18. Stromal Cell-Derived Factor-1 Alpha Is Decreased in Women With Migraine With Aura.

    Science.gov (United States)

    Liman, Thomas G; Neeb, Lars; Rosinski, Jana; Reuter, Uwe; Endres, Matthias

    2016-09-01

    Endothelial dysfunction may contribute to the pathophysiology of migraine with aura. Stromal cell-derived factor-1 alpha (SDF-1α) is involved in the maintenance of endothelial integrity via mobilization of vascular stem cells. We sought to determine whether SDF-1α levels are decreased in women with MA. In this post hoc analysis of a case-cohort study, levels of SDF-1α were determined by enzyme-linked immunosorbent assay. Endothelial function was assessed using peripheral arterial tonometry. Arterial stiffness was assessed by fingertip tonometry derived and heart-rate-adjusted augmentation index (AI). Twenty-eight women with MA and 27 age-matched healthy women were included in this study. Levels of SDF-1α were significantly lower in women with MA compared to age- and risk factor-matched healthy women (1763 ± 281 vs 2013 ± 263 pg/mL, P = 0.006). SDF-1α levels were positively correlated with AI in healthy women (r = 0.49, P = 0.009), but not in women with MA (r = 0.05, P = 0.78). SDF-1α levels were negatively correlated with CD144-positive endothelial microparticles (EMP; r = -0.31, P = .02), and activated CD62E-positive EMP (r = -0.35, P = .01). Levels of SDF-1α are decreased in women with MA and are associated with EMPs as a surrogate marker of endothelial dysfunction. This might contribute to the pathophysiology and vascular risk in MA, but evidence from larger prospective studies is warranted. © 2016 American Headache Society.

  19. Monocytes-derived macrophages mediated stable expression of human brain-derived neurotrophic factor, a novel therapeutic strategy for neuroAIDS.

    Directory of Open Access Journals (Sweden)

    Jing Tong

    Full Text Available HIV-1 associated dementia remains a significant public health burden. Clinical and experimental research has shown that reduced levels of brain-derived neurotrophic factor (BDNF may be a risk factor for neurological complications associated with HIV-1 infection. We are actively testing genetically modified macrophages for their possible use as the cell-based gene delivery vehicle for the central nervous system (CNS. It can be an advantage to use the natural homing/migratory properties of monocyte-derived macrophages to deliver potentially neuroprotective BDNF into the CNS, as a non-invasive manner. Lentiviral-mediated gene transfer of human (hBDNF plasmid was constructed and characterized. Defective lentiviral stocks were generated by transient transfection of 293T cells with lentiviral transfer plasmid together with packaging and envelope plasmids. High titer lentiviral vector stocks were harvested and used to transduce human neuronal cell lines, primary cultures of human peripheral mononocyte-derived macrophages (hMDM and murine myeloid monocyte-derived macrophages (mMDM. These transduced cells were tested for hBDNF expression, stability, and neuroprotective activity. The GenomeLab GeXP Genetic Analysis System was used to evaluate transduced cells for any adverse effects by assessing gene profiles of 24 reference genes. High titer vectors were prepared for efficient transduction of neuronal cell lines, hMDM, and mMDM. Stable secretion of high levels of hBDNF was detected in supernatants of transduced cells using western blot and ELISA. The conditioned media containing hBDNF were shown to be protective to neuronal and monocytic cell lines from TNF-α and HIV-1 Tat mediated cytotoxicity. Lentiviral vector-mediated gene transduction of hMDM and mMDM resulted in high-level, stable expression of the neuroprotective factorBDNF in vitro. These findings form the basis for future research on the potential use of BDNF as a novel therapy for neuroAIDS.

  20. Monocytes-derived macrophages mediated stable expression of human brain-derived neurotrophic factor, a novel therapeutic strategy for neuroAIDS.

    Science.gov (United States)

    Tong, Jing; Buch, Shilpa; Yao, Honghong; Wu, Chengxiang; Tong, Hsin-I; Wang, Youwei; Lu, Yuanan

    2014-01-01

    HIV-1 associated dementia remains a significant public health burden. Clinical and experimental research has shown that reduced levels of brain-derived neurotrophic factor (BDNF) may be a risk factor for neurological complications associated with HIV-1 infection. We are actively testing genetically modified macrophages for their possible use as the cell-based gene delivery vehicle for the central nervous system (CNS). It can be an advantage to use the natural homing/migratory properties of monocyte-derived macrophages to deliver potentially neuroprotective BDNF into the CNS, as a non-invasive manner. Lentiviral-mediated gene transfer of human (h)BDNF plasmid was constructed and characterized. Defective lentiviral stocks were generated by transient transfection of 293T cells with lentiviral transfer plasmid together with packaging and envelope plasmids. High titer lentiviral vector stocks were harvested and used to transduce human neuronal cell lines, primary cultures of human peripheral mononocyte-derived macrophages (hMDM) and murine myeloid monocyte-derived macrophages (mMDM). These transduced cells were tested for hBDNF expression, stability, and neuroprotective activity. The GenomeLab GeXP Genetic Analysis System was used to evaluate transduced cells for any adverse effects by assessing gene profiles of 24 reference genes. High titer vectors were prepared for efficient transduction of neuronal cell lines, hMDM, and mMDM. Stable secretion of high levels of hBDNF was detected in supernatants of transduced cells using western blot and ELISA. The conditioned media containing hBDNF were shown to be protective to neuronal and monocytic cell lines from TNF-α and HIV-1 Tat mediated cytotoxicity. Lentiviral vector-mediated gene transduction of hMDM and mMDM resulted in high-level, stable expression of the neuroprotective factorBDNF in vitro. These findings form the basis for future research on the potential use of BDNF as a novel therapy for neuroAIDS.

  1. Platelet-derived growth factor and spatiotemporal cues induce development of vascularized bone tissue by adipose-derived stem cells.

    Science.gov (United States)

    Hutton, Daphne L; Moore, Erika M; Gimble, Jeffrey M; Grayson, Warren L

    2013-09-01

    Vasculature is essential to the functional integration of a tissue-engineered bone graft to enable sufficient nutrient delivery and viability after implantation. Native bone and vasculature develop through intimately coupled, tightly regulated spatiotemporal cell-cell signaling. The complexity of these developmental processes has been a challenge for tissue engineers to recapitulate, resulting in poor codevelopment of both bone and vasculature within a unified graft. To address this, we cultured adipose-derived stromal/stem cells (ASCs), a clinically relevant, single cell source that has been previously investigated for its ability to give rise to vascularized bone grafts, and studied the effects of initial spatial organization of cells, the temporal addition of growth factors, and the presence of exogenous platelet-derived growth factor-BB (PDGF-BB) on the codevelopment of bone and vascular tissue structures. Human ASCs were aggregated into multicellular spheroids via the hanging drop method before encapsulation and subsequent outgrowth in fibrin gels. Cellular aggregation substantially increased vascular network density, interconnectivity, and pericyte coverage compared to monodispersed cultures. To form robust vessel networks, it was essential to culture ASCs in a purely vasculogenic medium for at least 8 days before the addition of osteogenic cues. Physiologically relevant concentrations of exogenous PDGF-BB (20 ng/mL) substantially enhanced both vascular network stability and osteogenic differentiation. Comparisons with the bone morphogenetic protein-2, another pro-osteogenic and proangiogenic growth factor, indicated that this potential to couple the formation of both lineages might be unique to PDGF-BB. Furthermore, the resulting tissue structure demonstrated the close association of mineral deposits with pre-existing vascular structures that have been described for developing tissues. This combination of a single cell source with a potent induction factor

  2. Genomic Structure and Variation of Nuclear Factor (Erythroid-Derived 2-Like 2

    Directory of Open Access Journals (Sweden)

    Hye-Youn Cho

    2013-01-01

    Full Text Available High-density mapping of mammalian genomes has enabled a wide range of genetic investigations including the mapping of polygenic traits, determination of quantitative trait loci, and phylogenetic comparison. Genome sequencing analysis of inbred mouse strains has identified high-density single nucleotide polymorphisms (SNPs for investigation of complex traits, which has become a useful tool for biomedical research of human disease to alleviate ethical and practical problems of experimentation in humans. Nuclear factor (erythroid-derived 2-like 2 (NRF2 encodes a key host defense transcription factor. This review describes genetic characteristics of human NRF2 and its homologs in other vertebrate species. NRF2 is evolutionally conserved and shares sequence homology among species. Compilation of publically available SNPs and other genetic mutations shows that human NRF2 is highly polymorphic with a mutagenic frequency of 1 per every 72 bp. Functional at-risk alleles and haplotypes have been demonstrated in various human disorders. In addition, other pathogenic alterations including somatic mutations and misregulated epigenetic processes in NRF2 have led to oncogenic cell survival. Comprehensive information from the current review addresses association of NRF2 variation and disease phenotypes and supports the new insights into therapeutic strategies.

  3. Serum brain-derived neurotrophic factor levels and personality traits in patients with major depression.

    Science.gov (United States)

    Nomoto, Hiroshi; Baba, Hajime; Satomura, Emi; Maeshima, Hitoshi; Takebayashi, Naoko; Namekawa, Yuki; Suzuki, Toshihito; Arai, Heii

    2015-03-04

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. Previous studies have demonstrated lower serum BDNF levels in patients with major depressive disorder (MDD) and reported an association between BDNF levels and depression-related personality traits in healthy subjects. The aim of the present study was to explore for a possible association between peripheral BDNF levels and personality traits in patients with MDD. In this cross-sectional study, a total of 123 inpatients with MDD (Diagnostic and Statistical Manual for Mental Disorders, 4th edition) at the Juntendo University Koshigaya Hospital were recruited. Serum levels of BDNF were measured. Personality traits were assessed using the 125-item short version of the Temperament and Character Inventory (TCI). Multiple regression analysis adjusted for age, sex, body mass index, dose of antidepressant, and depression severity showed that TCI Self-Directedness (SD) scores were negatively associated with serum BDNF levels (β = -0.23, p = 0.026). MDD patients who have low SD did not show the reduction in serum BDNF levels that is normally associated with depressive state. Our findings suggest that depression-related biological changes may not occur in these individuals.

  4. Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected].

    Directory of Open Access Journals (Sweden)

    Han-En Tsai

    Full Text Available Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200 showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma.

  5. Structural Properties of HIV Integrase. Lens Epithelium-derived Growth Factor Oligomers

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, K.; Diamond, T; Hwang, Y; Bushman, F; Van Duyne, G

    2010-01-01

    Integrase (IN) is the catalytic component of the preintegration complex, a large nucleoprotein assembly critical for the integration of the retroviral genome into a host chromosome. Although partial crystal structures of human immunodeficiency virus IN alone and its complex with the integrase binding domain of the host factor PSIP1/lens epithelium-derived growth factor (LEDGF)/p75 are available, many questions remain regarding the properties and structures of LEDGF-bound IN oligomers. Using analytical ultracentrifugation, multiangle light scattering, and small angle x-ray scattering, we have established the oligomeric state, stoichiometry, and molecular shapes of IN {center_dot} LEDGF complexes in solution. Analyses of intact IN tetramers bound to two different LEDGF truncations allow for placement of the integrase binding domain by difference analysis. Modeling of the small angle x-ray scattering envelopes using existing structural data suggests domain arrangements in the IN oligomers that support and extend existing biochemical data for IN {center_dot} LEDGF complexes and lend new insights into the quaternary structure of LEDGF-bound IN tetramers. These IN oligomers may be involved in stages of the viral life cycle other than integration, including assembly, budding, and early replication.

  6. Glycan structure of Gc Protein-derived Macrophage Activating Factor as revealed by mass spectrometry.

    Science.gov (United States)

    Borges, Chad R; Rehder, Douglas S

    2016-09-15

    Disagreement exists regarding the O-glycan structure attached to human vitamin D binding protein (DBP). Previously reported evidence indicated that the O-glycan of the Gc1S allele product is the linear core 1 NeuNAc-Gal-GalNAc-Thr trisaccharide. Here, glycan structural evidence is provided from glycan linkage analysis and over 30 serial glycosidase-digestion experiments which were followed by analysis of the intact protein by electrospray ionization mass spectrometry (ESI-MS). Results demonstrate that the O-glycan from the Gc1F protein is the same linear trisaccharide found on the Gc1S protein and that the hexose residue is galactose. In addition, the putative anti-cancer derivative of DBP known as Gc Protein-derived Macrophage Activating Factor (GcMAF, which is formed by the combined action of β-galactosidase and neuraminidase upon DBP) was analyzed intact by ESI-MS, revealing that the activating E. coli β-galactosidase cleaves nothing from the protein-leaving the glycan structure of active GcMAF as a Gal-GalNAc-Thr disaccharide, regardless of the order in which β-galactosidase and neuraminidase are applied. Moreover, glycosidase digestion results show that α-N-Acetylgalactosamindase (nagalase) lacks endoglycosidic function and only cleaves the DBP O-glycan once it has been trimmed down to a GalNAc-Thr monosaccharide-precluding the possibility of this enzyme removing the O-glycan trisaccharide from cancer-patient DBP in vivo.

  7. Absence of hippocampal mossy fiber sprouting in transgenic mice overexpressing brain-derived neurotrophic factor.

    Science.gov (United States)

    Qiao, X; Suri, C; Knusel, B; Noebels, J L

    2001-05-01

    Excess neuronal activity upregulates the expression of two neurotrophins, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in adult hippocampus. Nerve growth factor has been shown to contribute the induction of aberrant hippocampal mossy fiber sprouting in the inner molecular layer of the dentate gyrus, however the role of prolonged brain-derived neurotrophic factor exposure is uncertain. We examined the distribution and plasticity of mossy fibers in transgenic mice with developmental overexpression of brain-derived neurotrophic factor. Despite 2--3-fold elevated BDNF levels in the hippocampus sufficient to increase the intensity of neuropeptide Y immunoreactivity in interneurons, no visible changes in mossy fiber Timm staining patterns were observed in the inner molecular layer of adult mutant hippocampus compared to wild-type mice. In addition, no changes of the mRNA expression of two growth-associated proteins, GAP-43 and SCG-10 were found. These data suggest that early and persistent elevations of brain-derived neurotrophic factor in granule cells are not sufficient to elicit this pattern of axonal plasticity in the hippocampus.

  8. Plasma brain-derived neurotrophic factor and reverse dipping pattern of nocturnal blood pressure in patients with cardiovascular risk factors.

    Directory of Open Access Journals (Sweden)

    Manabu Kadoya

    Full Text Available Basic studies have shown that brain-derived neurotrophic factor (BDNF has critical roles in the survival, growth, maintenance, and death of central and peripheral neurons, while it is also involved in regulation of the autonomic nervous system. Furthermore, recent clinical studies have suggested potential role of plasma BDNF in the circulatory system.We investigated the mutual relationships among plasma BDNF, patterns of nocturnal blood pressure changes (dippers, non-dippers, extra-dippers, and reverse-dippers, and cardiac autonomic function as determined by heart rate variability (HRV.This was a cross-sectional study of patients registered in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA Study from October 2010 to November 2012.Two-hundred fifty patients with 1 or more cardiovascular risk factor(s (obesity, smoking, presence of cardiovascular event history, hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease were enrolled.Plasma BDNF levels (natural logarithm transformed were significantly (p = 0.001 lower in reverse-dipper patients (7.18±0.69 pg/ml, mean ± SD, n = 36 as compared to dippers (7.86±0.86 pg/ml, n = 100. Multiple logistic regression analysis showed that BDNF (odds ratios: 0.417, 95% confidence interval: 0.228-0.762, P = 0.004 was the sole factor significantly and independently associated with the reverse-dippers as compared with dippers. Furthermore, plasma BDNF level was significantly and positively correlated with the time-domain (SDNN, SDANN5, CVRR and frequency-domain (LF of HRV parameters. Finally, multiple logistic regression analyses showed that the relationship between plasma BDNF and the reverse-dippers was weakened, yet remained significant or borderline significant even after adjusting for HRV parameters.Low plasma BDNF was independently associated with patients showing a reverse-dipper pattern of nocturnal blood pressure, in which an imbalance of cardiac autonomic function

  9. Construction of eukaryotic expression vector with brain-derived neurotrophic factor receptor trkB gene

    Institute of Scientific and Technical Information of China (English)

    HUANG Tao; JIANG Xiao-dan; XU Zhong; YUAN Jun; DING Lian-shu; ZOU Yu-xi; XU Ru-xiang

    2005-01-01

    Objective: To construct an eukaryotic expression vector carrying rat brain-derived neurotrophic factor receptor trkB gene. Methods: Using the total RNA isolated from rat brain as template, the trkB gene was amplified by reverse-transcription-polymerase chain reaction (RT-PCR) with a pair of specific primers which contained the restrictive sites of EcoR I and BamH I. The amplified fragment of trkB gene was digested with EcoR I and BamH I, and then subcloned into cloning vector pMD18-T and expression vector pEGFP-C2 respectively. The recombinant plasmids were identified by restriction endonuclease enzyme analysis and PCR. Results: The amplified DNA fragment was about 1461 bp in length. Enzyme digestion and PCR analysis showed that the gene of trkB had been successfully cloned into vector pMD18-T and pEGFP-C2. Conclusions: The trkB gene of rat has been amplified and cloned into the eukaryotic expression vector pEGFP-C2.

  10. Grain Size Biasing of 230Th-derived Focusing Factors in the Panama Basin

    Science.gov (United States)

    Loveley, M. R.; Marcantonio, F.; Lyle, M. W.; Ibrahim, R.; Wang, J. K.; Hertzberg, J. E.

    2014-12-01

    greatest amounts of 230Th (up to 49%) in the finest grain-sized fraction (<4μm), which makes up 26-40% of the bulk samples analyzed. Although, redistribution of sediment has taken place, our analysis indicates that 230Th-derived focusing factors are being overestimated at thick sites and underestimated at thin sites.

  11. Factor analysis is more appropriate to identify overall dietary patterns associated with diabetes when compared with treelet transform analysis

    NARCIS (Netherlands)

    Schoenaker, D.A.J.M.; Dobson, A.; Soedamah-Muthu, S.S.; Mishra, G.D.

    2013-01-01

    Treelet transform (TT) is a proposed alternative to factor analysis for deriving dietary patterns. Before applying this method to nutrition data, further analyses are required to assess its validity in nutritional epidemiology. We aimed to compare dietary patterns from factor analysis and TT and the

  12. Thermal analysis of N-carbamoyl benzotriazole derivatives

    Directory of Open Access Journals (Sweden)

    Kos Ivan

    2015-06-01

    Full Text Available Thermal properties of N-carbamoyl benzotriazole derivatives and N,N’,N’’-tribenzyloxyisocyanuric acid were investigated using thermogravimetric analysis and differential scanning calorimetry. The results revealed a difference between structural analogs of N-carbamoyl benzotriazole derivatives. They seem to be in agreement with the previously proposed formation of N,N’,N’’-tribenzyloxyisocyanuric acid from 1-(N-benzyloxycarbamoyl benzotriazole, via an intermediary N-benzyloxyisocyanate acid, during heating. Substantially different thermal properties were observed for structural analogues, 1-(N-methoxycarbamoyl benzotriazole and 1-(N-ethoxycarbamoyl benzotriazole. In contrast to N-benzyloxyisocyanate, no corresponding reactions were observed for their decomposition products, i.e., methoxyisocyanate and ethoxyisocyanate.

  13. Stem cell-based delivery of brain-derived neurotrophic factor gene in the rat retina.

    Science.gov (United States)

    Park, Hae-Young Lopilly; Kim, Jie Hyun; Sun Kim, Hwa; Park, Chan Kee

    2012-08-21

    As an alternative to a viral vector, the application of stem cells to transfer specific genes is under investigation in various organs. Using this strategy may provide more effective method to supply neurotrophic factor to the neurodegenerative diseases caused by neurotrophic factor deprivation. This study investigated the possibility and efficacy of stem cell-based delivery of the brain-derived neurotrophic factor (BDNF) gene to rat retina. Rat BDNF cDNA was transduced into rat bone marrow mesenchymal stem cells (rMSCs) using a retroviral vector. Its incorporation into the experimental rat retina and the expression of BDNF after intravitreal injection or subretinal injection were detected by real-time PCR, western blot analysis, and immunohistochemical staining. For the incorporated rMSCs, retinal-specific marker staining was performed to investigate the changes in morphology and the characteristics of the stem cells. Transduction of the rMSCs by retrovirus was effective, and the transduced rMSCs expressed high levels of the BDNF gene and protein. The subretinal injection of rMSCs produced rMSC migration and incorporation into the rat retina (about 15.7% incorporation rate), and retinal BDNF mRNA and protein expression was increased at 4 weeks after transplantation. When subretinal injection of rMSCs was applied to axotomized rat retina, it significantly increased the expression of BDNF until 4 weeks after transplantation. Some of the transplanted rMSCs exhibited morphological changes, but the retinal-specific marker stain was not sufficient to indicate whether neuronal differentiation had occurred. Using mesenchymal stem cells to deliver the BDNF gene to the retina may provide new treatment for glaucoma.

  14. Glial cell line-derived neurotrophic factor (GDNF) as a novel candidate gene of anxiety.

    Science.gov (United States)

    Kotyuk, Eszter; Keszler, Gergely; Nemeth, Nora; Ronai, Zsolt; Sasvari-Szekely, Maria; Szekely, Anna

    2013-01-01

    Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor for dopaminergic neurons with promising therapeutic potential in Parkinson's disease. A few association analyses between GDNF gene polymorphisms and psychiatric disorders such as schizophrenia, attention deficit hyperactivity disorder and drug abuse have also been published but little is known about any effects of these polymorphisms on mood characteristics such as anxiety and depression. Here we present an association study between eight (rs1981844, rs3812047, rs3096140, rs2973041, rs2910702, rs1549250, rs2973050 and rs11111) GDNF single nucleotide polymorphisms (SNPs) and anxiety and depression scores measured by the Hospital Anxiety and Depression Scale (HADS) on 708 Caucasian young adults with no psychiatric history. Results of the allele-wise single marker association analyses provided significant effects of two single nucleotide polymorphisms on anxiety scores following the Bonferroni correction for multiple testing (p = 0.00070 and p = 0.00138 for rs3812047 and rs3096140, respectively), while no such result was obtained on depression scores. Haplotype analysis confirmed the role of these SNPs; mean anxiety scores raised according to the number of risk alleles present in the haplotypes (p = 0.00029). A significant sex-gene interaction was also observed since the effect of the rs3812047 A allele as a risk factor of anxiety was more pronounced in males. In conclusion, this is the first demonstration of a significant association between the GDNF gene and mood characteristics demonstrated by the association of two SNPs of the GDNF gene (rs3812047 and rs3096140) and individual variability of anxiety using self-report data from a non-clinical sample.

  15. Glial cell line-derived neurotrophic factor (GDNF as a novel candidate gene of anxiety.

    Directory of Open Access Journals (Sweden)

    Eszter Kotyuk

    Full Text Available Glial cell line-derived neurotrophic factor (GDNF is a neurotrophic factor for dopaminergic neurons with promising therapeutic potential in Parkinson's disease. A few association analyses between GDNF gene polymorphisms and psychiatric disorders such as schizophrenia, attention deficit hyperactivity disorder and drug abuse have also been published but little is known about any effects of these polymorphisms on mood characteristics such as anxiety and depression. Here we present an association study between eight (rs1981844, rs3812047, rs3096140, rs2973041, rs2910702, rs1549250, rs2973050 and rs11111 GDNF single nucleotide polymorphisms (SNPs and anxiety and depression scores measured by the Hospital Anxiety and Depression Scale (HADS on 708 Caucasian young adults with no psychiatric history. Results of the allele-wise single marker association analyses provided significant effects of two single nucleotide polymorphisms on anxiety scores following the Bonferroni correction for multiple testing (p = 0.00070 and p = 0.00138 for rs3812047 and rs3096140, respectively, while no such result was obtained on depression scores. Haplotype analysis confirmed the role of these SNPs; mean anxiety scores raised according to the number of risk alleles present in the haplotypes (p = 0.00029. A significant sex-gene interaction was also observed since the effect of the rs3812047 A allele as a risk factor of anxiety was more pronounced in males. In conclusion, this is the first demonstration of a significant association between the GDNF gene and mood characteristics demonstrated by the association of two SNPs of the GDNF gene (rs3812047 and rs3096140 and individual variability of anxiety using self-report data from a non-clinical sample.

  16. Paracrine Engineering of Human Explant-Derived Cardiac Stem Cells to Over-Express Stromal-Cell Derived Factor 1α Enhances Myocardial Repair.

    Science.gov (United States)

    Tilokee, Everad L; Latham, Nicholas; Jackson, Robyn; Mayfield, Audrey E; Ye, Bin; Mount, Seth; Lam, Buu-Khanh; Suuronen, Erik J; Ruel, Marc; Stewart, Duncan J; Davis, Darryl R

    2016-07-01

    First generation cardiac stem cell products provide indirect cardiac repair but variably produce key cardioprotective cytokines, such as stromal-cell derived factor 1α, which opens the prospect of maximizing up-front paracrine-mediated repair. The mesenchymal subpopulation within explant derived human cardiac stem cells underwent lentiviral mediated gene transfer of stromal-cell derived factor 1α. Unlike previous unsuccessful attempts to increase efficacy by boosting the paracrine signature of cardiac stem cells, cytokine profiling revealed that stromal-cell derived factor 1α over-expression prevented lv-mediated "loss of cytokines" through autocrine stimulation of CXCR4+ cardiac stem cells. Stromal-cell derived factor 1α enhanced angiogenesis and stem cell recruitment while priming cardiac stem cells to readily adopt a cardiac identity. As compared to injection with unmodified cardiac stem cells, transplant of stromal-cell derived factor 1α enhanced cells into immunodeficient mice improved myocardial function and angiogenesis while reducing scarring. Increases in myocardial stromal-cell derived factor 1α content paralleled reductions in myocyte apoptosis but did not influence long-term engraftment or the fate of transplanted cells. Transplantation of stromal-cell derived factor 1α transduced cardiac stem cells increased the generation of new myocytes, recruitment of bone marrow cells, new myocyte/vessel formation and the salvage of reversibly damaged myocardium to enhance cardiac repair after experimental infarction. Stem Cells 2016;34:1826-1835.

  17. Kernel parameter dependence in spatial factor analysis

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg

    2010-01-01

    feature space via the kernel function and then performing a linear analysis in that space. In this paper we shall apply a kernel version of maximum autocorrelation factor (MAF) [7, 8] analysis to irregularly sampled stream sediment geochemistry data from South Greenland and illustrate the dependence...

  18. Multistructure Statistical Model Applied To Factor Analysis

    Science.gov (United States)

    Bentler, Peter M.

    1976-01-01

    A general statistical model for the multivariate analysis of mean and covariance structures is described. Matrix calculus is used to develop the statistical aspects of one new special case in detail. This special case separates the confounding of principal components and factor analysis. (DEP)

  19. Monosaccharide-NAIM Derivatives for D-, L-Configurational Analysis

    Directory of Open Access Journals (Sweden)

    Chunchi Lin

    2011-01-01

    Full Text Available The D-, L-enantiomeric pairs of common monosaccharides (xylose, ribose, rhamnose, arabinose, fucose, glucose, mannose, galactose, N-acetylgalactosamine, glucuronic acid and galacturonic acid were derivatized with 2,3-naphthalenediamine to form the corresponding D-, L-aldo-NAIM derivatives. A simple and facile capillary electrophoretic method was established for sugar composition analysis by simultaneously determining the migration times of these aldo-NAIMs using borate buffer at high pH (100 mM, pH 9.0. The methodology is also applicable to sialic acid (ketose monosaccharides. The quantitation level of the proposed method was in the 10~500 ppm range and the LOD was 1 ppm. The enantioseparation of D, L pairs of aldo-NAIMs were also achieved by using modified sulfated-a-cyclodextrin as the chiral selector in phosphate buffer (300 mM, pH 3.0. In addition, the combination by reductive amination of amino-aldo-NAIM agent and D-, L-enantiomeric pairs of monosaccharides formed a diastereomeric pair for saccharide configuration analysis. Aldo-NAIM derivatives are thus shown to be rapid and efficient agents for analyzing saccharide compositions and configurations with good linearity and short analysis times via capillary electrophoresis.

  20. A bioactive molecule in a complex wound healing process: platelet-derived growth factor.

    Science.gov (United States)

    Kaltalioglu, Kaan; Coskun-Cevher, Sule

    2015-08-01

    Wound healing is considered to be particularly important after surgical procedures, and the most important wounds related to surgical procedures are incisional, excisional, and punch wounds. Research is ongoing to identify methods to heal non-closed wounds or to accelerate wound healing; however, wound healing is a complex process that includes many biological and physiological events, and it is affected by various local and systemic factors, including diabetes mellitus, infection, ischemia, and aging. Different cell types (such as platelets, macrophages, and neutrophils) release growth factors during the healing process, and platelet-derived growth factor is a particularly important mediator in most stages of wound healing. This review explores the relationship between platelet-derived growth factor and wound healing.

  1. Brain-derived neurotrophic factor and substantia nigra dopaminergic neurons in Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Haixia Ding; Meijiang Feng; Xinsheng Ding

    2008-01-01

    BACKGROUND:Parkinson's disease (PD) is a chronic, progressive neurodegenerative central nervous system disease which occurs in the substantia nigra-corpus striatum system. The main pathological feature of PD is selective dopaminergic neuronal loss with distinctive Lewy bodies in populations of surviving dopaminergic neurons. In the clinical and neuropathological diagnosis of PD, brain-derived neurotrophic factor mRNA expression in the substantia nigra pars compacta is reduced by 70%, and surviving dopaminergic neurons in the PD substantia nigra pars compacta express less brain-derived neurotrophic factor (BDNF) mRNA (20%) than their normal counterparts. In recent years, knowledge surrounding the relationship between neurotrophic factors and PD has increased, and detailed pathogenesis of the role of neurotrophic factors in PD becomes more important.

  2. Extraction and analysis of indole derivatives from fungal biomass.

    Science.gov (United States)

    Gartz, J

    1994-01-01

    The occurrence and extraction of indole derivatives in six species from four genera of higher fungi were investigated. By using pure methanol for extraction of the mushrooms analysis revealed the highest concentrations of psilocybin and baeocystin. The psilocin content of the species was higher by using aqueous solutions of alcohols than with methanol alone but was an artificial phenomenon caused by enzymatic destruction of psilocybin. The extraction with dilute acetic acid yielded better results than with the water containing alcohols. The simple one-step procedure with methanol for the quantitative extraction is still the safest method to obtain the genuine alkaloids from fungal biomass.

  3. Serum brain-derived neurotrophic factor levels and personality traits in patients with major depression

    OpenAIRE

    Nomoto, Hiroshi; Baba, Hajime; Satomura, Emi; Maeshima, Hitoshi; Takebayashi, Naoko; Namekawa, Yuki; Suzuki, Toshihito; Arai, Heii

    2015-01-01

    Background Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. Previous studies have demonstrated lower serum BDNF levels in patients with major depressive disorder (MDD) and reported an association between BDNF levels and depression-related personality traits in healthy subjects. The aim of the present study was to explore for a possible association between peripheral BDNF levels and personality traits in patients with MDD. Methods In this cross...

  4. Effects of Brain-Derived Neurotrophic Factor on Local Inflammation in Experimental Stroke of Rat

    OpenAIRE

    Yongjun Jiang; Ning Wei; Juehua Zhu; Tingting Lu; Zhaoyao Chen; Gelin Xu; Xinfeng Liu

    2010-01-01

    This study was aimed to investigate whether brain-derived neurotrophic factor (BDNF) can modulate local cerebral inflammation in ischemic stroke. Rats were subjected to ischemia by occluding the right middle cerebral artery (MCAO) for 2 hours. Rats were randomized as control, BDNF, and antibody groups. The local inflammation was evaluated on cellular, cytokine, and transcription factor levels with immunofluorescence, enzyme-linked immunosorbent assay, real-time qPCR, and electrophoretic mobil...

  5. TRPC3 Regulates Release of Brain-Derived Neurotrophic Factor From Human Airway Smooth Muscle

    OpenAIRE

    Vohra, Pawan K.; Thompson, Michael A.; Sathish, Venkatachalem; Kiel, Alexander; Jerde, Calvin; Pabelick, Christina M.; Singh, Brij B.; Prakash, Y. S.

    2013-01-01

    Exogenous brain-derived neurotrophic factor (BDNF) enhances Ca2+ signaling and cell proliferation in human airway smooth muscle (ASM), especially with inflammation. Human ASM also expresses BDNF, raising the potential for autocrine/paracrine effects. The mechanisms by which ASM BDNF secretion occurs are not known. Transient receptor potential channels (TRPCs) regulate a variety of intracellular processes including store-operated Ca2+ entry (SOCE; including in ASM) and secretion of factors suc...

  6. Pigment Epithelium-Derived Factor Inhibits Retinal Microvascular Dysfunction Induced By 12/15-Lipoxygenase-Derived Eicosanoids

    Science.gov (United States)

    Ibrahim, Ahmed S.; Tawfik, Amany M.; Hussein, Khaled A; Elshafey, Sally; Markand, Shanu; Rizk, Nasser; Duh, Elia J.; Smith, Sylvia B.; Al-Shabrawey, Mohamed

    2015-01-01

    We recently demonstrated that 12/15-lipoxygenase (LOX) derived metabolites, hydroxyeicosatetraenoic acids (HETEs), contribute to diabetic retinopathy (DR) via NADPH oxidase (NOX) and disruption of the balance in retinal levels of the vascular endothelial growth factor (VEGF) and Pigment Epithelium-Derived Factor (PEDF). Here, we test whether PEDF ameliorates retinal vascular injury induced by HETEs and the underlying mechanisms. Furthermore, we pursue the causal relationship between LOX-NOX system and regulation of PEDF expression during DR. For these purposes, we used an experimental eye model in which normal mice were injected intravitreally with 12/15HETE with/without PEDF. Thereafter, Fluorescein Angiography (FA) was used to evaluate the vascular leakage, followed by Optical coherence tomography (OCT) to assess the presence of angiogenesis. FA and OCT reported an increased vascular leakage and pre-retinal neovascularization, respectively, in response to 12-HETE that were not observed in PEDF-treated group. Moreover, PEDF significantly attenuated the increased levels of vascular cell and intercellular adhesion molecules, VCAM-1 and ICAM-1, elicited by 12-HETE injection. Accordingly, the direct relationship between HETE and PEDF has been explored through in-vitro studies using Müller cells (rMCs) and human retinal endothelial cells (HRECs). The results showed that HETEs triggered the secretion of TNF-α and IL-6, as well as activation of NFκB in rMCs and significantly increased permeability and reduced zonula occludens protein-1 (ZO-1) immunoreactivity in HRECs. All these effects were prevented in PEDF-treated cells. Furthermore, interest in PEDF regulation during DR has been expanded to include NOX system. Retinal PEDF was significantly restored in diabetic mice treated with NOX inhibitor, apocynin, or lacking NOX2 up to 80% of the control level. Collectively, our findings suggest that interfering with LOX-NOX signaling opens up a new direction for treating DR

  7. Exploratory Factor Analysis on H-index and its Derivative Indexes%基于H指数及扩展指数的探索性因子研究

    Institute of Scientific and Technical Information of China (English)

    杜湘; 张国飞

    2014-01-01

    6 694 articles in metallurgical science field are selected from SCIE database of web of science platform during 2010 to 2014 for the study.Then,according to the number issued in the big data envi-ronment,correlation between the number issued,citations,number of papers cited H index,G index, AR index,R index,A index and Ha index were analyzed by exploratory factor.Finally,the effectiveness of the productive author population and highly cited author population and the correlation among each in-dex were also analyzed.%以Web of science平台的SCI数据库中收录的2010—2014年间收录的冶金科学领域全部6694篇论文的元数据作为研究对象,利用探索性因子分析的方法分析在大数据环境下发文数量、被引用次数、篇均被引次数、H指数、G指数、AR指数、R指数、A指数、Ha指数之间的相关性,再综合分析高产作者和高被引作者评价的有效性和各指数之间的相关性。

  8. Platelet-Derived Short-Chain Polyphosphates Enhance the Inactivation of Tissue Factor Pathway Inhibitor by Activated Coagulation Factor XI

    Science.gov (United States)

    Puy, Cristina; Tucker, Erik I.; Ivanov, Ivan S.; Gailani, David; Smith, Stephanie A.; Morrissey, James H.; Gruber, András; McCarty, Owen J. T.

    2016-01-01

    Introduction Factor (F) XI supports both normal human hemostasis and pathological thrombosis. Activated FXI (FXIa) promotes thrombin generation by enzymatic activation of FXI, FIX, FX, and FV, and inactivation of alpha tissue factor pathway inhibitor (TFPIα), in vitro. Some of these reactions are now known to be enhanced by short-chain polyphosphates (SCP) derived from activated platelets. These SCPs act as a cofactor for the activation of FXI and FV by thrombin and FXIa, respectively. Since SCPs have been shown to inhibit the anticoagulant function of TFPIα, we herein investigated whether SCPs could serve as cofactors for the proteolytic inactivation of TFPIα by FXIa, further promoting the efficiency of the extrinsic pathway of coagulation to generate thrombin. Methods and Results Purified soluble SCP was prepared by size-fractionation of sodium polyphosphate. TFPIα proteolysis was analyzed by western blot. TFPIα activity was measured as inhibition of FX activation and activity in coagulation and chromogenic assays. SCPs significantly accelerated the rate of inactivation of TFPIα by FXIa in both purified systems and in recalcified plasma. Moreover, platelet-derived SCP accelerated the rate of inactivation of platelet-derived TFPIα by FXIa. TFPIα activity was not affected by SCP in recalcified FXI-depleted plasma. Conclusions Our data suggest that SCP is a cofactor for TFPIα inactivation by FXIa, thus, expanding the range of hemostatic FXIa substrates that may be affected by the cofactor functions of platelet-derived SCP. PMID:27764259

  9. Reduced serum concentrations of nerve growth factor, but not brain-derived neurotrophic factor, in chronic cannabis abusers.

    Science.gov (United States)

    Angelucci, Francesco; Ricci, Valerio; Spalletta, Gianfranco; Pomponi, Massimiliano; Tonioni, Federico; Caltagirone, Carlo; Bria, Pietro

    2008-12-01

    Chronic cannabis use produces effects within the central nervous system (CNS) which include deficits in learning and attention tasks and decreased brain volume. Neurotrophins, in particular nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), are proteins that serve as survival factors for CNS neurons. Deficits in the production and utilization of these proteins can lead to CNS dysfunctions including those associated with cannabis abuse. In this study we measured by enzyme-linked immunosorbent assay (ELISA) the NGF and BDNF serum levels in two groups of subjects: cannabis-dependent patients and healthy subjects. We found that NGF serum levels were significantly reduced in cannabis abusers as compared to healthy subjects. These findings indicate that NGF may have a role in the central action of cannabis and potentially in the neurotoxicity induced by this drug. These data also suggest that chronic cannabis consumption may be a risk factor for developing psychosis among drug users.

  10. Chemokine stromal cell-derived factor 1alpha activates basophils by means of CXCR4

    DEFF Research Database (Denmark)

    Jinquan, T; Jacobi, H H; Jing, C

    2000-01-01

    The CXC chemokine receptor 4 (CXCR4) is predominantly expressed on inactivated naive T lymphocytes, B lymphocytes, dendritic cells, and endothelial cells. CXC chemokine stromal cell-derived factor 1alpha (SDF-1alpha) is the only known ligand for CXCR4. To date, the CXCR4 expression and function...... of SDF-1alpha in basophils are unknown....

  11. Gender specific associations of serum levels of brain-derived neurotrophic factor in anxiety

    NARCIS (Netherlands)

    Molendijk, Marc L.; Bus, Boudewijn A. A.; Spinhoven, Philip; Penninx, Brenda W. J. H.; Prickaerts, Jos; Voshaar, Richard C. Oude; Elzinga, Bernet M.

    2012-01-01

    Objectives. Whereas animal models indicate that brain-derived neurotrophic factor (BDNF) plays a role in anxiety-related behaviour, little is known about BDNF in patients with an anxiety disorder. We tested the hypothesis that serum BDNF levels are low in patients with an anxiety disorder as compare

  12. Decreased levels of brain-derived neurotrophic factor in the remitted state of unipolar depressive disorder

    DEFF Research Database (Denmark)

    Hasselbalch, Jacob; Knorr, U; Bennike, B;

    2012-01-01

    Decreased levels of peripheral brain-derived neurotrophic factor (BDNF) have been associated with depression. It is uncertain whether abnormally low levels of BDNF in blood are present beyond the depressive state and whether levels of BDNF are associated with the course of clinical illness....

  13. Methodological considerations to determine the effect of exercise on brain-derived neurotrophic factor levels

    OpenAIRE

    Pareja Galeano, Helios; Alis, Rafael; Sanchís-Gomar, Fabián; Cabo, Helena; Cortell-Ballester, José; Gómez Cabrera, María del Carmen; Lucía Mulas, Alejandro; Viña, José

    2015-01-01

    Physical exercise up-regulates brain-derived neurotrophic factor (BDNF) in the brain and blood. However, there is yet no consensus about the adequate blood processing conditions to standardize its assessment. We aimed to find a reliable blood sample processing method to determine changes in BDNF due to exercise. 2.382 JCR (2015) Q2, 9/30 Medical laboratory technology UEM

  14. Differential Regulation of Brain-Derived Neurotrophic Factor Transcripts during the Consolidation of Fear Learning

    Science.gov (United States)

    Ressler, Kerry J.; Rattiner, Lisa M.; Davis, Michael

    2004-01-01

    Brain-derived neurotrophic factor (BDNF) has been implicated as a molecular mediator of learning and memory. The BDNF gene contains four differentially regulated promoters that generate four distinct mRNA transcripts, each containing a unique noncoding 5[prime]-exon and a common 3[prime]-coding exon. This study describes novel evidence for the…

  15. Elevated circulating stromal-derived factor-1 levels in sickle cell disease

    NARCIS (Netherlands)

    Landburg, P P; Nur, E; Maria, N; Brandjes, D P M; Biemond, B J; Schnog, J B; Duits, A J

    2009-01-01

    Inflammation and angiogenesis are of importance in the pathophysiology of sickle cell disease (SCD). Recently, the chemokine stromal-derived factor-1 (SDF-1) has been shown to be a key mediator of angiogenesis and inflammation. In this study we determined serum SDF-1 levels in consecutive adult

  16. Role of platelet-derived enclothelial cell growth factor/thymidine phosphorylase in fluoropyrimidine sensitivity

    NARCIS (Netherlands)

    de Bruin, M; van Capel, T; Van der Born, K; Kruyt, FA; Fukushinna, M; Hoekman, K; Pinedo, HM; Peters, GJ

    2003-01-01

    Platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (TP) catalyses the reversible phosphorolysis of thymidine to thymine and 2-deoxyribose-1-phosphate and is involved in the metabolism of fluoropyrimidines. It can also activate 5'-deoxyfluorouridine (5'DFUR) and possibl

  17. Human obesity associated with an intronic SNP in the brain-derived neurotrophic factor locus

    Science.gov (United States)

    Brain-derived neurotrophic factor (BDNF) plays a key role in energy balance. In population studies, SNPs of the BDNF locus have been linked to obesity, but the mechanism by which these variants cause weight gain is unknown. Here, we examined human hypothalamic BDNF expression in association with 44 ...

  18. Electroacupuncture upregulated platelet derived growth factor expression in spared dorsal root ganglion of cats

    Institute of Scientific and Technical Information of China (English)

    Xifeng Wang; Lianshuang Zhang; Xiaobo Xu; Wei Zhao; Guixiang Liu

    2012-01-01

    A bilateral spared dorsal root ganglion model was established in healthy adult cats by bilateral resection of L1-5 and L7-S2 dorsal root ganglia. L6 dorsal root ganglia were spared. Zusanli (ST36) and Xuanzhong (BL39) or Futu (ST32) and Sanyinjiao (SP6) were alternatively electro-stimulated on the right leg. Immunohistochemical staining of anti-serum platelet-derived growth factor demonstrated that the number of total neurons and medium-small sized platelet-derived growth factor positive neurons was significantly decreased on the 7th day following injury. After 7 days of acupuncture, the total number of positive and large neurons staining for platelet-derived growth factor on the acupuncture side significantly increased compared to the non-acupuncture side. After acupuncture for 14 days, the total positive and medium-small sized neurons significantly increased compared with the non-acupuncture side. Results indicate that acupuncture promoted the synthesis of platelet-derived growth factor in spared dorsal root ganglia.

  19. Elevated circulating stromal-derived factor-1 levels in sickle cell disease

    NARCIS (Netherlands)

    Landburg, P P; Nur, E; Maria, N; Brandjes, D P M; Biemond, B J; Schnog, J B; Duits, A J

    2009-01-01

    Inflammation and angiogenesis are of importance in the pathophysiology of sickle cell disease (SCD). Recently, the chemokine stromal-derived factor-1 (SDF-1) has been shown to be a key mediator of angiogenesis and inflammation. In this study we determined serum SDF-1 levels in consecutive adult sick

  20. Spectral derivative analysis of solar spectroradiometric measurements: Theoretical basis

    Science.gov (United States)

    Hansell, R. A.; Tsay, S.-C.; Pantina, P.; Lewis, J. R.; Ji, Q.; Herman, J. R.

    2014-07-01

    Spectral derivative analysis, a commonly used tool in analytical spectroscopy, is described for studying cirrus clouds and aerosols using hyperspectral, remote sensing data. The methodology employs spectral measurements from the 2006 Biomass-burning Aerosols in Southeast Asia field study to demonstrate the approach. Spectral peaks associated with the first two derivatives of measured/modeled transmitted spectral fluxes are examined in terms of their shapes, magnitudes, and positions from 350 to 750 nm, where variability is largest. Differences in spectral features between media are mainly associated with particle size and imaginary term of the complex refractive index. Differences in derivative spectra permit cirrus to be conservatively detected at optical depths near the optical thin limit of ~0.03 and yield valuable insight into the composition and hygroscopic nature of aerosols. Biomass-burning smoke aerosols/cirrus generally exhibit positive/negative slopes, respectively, across the 500-700 nm spectral band. The effect of cirrus in combined media is to increase/decrease the slope as cloud optical thickness decreases/increases. For thick cirrus, the slope tends to 0. An algorithm is also presented which employs a two model fit of derivative spectra for determining relative contributions of aerosols/clouds to measured data, thus enabling the optical thickness of the media to be partitioned. For the cases examined, aerosols/clouds explain ~83%/17% of the spectral signatures, respectively, yielding a mean cirrus cloud optical thickness of 0.08 ± 0.03, which compared reasonably well with those retrieved from a collocated Micropulse Lidar Network Instrument (0.09 ± 0.04). This method permits extracting the maximum informational content from hyperspectral data for atmospheric remote sensing applications.

  1. Hamiltonian analysis of higher derivative scalar-tensor theories

    CERN Document Server

    Langlois, David

    2015-01-01

    We perform a Hamiltonian analysis of a large class of scalar-tensor Lagrangians which depend quadratically on the second derivatives of a scalar field. By resorting to a convenient choice of dynamical variables, we show that the Hamiltonian can be written in a very simple form, where the Hamiltonian and the momentum constraints are easily identified. In the case of degenerate Lagrangians, which include the Horndeski and beyond Horndeski quartic Lagrangians, our analysis confirms that the dimension of the physical phase space is reduced by the primary and secondary constraints due to the degeneracy, thus leading to the elimination of the dangerous Ostrogradski ghost. We also present the Hamiltonian formulation for nondegenerate theories and find that they contain four degrees of freedom, as expected. We finally discuss the status of the unitary gauge from the Hamiltonian perspective.

  2. Hamiltonian analysis of higher derivative scalar-tensor theories

    Science.gov (United States)

    Langlois, David; Noui, Karim

    2016-07-01

    We perform a Hamiltonian analysis of a large class of scalar-tensor Lagrangians which depend quadratically on the second derivatives of a scalar field. By resorting to a convenient choice of dynamical variables, we show that the Hamiltonian can be written in a very simple form, where the Hamiltonian and the momentum constraints are easily identified. In the case of degenerate Lagrangians, which include the Horndeski and beyond Horndeski quartic Lagrangians, our analysis confirms that the dimension of the physical phase space is reduced by the primary and secondary constraints due to the degeneracy, thus leading to the elimination of the dangerous Ostrogradsky ghost. We also present the Hamiltonian formulation for nondegenerate theories and find that they contain four degrees of freedom, including a ghost, as expected. We finally discuss the status of the unitary gauge from the Hamiltonian perspective.

  3. Platelet-derived growth factor receptor/platelet-derived growth factor (PDGFR/PDGF) system is a prognostic and treatment response biomarker with multifarious therapeutic targets in cancers.

    Science.gov (United States)

    Appiah-Kubi, Kwaku; Wang, Ying; Qian, Hai; Wu, Min; Yao, Xiaoyuan; Wu, Yan; Chen, Yongchang

    2016-08-01

    Progress in cancer biology has led to an increasing discovery of oncogenic alterations of the platelet-derived growth factor receptors (PDGFRs) in cancers. In addition, their overexpression in numerous cancers invariably makes PDGFRs and platelet-derived growth factors (PDGFs) prognostic and treatment markers in some cancers. The oncologic alterations of the PDGFR/PDGF system affect the extracellular, transmembrane and tyrosine kinase domains as well as the juxtamembrane segment of the receptor. The receptor is also involved in fusions with intracellular proteins and receptor tyrosine kinase. These discoveries undoubtedly make the system an attractive oncologic therapeutic target. This review covers elementary biology of PDGFR/PDGF system and its role as a prognostic and treatment marker in cancers. In addition, the multifarious therapeutic targets of PDGFR/PDGF system are discussed. Great potential exists in the role of PDGFR/PDGF system as a prognostic and treatment marker and for further exploration of its multifarious therapeutic targets in safe and efficacious management of cancer treatments.

  4. Brain-derived neurotrophic factor enhances calcium regulatory mechanisms in human airway smooth muscle.

    Directory of Open Access Journals (Sweden)

    Amard J Abcejo

    Full Text Available Neurotrophins (NTs, which play an integral role in neuronal development and function, have been found in non-neuronal tissue (including lung, but their role is still under investigation. Recent reports show that NTs such as brain-derived neurotrophic factor (BDNF as well as NT receptors are expressed in human airway smooth muscle (ASM. However, their function is still under investigation. We hypothesized that NTs regulate ASM intracellular Ca(2+ ([Ca(2+](i by altered expression of Ca(2+ regulatory proteins. Human ASM cells isolated from lung samples incidental to patient surgery were incubated for 24 h (overnight in medium (control or 1 nM BDNF in the presence vs. absence of inhibitors of signaling cascades (MAP kinases; PI3/Akt; NFκB. Measurement of [Ca(2+](i responses to acetylcholine (ACh and histamine using the Ca(2+ indicator fluo-4 showed significantly greater responses following BDNF exposure: effects that were blunted by pathway inhibitors. Western analysis of whole cell lysates showed significantly higher expression of CD38, Orai1, STIM1, IP(3 and RyR receptors, and SERCA following BDNF exposure, effects inhibited by inhibitors of the above cascades. The functional significance of BDNF effects were verified by siRNA or pharmacological inhibition of proteins that were altered by this NT. Overall, these data demonstrate that NTs activate signaling pathways in human ASM that lead to enhanced [Ca(2+](i responses via increased regulatory protein expression, thus enhancing airway contractility.

  5. Analysis of Economic Factors Affecting Stock Market

    OpenAIRE

    Xie, Linyin

    2010-01-01

    This dissertation concentrates on analysis of economic factors affecting Chinese stock market through examining relationship between stock market index and economic factors. Six economic variables are examined: industrial production, money supply 1, money supply 2, exchange rate, long-term government bond yield and real estate total value. Stock market comprises fixed interest stocks and equities shares. In this dissertation, stock market is restricted to equity market. The stock price in thi...

  6. Analysis of plug-in hybrid electric vehicle utility factors

    Science.gov (United States)

    Bradley, Thomas H.; Quinn, Casey W.

    Plug-in hybrid electric vehicles (PHEVs) are hybrid electric vehicles that can be fueled from both conventional liquid fuels and grid electricity. To represent the total contribution of both of these fuels to the operation, energy use, and environmental impacts of PHEVs, researchers have developed the concept of the utility factor. As standardized in documents such as SAE J1711 and SAE J2841, the utility factor represents the proportion of vehicle distance travelled that can be allocated to a vehicle test condition so as to represent the real-world driving habits of a vehicle fleet. These standards must be used with care so that the results are understood within the context of the assumptions implicit in the standardized utility factors. This study analyzes and derives alternatives to the standard utility factors from the 2001 National Highway Transportation Survey, so as to understand the sensitivity of PHEV performance to assumptions regarding charging frequency, vehicle characteristics, driver characteristics, and means of defining the utility factor. Through analysis of these alternative utility factors, this study identifies areas where analysis, design, and policy development for PHEVs can be improved by alternative utility factor calculations.

  7. Brain-derived neurotrophic factor mediates the activity-dependent regulation of inhibition in neocortical cultures.

    Science.gov (United States)

    Rutherford, L C; DeWan, A; Lauer, H M; Turrigiano, G G

    1997-06-15

    The excitability of cortical circuits is modulated by interneurons that release the inhibitory neurotransmitter GABA. In primate and rodent visual cortex, activity deprivation leads to a decrease in the expression of GABA. This suggests that activity is able to adjust the strength of cortical inhibition, but this has not been demonstrated directly. In addition, the nature of the signal linking activity to GABA expression has not been determined. Activity is known to regulate the expression of the neurotrophin brain-derived neurotrophic factor (BDNF), and BDNF has been shown to influence the phenotype of GABAergic interneurons. We use a culture system from postnatal rat visual cortex to test the hypothesis that activity is regulating the strength of cortical inhibition through the regulation of BDNF. Cultures were double-labeled against GABA and the neuronal marker MAP2, and the percentage of neurons that were GABA-positive was determined. Blocking spontaneous activity in these cultures reversibly decreased the number of GABA-positive neurons without affecting neuronal survival. Voltage-clamp analysis of inhibitory currents demonstrated that activity blockade also decreased GABA-mediated inhibition onto pyramidal neurons and raised pyramidal neuron firing rates. All of these effects were prevented by incubation with BDNF during activity blockade, but not by neurotrophin 3 or nerve growth factor. Additionally, blockade of neurotrophin signaling mimicked the effects of activity blockade on GABA expression. These data suggest that activity regulates cortical inhibition through a BDNF-dependent mechanism and that this neurotrophin plays an important role in the control of cortical excitability.

  8. NF-κB Regulates B-Cell-Derived Nerve Growth Factor Expression

    Institute of Scientific and Technical Information of China (English)

    Klaus Heese; Noriko Inoue; Tohru Sawada

    2006-01-01

    In the mammalian brain, four neurotrophins have been identified: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5). NGF exerts an important role in the development and functions of the central and peripheral nervous system. However, it has recently been documented that several types of immune cells, such as mast cells, lymphocytes, basophils and eosinophils, produce,store and release NGF. Accumulating preclinical and clinical data indicate that dysfunctions of NGF and the other neurotrophins may contribute to impaired immune responses and concentration of NGF frequently correlates with disease severity. Thus, the aim of this study was to elucidate the potential signaling mechanisms of cytokineneurotrophins interactions contributing to increased NGF levels. Our data show that the transcription factorNF-κB plays a pivotal role in regulating B-cell-derived NGF expression.

  9. Hypoxia-inducible factor-1 α/platelet derived growth factor axis in HIV-associated pulmonary vascular remodeling

    Directory of Open Access Journals (Sweden)

    Bartolome Sonja

    2011-08-01

    Full Text Available Abstract Background Human immunodeficiency virus (HIV infected patients are at increased risk for the development of pulmonary arterial hypertension (PAH. Recent reports have demonstrated that HIV associated viral proteins induce reactive oxygen species (ROS with resultant endothelial cell dysfunction and related vascular injury. In this study, we explored the impact of HIV protein induced oxidative stress on production of hypoxia inducible factor (HIF-1α and platelet-derived growth factor (PDGF, critical mediators implicated in the pathogenesis of HIV-PAH. Methods The lungs from 4-5 months old HIV-1 transgenic (Tg rats were assessed for the presence of pulmonary vascular remodeling and HIF-1α/PDGF-BB expression in comparison with wild type controls. Human primary pulmonary arterial endothelial cells (HPAEC were treated with HIV-associated proteins in the presence or absence of pretreatment with antioxidants, for 24 hrs followed by estimation of ROS levels and western blot analysis of HIF-1α or PDGF-BB. Results HIV-Tg rats, a model with marked viral protein induced vascular oxidative stress in the absence of active HIV-1 replication demonstrated significant medial thickening of pulmonary vessels and increased right ventricular mass compared to wild-type controls, with increased expression of HIF-1α and PDGF-BB in HIV-Tg rats. The up-regulation of both HIF-1α and PDGF-B chain mRNA in each HIV-Tg rat was directly correlated with an increase in right ventricular/left ventricular+septum ratio. Supporting our in-vivo findings, HPAECs treated with HIV-proteins: Tat and gp120, demonstrated increased ROS and parallel increase of PDGF-BB expression with the maximum induction observed on treatment with R5 type gp-120CM. Pre-treatment of endothelial cells with antioxidants or transfection of cells with HIF-1α small interfering RNA resulted in abrogation of gp-120CM mediated induction of PDGF-BB, therefore, confirming that ROS generation and

  10. Association Between Brain-Derived Neurotrophic Factor Genotype and Upper Extremity Motor Outcome After Stroke.

    Science.gov (United States)

    Chang, Won Hyuk; Park, Eunhee; Lee, Jungsoo; Lee, Ahee; Kim, Yun-Hee

    2017-06-01

    The identification of intrinsic factors for predicting upper extremity motor outcome could aid the design of individualized treatment plans in stroke rehabilitation. The aim of this study was to identify prognostic factors, including intrinsic genetic factors, for upper extremity motor outcome in patients with subacute stroke. A total of 97 patients with subacute stroke were enrolled. Upper limb motor impairment was scored according to the upper limb of Fugl-Meyer assessment score at 3 months after stroke. The prediction of upper extremity motor outcome at 3 months was modeled using various factors that could potentially influence this impairment, including patient characteristics, baseline upper extremity motor impairment, functional and structural integrity of the corticospinal tract, and brain-derived neurotrophic factor genotype. Multivariate ordinal logistic regression models were used to identify the significance of each factor. The independent predictors of motor outcome at 3 months were baseline upper extremity motor impairment, age, stroke type, and corticospinal tract functional integrity in all stroke patients. However, in the group with severe motor impairment at baseline (upper limb score of Fugl-Meyer assessment stroke. Brain-derived neurotrophic factor genotype may be a potentially useful predictor of upper extremity motor outcome in patients with subacute stroke with severe baseline motor involvement. © 2017 American Heart Association, Inc.

  11. Reduced serum levels of oestradiol and brain derived neurotrophic factor in both diabetic women and HFD-feeding female mice.

    Science.gov (United States)

    Zhang, Yi; Zhang, Shan-Wen; Khandekar, Neeta; Tong, Shi-Fei; Yang, He-Qin; Wang, Wan-Ru; Huang, Xu-Feng; Song, Zhi-Yuan; Lin, Shu

    2017-04-01

    The estrogen levels in the pre and post menstrual phases interact with brain-derived neurotrophic factor in a complex manner, which influences the overall state of the body. To study the role of oestradiol and brain-derived neurotrophic factor in modulating obesity related type 2 diabetes and the interactions between two factors, we enrolled 15 diabetic premenopausal women and 15 diabetic postmenopausal women respectively, the same number of healthy pre and postmenopausal women were recruited as two control groups. The fasting blood glucose, insulin, lipids, estrogen, and brain-derived neurotrophic factor levels were measured through clinical tests. Additionally, we set up obese female mouse model to mimic human trial stated above, to verify the relationship between estrogen and brain-derived neurotrophic factor. Our findings revealed that there is a moderately positive correlation between brain-derived neurotrophic factor and oestradiol in females, and decreased brain-derived neurotrophic factor may worsen impaired insulin function. The results further confirmed that high fat diet-fed mice which exhibited impaired glucose tolerance, showed lower levels of oestradiol and decreased expression of brain-derived neurotrophic factor mRNA in the ventromedial hypothalamus. The level of brain-derived neurotrophic factor reduced on condition that the level of oestradiol is sufficiently low, such as women in postmenopausal period, which aggravates diabetes through feeding-related pathways. Increasing the level of brain-derived neurotrophic factor may help to alleviate the progression of the disease in postmenopausal women with diabetes.

  12. Use of RNAi silencing to target preconditioned glial cell line-derived neurotrophic factor in neuronal apoptosis

    Institute of Scientific and Technical Information of China (English)

    Hongliang Guo; Zhongxin Xu; Xinhua Li; Jing Mang; Ying Xing; Jinting He; Guihua Xu; Shijun Yan; Lifeng Liu; Chunli Mei

    2011-01-01

    Several studies have suggested that exogenous glial cell line-derived neurotrophic factor may protect neurons from cerebral ischemic injury. However, the mechanisms underlying the neuroprotective effects of endogenous glial cell line-derived neurotrophic factor remain unclear. The present experiments sought to elucidate the influence of various conditioned media on neuronal apoptosis, using a normal culture medium for astrocytes, an astrocyte medium highly expressing glial cell line-derived neurotrophic factor, and an astrocyte medium in which glial cell line-derived neurotrophic factor expression was silenced using RNAi technology. The results confirmed that the use of RNAi silencing to target pretreated glial cell line-derived neurotrophic factor expression promoted neuronal apoptosis. In addition, oxygen and glucose deprivation preconditioning was found to upregulate glial cell line-derived neurotrophic factor expression, and significantly reduce neuronal apoptosis.

  13. Molecular phylogeny of the antiangiogenic and neurotrophic serpin, pigment epithelium derived factor in vertebrates

    Science.gov (United States)

    Xu, Xuming; Zhang, Samuel Shao-Min; Barnstable, Colin J; Tombran-Tink, Joyce

    2006-01-01

    Background Pigment epithelium derived factor (PEDF), a member of the serpin family, regulates cell proliferation, promotes survival of neurons, and blocks growth of new blood vessels in mammals. Defining the molecular phylogeny of PEDF by bioinformatic analysis is one approach to understanding the link between its gene structure and its function in these biological processes. Results From a comprehensive search of available DNA databases we identified a single PEDF gene in all vertebrate species examined. These included four mammalian and six non-mammalian vertebrate species in which PEDF had not previously been described. A five gene cluster around PEDF was found in an approximate 100 kb region in mammals, birds, and amphibians. In ray-finned fish these genes are scattered over three chromosomes although only one PEDF gene was consistently found. The PEDF gene is absent in invertebrates including Drosophila melanogaster (D. melanogaster), Caenorhabditis elegans (C. elegans), and sea squirt (C. intestinalis). The PEDF gene is transcribed in all vertebrate phyla, suggesting it is biologically active throughout vertebrate evolution. The multiple actions of PEDF are likely conserved in evolution since it has the same gene structure across phyla, although the size of the gene ranges from 48.3 kb in X. tropicalis to 2.9 kb in fugu, with human PEDF at a size of 15.6 kb. A strong similarity in the proximal 200 bp of the PEDF promoter in mammals suggests the existence of a possible regulatory region across phyla. Using a non-synonymous/synonymous substitution rate ratio we show that mammalian and fish PEDFs have similar ratios of vertebrates and our studies suggest that the regulation and biological actions of this gene are preserved across vertebrates. This comprehensive analysis of the PEDF gene across phyla provides new information that will aid further characterization of common functional motifs of this serpin in biological processes. PMID:17020603

  14. Molecular phylogeny of the antiangiogenic and neurotrophic serpin, pigment epithelium derived factor in vertebrates

    Directory of Open Access Journals (Sweden)

    Barnstable Colin J

    2006-10-01

    Full Text Available Abstract Background Pigment epithelium derived factor (PEDF, a member of the serpin family, regulates cell proliferation, promotes survival of neurons, and blocks growth of new blood vessels in mammals. Defining the molecular phylogeny of PEDF by bioinformatic analysis is one approach to understanding the link between its gene structure and its function in these biological processes. Results From a comprehensive search of available DNA databases we identified a single PEDF gene in all vertebrate species examined. These included four mammalian and six non-mammalian vertebrate species in which PEDF had not previously been described. A five gene cluster around PEDF was found in an approximate 100 kb region in mammals, birds, and amphibians. In ray-finned fish these genes are scattered over three chromosomes although only one PEDF gene was consistently found. The PEDF gene is absent in invertebrates including Drosophila melanogaster (D. melanogaster, Caenorhabditis elegans (C. elegans, and sea squirt (C. intestinalis. The PEDF gene is transcribed in all vertebrate phyla, suggesting it is biologically active throughout vertebrate evolution. The multiple actions of PEDF are likely conserved in evolution since it has the same gene structure across phyla, although the size of the gene ranges from 48.3 kb in X. tropicalis to 2.9 kb in fugu, with human PEDF at a size of 15.6 kb. A strong similarity in the proximal 200 bp of the PEDF promoter in mammals suggests the existence of a possible regulatory region across phyla. Using a non-synonymous/synonymous substitution rate ratio we show that mammalian and fish PEDFs have similar ratios of Conclusion The PEDF gene first appears in vertebrates and our studies suggest that the regulation and biological actions of this gene are preserved across vertebrates. This comprehensive analysis of the PEDF gene across phyla provides new information that will aid further characterization of common functional motifs of

  15. The roles of glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor and nerve growth factor during the final stage of folliculogenesis: a focus on oocyte maturation.

    Science.gov (United States)

    Linher-Melville, Katja; Li, Julang

    2013-02-01

    Neurotrophic factors were first identified to promote the growth, survival or differentiation of neurons and have also been associated with the early stages of ovarian folliculogenesis. More recently, their effects on the final stage of follicular development, including oocyte maturation and early embryonic development, have been reported. Glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which are expressed in numerous peripheral tissues outside of the CNS, most notably the ovary, are now known to stimulate oocyte maturation in various species, also enhancing developmental competence. The mechanisms that underlie their actions in antral follicles, as well as the targets ultimately controlled by these factors, are beginning to emerge. GDNF, BDNF and NGF, alone or in combination, could be added to the media currently utilized for in vitro oocyte maturation, thereby potentially increasing the production and/or quality of early embryos.

  16. Postnatal roles of glial cell line-derived neurotrophic factor family members in nociceptors plasticity

    Institute of Scientific and Technical Information of China (English)

    Sacha A. Malin; Brian M. Davis

    2008-01-01

    The neurotrophin and glial cell line-derived neurotrophic factor (GDNF) family of growth factors have been extensively studied because of their proven ability to regulate development of the peripheral nervous system. The neurotrophin family,which includes nerve growth factor (NGF), NT-3, NT4/5 and BDNF, is also known for its ability to regulate the function of adult sensory neurons. Until recently, little was known concerning the role of the GNDF-family (that includes GDNF, artemin, neurturin and persephin) in adult sensory neuron function. Here we describe recent data that indicates that the GDNF family can regulate sensory neuron function, that some of its members are elevated in inflammatory pain models and that application of these growth factors produces pain in vivo. Finally we discuss how these two families of growth factors may converge on a single membrane receptor, TRPV 1, to produce long-lasting hyperalgesia.

  17. Liver-derived systemic factors drive β-cell hyperplasia in insulin resistant states

    Energy Technology Data Exchange (ETDEWEB)

    El Ouaamari, Abdelfattah; Kawamori, Dan; Dirice, Ercument; Liew, Chong Wee; Shadrach, Jennifer L.; Hu, Jiang; Katsuta, Hitoshi; Hollister-Lock, Jennifer; Qian, Weijun; Wagers, Amy J.; Kulkarni, Rohit N.

    2013-02-21

    Integrative organ cross-talk regulates key aspects of energy homeostasis and its dysregulation may underlie metabolic disorders such as obesity and diabetes. To test the hypothesis that cross-talk between the liver and pancreatic islets modulates β-cell growth in response to insulin resistance, we used the Liver-specific Insulin Receptor Knockout (LIRKO) mouse, a unique model that exhibits dramatic islet hyperplasia. Using complementary in vivo parabiosis and transplantation assays, and in vitro islet culture approaches, we demonstrate that humoral, non-neural, non-cell autonomous factor(s) induce β-cell proliferation in LIRKO mice. Furthermore, we report that a hepatocyte-derived factor(s) stimulates mouse and human β-cell proliferation in ex vivo assays, independent of ambient glucose and insulin levels. These data implicate the liver as a critical source of β-cell growth factors in insulin resistant states.

  18. Structures of a platelet-derived growth factor/propeptide complex and a platelet-derived growth factor/receptor complex

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Ann Hye-Ryong; Liu, Heli; Focia, Pamela J.; Chen, Xiaoyan; Lin, P. Charles; He, Xiaolin (Vanderbilt); (NWU)

    2010-07-13

    Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) are prototypic growth factors and receptor tyrosine kinases which have critical functions in development. We show that PDGFs share a conserved region in their prodomain sequences which can remain noncovalently associated with the mature cystine-knot growth factor domain after processing. The structure of the PDGF-A/propeptide complex reveals this conserved, hydrophobic association mode. We also present the structure of the complex between PDGF-B and the first three Ig domains of PDGFR{beta}, showing that two PDGF-B protomers clamp PDGFR{beta} at their dimerization seam. The PDGF-B:PDGFR{beta} interface is predominantly hydrophobic, and PDGFRs and the PDGF propeptides occupy overlapping positions on mature PDGFs, rationalizing the need of propeptides by PDGFs to cover functionally important hydrophobic surfaces during secretion. A large-scale structural organization and rearrangement is observed for PDGF-B upon receptor binding, in which the PDGF-B L1 loop, disordered in the structure of the free form, adopts a highly specific conformation to form hydrophobic interactions with the third Ig domain of PDGFR{beta}. Calorimetric data also shows that the membrane-proximal homotypic PDGFR{alpha} interaction, albeit required for activation, contributes negatively to ligand binding. The structural and biochemical data together offer insights into PDGF-PDGFR signaling, as well as strategies for PDGF-antagonism.

  19. What Is Rotating in Exploratory Factor Analysis?

    Science.gov (United States)

    Osborne, Jason W.

    2015-01-01

    Exploratory factor analysis (EFA) is one of the most commonly-reported quantitative methodology in the social sciences, yet much of the detail regarding what happens during an EFA remains unclear. The goal of this brief technical note is to explore what "rotation" is, what exactly is rotating, and why we use rotation when performing…

  20. Stepwise Variable Selection in Factor Analysis.

    Science.gov (United States)

    Kano, Yutaka; Harada, Akira

    2000-01-01

    Takes several goodness-of-fit statistics as measures of variable selection and develops backward elimination and forward selection procedures in exploratory factor analysis. A newly developed variable selection program, SEFA, can print several fit measures for a current model and models obtained by removing an internal variable or adding an…

  1. Multilevel exploratory factor analysis of discrete data

    NARCIS (Netherlands)

    Barendse, M.T.; Oort, F.J.; Jak, S.; Timmerman, M.E.

    2013-01-01

    Exploratory factor analysis (EFA) can be used to determine the dimensionality of a set of items. When data come from clustered subjects, such as pupils within schools or children within families, the hierarchical structure of the data should be taken into account. Standard multilevel EFA is only sui

  2. Combination effects of epidermal growth factor and glial cell line-derived neurotrophic factor on the in vitro developmental potential of porcine oocytes

    DEFF Research Database (Denmark)

    Valleh, Mehdi Vafaye; Rasmussen, Mikkel Aabech; Hyttel, Poul

    2016-01-01

    of improving this issue, the single and combined effects of epidermal growth factor (EGF) and glial cell line-derived neurotrophic factor (GDNF) on oocyte developmental competence were investigated. Porcine cumulus–oocyte cell complexes (COCs) were matured in serum-free medium supplemented with EGF (0, 10...... or 50 ng/ml) and/or GDNF (0, 10 or 50 ng/ml) for 44 h, and subsequently subjected to fertilization and cultured for 7 days in vitro. The in vitro-formed blastocysts derived from selected growth factor groups (i.e. EGF = 50 ng/ml; GDNF = 50 ng/ml; EGF = 50 ng/ml + GDNF = 50 ng/ml) were also used for m......RNA expression analysis, or were subjected to Hoechst staining. The results showed that the addition of EGF and/or GDNF during oocyte maturation dose dependently enhanced oocyte developmental competence. Compared with the embryos obtained from control or single growth factor-treated oocytes, treatment...

  3. An SPSSR -Menu for Ordinal Factor Analysis

    Directory of Open Access Journals (Sweden)

    Mario Basto

    2012-01-01

    Full Text Available Exploratory factor analysis is a widely used statistical technique in the social sciences. It attempts to identify underlying factors that explain the pattern of correlations within a set of observed variables. A statistical software package is needed to perform the calculations. However, there are some limitations with popular statistical software packages, like SPSS. The R programming language is a free software package for statistical and graphical computing. It offers many packages written by contributors from all over the world and programming resources that allow it to overcome the dialog limitations of SPSS. This paper offers an SPSS dialog written in theR programming language with the help of some packages, so that researchers with little or no knowledge in programming, or those who are accustomed to making their calculations based on statistical dialogs, have more options when applying factor analysis to their data and hence can adopt a better approach when dealing with ordinal, Likert-type data.

  4. Analysis of G-banding in tumor cell lines derived from human neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Junhua Zou; Yanhui Li

    2006-01-01

    BACKGROUND: The application of neural stem cell (NSC) is restricted because of its tumorigenesis, and the possible pathogenesis needs investigation.OBJECTIVE: To compare the differences of chromosomal G-banding between human NSCs (hNSCs) derived tumor cell line and hNSCs derived normal cell lines.DESIGN: A randomized controlled observation.SETTING: Building of Anatomy, Peking University Health Science Center.MATERIALS: The hNSC lines and hNSC-derived tumor cell lines were provided by the Research Center of Stem Cells, Peking University; DMEM/F12 (1:1) medium, N2 additive, B27 additive epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were produced by GIBCO BRL Company (USA); fetal bovine serum by HYCLONE Company (USA).METHODS: The experiments were carried out in the Department of Genetics, Peking University Health Science Center from February 2003 to July 2004. Human fetal striatal NSCs were inoculated hypodermically on the right scapular of nude mice; Normal human fetal striatal NSCs were cultured to 5-8 passages as controls. Karyotyping was performed on the 5th passage of hNSC-derived tumor cells at 6 weeks after hN-SC transplantation into nude mice (T1) and tumor cells at 15 weeks after transplantation (T2). Metaphase chromosomes were examined with microscope, G-banding cytogenetic analysis and karyotyping were performed according to the Cytoscan Karyotyping FISH and CGH software system (United biotechnology USA Corporation).MAIN OUTCOME MEASURES: G-banded analytical results of human fetal striatal nerve stem cells derived tumor cell lines (T1 and T2) of metaphase chromosomes were observed.RESULTS: ① Chromosome analysis of hNSC-derived tumor cell lines 1 (T1): Twenty-five well-spread metaphases were randomly selected for analysis. The karyotypes were 64, XX (8, 32%); 65, XX (1, 4%); 67,XX (5, 20%); 68, XX (11, 44%). The modal number of chromosomes in this cell lines was 68, which were all hypotriploid. The analysis of 8 G

  5. New Mathematical Derivations Applicable to Safety and Reliability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, J.A.; Ferson, S.

    1999-04-19

    Boolean logic expressions are often derived in safety and reliability analysis. Since the values of the operands are rarely exact, accounting for uncertainty with the tightest justifiable bounds is important. Accurate determination of result bounds is difficult when the inputs have constraints. One example of a constraint is that an uncertain variable that appears multiple times in a Boolean expression must always have the same value, although the value cannot be exactly specified. A solution for this repeated variable problem is demonstrated for two Boolean classes. The classes, termed functions with unate variables (including, but not limited to unate functions), and exclusive-or functions, frequently appear in Boolean equations for uncertain outcomes portrayed by logic trees (event trees and fault trees).

  6. ANALYSIS OF THE FACTORS AFFECTING THE AVERAGE

    Directory of Open Access Journals (Sweden)

    Carmen BOGHEAN

    2013-12-01

    Full Text Available Productivity in agriculture most relevantly and concisely expresses the economic efficiency of using the factors of production. Labour productivity is affected by a considerable number of variables (including the relationship system and interdependence between factors, which differ in each economic sector and influence it, giving rise to a series of technical, economic and organizational idiosyncrasies. The purpose of this paper is to analyse the underlying factors of the average work productivity in agriculture, forestry and fishing. The analysis will take into account the data concerning the economically active population and the gross added value in agriculture, forestry and fishing in Romania during 2008-2011. The distribution of the average work productivity per factors affecting it is conducted by means of the u-substitution method.

  7. Role of platelet-derived growth factor/platelet-derived growth factor receptor axis in the trafficking of circulating fibrocytes in pulmonary fibrosis.

    Science.gov (United States)

    Aono, Yoshinori; Kishi, Masami; Yokota, Yuki; Azuma, Momoyo; Kinoshita, Katsuhiro; Takezaki, Akio; Sato, Seidai; Kawano, Hiroshi; Kishi, Jun; Goto, Hisatsugu; Uehara, Hisanori; Izumi, Keisuke; Nishioka, Yasuhiko

    2014-12-01

    Circulating fibrocytes have been reported to migrate into the injured lungs, and contribute to fibrogenesis via CXCL12-CXCR4 axis. In contrast, we report that imatinib mesylate prevented bleomycin (BLM)-induced pulmonary fibrosis in mice by inhibiting platelet-derived growth factor receptor (PDGFR), even when it was administered only in the early phase. The goal of this study was to test the hypothesis that platelet-derived growth factor (PDGF) might directly contribute to the migration of fibrocytes to the injured lungs. PDGFR expression in fibrocytes was examined by flow cytometry and RT-PCR. The migration of fibrocytes was evaluated by using a chemotaxis assay for human fibrocytes isolated from peripheral blood. The numbers of fibrocytes triple-stained for CD45, collagen-1, and CXCR4 were also examined in lung digests of BLM-treated mice. PDGFR mRNA levels in fibrocytes isolated from patients with idiopathic pulmonary fibrosis were investigated by real-time PCR. Fibrocytes expressed both PDGFR-α and -β, and migrated in response to PDGFs. PDGFR inhibitors (imatinib, PDGFR-blocking antibodies) suppressed fibrocyte migration in vitro, and reduced the number of fibrocytes in the lungs of BLM-treated mice. PDGF-BB was a stronger chemoattractant than the other PDGFs in vitro, and anti-PDGFR-β-blocking antibody decreased the numbers of fibrocytes in the lungs compared with anti-PDGFR-α antibody in vivo. Marked expression of PDGFR-β was observed in fibrocytes from patients with idiopathic pulmonary fibrosis compared with healthy subjects. These results suggest that PDGF directly functions as a strong chemoattractant for fibrocytes. In particular, the PDGF-BB-PDGFR-β biological axis might play a critical role in fibrocyte migration into the fibrotic lungs.

  8. Brain-derived neurotrophic factor produced by human umbilical tissue-derived cells is required for its effect on hippocampal dendritic differentiation.

    Science.gov (United States)

    Alder, Janet; Kramer, Brian C; Hoskin, Casey; Thakker-Varia, Smita

    2012-06-01

    The potential for nonembryonic cells to promote differentiation of neuronal cells has therapeutic implications for regeneration of neurons damaged by stroke or injury and avoids many ethical and safety concerns. The authors have assessed the capacity of human umbilical tissue-derived cells (hUTC) and human mesenchymal stromal cells (hMSC) to enhance differentiation of rodent hippocampal neurons. Co-culture of hippocampal cells with hUTC or hMSC in transwell inserts for 3 days resulted in increase of several dendritic parameters including the number and length of primary dendrites. The effect of hUTC or hMSC on dendritic maturation was only apparent on neurons grown for 2 weeks in vitro prior to co-culture. Changes in dendritic morphology in the presence of hUTC were also accompanied by increased expression of the presynaptic marker synaptotagmin and the postsynaptic marker postsynaptic density protein 95 kDa (PSD95) suggesting that there may also be an increase in the number of synapses formed in the presence of hUTC. The effect of hUTC and hMSC on hippocampal cells in co-culture was comparable to those induced by treatment with recombinant human brain-derived neurotrophic factor (BDNF) implying that a similar factor may be released from hUTC or hMSC. Analysis of hUTC-conditioned medium by ELISA demonstrated that BDNF was indeed secreted. An antibody that blocks the actions of BDNF partially inhibited the actions of hUTC on dendritic morphology suggesting that BDNF is at least one of the factors secreted from the cells to promote dendritic maturation. These results indicate that hUTC secrete biologically active BDNF, which can affect dendritic morphology.

  9. Sequential process in brain-derived neurotrophic factor-induced functional periodontal tissue regeneration.

    Science.gov (United States)

    Konishi, Akihiro; Takeda, Katsuhiro; Fujita, Tsuyoshi; Kajiya, Mikihito; Matsuda, Shinji; Kittaka, Mizuho; Shiba, Hideki; Kurihara, Hidemi

    2016-04-01

    We recently demonstrated that brain-derived neurotrophic factor (BDNF) promotes periodontal tissue regeneration. The purpose of this study was to establish an essential component of a rational approach for the clinical application of BDNF in periodontal regenerative therapy. Here, we assessed the sequence of early events in BDNF-induced periodontal tissue regeneration, especially from the aspect of cementum regeneration. Brain-derived neurotrophic factor was applied into experimental periodontal defects in Beagle dogs. The localization of cells positive for neurotrophic tyrosine kinase, receptor, type 2, proliferating cell nuclear antigen, osteopontin, integrin αVβ3, and integrin α2β1 was evaluated by immunohistochemistry. The effects of BDNF on adhesion of cultured human periodontal ligament cells was examined by an in vitro study. The results suggest that BDNF could induce rapid cementum regeneration by stimulating adhesion, proliferation, and differentiation of periodontal ligament cells in the early regenerative phase, resulting in enhancement of periodontal tissue regeneration.

  10. Gastrodin promotes the secretion of brain-derived neurotrophic factor in the injured spinal cord

    Institute of Scientific and Technical Information of China (English)

    Changwei Song; Shiqiang Fang; Gang Lv; Xifan Mei

    2013-01-01

    Gastrodin, an active component of tall gastrodia tuber, is widely used in the treatment of dizziness, paralysis, epilepsy, stroke and dementia, and exhibits a neuroprotective effect. A rat model of spinal cord injury was established using Allen's method, and gastrodin was administered via the subarachnoid cavity and by intraperitoneal injection for 7 days. Results show that gastrodin promoted the secretion of brain-derived neurotrophic factor in rats with spinal cord injury. After gastrodin treatment, the maximum angle of the inclined plane test, and the Basso, Beattie and Bresnahan scores increased. Moreover, gastrodin improved neural tissue recovery in the injured spinal cord. These results demonstrate that gastrodin promotes the secretion of brain-derived neurotrophic factor, contributes to the recovery of neurological function, and protects neural cells against injury.

  11. Mathematical model for blood flow autoregulation by endothelium-derived relaxing factor

    CERN Document Server

    Chernyavsky, I L; Chernyavsky, Igor L.; Kudryashov, Nikolai A.

    2006-01-01

    The fluid shear stress is an important regulator of the cardiovascular system via the endothelium-derived relaxing factor (EDRF) that is Nitric Oxide. This mechanism involves biochemical reactions in an arterial wall. The autoregulation process is managed by the vascular tonus and gives the negative feedback for the shear stress changing. A new mathematical model for the autoregulation of a blood flow through arteria under the constant transmural pressure is presented. Endothelium-derived relaxing factor Nitric Oxide, the multi-layer structure of an arterial wall, and kinetic-diffusion processes are taken into consideration. The limit case of the thin-wall artery is analytically studied. The stability condition for a stationary point of the linearized system is given. The exact stationary solutions of the origin system are found. The numerical simulation for the autoregulation system is presented. It is shown the arteria adaptation to an initial radial perturbation and the transition of the system to new equi...

  12. Cloning, expression and identification of an isoform of human stromal cell derived factor-1α

    OpenAIRE

    LIANG, YIN-KU; Ping, Wei; BIAN, LIU-JIAO

    2015-01-01

    Human stromal cell derived factor-1α (hSDF-1α), a chemotactic factor of stem cells, regulates inflammation, promotes the mobilization of stem cells and induces angiogenesis following ischemia. Six SDF-1 isoforms, SDF-1α, SDF-1β, SDF-1γ, SDF-1δ, SDF-1ε and SDF-1ϕ, which all contain a signal peptide at the N-terminus, have been reported. In the present study a special isoform of hSDF-1α is described that does not contain the N-terminal signal peptide sequence. The hSDF-1α gene was cloned with t...

  13. Human Bronchial Epithelial Cell-Derived Factors from Severe Asthmatic Subjects Stimulate Eosinophil Differentiation.

    Science.gov (United States)

    Salter, Brittany M A; Smith, Steven G; Mukherjee, Manali; Plante, Sophie; Krisna, Sakktee; Nusca, Graeme; Oliveria, John Paul; Irshad, Anam; Gauvreau, Gail M; Chakir, Jamila; Nair, Parameswaran; Sehmi, Roma

    2017-08-30

    Activated bronchial epithelial cells release alarmins, including thymic stromal lymphopoietin (TSLP) that drive type 2 inflammatory responses. We hypothesize that bronchial epithelial-derived factors enhance in situ eosinophil differentiation and maturation from myeloid precursors, a process that is driven by an IL-5 rich micro-environment within asthma airways. To assess the eosinophilopoietic potential of epithelial-derived factors, eosinophil/basophil colony forming units (Eo/B-CFU) were enumerated in 14-day methylcellulose cultures of blood-derived mononuclear cells (NAMNCs) incubated with bronchial epithelial cell supernatants (BECSN) from healthy non-atopic controls (NC; n = 8), mild atopic asthmatics (MA; n = 9) and severe asthmatics (SA; n = 5). Receptor blocking antibodies were used to evaluate the contribution of alarmins. Modulation of mRNA expression of transcription factors crucial for eosinophil differentiation was evaluated. BECSN stimulated the clonogenic expansion of eosinophil progenitors, in vitro. In the presence of IL-5, Eo/B-CFU growth was significantly greater in co-cultures of BESCN from SA, compared to MA and NC. This effect was attenuated by a TSLP receptor blocking antibody but not by an ST2 antibody. Recombinant human TSLP (optimal at 100 pg/ml) stimulated significant Eo/B-CFU growth, which was significantly enhanced in presence of IL-5 (1 ng/ml). Overnight culture of CD34+ cells with IL-5 and TSLP synergistically increased GATA-2 and CEBP-alpha mRNA expression. The eosinophilopoietic potential of factors derived from bronchial epithelial cells is increased in severe asthma. Our data suggest that TSLP is a key alarmin produced by bronchial epithelial cells, which promotes in situ eosinophilopoiesis in a type 2 rich microenvironment.

  14. Mature and Precursor Brain-Derived Neurotrophic Factor Have Individual Roles in the Mouse Olfactory Bulb

    OpenAIRE

    Thomas Gerald Mast; Debra Ann Fadool

    2012-01-01

    BACKGROUND: Sensory deprivation induces dramatic morphological and neurochemical changes in the olfactory bulb (OB) that are largely restricted to glomerular and granule layer interneurons. Mitral cells, pyramidal-like neurons, are resistant to sensory-deprivation-induced changes and are associated with the precursor to brain-derived neurotrophic factor (proBDNF); here, we investigate its unknown function in the adult mouse OB. PRINCIPAL FINDINGS: As determined using brain-slice electrophysio...

  15. A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth

    OpenAIRE

    Liwei Lang; Xiaoyu Liu; Yan Li; Qing Zhou; Ping Xie; Chunhong Yan; Xiaoguang Chen

    2014-01-01

    The dineolignan manassantin A from Saururaceae was recently identified as a hypoxia-inducible factor 1 (HIF-1) inhibitor, but its in-vivo anti-tumor effect has not been explored. We synthesized a series of manassantin A derivatives, and found that replacing the central tetrahydrofuran moiety with a cyclopentane ring yielded a compound (LXY6006) with increased HIF-1-inhibitory activity yet decreased stereochemically complexity amenable to a simplified synthesis scheme. LXY6006 inhibited HIF-1α...

  16. Full-facial rejuvenation with autologous platelet-derived growth factors

    OpenAIRE

    2012-01-01

    The platelets used in oral, maxillofacial and plastic surgery are generally grouped as concentrated platelet rich plasma. The general principle of production consists of a centrifugation, making it possible to eliminate red blood cells, then acellular plasma, to preserve only the concentrated platelets. Aim to evaluate the efficacy of a three session of injections of autologous platelet-derived growth factors for full-face rejuvenation including the perioral and periorbital regions; 16 patien...

  17. Effect of Brain-Derived Neurotrophic Factor Haploinsufficiency on Stress-Induced Remodeling of Hippocampal Neurons

    OpenAIRE

    Magariños, A.M.; Li, C. J.; Toth, J. Gal; Bath, K.G.; Jing, D; Lee, F S; MCEWEN, B. S.

    2011-01-01

    Chronic restraint stress (CRS) induces the remodeling (i.e., retraction and simplification) of the apical dendrites of hippocampal CA3 pyramidal neurons in rats, suggesting that intrahippocampal connectivity can be affected by a prolonged stressful challenge. Since the structural maintenance of neuronal dendritic arborizations and synaptic connectivity requires neurotrophic support, we investigated the potential role of brain derived neurotrophic factor (BDNF), a neurotrophin enriched in the ...

  18. Brain-derived Neurotrophic Factor and Epilepsy—A Missing Link?

    OpenAIRE

    SCHARFMAN, HELEN E.

    2005-01-01

    It has been known for some time that brain-derived neurotrophic factor (BDNF) is critical to normal development of the CNS, and more recently, studies also have documented the ability of BDNF to modify adult CNS structure and function. Therefore, it is no surprise that BDNF has been linked to diseases, such as epilepsy, which may involve abnormal cortical development or altered brain structure and function after maturity. This review evaluates the evidence, particularly from recent studies, t...

  19. Plasma-derived versus recombinant factor concentrates in PUPs: a never ending debate?

    Science.gov (United States)

    Berntorp, Erik

    2017-01-31

    Inhibitor development in haemophilia is a serious complication to treatment with factor concentrates. Since the advent of more pure products, especially developed using recombinant DNA technology, some studies have shown an increased incidence of inhibitors in previously untreated patients (PUPs) receiving recombinant products whereas plasma-derived concentrates sometimes have been claimed to have a protective role, probably due to the content of von Willebrand factor (VWF). In fact, experiments indicate that the VWF may block uptake of factor VIII into macrophages for further processing to the immune system. Also, a competition between VWF and inhibitor binding to the C2 domain of factor VIII has been suggested. Recently, large cohort and surveillance studies have created a vigorous debate about the role of product class for inhibitor development as results have been conflicting. The only randomised prospective study, the SIPPET study, was published in 2016, and substantiated previous reports claiming that plasma derived concentrates give less inhibitors in patients with severe haemophilia A, previously not exposed to factor VIII. The debate will continue.

  20. Brain-derived neurotrophic factor and its receptors in Bergmann glia cells.

    Science.gov (United States)

    Poblete-Naredo, Irais; Guillem, Alain M; Juárez, Claudia; Zepeda, Rossana C; Ramírez, Leticia; Caba, Mario; Hernández-Kelly, Luisa C; Aguilera, José; López-Bayghen, Esther; Ortega, Arturo

    2011-12-01

    Brain-derived neurotrophic factor is an abundant and widely distributed neurotrophin expressed in the Central Nervous System. It is critically involved in neuronal differentiation and survival. The expression of brain-derived neurotrophic factor and that of its catalytic active cognate receptor (TrkB) has been extensively studied in neuronal cells but their expression and function in glial cells is still controversial. Despite of this fact, brain-derived neurotrophic factor is released from astrocytes upon glutamate stimulation. A suitable model to study glia/neuronal interactions, in the context of glutamatergic synapses, is the well-characterized culture of chick cerebellar Bergmann glia cells. Using, this system, we show here that BDNF and its functional receptor are present in Bergmann glia and that BDNF stimulation is linked to the activation of the phosphatidyl-inositol 3 kinase/protein kinase C/mitogen-activated protein kinase/Activator Protein-1 signaling pathway. Accordingly, reverse transcription-polymerase chain reaction (RT-PCR) experiments predicted the expression of full-length and truncated TrkB isoforms. Our results suggest that Bergmann glia cells are able to express and respond to BDNF stimulation favoring the notion of their pivotal role in neuroprotection. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Study of brain-derived neurotrophic factor gene transgenic neural stem cells in the rat retina

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xue-mei; YUAN Hui-ping; WU Dong-lai; ZHOU Xin-rong; SUN Da-wei; LI Hong-yi; SHAO Zheng-bo

    2009-01-01

    Background Neural stem cells (NSCs) transplantation and gene therapy have been widely investigated for treating the cerebullar and myelonic injuries, however, studies on the ophthalmology are rare. The aim of this study was to investigate the migration and differentiation of brain-derived neurotrophic factor (BDNF) gene transgenic NSCs transplanted into the normal rat retinas. Methods NSCs were cultured and purified in vitro and infected with recombinant retrovirus pLXSN-BDNF and pLXSN respectively, to obtain the BDNF overexpressed NSCs (BDNF-NSCs) and control cells (p-NSCs). The expression of BDNF genes in two transgenic NSCs and untreated NSCs were measured by fluorescent quantitative polymerase chain reaction (FQ-PCR) and enzyme-linked immunosorbent assay (ELISA). BDNF-NSCs and NSCs were infected with adeno-associated viruses-enhanced green fluorescent protein (AAV-EGFP) to track them in vivo and served as donor cells for transplantation into the subretinal space of normal rat retinas, phosphated buffer solution (PBS) served as pseudo transplantation for a negative control. Survival, migration, and differentiation of donor cells in host retinas were observed and analyzed with Heidelberg retina angiograph (HRA) and immunohistochemistry, respectively. Results NSCs were purified successfully by limiting dilution assay. The expression of BDNF gene in BDNF-NSCs was the highest among three groups both at mRNA level tested by FQ-PCR (P<0.05) and at protein level measured by ELISA (P<0.05), which showed that BDNF was overexpressed in BDNF-NSCs. The results of HRA demonstrated that graft cells could survive well and migrate into the host retinas, while the immunohistochemical analysis revealed that transplanted BDNF-NSCs differentiated into neuron more efficiently compared with the control NSCs 2 months after transplantation. Conclusions The seed cells of NSCs highly secreting BDNF were established. BDNF can promote NSCs to migrate and differentiate into neural cells in

  2. Association between smoking behaviour and genetic variants of glial cell line-derived neurotrophic factor

    Indian Academy of Sciences (India)

    ESZTER KOTYUK; NORA NEMETH; ZSOLT RONAI; ZSOLT DEMETROVICS; MARIA SASVARI-SZEKELY; ANNA SZEKELY

    2016-12-01

    Glial cell line-derived neurotrophic factor (GDNF) promotes development and differentiation of dopaminergic neurons, thus it has an important role in dopamine-related neuropsychiatric disorders. Since the role of dopamine system in smoking iswell established, we hypothesized that GDNF gene variants may affect smoking behaviour. Self-reported data on smoking behaviour (never smoked, quit, occasional, or regular smokers) and level of nicotine addiction (Hooked on Nicotine Checklist and Fagerstrom Nicotine Addiction Scale), anxiety, as well as buccal samples were obtained from 930 Hungarian young adults (18–35 years). Genetic analysis involved eight GDNF single-nucleotide polymorphisms (SNP) (rs1981844, rs3812047, rs3096140, rs2973041, rs2910702, rs1549250, rs2973050 and rs11111). Allele-wise association analyses of the eight GDNF SNPs provided a significant association between smoking behaviour and rs3096140 (P = 0.0039). The minor allele (C) was more frequent in those groups who smoked in some form (quit, occasional or regular smokers) as compared to those who neversmoked (P = 0.0046). This result remained significant after Bonferroni correction for multiple testing. In the ever smoking group, no significant differences were found in the level of nicotine addiction by the alleles of these polymorphisms. Also, nosignificant interaction of rs3096140 and smoking categories were observed on anxiety mean scores. Although previous data demonstrated an association between GDNF rs2910704 and severity of methamphetamine use to the best of our knowledge, this is the first study on the role of GDNF genetic variations in smoking behaviour. Our results suggest that GDNF rs3096140 might be involved in the genetic background of smoking, independent of anxiety characteristics.

  3. Pigment Epithelium-derived Factor in Cataractous Aqueous Humor and Lens Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    Tian Liu; Yizhi Liu; Mingxing Wu

    2006-01-01

    Purpose:To study the characteristics of PEDF in cataractous aqueous humor and its expression in human lens epithelium.Methods:The PEDF concentration in the aqueous humor was measured by enzyme linked immunosorbent assay in senile (130cases) and congenital (18cases) cataract patients who underwent cataract phacoemulsification extraction surgery. Anterior lens capsular specimens were obtained from these patients to count lens epithelial cells(LEC) density. The Lens Opacities Classification System Ⅲ was used to classify the senile cataracts as cortical, nuclear, posterior subcapsular and mixed types of opacity, and quantitative analysis of the nuclear opacities was performed by Pentacam Scheimpflug imaging system. Anterior lens capsular specimens from another senile(10cases) and congenital (10cases) cataract were collected for immunofluorescence with polyclonal antibodies specific to human pigment epithelium-derived factor(PEDF).Results:The mean aqueous level of PEDF was(178. 9±87. 5)ng/ml, and there was negative linear correlation of PEDF level and age (r=0. 811, P < 0. 001) . In senile cases, the aqueous PEDF concentration decreased with increasing nuclear opacities(r=0. 447, P < 0.01 ), and the mean PEDF level in nuclear cataract was significantly lower than that in posterior subcapsular opacity (P < 0.01 ) . PEDF immunostaining was detected in LEC of all capsular specimens.Conclusion :The PEDF level in human aqueous humor is related to age, types of cataracts and lens opacity. PEDF also express in human LEC. The study results suggest PEDF may regulate and/or protect LEC by paracrine and autocrine, and lack of PEDF may play a role in cataractogenesis.

  4. Stromal cell-derived factor 1 regulates the actin organization of chondrocytes and chondrocyte hypertrophy.

    Directory of Open Access Journals (Sweden)

    Koichi Murata

    Full Text Available Stromal cell-derived factor 1 (SDF-1/CXCL12/PBSF plays important roles in the biological and physiological functions of haematopoietic and mesenchymal stem cells. This chemokine regulates the formation of multiple organ systems during embryogenesis. However, its roles in skeletal development remain unclear. Here we investigated the roles of SDF-1 in chondrocyte differentiation. We demonstrated that SDF-1 protein was expressed at pre-hypertrophic and hypertrophic chondrocytes in the newly formed endochondral callus of rib fracture as well as in the growth plate of normal mouse tibia by immunohistochemical analysis. Using SDF-1(-/- mouse embryo, we histologically showed that the total length of the whole humeri of SDF-1(-/- mice was significantly shorter than that of wild-type mice, which was contributed mainly by shorter hypertrophic and calcified zones in SDF-1(-/- mice. Actin cytoskeleton of hypertrophic chondrocytes in SDF-1(-/- mouse humeri showed less F-actin and rounder shape than that of wild-type mice. Primary chondrocytes from SDF-1(-/- mice showed the enhanced formation of philopodia and loss of F-actin. The administration of SDF-1 to primary chondrocytes of wild-type mice and SDF-1(-/- mice promoted the formation of actin stress fibers. Organ culture of embryonic metatarsals from SDF-1(-/- mice showed the growth delay, which was recovered by an exogenous administration of SDF-1. mRNA expression of type X collagen in metatarsals and in primary chondrocytes of SDF-1(-/- mouse embryo was down-regulated while the administration of SDF-1 to metatarsals recovered. These data suggests that SDF-1 regulates the actin organization and stimulates bone growth by mediating chondrocyte hypertrophy.

  5. Association between smoking behaviour and genetic variants of glial cell line-derived neurotrophic factor.

    Science.gov (United States)

    Kotyuk, Eszter; Nemeth, Nora; Ronai, Zsolt; Demetrovics, Zsolt; Sasvari-Szekely, Maria; Szekely, Anna

    2016-12-01

    Glial cell line-derived neurotrophic factor (GDNF) promotes development and differentiation of dopaminergic neurons, thus it has an important role in dopamine-related neuropsychiatric disorders. Since the role of dopamine system in smoking is well established, we hypothesized that GDNF gene variants may affect smoking behaviour. Self-reported data on smoking behaviour (never smoked, quit, occasional, or regular smokers) and level of nicotine addiction (Hooked on Nicotine Checklist and Fagerstrom Nicotine Addiction Scale), anxiety, as well as buccal samples were obtained from 930 Hungarian young adults (18-35 years). Genetic analysis involved eight GDNF single-nucleotide polymorphisms (SNP) (rs1981844, rs3812047, rs3096140, rs2973041, rs2910702, rs1549250, rs2973050 and rs11111). Allele-wise association analyses of the eight GDNF SNPs provided a significant association between smoking behaviour and rs3096140 (P=0.0039). The minor allele (C) was more frequent in those groups who smoked in some form (quit, occasional or regular smokers) as compared to those who never smoked (P = 0.0046). This result remained significant after Bonferroni correction for multiple testing. In the ever smoking group, no significant differences were found in the level of nicotine addiction by the alleles of these polymorphisms. Also, no significant interaction of rs3096140 and smoking categories were observed on anxiety mean scores. Although previous data demonstrated an association between GDNF rs2910704 and severity of methamphetamine use to the best of our knowledge, this is the first study on the role of GDNF genetic variations in smoking behaviour. Our results suggest that GDNF rs3096140 might be involved in the genetic background of smoking, independent of anxiety characteristics.

  6. Characterizing the role of brain derived neurotrophic factor genetic variation in Alzheimer's disease neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Robyn A Honea

    Full Text Available There is accumulating evidence that neurotrophins, like brain-derived neurotrophic factor (BDNF, may impact aging and Alzheimer's Disease. However, traditional genetic association studies have not found a clear relationship between BDNF and AD. Our goal was to test whether BDNF single nucleotide polymorphisms (SNPs impact Alzheimer's Disease-related brain imaging and cognitive markers of disease. We completed an imaging genetics study on 645 Alzheimer's Disease Neuroimaging Initiative participants (ND=175, MCI=316, AD=154 who had cognitive, brain imaging, and genetics data at baseline and a subset of those with brain imaging data at two years. Samples were genotyped using the Illumina Human610-Quad BeadChip. 13 SNPs in BDNF were identified in the dataset following quality control measures (rs6265(Val66Met, rs12273363, rs11030094, rs925946, rs1050187, rs2203877, rs11030104, rs11030108, rs10835211, rs7934165, rs908867, rs1491850, rs1157459. We analyzed a subgroup of 8 SNPs that were in low linkage disequilibrium with each other. Automated brain morphometric measures were available through ADNI investigators, and we analyzed baseline cognitive scores, hippocampal and whole brain volumes, and rates of hippocampal and whole brain atrophy and rates of change in the ADAS-Cog over one and two years. Three out of eight BDNF SNPs analyzed were significantly associated with measures of cognitive decline (rs1157659, rs11030094, rs11030108. No SNPs were significantly associated with baseline brain volume measures, however six SNPs were significantly associated with hippocampal and/or whole brain atrophy over two years (rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850. We also found an interaction between the BDNF Val66Met SNP and age with whole brain volume. Our imaging-genetics analysis in a large dataset suggests that while BDNF genetic variation is not specifically associated with a diagnosis of AD, it appears to play a role in AD

  7. Effect of brain-derived neurotrophic factor haploinsufficiency on stress-induced remodeling of hippocampal neurons.

    Science.gov (United States)

    Magariños, A M; Li, C J; Gal Toth, J; Bath, K G; Jing, D; Lee, F S; McEwen, B S

    2011-03-01

    Chronic restraint stress (CRS) induces the remodeling (i.e., retraction and simplification) of the apical dendrites of hippocampal CA3 pyramidal neurons in rats, suggesting that intrahippocampal connectivity can be affected by a prolonged stressful challenge. Since the structural maintenance of neuronal dendritic arborizations and synaptic connectivity requires neurotrophic support, we investigated the potential role of brain derived neurotrophic factor (BDNF), a neurotrophin enriched in the hippocampus and released from neurons in an activity-dependent manner, as a mediator of the stress-induced dendritic remodeling. The analysis of Golgi-impregnated hippocampal sections revealed that wild type (WT) C57BL/6 male mice showed a similar CA3 apical dendritic remodeling in response to three weeks of CRS to that previously described for rats. Haploinsufficient BDNF mice (BDNF(±) ) did not show such remodeling, but, even without CRS, they presented shorter and simplified CA3 apical dendritic arbors, like those observed in stressed WT mice. Furthermore, unstressed BDNF(±) mice showed a significant decrease in total hippocampal volume. The dendritic arborization of CA1 pyramidal neurons was not affected by CRS or genotype. However, only in WT mice, CRS induced changes in the density of dendritic spine shape subtypes in both CA1 and CA3 apical dendrites. These results suggest a complex role of BDNF in maintaining the dendritic and spine morphology of hippocampal neurons and the associated volume of the hippocampal formation. The inability of CRS to modify the dendritic structure of CA3 pyramidal neurons in BDNF(±) mice suggests an indirect, perhaps permissive, role of BDNF in mediating hippocampal dendritic remodeling.

  8. Platelet-derived growth factor receptor-β in myocyte was upregulated by angiotensin II

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    To observe the regulation of platelet-derived growth factor (PDGF) receptor-βin myocyte stimulated by angiotensin II (AngII) at both integrated and cellular levels and reveal the signal transduction mechanism in cell, two kidneys, one clip (2K1C) renal hypertension were performed by placing a sliver clip around the left renal artery. Blood pressure and the ratio of left ventricular weight to body weight were measured at 4 and 8 weeks after operation. The content of AngII in heart was detected by radioimmunology assay; the protein level of PDGF receptor-βin heart was measured by Western blot analysis. The alteration of PDGF receptor-βstimulated by AngII and several inhibitors was observed on cultured neonatal rat ventricular myocyte (NRVM). The content of AngII in heart of 2K1C renal hypertensive rat at 4 and 8 weeks after operation was increased. Compared with sham group, 4 and 8 weeks after operation, PDGF receptor-βin heart of 2K1C group was upregulated by 100.3% and 127.1% (P < 0.05), respectively. This upregulation could be inhibited by captopril. For cultured myocyte, PDGF receptor-βwas increased by 47.1% after being stimulated by AngII and this upregulation could be inhibited by losartan which was an inhibitor of AT1 receptor. PLC inhibitor (U73122) and MEK inhibitor (PD98059) could partly inhibit PDGF receptor-βupregulation induced by AngII. These results suggested that AngII could upregulate PDGF receptor-βin myocyte by its AT1 receptor and this effect was at least partly dependent on PLC and extracellular signal-regulated kinase (ERK).

  9. Genetic and molecular analysis of wild-derived arrhythmic mice.

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Watanabe

    Full Text Available A new circadian variant was isolated by screening the intercross offspring of wild-caught mice (Mus musculus castaneus. This variant was characterized by an initial maintenance of damped oscillations and subsequent loss of rhythmicity after being transferred from light-dark (LD cycles to constant darkness (DD. To map the genes responsible for the persistence of rhythmicity (circadian ratio and the length of free-running period (tau, quantitative trait locus (QTL analysis was performed using F(2 mice obtained from an F(1 cross between the circadian variant and C57BL/6J mice. As a result, a significant QTL with a main effect for circadian ratio (Arrhythmicity; Arrh-1 was mapped on Chromosome (Chr 8. For tau, four significant QTLs, Short free-running period (Sfp-1 (Chr 1, Sfp-2 (Chr 6, Sfp-3 (Chr 8, Sfp-4 (Chr 11 were determined. An epistatic interaction was detected between Chr 3 (Arrh-2 and Chr 5 (Arrh-3. An in situ hybridization study of clock genes and mouse Period1::luciferase (mPer1::luc real-time monitoring analysis in the suprachiasmatic nucleus (SCN suggested that arrhythmicity in this variant might not be attributed to core circadian mechanisms in the SCN neurons. Our strategy using wild-derived variant mice may provide a novel opportunity to evaluate circadian and its related disorders in human that arise from the interaction between multiple variant genes.

  10. Systematic in vitro and in vivo characterization of Leukemia-inhibiting factor- and Fibroblast growth factor-derived porcine induced pluripotent stem cells

    DEFF Research Database (Denmark)

    Secher, Jan Ole Bertelsen; Ceylan, Ahmet; Mazzoni, Gianluca;

    2017-01-01

    Derivation and stable maintenance of porcine induced pluripotent stem cells (piPSCs) is challenging. We herein systematically analyzed two piPSC lines, derived by lentiviral transduction and cultured under either leukemia inhibitory factor (LIF) or fibroblast growth factor (FGF) conditions, to shed...

  11. Systematic in vitro and in vivo characterization of Leukemia-inhibiting factor- and Fibroblast growth factor-derived porcine induced pluripotent stem cells

    DEFF Research Database (Denmark)

    Secher, Jan O; Ceylan, Ahmet; Mazzoni, Gianluca

    2017-01-01

    Derivation and stable maintenance of porcine induced pluripotent stem cells (piPSCs) is challenging. We herein systematically analyzed two piPSC lines, derived by lentiviral transduction and cultured under either leukemia inhibitory factor (LIF) or fibroblast growth factor (FGF) conditions, to sh...

  12. Nominal Performance Biosphere Dose Conversion Factor Analysis

    Energy Technology Data Exchange (ETDEWEB)

    M.A. Wasiolek

    2005-04-28

    This analysis report is one of the technical reports containing documentation of the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the Total System Performance Assessment (TSPA) for the license application (LA) for the Yucca Mountain repository. This analysis report describes the development of biosphere dose conversion factors (BDCFs) for the groundwater exposure scenario, and the development of conversion factors for assessing compliance with the groundwater protection standards. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and provides an understanding of how this analysis report contributes to biosphere modeling. This report is one of two reports that develop BDCFs, which are input parameters for the TSPA-LA model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the ERMYN conceptual model and mathematical model. The input parameter reports, shown to the right of the ''Biosphere Model Report'' in Figure 1-1, contain detailed description of the model input parameters, their development, and the relationship between the parameters and specific features events and processes (FEPs). This report describes biosphere model calculations and their output, the BDCFs, for the groundwater exposure scenario. This analysis receives direct input from the outputs of the ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) and the five analyses that develop parameter values for the biosphere model (BSC 2005 [DIRS 172827]; BSC 2004 [DIRS 169672]; BSC 2004 [DIRS 169673]; BSC 2004 [DIRS 169458]; BSC 2004 [DIRS 169459]). The results of this report are further analyzed in the ''Biosphere Dose Conversion Factor Importance and Sensitivity Analysis

  13. Phasor analysis of binary diffraction gratings with different fill factors

    Energy Technology Data Exchange (ETDEWEB)

    MartInez, Antonio [Departamento de Ciencia de Materiales, Optica y TecnologIa Electronica, Universidad Miguel Hernandez, 03202 Elche (Spain); Sanchez-Lopez, Ma del Mar [Instituto de BioingenierIa y Departamento de Fisica y Arquitectura de Computadores, Universidad Miguel Hernandez, 03202 Elche (Spain); Moreno, Ignacio [Departamento de Ciencia de Materiales, Optica y TecnologIa Electronica, Universidad Miguel Hernandez, 03202 Elche (Spain)

    2007-09-11

    In this work, we present a simple analysis of binary diffraction gratings with different slit widths relative to the grating period. The analysis is based on a simple phasor technique directly derived from the Huygens principle. By introducing a slit phasor and a grating phasor, the intensity of the diffracted orders and the grating's resolving power can be easily obtained without applying the usual Fourier transform operations required for these calculations. The proposed phasor technique is mathematically equivalent to the Fourier transform calculation of the diffraction order amplitude, and it can be useful to explain binary diffraction gratings in a simple manner in introductory physics courses. This theoretical analysis is illustrated with experimental results using a liquid crystal device to display diffraction gratings with different fill factors.

  14. A kernel version of spatial factor analysis

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg

    2009-01-01

    . Schölkopf et al. introduce kernel PCA. Shawe-Taylor and Cristianini is an excellent reference for kernel methods in general. Bishop and Press et al. describe kernel methods among many other subjects. Nielsen and Canty use kernel PCA to detect change in univariate airborne digital camera images. The kernel...... version of PCA handles nonlinearities by implicitly transforming data into high (even infinite) dimensional feature space via the kernel function and then performing a linear analysis in that space. In this paper we shall apply kernel versions of PCA, maximum autocorrelation factor (MAF) analysis...

  15. What Is Rotating in Exploratory Factor Analysis?

    Directory of Open Access Journals (Sweden)

    Jason W. Osborne

    2015-01-01

    Full Text Available Exploratory factor analysis (EFA is one of the most commonly-reported quantitative methodology in the social sciences, yet much of the detail regarding what happens during an EFA remains unclear. The goal of this brief technical note is to explore what - rotation- is, what exactly is rotating, and why we use rotation when performing EFAs. Some commentary about the relative utility and desirability of different rotation methods concludes the narrative.

  16. A Beginner’s Guide to Factor Analysis: Focusing on Exploratory Factor Analysis

    Directory of Open Access Journals (Sweden)

    An Gie Yong

    2013-10-01

    Full Text Available The following paper discusses exploratory factor analysis and gives an overview of the statistical technique and how it is used in various research designs and applications. A basic outline of how the technique works and its criteria, including its main assumptions are discussed as well as when it should be used. Mathematical theories are explored to enlighten students on how exploratory factor analysis works, an example of how to run an exploratory factor analysis on SPSS is given, and finally a section on how to write up the results is provided. This will allow readers to develop a better understanding of when to employ factor analysis and how to interpret the tables and graphs in the output.

  17. Serum brain-derived neurotrophic factor (BDNF) levels in schizophrenia: A systematic review

    Science.gov (United States)

    Cui, Huiru; Jin, Yi; Wang, Jijun; Weng, Xuchu; Li, Chunbo

    2012-01-01

    Background There is increasing interest in the role of brain-derived neurotrophic factor (BDNF) in the onset and course of schizophrenia, but there are conflicting reports about serum levels of BDNF in patients with schizophrenia. Aim Conduct a meta-analysis combining studies from China and other countries that have evaluated the relationship of serum BDNF levels to schizophrenia. Method We used Cochrane methodology and RevMan 5.1 software to identify and pool the results of studies. Electronic searches of western and Chinese registries and follow-up assessment of references located 268 potential articles. Twenty-five articles (20 in English and 5 in Chinese) published before December 2011 that used case-control methods, included patients with schizophrenia who had no concurrent disorders, and used ELISA technology to assess serum BDNF were included in the analysis. The main outcome was the pooled standardized mean difference (SMD) between cases and controls. The quality of the studies was independently assessed by two raters using the GRADE system. The heterogeneity, sensitivity and potential publication bias of the studies was evaluated using RevMan. Results The pooled sample included 1663 patients with schizophrenia and 1355 controls. Fifteen of the included studies were rated as ‘poor quality’ and 10 were rated as ‘very poor quality’. The results of the studies were quite heterogenous (I2=95%) but subgroup analyses found that the heterogeneity was not related to country of origin, sample size, age, gender, prior use of antipsychotic medication, or study quality. The pooled SMD (computed using a random-effect model because of study heterogeneity) was -0.74 (95% CI, -0.99∼-0.50; Z=5.99, pbias. Conclusion Despite the robust statistical findings of lower serum BDNF in patients with schizophrenia than in controls, given the low quality of the available studies and the substantial heterogeneity between studies, the evidence of lower serum BDNF in patients

  18. The impact of adipose tissue-derived factors on the hypothalamic-pituitary-gonadal (HPG) axis.

    Science.gov (United States)

    Tsatsanis, Christos; Dermitzaki, Eirini; Avgoustinaki, Pavlina; Malliaraki, Niki; Mytaras, Vasilis; Margioris, Andrew N

    2015-01-01

    Adipose tissue produces factors, including adipokines, cytokines and chemokines which, when released, systemically exert endocrine effects on multiple tissues thereby affecting their physiology. Adipokines also affect the hypothalamic-pituitary-gonadal (HPG) axis both centrally, at the hypothalamic-pituitary level, and peripherally acting on the gonads themselves. Among the adipokines, leptin, adiponectin, resistin, chemerin and the peptide kisspeptin have pleiotropic actions on the HPG axis affecting male and female fertility. Furthermore, adipokines and adipose tissue-produced factors readily affect the immune system resulting in inflammation, which in turn impact the HPG axis, thus evidencing a link between metabolic inflammation and fertility. In this review we provide an overview of the existing extensive bibliography on the crosstalk between adipose tissue-derived factors and the HPG axis, with particular focus on the impact of obesity and the metabolic syndrome on gonadal function and fertility.

  19. Consequences of brain-derived neurotrophic factor withdrawal in CNS neurons and implications in disease.

    Science.gov (United States)

    Mariga, Abigail; Mitre, Mariela; Chao, Moses V

    2017-01-01

    Growth factor withdrawal has been studied across different species and has been shown to have dramatic consequences on cell survival. In the nervous system, withdrawal of nerve growth factor (NGF) from sympathetic and sensory neurons results in substantial neuronal cell death, signifying a requirement for NGF for the survival of neurons in the peripheral nervous system (PNS). In contrast to the PNS, withdrawal of central nervous system (CNS) enriched brain-derived neurotrophic factor (BDNF) has little effect on cell survival but is indispensible for synaptic plasticity. Given that most early events in neuropsychiatric disorders are marked by a loss of synapses, lack of BDNF may thus be an important part of a cascade of events that leads to neuronal degeneration. Here we review reports on the effects of BDNF withdrawal on CNS neurons and discuss the relevance of the loss in disease.

  20. Increased serum brain-derived neurotrophic factor (BDNF) levels in patients with narcolepsy

    DEFF Research Database (Denmark)

    Klein, Anders B; Jennum, Poul; Knudsen, Stine

    2013-01-01

    in hypocretin neurons in hypothalamus in post-mortem tissue. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are important for activity-dependent neuronal function and synaptic modulation and it is considered that these mechanisms are important in sleep regulation. We hypothesised......Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, sudden loss of muscle tone (cataplexy), fragmentation of nocturnal sleep and sleep paralysis. The symptoms of the disease strongly correlate with a reduction in hypocretin levels in CSF and a reduction...... that serum levels of these factors are altered in patients with narcolepsy compared to healthy controls without sleep disturbances. Polysomnography data was obtained and serum BDNF and NGF levels measured using ELISA, while hypocretin was measured using RIA. Serum BDNF levels were significantly higher...

  1. Influence of storage conditions on the release of growth factors in platelet-rich blood derivatives

    Directory of Open Access Journals (Sweden)

    Düregger Katharina

    2016-09-01

    Full Text Available Thrombocytes can be concentrated in blood derivatives and used as autologous transplants e.g. for wound treatment due to the release of growth factors such as platelet derived growth factor (PDGF. Conditions for processing and storage of these platelet-rich blood derivatives influence the release of PDGF from the platelet-bound α-granules into the plasma. In this study Platelet rich plasma (PRP and Platelet concentrate (PC were produced with a fully automated centrifugation system. Storage of PRP and PC for 1 h up to 4 months at temperatures between −20°C and +37°C was applied with the aim of evaluating the influence on the amount of released PDGF. Storage at −20°C resulted in the highest release of PDGF in PRP and a time dependency was determined: prolonged storage up to 1 month in PRP and 10 days in PC increased the release of PDGF. Regardless of the storage conditions, the release of PDGF per platelet was higher in PC than in PRP.

  2. Factor analysis identifies subgroups of constipation

    Institute of Scientific and Technical Information of China (English)

    Philip G Dinning; Mike Jones; Linda Hunt; Sergio E Fuentealba; Jamshid Kalanter; Denis W King; David Z Lubowski; Nicholas J Talley; Ian J Cook

    2011-01-01

    AIM: To determine whether distinct symptom groupings exist in a constipated population and whether such grouping might correlate with quantifiable pathophysiological measures of colonic dysfunction. METHODS: One hundred and ninety-one patients presenting to a Gastroenterology clinic with constipation and 32 constipated patients responding to a newspaper advertisement completed a 53-item, wide-ranging selfreport questionnaire. One hundred of these patients had colonic transit measured scintigraphically. Factor analysis determined whether constipation-related symptoms grouped into distinct aspects of symptomatology. Cluster analysis was used to determine whether individual patients naturally group into distinct subtypes. RESULTS: Cluster analysis yielded a 4 cluster solution with the presence or absence of pain and laxative unresponsiveness providing the main descriptors. Amongst all clusters there was a considerable proportion of patients with demonstrable delayed colon transit, irritable bowel syndrome positive criteria and regular stool frequency. The majority of patients with these characteristics also reported regular laxative use. CONCLUSION: Factor analysis identified four constipation subgroups, based on severity and laxative unresponsiveness, in a constipated population. However, clear stratification into clinically identifiable groups remains imprecise.

  3. The thermal analysis and derivative bronzes cast to plaster moulds

    Directory of Open Access Journals (Sweden)

    B. Pisarek

    2009-07-01

    Full Text Available It plaster moulds gets casted the alloys of following metals: Al, Cu, Ag, Au in precise and artistic founding. The investigation of the crys-tallization of bronzes in hot plaster moulds the method of the thermal analysis and derivative (TDA was not realized out so far. Probe TDAg and tripod enabling the execution of measurements on inductive casting machine INDUTHERM-VC 500D were designed for this technology especially. It was confirmed that one the method TDA can identify the crystallization process of the bronze in hot plaster moulds. The investigations of the superficial distribution of the concentration of elements in the microstructure of the studied grades of the bronze on X-ray microanalizer were conducted. It results that they be subject to in bronze CuSn10-C (B10 and the CuSn5Zn5Pb5-C (B555 of strong microsegregation from conducted investigations: Pb, Sn and Sb. The single separates of intermetallic phase κ was identified in the bronze B10 rich first of all in Zn, Sn, Sb and Fe, and two intermetallic phase, one rich were identified in the bronze B555 first of all in Zn, Sb, (Nor, Fe and second rich in Sn, Sb, (Nor, Fe. The most homogeneous microstructure from the bronze CuAl10Fe5Ni5-C (BA1055 is characterizes among the studied grades of the bronze in the cast state.

  4. Derivation of Boundary Manikins: A Principal Component Analysis

    Science.gov (United States)

    Young, Karen; Margerum, Sarah; Barr, Abbe; Ferrer, Mike A.; Rajulu, Sudhakar

    2008-01-01

    When designing any human-system interface, it is critical to provide realistic anthropometry to properly represent how a person fits within a given space. This study aimed to identify a minimum number of boundary manikins or representative models of subjects anthropometry from a target population, which would realistically represent the population. The boundary manikin anthropometry was derived using, Principal Component Analysis (PCA). PCA is a statistical approach to reduce a multi-dimensional dataset using eigenvectors and eigenvalues. The measurements used in the PCA were identified as those measurements critical for suit and cockpit design. The PCA yielded a total of 26 manikins per gender, as well as their anthropometry from the target population. Reduction techniques were implemented to reduce this number further with a final result of 20 female and 22 male subjects. The anthropometry of the boundary manikins was then be used to create 3D digital models (to be discussed in subsequent papers) intended for use by designers to test components of their space suit design, to verify that the requirements specified in the Human Systems Integration Requirements (HSIR) document are met. The end-goal is to allow for designers to generate suits which accommodate the diverse anthropometry of the user population.

  5. A kernel version of spatial factor analysis

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg

    2009-01-01

    of PCA and related techniques. An interesting dilemma in reduction of dimensionality of data is the desire to obtain simplicity for better understanding, visualization and interpretation of the data on the one hand, and the desire to retain sufficient detail for adequate representation on the other hand......Based on work by Pearson in 1901, Hotelling in 1933 introduced principal component analysis (PCA). PCA is often used for general feature generation and linear orthogonalization or compression by dimensionality reduction of correlated multivariate data, see Jolliffe for a comprehensive description...... version of PCA handles nonlinearities by implicitly transforming data into high (even infinite) dimensional feature space via the kernel function and then performing a linear analysis in that space. In this paper we shall apply kernel versions of PCA, maximum autocorrelation factor (MAF) analysis...

  6. Pigment epithelium-derived factor mediates impaired lung vascular development in neonatal hyperoxia.

    Science.gov (United States)

    Chetty, Anne; Bennett, Michelle; Dang, Linh; Nakamura, Daisy; Cao, Gong-Jie; Mujahid, Sana; Volpe, MaryAnn; Herman, Ira; Becerra, S Patricia; Nielsen, Heber C

    2015-03-01

    Bronchopulmonary dysplasia is a chronic lung disease of preterm infants characterized by arrested microvascularization and alveolarization. Studies show the importance of proangiogenic factors for alveolarization, but the importance of antiangiogenic factors is unknown. We proposed that hyperoxia increases the potent angiostatin, pigment epithelium-derived factor (PEDF), in neonatal lungs, inhibiting alveolarization and microvascularization. Wild-type (WT) and PEDF(-/-) mice were exposed to room air (RA) or 0.9 fraction of inspired oxygen from Postnatal Day 5 to 13. PEDF protein was increased in hyperoxic lungs compared with RA-exposed lungs (P epithelium. Hyperoxia reduced alveolarization in WT mice (P lung microvascularization by vascular endothelial growth factor and PEDF was studied in vitro using MFLM-91U cells, a fetal mouse lung endothelial cell line. Vascular endothelial growth factor stimulation of proliferation, migration, and capillary tube formation was inhibited by PEDF. MFLM-91U cells exposed to conditioned medium (CM) from E17 fetal mouse lung type II (T2) cells cultured in 0.9 fraction of inspired oxygen formed fewer capillary tubes than CM from T2 cells cultured in RA (hyperoxia CM, 51 ± 10% of RA CM, P < 0.05), an effect abolished by PEDF antibody. We conclude that PEDF mediates reduced vasculogenesis and alveolarization in neonatal hyperoxia. Bronchopulmonary dysplasia likely results from an altered balance between pro- and antiangiogenic factors.

  7. Nominal Performance Biosphere Dose Conversion Factor Analysis

    Energy Technology Data Exchange (ETDEWEB)

    M. Wasiolek

    2004-09-08

    This analysis report is one of the technical reports containing documentation of the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the Total System Performance Assessment (TSPA) for the license application (LA) for the Yucca Mountain repository. This analysis report describes the development of biosphere dose conversion factors (BDCFs) for the groundwater exposure scenario, and the development of conversion factors for assessing compliance with the groundwater protection standard. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and provides an understanding of how this analysis report contributes to biosphere modeling. This report is one of two reports that develop biosphere BDCFs, which are input parameters for the TSPA-LA model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the ERMYN conceptual model and mathematical model. The input parameter reports, shown to the right of the ''Biosphere Model Report'' in Figure 1-1, contain detailed description of the model input parameters, their development, and the relationship between the parameters and specific features events and processes (FEPs). This report describes biosphere model calculations and their output, the BDCFs, for the groundwater exposure scenario. The objectives of this analysis are to develop BDCFs for the groundwater exposure scenario for the three climate states considered in the TSPA-LA as well as conversion factors for evaluating compliance with the groundwater protection standard. The BDCFs will be used in performance assessment for calculating all-pathway annual doses for a given concentration of radionuclides in groundwater. The conversion factors will be used for calculating gross alpha particle

  8. Breaking the mold: transcription factors in the anucleate platelet and platelet-derived microparticles

    Directory of Open Access Journals (Sweden)

    Katie L Lannan

    2015-02-01

    Full Text Available Platelets are small anucleate blood cells derived from megakaryocytes. In addition to their pivotal roles in hemostasis, platelets are the smallest, yet most abundant, immune cell and regulate inflammation, immunity, and disease progression. Although platelets lack DNA, and thus no functional transcriptional activities, they are nonetheless rich sources of RNAs, possess an intact spliceosome, and are thus capable of synthesizing proteins. Previously, it was thought that platelet RNAs and translational machinery were remnants from the megakaryocyte. We now know that the initial description of platelets as cellular fragments is an antiquated notion, as mounting evidence suggests otherwise. Therefore, it is reasonable to hypothesize that platelet transcription factors are not vestigial remnants from megakaryoctes, but have important, if only partly understood functions. Proteins play multiple cellular roles to minimize energy expenditure for maximum cellular function; thus, the same can be expected for transcription factors. In fact, numerous transcription factors have non-genomic roles, both in platelets and in nucleated cells. Our lab and others have discovered the presence and nongenomic roles of transcription factors in platelets, such as the nuclear factor kappa β (NFκB family of proteins and peroxisome proliferator activated receptor gamma (PPARγ. In addition to numerous roles in regulating platelet activation, functional transcription factors can be transferred to vascular and immune cells through platelet microparticles. This method of transcellular delivery of key immune molecules may be a vital mechanism by which platelet transcription factors regulate inflammation and immunity. At the very least, platelets are an ideal model cell to dissect out the nongenomic roles of transcription factors in nucleated cells. There is abundant evidence to suggest that transcription factors in platelets play key roles in regulating inflammatory and

  9. OTC Derivatives and Global Economic Activity: An Empirical Analysis

    Directory of Open Access Journals (Sweden)

    Gordon Bodnar

    2017-06-01

    Full Text Available That the global market for derivatives has expanded beyond recognition is well known. What is not know is how this market interacts with economic activity. We provide the first empirical characterization of interdependencies between OECD economic activity and the global OTC derivatives market. To this end, we apply a vector-error correction model to OTC derivatives disaggregated across instruments and counterparties. The results indicate that with one exception, the heterogeneity of OTC contracts is too pronounced to be reliably summarized by our measures of economic activity. The one exception is interest-rate derivatives held by Other Financial Institutions.

  10. Exploratory factor analysis in Rehabilitation Psychology: a content analysis.

    Science.gov (United States)

    Roberson, Richard B; Elliott, Timothy R; Chang, Jessica E; Hill, Jessica N

    2014-11-01

    Our objective was to examine the use and quality of exploratory factor analysis (EFA) in articles published in Rehabilitation Psychology. Trained raters examined 66 separate exploratory factor analyses in 47 articles published between 1999 and April 2014. The raters recorded the aim of the EFAs, the distributional statistics, sample size, factor retention method(s), extraction and rotation method(s), and whether the pattern coefficients, structure coefficients, and the matrix of association were reported. The primary use of the EFAs was scale development, but the most widely used extraction and rotation method was principle component analysis, with varimax rotation. When determining how many factors to retain, multiple methods (e.g., scree plot, parallel analysis) were used most often. Many articles did not report enough information to allow for the duplication of their results. EFA relies on authors' choices (e.g., factor retention rules extraction, rotation methods), and few articles adhered to all of the best practices. The current findings are compared to other empirical investigations into the use of EFA in published research. Recommendations for improving EFA reporting practices in rehabilitation psychology research are provided.

  11. Platelet-derived growth factor and platelet-derived growth factor receptor-α expression in the normal human thymus and thymoma

    Science.gov (United States)

    Cimpean, Anca Maria; Ceauşu, Raluca; Encică, Svetlana; Gaje, Pusa Nela; Ribatti, Domenico; Raica, Marius

    2011-01-01

    Platelet-derived growth factor (PDGF) and its receptors (PDGFRs) are strongly involved in the normal development of several organs, tumour angiogenesis and malignant progression and metastasis. Few studies concerning their expression, distribution and role in normal and pathological human thymus are available in the literature. The aim of this study has been to analyse the immunohistochemical expression of PDGF and PDGFR-α in prenatal and postnatal normal human thymus and thymomal biopsy specimens. The results demonstrated immunoreactivity to both PDGF and PDGFR-α in all specimens, but the intensity, distribution and number of positive cells were different in normal thymus and thymomas, and also among different tumour types. PDGF and PDGFR-α were weakly expressed in foetal and postnatal humans with a different distribution between cortex and medulla in both blood vessels and epithelial cells, whereas they were overexpressed in thymoma, especially in type B2 and B3, in the tumour epithelial cells. Overall, these data suggest that PDGF and PDGFR-α may be involved in the pathophysiology of the human thymus. PMID:21645144

  12. Platelet-derived growth factor and platelet-derived growth factor receptor-α expression in the normal human thymus and thymoma.

    Science.gov (United States)

    Cimpean, Anca Maria; Ceauşu, Raluca; Encică, Svetlana; Gaje, Pusa Nela; Ribatti, Domenico; Raica, Marius

    2011-10-01

    Platelet-derived growth factor (PDGF) and its receptors (PDGFRs) are strongly involved in the normal development of several organs, tumour angiogenesis and malignant progression and metastasis. Few studies concerning their expression, distribution and role in normal and pathological human thymus are available in the literature. The aim of this study has been to analyse the immunohistochemical expression of PDGF and PDGFR-α in prenatal and postnatal normal human thymus and thymomal biopsy specimens. The results demonstrated immunoreactivity to both PDGF and PDGFR-α in all specimens, but the intensity, distribution and number of positive cells were different in normal thymus and thymomas, and also among different tumour types. PDGF and PDGFR-α were weakly expressed in foetal and postnatal humans with a different distribution between cortex and medulla in both blood vessels and epithelial cells, whereas they were overexpressed in thymoma, especially in type B2 and B3, in the tumour epithelial cells. Overall, these data suggest that PDGF and PDGFR-α may be involved in the pathophysiology of the human thymus.

  13. The suppression of fibroblast growth factor 2/fibroblast growth factor 4-dependent tumour angiogenesis and growth by the anti-growth factor activity of dextran derivative (CMDB7).

    OpenAIRE

    Bagheri-Yarmand, R.; Kourbali, Y; Mabilat, C; Morère, J. F.; Martin, A; Lu, H; Soria, C; Jozefonvicz, J; Crépin, M

    1998-01-01

    Our previous studies showed that carboxymethyl benzylamide dextran (CMDB7) blocks basic fibroblast growth factor (FGF-2)-dependent cell proliferation of a human breast epithelial line (HBL100), suggesting its potential role as a potent antiangiogenic substance. The derived cell line (HH9), which was transformed with the hst/FGF4 gene, has been shown to be highly proliferative in vitro and to induce angiogenic tumours in nude mice. We show here that CMDB7 inhibits the mitogenic activities of t...

  14. Nerve growth factor, brain-derived neurotrophic factor, and the chronobiology of mood: a new insight into the "neurotrophic hypothesis"

    Directory of Open Access Journals (Sweden)

    Tirassa P

    2015-10-01

    Full Text Available Paola Tirassa,1 Adele Quartini,2 Angela Iannitelli2–4 1National Research Council (CNR, Institute of Cell Biology and Neurobiology (IBCN, 2Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine – "Sapienza" University of Rome, 3Italian Psychoanalytical Society (SPI, Rome, Italy; 4International Psychoanalytical Association (IPA, London, UKAbstract: The light information pathways and their relationship with the body rhythms have generated a new insight into the neurobiology and the neurobehavioral sciences, as well as into the clinical approaches to human diseases associated with disruption of circadian cycles. Light-based strategies and/or drugs acting on the circadian rhythms have widely been used in psychiatric patients characterized by mood-related disorders, but the timing and dosage use of the various treatments, although based on international guidelines, are mainly dependent on the psychiatric experiences. Further, many efforts have been made to identify biomarkers able to disclose the circadian-related aspect of diseases, and therefore serve as diagnostic, prognostic, and therapeutic tools in clinic to assess the different mood-related symptoms, including pain, fatigue, sleep disturbance, loss of interest or pleasure, appetite, psychomotor changes, and cognitive impairments. Among the endogenous factors suggested to be involved in mood regulation, the neurotrophins, nerve growth factor, and brain-derived neurotrophic factor show anatomical and functional link with the circadian system and mediate some of light-induced effects in brain. In addition, in humans, both nerve growth factor and brain-derived neurotrophic factor have showed a daily rhythm, which correlate with the morningness–eveningness dimensions, and are influenced by light, suggesting their potential role as biomarkers for chronotypes and/or chronotherapy. The evidences of the relationship between the diverse mood-related disorders

  15. Connective tissue growth factor differentially binds to members of the cystine knot superfamily and potentiates platelet-derived growth factor-B signaling in rabbit corneal fibroblast cells.

    Science.gov (United States)

    Pi, Liya; Chung, Pei-Yu; Sriram, Sriniwas; Rahman, Masmudur M; Song, Wen-Yuan; Scott, Edward W; Petersen, Bryon E; Schultz, Gregory S

    2015-11-26

    To study the binding of connective tissue growth factor (CTGF) to cystine knot-containing ligands and how this impacts platelet-derived growth factor (PDGF)-B signaling. The binding strengths of CTGF to cystine knot-containing growth factors including vascular endothelial growth factor (VEGF)-A, PDGF-B, bone morphogenetic protein (BMP)-4, and transforming growth factor (TGF)-β1 were compared using the LexA-based yeast two-hybrid system. EYG48 reporter strain that carried a wild-type LEU2 gene under the control of LexA operators and a lacZ reporter plasmid (p80p-lacZ) containing eight high affinity LexA binding sites were used in the yeast two-hybrid analysis. Interactions between CTGF and the tested growth factors were evaluated based on growth of transformed yeast cells on selective media and colorimetric detection in a liquid β-galactosidase activity assay. Dissociation constants of CTGF to VEGF-A isoform 165 or PDGF-BB homo-dimer were measured in surface plasma resonance (SPR) analysis. CTGF regulation in PDGF-B presentation to the PDGF receptor β (PDGFRβ) was also quantitatively assessed by the SPR analysis. Combinational effects of CTGF protein and PDGF-BB on activation of PDGFRβ and downstream signaling molecules ERK1/2 and AKT were assessed in rabbit corneal fibroblast cells by Western analysis. In the LexA-based yeast two-hybrid system, cystine knot motifs of tested growth factors were fused to the activation domain of the transcriptional factor GAL4 while CTGF was fused to the DNA binding domain of the bacterial repressor protein LexA. Yeast co-transformants containing corresponding fusion proteins for CTGF and all four tested cystine knot motifs survived on selective medium containing galactose and raffinose but lacking histidine, tryptophan, and uracil. In liquid β-galactosidase assays, CTGF expressing cells that were co-transformed with the cystine knot of VEGF-A had the highest activity, at 29.88 ± 0.91 fold above controls (P rabbit corneal

  16. Neuroprotection elicited by nerve growth factor and brain-derived neurotrophic factor released from astrocytes in response to methylmercury.

    Science.gov (United States)

    Takemoto, Takuya; Ishihara, Yasuhiro; Ishida, Atsuhiko; Yamazaki, Takeshi

    2015-07-01

    The protective roles of astrocytes in neurotoxicity induced by environmental chemicals, such as methylmercury (MeHg), are largely unknown. We found that conditioned medium of MeHg-treated astrocytes (MCM) attenuated neuronal cell death induced by MeHg, suggesting that astrocytes-released factors can protect neuronal cells. The increased expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) was observed in MeHg-treated astrocytes. NGF and BDNF were detected in culture media as homodimers, which are able to bind specific tyrosine kinase receptors, tropomyosin related kinase (Trk) A and TrkB, respectively. The TrkA antagonist and TrkB antagonist abolished the protective effects of MCM in neuronal cell death induced by MeHg. Taken together, astrocytes synthesize and release NGF and BDNF in response to MeHg to protect neurons from MeHg toxicity. This study is considered to show a novel defense mechanism against MeHg-induced neurotoxicity.

  17. Myeloid-Derived Vascular Endothelial Growth Factor and Hypoxia-Inducible Factor Are Dispensable for Ocular Neovascularization—Brief Report

    Science.gov (United States)

    Liyanage, Sidath E.; Fantin, Alessandro; Villacampa, Pilar; Lange, Clemens A.; Denti, Laura; Cristante, Enrico; Smith, Alexander J.; Ali, Robin R.; Luhmann, Ulrich F.

    2016-01-01

    Objective— Ocular neovascularization (ONV) is a pathological feature of sight-threatening human diseases, such as diabetic retinopathy and age-related macular degeneration. Macrophage depletion in mouse models of ONV reduces the formation of pathological blood vessels, and myeloid cells are widely considered an important source of the vascular endothelial growth factor A (VEGF). However, the importance of VEGF or its upstream regulators hypoxia-inducible factor-1α (HIF1α) and hypoxia-inducible factor-2α (HIF2α) as myeloid-derived regulators of ONV remains to be determined. Approach and Results— We used 2 mouse models of ONV, choroidal neovascularization and oxygen-induced retinopathy, to show that Vegfa is highly expressed by several cell types, but not myeloid cells during ONV. Moreover, myeloid-specific VEGF ablation did not reduce total ocular VEGF during choroidal neovascularization or oxygen-induced retinopathy. In agreement, the conditional inactivation of Vegfa, Hif1a, or Epas1 in recruited and resident myeloid cells that accumulated at sites of neovascularization did not significantly reduce choroidal neovascularization or oxygen-induced retinopathy. Conclusions— The finding that myeloid cells are not a significant local source of VEGF in these rodent models of ONV suggests that myeloid function in neovascular eye disease differs from skin wound healing and other neovascular pathologies. PMID:26603154

  18. Mature and precursor brain-derived neurotrophic factor have individual roles in the mouse olfactory bulb.

    Directory of Open Access Journals (Sweden)

    Thomas Gerald Mast

    Full Text Available BACKGROUND: Sensory deprivation induces dramatic morphological and neurochemical changes in the olfactory bulb (OB that are largely restricted to glomerular and granule layer interneurons. Mitral cells, pyramidal-like neurons, are resistant to sensory-deprivation-induced changes and are associated with the precursor to brain-derived neurotrophic factor (proBDNF; here, we investigate its unknown function in the adult mouse OB. PRINCIPAL FINDINGS: As determined using brain-slice electrophysiology in a whole-cell configuration, brain-derived neurotrophic factor (BDNF, but not proBDNF, increased mitral cell excitability. BDNF increased mitral cell action potential firing frequency and decreased interspike interval in response to current injection. In a separate set of experiments, intranasal delivery of neurotrophic factors to awake, adult mice was performed to induce sustained interneuron neurochemical changes. ProBDNF, but not BDNF, increased activated-caspase 3 and reduced tyrosine hydroxylase immunoreactivity in OB glomerular interneurons. In a parallel set of experiments, short-term sensory deprivation produced by unilateral naris occlusion generated an identical phenotype. CONCLUSIONS: Our results indicate that only mature BDNF increases mitral cell excitability whereas proBDNF remains ineffective. Our demonstration that proBDNF activates an apoptotic marker in vivo is the first for any proneurotrophin and establishes a role for proBDNF in a model of neuronal plasticity.

  19. Glial cell line-derived neurotrophic factor influences proliferation of osteoblastic cells.

    Science.gov (United States)

    Gale, Zoe; Cooper, Paul R; Scheven, Ben A

    2012-02-01

    Little is known about the role of neurotrophic growth factors in bone metabolism. This study investigated the short-term effects of glial cell line-derived neurotrophic factor (GDNF) on calvarial-derived MC3T3-E1 osteoblasts. MC3T3-E1 expressed GDNF as well as its canonical receptors, GFRα1 and RET. Addition of recombinant GDNF to cultures in serum-containing medium modestly inhibited cell growth at high concentrations; however, under serum-free culture conditions GDNF dose-dependently increased cell proliferation. GDNF effects on cell growth were inversely correlated with its effect on alkaline phosphatase (AlP) activity showing a significant dose-dependent inhibition of relative AlP activity with increasing concentrations of GDNF in serum-free culture medium. Live/dead and lactate dehydrogenase assays demonstrated that GDNF did not significantly affect cell death or survival under serum-containing and serum-free conditions. The effect of GDNF on cell growth was abolished in the presence of inhibitors to GFRα1 and RET indicating that GDNF stimulated calvarial osteoblasts via its canonical receptors. Finally, this study found that GDNF synergistically increased tumor necrosis factor-α (TNF-α)-stimulated MC3T3-E1 cell growth suggesting that GDNF interacted with TNF-α-induced signaling in osteoblastic cells. In conclusion, this study provides evidence for a direct, receptor-mediated effect of GDNF on osteoblasts highlighting a novel role for GDNF in bone physiology.

  20. Secretome analysis of human oligodendrocytes derived from neural stem cells.

    Directory of Open Access Journals (Sweden)

    Woo Kyung Kim

    Full Text Available In this study, we investigated the secretome of human oligodendrocytes (F3.Olig2 cells generated from human neural stem cells by transduction with the gene encoding the Olig2 transcription factor. Using mRNA sequencing and protein cytokine arrays, we identified a number of biologically important secretory proteins whose expression has not been previously reported in oligodendrocytes. We found that F3.Olig2 cells secrete IL-6, PDGF-AA, GRO, GM-CSF, and M-CSF, and showed prominent expression of their corresponding receptors. Co-expression of ligands and receptors suggests that autocrine signaling loops may play important roles in both differentiation and maintenance of oligodendrocytes. We also found that F3.Olig2 cells secrete matrix metalloproteinases and matrix metalloproteinase-associated proteins associated with functional competence of oligodendrocytes. The results of our secretome analysis provide insights into the functional and molecular details of human oligodendrocytes. To the best of our knowledge, this is the first systematic analysis of the secretome of oligodendrocytes.

  1. Sensitivity analysis of the GNSS derived Victoria plate motion

    Science.gov (United States)

    Apolinário, João; Fernandes, Rui; Bos, Machiel

    2014-05-01

    Fernandes et al. (2013) estimated the angular velocity of the Victoria tectonic block from geodetic data (GNSS derived velocities) only.. GNSS observations are sparse in this region and it is therefore of the utmost importance to use the available data (5 sites) in the most optimal way. Unfortunately, the existing time-series were/are affected by missing data and offsets. In addition, some time-series were close to the considered minimal threshold value to compute one reliable velocity solution: 2.5-3.0 years. In this research, we focus on the sensitivity of the derived angular velocity to changes in the data (longer data-span for some stations) by extending the used data-span: Fernandes et al. (2013) used data until September 2011. We also investigate the effect of adding other stations to the solution, which is now possible since more stations became available in the region. In addition, we study if the conventional power-law plus white noise model is indeed the best stochastic model. In this respect, we apply different noise models using HECTOR (Bos et al. (2013), which can use different noise models and estimate offsets and seasonal signals simultaneously. The seasonal signal estimation is also other important parameter, since the time-series are rather short or have large data spans at some stations, which implies that the seasonal signals still can have some effect on the estimated trends as shown by Blewitt and Lavellee (2002) and Bos et al. (2010). We also quantify the magnitude of such differences in the estimation of the secular velocity and their effect in the derived angular velocity. Concerning the offsets, we investigate how they can, detected and undetected, influence the estimated plate motion. The time of offsets has been determined by visual inspection of the time-series. The influence of undetected offsets has been done by adding small synthetic random walk signals that are too small to be detected visually but might have an effect on the

  2. Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve:viscoelasticity characterization

    Institute of Scientific and Technical Information of China (English)

    Xue-man Lv; Yan Liu; Fei Wu; Yi Yuan; Min Luo

    2016-01-01

    The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 μg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery.

  3. Analysis of Ultra Linguistic Factors in Interpretation

    Institute of Scientific and Technical Information of China (English)

    姚嘉

    2015-01-01

    The quality of interpretation is a dynamic conception, involving a good deal of variables, such as the participants, the situations, working conditions, cultures etc.. Therefore, in interpretation, those static elements, such as traditional grammars and certain linguistic rules can not be counted as the only criteria for the quality of interpretation. That is, there are many other non-language elements—Ultra-linguistic factors that play an important role in interpretation. Ultra-linguistic factors get rid of the bounding of traditional grammar and parole, and reveal the facts in an indirect way. This paper gives a brief analysis of Ultra Lin⁃guistic elements in interpretation in order to achieve better result in interpretation practice.

  4. Meta-analysis of factors that affect the utilization efficiency of phosphorus in lactating dairy cows

    NARCIS (Netherlands)

    Klop, G.; Ellis, J.L.; Bannink, A.; Kebreab, E.; France, J.; Dijkstra, J.

    2013-01-01

    meta-analysis investigation based on literature data was conducted to estimate the effect size of nutritional and animal factors on phosphorus (P) excretion in feces and concentrations of P in milk. Two data sets were created for statistical analysis: One to derive prediction equations for P in

  5. Meta-analysis of factors that affect the utilization efficiency of phosphorus in lactating dairy cows

    NARCIS (Netherlands)

    Klop, G.; Ellis, J.L.; Bannink, A.; Kebreab, E.; France, J.; Dijkstra, J.

    2013-01-01

    meta-analysis investigation based on literature data was conducted to estimate the effect size of nutritional and animal factors on phosphorus (P) excretion in feces and concentrations of P in milk. Two data sets were created for statistical analysis: One to derive prediction equations for P in fece

  6. Brain-Derived Neurotrophic Factor Predicts Mortality Risk in Older Women

    DEFF Research Database (Denmark)

    Krabbe, K.S.; Mortensen, E.L.; Avlund, K.

    2009-01-01

    OBJECTIVES To test the hypothesis that low circulating brain-derived neurotrophic factor (BDNF), a secretory member of the neurotrophin family that has a protective role in neurodegeneration and stress responses and a regulatory role in metabolism, predicts risk of all-cause mortality in 85-year...... was measured in plasma and serum. The Danish National Register of Patients was used to collect data on morbidity. The primary outcome in Cox regression analyses was all-cause mortality. RESULTS Women with low plasma BDNF (lowest tertile) had greater all-cause mortality risk than women with high plasma BDNF...

  7. Molecular mechanisms underlying the regulation of brain-derived neurotrophic factor (BDNF) translation in dendrites

    OpenAIRE

    Pinheiro, Vera Lúcia Margarido

    2010-01-01

    Dissertação de mestrado em Biologia Celular e Molecular apresentada ao Departamento de Ciências da Vida da Faculdade de Ciências e Tecnologia da Universidade de Coimbra A especificidade espacial e temporal subjacente à diversidade de processos de plasticidade sináptica que ocorrem no sistema nervoso central está profundamente relacionada com a disponibilidade da proteína brain-derived neurotrophic factor (BDNF) em domínios sub-celulares distintos, especialmente na área pós-sinápti...

  8. Expression and functional characterization of platelet-derived growth factor receptor-like gene

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the role of platelet-derived growth factor receptor-like gene(PDGFRL)in the anti-cancer therapy for colorectal cancers(CRC).METHODS:PDGFRL mRNA and protein levels were measured by reverse transcription-polymerase chain reaction(RT-PCR)and immunohistochemistry in CRC and colorectal normal tissues.PDGFRL prokaryotic expression vector was carried out in Escherichia coli(E.coli),and purified by immobilized metal affinity chromatography.The effect of PDGFRL protein on CRC HCT-116 cells was det...

  9. Brain-derived neurotrophic factor and early-life stress: Multifaceted interplay

    Indian Academy of Sciences (India)

    NATALYA P BONDAR; TATIANA I MERKULOVA

    2016-12-01

    The brain-derived neurotrophic factor (BDNF) is a key regulator of neural development and plasticity. Longtermchanges in the BDNF pathway are associated with childhood adversity and adult depression symptoms.Initially, stress-induced decreases in the BDNF pathway were found in some studies, but subsequent reportsindicated the relationship between stress and BDNF to be much more complex, and the concept wassignificantly revised. In the present mini-review, we focus on the structure and regulation of the Bbnf geneas well as on the stress–BDNF interactions under early-life adverse conditions.

  10. Activation of Complement by Pigment Epithelium-Derived Factor in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Vogt, Leonie M.; Talens, Simone; Kwasniewicz, Ewa

    2017-01-01

    neoepitope in C4d, several molecules that were specifically bound to C4d were identified from pooled synovial fluid (SF) from four rheumatoid arthritis (RA) patients. One of these molecules, pigment epithelium-derived factor (PEDF), is a broadly expressed multifunctional member of the serine proteinase...... inhibitor family. Using ELISA, we confirmed the presence of various amounts of complexes between PEDF and C4d in the SF from 30 RA patients, whereas none were detected in SF from control subjects. Correlation analyses suggested that, in arthritis patients, C4d-PEDF complexes found in sera arise from...

  11. The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans

    DEFF Research Database (Denmark)

    Huang, T; Larsen, K T; Ried-Larsen, M

    2014-01-01

    The purpose of this study was to summarize the effects of physical activity and exercise on peripheral brain-derived neurotrophic factor (BDNF) in healthy humans. Experimental and observational studies were identified from PubMed, Web of Knowledge, Scopus, and SPORT Discus. A total of 32 articles...... met the inclusion criteria. Evidence from experimental studies suggested that peripheral BDNF concentrations were elevated by acute and chronic aerobic exercise. The majority of the studies suggested that strength training had no influence on peripheral BDNF. The results from most observational...

  12. Molecular mechanisms underlying the regulation of brain-derived neurotrophic factor (BDNF) translation in dendrites

    OpenAIRE

    Pinheiro, Vera Lúcia Margarido

    2010-01-01

    Dissertação de mestrado em Biologia Celular e Molecular apresentada ao Departamento de Ciências da Vida da Faculdade de Ciências e Tecnologia da Universidade de Coimbra A especificidade espacial e temporal subjacente à diversidade de processos de plasticidade sináptica que ocorrem no sistema nervoso central está profundamente relacionada com a disponibilidade da proteína brain-derived neurotrophic factor (BDNF) em domínios sub-celulares distintos, especialmente na área pós-sinápti...

  13. Sordarin derivatives induce a novel conformation of the yeast ribosome translocation factor eEF2

    DEFF Research Database (Denmark)

    Søe, Rikke; Mosley, R.T.; Justice, M.

    2007-01-01

    The sordarins are fungal specific inhibitors of the translation factor eEF2, which catalyses the translocation of tRNA and mRNA after peptide bond formation. We have determined the crystal structures of eEF2 in complex with two novel sordarin derivatives. In both structures, the three domains of ......-ray structures of eEF2, EF-G and an EF-G homologue, we suggest that the conformation of EF-G stalled on the 70S ribosome by fusidic acid is similar to that of eEF2 trapped on the 80S ribosome by sordarin....

  14. Circulating levels of brain-derived neurotrophic factor: correlation with mood, cognition and motor function.

    Science.gov (United States)

    Teixeira, Antonio Lucio; Barbosa, Izabela Guimarães; Diniz, Breno Satler; Kummer, Arthur

    2010-12-01

    Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the CNS, where it plays several pivotal roles in synaptic plasticity and neuronal survival. As a consequence, BDNF has become a key target in the physiopathology of several neurological and psychiatric diseases. Recent studies have consistently reported altered levels of BDNF in the circulation (i.e., serum or plasma) of patients with major depression, bipolar disorder, Alzheimer's disease, Huntington's disease and Parkinson's disease. Correlations between serum BDNF levels and affective, cognitive and motor symptoms have also been described. BDNF appears to be an unspecific biomarker of neuropsychiatric disorders characterized by neurodegenerative changes.

  15. Brain-derived neurotrophic factor and epilepsy--a missing link?

    Science.gov (United States)

    Scharfman, Helen E

    2005-01-01

    It has been known for some time that brain-derived neurotrophic factor (BDNF) is critical to normal development of the CNS, and more recently, studies also have documented the ability of BDNF to modify adult CNS structure and function. Therefore, it is no surprise that BDNF has been linked to diseases, such as epilepsy, which may involve abnormal cortical development or altered brain structure and function after maturity. This review evaluates the evidence, particularly from recent studies, that BDNF contributes to the development of temporal lobe epilepsy (TLE).

  16. Factor Rotation and Standard Errors in Exploratory Factor Analysis

    Science.gov (United States)

    Zhang, Guangjian; Preacher, Kristopher J.

    2015-01-01

    In this article, we report a surprising phenomenon: Oblique CF-varimax and oblique CF-quartimax rotation produced similar point estimates for rotated factor loadings and factor correlations but different standard error estimates in an empirical example. Influences of factor rotation on asymptotic standard errors are investigated using a numerical…

  17. Effects of brain-derived neurotrophic factor on local inflammation in experimental stroke of rat.

    Science.gov (United States)

    Jiang, Yongjun; Wei, Ning; Zhu, Juehua; Lu, Tingting; Chen, Zhaoyao; Xu, Gelin; Liu, Xinfeng

    2010-01-01

    This study was aimed to investigate whether brain-derived neurotrophic factor (BDNF) can modulate local cerebral inflammation in ischemic stroke. Rats were subjected to ischemia by occluding the right middle cerebral artery (MCAO) for 2 hours. Rats were randomized as control, BDNF, and antibody groups. The local inflammation was evaluated on cellular, cytokine, and transcription factor levels with immunofluorescence, enzyme-linked immunosorbent assay, real-time qPCR, and electrophoretic mobility shift assay, respectively. Exogenous BDNF significantly improved motor-sensory, sensorimotor function, and vestibulomotor function, while BDNF did not decrease the infarct volume. Exogenous BDNF increased the number of both activated and phagocytotic microglia in brain. BDNF upregulated interleukin10 and its mRNA expression, while downregulated tumor necrosis factor α and its mRNA expression. BDNF also increased DNA-binding activity of nuclear factor-kappa B. BDNF antibody, which blocked the activity of endogenous BDNF, showed the opposite effect of exogenous BDNF. Our data indicated that BDNF may modulate local inflammation in ischemic brain tissues on the cellular, cytokine, and transcription factor levels.

  18. Effects of Brain-Derived Neurotrophic Factor on Local Inflammation in Experimental Stroke of Rat

    Directory of Open Access Journals (Sweden)

    Yongjun Jiang

    2010-01-01

    Full Text Available This study was aimed to investigate whether brain-derived neurotrophic factor (BDNF can modulate local cerebral inflammation in ischemic stroke. Rats were subjected to ischemia by occluding the right middle cerebral artery (MCAO for 2 hours. Rats were randomized as control, BDNF, and antibody groups. The local inflammation was evaluated on cellular, cytokine, and transcription factor levels with immunofluorescence, enzyme-linked immunosorbent assay, real-time qPCR, and electrophoretic mobility shift assay, respectively. Exogenous BDNF significantly improved motor-sensory, sensorimotor function, and vestibulomotor function, while BDNF did not decrease the infarct volume. Exogenous BDNF increased the number of both activated and phagocytotic microglia in brain. BDNF upregulated interleukin10 and its mRNA expression, while downregulated tumor necrosis factor α and its mRNA expression. BDNF also increased DNA-binding activity of nuclear factor-kappa B. BDNF antibody, which blocked the activity of endogenous BDNF, showed the opposite effect of exogenous BDNF. Our data indicated that BDNF may modulate local inflammation in ischemic brain tissues on the cellular, cytokine, and transcription factor levels.

  19. Model correction factor method for system analysis

    DEFF Research Database (Denmark)

    Ditlevsen, Ove Dalager; Johannesen, Johannes M.

    2000-01-01

    The Model Correction Factor Method is an intelligent response surface method based on simplifiedmodeling. MCFM is aimed for reliability analysis in case of a limit state defined by an elaborate model. Herein it isdemonstrated that the method is applicable for elaborate limit state surfaces on which...... severallocally most central points exist without there being a simple geometric definition of the corresponding failuremodes such as is the case for collapse mechanisms in rigid plastic hinge models for frame structures. Taking as simplifiedidealized model a model of similarity with the elaborate model...... surface than existing in the idealized model....

  20. Brain-derived neurotrophic factor expression predicts adverse pathological & clinical outcomes in human breast cancer

    Directory of Open Access Journals (Sweden)

    Mokbel Kefah

    2011-07-01

    Full Text Available Abstract Introduction Brain-derived neurotrophic factor (BDNF has established physiological roles in the development and function of the vertebrate nervous system. BDNF has also been implicated in several human malignancies, including breast cancer (BC. However, the precise biological role of BDNF and its utility as a novel biomarker have yet to be determined. The objective of this study was to determine the mRNA and protein expression of BDNF in a cohort of women with BC. Expression levels were compared with normal background tissues and evaluated against established pathological parameters and clinical outcome over a 10 year follow-up period. Methods BC tissues (n = 127 and normal tissues (n = 33 underwent RNA extraction and reverse transcription, BDNF transcript levels were determined using real-time quantitative PCR. BDNF protein expression in mammary tissues was assessed with standard immuno-histochemical methodology. Expression levels were analyzed against tumour size, grade, nodal involvement, TNM stage, Nottingham Prognostic Index (NPI and clinical outcome over a 10 year follow-up period. Results Immuno-histochemical staining revealed substantially greater BDNF expression within neoplastic cells, compared to normal mammary epithelial cells. Significantly higher mRNA transcript levels were found in the BC specimens compared to background tissues (p = 0.007. The expression of BDNF mRNA was demonstrated to increase with increasing NPI; NPI-1 vs. NPI-2 (p = 0.009. Increased BDNF transcript levels were found to be significantly associated with nodal positivity (p = 0.047. Compared to patients who remained disease free, higher BDNF expression was significantly associated with local recurrence (LR (p = 0.0014, death from BC (p = 0.018 and poor prognosis overall (p = 0.013. After a median follow up of 10 years, higher BDNF expression levels were significantly associated with reduced overall survival (OS (106 vs. 136 months, p = 0.006. BDNF

  1. Brain-derived neurotrophic factor inducing angiogenesis through modulation of matrix-degrading proteases

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background Recent studies have proved that brain-derived neurotrophic factor (BDNF) possesses angiogenic activity in vitro and in vivo. However, the proangiogenic mechanism of BDNF has not yet been provided with enough information. To explore the proangiogenic mechanism of BDNF, we investigated the effects of BDNF on extracellular proteolytic enzymes, including matrix metalloproteinases (MMPs) and serine proteases, particularly the urokinase-type plasminogen activator (uPA)-plasmin system in human umbilical vein endothelial cells (HUVECs) model. Methods Tube formation assay was performed in vitro to evaluate the effects of BDNF on angiogenesis. The HUVECs were treated with various concentrations of BDNF (25-400 ng/ml) for different (6-48 hours), reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assay MMP-2, MMP-9, TIMP-1, and TIMP-2 mRNA in HUVECs, and the conditioned medium was analyzed for MMP and uPA activity by gelatin zymography and fibrin zymography, respectively. uPA, plasminogen activator inhibitor (PAI)-1, tissue inhibitors of metalloproteinase (TIMP)-1, and TIMP-2 were quantified by western blotting analysis. Results BDNF elicited robust and elongated angiogeneis in two-dimensional cultures of HUVECs in comparison with control. The stimulation of serum-starved HUVECs with BDNF caused obvious increase in MMP-2 and MMP-9 mRNA expression and induced the pro-MMP-2 and pro-MMP-9 activation without significant differences in proliferation. However, BDNF had no effect on TIMP-1 and TIMP-2 production. BDNF increased uPA and PAI-1 production in a dose-dependent manner. Maximal activation of uPA and PAI-1 expression in HUVECs was induced by 100 ng/ml BDNF, while effects of 200 ng/ml and 400 ng/ml BDNF were slightly reduced in comparison with with those of 100 ng/ml. Protease activity for uPA was also increased by BDNF in a dose-dependent manner. BDNF also stimulated uPA and PAI-1 production beyond that in control cultures in a time

  2. Intragraft platelet-derived growth factor-alpha and transforming growth factor-beta1 during the development of accelerated graft vascular disease after clinical heart transplantation

    NARCIS (Netherlands)

    de Groot-Kruseman, H A; Baan, C C; Mol, W M; Niesters, H G; Maat, A P; Balk, A H; Weimar, W

    1999-01-01

    This study was to determine whether the growth factors platelet-derived growth factor-alpha (PDGF-alpha) and transforming growth factor-beta1 (TGF-beta1) contribute to the development of graft vascular disease (GVD) after clinical heart transplantation. We analysed intragraft PDGF-alpha and TGF-beta

  3. Crystallization and preliminary crystallographic data for a ternary complex between tissue factor, factor VIIa and a BPTI-derived inhibitor

    Science.gov (United States)

    Stura, Enrico A.; Ruf, Wolfram; Wilson, Ian A.

    1996-10-01

    The binding of tissue factor (TF) with the serine protease coagulation factor VIIa (VIIa) is the initial trigger for activation of the coagulation protease cascades. In complex with TF, VIIa has profoundly enhanced function in the limited proteolytic activation of the natural substrate factors X and IX. Here we report the screening and identification of crystallization conditions to produce diffraction quality crystals of the complex between TF · VIIa and a potent inhibitor (5L 15) derived from mutagenesis of the bovine pancreatic trypsin inhibitor (BPTI) sequence. The complex crystals were obtained from the soluble extracellular domain of tissue factor, expressed in Escherichia coli as a fusion protein, VIIa expressed in mammalian cells and recombinant 5L15. Because only 1.5 mg of complex were available for this work, a reverse screening based strategy was used in the search and optimization of the crystallization conditions. Two different crystal forms were obtained from polyethylene glycol 4000 and monomethyl polyethylene glycol 2000 with cacodylate buffer at pH 6.5 in the presence of sodium and calcium ions. The addition of magnesium and zinc have profound effects on the crystallization. Both crystal forms are trigonal with cell parameters a = b = 129.3 Å, c = 110.8 Å and a = b = 67.2 Å, c = 314.8 Å diffracting to 7 and 3.2 Å resolution, respectively, each with one molecule in the asymmetric unit. Complete data sets have been collected from each of these forms to the resolution to which the crystals diffract. A structural understanding of the interaction of VIIa with its cofactor TF to form a binary enzyme, and its inhibition by 5L15 will provide a basis for the development of antithrombotic strategies.

  4. Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Biaoru Li

    Full Text Available Fetal stem cells isolated from umbilical cord blood (UCB possess a great capacity for proliferation and differentiation and serve as a valuable model system to study gene regulation. Expanded knowledge of the molecular control of hemoglobin synthesis will provide a basis for rational design of therapies for β-hemoglobinopathies. Transcriptome data are available for erythroid progenitors derived from adult stem cells, however studies to define molecular mechanisms controlling globin gene regulation during fetal erythropoiesis are limited. Here, we utilize UCB-CD34+ stem cells induced to undergo erythroid differentiation to characterize the transcriptome and transcription factor networks (TFNs associated with the γ/β-globin switch during fetal erythropoiesis. UCB-CD34+ stem cells grown in the one-phase liquid culture system displayed a higher proliferative capacity than adult CD34+ stem cells. The γ/β-globin switch was observed after day 42 during fetal erythropoiesis in contrast to adult progenitors where the switch occurred around day 21. To gain insights into transcription factors involved in globin gene regulation, microarray analysis was performed on RNA isolated from UCB-CD34+ cell-derived erythroid progenitors harvested on day 21, 42, 49 and 56 using the HumanHT-12 Expression BeadChip. After data normalization, Gene Set Enrichment Analysis identified transcription factors (TFs with significant changes in expression during the γ/β-globin switch. Forty-five TFs were silenced by day 56 (Profile-1 and 30 TFs were activated by day 56 (Profile-2. Both GSEA datasets were analyzed using the MIMI Cytoscape platform, which discovered TFNs centered on KLF4 and GATA2 (Profile-1 and KLF1 and GATA1 for Profile-2 genes. Subsequent shRNA studies in KU812 leukemia cells and human erythroid progenitors generated from UCB-CD34+ cells supported a negative role of MAFB in γ-globin regulation. The characteristics of erythroblasts derived from UCB-CD34

  5. Scalable group level probabilistic sparse factor analysis

    DEFF Research Database (Denmark)

    Hinrich, Jesper Løve; Nielsen, Søren Føns Vind; Riis, Nicolai Andre Brogaard

    2017-01-01

    Many data-driven approaches exist to extract neural representations of functional magnetic resonance imaging (fMRI) data, but most of them lack a proper probabilistic formulation. We propose a scalable group level probabilistic sparse factor analysis (psFA) allowing spatially sparse maps, component...... pruning using automatic relevance determination (ARD) and subject specific heteroscedastic spatial noise modeling. For task-based and resting state fMRI, we show that the sparsity constraint gives rise to components similar to those obtained by group independent component analysis. The noise modeling...... shows that noise is reduced in areas typically associated with activation by the experimental design. The psFA model identifies sparse components and the probabilistic setting provides a natural way to handle parameter uncertainties. The variational Bayesian framework easily extends to more complex...

  6. Disruptive Event Biosphere Dose Conversion Factor Analysis

    Energy Technology Data Exchange (ETDEWEB)

    M. Wasiolek

    2004-09-08

    This analysis report is one of the technical reports containing documentation of the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the total system performance assessment (TSPA) for the license application (LA) for the Yucca Mountain repository. This analysis report describes the development of biosphere dose conversion factors (BDCFs) for the volcanic ash exposure scenario, and the development of dose factors for calculating inhalation dose during volcanic eruption. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and provides an understanding of how this analysis report contributes to biosphere modeling. This report is one of two reports that develop biosphere BDCFs, which are input parameters for the TSPA model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the ERMYN conceptual model and mathematical model. The input parameter reports, shown to the right of the Biosphere Model Report in Figure 1-1, contain detailed descriptions of the model input parameters, their development and the relationship between the parameters and specific features, events and processes (FEPs). This report describes biosphere model calculations and their output, the BDCFs, for the volcanic ash exposure scenario. This analysis receives direct input from the outputs of the ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) and from the five analyses that develop parameter values for the biosphere model (BSC 2004 [DIRS 169671]; BSC 2004 [DIRS 169672]; BSC 2004 [DIRS 169673]; BSC 2004 [DIRS 169458]; and BSC 2004 [DIRS 169459]). The results of this report are further analyzed in the ''Biosphere Dose Conversion Factor Importance and Sensitivity Analysis''. The objective of this

  7. Endothelium-derived hyperpolarizing factor contributes to hypoxia-induced skeletal muscle vasodilation in humans.

    Science.gov (United States)

    Spilk, Samson; Herr, Michael D; Sinoway, Lawrence I; Leuenberger, Urs A

    2013-12-01

    Systemic hypoxia causes skeletal muscle vasodilation, thereby preserving O2 delivery to active tissues. Nitric oxide (NO), adenosine, and prostaglandins contribute to this vasodilation, but other factors may also play a role. We tested the hypothesis that regional inhibition of endothelium-derived hyperpolarizing factor with the cytochrome P-450 2C9 antagonist fluconazole, alone or combined with the NO synthase antagonist N(G)-monomethyl-L-arginine (L-NMMA), attenuates hypoxia-induced vasodilation. We compared forearm blood flow (FBF) and skin blood flow before and during brachial artery infusion of fluconazole (0.3 mg/min; trial 1) or fluconazole + L-NMMA (50 mg over 10 min; trial 2) and during systemic hypoxia (10 min, arterial Po2 ~37 mmHg) in infused (experimental) and control forearms of 12 healthy humans. During normoxia, fluconazole and fluconazole + L-NMMA reduced (P vasodilation and could be particularly relevant when other vasodilator systems are impaired.

  8. Role of brain-derived neurotrophic factor in the aetiology of depression: implications for pharmacological treatment.

    Science.gov (United States)

    Castrén, Eero; Rantamäki, Tomi

    2010-01-01

    Brain-derived neurotrophic factor (BDNF) is a critical mediator of activity-dependent neuronal plasticity in the cerebral cortex. Deficits in neurotrophic factors have been proposed to underlie mood disorders. However, recent evidence suggests that mood disorders may be produced by abnormalities in the adaptation of neural networks to environmental conditions. Antidepressants may act by enhancing neuronal plasticity, which allows environmental inputs to modify the neuronal networks to better fine tune the individual to the outside world. Recent observations in the visual cortex directly support this idea. According to the network hypothesis of depression, changes in the levels of neurotrophins including BDNF may not directly produce depression or an antidepressant effect, but neurotrophins may act as critical tools in the process whereby environmental conditions guide neuronal networks to better adapt to the environment. This hypothesis suggests that antidepressant drugs should not be used alone but should always be combined with rehabilitation to guide the plastic networks within the brain.

  9. Acute strength exercise and the involvement of small or large muscle mass on plasma brain-derived neurotrophic factor levels

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Correia

    2010-01-01

    Full Text Available OBJECTIVE: Blood neurotrophins, such as the brain-derived neurotrophic factor, are considered to be of great importance in mediating the benefits of physical exercise. In this study, the effect of acute strength exercise and the involvement of small versus large muscle mass on the levels of plasma brain-derived neurotrophic factor were evaluated in healthy individuals. METHODS: The concentric strengths of knee (large and elbow (small flexor and extensor muscles were measured on two separate days. Venous blood samples were obtained from 16 healthy subjects before and after exercise. RESULTS: The levels of brain-derived neurotrophic factor in the plasma did not significantly increase after both arm and leg exercise. There was no significant difference in the plasma levels of the brain-derived neurotrophic factor in the arms and legs. CONCLUSION: The present results demonstrate that acute strength exercise does not induce significant alterations in the levels of brain-derived neurotrophic factor plasma concentrations in healthy individuals. Considering that its levels may be affected by various factors, such as exercise, these findings suggest that the type of exercise program may be a decisive factor in altering peripheral brain-derived neurotrophic factor.

  10. Association of brain-derived neurotrophic factor and nerve growth factor gene polymorphisms with susceptibility to migraine

    Directory of Open Access Journals (Sweden)

    Coskun S

    2016-07-01

    Full Text Available Salih Coskun,1 Sefer Varol,2 Hasan H Ozdemir,2 Elif Agacayak,3 Birsen Aydın,4 Oktay Kapan,5 Mehmet Akif Camkurt,6 Saban Tunc,7 Mehmet Ugur Cevik2 1Department of Medical Genetics, 2Department of Neurology, 3Department of Obstetrics and Gynecology, Medical Faculty, Dicle University, Diyarbakır, Turkey; 4Department of Neurology, Diyarbakır Education and Research Hospital, Diyarbakır, Turkey; 5Department of Neurology, Elaziğ Education and Research Hospital, Elaziğ, Turkey; 6Department of Psychiatry, Afsin State Hospital, Kahramanmaras, Turkey; 7Laboratory of Molecular Genetics, Medical Faculty, Dicle University, Diyarbakır, Turkey Abstract: Migraine is one of the most common neurological diseases worldwide. Migraine pathophysiology is very complex. Genetic factors play a major role in migraine. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF and nerve growth factor (NGF, play an important role in central nervous system functioning, development, and modulation of pain. This study investigates whether polymorphisms in the BDNF and NGF genes are associated with migraine disease in a Turkish case–control population. Overall, 576 subjects were investigated (288 patients with migraine and 288 healthy controls for the following polymorphisms: rs6265(G/A, rs8192466(C/T, rs925946(G/T, rs2049046(A/T, and rs12273363(T/C in the BDNF gene, and rs6330(C/T, rs11466112(C/T, rs11102930(C/A, and rs4839435(G/A in the NGF gene using 5'-exonuclease allelic discrimination assays. We found no differences in frequency of the analyzed eight polymorphisms between migraine and control groups. However, the frequency of minor A alleles of rs6265 in BDNF gene was borderline significant in the patients compared with the healthy controls (P=0.049; odds ratios [ORs] [95% confidence intervals {CIs}] =0.723 [0.523–0.999]. Moreover, when the migraine patients were divided into two subgroups, migraine with aura (MA and migraine without aura (MO, the

  11. Brain-derived neurotrophic factor expression is higher in brain tissue from patients with refractory epilepsy than in normal controls

    Institute of Scientific and Technical Information of China (English)

    Yudan Lv; Jiqing Qiu; Zan Wang; Li Cui; Hongmei Meng; Weihong Lin

    2011-01-01

    The role of the brain-derived neurotrophic factor in epilepsy remains controversial. The present study utilized light and electron microscopy to investigate pathological and ultrastructural changes in brain tissue obtained from the seizure foci of 24 patients with temporal epilepsy. We found that epileptic tissue showed neuronal degeneration, glial cell proliferation, nuclear vacuolization, and neural cell tropism. Immunoelectron microscopy and immunohistochemistry showed that brain-derived neurotrophic factor was expressed at significantly higher levels in patients with refractory temporal epilepsy compared with normal controls, demonstrating that the pathological changes within seizure foci in patients with refractory epilepsy are associated with brain-derived neurotrophic factor expression alterations.

  12. Reversal of impaired wound healing in irradiated rats by platelet-derived growth factor-BB

    Energy Technology Data Exchange (ETDEWEB)

    Mustoe, T.A.; Purdy, J.; Gramates, P.; Deuel, T.F.; Thomason, A.; Pierce, G.F. (Washington Univ. Medical Center, St. Louis, MO (USA))

    1989-10-01

    This study examined the potential influence of platelet-derived growth factor-BB homodimers (PDGF-BB) on surgical incisions in irradiated animals with depressed wound healing. Rats were irradiated with either 800 rads total body or 2,500 rads surface irradiation. Parallel dorsal skin incisions were made 2 days later, and PDGF-BB was applied topically a single time to one of two incisions. In total body-irradiated rats, bone marrow-derived elements were severely depressed, wound macrophages were virtually eliminated, and PDGF-BB treatment was ineffective. However, in surface-irradiated rats, PDGF-BB treatment recruited macrophages into wounds and partially reversed impaired healing on day 7 (p less than 0.005) and day 12 (p less than 0.001). PDGF-BB-treated wounds were 50 percent stronger than the paired control wounds. The results suggest PDGF requires bone marrow-derived cells, likely wound macrophages, for activity and that it may be useful as a topical agent in postirradiation surgical incisions.

  13. Derivative spectrophotometric analysis of benzophenone (as an impurity in phenytoin

    Directory of Open Access Journals (Sweden)

    Walash Mohamed

    2011-12-01

    Full Text Available Abstract Three simple and rapid spectrophotometric methods were developed for detection and trace determination of benzophenone (the main impurity in phenytoin bulk powder and pharmaceutical formulations. The first method, zero-crossing first derivative spectrophotometry, depends on measuring the first derivative trough values at 257.6 nm for benzophenone. The second method, zero-crossing third derivative spectrophotometry, depends on measuring the third derivative peak values at 263.2 nm. The third method, ratio first derivative spectrophotometry, depends on measuring the peak amplitudes of the first derivative of the ratio spectra (the spectra of benzophenone divided by the spectrum of 5.0 μg/mL phenytoin solution at 272 nm. The calibration graphs were linear over the range of 1-10 μg/mL. The detection limits of the first and the third derivative methods were found to be 0.04 μg/mL and 0.11 μg/mL and the quantitation limits were 0.13 μg/mL and 0.34 μg/mL, respectively, while for the ratio derivative method, the detection limit was 0.06 μg/mL and the quantitation limit was 0.18 μg/mL. The proposed methods were applied successfully to the assay of the studied drug in phenytoin bulk powder and certain pharmaceutical preparations. The results were statistically compared to those obtained using a polarographic method and were found to be in good agreement.

  14. Brain-derived neurotrophic factor increases vascular endothelial growth factor expression and enhances angiogenesis in human chondrosarcoma cells.

    Science.gov (United States)

    Lin, Chih-Yang; Hung, Shih-Ya; Chen, Hsien-Te; Tsou, Hsi-Kai; Fong, Yi-Chin; Wang, Shih-Wei; Tang, Chih-Hsin

    2014-10-15

    Chondrosarcomas are a type of primary malignant bone cancer, with a potent capacity for local invasion and distant metastasis. Brain-derived neurotrophic factor (BDNF) is commonly upregulated during neurogenesis. The aim of the present study was to examine the mechanism involved in BDNF-mediated vascular endothelial growth factor (VEGF) expression and angiogenesis in human chondrosarcoma cells. Here, we knocked down BDNF expression in chondrosarcoma cells and assessed their capacity to control VEGF expression and angiogenesis in vitro and in vivo. We found knockdown of BDNF decreased VEGF expression and abolished chondrosarcoma conditional medium-mediated angiogenesis in vitro as well as angiogenesis effects in vivo in the chick chorioallantoic membrane and Matrigel plug nude mouse models. In addition, in the xenograft tumor angiogenesis model, the knockdown of BDNF significantly reduced tumor growth and tumor-associated angiogenesis. BDNF increased VEGF expression and angiogenesis through the TrkB receptor, PLCγ, PKCα, and the HIF-1α signaling pathway. Finally, we analyzed samples from chondrosarcoma patients by immunohistochemical staining. The expression of BDNF and VEGF protein in 56 chondrosarcoma patients was significantly higher than in normal cartilage. In addition, the high level of BDNF expression correlated strongly with VEGF expression and tumor stage. Taken together, our results indicate that BDNF increases VEGF expression and enhances angiogenesis through a signal transduction pathway that involves the TrkB receptor, PLCγ, PKCα, and the HIF-1α. Therefore, BDNF may represent a novel target for anti-angiogenic therapy for human chondrosarcoma.

  15. Music exposure differentially alters the levels of brain-derived neurotrophic factor and nerve growth factor in the mouse hypothalamus.

    Science.gov (United States)

    Angelucci, Francesco; Ricci, Enzo; Padua, Luca; Sabino, Andrea; Tonali, Pietro Attilio

    2007-12-18

    It has been reported that music may have physiological effects on blood pressure, cardiac heartbeat, respiration, and improve mood state in people affected by anxiety, depression and other psychiatric disorders. However, the physiological bases of these phenomena are not clear. Hypothalamus is a brain region involved in the regulation of body homeostasis and in the pathophysiology of anxiety and depression through the modulation of hypothalamic-pituitary-adrenal (HPA) axis. Hypothalamic functions are also influenced by the presence of the neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which are proteins involved in the growth, survival and function of neurons in the central nervous system. The aim of this study was to investigate the effect of music exposure in mice on hypothalamic levels of BDNF and NGF. We exposed young adult mice to slow rhythm music (6h per day; mild sound pressure levels, between 50 and 60 dB) for 21 consecutive days. At the end of the treatment mice were sacrificed and BDNF and NGF levels in the hypothalamus were measured by enzyme-linked immunosorbent assay (ELISA). We found that music exposure significantly enhanced BDNF levels in the hypothalamus. Furthermore, we observed that music-exposed mice had decreased NGF hypothalamic levels. Our results demonstrate that exposure to music in mice can influence neurotrophin production in the hypothalamus. Our findings also suggest that physiological effects of music might be in part mediated by modulation of neurotrophins.

  16. APP-dependent glial cell line-derived neurotrophic factor gene expression drives neuromuscular junction formation.

    Science.gov (United States)

    Stanga, Serena; Zanou, Nadège; Audouard, Emilie; Tasiaux, Bernadette; Contino, Sabrina; Vandermeulen, Gaëlle; René, Frédérique; Loeffler, Jean-Philippe; Clotman, Frédéric; Gailly, Philippe; Dewachter, Ilse; Octave, Jean-Noël; Kienlen-Campard, Pascal

    2016-05-01

    Besides its crucial role in the pathogenesis of Alzheimer's disease, the knowledge of amyloid precursor protein (APP) physiologic functions remains surprisingly scarce. Here, we show that APP regulates the transcription of the glial cell line-derived neurotrophic factor (GDNF). APP-dependent regulation of GDNF expression affects muscle strength, muscular trophy, and both neuronal and muscular differentiation fundamental for neuromuscular junction (NMJ) maturation in vivo In a nerve-muscle coculture model set up to modelize NMJ formation in vitro, silencing of muscular APP induces a 30% decrease in secreted GDNF levels and a 40% decrease in the total number of NMJs together with a significant reduction in the density of acetylcholine vesicles at the presynaptic site and in neuronal maturation. These defects are rescued by GDNF expression in muscle cells in the conditions where muscular APP has been previously silenced. Expression of GDNF in muscles of amyloid precursor protein null mice corrected the aberrant synaptic morphology of NMJs. Our findings highlight for the first time that APP-dependent GDNF expression drives the process of NMJ formation, providing new insights into the link between APP gene regulatory network and physiologic functions.-Stanga, S., Zanou, N., Audouard, E., Tasiaux, B., Contino, S., Vandermeulen, G., René, F., Loeffler, J.-P., Clotman, F., Gailly, P., Dewachter, I., Octave, J.-N., Kienlen-Campard, P. APP-dependent glial cell line-derived neurotrophic factor gene expression drives neuromuscular junction formation.

  17. Intrinsic regulation of hemangioma involution by platelet-derived growth factor

    Science.gov (United States)

    Roach, E E; Chakrabarti, R; Park, N I; Keats, E C; Yip, J; Chan, N G; Khan, Z A

    2012-01-01

    Infantile hemangioma is a vascular tumor that exhibits a unique natural cycle of rapid growth followed by involution. Previously, we have shown that hemangiomas arise from CD133+ stem cells that differentiate into endothelial cells when implanted in immunodeficient mice. The same clonally expanded stem cells also produced adipocytes, thus recapitulating the involuting phase of hemangioma. In the present study, we have elucidated the intrinsic mechanisms of adipocyte differentiation using hemangioma-derived stem cells (hemSCs). We found that platelet-derived growth factor (PDGF) is elevated during the proliferating phase and may inhibit adipocyte differentiation. hemSCs expressed high levels of PDGF-B and showed sustained tyrosine phosphorylation of PDGF receptors under basal (unstimulated) conditions. Inhibition of PDGF receptor signaling caused enhanced adipogenesis in hemSCs. Furthermore, exposure of hemSCs to exogenous PDGF-BB reduced the fat content and the expression of adipocyte-specific transcription factors. We also show that these autogenous inhibitory effects are mediated by PDGF receptor-β signaling. In summary, this study identifies PDGF signaling as an intrinsic negative regulator of hemangioma involution and highlights the therapeutic potential of disrupting PDGF signaling for the treatment of hemangiomas. PMID:22717583

  18. Hepatoma-derived growth factor-related protein 2 promotes DNA repair by homologous recombination

    Science.gov (United States)

    Baude, Annika; Aaes, Tania Løve; Zhai, Beibei; Al-Nakouzi, Nader; Oo, Htoo Zarni; Daugaard, Mads; Rohde, Mikkel; Jäättelä, Marja

    2016-01-01

    We have recently identified lens epithelium-derived growth factor (LEDGF/p75, also known as PSIP1) as a component of the homologous recombination DNA repair machinery. Through its Pro-Trp-Trp-Pro (PWWP) domain, LEDGF/p75 binds to histone marks associated with active transcription and promotes DNA end resection by recruiting DNA endonuclease retinoblastoma-binding protein 8 (RBBP8/CtIP) to broken DNA ends. Here we show that the structurally related PWWP domain-containing protein, hepatoma-derived growth factor-related protein 2 (HDGFRP2), serves a similar function in homologous recombination repair. Its depletion compromises the survival of human U2OS osteosarcoma and HeLa cervix carcinoma cells and impairs the DNA damage-induced phosphorylation of replication protein A2 (RPA2) and the recruitment of DNA endonuclease RBBP8/CtIP to DNA double strand breaks. In contrast to LEDGF/p75, HDGFRP2 binds preferentially to histone marks characteristic for transcriptionally silent chromatin. Accordingly, HDGFRP2 is found in complex with the heterochromatin-binding chromobox homologue 1 (CBX1) and Pogo transposable element with ZNF domain (POGZ). Supporting the functionality of this complex, POGZ-depleted cells show a similar defect in DNA damage-induced RPA2 phosphorylation as HDGFRP2-depleted cells. These data suggest that HDGFRP2, possibly in complex with POGZ, recruits homologous recombination repair machinery to damaged silent genes or to active genes silenced upon DNA damage. PMID:26721387

  19. Tropism mechanism of stem cells targeting injured brain tissues by stromal cell-derived factor-1

    Institute of Scientific and Technical Information of China (English)

    ZHANG Sai; LIU Xiao-zhi; LIU Zhen-lin; SHANG Chong-zhi; HU Qun-liang

    2009-01-01

    Objective: To explore the role and function of stromal cell-derived factor- 1 (SDF- 1) in stem cells migrating into injured brain area.Methods: Rat-derived nerve stem cells (NSCs) were isolated and cultured routinely. Transwell system was used to observe the migration ability of NSCs into injured nerve cells. Immunocytochemistry was used to explore the expression of chemotactic factor receptor-4 (CXCR-4) in NSCs. In vivo, we applied immunofluorescence technique to observe the migration of NSCs into injured brain area. Immunofluorescence technique and Western blotting were used to test expression level of SDF- 1. After AMD3100 (a special chemical blocker) blocking CXCR-4, the migration ability of NSCs was tested in vivo and in vitro, respectively.Results: NSCs displayed specific tropism for injured nerve cells or traumatic brain area in vivo and in vitro. The expression level of SDF-1 in traumatic brain area increased remarkably and the expression level of CXCR-4 in the NSCs increased simultaneously. After AMD3100 blocking the expression of CXCR-4, the migration ability of NSCs decreased significantly both in vivo and in vitro.Conclusions: SDF-1 may play a key role in stem cells migrating into injured brain area through specially combining with CXCR-4.

  20. Brain-derived neurotrophic factor promotes central nervous system myelination via a direct effect upon oligodendrocytes.

    Science.gov (United States)

    Xiao, Junhua; Wong, Agnes W; Willingham, Melanie M; van den Buuse, Maarten; Kilpatrick, Trevor J; Murray, Simon S

    2010-01-01

    The extracellular factors that are responsible for inducing myelination in the central nervous system (CNS) remain elusive. We investigated whether brain-derived neurotrophic factor (BDNF) is implicated, by first confirming that BDNF heterozygous mice exhibit delayed CNS myelination during early postnatal development. We next established that the influence of BDNF upon myelination was direct, by acting on oligodendrocytes, using co-cultures of dorsal root ganglia neurons and oligodendrocyte precursor cells. Importantly, we found that BDNF retains its capacity to enhance myelination of neurons or by oligodendrocytes derived from p75NTR knockout mice, indicating the expression of p75NTR is not necessary for BDNF-induced myelination. Conversely, we observed that phosphorylation of TrkB correlated with myelination, and that inhibiting TrkB signalling also inhibited the promyelinating effect of BDNF, suggesting that BDNF enhances CNS myelination via activating oligodendroglial TrkB-FL receptors. Together, our data reveal a previously unknown role for BDNF in potentiating the normal development of CNS myelination, via signalling within oligodendrocytes.

  1. Mayo Older Americans Normative Studies: Factor Analysis of an Expanded Neuropsychological Battery

    OpenAIRE

    Greenaway, Melanie C.; Smith, Glenn E.; Tangalos, Eric G.; Geda, Yonas E.; Ivnik, Robert J.

    2008-01-01

    The Mayo Cognitive Factor Scores were derived from a “core battery” consisting of the WAIS-R, WMS-R, and Auditory Verbal Learning Test. The present study sought to clarify the factor structure of an expanded neuropsychological battery in normal elderly controls. Confirmatory factor analysis was performed on the WAIS-III, WRAT-3 Reading, Boston Naming Test, Controlled Oral Word Association Test, Category Fluency, Rey-Osterrieth Complex Figure, Visual Form Discrimination, and Trail Making Test ...

  2. A comparison of the dietary patterns derived by principal component analysis and cluster analysis in older Australians.

    Science.gov (United States)

    Thorpe, Maree G; Milte, Catherine M; Crawford, David; McNaughton, Sarah A

    2016-02-29

    Despite increased use of dietary pattern methods in nutritional epidemiology, there have been few direct comparisons of methods. Older adults are a particularly understudied population in the dietary pattern literature. This study aimed to compare dietary patterns derived by principal component analysis (PCA) and cluster analysis (CA) in older adults and to examine their associations with socio-demographic and health behaviours. Men (n = 1888) and women (n = 2071) aged 55-65 years completed a 111-item food frequency questionnaire in 2010. Food items were collapsed into 52 food groups and dietary patterns were determined by PCA and CA. Associations between dietary patterns and participant characteristics were examined using Chi-square analysis. The standardised PCA-derived dietary patterns were compared across the clusters using one-way ANOVA. PCA identified four dietary patterns in men and two dietary patterns in women. CA identified three dietary patterns in both men and women. Men in cluster 1 (fruit, vegetables, wholegrains, fish and poultry) scored higher on PCA factor 1 (vegetable dishes, fruit, fish and poultry) and factor 4 (vegetables) compared to factor 2 (spreads, biscuits, cakes and confectionery) and factor 3 (red meat, processed meat, white-bread and hot chips) (mean, 95% CI; 0.92, 0.82-1.02 vs. 0.74, 0.63-0.84 vs. -0.43, -0.50- -0.35 vs. 0.60 0.46-0.74, respectively). Women in cluster 1 (fruit, vegetables and fish) scored highest on PCA factor 1 (fruit, vegetables and fish) compared to factor 2 (processed meat, hot chips cakes and confectionery) (1.05, 0.97-1.14 vs. -0.14, -0.21- -0.07, respectively). Cluster 3 (small eaters) in both men and women had negative factor scores for all the identified PCA dietary patterns. Those with dietary patterns characterised by higher consumption of red and processed meat and refined grains were more likely to be Australian-born, have a lower level of education, a higher BMI, smoke and did not meet physical

  3. Peripheral brain-derived neurotrophic factor is related to cardiovascular risk factors in active and inactive elderly men

    Directory of Open Access Journals (Sweden)

    A. Zembron-Lacny

    2016-01-01

    Full Text Available Regular exercise plays an important preventive and therapeutic role in heart and vascular diseases, and beneficially affects brain function. In blood, the effects of exercise appear to be very complex and could include protection of vascular endothelial cells via neurotrophic factors and decreased oxidative stress. The purpose of this study was to identify the age-related changes in peripheral brain-derived neurotrophic factor (BDNF and its relationship to oxidative damage and conventional cardiovascular disease (CVD biomarkers, such as atherogenic index, C-reactive protein (hsCRP and oxidized LDL (oxLDL, in active and inactive men. Seventeen elderly males (61-80 years and 17 young males (20-24 years participated in this study. According to the 6-min Åstrand-Rhyming bike test, the subjects were classified into active and inactive groups. The young and elderly active men had a significantly better lipoprotein profile and antioxidant status, as well as reduced oxidative damage and inflammatory state. The active young and elderly men had significantly higher plasma BDNF levels compared to their inactive peers. BDNF was correlated with VO2max (r=0.765, P<0.001. In addition, we observed a significant inverse correlation of BDNF with atherogenic index (TC/HDL, hsCRP and oxLDL. The findings demonstrate that a high level of cardiorespiratory fitness reflected in VO2max was associated with a higher level of circulating BDNF, which in turn was related to common CVD risk factors and oxidative damage markers in young and elderly men.

  4. Statistically derived factors of varied importance to audiologists when making a hearing aid brand preference decision.

    Science.gov (United States)

    Johnson, Earl E; Mueller, H Gustav; Ricketts, Todd A

    2009-01-01

    To determine the amount of importance audiologists place on various items related to their selection of a preferred hearing aid brand manufacturer. Three hundred forty-three hearing aid-dispensing audiologists rated a total of 32 randomized items by survey methodology. Principle component analysis identified seven orthogonal statistical factors of importance. In rank order, these factors were Aptitude of the Brand, Image, Cost, Sales and Speed of Delivery, Exposure, Colleague Recommendations, and Contracts and Incentives. While it was hypothesized that differences among audiologists in the importance ratings of these factors would dictate their preference for a given brand, that was not our finding. Specifically, mean ratings for the six most important factors did not differ among audiologists preferring different brands. A statistically significant difference among audiologists preferring different brands was present, however, for one factor: Contracts and Incentives. Its assigned importance, though, was always lower than that for the other six factors. Although most audiologists have a preferred hearing aid brand, differences in the perceived importance of common factors attributed to brands do not largely determine preference for a particular brand.

  5. Attitude Exploration Using Factor Analysis Technique

    Directory of Open Access Journals (Sweden)

    Monika Raghuvanshi

    2016-12-01

    Full Text Available Attitude is a psychological variable that contains positive or negative evaluation about people or an environment. The growing generation possesses learning skills, so if positive attitude is inculcated at the right age, it might therefore become habitual. Students in the age group 14-20 years from the city of Bikaner, India, are the target population for this study. An inventory of 30Likert-type scale statements was prepared in order to measure attitude towards the environment and matters related to conservation. The primary data is collected though a structured questionnaire, using cluster sampling technique and analyzed using the IBM SPSS 23 statistical tool. Factor analysis is used to reduce 30 variables to a smaller number of more identifiable groups of variables. Results show that students “need more regulation and voluntary participation to protect the environment”, “need conservation of water and electricity”, “are concerned for undue wastage of water”, “need visible actions to protect the environment”, “need strengthening of the public transport system”, “are a little bit ignorant about the consequences of global warming”, “want prevention of water pollution by industries”, “need changing of personal habits to protect the environment”, and “don’t have firsthand experience of global warming”. Analysis revealed that nine factors obtained could explain about 58.5% variance in the attitude of secondary school students towards the environment in the city of Bikaner, India. The remaining 39.6% variance is attributed to other elements not explained by this analysis. A global campaign for improvement in attitude about environmental issues and its utility in daily lives may boost positive youth attitudes, potentially impacting worldwide. A cross-disciplinary approach may be developed by teaching along with other related disciplines such as science, economics, and social studies etc.

  6. Dose-effect relationships, epidemiological analysis and the derivation of low dose risk

    Energy Technology Data Exchange (ETDEWEB)

    Leenhouts, H P [Bennekom (Netherlands); Chadwick, K H, E-mail: kennethhchadwick@aol.com [Cowan Head, Kendal (United Kingdom)

    2011-03-01

    This paper expands on our recent comments in a letter to this journal about the analysis of epidemiological studies and the determination of low dose RBE of low LET radiation (Chadwick and Leenhouts 2009 J. Radiol. Prot. 29 445-7). Using the assumption that radiation induced cancer arises from a somatic mutation (Chadwick and Leenhouts 2011 J. Radiol. Prot. 31 41-8) a model equation is derived to describe cancer induction as a function of dose. The model is described briefly, evidence is provided in support of it, and it is applied to a set of experimental animal data. The results are compared with a linear fit to the data as has often been done in epidemiological studies. The article presents arguments to support several related messages which are relevant to epidemiological analysis, the derivation of low dose risk and the weighting factor of sparsely ionising radiations. The messages are: (a) cancer incidence following acute exposure should, in principle, be fitted to a linear-quadratic curve with cell killing using all the data available; (b) the acute data are dominated by the quadratic component of dose; (c) the linear fit of any acute data will essentially be dependent on the quadratic component and will be unrelated to the effectiveness of the radiation at low doses; consequently, (d) the method used by ICRP to derive low dose risk from the atomic bomb survivor data means that it is unrelated to the effectiveness of the hard gamma radiation at low radiation doses; (e) the low dose risk value should, therefore, not be used as if it were representative for hard gamma rays to argue for an increased weighting factor for tritium and soft x-rays even though there are mechanistic reasons to expect this; (f) epidemiological studies of chronically exposed populations supported by appropriate cellular radiobiological studies have the best chance of revealing different RBE values for different sparsely ionising radiations.

  7. Role of non-nitric oxide non-prostaglandin endothelium-derived relaxing factor(s in bradykinin vasodilation

    Directory of Open Access Journals (Sweden)

    A.C. Resende

    1998-09-01

    Full Text Available The most conspicuous effect of bradykinin following its administration into the systemic circulation is a transient hypotension due to vasodilation. In the present study most of the available evidence regarding the mechanisms involved in bradykinin-induced arterial vasodilation is reviewed. It has become firmly established that in most species vasodilation in response to bradykinin is mediated by the release of endothelial relaxing factors following the activation of B2-receptors. Although in some cases the action of bradykinin is entirely mediated by the endothelial release of nitric oxide (NO and/or prostacyclin (PGI2, a large amount of evidence has been accumulated during the last 10 years indicating that a non-NO/PGI2 factor accounts for bradykinin-induced vasodilation in a wide variety of perfused vascular beds and isolated small arteries from several species including humans. Since the effect of the non-NO/PGI2 endothelium-derived relaxing factor is practically abolished by disrupting the K+ electrochemical gradient together with the fact that bradykinin causes endothelium-dependent hyperpolarization of vascular smooth muscle cells, the action of such factor has been attributed to the opening of K+ channels in these cells. The pharmacological characteristics of these channels are not uniform among the different blood vessels in which they have been examined. Although there is some evidence indicating a role for KCa or KV channels, our findings in the mesenteric bed together with other reports indicate that the K+ channels involved do not correspond exactly to any of those already described. In addition, the chemical identity of such hyperpolarizing factor is still a matter of controversy. The postulated main contenders are epoxyeicosatrienoic acids or endocannabinoid agonists for the CB1-receptors. Based on the available reports and on data from our laboratory in the rat mesenteric bed, we conclude that the NO/PGI2-independent endothelium

  8. Brain-derived neurotrophic factor induces neuron-like cellular differentiation of mesenchymal stem cells derived from human umbilical cord blood cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Lei Chen; Guozhen Hui; Zhongguo Zhang; Bing Chen; Xiaozhi Liu; Zhenlin Liu; Hongliang Liu; Gang Li; Zhiguo Su; Junfei Wang

    2011-01-01

    Human umbilical cord blood was collected from full-term deliveries scheduled for cesarean section. Mononuclear cells were isolated, amplified and induced as mesenchymal stem cells. Isolated mesenchymal stem cells tested positive for the marker CD29, CD44 and CD105 and negative for typical hematopoietic and endothelial markers. Following treatment with neural induction medium containing brain-derived neurotrophic factor for 7 days, the adherent cells exhibited neuron-like cellular morphology. Immunohistochemical staining and reverse transcription-PCR revealed that the induced mesenchymal stem cells expressed the markers for neuron-specific enolase and neurofilament. The results demonstrated that human umbilical cord blood-derived mesenchymal stem cells can differentiate into neuron-like cells induced by brain-derived neurotrophic factor in vitro.

  9. Improving Your Exploratory Factor Analysis for Ordinal Data: A Demonstration Using FACTOR

    Directory of Open Access Journals (Sweden)

    James Baglin

    2014-06-01

    Full Text Available Exploratory factor analysis (EFA methods are used extensively in the field of assessment and evaluation. Due to EFA's widespread use, common methods and practices have come under close scrutiny. A substantial body of literature has been compiled highlighting problems with many of the methods and practices used in EFA, and, in response, many guidelines have been proposed with the aim to improve application. Unfortunately, implementing recommended EFA practices has been restricted by the range of options available in commercial statistical packages and, perhaps, due to an absence of clear, practical - how-to' demonstrations. Consequently, this article describes the application of methods recommended to get the most out of your EFA. The article focuses on dealing with the common situation of analysing ordinal data as derived from Likert-type scales. These methods are demonstrated using the free, stand-alone, easy-to-use and powerful EFA package FACTOR (http://psico.fcep.urv.es/utilitats/factor/, Lorenzo-Seva & Ferrando, 2006. The demonstration applies the recommended techniques using an accompanying dataset, based on the Big 5 personality test. The outcomes obtained by the EFA using the recommended procedures through FACTOR are compared to the default techniques currently available in SPSS.

  10. Clinical Analysis on Myeloid and Lymphoid Neoplasms with t (4; 22) Induced Abnormalities of the Platelet-derived Growth Factor Receptor Alpha%t(4;22)致血小板源性生长因子受体α异常的髓系/淋巴系肿瘤临床分析

    Institute of Scientific and Technical Information of China (English)

    崔菊亚; 孟文彤; 卢忠平; 朱焕玲

    2011-01-01

    Objective To observe the clinical features of myeloid and lymphoid neoplasms with t (4; 22) induced abnormalities of the platelet-derived growth factor receptor alpha (PDGFRA) to increase the identification and reduce the misdiagnosis. Methods The clinical data of one patient with myeloid and lymphoid neoplasm with t (4; 22) induced abnormalities of PDGFRA diagnosed in June 2010 was retrospectively analyzed. We summarized the clinical features, morphology, genetics, diagnostic criteria and therapy about this kind of disease. Results The patient had a clinical manifestation and bone marrow smear result of chronic myelogenous leukemia (CML). But the result of genetic analysis found no translocation of chromosomes 9 and 22 juxtaposing BCR and ABL gens. Cytogenetic analysis showed an abnormal karyotype with rearrangement of chromosomes 4 and 22. So the patient was diagnosed myeloid and lymphoid neoplasms with t (4; 22) induced abnormalities of PDGFRA. After receiving interferon and hydroxyurea,the patient achieved complete hematologic remission. Conclusion Myeloid and lymphoid neoplasms with t (4; 22) induced abnormalities of PDGFRA is a rare kind of disease. Its clinical feature is similar to that of CML. The key of diagnosis is genetics.%目的 观察t(4;22)致血小板源性生长因子受体a(the platelet-derived growth factor receptor alpha,PDGFRA)异常的髓系/淋巴系肿瘤的临床特点.方法 对2010年6月收治的1例t(4;22)致PDGFRA异常的髓系/淋巴系肿瘤患者的临床资料进行回顾性分析,并对其临床特点、实验室检查、诊断、治疗进行总结.结果 该疾病临床表现及骨髓涂片检查类似慢性粒细胞白血病(chronic myelogenous leukemia,CML),但无CML特征性Ph染色体和(或)BCR/ABL融合基因,而细胞遗传学检测显示4号与22号染色体易位.诊断为t(4;22)致PDGFRA异常的髓系/淋巴系肿瘤.采用羟基脲及干扰素治疗后可获得完全血液学缓解.结论 t(4;22)致PDGFRA异常的

  11. Danger signal-dependent activation of human dendritic cells by plasma-derived factor VIII products.

    Science.gov (United States)

    Miller, L; Weissmüller, S; Ringler, E; Crauwels, P; van Zandbergen, G; Seitz, R; Waibler, Z

    2015-08-01

    Treatment of haemophilia A by infusions of the clotting factor VIII (FVIII) results in the development of inhibitors/anti-drug antibodies in up to 25 % of patients. Mechanisms leading to immunogenicity of FVIII products are not yet fully understood. Amongst other factors, danger signals as elicited upon infection or surgery have been proposed to play a role. In the present study, we focused on effects of danger signals on maturation and activation of dendritic cells (DC) in the context of FVIII application. Human monocyte-derived DC were treated with FVIII alone, with a danger signal alone or a combination of both. By testing more than 60 different healthy donors, we show that FVIII and the bacterial danger signal lipopolysaccharide synergise in increasing DC activation, as characterised by increased expression of co-stimulatory molecules and secretion of pro-inflammatory cytokines. The degree and frequency of this synergistic activation correlate with CD86 expression levels on immature DC prior to stimulation. In our assay system, plasma-derived but not recombinant FVIII products activate human DC in a danger signal-dependent manner. Further tested danger signals, such as R848 also induced DC activation in combination with FVIII, albeit not in every tested donor. In our hands, human DC but not human B cells or macrophages could be activated by FVIII in a danger signal-dependent manner. Our results suggest that immunogenicity of FVIII is a result of multiple factors including the presence of danger, predisposition of the patient, and the choice of a FVIII product for treatment.

  12. Brain-derived neurotrophic factor deficiency restricts proliferation of oligodendrocyte progenitors following cuprizone-induced demyelination.

    Science.gov (United States)

    Tsiperson, Vladislav; Huang, Yangyang; Bagayogo, Issa; Song, Yeri; VonDran, Melissa W; DiCicco-Bloom, Emanuel; Dreyfus, Cheryl F

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that through its neurotrophic tyrosine kinase, receptor, type 2 (TrkB) receptor, increases 5-bromo-2-deoxyuridine incorporation in oligodendrocyte progenitor cells (OPCs) in culture. Roles in vivo are less well understood; however, increases in numbers of OPCs are restricted in BDNF+/- mice following cuprizone-elicited demyelination. Here, we investigate whether these blunted increases in OPCs are associated with changes in proliferation. BDNF+/+ and BDNF+/- mice were fed cuprizone-containing or control feed. To assess effects on OPC numbers, platelet-derived growth factor receptor alpha (PDGFRα)+ or NG2+ cells were counted. To monitor DNA synthesis, 5-ethynyl-2'-deoxyuridine (EdU) was injected intraperitoneally and colocalized with PDGFRα+ cells. Alternatively, proliferating cell nuclear antigen (PCNA) was colocalized with PDGFRα or NG2. Labeling indices were determined in the BDNF+/+ and BDNF+/- animals. After 4 or 5 weeks of control feed, BDNF+/- mice exhibit similar numbers of OPCs compared with BDNF+/+ animals. The labeling indices for EdU and PCNA also were not significantly different, suggesting that neither the DNA synthesis phase (S phase) nor the proliferative pool size was different between genotypes. In contrast, when mice were challenged by cuprizone for 4 or 5 weeks, increases in OPCs observed in BDNF+/+ mice were reduced in the BDNF+/- mice. This difference in elevations in cell number was accompanied by decreases in EdU labeling and PCNA labeling without changes in cell death, indicating a reduction in the DNA synthesis and the proliferative pool. Therefore, levels of BDNF influence the proliferation of OPCs resulting from a demyelinating lesion.

  13. Influence of basement membrane proteins and endothelial cell-derived factors on the morphology of human fetal-derived astrocytes in 2D.

    Directory of Open Access Journals (Sweden)

    Amanda F Levy

    Full Text Available Astrocytes are the most prevalent type of glial cell in the brain, participating in a variety of diverse functions from regulating cerebral blood flow to controlling synapse formation. Astrocytes and astrocyte-conditioned media are widely used in models of the blood-brain barrier (BBB, however, very little is known about astrocyte culture in 2D. To test the hypothesis that surface coating and soluble factors influence astrocyte morphology in 2D, we quantitatively analyzed the morphology of human fetal derived astrocytes on glass, matrigel, fibronectin, collagen IV, and collagen I, and after the addition soluble factors including platelet-derived growth factor (PDGF, laminin, basic fibroblast growth factor (bFGF, and leukemia inhibitory factor (LIF. Matrigel surface coatings, as well as addition of leukemia inhibitory factor (LIF to the media, were found to have the strongest effects on 2D astrocyte morphology, and may be important in improving existing BBB models. In addition, the novel set of quantitative parameters proposed in this paper provide a test for determining the influence of compounds on astrocyte morphology, both to screen for new endothelial cell-secreted factors that influence astrocytes, and to determine in a high-throughput way which factors are important for translation to more complex, 3D BBB models.

  14. Analyses toward factors influencing sealing clearance of a metal rubber seal and derivation of a calculation formula

    National Research Council Canada - National Science Library

    Yan Hui Zhao Yalei Liu Jianguo Jiang Hongyuan

    2016-01-01

    .... By combining the temperature and elasticity factors of metal rubber with the elastic mechanics theory, the calculation formula of the sealing clearance has been derived, and the values of the sealing...

  15. Effect of glial cell line-derived neurotrophic factor on retinal function after experimental branch retinal vein occlusion

    DEFF Research Database (Denmark)

    Ejstrup, Rasmus; Dornonville de la Cour, Morten; Kyhn, Maria Voss;

    2012-01-01

    The objective of the study was to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on the multifocal electroretinogram (mfERG) following an induced branch retinal vein occlusion (BRVO) in pigs.......The objective of the study was to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on the multifocal electroretinogram (mfERG) following an induced branch retinal vein occlusion (BRVO) in pigs....

  16. Pigment Epithelium-Derived Factor Alleviates Tamoxifen-Induced Endometrial Hyperplasia.

    Science.gov (United States)

    Goldberg, Keren; Bar-Joseph, Hadas; Grossman, Hadas; Hasky, Noa; Uri-Belapolsky, Shiri; Stemmer, Salomon M; Chuderland, Dana; Shalgi, Ruth; Ben-Aharon, Irit

    2015-12-01

    Tamoxifen is a cornerstone component of adjuvant endocrine therapy for patients with hormone-receptor-positive breast cancer. Its significant adverse effects include uterine hyperplasia, polyps, and increased risk of endometrial cancer. However, the underlying molecular mechanism remains unclear. Excessive angiogenesis, a hallmark of tumorigenesis, is a result of disrupted balance between pro- and anti-angiogenic factors. VEGF is a pro-angiogenic factor shown to be elevated by tamoxifen in the uterus. Pigment epithelium-derived factor (PEDF) is a potent anti-angiogenic factor that suppresses strong pro-angiogenic factors, such as VEGF. Our aim was to investigate whether angiogenic balance plays a role in tamoxifen-induced uterine pathologies, elucidate the molecular impairment in that network, and explore potential intervention to offset the proposed imbalance elicited by tamoxifen. Using in vivo mouse models, we demonstrated that tamoxifen induced a dose-dependent shift in endogenous uterine angiogenic balance favoring VEGF over PEDF. Treatment with recombinant PEDF (rPEDF) abrogated tamoxifen-induced uterine hyperplasia and VEGF elevation, resulting in reduction of blood vessels density. Exploring the molecular mechanism revealed that tamoxifen promoted survival and malignant transformation pathways, whereas rPEDF treatment prevents these changes. Activation of survival pathways was decreased, demonstrated by reduction in AKT phosphorylation concomitant with elevation in JNK phosphorylation. Estrogen receptor-α and c-Myc oncoprotein levels were reduced. Our findings provide novel insight into the molecular mechanisms tamoxifen induces in the uterus, which may become the precursor events of subsequent endometrial hyperplasia and cancer. We demonstrate that rPEDF may serve as a useful intervention to alleviate the risk of tamoxifen-induced endometrial pathologies.

  17. Expression of brain-derived neurotrophic factor mRNA in rat hippocampus after treatment with antipsychotic drugs.

    Science.gov (United States)

    Bai, Ou; Chlan-Fourney, Jennifer; Bowen, Rudy; Keegan, David; Li, Xin-Min

    2003-01-01

    Typical and atypical antipsychotic drugs, though both effective, act on different neurotransmitter receptors and are dissimilar in some clinical effects and side effects. The typical antipsychotic drug haloperidol has been shown to cause a decrease in the expression of brain-derived neurotrophic factor (BDNF), which plays an important role in neuronal cell survival, differentiation, and neuronal connectivity. However, it is still unknown whether atypical antipsychotic drugs similarly regulate BDNF expression. We examined the effects of chronic (28 days) administration of typical and atypical antipsychotic drugs on BDNF mRNA expression in the rat hippocampus using in situ hybridization. Quantitative analysis revealed that the typical antipsychotic drug haloperidol (1 mg/kg) down-regulated BDNF mRNA expression in both CA1 (P BDNF mRNA expression in CA1, CA3, and dentate gyrus regions of the rat hippocampus compared with their respective controls (P BDNF mRNA expression in rat hippocampus.

  18. Factorial invariance in multilevel confirmatory factor analysis.

    Science.gov (United States)

    Ryu, Ehri

    2014-02-01

    This paper presents a procedure to test factorial invariance in multilevel confirmatory factor analysis. When the group membership is at level 2, multilevel factorial invariance can be tested by a simple extension of the standard procedure. However level-1 group membership raises problems which cannot be appropriately handled by the standard procedure, because the dependency between members of different level-1 groups is not appropriately taken into account. The procedure presented in this article provides a solution to this problem. This paper also shows Muthén's maximum likelihood (MUML) estimation for testing multilevel factorial invariance across level-1 groups as a viable alternative to maximum likelihood estimation. Testing multilevel factorial invariance across level-2 groups and testing multilevel factorial invariance across level-1 groups are illustrated using empirical examples. SAS macro and Mplus syntax are provided.

  19. Physiological Factors Analysis in Unpressurized Aircraft Cabins

    Science.gov (United States)

    Patrao, Luis; Zorro, Sara; Silva, Jorge

    2016-11-01

    Amateur and sports flight is an activity with growing numbers worldwide. However, the main cause of flight incidents and accidents is increasingly pilot error, for a number of reasons. Fatigue, sleep issues and hypoxia, among many others, are some that can be avoided, or, at least, mitigated. This article describes the analysis of psychological and physiological parameters during flight in unpressurized aircraft cabins. It relates cerebral oximetry and heart rate with altitude, as well as with flight phase. The study of those parameters might give clues on which variations represent a warning sign to the pilot, thus preventing incidents and accidents due to human factors. Results show that both cerebral oximetry and heart rate change along the flight and altitude in the alert pilot. The impaired pilot might not reveal these variations and, if this is detected, he can be warned in time.

  20. Prostate-derived Ets factor, an oncogenic driver in breast cancer.

    Science.gov (United States)

    Sood, Ashwani K; Geradts, Joseph; Young, Jessica

    2017-05-01

    Prostate-derived Ets factor (PDEF), a member of the Ets family of transcription factors, differs from other family members in its restricted expression in normal tissues and its unique DNA-binding motif. These interesting attributes coupled with its aberrant expression in cancer have rendered PDEF a focus of increasing interest by tumor biologists. This review provides a current understanding of the characteristics of PDEF expression and its role in breast cancer. The bulk of the evidence is consistent with PDEF overexpression in most breast tumors and an oncogenic role for this transcription factor in breast cancer. In addition, high PDEF expression in estrogen receptor-positive breast tumors showed significant correlation with poor overall survival in several independent cohorts of breast cancer patients. Together, these findings demonstrate PDEF to be an oncogenic driver of breast cancer and a biomarker of poor prognosis in this cancer. Based on this understanding and the limited expression of PDEF in normal human tissues, the development of PDEF-based therapeutics for prevention and treatment of breast cancer is also discussed.

  1. Reduced neuroplasticity in aged rats: a role for the neurotrophin brain-derived neurotrophic factor.

    Science.gov (United States)

    Calabrese, Francesca; Guidotti, Gianluigi; Racagni, Giorgio; Riva, Marco A

    2013-12-01

    Aging is a physiological process characterized by a significant reduction of neuronal plasticity that might contribute to the functional defects observed in old subjects. Even if the neurobiological mechanisms that contribute to such impairment remain largely unknown, a role for neurotrophic molecules, such as the neurotrophin brain-derived neurotrophic factor (BDNF), has been postulated. On this basis, the purpose of this study was to provide a detailed investigation of the BDNF system, at transcriptional and translational levels, in the ventral and dorsal hippocampus and in the prefrontal cortex of middle-aged and old rats, compared with in adult animals. The expression of major players in BDNF regulation and response, including the transcription factors, calcium-responsive transcription factor, cyclic adenosine monophosphate (cAMP) responsive element-binding protein (CREB), and neuronal Per Arnt Sim (PAS) domain protein 4, and the high-affinity receptor tropomyosin receptor kinase B (TrkB), was also analyzed. Our results demonstrate that the BDNF system is affected at different levels in aged rats with global impairment including reduced transcription, impaired protein synthesis and processing, and decreased activation of the TrkB receptors. These modifications might contribute to the cognitive deficits associated with aging and suggest that pharmacological strategies aimed at restoring reduced neurotrophism might be useful to counteract age-related cognitive decline.

  2. Derivation of Accident-Specific Material-at-Risk Equivalency Factors

    Energy Technology Data Exchange (ETDEWEB)

    Jason P. Andrus; Dr. Chad L. Pope

    2012-05-01

    A novel method for calculating material at risk (MAR) dose equivalency developed at the Idaho National Laboratory (INL) now allows for increased utilization of dose equivalency for facility MAR control. This method involves near-real time accounting for the use of accident and material specific release and transport. It utilizes all information from the committed effective dose equation and the five factor source term equation to derive dose equivalency factors which can be used to establish an overall facility or process MAR limit. The equivalency factors allow different nuclide spectrums to be compared for their respective dose consequences by relating them to a specific quantity of an identified reference nuclide. The ability to compare spectrums to a reference limit ensures that MAR limits are in fact bounding instead of attempting to establish a representative or bounding spectrum which may lead to unintended or unanalyzed configurations. This methodology is then coupled with a near real time material tracking system which allows for accurate and timely material composition information and corresponding MAR equivalency values. The development of this approach was driven by the complex nature of processing operations in some INL facilities. This type of approach is ideally suited for facilities and processes where the composition of the MAR and possible release mechanisms change frequently but in well defined fashions and in a batch-type nature.

  3. Axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF.

    Directory of Open Access Journals (Sweden)

    Keiko Miwa

    Full Text Available Molecular signaling of cardiac autonomic innervation is an unresolved issue. Here, we show that glial cell line-derived neurotrophic factor (GDNF promotes cardiac sympathetic innervation in vitro and in vivo. In vitro, ventricular myocytes (VMs and sympathetic neurons (SNs isolated from neonatal rat ventricles and superior cervical ganglia were cultured at a close distance. Then, morphological and functional coupling between SNs and VMs was assessed in response to GDNF (10 ng/ml or nerve growth factor (50 ng/ml. As a result, fractions of neurofilament-M-positive axons and synapsin-I-positive area over the surface of VMs were markedly increased with GDNF by 9-fold and 25-fold, respectively, compared to control without neurotrophic factors. Pre- and post-synaptic stimulation of β1-adrenergic receptors (BAR with nicotine and noradrenaline, respectively, resulted in an increase of the spontaneous beating rate of VMs co-cultured with SNs in the presence of GDNF. GDNF overexpressing VMs by adenovirus vector (AdGDNF-VMs attracted more axons from SNs compared with mock-transfected VMs. In vivo, axon outgrowth toward the denervated myocardium in adult rat hearts after cryoinjury was also enhanced significantly by adenovirus-mediated GDNF overexpression. GDNF acts as a potent chemoattractant for sympathetic innervation of ventricular myocytes, and is a promising molecular target for regulation of cardiac function in diseased hearts.

  4. Axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF).

    Science.gov (United States)

    Miwa, Keiko; Lee, Jong-Kook; Takagishi, Yoshiko; Opthof, Tobias; Fu, Xianming; Hirabayashi, Masumi; Watabe, Kazuhiko; Jimbo, Yasuhiko; Kodama, Itsuo; Komuro, Issei

    2013-01-01

    Molecular signaling of cardiac autonomic innervation is an unresolved issue. Here, we show that glial cell line-derived neurotrophic factor (GDNF) promotes cardiac sympathetic innervation in vitro and in vivo. In vitro, ventricular myocytes (VMs) and sympathetic neurons (SNs) isolated from neonatal rat ventricles and superior cervical ganglia were cultured at a close distance. Then, morphological and functional coupling between SNs and VMs was assessed in response to GDNF (10 ng/ml) or nerve growth factor (50 ng/ml). As a result, fractions of neurofilament-M-positive axons and synapsin-I-positive area over the surface of VMs were markedly increased with GDNF by 9-fold and 25-fold, respectively, compared to control without neurotrophic factors. Pre- and post-synaptic stimulation of β1-adrenergic receptors (BAR) with nicotine and noradrenaline, respectively, resulted in an increase of the spontaneous beating rate of VMs co-cultured with SNs in the presence of GDNF. GDNF overexpressing VMs by adenovirus vector (AdGDNF-VMs) attracted more axons from SNs compared with mock-transfected VMs. In vivo, axon outgrowth toward the denervated myocardium in adult rat hearts after cryoinjury was also enhanced significantly by adenovirus-mediated GDNF overexpression. GDNF acts as a potent chemoattractant for sympathetic innervation of ventricular myocytes, and is a promising molecular target for regulation of cardiac function in diseased hearts.

  5. Effects of enamel matrix derivative and transforming growth factor-β1 on human osteoblastic cells

    Directory of Open Access Journals (Sweden)

    Rosa Adalberto L

    2011-07-01

    Full Text Available Abstract Background Extracellular matrix proteins are key factors that influence the regenerative capacity of tissues. The objective of the present study was to evaluate the effects of enamel matrix derivative (EMD, TGF-β1, and the combination of both factors (EMD+TGF-β1 on human osteoblastic cell cultures. Methods Cells were obtained from alveolar bone of three adult patients using enzymatic digestion. Effects of EMD, TGF-β1, or a combination of both were analyzed on cell proliferation, bone sialoprotein (BSP, osteopontin (OPN and alkaline phosphatase (ALP immunodetection, total protein synthesis, ALP activity and bone-like nodule formation. Results All treatments significantly increased cell proliferation compared to the control group at 24 h and 4 days. At day 7, EMD group showed higher cell proliferation compared to TGF-β1, EMD + TGF-β1 and the control group. OPN was detected in the majority of the cells for all groups, whereas fluorescence intensities for ALP labeling were greater in the control than in treated groups; BSP was not detected in all groups. All treatments decreased ALP levels at 7 and 14 days and bone-like nodule formation at 21 days compared to the control group. Conclusions The exposure of human osteoblastic cells to EMD, TGF-β1 and the combination of factors in vitro supports the development of a less differentiated phenotype, with enhanced proliferative activity and total cell number, and reduced ALP activity levels and matrix mineralization.

  6. Brain-derived neurotrophic factor as a drug target for CNS disorders.

    Science.gov (United States)

    Pezet, Sophie; Malcangio, Marzia

    2004-10-01

    Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of trophic factors. BDNF is widely and abundantly expressed in the CNS and is available to some peripheral nervous system neurons that uptake the neurotrophin produced by peripheral tissues. BDNF promotes survival and differentiation of certain neuronal populations during development. In adulthood, BDNF can modulate neuronal synaptic strength and has been implicated in hippocampal mechanisms of learning and memory and spinal mechanisms for pain. Several CNS disorders are associated with a decrease in trophic support. As BDNF and its high affinity receptor are abundant throughout the whole CNS, and BDNF is a potent neuroprotective agent, this trophic factor is a good candidate for therapeutic treatment of some of CNS disorders. This review aims to correlate the features of some CNS disorders (Parkinson's disease, Alzheimer's disease, depression, epilepsy and chronic pain) to changes in BDNF expression in the brain. The cellular and molecular mechanism by which BDNF might be a therapeutic strategy are critically examined.

  7. Analysis of the action of euxanthone, a plant-derived compound that stimulates neurite outgrowth.

    Science.gov (United States)

    Naidu, M; Kuan, C-Y K; Lo, W-L; Raza, M; Tolkovsky, A; Mak, N-K; Wong, R N-S; Keynes, R

    2007-09-21

    We have investigated the neurite growth-stimulating properties of euxanthone, a xanthone derivative isolated from the Chinese medicinal plant Polygala caudata. Euxanthone was shown to exert a marked stimulatory action on neurite outgrowth from chick embryo dorsal root ganglia explanted in collagen gels, in the absence of added neurotrophins. It was also shown to promote cell survival in explanted chick embryo ganglia, and to stimulate neurite outgrowth from isolated adult rat primary sensory neurons in vitro. The further finding that euxanthone stimulates neurite outgrowth from explants of chick embryo retina and ventral spinal cord suggests an action on signaling pathways downstream of neuronal receptors for specific neurotrophic factors. Consistent with this, euxanthone did not promote neurite outgrowth from non-transfected PC12 cells, or from PC12 cells transfected with TrkB or TrkC, under conditions in which these cells extended neurites in response to, respectively, the neurotrophins nerve growth factor, brain-derived neurotrophic factor and neurotrophin 3. Western blot analysis of euxanthone-stimulated dorsal root ganglion explants showed that expression of phospho-mitogen-activated protein (MAP) kinase was up-regulated after 1 h of euxanthone-treatment. Inhibition of the MAP kinase pathway using PD98059, a specific inhibitor of MAP kinase kinase, blocked all euxanthone-stimulated neurite outgrowth. However, analysis of phospho-Akt expression indicated that the phosphatidylinositol-3 kinase-Akt pathway, another major signaling pathway engaged by neurotrophins, is not significantly activated by euxanthone. These results suggest that euxanthone promotes neurite outgrowth by selectively activating the MAP kinase pathway.

  8. Safety of recombinant human platelet-derived growth factor-BB in Augment® Bone Graft

    Directory of Open Access Journals (Sweden)

    Luis A Solchaga

    2012-12-01

    Full Text Available This article discusses nonclinical and clinical data regarding the safety of recombinant human platelet-derived growth factor-BB as a component of the Augment® Bone Graft (Augment. Augment is a bone graft substitute intended to be used as an alternative to autologous bone graft in the fusion of hindfoot and ankle joints. Nonclinical studies included assessment of the pharmacokinetic profile of intravenously administered recombinant human platelet-derived growth factor-BB in rat and dog, effects of intravenous administration of recombinant human platelet-derived growth factor-BB in a reproductive and development toxicity study in rats, and chronic toxicity and carcinogenicity of Augment in a 12-month implantation model. These studies showed that systemic exposure was brief and clearance was rapid. No signs of toxicity, carcinogenicity, or tumor promotion were observed even with doses far exceeding the maximum clinical dose. Results of clinical trials (605 participants and commercial use of recombinant human platelet-derived growth factor-BB containing products indicate that these products are not associated with increased incidence of adverse events or cancer. The safety data presented provide evidence that recombinant human platelet-derived growth factor-BB is a safe therapeutic when used in combination products as a single administration during surgical procedures for bone repair and fusion. There is no evidence associating use of recombinant human platelet-derived growth factor-BB in Augment with chronic toxicity, carcinogenicity, or tumor promotion.

  9. Derivation of a clinical decision rule for predictive factors for the development of pharyngocutaneous fistula postlaryngectomy.

    Science.gov (United States)

    Cecatto, Suzana Boltes; Monteiro-Soares, Matilde; Henriques, Teresa; Monteiro, Eurico; Moura, Carla Isabel Ferreira Pinto

    2015-01-01

    Pharyngocutaneous fistula after larynx and hypopharynx cancer surgery can cause several damages. This study's aim was to derive a clinical decision rule to predict pharyngocutaneous fistula development after pharyngolaryngeal cancer surgery. A retrospective cohort study was conducted, including all patients performing total laryngectomy/pharyngolaryngectomy (n=171). Association between pertinent variables and pharyngocutaneous fistula development was assessed and a predictive model proposed. American Society of Anesthesiologists scale, chemoradiotherapy, and tracheotomy before surgery were associated with fistula in the univariate analysis. In the multivariate analysis, only American Society of Anesthesiologists maintained statistical significance. Using logistic regression, a predictive model including the following was derived: American Society of Anesthesiologists, alcohol, chemoradiotherapy, tracheotomy, hemoglobin and albumin pre-surgery, local extension, N-classification, and diabetes mellitus. The model's score area under the curve was 0.76 (95% CI 0.64-0.87). The high-risk group presented specificity of 93%, positive likelihood ratio of 7.10, and positive predictive value of 76%. Including the medium-low, medium-high, and high-risk groups, a sensitivity of 92%, negative likelihood ratio of 0.25, and negative predictive value of 89% were observed. A clinical decision rule was created to identify patients with high risk of pharyngocutaneous fistula development. Prognostic accuracy measures were substantial. Nevertheless, it is essential to conduct larger prospective studies for validation and refinement. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  10. Analysis of fuelling requirements in ITER H-modes with SOLPS-EPED1 derived scalings

    Science.gov (United States)

    Polevoi, A. R.; Loarte, A.; Kukushkin, A. S.; Pacher, H. D.; Pacher, G. W.; Köchl, F.

    2017-02-01

    Fuelling requirements for ITER are analysed in relation to pellet fuelling and ELM pacing, and a divertor power load control consistent with the ITER pumping and fuel throughput capabilities. The plasma parameters at the separatrix and the particle sources are derived from scalings based on SOLPS simulations. Effective transport coefficients in the H-mode pedestal are derived from EPED1 + SOLPS scalings for the pedestal height and width. 1.5D transport is simulated in the ASTRA framework. The operating window for ITER DT plasmas with the required fusion performance and level of ELM, and divertor power load control compatible with ITER fuelling and pumping capabilities, is determined. It is shown that the flexibility of the ITER fuelling systems, comprising pellet and gas injection systems, enables operation with Q  =  10, which was found to be marginal in previous studies following a similar approach but with different assumptions. The present assessment shows that a reduction of by a factor ~2 (from 9 to 5  ×  1019 m-3) in 15 MA H-mode plasmas leads to a reduction in the required pellet fuelling rate by a factor of four. Results of the analysis of the fuelling requirements for a range of ITER scenarios are found to be similar to those obtained with the JINTRAC code that included 2D modelling of the edge plasma.

  11. Conformational analysis of starch derivatives by FTIR spectroscopy

    NARCIS (Netherlands)

    Bruijnes, C.; Bosman, R.; Bareman, P.; Besemer, A.

    1989-01-01

    Infrared spectroscopy appears to be a helpful tool for conformational analyses of starch derivatives. In this study spectral changes in the fmgerprint region between 1200 and 900 cm-1 are related to changes in tertiary structures of β-cyclodextrin and linear dextrin inclusion complexes, linear dextr

  12. Lagrangian supersymmetries depending on derivatives. Global analysis and cohomology

    CERN Document Server

    Giachetta, G; Sardanashvily, G

    2004-01-01

    Lagrangian contact supersymmetries (depending on derivatives of arbitrary order) are treated in very general setting. The cohomology of the variational bicomplex on an arbitrary graded manifold and the iterated cohomology of a generic nilpotent contact supersymmetry are computed. In particular, the first variational formula and conservation laws for Lagrangian systems on graded manifolds using contact supersymmetries are obtained.

  13. Characterization and proteomic analysis of ovarian cancer-derived exosomes.

    Science.gov (United States)

    Liang, Bing; Peng, Peng; Chen, She; Li, Lin; Zhang, Meijun; Cao, Dongyan; Yang, Jiaxin; Li, Haixia; Gui, Ting; Li, Xialu; Shen, Keng

    2013-03-27

    Ovarian cancer is the most lethal type of cancer among all frequent gynecologic malignancies, because most patients present with advanced disease at diagnosis. Exosomes are important intercellular communication vehicles, released by various cell types. Here we presented firstly the protein profile of highly purified exosomes derived from two ovarian cancer cell lines, OVCAR-3 and IGROV1. The exosomes derived from ovarian cancer cell lines were round and mostly 30-100 nm in diameter when viewed under an electron microscope. The exosomal marker proteins TSG101 and Alix were detected in exosome preparations. The range of density was between 1.09 g/ml and 1.15 g/ml. A total of 2230 proteins were identified from two ovarian cell-derived exosomes. Among them, 1017 proteins were identified in both exosomes including all of the major exosomal protein markers. There were 380 proteins that are not reported in the ExoCarta database. In addition to common proteins from exosomes of various origins, our results showed that ovarian cancer-derived exosomes also carried tissue specific proteins associated with tumorigenesis and metastasis, especially in ovarian carcinoma. Based on the known roles of exosomes in cellular communication, these data indicate that exosomes released by ovarian cancer cells may play important roles in ovarian cancer progression and provide a potential source of blood-based protein biomarkers.

  14. A Histologically Distinctive Interstitial Pneumonia Induced by Overexpression of the Interleukin 6, Transforming Growth Factor β1, or Platelet-Derived Growth Factor B Gene

    Science.gov (United States)

    Yoshida, Mitsuhiro; Sakuma, Junko; Hayashi, Seiji; Abe, Kin'ya; Saito, Izumu; Harada, Shizuko; Sakatani, Mitsunoir; Yamamoto, Satoru; Matsumoto, Norinao; Kaneda, Yasufumi; Kishmoto, Tadamitsu

    1995-10-01

    Interstitial pneumonia is characterized by alveolitis with resulting fibrosis of the interstitium. To determine the relevance of humoral factors in the pathogenesis of interstitial pneumonia, we introduced expression vectors into Wistar rats via the trachea to locally overexpress humoral factors in the lungs. Human interleukin (IL) 6 and IL-6 receptor genes induced lymphocytic alveolitis without marked fibroblast proliferation. In contrast, overexpression of human transforming growth factor β1 or human platelet-derived growth factor B gene induced only mild or apparent cellular infiltration in the alveoli, respectively. However, both factors induced significant proliferation of fibroblasts and deposition of collagen fibrils. These histopathologic changes induced by the transforming growth factor β1 and platelet-derived growth factor B gene are partly akin to those changes seen in lung tissues from patients with pulmonary fibrosis and markedly contrast with the changes induced by overexpression of the IL-6 and IL-6 receptor genes that mimics lymphocytic interstitial pneumonia.

  15. Practical Considerations for Using Exploratory Factor Analysis in Educational Research

    Science.gov (United States)

    Beavers, Amy S.; Lounsbury, John W.; Richards, Jennifer K.; Huck, Schuyler W.; Skolits, Gary J.; Esquivel, Shelley L.

    2013-01-01

    The uses and methodology of factor analysis are widely debated and discussed, especially the issues of rotational use, methods of confirmatory factor analysis, and adequate sample size. The variety of perspectives and often conflicting opinions can lead to confusion among researchers about best practices for using factor analysis. The focus of the…

  16. Density analysis of the neutron structure factor and the determination of the pair potential of krypton

    Science.gov (United States)

    Barocchi, F.; Zoppi, M.; Egelstaff, P. A.

    1985-04-01

    We propose a method of analysis of the density behavior of the experimental neutron scattering structure factor which permits us to derive directly from the experimental results an ``experimental'' pair potential. We apply the method to the recent results of Teitsma and Egelstaff in krypton gas and derive a pair potential which is in good agreement with the empirical potential of Barker et al. Some discrepancies in the range 4

  17. The development of stochastic process modeling through risk analysis derived from scheduling of NPP project

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kwang Ho; Roh, Myung Sub [KEPCO International Nuclear Graduate School, Ulsan (Korea, Republic of)

    2013-10-15

    There are so many different factors to consider when constructing a nuclear power plant successfully from planning to decommissioning. According to PMBOK, all projects have nine domains from a holistic project management perspective. They are equally important to all projects, however, this study focuses mostly on the processes required to manage timely completion of the project and conduct risk management. The overall objective of this study is to let you know what the risk analysis derived from scheduling of NPP project is, and understand how to implement the stochastic process modeling through risk management. Building the Nuclear Power Plant is required a great deal of time and fundamental knowledge related to all engineering. That means that integrated project scheduling management with so many activities is necessary and very important. Simulation techniques for scheduling of NPP project using Open Plan program, Crystal Ball program, and Minitab program can be useful tools for designing optimal schedule planning. Thus far, Open Plan and Monte Carlo programs have been used to calculate the critical path for scheduling network analysis. And also, Minitab program has been applied to monitor the scheduling risk. This approach to stochastic modeling through risk analysis of project activities is very useful for optimizing the schedules of activities using Critical Path Method and managing the scheduling control of NPP project. This study has shown new approach to optimal scheduling of NPP project, however, this does not consider the characteristic of activities according to the NPP site conditions. Hence, this study needs more research considering those factors.

  18. Investigating the neurobiology of music: brain-derived neurotrophic factor modulation in the hippocampus of young adult mice.

    Science.gov (United States)

    Angelucci, Francesco; Fiore, Marco; Ricci, Enzo; Padua, Luca; Sabino, Andrea; Tonali, Pietro Attilio

    2007-09-01

    It has been shown that music might be able to improve mood state in people affected by psychiatric disorders, ameliorate cognitive deficits in people with dementia and increase motor coordination in Parkinson patients. Robust experimental evidence explaining the central effects of music, however, is missing. This study was designed to investigate the effect of music on brain neurotrophin production and behavior in the mouse. We exposed young adult mice to music with a slow rhythm (6 h/day; mild sound pressure levels, between 50 and 60 db) for 21 consecutive days. At the end of the treatment, mice were tested for passive avoidance learning and then killed for analysis of brain-derived neurotrophic factor (BDNF) and nerve growth factor with enzyme-linked immunosorbent assay (ELISA) in selected brain regions. We found that music-exposed mice showed increased BDNF, but not nerve growth factor in the hippocampus. Furthermore, we observed that music exposure significantly enhanced learning performance, as measured by the passive avoidance test. Our results demonstrate that exposure to music can modulate the activity of the hippocampus by influencing BDNF production. Our findings also suggest that music exposure might be of help in several central nervous system pathologies.

  19. Additive clinical value of serum brain-derived neurotrophic factor for prediction of chronic heart failure outcome.

    Science.gov (United States)

    Kadowaki, Shinpei; Shishido, Tetsuro; Honda, Yuki; Narumi, Taro; Otaki, Yoichiro; Kinoshita, Daisuke; Nishiyama, Satoshi; Takahashi, Hiroki; Arimoto, Takanori; Miyamoto, Takuya; Watanabe, Tetsu; Kubota, Isao

    2016-04-01

    The importance of the central nervous system in cardiovascular events has been recognized. Recently, brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, is involved in depression mechanisms and also in stress and anxiety. Because BDNF is reported about cardioprotective role, we elucidated whether BDNF is associated with cardiovascular events in patients with chronic heart failure (CHF). We examined serum BDNF levels in 134 patients with CHF and 23 control subjects. The patients were followed to register cardiac events for a median of 426 days. BDNF was significantly lower in CHF patients than in control subjects (25.8 ± 8.4 vs 14.7 ± 8.4, P BDNF was also lower in patients with cardiac events than in event-free patients (16.1 ± 8.0 vs 12.5 ± 8.5, P BDNF was determined by performing receiver operating characteristic curve analysis. Kaplan-Meier analysis demonstrated that patients with low levels of BDNF experienced higher rates of cardiac events than those with high levels of BDNF. Multivariate Cox hazard analysis demonstrated that low BDNF levels (≤12.4 ng/mL) were an independent prognostic factor for cardiac events (hazard ratio 2.932, 95 % confidence interval 1.622-5.301; P = 0.0004). Adding levels of BDNF to the model with BNP levels, age, and eGFR for the prediction of cardiac events yielded significant net reclassification improvement of 0.429 (P BDNF levels were found in patients with CHF, and these levels were found to be independently associated with an increased risk of cardiac events.

  20. Dispersive analysis of the scalar form factor of the nucleon

    CERN Document Server

    Hoferichter, M; Kubis, B; Meißner, U -G

    2012-01-01

    Based on the recently proposed Roy-Steiner equations for pion-nucleon scattering, we derive a system of coupled integral equations for the pi pi --> N-bar N and K-bar K --> N-bar N S-waves. These equations take the form of a two-channel Muskhelishvili-Omnes problem, whose solution in the presence of a finite matching point is discussed. We use these results to update the dispersive analysis of the scalar form factor of the nucleon fully including K-bar K intermediate states. In particular, we determine the correction Delta_sigma=sigma(2M_pi^2)-sigma_{pi N}, which is needed for the extraction of the pion-nucleon sigma term from pi N scattering, as a function of pion-nucleon subthreshold parameters and the pi N coupling constant.

  1. Accelerated Gibbs Sampling for Infinite Sparse Factor Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Andrzejewski, D M

    2011-09-12

    The Indian Buffet Process (IBP) gives a probabilistic model of sparse binary matrices with an unbounded number of columns. This construct can be used, for example, to model a fixed numer of observed data points (rows) associated with an unknown number of latent features (columns). Markov Chain Monte Carlo (MCMC) methods are often used for IBP inference, and in this technical note, we provide a detailed review of the derivations of collapsed and accelerated Gibbs samplers for the linear-Gaussian infinite latent feature model. We also discuss and explain update equations for hyperparameter resampling in a 'full Bayesian' treatment and present a novel slice sampler capable of extending the accelerated Gibbs sampler to the case of infinite sparse factor analysis by allowing the use of real-valued latent features.

  2. [The role of platelet-derived growth factor and ras P21 in experimental hepatocarcinogenesis].

    Science.gov (United States)

    Zheng, J; Ruan, Y; Liu, B

    1996-04-01

    In order to explore whether platelet-derived growth factor (PDGF) is involved in hepatocarcinogenesis, expression of PDGF-beta chain and ras P21 were investigated using immunohistochemical method in hepatocarcinoma induced with diethylnitrosamine (DENA). Elevated PDGF-beta chain and P21 protein levels were found in hepatocytes in the early stages after DENA administration. Along with the progression of hepatocarcinogenesis, immunopositive cells were increased with the formation of various foci and nodules and the staining was usually stronger in the peripheral parts of nodules. In addition, PDGF-beta and P21 often expressed simultaneously in the smae lesions, where the cells were also positive for AFP expression. The results suggest that abnormal expression of PDGF might be an early specific event during hepatocarcinogenesis and might be involved in the malignant transformation of the hepatocytes by autocrine as well through ras P21 signal pathways.

  3. Aerobic Exercise Does Not Predict Brain Derived Neurotrophic Factor And Cortisol Alterations in Depressed Patients.

    Science.gov (United States)

    Lamego, Murilo Khede; de Souza Moura, Antonio Marcos; Paes, Flávia; Ferreira Rocha, Nuno Barbosa; de Sá Filho, Alberto Souza; Lattari, Eduardo; Rimes, Ridson; Manochio, João; Budde, Henning; Wegner, Mirko; Mura, Gioia; Arias-Carrión, Oscar; Yuan, Ti-Fei; Nardi, Antonio Egidio; Machado, Sergio

    2015-01-01

    The pathophysiology of depression is related to neurobiological changes that occur in the monoamine system, hypothalamic-pituitary-adrenal axis, neurogenesis system and the neuroimmune system. In recent years, there has been a growing interest in the research of the effects of exercise on brain function, with a special focus on its effects on brain-derived neurotrophic factor (BDNF), cortisol and other biomarkers. Thus, the aim of this study is to present a review investigating the acute and chronic effects of aerobic exercise on BDNF and cortisol levels in individuals with depression. It was not possible to establish an interaction between aerobic exercise and concentration of BDNF and cortisol, which may actually be the result of the divergence of methods, such as type of exercises, duration of the sessions, and prescribed intensity and frequency of sessions.

  4. Contribution of endothelium-derived hyperpolarizing factor to exercise-induced vasodilation in health and hypercholesterolemia.

    Science.gov (United States)

    Ozkor, Muhiddin A; Hayek, Salim S; Rahman, Ayaz M; Murrow, Jonathan R; Kavtaradze, Nino; Lin, Ji; Manatunga, Amita; Quyyumi, Arshed A

    2015-02-01

    The role of endothelium-derived hyperpolarizing factor (EDHF) in either the healthy circulation or in those with hypercholesterolemia is unknown. In healthy and hypercholesterolemic subjects, we measured forearm blood flow (FBF) using strain-gauge plethysmography at rest, during graded handgrip exercise, and after sodium nitroprusside infusion. Measurements were repeated after l-NMMA, tetraethylammonium (TEA), and combined infusions. At rest, l-NMMA infusion reduced FBF in healthy but not hypercholesterolemic subjects. At peak exercise, vasodilation was lower in hypercholesterolemic compared to healthy subjects (274% vs 438% increase in FBF, p=0.017). TEA infusion reduced exercise-induced vasodilation in both healthy and hypercholesterolemic subjects (27%, pvasodilation in hypercholesterolemia. In conclusion, exercise-induced vasodilation is impaired and predominantly mediated by EDHF in hypercholesterolemic subjects. CLINICAL TRIAL REGISTRATION IDENTIFIER NCT00166166:

  5. Implication of platelet-derived growth factor receptor alpha in prostate cancer skeletal metastasis

    Institute of Scientific and Technical Information of China (English)

    Qingxin Liu; Danielle Jernigan; Yun Zhang; Alessandro Fatatis

    2011-01-01

    Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients.The skeleton is frequently targeted by disseminated cancer cells andrepresents the sole site of spread in more than 80% of prostate cancer cases.Compatibility between select malignant phenotypes and the microenvironment of colonized tissues is broadly recognized as the culprit for the organ-tropism of cancer cells.Here,we review our recent studies showing that the expression of platelet-derived growth factor receptor alpha (PDGFRα) supports the survival and growth of prostate cancer cells in the skeleton and that the soluble fraction of bone marrow activates PDGFRα in a ligand-independent fashion.Finally,we offer pre-clinical evidence that this receptor is a viable target for therapy.

  6. Brain-derived neurotrophic factor and exercise in fibromyalgia syndrome patients: a mini review.

    Science.gov (United States)

    Nugraha, Boya; Karst, Matthias; Engeli, Stefan; Gutenbrunner, Christoph

    2012-09-01

    Fibromyalgia syndrome (FMS) is a common chronic pain condition characterized by chronic widespread pain and decreased pain threshold, with hyperalgesia and allodynia. Associated signs include fatigue, morning stiffness, non-restorative sleep, mood disturbance, depression, irritable bowel syndrome, and headache. In addition to the administration of drugs, psychological therapies treatment of FMS mainly consists of physical therapies. Although the precise pathogenesis of FMS remains elucidated, modern understanding conceptualizes FMS as central sensitization as a consequence of altered endogenous pain- and stress-response system and continuous nociceptive input. Altered brain-derived neurotrophic factor (BDNF) levels in FMS suggest that BDNF--well known for its effects on neuronal plasticity--is involved in this sensitization process. Exercise leads to changes in serum BDNF levels, too. This association highlights the importance of exercise in FMS and other chronic pain conditions.

  7. Association of coatomer proteins with the beta-receptor for platelet-derived growth factor

    DEFF Research Database (Denmark)

    Hansen, Klaus; Rönnstrand, L; Rorsman, C

    1997-01-01

    of intracellular vesicle transport. In order to explore the functional significance of the interaction between alpha- and beta'-COP and the PDGF receptor, a receptor mutant was made in which the conserved histidine residue 928 was mutated to an alanine residue. The mutant receptor, which was unable to bind alpha......The nonreceptor tyrosine kinase Src binds to and is activated by the beta-receptor for platelet-derived growth factor (PDGF). The interaction leads to Src phosphorylation of Tyr934 in the kinase domain of the receptor. In the course of the functional characterization of this phosphorylation, we...... noticed that components of 136 and 97 kDa bound to a peptide from this region of the receptor in a phosphorylation-independent manner. These components have now been purified and identified as alpha- and beta'-coatomer proteins (COPs), respectively. COPs are a family of proteins involved in the regulation...

  8. [BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF): NEUROBIOLOGY AND MARKER VALUE IN NEUROPSYCHIATRY].

    Science.gov (United States)

    Levada, O A; Cherednichenko, N V

    2015-01-01

    In this review current publications about neurobiology and marker value of brain derived neurotrophic factor (BDNF) in neuropsychiatry are analyzed. It is shown that BDNF is an important member of the family of neurotrophins which widely represented in various structures of the CNS. In prenatal period BDNF is involved in all stages of neuronal networks formation, and in the postnatal period its main role is maintaining the normal brain architectonics, involvement in the processes of neurogenesis and realization of neuroprotective functions. BDNF plays an important role in learning and memory organization, food and motor behavior. BDNF brain expression decreases with age, as well as in degenerative and vascular dementias, affective, anxiety, and behavioral disorders. The reducing of BDNF serum, level reflects the decreasing of its cerebral expression and could be used as a neurobiological marker of these pathological processes but the rising of its concentration could indicate the therapy effectiveness.

  9. Brain-derived neurotrophic factor in mood disorders and antidepressant treatments.

    Science.gov (United States)

    Castrén, Eero; Kojima, Masami

    2017-01-01

    Levels of brain-derived neurotrophic factor (BDNF) are reduced in the brain and serum of depressed patients and at least the reduction in serum levels is reversible upon successful treatment. These data, together with a wealth of reports using different animal models with depression-like behavior or manipulation of expression of BDNF or its receptor TrkB have implicated BDNF in the pathophysiology of depression as well as in the mechanism of action of antidepressant treatments. Recent findings have shown that posttranslational processing of BDNF gene product can yield different molecular entities that differently influence signaling through BNDF receptor TrkB and the pan-neurotrophin receptor p75(NTR). We will here review these data and discuss new insights into the possible pathophysiological roles of those new BDNF subtypes as well as recent findings on the role of BDNF mediated neuronal plasticity in mood disorders and their treatments.

  10. Derivation and application of the energy dissipation factor in the design of fishways

    Science.gov (United States)

    Towler, Brett; Mulligan, Kevin; Haro, Alexander J.

    2015-01-01

    Reducing turbulence and associated air entrainment is generally considered advantageous in the engineering design of fish passage facilities. The well-known energy dissipation factor, or EDF, correlates with observations of the phenomena. However, inconsistencies in EDF forms exist and the bases for volumetric energy dissipation rate criteria are often misunderstood. A comprehensive survey of EDF criteria is presented. Clarity in the application of the EDF and resolutions to these inconsistencies are provided through formal derivations; it is demonstrated that kinetic energy represents only 1/3 of the total energy input for the special case of a broad-crested weir. Specific errors in published design manuals are identified and resolved. New, fundamentally sound, design equations for culvert outlet pools and standard Denil Fishway resting pools are developed. The findings underscore the utility of EDF equations, demonstrate the transferability of volumetric energy dissipation rates, and provide a foundation for future refinement of component-, species-, and life-stage-specific EDF criteria.

  11. Gonadectomy affects brain derived neurotrophic factor in rats after chronic constriction nerve injury

    Institute of Scientific and Technical Information of China (English)

    Xin ZHAO; Xin WANG; Shu-yun ZHENG; Jian-guo XU

    2004-01-01

    AIM: To assess the effect of gonadectomy on brain derived neurotrophic factor (BDNF) expression in neuropathic pain. METHODS: Using chronic constriction injury (CCI) model, we detected BDNF mRNA in dorsal root ganglion and protein content in spinal cord by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay respectively. The time point we chose was post CCI operation d 0, 3, 7, 14, and 21.RESULTS: After CCI surgery, BDNF mRNA in ipsilateral DRGs was upregulated and reached its maximum on post operation d 7. BDNF protein level in ipsilateral spinal cord was also increased and reached its maximum on post operation d 14. The magnitude of this increase in gonadectomy (GDX) rats was significantly smaller than the GDX-sham rats at each time point. CONCLUSION: Gonadectomy reduced the BDNF increment after CCI surgery.Estrogen may affect nociceptive processing by its effect on BDNF.

  12. Pharmacokinetics of intravitreal glial cell line-derived neurotrophic factor: experimental studies in pigs

    DEFF Research Database (Denmark)

    Ejstrup, Rasmus; Kiilgaard, J F; Tucker, B A;

    2010-01-01

    The purpose of this study was to establish the intravitreal (ITV) pharmacokinetics of glial cell line-derived neurotrophic factor (GDNF) and observe possible complications after ITV injection. Twenty Danish landrace pigs and 34 eyes were included in the study; 30 were injected with 100 ng of GDNF......, two controls were injected without GDNF, and two received no injection. At post-injection time points of 1, 2, 3, 6 hours (h), 1, 2, 4 or 7 days (d) eyes were enucleated and the ITV concentration of GDNF (cGDNF) was determined by enzyme-linked immunosorbent assay, and activity was tested using...... a retinal ganglion cell line (RGC5) bioassay. Indirect ophthalmoscopy, intraocular pressure assessment, and fundus photography were performed before enucleation. There was initial variability in the cGDNF, but after 24h GDNF was cleared in a monoexponential fashion with a half-life of 37 h (CL 33-43 h...

  13. Glial cell line-derived neurotrophic factor (GDNF therapy for Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Shingo,Tetsuro

    2007-04-01

    Full Text Available Many studies using animals clarify that glial cell line-derived neurotrophic factor (GDNF has strong neuroprotective and neurorestorative effects on dopaminergic neurons. Several pilot studies clarified the validity of continuous intraputaminal GDNF infusion to patients with Parkinson's disease (PD, although a randomized controlled trial of GDNF therapy published in 2006 resulted in negative outcomes, and controversy remains about the efficacy and safety of the treatment. For a decade, our laboratory has investigated the efficacy and the most appropriate method of GDNF administration using animals, and consequently we have obtained some solid data that correspond to the results of clinical trials. In this review, we present an outline of our studies and other key studies related to GDNF, the current state of the research, problems to be overcome, and predictions regarding the use of GDNF therapy for PD in the future.

  14. A synthetic manassantin a derivative inhibits hypoxia-inducible factor 1 and tumor growth.

    Science.gov (United States)

    Lang, Liwei; Liu, Xiaoyu; Li, Yan; Zhou, Qing; Xie, Ping; Yan, Chunhong; Chen, Xiaoguang

    2014-01-01

    The dineolignan manassantin A from Saururaceae was recently identified as a hypoxia-inducible factor 1 (HIF-1) inhibitor, but its in-vivo anti-tumor effect has not been explored. We synthesized a series of manassantin A derivatives, and found that replacing the central tetrahydrofuran moiety with a cyclopentane ring yielded a compound (LXY6006) with increased HIF-1-inhibitory activity yet decreased stereochemically complexity amenable to a simplified synthesis scheme. LXY6006 inhibited HIF-1α nuclear accumulation induced by hypoxia, and inhibited cancer cell growth as a consequence of G2/M arrest. Oral administration of LXY6006 significantly inhibited growth of breast, lung, and pancreatic tumors implanted in nude mice. These results indicate that LXY6006 represents a novel class of agents targeting a broad range of human cancers.

  15. A synthetic manassantin a derivative inhibits hypoxia-inducible factor 1 and tumor growth.

    Directory of Open Access Journals (Sweden)

    Liwei Lang

    Full Text Available The dineolignan manassantin A from Saururaceae was recently identified as a hypoxia-inducible factor 1 (HIF-1 inhibitor, but its in-vivo anti-tumor effect has not been explored. We synthesized a series of manassantin A derivatives, and found that replacing the central tetrahydrofuran moiety with a cyclopentane ring yielded a compound (LXY6006 with increased HIF-1-inhibitory activity yet decreased stereochemically complexity amenable to a simplified synthesis scheme. LXY6006 inhibited HIF-1α nuclear accumulation induced by hypoxia, and inhibited cancer cell growth as a consequence of G2/M arrest. Oral administration of LXY6006 significantly inhibited growth of breast, lung, and pancreatic tumors implanted in nude mice. These results indicate that LXY6006 represents a novel class of agents targeting a broad range of human cancers.

  16. Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Pedersen, Bente Klarlund; Kessing, Lars Vedel

    2014-01-01

    Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case......-control designs. The aim of this study was to investigate whether BDNF and NT-3 levels differ between patients with rapid cycling bipolar disorder and healthy control subjects and whether BDNF and NT-3 levels alter with affective states in rapid cycling bipolar disorder patients. Plasma levels of BDNF and NT-3...... were measured in 37 rapid cycling bipolar disorder patients and in 40 age- and gender matched healthy control subjects using enzyme-linked immunosorbent assay (ELISA). In a longitudinal design, repeated measurements of BDNF and NT-3 were evaluated in various affective states in bipolar disorder...

  17. Platelet-Derived Growth Factor as a Therapeutic Target for Systemic Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Hideto Kameda

    2007-01-01

    Full Text Available Some systemic rheumatic diseases and disorders, especially fibrotic and vascular disorders, are often refractory to corticosteroid therapy. Recently, ever accumulating evidence suggests that platelet-derived growth factor (PDGF is involved in those refractory diseases. Imatinib mesylate inhibits the activation of PDGF receptor as well as c-Abl, Bcr-Abl and c-Kit tyrosine kinases. It has therefore been widely used for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Imatinib effectively suppresses the activation and proliferation of fibroblasts, mesangial cells and smooth muscle cells both in vitro and in vivo. Additionally, it has recently been reported that some patients with rheumatoid arthritis or idiopathic pulmonary arterial hypertension demonstrated a good clinical response to imatinib therapy. Imatinib may therefore overcome the limitations of current therapeutic strategy with corticosteroids and immunosuppressive agents for refractory diseases, such as systemic sclerosis and interstitial lung diseases, without clinical intolerability.

  18. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Brassard, Patrice; Adser, Helle

    2009-01-01

    Brain-derived neurotrophic factor (BDNF) has an important role in regulating maintenance, growth and survival of neurons. However, the main source of circulating BDNF in response to exercise is unknown. To identify whether the brain is a source of BDNF during exercise, eight volunteers rowed for 4...... h while simultaneous blood samples were obtained from the radial artery and the internal jugular vein. To further identify putative cerebral region(s) responsible for BDNF release, mouse brains were dissected and analysed for BDNF mRNA expression following treadmill exercise. In humans, a BDNF...... release from the brain was observed at rest (P exercise (P exercise, the brain contributed 70-80% of circulating BDNF, while that contribution decreased following 1 h of recovery. In mice, exercise induced a three...

  19. Matrine inhibits proliferation of mouse skin fibroblasts induced by platelet-derived growth factor-BB

    Institute of Scientific and Technical Information of China (English)

    WU Yan-an; GAO Chun-fang; WANG Hao; HUANG Chao; KONG Xian-tao

    2001-01-01

    To study the effect of matrine on proliferation of mouse skin fibroblasts induced by platelet-derived growth factor-BB (PDGF-BB). Methods: Mouse skin fibroblasts were obtained from newborn ⅠCR mice and propagated in vitro. Proliferation of cell was analyzed by mitochondrial reduction of tetrazolium salt MTT and actual cell count. Results: Matrine (50 to 500 μg/ml) caused dose-dependent reduction of serum-stimulated cell growth. Growth inhibition was totally reversed after removal of the drug. Matrine also inhibited PDGF-BB induced cell growth dose-dependently. Conclusion: Matrine exhibits potent anti-proliferation effect on mouse skin fibroblast. This effect appears to be mediated by decrease of PDGF-induced growth. These results suggest that matrine might have preventive and therapeutic implication in skin fibrosis.

  20. Serum brain-derived neurotrophic factor levels in different neurological diseases.

    Science.gov (United States)

    Ventriglia, Mariacarla; Zanardini, Roberta; Bonomini, Cristina; Zanetti, Orazio; Volpe, Daniele; Pasqualetti, Patrizio; Gennarelli, Massimo; Bocchio-Chiavetto, Luisella

    2013-01-01

    Consistent evidence indicates the involvement of the brain-derived neurotrophic factor (BDNF) in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). In the present study, we compared serum BDNF in 624 subjects: 266 patients affected by AD, 28 by frontotemporal dementia (FTD), 40 by Lewy body dementia (LBD), 91 by vascular dementia (VAD), 30 by PD, and 169 controls. Our results evidenced lower BDNF serum levels in AD, FTD, LBD, and VAD patients (P benzodiazepines (P = 0.020). In conclusion, our results support the role of BDNF alterations in neurodegenerative mechanisms common to different forms of neurological disorders and underline the importance of including drug treatment in the analyses to avoid confounding effects.

  1. The brain derived neurotrophic factor and influences of stress in depression.

    Science.gov (United States)

    Kimpton, Jessica

    2012-09-01

    Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family and is widely expressed throughout the central nervous system (CNS). BDNF is involved in proliferation, differentiation, survival and death of neuronal and non-neuronal cells in the developing and adult CNS. The BDNF hypothesis of depression postulates that a reduction in BDNF is directly involved in the pathophysiology of depression, whilst anti-depressant mediated restoration of BDNF is responsible for the alleviation of the depressive state. This hypothesis is drawn from several studies implicating BDNF in depression and has received considerable support, which will be reviewed in this paper. This review will also discuss the implications of the functional Val66Met polymorphism of the gene encoding BDNF, which may reduce BDNF expression particularly when exposed to stress and thus may play a critical role in the pathogenesis of depression.

  2. Cell-based delivery of brain-derived neurotrophic factor in experimental allergic encephalomyelitis.

    Science.gov (United States)

    Makar, Tapas K; Nimmagadda, Vamshi K C; Trisler, David; Bever, Christopher T

    2014-08-01

    Brain-derived neurotrophic factor (BDNF) is a pleiotropic cytokine with neuroprotective properties that has been identified as a potential therapeutic agent for diseases of the central nervous system (CNS). The use of BDNF has been limited by a short serum half-life and poor penetration of the blood-brain barrier. To address this limitation we have explored cell-based approaches to delivery. We have used experimental allergic encephalomyelitis (EAE), an inflammatory disease of the CNS, as a model system. We engineered hematopoietic stem cells to produce BDNF to determine the feasibility and effectiveness of cell-based delivery of BDNF into the CNS in EAE. We review those studies here.

  3. Brain-derived neurotrophic factor (BDNF) overexpression in the forebrain results in learning and memory impairments.

    Science.gov (United States)

    Cunha, Carla; Angelucci, Andrea; D'Antoni, Angela; Dobrossy, Mate D; Dunnett, Stephen B; Berardi, Nicoletta; Brambilla, Riccardo

    2009-03-01

    In this study we analyzed the effect on behavior of a chronic exposure to brain-derived neurotrophic factor (BDNF), by analysing a mouse line overexpressing BDNF under the alphaCaMKII promoter, which drives the transgene expression exclusively to principal neurons of the forebrain. BDNF transgenic mice and their WT littermates were examined with a battery of behavioral tests, in order to evaluate motor coordination, learning, short and long-term memory formation. Our results demonstrate that chronic BDNF overexpression in the central nervous system (CNS) causes learning deficits and short-term memory impairments, both in spatial and instrumental learning tasks. This observation suggests that a widespread increase in BDNF in forebrain networks may result in adverse effects on learning and memory formation.

  4. Label-free nanopore proximity bioassay for platelet-derived growth factor detection.

    Science.gov (United States)

    Zhang, Ling; Zhang, Kaixiang; Liu, Guangchao; Liu, Mengjia; Liu, Yang; Li, Jinghong

    2015-06-02

    Rapid and sensitive detection of biomarkers with ultralow concentrations remains a great challenge in disease diagnostics. Herein, we present a label-free α-hemolysin (α-HL) nanopore proximity bioassay for protein biomarker detection by a binding-induced DNA strand displacement strategy. In this bioassay, an individual target protein, platelet-derived growth factor B-chain (PDGF-BB), was selectively recognized by two oligonucleotide affinity ligands in which an output DNA was released and translocated through α-HL nanopore with a spikelike short current block. The frequency of the current block events had a linear relationship with the concentration of PDGF-BB with a wide linear dynamic range of 5 orders of magnitude and a detection limit at 500 fM. The selectivity and anti-interference capability of this bioassay show great potential for biomarker detection in bioanalytical chemistry.

  5. Inhibition of platelet-derived growth factor signaling prevents muscle fiber growth during skeletal muscle hypertrophy.

    Science.gov (United States)

    Sugg, Kristoffer B; Korn, Michael A; Sarver, Dylan C; Markworth, James F; Mendias, Christopher L

    2017-03-01

    The platelet-derived growth factor receptors alpha and beta (PDGFRα and PDGFRβ) mark fibroadipogenic progenitor cells/fibroblasts and pericytes in skeletal muscle, respectively. While the role that these cells play in muscle growth and development has been evaluated, it was not known whether the PDGF receptors activate signaling pathways that control transcriptional and functional changes during skeletal muscle hypertrophy. To evaluate this, we inhibited PDGFR signaling in mice subjected to a synergist ablation muscle growth procedure, and performed analyses 3 and 10 days after induction of hypertrophy. The results from this study indicate that PDGF signaling is required for fiber hypertrophy, extracellular matrix production, and angiogenesis that occur during muscle growth. © 2017 Federation of European Biochemical Societies.

  6. Therapeutic Potential of Adipose-Derived Therapeutic Factor Concentrate for Treating Critical Limb Ischemia.

    Science.gov (United States)

    Procházka, Václav; Jurčíková, Jana; Laššák, Ondrej; Vítková, Kateřina; Pavliska, Lubomír; Porubová, Ludmila; Buszman, Piotr P; Krauze, Agata; Fernandez, Carlos; Jalůvka, František; Špačková, Iveta; Lochman, Ivo; Jana, Dvořáčková; Merfeld-Clauss, Stephanie; March, Keith L; Traktuev, Dmitry O; Johnstone, Brian H

    2016-01-01

    Transplantation of adipose-derived stem cells (ADSCs) is an emerging therapeutic option for addressing intractable diseases such as critical limb ischemia (CLI). Evidence suggests that therapeutic effects of ADSCs are primarily mediated through paracrine mechanisms rather than transdifferentiation. These secreted factors can be captured in conditioned medium (CM) and concentrated to prepare a therapeutic factor concentrate (TFC) composed of a cocktail of beneficial growth factors and cytokines that individually and in combination demonstrate disease-modifying effects. The ability of a TFC to promote reperfusion in a rabbit model of CLI was evaluated. A total of 27 adult female rabbits underwent surgery to induce ischemia in the left hindlimb. An additional five rabbits served as sham controls. One week after surgery, the ischemic limbs received intramuscular injections of either (1) placebo (control medium), (2) a low dose of TFC, or (3) a high dose of TFC. Limb perfusion was serially assessed with a Doppler probe. Blood samples were analyzed for growth factors and cytokines. Tissue was harvested postmortem on day 35 and assessed for capillary density by immunohistochemistry. At 1 month after treatment, tissue perfusion in ischemic limbs treated with a high dose of TFC was almost double (p < 0.05) that of the placebo group [58.8 ± 23 relative perfusion units (RPU) vs. 30.7 ± 13.6 RPU; mean ± SD]. This effect was correlated with greater capillary density in the affected tissues and with transiently higher serum levels of the angiogenic and prosurvival factors vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). The conclusions from this study are that a single bolus administration of TFC demonstrated robust effects for promoting tissue reperfusion in a rabbit model of CLI and that a possible mechanism of revascularization was promotion of angiogenesis by TFC. Results of this study demonstrate that TFC represents a potent

  7. Stromal cell-derived factor-1 potentiates bone morphogenetic protein-2 induced bone formation.

    Science.gov (United States)

    Higashino, Kosaku; Viggeswarapu, Manjula; Bargouti, Maggie; Liu, Hui; Titus, Louisa; Boden, Scott D

    2011-02-01

    The mechanisms driving bone marrow stem cell mobilization are poorly understood. A recent murine study found that circulating bone marrow-derived osteoprogenitor cells (MOPCs) were recruited to the site of recombinant human bone morphogenetic protein-2 (BMP-2)-induced bone formation. Stromal cell-derived factor-1α (SDF-1α) and its cellular receptor CXCR4 have been shown to mediate the homing of stem cells to injured tissues. We hypothesized that chemokines, such as SDF-1, are also involved with mobilization of bone marrow cells. The CD45(-) fraction is a major source of MOPCs. In this report we determined that the addition of BMP-2 or SDF-1 to collagen implants increased the number of MOPCs in the peripheral blood. BMP-2-induced mobilization was blocked by CXCR4 antibody, confirming the role of SDF-1 in mobilization. We determined for the first time that addition of SDF-1 to implants containing BMP-2 enhances mobilization, homing of MOPCs to the implant, and ectopic bone formation induced by suboptimal BMP-2 doses. These results suggest that SDF-1 increases the number of osteoprogenitor cells that are mobilized from the bone marrow and then home to the implant. Thus, addition of SDF-1 to BMP-2 may improve the efficiency of BMPs in vivo, making their routine use for orthopaedic applications more affordable and available to more patients.

  8. Astrocyte-derived vascular endothelial growth factor stabilizes vessels in the developing retinal vasculature.

    Directory of Open Access Journals (Sweden)

    Andrew Scott

    Full Text Available Vascular endothelial growth factor (VEGF plays a critical role in normal development as well as retinal vasculature disease. During retinal vascularization, VEGF is most strongly expressed by not yet vascularized retinal astrocytes, but also by retinal astrocytes within the developing vascular plexus, suggesting a role for retinal astrocyte-derived VEGF in angiogenesis and vessel network maturation. To test the role of astrocyte-derived VEGF, we used Cre-lox technology in mice to delete VEGF in retinal astrocytes during development. Surprisingly, this only had a minor impact on retinal vasculature development, with only small decreases in plexus spreading, endothelial cell proliferation and survival observed. In contrast, astrocyte VEGF deletion had more pronounced effects on hyperoxia-induced vaso-obliteration and led to the regression of smooth muscle cell-coated radial arteries and veins, which are usually resistant to the vessel-collapsing effects of hyperoxia. These results suggest that VEGF production from retinal astrocytes is relatively dispensable during development, but performs vessel stabilizing functions in the retinal vasculature and might be relevant for retinopathy of prematurity in humans.

  9. Control of angiogenesis by galectins involves the release of platelet-derived proangiogenic factors.

    Directory of Open Access Journals (Sweden)

    Julia Etulain

    Full Text Available Platelets contribute to vessel formation through the release of angiogenesis-modulating factors stored in their α-granules. Galectins, a family of lectins that bind β-galactoside residues, are up-regulated in inflammatory and cancerous tissues, trigger platelet activation and mediate vascularization processes. Here we aimed to elucidate whether the release of platelet-derived proangiogenic molecules could represent an alternative mechanism through which galectins promote neovascularization. We show that different members of the galectin family can selectively regulate the release of angiogenic molecules by human platelets. Whereas Galectin (Gal-1, -3, and -8 triggered vascular endothelial growth factor (VEGF release, only Gal-8 induced endostatin secretion. Release of VEGF induced by Gal-8 was partially prevented by COX-1, PKC, p38 and Src kinases inhibitors, whereas Gal-1-induced VEGF secretion was inhibited by PKC and ERK blockade, and Gal-3 triggered VEGF release selectively through a PKC-dependent pathway. Regarding endostatin, Gal-8 failed to stimulate its release in the presence of PKC, Src and ERK inhibitors, whereas aspirin or p38 inhibitor had no effect on endostatin release. Despite VEGF or endostatin secretion, platelet releasates generated by stimulation with each galectin stimulated angiogenic responses in vitro including endothelial cell proliferation and tubulogenesis. The platelet angiogenic activity was independent of VEGF and was attributed to the concerted action of other proangiogenic molecules distinctly released by each galectin. Thus, secretion of platelet-derived angiogenic molecules may represent an alternative mechanism by which galectins promote angiogenic responses and its selective blockade may lead to the development of therapeutic strategies for angiogenesis-related diseases.

  10. Meta analysis of relationship between serum brain derived neurotrophic factor level and post stroke depression%血清脑源性神经营养因子水平与脑卒中后抑郁关系的meta分析

    Institute of Scientific and Technical Information of China (English)

    蒋华玉; 王永刚

    2014-01-01

    Aim:To explore the relationship between serum brain derived neurotrophic factor ( BDNF) level and post stroke depression ( PSD) .Methods:Prospective randomized controlled trails of the relationship between serum BDNF level and PSD were selected from database such as PubMed ,CNKI,VIP Data,Wangfang Data.Review Manager 5.2 was used for the meta analysis .Results:Five case-control studies were collected , there were 222 PSD patients and 230 stroke patients without depression.The Heterogeneity among the 5 studies was significant(χ2 =35.13,P<0.001,I2 =89%).The random effects model was chosen .The result showed that there were no significant differences in the serum BDNF level between PSD patients and the stroke patients without depression (Z=0.39,P=0.70).Conclusion:These analysis suggested that the PSD patients'serum BDNF level is not different from stroke patients without depression .%目的:探讨血清脑源性神经营养因子( BDNF)水平与脑卒中后抑郁( PSD)的关系。方法:在万方、中国知网、维普数据库及PubMed中进行检索,纳入关于血清BDNF水平与PSD关系的所有临床病例对照试验,病例组为PSD患者,对照组为非PSD患者。应用Review Manager 5.2进行meta分析。结果:共纳入符合要求的研究5项,其中病例组222例,对照组230例。因各研究间存在高度异质性(χ2=35.13,P<0.001,I2=89%),选择随机效应模型,结果显示,两组血清BDNF水平差异无统计学意义( Z=0.39,P=0.70)。结论:尚不能认为PSD患者血清BDNF水平较非PSD患者有明显变化。

  11. Characterization of a receptor for human monocyte-derived neutrophil chemotactic factor/interleukin-8

    Energy Technology Data Exchange (ETDEWEB)

    Grob, P.M.; David, E.; Warren, T.C.; DeLeon, R.P.; Farina, P.R.; Homon, C.A. (Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT (USA))

    1990-05-15

    Monocyte-derived neutrophil chemotactic factor/interleukin-8 (MDNCF/IL-8) is an 8,000-dalton protein produced by monocytes which exhibits activity as a chemoattractant for neutrophils with maximal activity achieved at a concentration of 50 ng/ml. This polypeptide has been iodinated by chloramine-T methodology (350 Ci/mM), and specific receptors for MDNCF/IL-8 have been detected on human neutrophils, U937 cells, THP-1 cells, and dimethyl sulfoxide-differentiated HL-60 cells. The binding of MDNCF/IL-8 to human neutrophils is not inhibited by interleukin-1 alpha, tumor necrosis factor-alpha, insulin, or epidermal growth factor. In addition, chemoattractants such as C5a, fMet-Leu-Phe, leukotriene B4, and platelet-activating factor fail to inhibit binding, suggesting that MDNCF/IL-8 utilizes a unique receptor. The receptor for MDNCF/IL-8 is apparently glycosylated since ligand binding is inhibited by the presence of wheat germ agglutinin, a lectin with a binding specificity for N-acetylglucosamine and neuraminic acid. Steady state binding experiments indicate Kd values of 4 and 0.5 nM and receptor numbers of 75,000 and 7,400 for human neutrophils and differentiated HL-60 cells, respectively. 125I-MDNCF/IL-8 bound to human neutrophils is rapidly internalized and subsequently released from cells as trichloroacetic acid-soluble radioactivity. Affinity labeling experiments suggest that the human neutrophil MDNCF/IL-8 receptor exhibits a mass of approximately 58,000 daltons.

  12. Analysis of transfer reactions: determination of spectroscopic factors

    Energy Technology Data Exchange (ETDEWEB)

    Keeley, N. [CEA Saclay, Dept. d' Astrophysique, de Physique des Particules de Physique Nucleaire et de l' Instrumentation Associee (DSM/DAPNIA/SPhN), 91- Gif sur Yvette (France); The Andrzej So an Institute for Nuclear Studies, Dept. of Nuclear Reactions, Warsaw (Poland)

    2007-07-01

    An overview of the most popular models used for the analysis of direct reaction data is given, concentrating on practical aspects. The 4 following models (in order of increasing sophistication): the distorted wave born approximation (DWBA), the adiabatic model, the coupled channels born approximation, and the coupled reaction channels are briefly described. As a concrete example, the C{sup 12}(d,p)C{sup 13} reaction at an incident deuteron energy of 30 MeV is analysed with progressively more physically sophisticated models. The effect of the choice of the reaction model on the spectroscopic information extracted from the data is investigated and other sources of uncertainty in the derived spectroscopic factors are discussed. We have showed that the choice of the reaction model can significantly influence the nuclear structure information, particularly the spectroscopic factors or amplitudes but occasionally also the spin-parity, that we wish to extract from direct reaction data. We have also demonstrated that the DWBA can fail to give a satisfactory description of transfer data but when the tenets of the theory are fulfilled DWBA can work very well and will yield the same results as most sophisticated models. The use of global rather than fitted optical potentials can also lead to important differences in the extracted spectroscopic factors.

  13. In Silico Antitubercular Activity Analysis of Benzofuran and Naphthofuran Derivatives

    Directory of Open Access Journals (Sweden)

    Prashantha Karunakar

    2014-01-01

    Full Text Available For the human health, Mycobacterium tuberculosis (MTB is the deadliest enemy since decades due to its multidrug resistant strains. During latent stage of tuberculosis infection, MTB consumes nitrate as the alternate mechanism of respiration in the absence of oxygen, thus increasing its survival and virulence. NarL is a nitrate/nitrite response transcriptional regulatory protein of two-component signal transduction system which regulates nitrate reductase and formate dehydrogenase for MTB adaptation to anaerobic condition. Phosphorylation by sensor kinase (NarX is the primary mechanism behind the activation of NarL although many response regulators get activated by small molecule phospho-donors in the absence of sensor kinase. Using in silico approach, the molecular docking of benzofuran and naphthofuran derivatives and dynamic study of benzofuran derivative were performed. It was observed that compound Ethyl 5-bromo-3-ethoxycarbonylamino-1-benzofuran-2-carboxylate could be stabilized at the active site for over 10 ns of simulation. Here we suggest that derivatives of benzofuran moiety can lead to developing novel antituberculosis drugs.

  14. Genome-wide identification of Bcl11b gene targets reveals role in brain-derived neurotrophic factor signaling.

    Directory of Open Access Journals (Sweden)

    Bin Tang

    Full Text Available B-cell leukemia/lymphoma 11B (Bcl11b is a transcription factor showing predominant expression in the striatum. To date, there are no known gene targets of Bcl11b in the nervous system. Here, we define targets for Bcl11b in striatal cells by performing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq in combination with genome-wide expression profiling. Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b. ChIP-seq analysis demonstrated that Bcl11b bound a mixture of coding and non-coding sequences that were within 10 kb of the transcription start site of an annotated gene. Integrating all ChIP-seq hits with the microarray expression data, 248 direct targets of Bcl11b were identified. Functional analysis on the integrated gene target list identified several zinc-finger encoding genes as Bcl11b targets, and further revealed a significant association of Bcl11b to brain-derived neurotrophic factor/neurotrophin signaling. Analysis of ChIP-seq binding regions revealed significant consensus DNA binding motifs for Bcl11b. These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders. Specific targeting of the Bcl11b-DNA interaction could represent a novel therapeutic approach to lowering BDNF signaling specifically in striatal cells.

  15. Sample Preparation for Headspace GC Analysis of Residual Solvents in Hyaluronic Acid Derivative Fiber

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hoon Joo; Kim, Dong Min; Yang, Jeong Soo [LG life Sciences, Ltd./R and D Park, Daejeon (Korea, Republic of); Kim, Chan Wha [Korea University, Seoul (Korea, Republic of)

    2006-02-15

    The aim of this study is to develop efficient sample preparation method for HS-GC analysis of residual solvents in HA derivative fiber. Compared to direct extraction of residual solvents from HA derivative fiber, the extraction through the hydrolysis of HA derivative fiber by HAse gave more complete and higher reproducible quantification of residual solvent. To validate HS-GC analysis method of residual solvents, specificity, limits of detection and quantification, linearity, accuracy and precision are investigated in the study. HA derivative fiber was hydrolyzed using HAse for headspace gas chromatographic analysis of residual solvents of ethanol, acetone and isopropanol in HA derivative fiber. This study showed that the developed method had specificity, linearity, accuracy and precision. In addition, it demonstrated that HS-GC coupled with matrix-breaking method such as hydrolysis was available for the determination of residual solvents in a matrix like HA derivative fiber.

  16. The Construct Validity of Scores on the Ways of Coping Questionnaire: Confirmatory Analysis of Alternative Factor Structures.

    Science.gov (United States)

    Edwards, Jeffrey R.; O'Neill, Regina M.

    1998-01-01

    Confirmatory factor analysis was used to evaluate alternative factor structures, based on previous exploratory factor analyses and coping dimensions derived from the theory of R. Lazarus, for the Ways of Coping Questionnaire (S. Folkman and R. Lazarus, 1988). Results from responses of 654 college graduates provide little support for the factor…

  17. Mesenchymal stem cells expressing brain-derived neurotrophic factor enhance endogenous neurogenesis in an ischemic stroke model.

    Science.gov (United States)

    Jeong, Chang Hyun; Kim, Seong Muk; Lim, Jung Yeon; Ryu, Chung Heon; Jun, Jin Ae; Jeun, Sin-Soo

    2014-01-01

    Numerous studies have reported that mesenchymal stem cells (MSCs) can ameliorate neurological deficits in ischemic stroke models. Among the various hypotheses that have been suggested to explain the therapeutic mechanism underlying these observations, neurogenesis is thought to be critical. To enhance the therapeutic benefits of human bone marrow-derived MSCs (hBM-MSCs), we efficiently modified hBM-MSCs by introduction of the brain-derived neurotrophic factor (BDNF) gene via adenoviral transduction mediated by cell-permeable peptides and investigated whether BDNF-modified hBM-MSCs (MSCs-BDNF) contributed to functional recovery and endogenous neurogenesis in a rat model of middle cerebral artery occlusion (MCAO). Transplantation of MSCs induced the proliferation of 5-bromo-2'-deoxyuridine (BrdU-) positive cells in the subventricular zone. Transplantation of MSCs-BDNF enhanced the proliferation of endogenous neural stem cells more significantly, while suppressing cell death. Newborn cells differentiated into doublecortin (DCX-) positive neuroblasts and Neuronal Nuclei (NeuN-) positive mature neurons in the subventricular zone and ischemic boundary at higher rates in animals with MSCs-BDNF compared with treatment using solely phosphate buffered saline (PBS) or MSCs. Triphenyltetrazolium chloride staining and behavioral analysis revealed greater functional recovery in animals with MSCs-BDNF compared with the other groups. MSCs-BDNF exhibited effective therapeutic potential by protecting cell from apoptotic death and enhancing endogenous neurogenesis.

  18. Mesenchymal Stem Cells Expressing Brain-Derived Neurotrophic Factor Enhance Endogenous Neurogenesis in an Ischemic Stroke Model

    Directory of Open Access Journals (Sweden)

    Chang Hyun Jeong

    2014-01-01

    Full Text Available Numerous studies have reported that mesenchymal stem cells (MSCs can ameliorate neurological deficits in ischemic stroke models. Among the various hypotheses that have been suggested to explain the therapeutic mechanism underlying these observations, neurogenesis is thought to be critical. To enhance the therapeutic benefits of human bone marrow-derived MSCs (hBM-MSCs, we efficiently modified hBM-MSCs by introduction of the brain-derived neurotrophic factor (BDNF gene via adenoviral transduction mediated by cell-permeable peptides and investigated whether BDNF-modified hBM-MSCs (MSCs-BDNF contributed to functional recovery and endogenous neurogenesis in a rat model of middle cerebral artery occlusion (MCAO. Transplantation of MSCs induced the proliferation of 5-bromo-2′-deoxyuridine (BrdU- positive cells in the subventricular zone. Transplantation of MSCs-BDNF enhanced the proliferation of endogenous neural stem cells more significantly, while suppressing cell death. Newborn cells differentiated into doublecortin (DCX- positive neuroblasts and Neuronal Nuclei (NeuN- positive mature neurons in the subventricular zone and ischemic boundary at higher rates in animals with MSCs-BDNF compared with treatment using solely phosphate buffered saline (PBS or MSCs. Triphenyltetrazolium chloride staining and behavioral analysis revealed greater functional recovery in animals with MSCs-BDNF compared with the other groups. MSCs-BDNF exhibited effective therapeutic potential by protecting cell from apoptotic death and enhancing endogenous neurogenesis.

  19. In vivo induction of glial cell proliferation and axonal outgrowth and myelination by brain-derived neurotrophic factor.

    NARCIS (Netherlands)

    Groot, D.M. de; Coenen, A.J.M.; Verhofstad, A.A.J.; Herp, F. van; Martens, G.J.M.

    2006-01-01

    Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of neuronal cell survival and differentiation factors but is thought to be involved in neuronal cell proliferation and myelination as well. To explore the role of BDNF in vivo, we employed the intermediate pituitary melanotr

  20. Connective tissue growth factor differentially binds to members of the cystine knot superfamily and potentiates platelet-derived growth factor-B signaling in rabbit corneal fibroblast cells

    Institute of Scientific and Technical Information of China (English)

    Liya; Pi; Pei-Yu; Chung; Sriniwas; Sriram; Masmudur; M; Rahman; Wen-Yuan; Song; Edward; W; Scott; Bryon; E; Petersen; Gregory; S; Schultz

    2015-01-01

    AIM:To study the binding of connective tissue growth factor(CTGF) to cystine knot-containing ligands and how this impacts platelet-derived growth factor(PDGF)-B signaling. METHODS:The binding strengths of CTGF to cystine knot-containing growth factors including vascular en-dothelial growth factor(VEGF)-A,PDGF-B,bone morphogenetic protein(BMP)-4,and transforming growth factor(TGF)-β1 were compared using the LexA-based yeast two-hybrid system. EYG48 reporter strain that carried a wild-type LEU2 gene under the control of Lex A operators and a lac Z reporter plasmid(p80plac Z) containing eight high affinity Lex A binding sites were used in the yeast two-hybrid analysis. Interactions between CTGF and the tested growth factors were evaluated based on growth of transformed yeast cells on selective media and colorimetric detection in a liquid β-galactosidase activity assay. Dissociation constants of CTGF to VEGF-A isoform 165 or PDGF-BB homo-dimer were measured in surface plasma resonance(SPR) analysis. CTGF regulation in PDGF-B presentation to the PDGF receptor β(PDGFRβ) was also quantitatively assessed by the SPR analysis. Combinational effects of CTGF protein and PDGF-BB on activation of PDGFRβ and downstream signaling molecules ERK1/2 and AKT were assessed in rabbit corneal fibroblast cells by Western analysis. RESULTS:In the LexA-based yeast two-hybrid system,cystine knot motifs of tested growth factors were fused to the activation domain of the transcriptional factor GAL4 while CTGF was fused to the DNA binding domain of the bacterial repressor protein Lex A. Yeast cotransformants containing corresponding fusion proteins for CTGF and all four tested cystine knot motifs survived on selective medium containing galactose and raffinose but lacking histidine,tryptophan,and uracil. In liquid β-galactosidase assays,CTGF expressing cells that were co-transformed with the cystine knot of VEGF-A had the highest activity,at 29.88 ± 0.91 fold above controls(P < 0

  1. Dipeptide Mimetic of the Brain-derived Neurotrophic Factor Prevents Impairments of Neurogenesis in Stressed Mice.

    Science.gov (United States)

    Gudasheva, T A; Povarnina, P Yu; Seredenin, S B

    2017-02-01

    Brain-derived neurotrophic factor (BDNF) plays the central role in the mechanisms of regulation of neurogenesis and neuroplasticity. Impairment of these mechanisms is considered as one of the main etiological factors of depression. Dimeric dipeptide mimetic of BDNF loop 4 bis-(N-monosuccinyl-l-seryl-l-lysine) hexamethylenediamide (GSB-106) was synthesized at the V. V. Zakusov Research Institute of Pharmacology. In vivo experiments revealed significant antidepressant properties of GSB-106 in doses of 0.1-10 mg/kg (intraperitoneally and orally). Effects of GSB-106 on hippocampal neurogenesis were studied in mice subjected to chronic predator stress. Proliferative activity in the subgranular zone of the dental gyrus was assessed immunohistochemically by Ki-67 expression (a marker of dividing cells). It was found that GSB-106 (10 mg/kg, intraperitoneally, 5 days) completely prevents neurogenesis disturbances in stressed mice. These findings suggest that GSB-106 is a promising candidate for the development of antidepressant agents with BDNF-like mechanism of action.

  2. Correlation between Chromatograph Capacity Factors and Structural Parameters of Indole Derivatives

    Institute of Scientific and Technical Information of China (English)

    ZHENG Qing; WANG Zun-Yao; SUN Li; YU Bin

    2005-01-01

    Sixteen indole derivatives have been computed at B3LYP/6-311G** level using density functional theory (DFT). Based on linear solvation energy theory, the structural para- meters were employed to present correlation between the parameters of chromatograph capacity factor (CCF) and molecular structural parameters. As a result, the correlation equation of the reversed phased high performance liquid chromatograph capacity factor to the intercept lgk'w and slope S of CCF were obtained, from which the correlation coefficients of lgk'w to the structural parameters are r2 = 0.9596 and q2 = 0.9262. While the correlation coefficients of the parameter S with structures are r2 = 0.9750 and q2 = 0.9252. Moreover, the effect of water as solvent on the present two models was also considered using SCRF method, and the result shows that the predicting capacity of correlation equation of lgkw' increases, while that of the model for S decreases slightly. Both two correlation equations achieved in this work are more advantageous than those using theoretical descriptors from molecular connectivity indices.

  3. Conditional ablation of brain-derived neurotrophic factor-TrkB signaling impairs striatal neuron development.

    Science.gov (United States)

    Li, Yun; Yui, Daishi; Luikart, Bryan W; McKay, Renée M; Li, Yanjiao; Rubenstein, John L; Parada, Luis F

    2012-09-18

    Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), are associated with the physiology of the striatum and the loss of its normal functioning under pathological conditions. The role of BDNF and its downstream signaling in regulating the development of the striatum has not been fully investigated, however. Here we report that ablation of Bdnf in both the cortex and substantia nigra depletes BDNF in the striatum, and leads to impaired striatal development, severe motor deficits, and postnatal lethality. Furthermore, striatal-specific ablation of TrkB, the gene encoding the high-affinity receptor for BDNF, is sufficient to elicit an array of striatal developmental abnormalities, including decreased anatomical volume, smaller neuronal nucleus size, loss of dendritic spines, reduced enkephalin expression, diminished nigral dopaminergic projections, and severe deficits in striatal dopamine signaling through DARPP32. In addition, TrkB ablation in striatal neurons elicits a non-cell-autonomous reduction of tyrosine hydroxylase protein level in the axonal projections of substantia nigral dopaminergic neurons. Thus, our results establish an essential function for TrkB in regulating the development of striatal neurons.

  4. Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor

    Science.gov (United States)

    Chen, Hong; Yang, Georgiana Zong Xin; Getachew, Hoheteberhan; Acosta, Camilo; Sierra Sánchez, Carlos; Konofagou, Elisa E.

    2016-06-01

    The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain.

  5. The Non-Survival Effects of Glial Cell Line-Derived Neurotrophic Factor on Neural Cells

    Directory of Open Access Journals (Sweden)

    Daniel Cortés

    2017-08-01

    Full Text Available Glial cell line-derived neurotrophic factor (GDNF was first characterized as a survival-promoting molecule for dopaminergic neurons (DANs. Afterwards, other cells were also discovered to respond to GDNF not only as a survival factor but also as a protein supporting other cellular functions, such as proliferation, differentiation, maturation, neurite outgrowth and other phenomena that have been less studied than survival and are now more extendedly described here in this review article. During development, GDNF favors the commitment of neural precursors towards dopaminergic, motor, enteric and adrenal neurons; in addition, it enhances the axonal growth of some of these neurons. GDNF also induces the acquisition of a dopaminergic phenotype by increasing the expression of Tyrosine Hydroxylase (TH, Nurr1 and other proteins that confer this identity and promote further dendritic and electrical maturation. In motor neurons (MNs, GDNF not only promotes proliferation and maturation but also participates in regenerating damaged axons and modulates the neuromuscular junction (NMJ at both presynaptic and postsynaptic levels. Moreover, GDNF modulates the rate of neuroblastoma (NB and glioblastoma cancer cell proliferation. Additionally, the presence or absence of GDNF has been correlated with conditions such as depression, pain, muscular soreness, etc. Although, the precise role of GDNF is unknown, it extends beyond a survival effect. The understanding of the complete range of properties of this trophic molecule will allow us to investigate its broad mechanisms of action to accelerate and/or improve therapies for the aforementioned pathological conditions.

  6. Activation of 5-HT7 receptors increases neuronal platelet-derived growth factor β receptor expression.

    Science.gov (United States)

    Vasefi, Maryam S; Kruk, Jeff S; Liu, Hui; Heikkila, John J; Beazely, Michael A

    2012-03-09

    Several antipsychotics have a high affinity for 5-HT7 receptors yet despite intense interest in the 5-HT7 receptor as a potential drug target to treat psychosis, the function and signaling properties of 5-HT7 receptors in neurons remain largely uncharacterized. In primary mouse hippocampal and cortical neurons, as well as in the SH-SY5Y cell line, incubation with 5-HT, 5-carboxamidotryptamine (5-CT), or 5-HT7 receptor-selective agonists increases the expression of platelet-derived growth factor (PDGF)β receptors. The increased PDGFβ receptor expression is cyclic AMP-dependent protein kinase (PKA)-dependent, suggesting that 5-HT7 receptors couple to Gα(s) in primary neurons. Interestingly, up-regulated PDGFβ receptors display an increased basal phosphorylation state at the phospholipase Cγ-activating tyrosine 1021. This novel linkage between the 5-HT7 receptor and the PDGF system may be an important GPCR-neurotrophic factor signaling pathway in neurons.

  7. Treatment with glial derived neurotropic factor (GDNF attenuates oxidative damages of spinal

    Directory of Open Access Journals (Sweden)

    Tao Li

    2016-05-01

    Full Text Available Spinal cord injury (SCI is a serious and debilitating issue being suffered by wide population worldwide. Extensive treatment approaches have been tested and being verified for their efficacy. Owing to the nature of central nervous system (CNS, the resident stem cells would be triggered in response to any sort of trauma with nerve factors as their communication signals. Apart from physical injuries, damages due to oxidative stress also need to be addressed while CNS repair mechanism takes place. This study looks at the potential of glial derived nerve factor (GDNF in addressing the SCI in regard to oxidative damages. A total of 60 Wistar rats were clustered into five groups and GDNF at various concentrations was tested in each group. Assessments in terms of oxidative stress parameters were noted and analyzed accordingly. It was noted that GDNF had reduced oxidative damages and increased the levels of anti-oxidants in dose-dependent manner (p < 0.05. Though treatment with 10 mg/mL and 20 mg/mL showed significant changes as compared to control group, these treatment modalities remained insignificant among each other. In conclusion, we demonstrated that GDNF exerted a neuro-protective effect on CNS by inducing anti-oxidants and reducing the levels of oxidative stress in SCI induced rat models.

  8. Glial cell line-derived neurotrophic factor protects against high-fat diet-induced obesity.

    Science.gov (United States)

    Mwangi, Simon Musyoka; Nezami, Behtash Ghazi; Obukwelu, Blessing; Anitha, Mallappa; Marri, Smitha; Fu, Ping; Epperson, Monica F; Le, Ngoc-Anh; Shanmugam, Malathy; Sitaraman, Shanthi V; Tseng, Yu-Hua; Anania, Frank A; Srinivasan, Shanthi

    2014-03-01

    Obesity is a growing epidemic with limited effective treatments. The neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) was recently shown to enhance β-cell mass and improve glucose control in rodents. Its role in obesity is, however, not well characterized. In this study, we investigated the ability of GDNF to protect against high-fat diet (HFD)-induced obesity. GDNF transgenic (Tg) mice that overexpress GDNF under the control of the glial fibrillary acidic protein promoter and wild-type (WT) littermates were maintained on a HFD or regular rodent diet for 11 wk, and weight gain, energy expenditure, and insulin sensitivity were monitored. Differentiated mouse brown adipocytes and 3T3-L1 white adipocytes were used to study the effects of GDNF in vitro. Tg mice resisted the HFD-induced weight gain, insulin resistance, dyslipidemia, hyperleptinemia, and hepatic steatosis seen in WT mice despite similar food intake and activity levels. They exhibited significantly (PGDNF enhanced β-adrenergic-mediated cAMP release in brown adipocytes and suppressed lipid accumulation in differentiated 3T3L-1 cells through a p38MAPK signaling pathway. Our studies demonstrate a novel role for GDNF in the regulation of high-fat diet-induced obesity through increased energy expenditure. They show that GDNF and its receptor agonists may be potential targets for the treatment or prevention of obesity.

  9. Imipramine induces brain-derived neurotrophic factor mRNA expression in cultured astrocytes.

    Science.gov (United States)

    Takano, Katsura; Yamasaki, Hiroshi; Kawabe, Kenji; Moriyama, Mitsuaki; Nakamura, Yoichi

    2012-01-01

    Depression is one of the most prevalent and livelihood-threatening forms of mental illnesses and the neural circuitry underlying depression remains incompletely understood. Recent studies suggest that the neuronal plasticity involved with brain-derived neurotrophic factor (BDNF) plays an important role in the recovery from depression. Some antidepressants are reported to induce BDNF expression in vivo; however, the mechanisms have been considered solely in neurons and not fully elucidated. In the present study, we evaluated the effects of imipramine, a classic tricyclic antidepressant drug, on BDNF expression in cultured rat brain astrocytes. Imipramine dose-dependently increased BDNF mRNA expression in astrocytes. The imipramine-induced BDNF increase was suppressed with inhibitors for protein kinase A (PKA) or MEK/ERK. Moreover, imipramine exposure activated transcription factor cAMP response element binding protein (CREB) in a dose-dependent manner. These results suggested that imipramine induced BDNF expression through CREB activation via PKA and/or ERK pathways. Imipramine treatment in depression might exert antidepressant action through BDNF production from astrocytes, and glial BDNF expression might be a target of developing novel antidepressants.

  10. Brain-derived neurotrophic factor Val66Met polymorphism and early life adversity affect hippocampal volume.

    Science.gov (United States)

    Carballedo, Angela; Morris, Derek; Zill, Peter; Fahey, Ciara; Reinhold, Elena; Meisenzahl, Eva; Bondy, Brigitta; Gill, Michael; Möller, Hans-Jürgen; Frodl, Thomas

    2013-03-01

    The interaction between adverse life events during childhood and genetic factors is associated with a higher risk to develop major depressive disorder (MDD). One of the polymorphisms found to be associated with MDD is the Val66MET polymorphism of brain-derived neurotrophic factor (BDNF). The aim of our two-center study was to determine how the BDNF Val66Met polymorphism and childhood adversity affect the volumetric measures of the hippocampus in healthy individuals and people with MDD. In this two-center study, 62 adult patients with MDD and 71 healthy matched controls underwent high-resolution magnetic resonance imaging. We used manual tracing of the bilateral hippocampal structure with help of the software BRAINS2, assessed childhood adversity using the Childhood Trauma Questionnaire and genotyped Val66Met BDNF SNP (rs6265). MDD patients had smaller hippocampal volumes, both in the left and right hemispheres (F = 5.4, P = 0.022). We also found a significant interaction between BDNF allele and history of childhood adversity (F = 6.1, P = 0.015): Met allele carriers in our samples showed significantly smaller hippocampal volumes when they did have a history of childhood adversity, both in patients and controls. Our results highlight how relevant stress-gene interactions are for hippocampal volume reductions. Subjects exposed to early life adversity developed smaller hippocampal volumes when they carry the Met-allele of the BDNF polymorphism.

  11. The Effects of 12 Weeks Regular Aerobic Exercise on Brain-derived Neurotrophic Factor and Inflammatory Factors in Juvenile Obesity and Type 2 Diabetes Mellitus

    OpenAIRE

    Lee, Sung Soo; Yoo, Jae Ho; Kang, Sung; Woo, Jin Hee; Shin, Ki Ok; Kim, Kwi Beak; Cho, Su Youn; Roh, Hee Tae; Kim, Young Il

    2014-01-01

    [Purpose] The purpose of this study was to investigate the effects of 12 weeks regular aerobic exercise on brain-derived neurotrophic factor (BDNF) and inflammatory factors in juvenile obesity and type 2 diabetes mellitus (T2DM). Obesity and T2DM, typically common among adults, have recently become more prevalent in the Korean juvenile population, affecting not only their lipid profiles and oxidant stress levels, but also their BDNF and inflammatory factor levels. [Subjects] This study enroll...

  12. Stromal cell-derived factor-1/CXCR4 signaling modifies the capillary-like organization of human embryonic stem cell-derived endothelium in vitro.

    Science.gov (United States)

    Chen, Tong; Bai, Hao; Shao, Ying; Arzigian, Melanie; Janzen, Viktor; Attar, Eyal; Xie, Yi; Scadden, David T; Wang, Zack Z

    2007-02-01

    The molecular mechanisms that regulate human blood vessel formation during early development are largely unknown. Here we used human ESCs (hESCs) as an in vitro model to explore early human vasculogenesis. We demonstrated that stromal cell-derived factor-1 (SDF-1) and CXCR4 were expressed concurrently with hESC-derived embryonic endothelial differentiation. Human ESC-derived embryonic endothelial cells underwent dose-dependent chemotaxis to SDF-1, which enhanced vascular network formation in Matrigel. Blocking of CXCR4 signaling abolished capillary-like structures induced by SDF-1. Inhibition of the SDF-1/CXCR4 signaling pathway by AMD3100, a CXCR4 antagonist, disrupted the endothelial sprouting outgrowth from human embryoid bodies, suggesting that the SDF-1/CXCR4 axis plays a critical role in regulating initial vessel formation, and may function as a morphogen during human embryonic vascular development.

  13. Derivatives of Dictyostelium differentiation-inducing factors inhibit lysophosphatidic acid–stimulated migration of murine osteosarcoma LM8 cells

    Energy Technology Data Exchange (ETDEWEB)

    Kubohara, Yuzuru, E-mail: ykuboha@juntendo.ac.jp [Department of Molecular and Cellular Biology, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi 371-8512 (Japan); Department of Health Science, Juntendo University Graduate School of Health and Sports Science, Inzai 270-1695 (Japan); Komachi, Mayumi [Department of Molecular and Cellular Biology, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi 371-8512 (Japan); Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Homma, Yoshimi [Department of Biomolecular Science, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295 (Japan); Kikuchi, Haruhisa; Oshima, Yoshiteru [Laboratory of Natural Product Chemistry, Tohoku University Graduate School of Pharmaceutical Sciences, Aoba-yama, Aoba-ku, Sendai 980-8578 (Japan)

    2015-08-07

    Osteosarcoma is a common metastatic bone cancer that predominantly develops in children and adolescents. Metastatic osteosarcoma remains associated with a poor prognosis; therefore, more effective anti-metastatic drugs are needed. Differentiation-inducing factor-1 (DIF-1), −2, and −3 are novel lead anti-tumor agents that were originally isolated from the cellular slime mold Dictyostelium discoideum. Here we investigated the effects of a panel of DIF derivatives on lysophosphatidic acid (LPA)-induced migration of mouse osteosarcoma LM8 cells by using a Boyden chamber assay. Some DIF derivatives such as Br-DIF-1, DIF-3(+2), and Bu-DIF-3 (5–20 μM) dose-dependently suppressed LPA-induced cell migration with associated IC{sub 50} values of 5.5, 4.6, and 4.2 μM, respectively. On the other hand, the IC{sub 50} values of Br-DIF-1, DIF-3(+2), and Bu-DIF-3 versus cell proliferation were 18.5, 7.2, and 2.0 μM, respectively, in LM8 cells, and >20, 14.8, and 4.3 μM, respectively, in mouse 3T3-L1 fibroblasts (non-transformed). Together, our results demonstrate that Br-DIF-1 in particular may be a valuable tool for the analysis of cancer cell migration, and that DIF derivatives such as DIF-3(+2) and Bu-DIF-3 are promising lead anti-tumor agents for the development of therapies that suppress osteosarcoma cell proliferation, migration, and metastasis. - Highlights: • LPA induces cell migration (invasion) in murine osteosarcoma LM8 cells. • DIFs are novel lead anti-tumor agents found in Dictyostelium discoideum. • We examined the effects of DIF derivatives on LPA-induced LM8 cell migration in vitro. • Some of the DIF derivatives inhibited LPA-induced LM8 cell migration.

  14. A thermoreversible polymer mediates controlled release of glial cell line-derived neurotrophic factor to enhance kidney regeneration.

    Science.gov (United States)

    Gheisari, Yousof; Yokoo, Takashi; Matsumoto, Kei; Fukui, Akira; Sugimoto, Naomi; Ohashi, Toya; Kawamura, Tetsuya; Hosoya, Tatsuo; Kobayashi, Eiji

    2010-08-01

    Previously, we reported that human mesenchymal stem cells (hMSCs) that were cultivated in growing embryos differentiated in an appropriate developmental milieu, thereby facilitating the development of a functional renal unit. However, this approach required transfection with an adenovirus that expressed glial cell line-derived neurotrophic factor (GDNF) to enhance the development of hMSC-derived renal tissue, and safety issues restrict the clinical use of such viral vectors. To circumvent this problem, we tested an artificial polymer as a means to diffuse GDNF. This GDNF-polymer, which exists in liquid form at 4 degrees C but becomes a hydrogel upon heating to 37 degrees C, was used as a thermoreversible switch, allowing the injection of hMSCs at low viscosity using a mouth pipette, with subsequent slow diffusion of GDNF as it solidified. The polymer, which was dissolved in a solution of GDNF at 4 degrees C and then maintained at 37 degrees C, acted as a diffuser of GDNF for more than 48 h. LacZ-transfected hMSCs and the GDNF-polymer (at 4 degrees C) were placed in the nephrogenic sites of growing rat embryos that were maintained at 37 degrees C. Forty-eight hours later, the resultant kidney anlagen were dissected out and allowed to continue developing for 6 days in vitro. Whole-organ X-Gal staining and fluorescence activated cell sorter analysis showed that the number of hMSC-derived cells was significantly increased in developed anlagen that have been generated from hMSCs plus GDNF-polymer compared with those from hMSCs plus GDNF-containing medium and was comparable to those from adenovirus-transfected hMSCs. These findings suggest that the GDNF-polymer can be used as a diffuser of GDNF for kidney organogenesis.

  15. TRPC3 regulates release of brain-derived neurotrophic factor from human airway smooth muscle.

    Science.gov (United States)

    Vohra, Pawan K; Thompson, Michael A; Sathish, Venkatachalem; Kiel, Alexander; Jerde, Calvin; Pabelick, Christina M; Singh, Brij B; Prakash, Y S

    2013-12-01

    Exogenous brain-derived neurotrophic factor (BDNF) enhances Ca(2+) signaling and cell proliferation in human airway smooth muscle (ASM), especially with inflammation. Human ASM also expresses BDNF, raising the potential for autocrine/paracrine effects. The mechanisms by which ASM BDNF secretion occurs are not known. Transient receptor potential channels (TRPCs) regulate a variety of intracellular processes including store-operated Ca(2+) entry (SOCE; including in ASM) and secretion of factors such as cytokines. In human ASM, we tested the hypothesis that TRPC3 regulates BDNF secretion. At baseline, intracellular BDNF was present, and BDNF secretion was detectable by enzyme linked immunosorbent assay (ELISA) of cell supernatants or by real-time fluorescence imaging of cells transfected with GFP-BDNF vector. Exposure to the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) (20ng/ml, 48h) or a mixture of allergens (ovalbumin, house dust mite, Alternaria, and Aspergillus extracts) significantly enhanced BDNF secretion and increased TRPC3 expression. TRPC3 knockdown (siRNA or inhibitor Pyr3; 10μM) blunted BDNF secretion, and prevented inflammation effects. Chelation of extracellular Ca(2+) (EGTA; 1mM) or intracellular Ca(2+) (BAPTA; 5μM) significantly reduced secreted BDNF, as did the knockdown of SOCE proteins STIM1 and Orai1 or plasma membrane caveolin-1. Functionally, secreted BDNF had autocrine effects suggested by phosphorylation of high-affinity tropomyosin-related kinase TrkB receptor, prevented by chelating extracellular BDNF with chimeric TrkB-Fc. These data emphasize the role of TRPC3 and Ca(2+) influx in the regulation of BDNF secretion by human ASM and the enhancing effects of inflammation. Given the BDNF effects on Ca(2+) and cell proliferation, BDNF secretion may contribute to altered airway structure and function in diseases such as asthma.

  16. Brain-derived neurotrophic factor signaling is altered in the forebrain of Engrailed-2 knockout mice.

    Science.gov (United States)

    Zunino, G; Messina, A; Sgadò, P; Baj, G; Casarosa, S; Bozzi, Y

    2016-06-02

    Engrailed-2 (En2), a homeodomain transcription factor involved in regionalization and patterning of the midbrain and hindbrain regions has been associated to autism spectrum disorders (ASDs). En2 knockout (En2(-/-)) mice show ASD-like features accompanied by a significant loss of GABAergic subpopulations in the hippocampus and neocortex. Brain-derived neurotrophic factor (BDNF) is a crucial factor for the postnatal development of forebrain GABAergic neurons, and altered GABA signaling has been hypothesized to underlie the symptoms of ASD. Here we sought to determine whether interneuron loss in the En2(-/-) forebrain might be related to altered expression of BDNF and its signaling receptors. We first evaluated the expression of different BDNF mRNA isoforms in the neocortex and hippocampus of wild-type (WT) and En2(-/-) mice. Quantitative RT-PCR showed a marked down-regulation of several splicing variants of BDNF mRNA in the neocortex but not hippocampus of adult En2(-/-) mice, as compared to WT controls. Accordingly, levels of mature BDNF protein were lower in the neocortex but not hippocampus of En2(-/-) mice, as compared to WT. Increased levels of phosphorylated TrkB and decreased levels of p75 receptor were also detected in the neocortex of mutant mice. Accordingly, the expression of low density lipoprotein receptor (LDLR) and RhoA, two genes regulated via p75 was significantly altered in forebrain areas of mutant mice. These data indicate that BDNF signaling alterations might be involved in the anatomical changes observed in the En2(-/-) forebrain and suggest a pathogenic role of altered BDNF signaling in this mouse model of ASD.

  17. Parvalbumin immunoreactivity is enhanced by brain-derived neurotrophic factor in organotypic cultures of rat retina.

    Science.gov (United States)

    Rickman, D W

    1999-11-15

    The rodent retina undergoes considerable postnatal neurogenesis and phenotypic differentiation, and it is likely that diffusible neurotrophic factors contribute to this development and to the subsequent formation of functional retinal circuitry. Accordingly, perturbation of specific neurotrophin ligand-receptor interactions has provided valuable information as to the fundamental processes underlying this development. In the present studies we have built upon our previous observation that suppression of expression of trk(B), the high-affinity receptor for brain-derived neurotrophic factor (BDNF), in the postnatal rat retina results in the alteration of a specific interneuron in the rod pathway-the parvalbumin (PV)-immunoreactive AII amacrine cell. Here, we isolated retinas from newborn rats and maintained them in organotypic culture for up to 14 days (approximating the time of eye opening, in vivo) in the presence of individual neurotrophins [BDNF or nerve growth factor (NGF)]. We then examined histological sections of cultures for PV immunoreactivity. In control cultures, only sparse PV-immunostained cells were observed. In cultures supplemented with NGF, numerous lightly immunostained somata were present in the inner nuclear layer (INL) at the border of the inner plexiform layer (IPL). Many of these cells had rudimentary dendritic arborizations in the IPL. Cultures supplemented with BDNF displayed numerous well-immunostained somata at the INL/IPL border that gave rise to elaborate dendritic arborizations that approximated the morphology of mature AII amacrine cells in vivo. These observations indicate that neurotrophins have specific effects upon the neurochemical and, perhaps, morphological differentiation of an important interneuron in a specific functional retinal circuit.

  18. Osteogenic Differentiation of Adipose-Derived Stem Cells Is Hypoxia-Inducible Factor-1 Independent

    Science.gov (United States)

    Sahai, Suchit; Williams, Amanda; Skiles, Matthew L.

    2013-01-01

    Tissue engineering is a promising approach to repair critical-size defects in bone. Damage to vasculature at the defect site can create a lower O2 environment compared with healthy bone. Local O2 levels influence stem cell behavior, as O2 is not only a nutrient, but also a signaling molecule. The hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates a wide range of O2-related genes and its contribution in bone repair/formation is an important area that can be exploited. In this study, we examined the effect of low O2 environments (1% and 2% O2) on the osteogenic differentiation of adipose-derived stem cells in both two-dimensional (2-D) and three-dimensional (3-D) culture systems. To determine the role of HIF-1 in the differentiation process, an inhibitor was used to block the HIF-1 activity. The samples were examined for osteogenesis markers as measured by quantification of the alkaline phosphatase (ALP) activity, mineral deposition, and expression of osteonectin (ON) and osteopontin (OPN). Results show a downregulation of the osteogenic markers (ALP activity, mineralization, ON, OPN) in both 1% and 2% O2 when compared to 20% O2 in both 2-D and 3-D culture. Vascular endothelial growth factor secretion over 28 days was significantly higher in low O2 environments and HIF-1 inhibition reduced this effect. The inhibition of the HIF-1 activity did not have a significant impact on the expression of the osteogenic markers, suggesting HIF-1-independent inhibition of osteogenic differentiation in hypoxic conditions. PMID:23394201

  19. Platelet-Derived Growth Factor: A Key Factor in the Pathogenesis of Graves' Ophthalmopathy and Potential Target for Treatment

    Science.gov (United States)

    Virakul, Sita; van Steensel, Leendert; Dalm, Virgil A.S.H.; Paridaens, Dion; van Hagen, P. Martin; Dik, Willem A.

    2014-01-01

    Activation of orbital fibroblasts resulting in excessive proliferation, cytokine and hyaluronan production and differentiation into adipocytes, is a main determinant of orbital tissue inflammation and tissue expansion in Graves' ophthalmopathy (GO). During the last years we have shown that the platelet-derived growth factor (PDGF) isoforms PDGF-AA, PDGF-AB and PDGF-BB are increased in orbital tissue from GO patients with active and inactive disease. These PDGF isoforms exhibit the capacity to stimulate proliferation, hyaluronan and cytokine/chemokine production by orbital fibroblasts. Moreover, PDGF-AB and PDGF-BB increase thyroid stimulating hormone receptor (TSHR) expression by orbital fibroblasts, which enhances the orbital fibroblast activating capacity of the THSR stimulatory autoantibodies present in Graves' disease (GD) patients. Of these PDGF isoforms PDGF-BB exhibits the strongest orbital fibroblast activating effects, which is likely related to its ability to bind both the PDGF-receptor (PDGF-R)α and PDGF-Rβ chains. Thus the PDGF-system fulfills important roles in orbital fibroblast activation in both active and inactive GO, which supports a therapeutic rationale for blocking PDGF signaling in GO. Tyrosine kinase inhibitors (TKIs) may be candidates to target PDGF signaling. Of several TKIs tested dasatinib exhibited the highest potency to block PDGF-R signaling in orbital fibroblasts and may represent a promising compound for the treatment of GO as it was effective at low dosage and is associated with less side effects compared to imatinib mesylate and nilotinib. In this review the contribution of PDGF to the pathophysiology of GO as well as therapeutic approaches to target this PDGF-system will be addressed. PMID:25759797

  20. Mechanisms Underlying Enhanced Noradrenaline-Induced Femoral Arterial Contractions of Spontaneously Hypertensive Rats: Involvement of Endothelium-Derived Factors and Cyclooxygenase-Derived Prostanoids.

    Science.gov (United States)

    Matsumoto, Takayuki; Watanabe, Shun; Iguchi, Maika; Ando, Makoto; Oda, Mirai; Nagata, Mako; Yamada, Kosuke; Taguchi, Kumiko; Kobayashi, Tsuneo

    2016-01-01

    We investigated the relationship between noradrenaline (NAd)-induced contractions, endothelial function, and hypertension in femoral arteries isolated from spontaneously hypertensive rats (SHR). In the femoral arteries of SHR, vs. age-matched control Wistar Kyoto (WKY) rats, contractions induced by NAd were increased. These effects were enhanced by endothelial denudation, which abolished the differences between the two groups. NAd-induced contractions were enhanced by nitric oxide (NO) synthase inhibition, and further increased by the blockade of endothelium-derived hyperpolarizing factor (EDHF). Conversely, NAd-induced contractions were inhibited by cyclooxygenase (COX) inhibition. In addition, in SHR arteries, acetylcholine-induced relaxation was reduced, and components of endothelium-derived factors were altered, such as increased COX-derived vasoconstrictor prostanoids, reduced EDHF, and preserved NO-mediated relaxation. In the femoral arteries of SHR, the production of prostanoids [6-keto prostaglandin (PG)F1α (a metabolite of prostacyclin (PGI2), PGE2, and PGF2α] and COX-2 protein were increased compared with that in WKY rats. By contrast, contractions induced by beraprost (a stable PGI2 analogue), PGE2, and U46619 (thromboxane/prostanoid receptor agonist) were similar between the SHR and WKY groups. Thus, NAd-induced femoral arterial contractions are augmented in SHR resulting from endothelial dysfunction and increased COX-derived vasoconstrictor prostanoid levels.

  1. A Hierarchical Linear Model with Factor Analysis Structure at Level 2

    Science.gov (United States)

    Miyazaki, Yasuo; Frank, Kenneth A.

    2006-01-01

    In this article the authors develop a model that employs a factor analysis structure at Level 2 of a two-level hierarchical linear model (HLM). The model (HLM2F) imposes a structure on a deficient rank Level 2 covariance matrix [tau], and facilitates estimation of a relatively large [tau] matrix. Maximum likelihood estimators are derived via the…

  2. Perturbation analysis for best approximation and the polar factor by subunitary matrices

    Institute of Scientific and Technical Information of China (English)

    Xinguo LIU; Weiguo WANG; Yimin WEI

    2008-01-01

    This paper is a continuation and improvement over the results of Laszkiewicz and Zietak [BIT, 2006, 46: 345-366], studying perturbation analysis for polar decomposition. Some basic properties of best approximation subunitary matrices are investigated in detail. The perturbation bounds of the polar factor are also derived.

  3. The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects memory performance in older adults

    OpenAIRE

    Azeredo,Lucas A.; Tatiana De Nardi; Levandowski, Mateus L.; Tractenberg,Saulo G.; Julia Kommers-Molina; Andrea Wieck; Tatiana Q. Irigaray; Irênio G. da Silva Filho; Rodrigo Grassi-Oliveira

    2017-01-01

    Objective: Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF) is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cogni...

  4. Structural analysis of fungus-derived FAD glucose dehydrogenase.

    Science.gov (United States)

    Yoshida, Hiromi; Sakai, Genki; Mori, Kazushige; Kojima, Katsuhiro; Kamitori, Shigehiro; Sode, Koji

    2015-08-27

    We report the first three-dimensional structure of fungus-derived glucose dehydrogenase using flavin adenine dinucleotide (FAD) as the cofactor. This is currently the most advanced and popular enzyme used in glucose sensor strips manufactured for glycemic control by diabetic patients. We prepared recombinant nonglycosylated FAD-dependent glucose dehydrogenase (FADGDH) derived from Aspergillus flavus (AfGDH) and obtained the X-ray structures of the binary complex of enzyme and reduced FAD at a resolution of 1.78 Å and the ternary complex with reduced FAD and D-glucono-1,5-lactone (LGC) at a resolution of 1.57 Å. The overall structure is similar to that of fungal glucose oxidases (GOxs) reported till date. The ternary complex with reduced FAD and LGC revealed the residues recognizing the substrate. His505 and His548 were subjected for site-directed mutagenesis studies, and these two residues were revealed to form the catalytic pair, as those conserved in GOxs. The absence of residues that recognize the sixth hydroxyl group of the glucose of AfGDH, and the presence of significant cavity around the active site may account for this enzyme activity toward xylose. The structural information will contribute to the further engineering of FADGDH for use in more reliable and economical biosensing technology for diabetes management.

  5. Housing price forecastability: A factor analysis

    DEFF Research Database (Denmark)

    Bork, Lasse; Møller, Stig Vinther

    of the model stays high at longer horizons. The estimated factors are strongly statistically signi…cant according to a bootstrap resampling method which takes into account that the factors are estimated regressors. The simple three-factor model also contains substantial out-of-sample predictive power...

  6. A Second Generation Nonlinear Factor Analysis.

    Science.gov (United States)

    Etezadi-Amoli, Jamshid; McDonald, Roderick P.

    1983-01-01

    Nonlinear common factor models with polynomial regression functions, including interaction terms, are fitted by simultaneously estimating the factor loadings and common factor scores, using maximum likelihood and least squares methods. A Monte Carlo study gives support to a conjecture about the form of the distribution of the likelihood ratio…

  7. Cholinergic neurons regulate secretion of glial cell line-derived neurotrophic factor by skeletal muscle cells in culture.

    Science.gov (United States)

    Vianney, John-Mary; Spitsbergen, John M

    2011-05-16

    Glial cell line-derived neurotrophic factor (GDNF) has been identified as a potent survival factor for both central and peripheral neurons. GDNF has been shown to be a potent survival factor for motor neurons during programmed cell death and continuous treatment with GDNF maintains hyperinnervation of skeletal muscle in adulthood. However, little is known about factors regulating normal production of endogenous GDNF in skeletal muscle. This study aimed to examine the role that motor neurons play in regulating GDNF secretion by skeletal muscle. A co-culture of skeletal muscle cells (C2C12) and cholinergic neurons, glioma×neuroblastoma hybrid cells (NG108-15) were used to create nerve-muscle interactions in vitro. Acetylcholine receptors (AChRs) on nerve-myotube co-cultures were blocked with alpha-bungarotoxin (α-BTX). GDNF protein content in cells and in culture medium was analyzed by enzyme-linked immunosorbant assay (ELISA) and western blotting. GDNF localization was examined by immunocytochemistry. The nerve-muscle co-culture study indicated that the addition of motor neurons to skeletal muscle cells reduced the secretion of GDNF by skeletal muscle. The results also showed that blocking AChRs with α-BTX reversed the action of neural cells on GDNF secretion by skeletal muscle. Although ELISA results showed no GDNF in differentiated NG108-15 cells grown alone, immunocytochemical analysis showed that GDNF was localized in NG108-15 cells co-cultured with C2C12 myotubes. These results suggest that motor neurons may be regulating their own supply of GDNF secreted by skeletal muscle and that activation of AChRs may be involved in this process. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Theobromine up-regulates cerebral brain-derived neurotrophic factor and facilitates motor learning in mice.

    Science.gov (United States)

    Yoneda, Mitsugu; Sugimoto, Naotoshi; Katakura, Masanori; Matsuzaki, Kentaro; Tanigami, Hayate; Yachie, Akihiro; Ohno-Shosaku, Takako; Shido, Osamu

    2017-01-01

    Theobromine, which is a caffeine derivative, is the primary methylxanthine produced by Theobroma cacao. Theobromine works as a phosphodiesterase (PDE) inhibitor to increase intracellular cyclic adenosine monophosphate (cAMP). cAMP activates the cAMP-response element-binding protein (CREB), which is involved in a large variety of brain processes, including the induction of the brain-derived neurotrophic factor (BDNF). BDNF supports cell survival and neuronal functions, including learning and memory. Thus, cAMP/CREB/BDNF pathways play an important role in learning and memory. Here, we investigated whether orally administered theobromine could act as a PDE inhibitor centrally and affect cAMP/CREB/BDNF pathways and learning behavior in mice. The mice were divided into two groups. The control group (CN) was fed a normal diet, whereas the theobromine group (TB) was fed a diet supplemented with 0.05% theobromine for 30 days. We measured the levels of theobromine, phosphorylated vasodilator-stimulated phosphoprotein (p-VASP), phosphorylated CREB (p-CREB), and BDNF in the brain. p-VASP was used as an index of cAMP increases. Moreover, we analyzed the performance of the mice on a three-lever motor learning task. Theobromine was detectable in the brains of TB mice. The brain levels of p-VASP, p-CREB, and BDNF were higher in the TB mice compared with those in the CN mice. In addition, the TB mice performed better on the three-lever task than the CN mice did. These results strongly suggested that orally administered theobromine acted as a PDE inhibitor in the brain, and it augmented the cAMP/CREB/BDNF pathways and motor learning in mice.

  9. Placental and cord blood brain derived neurotrophic factor levels are decreased in nondiabetic macrosomia.

    Science.gov (United States)

    Cai, Qian-Ying; Zhang, Heng-Xin; Wang, Chen-Chen; Sun, Hao; Sun, Shu-Qiang; Wang, Yu-Huan; Yan, Hong-Tao; Yang, Xin-Jun

    2017-08-01

    To measure levels of placental brain derived neurotrophic factor (BDNF) gene expression and umbilical cord blood BDNF in neonates with nondiabetic macrosomia and determine associations between these levels and macrosomia. This case-control study included 58 nondiabetic macrosomic and 59 normal birth weight mother-infant pairs. Data were collected from interviews and our hospital's database. BDNF gene expression was quantified in placental tissues using quantitative real-time polymerase chain reaction (n = 117). Umbilical cord blood BDNF levels were measured by enzyme-linked immunosorbent assay (n = 90). Multivariate logistic regression models were used to evaluate associations between BDNF levels and macrosomia. Placental BDNF gene expression (P = 0.026) and cord blood BDNF (P = 0.008) were lower in neonates with nondiabetic macrosomia than in normal birth weight controls. Cord blood BDNF was significantly lower in vaginally delivered macrosomic neonates than vaginally delivered controls (P = 0.014), but cord BDNF did not differ between vaginal and cesarean section delivery modes in macrosomic neonates. Cord blood BDNF was positively associated with gestational age in control neonates (r = 0.496, P macrosomia (adjusted odds ratio 0.992; 95% confidence interval 0.986-0.998). Both placental BDNF gene expression and cord blood BDNF were downregulated in neonates with nondiabetic macrosomia compared with normal birth weight neonates. Cord BDNF may partly derive from BDNF secreted by the placenta. Higher cord plasma BDNF levels protected against nondiabetic macrosomia.

  10. Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier.

    Science.gov (United States)

    Peng, Yu-Shiang; Lai, Po-Liang; Peng, Sydney; Wu, His-Chin; Yu, Siang; Tseng, Tsan-Yun; Wang, Li-Fang; Chu, I-Ming

    2014-01-01

    Parkinson's disease is known to result from the loss of dopaminergic neurons. Direct intracerebral injections of high doses of recombinant glial cell line-derived neurotrophic factor (GDNF) have been shown to protect adult nigral dopaminergic neurons. Because GDNF does not cross the blood-brain barrier, intracerebral gene transfer is an ideal option. Chitosan (CHI) is a naturally derived material that has been used for gene transfer. However, the low water solubility often leads to decreased transfection efficiency. Grafting of highly water-soluble polyethylene imines (PEI) and polyethylene glycol onto polymers can increase their solubility. The purpose of this study was to design a non-viral gene carrier with improved water solubility as well as enhanced transfection efficiency for treating Parkinsonism. Two molecular weights (Mw =600 and 1,800 g/mol) of PEI were grafted onto CHI (PEI600-g-CHI and PEI1800-g-CHI, respectively) by opening the epoxide ring of ethylene glycol diglycidyl ether (EX-810). This modification resulted in a non-viral gene carrier with less cytotoxicity. The transfection efficiency of PEI600-g-CHI/deoxyribonucleic acid (DNA) polyplexes was significantly higher than either PEI1800-g-CHI/DNA or CHI/DNA polyplexes. The maximal GDNF expression of PEI600-g-CHI/DNA was at the polymer:DNA weight ratio of 10:1, which was 1.7-fold higher than the maximal GDNF expression of PEI1800-g-CHI/DNA. The low toxicity and high transfection efficiency of PEI600-g-CHI make it ideal for application to GDNF gene therapy, which has potential for the treatment of Parkinson's disease.

  11. Role of pigment epithelium-derived factor in the involution of hemangioma: Autocrine growth inhibition of hemangioma-derived endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung-Jin [Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Department of Biomedical Science, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Yun, Jang-Hyuk; Heo, Jong-Ik [Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Lee, Eun Hui [Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Min, Hye Sook [Department of Pathology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of); Choi, Tae Hyun, E-mail: psthchoi@snu.ac.kr [Department of Plastic and Reconstructive Surgery, Seoul National University Children’s Hospital, Seoul 110-744 (Korea, Republic of); Department of Pediatric Plastic and Reconstructive Surgery, Seoul National University Children’s Hospital, Seoul 110-744 (Korea, Republic of); Cho, Chung-Hyun, E-mail: iamhyun@snu.ac.kr [Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Department of Biomedical Science, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Ischemic/Hypoxic Disease Institute, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Cancer Research Institute, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of)

    2014-11-14

    Highlights: • PEDF was expressed and induced during the involuting phase of IH. • PEDF inhibited the cell growth of the involuting HemECs in an autocrine manner. • PEDF suppression restored the impaired cell growth of the involuting HemECs. - Abstract: Hemangioma is a benign tumor derived from abnormal blood vessel growth. Unlike other vascular tumor counterparts, a hemangioma is known to proliferate during its early stage but it is followed by a stage of involution where regression of the tumor occurs. The critical onset leading to the involution of hemangioma is currently not well understood. This study focused on the molecular identities of the involution of hemangioma. We demonstrated that a soluble factor released from the involuting phase of hemangioma-derived endothelial cells (HemECs) and identified pigment epithelium-derived factor (PEDF) as an anti-angiogenic factor that was associated with the growth inhibition of the involuting HemECs. The growth inhibition of the involuting HemECs was reversed by suppression of PEDF in the involuting HemECs. Furthermore, we found that PEDF was more up-regulated in the involuting phase of hemangioma tissues than in the proliferating or the involuted. Taken together, we propose that PEDF accelerates the involution of hemangioma by growth inhibition of HemECs in an autocrine manner. The regulatory mechanism of PEDF expression could be a potential therapeutic target to treat hemangiomas.

  12. The niche-derived glial cell line-derived neurotrophic factor (GDNF induces migration of mouse spermatogonial stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Lisa Dovere

    Full Text Available In mammals, the biological activity of the stem/progenitor compartment sustains production of mature gametes through spermatogenesis. Spermatogonial stem cells and their progeny belong to the class of undifferentiated spermatogonia, a germ cell population found on the basal membrane of the seminiferous tubules. A large body of evidence has demonstrated that glial cell line-derived neurotrophic factor (GDNF, a Sertoli-derived factor, is essential for in vivo and in vitro stem cell self-renewal. However, the mechanisms underlying this activity are not completely understood. In this study, we show that GDNF induces dose-dependent directional migration of freshly selected undifferentiated spermatogonia, as well as germline stem cells in culture, using a Boyden chamber assay. GDNF-induced migration is dependent on the expression of the GDNF co-receptor GFRA1, as shown by migration assays performed on parental and GFRA1-transduced GC-1 spermatogonial cell lines. We found that the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP is specifically expressed in undifferentiated spermatogonia. VASP belongs to the ENA/VASP family of proteins implicated in actin-dependent processes, such as fibroblast migration, axon guidance, and cell adhesion. In intact seminiferous tubules and germline stem cell cultures, GDNF treatment up-regulates VASP in a dose-dependent fashion. These data identify a novel role for the niche-derived factor GDNF, and they suggest that GDNF may impinge on the stem/progenitor compartment, affecting the actin cytoskeleton and cell migration.

  13. The niche-derived glial cell line-derived neurotrophic factor (GDNF) induces migration of mouse spermatogonial stem/progenitor cells.

    Science.gov (United States)

    Dovere, Lisa; Fera, Stefania; Grasso, Margherita; Lamberti, Dante; Gargioli, Cesare; Muciaccia, Barbara; Lustri, Anna Maria; Stefanini, Mario; Vicini, Elena

    2013-01-01

    In mammals, the biological activity of the stem/progenitor compartment sustains production of mature gametes through spermatogenesis. Spermatogonial stem cells and their progeny belong to the class of undifferentiated spermatogonia, a germ cell population found on the basal membrane of the seminiferous tubules. A large body of evidence has demonstrated that glial cell line-derived neurotrophic factor (GDNF), a Sertoli-derived factor, is essential for in vivo and in vitro stem cell self-renewal. However, the mechanisms underlying this activity are not completely understood. In this study, we show that GDNF induces dose-dependent directional migration of freshly selected undifferentiated spermatogonia, as well as germline stem cells in culture, using a Boyden chamber assay. GDNF-induced migration is dependent on the expression of the GDNF co-receptor GFRA1, as shown by migration assays performed on parental and GFRA1-transduced GC-1 spermatogonial cell lines. We found that the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP) is specifically expressed in undifferentiated spermatogonia. VASP belongs to the ENA/VASP family of proteins implicated in actin-dependent processes, such as fibroblast migration, axon guidance, and cell adhesion. In intact seminiferous tubules and germline stem cell cultures, GDNF treatment up-regulates VASP in a dose-dependent fashion. These data identify a novel role for the niche-derived factor GDNF, and they suggest that GDNF may impinge on the stem/progenitor compartment, affecting the actin cytoskeleton and cell migration.

  14. Increased stromal-cell-derived factor 1 enhances the homing of bone marrow derived mesenchymal stem cells in dilated cardiomyopathy in rats

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yan-li; Michael Fu; ZHANG Hai-feng; LI Xin-li; DI Ruo-min; YAO Wen-ming; LI Dian-fu; FENG Jian-lin; HUANG Jun; CAO Ke-jiang

    2010-01-01

    Background Stem cell transplantation has been shown to have beneficial effects on dilated cardiomyopathy. However,mechanism for stem cell homing to cardiac tissue in dilated cardiomyopathy has not yet been elucidated.Methods Mesenchymal stem cells were obtained from rat bone marrow, expanded in vitro, and labeled with 99mTc.Cardiomyopathy model was induced by doxorubicin in rats. 99mTc labeled cells were infused into the left ventricles in cardiomyopathy and control rats. Sixteen hours after injection, animals were sacrificed and different tissues were harvested to measure specific radioactivity. By use of real-time polymerase chain reaction and immunohistochemistry,Mrna and protein expressions for stromal-cell-derived factor 1 in cardiac tissue were measured.Results Labeling efficiency of mesenchymal stem cells was (70.0±11.2)%. Sixteen hours after mesenchymal stem cell transplantation, the heart-to-muscle radioactivity ratio was increased significantly in cardiomyopathy hearts as compared to control hearts. Both Mrna and rotein expressions of stromal-cell-derived factor 1 were up-regulated in cardiomyopathy hearts as compared with control hearts.Conclusion In dilated cardiomyopathy induced by doxorubicin up-regulated expression of stromal-cell-derived factor 1in heart may induce mesenchymal stem cells home to the heart.

  15. The radiation Q factors obtained from the partial derivatives of the phase of the reflection coefficient of an elastic plate.

    Science.gov (United States)

    Lenoir, O; Conoir, J M; Izbicki, J L

    2003-08-01

    The phase gradient method is applied to study the partial derivatives of the phase of the reflection coefficient of a fluid-loaded elastic plate. We consider the derivatives with respect to the frequency f, the incidence angle theta, the phase velocities of the longitudinal and transverse waves propagating in the plate, cL and cT, respectively, and the phase velocity in the fluid cF. The partial derivatives with respect to f, cL, cT, cF are linked by a relation involving products of one of these variables with the corresponding partial derivative. At a resonance frequency, the product of frequency with the frequency phase derivative can be identified as a radiation quality factor. By analogy, the other products correspond to quality factors. It can be shown that the product assigned to the fluid phase velocity corresponds to an angular radiation quality factor. The products assigned to the longitudinal and transverse phase velocities are identified as longitudinal and transverse radiation quality factors. These quality factors are shown to be related to stored energies associated with either standing waves across the plate, guided waves, longitudinal waves or transverse waves. A reactive power balance between the plate and the fluid is also established.

  16. NOAA/NESDIS Satellite Derived Surface Oil Analysis Products

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NESDIS Experimental Marine Pollution Surveillance Report (EMPSR) and the Daily Composite product are new products of the NOAA Satellite Analysis Branch and...

  17. Prostate-Derived Ets Transcription Factor Overexpression is Associated with Nodal Metastasis, Hormone Receptor Positivity in Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Simon Turcotte

    2007-10-01

    Full Text Available Prostate-derived Ets transcription factor (PDEF has recently been associated with invasive breast cancer, but no expression profile has been defined in clinical specimens. We undertook a comprehensive PDEF transcriptional expression study of 86 breast cancer clinical specimens, several cell lines, normal tissues. PDEF expression profile was analyzed according to standard clinicopathologic parameters, compared with hormonal receptor, HER-2/neu status, to the expression of the new tumor biomarker Dikkopf-1 (DKK1. Wide ranging PDEF overexpression was observed in 74% of tested tumors, at higher levels than the average expression found in normal breasts. High PDEF expression was associated with hormone receptor positivity (P < .001, moderate to good differentiation (less than grade III, P = .01, dissemination to axillary lymph nodes (P = .002. PDEF was an independent risk factor for nodal involvement (multivariate analysis, odds ratio 1.250, P = .002. It was expressed in a different subgroup compared to DKK1-expressing tumors (P < .001. Our data imply that PDEF mRNA expression could be useful in breast cancer molecular staging. Further insights into PDEF functions at the protein level, possible links with hormone receptors biology, bear great potential for new therapeutic avenues.

  18. [Effects of PRF and released three growth factors on migration of rat adipose tissue-derived stem cells].

    Science.gov (United States)

    Gao, Jie; Wang, Ming-guo; Yang, Shuai; Li, Xiu-mei; Yang, Shi-mao; Li, Xue

    2015-12-01

    To analyze the effects of PRF and released three growth factors on migration of rat adipose tissue-derived stem cells and to investigate the mechanism of migration. The inguinal adipose tissue of rat was excised at aseptic condition to obtain primary ADSCs by enzyme digestion. Multi-directional differentiation was used to identify the ADSCs. PRF membrane was acquired through one time centrifuge. The cell migration was examined by Transwell assay and wound healing assay. The mRNA expression of MMP2 and MT1-MMP was tested by real-time PCR. Statistical analysis was performed using SPSS 13.0 software package. Cell migration test showed that the migration of rat ADSCs in PRF group were significantly higher than those in the negative group(PPRF group than control group (PPRF and three growth factors consistently enhanced the migration of rat ADSCs in a dose-response manner. The migration increase of rat ADSCs may be associated with the up-regulation of MMP2 and MT1-MMP gene expression.

  19. Estradiol increases expression of the brain-derived neurotrophic factor after acute administration of ethanol in the neonatal rat cerebellum.

    Science.gov (United States)

    Firozan, Bita; Goudarzi, Iran; Elahdadi Salmani, Mahmoud; Lashkarbolouki, Taghi; Rezaei, Arezou; Abrari, Kataneh

    2014-06-05

    Recently it has been shown that estradiol prevents the toxicity of ethanol in developing cerebellum. The neuroprotective effect of estradiol is not due to a single phenomenon but rather encompasses a spectrum of independent proccesses. According to the specific timing of Purkinje cell vulnerability to ethanol and several protective mechanisms of estradiol, we considered the neurotrophin system, as a regulator of differentiation, maturation and survival of neurons during CNS development. Interactions between estrogen and Brain derived neurotrophic factor (BDNF, an essential factor in neuronal survival) lead us to investigate involvement of BDNF pathway in neuroprotective effects of estrogen against ethanol toxicity. In this study, 17β-estradiol (300-900μg/kg) was injected subcutaneously in postnatal day (PD) 4, 30min prior to intraperitoneal injection of ethanol (6g/kg) in rat pups. Eight hours after injection of ethanol, BDNF mRNA and protein levels were assayed. Behavioral studies, including rotarod and locomotor activity tests were performed in PD 21-23 and histological study was performed after completion of behavioral tests in PD 23. Our results indicated that estradiol increased BDNF mRNA and protein levels in the presence of ethanol. We also observed that pretreatment with estradiol significantly attenuated ethanol-induced motoric impairment. Histological analysis also demonstrated that estradiol prevented Purkinje cell loss following ethanol treatment. These results provide evidence on the possible mechanisms of estradiol neuroprotection against ethanol toxicity.

  20. An analysis of reverberation fluctuation by mean square derivation

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A method for evaluating the fluctuation of the reverberation envelope is proposed and examined through simulation and real data in this paper.This method is different from the coefficient of variation which is only a function of the first and second order moment of the reverberation statistical model.By using the standard variance of the mean square derivate(MSD) of the reverberation envelope,the paper shows that the reverberation fluctuation is a function of the bandwidth of the emitted signal,and that a large value of the square variance means little fluctuation of the reverberation envelope.Theoretical studies show that the standard variance is proportional to the bandwidth of the emitted signal,so we conclude that less time width or larger bandwidth of the transmitted signal produces less fluctuation.Simulation and real active sonar data processing are used to verify this conclusion.

  1. The composition analysis of coal-derived light oil

    Institute of Scientific and Technical Information of China (English)

    GAO Zhen-nan; LIU Li-lin; ZHU Xiao-man; LI Wen-bo

    2008-01-01

    The composition of coal-derived light oil (IBP-220 ℃) was separated into 5 fractions by atmospheric distillation and analyzed by gas chromatography/mass spec-trometry (GC/MS). The light oil was made at 0.1 t/d coal direct liquefaction bench scale unit (BSU) at China Coal Research Institute (CCRI). Six groups of organics, including acyclic hydrocarbon, alicyclic hydrocarbon, aromatics, phenols, polynuclear aromatics and heterocyclics, were found and 80 compounds were tentatively identified in total. Alicyclic hydrocarbon is the main component of the light oil compared to other groups whether in relative mass percentage or the number of compounds in group. The predominant oxy-gen-contained compound is phenols, and the nitrogen-containing compound is pyridine.No sulfur-containing compound is detected.

  2. Disruptive Event Biosphere Doser Conversion Factor Analysis

    Energy Technology Data Exchange (ETDEWEB)

    M. Wasiolek

    2000-12-28

    The purpose of this report was to document the process leading to, and the results of, development of radionuclide-, exposure scenario-, and ash thickness-specific Biosphere Dose Conversion Factors (BDCFs) for the postulated postclosure extrusive igneous event (volcanic eruption) at Yucca Mountain. BDCF calculations were done for seventeen radionuclides. The selection of radionuclides included those that may be significant dose contributors during the compliance period of up to 10,000 years, as well as radionuclides of importance for up to 1 million years postclosure. The approach documented in this report takes into account human exposure during three different phases at the time of, and after, volcanic eruption. Calculations of disruptive event BDCFs used the GENII-S computer code in a series of probabilistic realizations to propagate the uncertainties of input parameters into the output. The pathway analysis included consideration of different exposure pathway's contribution to the BDCFs. BDCFs for volcanic eruption, when combined with the concentration of radioactivity deposited by eruption on the soil surface, allow calculation of potential radiation doses to the receptor of interest. Calculation of radioactivity deposition is outside the scope of this report and so is the transport of contaminated ash from the volcano to the location of the receptor. The integration of the biosphere modeling results (BDCFs) with the outcomes of the other component models is accomplished in the Total System Performance Assessment (TSPA), in which doses are calculated to the receptor of interest from radionuclides postulated to be released to the environment from the potential repository at Yucca Mountain.

  3. Nominal Performance Biosphere Dose Conversion Factor Analysis

    Energy Technology Data Exchange (ETDEWEB)

    M. Wasiolek

    2000-12-21

    The purpose of this report was to document the process leading to development of the Biosphere Dose Conversion Factors (BDCFs) for the postclosure nominal performance of the potential repository at Yucca Mountain. BDCF calculations concerned twenty-four radionuclides. This selection included sixteen radionuclides that may be significant nominal performance dose contributors during the compliance period of up to 10,000 years, five additional radionuclides of importance for up to 1 million years postclosure, and three relatively short-lived radionuclides important for the human intrusion scenario. Consideration of radionuclide buildup in soil caused by previous irrigation with contaminated groundwater was taken into account in the BDCF development. The effect of climate evolution, from the current arid conditions to a wetter and cooler climate, on the BDCF values was evaluated. The analysis included consideration of different exposure pathway's contribution to the BDCFs. Calculations of nominal performance BDCFs used the GENII-S computer code in a series of probabilistic realizations to propagate the uncertainties of input parameters into the output. BDCFs for the nominal performance, when combined with the concentrations of radionuclides in groundwater allow calculation of potential radiation doses to the receptor of interest. Calculated estimates of radionuclide concentration in groundwater result from the saturated zone modeling. The integration of the biosphere modeling results (BDCFs) with the outcomes of the other component models is accomplished in the Total System Performance Assessment (TSPA) to calculate doses to the receptor of interest from radionuclides postulated to be released to the environment from the potential repository at Yucca Mountain.

  4. LXY6090 – a novel manassantin A derivative – limits breast cancer growth through hypoxia-inducible factor-1 inhibition

    OpenAIRE

    Lai, Fangfang; Liu, Qian; LIU, Xiaoyu; Ji, Ming; Xie, Ping; Chen, Xiaoguang

    2016-01-01

    Hypoxia-inducible factor-1 (HIF-1) represents a novel antitumor target owing to its involvement in vital processes considered hallmarks of cancer phenotypes. Manassantin A (MA) derived from Saururus cernuus has been reported as a selective HIF-1 inhibitor. Herein, the structure of MA was optimized to achieve new derivatives with simple chemical properties while retaining its activity. LXY6090 was designed to replace the central tetrahydrofuran moiety of MA with a cyclopentane ring and was ide...

  5. A discrete-time two-factor model for pricing bonds and interest rate derivatives under random volatility

    OpenAIRE

    Heston, Steven L.; Nandi, Saikat

    1999-01-01

    This paper develops a discrete-time two-factor model of interest rates with analytical solutions for bonds and many interest rate derivatives when the volatility of the short rate follows a GARCH process that can be correlated with the level of the short rate itself. Besides bond and bond futures, the model yields analytical solutions for prices of European options on discount bonds (and futures) as well as other interest rate derivatives such as caps, floors, average rate options, yield curv...

  6. Influence of pigment epithelium-derived factor on outcome after striatal cerebral ischemia in the mouse.

    Directory of Open Access Journals (Sweden)

    Marietta Zille

    Full Text Available We here suggest that pigment epithelium-derived factor (PEDF does not have an effect on lesion size, behavioral outcome, cell proliferation, or cell death after striatal ischemia in the mouse. PEDF is a neurotrophic factor with neuroprotective, antiangiogenic, and antipermeability effects. It influences self-renewal of neural stem cells and proliferation of microglia. We investigated whether intraventricular infusion of PEDF reduces infarct size and cell death, ameliorates behavioral outcome, and influences cell proliferation in the one-hour middle cerebral artery occlusion (MCAO mouse model of focal cerebral ischemia. C57Bl6/N mice were implanted with PEDF or artificial cerebrospinal fluid (control osmotic pumps and subjected to 60-minute MCAO 48 hours after pump implantation. They received daily BrdU injections for 7 days after MCAO in order to investigate cell proliferation. Infarct volumes were determined 24 hours after reperfusion using magnetic resonance imaging. We removed the pumps on day 5 and performed behavioral testing between day 7 and 21. Immunohistochemical staining was performed to determine the effect of PEDF on cell proliferation and cell death. Our model produced an ischemic injury confined solely to striatal damage. We detected no reduction in infarct sizes and cell death in PEDF- vs. CSF-infused MCAO mice. Behavioral outcome and cell proliferation did not differ between the groups. However, we cannot exclude that PEDF might work under different conditions in stroke. Further studies will elucidate the effect of PEDF treatment on cell proliferation and behavioral outcome in moderate to severe ischemic injury in the brain.

  7. Pigment Epithelium Derived Factor Peptide Protects Murine Hepatocytes from Carbon Tetrachloride-Induced Injury.

    Directory of Open Access Journals (Sweden)

    Shou-Chuan Shih

    Full Text Available Fibrogenesis is induced by repeated injury to the liver and reactive regeneration and leads eventually to liver cirrhosis. Pigment epithelium derived factor (PEDF has been shown to prevent liver fibrosis induced by carbon tetrachloride (CCl4. A 44 amino acid domain of PEDF (44-mer was found to have a protective effect against various insults to several cell types. In this study, we investigated the capability of synthetic 44-mer to protect against liver injury in mice and in primary cultured hepatocytes. Acute liver injury, induced by CCl4, was evident from histological changes, such as cell necrosis, inflammation and apoptosis, and a concomitant reduction of glutathione (GSH and GSH redox enzyme activities in the liver. Intraperitoneal injection of the 44-mer into CCl4-treated mice abolished the induction of AST and ALT and markedly reduced histological signs of liver injury. The 44-mer treatment can reduce hepatic oxidative stress as evident from lower levels of lipid hydroperoxide, and higher levels of GSH. CCl4 caused a reduction of Bcl-xL, PEDF and PPARγ, which was markedly restored by the 44-mer treatment. Consequently, the 44-mer suppressed liver fibrosis induced by repeated CCl4 injury. Furthermore, our observations in primary culture of rat hepatocytes showed that PEDF and the 44-mer protected primary rat hepatocytes against apoptosis induced by serum deprivation and TGF-β1. PEDF/44-mer induced cell protective STAT3 phosphorylation. Pharmacological STAT3 inhibition prevented the antiapoptotic action of PEDF/44-mer. Among several PEDF receptor candidates that may be responsible for hepatocyte protection, we demonstrated that PNPLA2 was essential for PEDF/44-mer-mediated STAT3 phosphorylation and antiapoptotic activity by using siRNA to selectively knockdown PNPLA2. In conclusion, the PEDF 44-mer protects hepatocytes from single and repeated CCl4 injury. This protective effect may stem from strengthening the counter oxidative stress

  8. cAMP-mediated secretion of brain-derived neurotrophic factor in developing airway smooth muscle.

    Science.gov (United States)

    Thompson, Michael A; Britt, Rodney D; Kuipers, Ine; Stewart, Alecia; Thu, James; Pandya, Hitesh C; MacFarlane, Peter; Pabelick, Christina M; Martin, Richard J; Prakash, Y S

    2015-10-01

    Moderate hyperoxic exposure in preterm infants contributes to subsequent airway dysfunction and to risk of developing recurrent wheeze and asthma. The regulatory mechanisms that can contribute to hyperoxia-induced airway dysfunction are still under investigation. Recent studies in mice show that hyperoxia increases brain-derived neurotrophic factor (BDNF), a growth factor that increases airway smooth muscle (ASM) proliferation and contractility. We assessed the mechanisms underlying effects of moderate hyperoxia (50% O2) on BDNF expression and secretion in developing human ASM. Hyperoxia increased BDNF secretion, but did not alter endogenous BDNF mRNA or intracellular protein levels. Exposure to hyperoxia significantly increased [Ca2+]i responses to histamine, an effect blunted by the BDNF chelator TrkB-Fc. Hyperoxia also increased ASM cAMP levels, associated with reduced PDE4 activity, but did not alter protein kinase A (PKA) activity or adenylyl cyclase mRNA levels. However, 50% O2 increased expression of Epac2, which is activated by cAMP and can regulate protein secretion. Silencing RNA studies indicated that Epac2, but not Epac1, is important for hyperoxia-induced BDNF secretion, while PKA inhibition did not influence BDNF secretion. In turn, BDNF had autocrine effects of enhancing ASM cAMP levels, an effect inhibited by TrkB and BDNF siRNAs. Together, these novel studies suggest that hyperoxia can modulate BDNF secretion, via cAMP-mediated Epac2 activation in ASM, resulting in a positive feedback effect of BDNF-mediated elevation in cAMP levels. The potential functional role of this pathway is to sustain BDNF secretion following hyperoxic stimulus, leading to enhanced ASM contractility and proliferation.

  9. Developmental traumatic brain injury decreased brain derived neurotrophic factor expression late after injury.

    Science.gov (United States)

    Schober, Michelle Elena; Block, Benjamin; Requena, Daniela F; Hale, Merica A; Lane, Robert H

    2012-06-01

    Pediatric traumatic brain injury (TBI) is a major cause of acquired cognitive dysfunction in children. Hippocampal Brain Derived Neurotrophic Factor (BDNF) is important for normal cognition. Little is known about the effects of TBI on BDNF levels in the developing hippocampus. We used controlled cortical impact (CCI) in the 17 day old rat pup to test the hypothesis that CCI would first increase rat hippocampal BDNF mRNA/protein levels relative to SHAM and Naïve rats by post injury day (PID) 2 and then decrease BDNF mRNA/protein by PID14. Relative to SHAM, CCI did not change BDNF mRNA/protein levels in the injured hippocampus in the first 2 days after injury but did decrease BDNF protein at PID14. Surprisingly, BDNF mRNA decreased at PID 1, 3, 7 and 14, and BDNF protein decreased at PID 2, in SHAM and CCI hippocampi relative to Naïve. In conclusion, TBI decreased BDNF protein in the injured rat pup hippocampus 14 days after injury. BDNF mRNA levels decreased in both CCI and SHAM hippocampi relative to Naïve, suggesting that certain aspects of the experimental paradigm (such as craniotomy, anesthesia, and/or maternal separation) may decrease the expression of BDNF in the developing hippocampus. While BDNF is important for normal cognition, no inferences can be made regarding the cognitive impact of any of these factors. Such findings, however, suggest that meticulous attention to the experimental paradigm, and possible inclusion of a Naïve group, is warranted in studies of BDNF expression in the developing brain after TBI.

  10. Platelet-derived growth factor involvement in myocardial remodeling following infarction.

    Science.gov (United States)

    Zhao, Wenyuan; Zhao, Tieqiang; Huang, Valerie; Chen, Yuanjian; Ahokas, Robert A; Sun, Yao

    2011-11-01

    Cardiac remodeling occurs in the infarcted heart (MI). The underlying regulatory mechanisms are under investigation. Platelet-derived growth factor (PDGF) is a family of growth factors that stimulates cell growth, differentiation and migration. Herein, we sought to determine whether PDGF is involved in cardiac repair/remodeling following MI. The temporal and spatial expressions of PDGF isoforms (A, B, C and D) and PDGF receptor (PDGFR)-α and β as well as cell types expressing PDGF were examined in the infarcted rat heart. Sham-operated rats served as controls. We found that the normal myocardium expressed all PDGF isoforms, and cell types expressing PDGF were primarily interstitial cells. Following MI, PDGF-A and D were significantly increased in the infarcted myocardium during 6 weeks of the observation period and cells expressing PDGF-A and D were primarily endothelial cells, macrophages and myofibroblasts (myoFb). PDGF-B and C expressions were, however, reduced in the infarcted heart. In the noninfarcted myocardium, PDGF-D expression was increased in the late stage of MI and cells expressing PDGF-D were predominantly fibroblasts. Both PDGFR-α and β were significantly increased in the infarcted myocardium in the early and late stages of MI and in the noninfarcted myocardium in the late stage of MI. Enhanced PDGF-A, PDGF-D and PDGFR are coincident with angiogenesis, and inflammatory and fibrogenic responses in the infarcted myocardium, suggesting their regulation on cardiac repair. Elevated PDGF-D in the noninfarcted myocardium suggests its involvement in the development of interstitial fibrosis that appears in the late stage of MI.

  11. Brain-derived neurotrophic factor from microglia: a molecular substrate for neuropathic pain.

    Science.gov (United States)

    Trang, Tuan; Beggs, Simon; Salter, Michael W

    2011-02-01

    One of the most significant advances in pain research is the realization that neurons are not the only cell type involved in the etiology of chronic pain. This realization has caused a radical shift from the previous dogma that neuronal dysfunction alone accounts for pain pathologies to the current framework of thinking that takes into account all cell types within the central nervous system (CNS). This shift in thinking stems from growing evidence that glia can modulate the function and directly shape the cellular architecture of nociceptive networks in the CNS. Microglia, in particular, are increasingly recognized as active principal players that respond to changes in physiological homeostasis by extending their processes toward the site of neural damage, and by releasing specific factors that have profound consequences on neuronal function and that contribute to CNS pathologies caused by disease or injury. A key molecule that modulates microglia activity is ATP, an endogenous ligand of the P2 receptor family. Microglia expresses several P2 receptor subtypes, and of these the P2X4 receptor subtype has emerged as a core microglia-neuron signaling pathway: activation of this receptor drives the release of brain-derived neurotrophic factor (BDNF), a cellular substrate that causes disinhibition of pain-transmitting spinal lamina I neurons. Converging evidence points to BDNF from spinal microglia as being a critical microglia-neuron signaling molecule that gates aberrant nociceptive processing in the spinal cord. The present review highlights recent advances in our understanding of P2X4 receptor-mediated signaling and regulation of BDNF in microglia, as well as the implications for microglia-neuron interactions in the pathobiology of neuropathic pain.

  12. Glial cell line-derived neurotrophic factor induced the differentiation of amniotic fluid-derived stem cells into vascular endothelial-like cells in vitro.

    Science.gov (United States)

    Zhang, Ruyu; Lu, Ying; Li, Ju; Wang, Jia; Liu, Caixia; Gao, Fang; Sun, Dong

    2016-02-01

    Amniotic fluid-derived stem cells (AFSCs) are a novel source of stem cells that are isolated and cultured from second trimester amniocentesis. Glial cell line-derived neurotrophic factor (GDNF) acts as a tissue morphogen and regulates stem cell proliferation and differentiation. This study investigated the effect of an adenovirus-mediated GDNF gene, which was engineered into AFSCs, on the cells' biological properties and whether GDNF in combination with AFSCs can be directionally differentiated into vascular endothelial-like cells in vitro. AFSCs were isolated and cultured using the plastic adherence method in vitro and identified by the transcription factor Oct-4, which is the primary marker of pluripotent stem cells. AFSCs were efficiently transfected by a GFP-labeled plasmid system of an adenovirus vector carrying the GDNF gene (Ad-GDNF-GFP). Transfected AFSCs stably expressed GDNF. Transfected AFSCs were cultured in endothelial growth medium-2 containing vascular endothelial growth factor. After 1 week, AFSCs were positive for von Willebrand factor (vWF) and CD31, which are markers of endothelial cells, and the recombinant GDNF group was significantly higher than undifferentiated controls and the GFP only group. These results demonstrated that AFSCs differentiated into vascular endothelial-like cells in vitro, and recombinant GDNF promoted differentiation. The differentiation-induced AFSCs may be used as seed cells to provide a new manner of cell and gene therapies for transplantation into the vascular injury site to promote angiogenesis.

  13. Role of exercise-induced brain-derived neurotrophic factor production in the regulation of energy homeostasis in mammals

    DEFF Research Database (Denmark)

    Pedersen, Bente K; Pedersen, Maria; Krabbe, Karen S

    2009-01-01

    Brain-derived neurotrophic factor (BDNF) has been shown to regulate neuronal development and plasticity and plays a role in learning and memory. Moreover, it is well established that BDNF plays a role in the hypothalamic pathway that controls body weight and energy homeostasis. Recent evidence...... and independently so in patients with type 2 diabetes. Brain-derived neurotrophic factor is expressed in non-neurogenic tissues, including skeletal muscle, and exercise increases BDNF levels not only in the brain and in plasma, but in skeletal muscle as well. Brain-derived neurotrophic factor mRNA and protein...... expression was increased in muscle cells that were electrically stimulated, and BDNF increased phosphorylation of AMP-activated protein kinase (AMPK) and acetyl coenzyme A carboxylase-beta (ACCbeta) and enhanced fatty oxidation both in vitro and ex vivo. These data identify BDNF as a contraction...

  14. Decreased glial cell line-derived neurotrophic factor levels in patients with depression: a meta-analytic study.

    Science.gov (United States)

    Lin, Pao-Yen; Tseng, Ping-Tao

    2015-04-01

    Glial cell-line derived neurotrophic factor (GDNF) has been shown to promote development, differentiation, and protection of CNS neurons and was thought to play an important role in various neuropsychiatric disorders. Several studies have examined the GDNF levels in patients with depression but shown inconsistent results. In this study, we compared blood GDNF levels between depressive patients and control subjects through meta-analytic method. The effect sizes (ESs) from all eligible studies were synthesized by using a random effect model. In this meta-analysis, we included 526 patients and 502 control subjects from 12 original articles. Compared to control subjects, blood GDNF levels are significantly decreased in patients with depression (ES = -0.62, p = 0.0011). However, significant heterogeneity was found among included studies. Through subgroup analysis, we found that GDNF was still decreased in studies with major depressive disorder (ES = -0.73, p = 0.0001); in studies with non-old-age depression (ES = -1.25, p = 0.0001), but not with old-age depression; and in studies using serum samples (ES = -0.86, p GDNF levels as a biomarker of depression as a whole, but the results were modulated by psychiatric diagnosis, age of included subjects, and sampling sources. With these results, future studies are required to examine whether effective antidepressant treatment is associated with an increase in serum GDNF levels.

  15. Mapping of landslides under dense vegetation cover using object - oriented analysis and LiDAR derivatives

    NARCIS (Netherlands)

    Van Den Eeckhout, Miet; Kerle, Norman; Hervas, Javier; Supper, Robert; Margottini, C.; Canuti, P.; Sassa, K.

    2013-01-01

    Light Detection and Ranging (LiDAR) and its wide range of derivative products have become a powerful tool in landslide research, particularly for landslide identification and landslide inventory mapping. In contrast to the many studies that use expert-based analysis of LiDAR derivatives to identify

  16. Mapping of landslides under dense vegetation cover using object - oriented analysis and LiDAR derivatives

    NARCIS (Netherlands)

    Van Den Eeckhout, Miet; Kerle, N.; Hervas, Javier; Supper, Robert; Margottini, C.; Canuti, P.; Sassa, K.

    2013-01-01

    Light Detection and Ranging (LiDAR) and its wide range of derivative products have become a powerful tool in landslide research, particularly for landslide identification and landslide inventory mapping. In contrast to the many studies that use expert-based analysis of LiDAR derivatives to identify

  17. Elevated expression of brain-derived neurotrophic factor facilitates visual imprinting in chicks.

    Science.gov (United States)

    Suzuki, Keiko; Maekawa, Fumihiko; Suzuki, Shingo; Nakamori, Tomoharu; Sugiyama, Hayato; Kanamatsu, Tomoyuki; Tanaka, Kohichi; Ohki-Hamazaki, Hiroko

    2012-12-01

    With the aim of elucidating the neural mechanisms of early learning, we studied the role of brain-derived neurotrophic factor (BDNF) in visual imprinting in birds. The telencephalic neural circuit connecting the visual Wulst and intermediate medial mesopallium is critical for imprinting, and the core region of the hyperpallium densocellulare (HDCo), situated at the center of this circuit, has a key role in regulating the activity of the circuit. We found that the number of BDNF mRNA-positive cells in the HDCo was elevated during the critical period, particularly at its onset, on the day of hatching (P0). After imprinting training on P1, BDNF mRNA-positive cells in the HDCo increased in number, and tyrosine phosphorylation of TrkB was observed. BDNF infusion into the HDCo at P1 induced imprinting, even with a weak training protocol that does not normally induce imprinting. In contrast, K252a, an antagonist of Trk, inhibited imprinting. Injection of BDNF at P7, after the critical period, did not elicit imprinting. These results suggest that BDNF promotes the induction of imprinting through TrkB exclusively during the critical period. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.

  18. EXPRESSING HUMAN MATURED BRAIN-DERIVED NEUROTROPHIC FACTOR GENE IN E. Coli AND DETERMINING ITS BIOACTIVITY

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective Expressing the human matured brain-derived neurotrophic factor (mBDNF) gene in E.Coli and determining its bioactivity. Methods The resulting gene of mBDNF was subcloned into the EcoRI-BamHI site of the expression vector plasmid pBV220. The ligation products were used to transform the competent E. Coli DH5α. The proteins of mBDNF were experessed by temperature inducing. The expression products were dealed with solubilizing inclusion bodies and refolding protein. It was introduced into the embryonic chicken DRG to test whether the expressed mBDNF is a biologically active protein. Results The recombinant plasmid pBV/mBDNF was successfully constructed. By temperature inducing,under the control of the bacteriophage λ PL promoter, the experessed mBDNF protein was a 14Kd non-fusion protein,which existed in E. Coli as inclusion bodies. The size of expressed mBDNF is identical to the prediction. Bioactivity of the products was proved that it could support the cell survival and neurite growth in the primary cultures of embryonic 8-day-old chicken DRG neurons as compared to control.Conclusion The mBDNF gene can be expressed bioactively in E. Coli.

  19. Platelet-derived growth factor receptor beta is critical for zebrafish intersegmental vessel formation.

    Directory of Open Access Journals (Sweden)

    Katie M Wiens

    Full Text Available BACKGROUND: Platelet-derived growth factor receptor beta (PDGFRbeta is a tyrosine kinase receptor known to affect vascular development. The zebrafish is an excellent model to study specific regulators of vascular development, yet the role of PDGF signaling has not been determined in early zebrafish embryos. Furthermore, vascular mural cells, in which PDGFRbeta functions cell autonomously in other systems, have not been identified in zebrafish embryos younger than 72 hours post fertilization. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate the role of PDGFRbeta in zebrafish vascular development, we cloned the highly conserved zebrafish homolog of PDGFRbeta. We found that pdgfrbeta is expressed in the hypochord, a developmental structure that is immediately dorsal to the dorsal aorta and potentially regulates blood vessel development in the zebrafish. Using a PDGFR tyrosine kinase inhibitor, a morpholino oligonucleotide specific to PDGFRbeta, and a dominant negative PDGFRbeta transgenic line, we found that PDGFRbeta is necessary for angiogenesis of the intersegmental vessels. SIGNIFICANCE/CONCLUSION: Our data provide the first evidence that PDGFRbeta signaling is required for zebrafish angiogenesis. We propose a novel mechanism for zebrafish PDGFRbeta signaling that regulates vascular angiogenesis in the absence of mural cells.

  20. Peri-Synaptic Glia Recycles Brain-Derived Neurotrophic Factor for LTP Stabilization and Memory Retention.

    Science.gov (United States)

    Vignoli, Beatrice; Battistini, Giulia; Melani, Riccardo; Blum, Robert; Santi, Spartaco; Berardi, Nicoletta; Canossa, Marco

    2016-11-23

    Glial cells respond to neuronal activation and release neuroactive molecules (termed "gliotransmitters") that can affect synaptic activity and modulate plasticity. In this study, we used molecular genetic tools, ultra-structural microscopy, and electrophysiology to assess the role of brain-derived neurotrophic factor (BDNF) on cortical gliotransmission in vivo. We find that glial cells recycle BDNF that was previously secreted by neurons as pro-neurotrophin following long-term potentiation (LTP)-inducing electrical stimulation. Upon BDNF glial recycling, we observed tight, temporal, highly localized TrkB phosphorylation on adjacent neurons, a process required to sustain LTP. Engagement of BDNF recycling by astrocytes represents a novel mechanism by which cortical synapses can expand BDNF action and provide synaptic changes that are relevant for the acquisition of new memories. Accordingly, mice deficient in BDNF glial recycling fail to recognize familiar from novel objects, indicating a physiological requirement for this process in memory consolidation. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Serum brain-derived neurotrophic factor (BDNF) levels in attention deficit-hyperactivity disorder (ADHD).

    Science.gov (United States)

    Scassellati, Catia; Zanardini, Roberta; Tiberti, Alessandra; Pezzani, Marco; Valenti, Vera; Effedri, Paola; Filippini, Elena; Conte, Stefano; Ottolini, Alberto; Gennarelli, Massimo; Bocchio-Chiavetto, Luisella

    2014-03-01

    It has been proposed that the neurotrophin brain-derived neurotrophic factor (BDNF) may be involved in attention deficit-hyperactivity disorder (ADHD) etiopathogenesis. Alterations in BDNF serum levels have been observed in childhood/adulthood neurodevelopmental pathologies, but no evidence is available for BDNF serum concentrations in ADHD. The study includes 45 drug-naïve ADHD children and 45 age-sex matched healthy subjects. Concentration of serum BDNF was determined by the ELISA method. BDNF serum levels in patients with ADHD were not different from those of controls (mean ± SD; ADHD: 39.33 ± 10.41 ng/ml; controls: 38.82 ± 8.29 ng/ml, t = -0.26, p = 0.80). Our findings indicate no alteration of serum BDNF levels in untreated patients with ADHD. A further stratification for cognitive, neuropsychological and psychopathological assessment in a larger sample could be useful to clarify the role of BDNF in the endophenotype characterization of ADHD.

  2. Decreased brain-derived neurotrophic factor plasma levels in psoriasis patients

    Directory of Open Access Journals (Sweden)

    A.R. Brunoni

    2015-08-01

    Full Text Available Brain-derived neurotrophic factor (BDNF is associated with neuroplasticity and synaptic strength, and is decreased in conditions associated with chronic stress. Nevertheless, BDNF has not yet been investigated in psoriasis, a chronic inflammatory systemic disease that is exacerbated by stress. Therefore, our aim was to determine BDNF plasma levels in psoriasis patients and healthy controls. Adult patients (n=94 presenting with psoriasis for at least 1 year were enrolled, and age- and gender-matched with healthy controls (n=307 from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil. Participants had neither a previous history of coronary artery disease nor current episode of major depression. BDNF plasma levels were determined using the Promega ELISA kit. A general linear model was used to compare BDNF levels in psoriasis patients and controls, with age, gender, systolic blood pressure, serum fasting glucose, blood lipid levels, triglycerides, smoking status, and body mass index examined. After adjusting for clinical and demographic variables, significantly decreased BNDF plasma levels were observed in psoriasis patients (P=0.01 (estimated marginal means of 3922 pg/mL; 95%CI=2660-5135 compared with controls (5788 pg/mL; 95%CI=5185-6442. Similar BDNF levels were found in both mild and severe cases of psoriasis. Our finding, that BDNF is decreased in psoriasis, supports the concept of a brain-skin connection in psoriasis. Further studies should determine if BDNF is increased after specific psoriasis treatments, and associated with different disease stages.

  3. Disruption of Stromal-Derived Factor-1/Chemokine Receptor 4 by Simvastatin

    Directory of Open Access Journals (Sweden)

    A Jalili

    2010-03-01

    Full Text Available Background: The alpha chemokine, stromal-derived factor (SDF-1 is produced by bone marrow stromal cells and other cells, especially damaged tissues. SDF-1 receptor, a chemokine receptor 4 (CXCR4, is expressed on inflammatory cells and that SDF-1/CXCR4 axis plays a critical role in migration of inflammatory cells. In cardiovascular diseases, SDF-1 is produced by endothelial cells and plaques and that SDF-1 chemoattracts monocytes to the endothelial cells resulting in a local inflammation. Simvastatin, a cholesterol-lowering agent, is a general drug for treatment of cardiovascular diseases. However, its molecular mechanism has not yet been completely elucidated.Method: Herein, we investigated the role of simvastatin on the SDF- 1/CXCR4 axis by employing flow cytometry, RT-PCR, chemotaxis and adhesion assays. Results: Simvastatin (i downregulates CXCR4 expression on monocytic cell line (THP-1 and primary monocyte in a dose-dependent manner, (ii inhibits adhesion of monocytes to endothelial cells and (iii decreases SDF-1 production by endothelial cells. Moreover, preincubation with simvastatin significantly decreased the migration of THP-1 towards the SDF-1 gradient.Conclusion: All together our data indicate that simvastatin inhibits the binding of monocytes to endothelial cells through disrupting of the SDF-1/CXCR4 axis.

  4. Resilience to chronic stress is mediated by hippocampal brain-derived neurotrophic factor.

    Science.gov (United States)

    Taliaz, Dekel; Loya, Assaf; Gersner, Roman; Haramati, Sharon; Chen, Alon; Zangen, Abraham

    2011-03-23

    Chronic stress is a trigger for several psychiatric disorders, including depression; however, critical individual differences in resilience to both the behavioral and the neurochemical effects of stress have been reported. A prominent mechanism by which the brain reacts to acute and chronic stress is activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is inhibited by the hippocampus via a polysynaptic circuit. Alterations in secretion of stress hormones and levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were implicated in depression and the effects of antidepressant medications. However, the potential role of hippocampal BDNF in behavioral resilience to chronic stress and in the regulation of the HPA axis has not been evaluated. In the present study, Sprague Dawley rats were subjected to 4 weeks of chronic mild stress (CMS) to induce depressive-like behaviors after lentiviral vectors were used to induce localized BDNF overexpression or knockdown in the hippocampus. The behavioral outcome was measured during 3 weeks after the CMS procedure, then plasma samples were taken for measurements of corticosterone levels, and finally hippocampal tissue was taken for BDNF measurements. We found that hippocampal BDNF expression plays a critical role in resilience to chronic stress and that reduction of hippocampal BDNF expression in young, but not adult, rats induces prolonged elevations in corticosterone secretion. The present study describes a mechanism for individual differences in responses to chronic stress and implicates hippocampal BDNF in the development of neural circuits that control adequate stress adaptations.

  5. The Pattern of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampus of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Iraj Salehi

    2010-06-01

    Full Text Available Objective(sThe aim of this study was to evaluate the effects of regular exercise in preventing diabetes complication in the hippocampus of streptozotocin (STZ-induced diabetic rat.Materials and MethodsA total of 48 male wistar rats were divided into four groups (control, control exercise, diabetic and diabetic exercise. Diabetes was induced by injection of single dose of STZ. Exercise was performed for one hr every day, over a period of 8 weeks. The antioxidant enzymes (SOD, GPX, CAT and GR and oxidant indexes with brain-derived neurotrophic factor (BDNF protein and its mRNA and apoptosis were measured in hippocampus of rats. ResultsA significant decrease in antioxidant enzymes activities and increased malondialdehyde (MDA level were observed in diabetic rats (P= 0.004. In response to exercise, antioxidant enzymes activities increased (P= 0.004. In contrast, MDA level decreased in diabetic rats (P= 0.004. Induction of diabetes caused an increase of BDNF protein and its mRNA expression. In response to exercise, BDNF protein and its mRNA expression reduced in hippocampus of diabetic rats. ConclusionDiabetes induced oxidative stress and increased BDNF gene expression. Exercise ameliorated oxidative stress and decreased BDNF gene expression.

  6. Platelet-derived growth factors and their receptors in normal and malignant hematopoiesis

    Science.gov (United States)

    Demoulin, Jean-Baptiste; Montano-Almendras, Carmen P.

    2012-01-01

    Platelet-derived growth factors (PDGF) bind to two closely related receptor tyrosine kinases, PDGF receptor α and β, which are encoded by the PDGFRA and PDGFRB genes. Aberrant activation of PDGF receptors occurs in myeloid malignancies associated with hypereosinophilia, due to chromosomal alterations that produce fusion genes, such as ETV6-PDGFRB or FIP1L1-PDGFRA. Most patients are males and respond to low dose imatinib, which is particularly effective against PDGF receptor kinase activity. Recently, activating point mutations in PDGFRA were also described in hypereosinophilia. In addition, autocrine loops have been identified in large granular lymphocyte leukemia and HTLV-transformed lymphocytes, suggesting new possible indications for tyrosine kinase inhibitor therapy. Although PDGF was initially purified from platelets more than 30 years ago, its physiological role in the hematopoietic system remains unclear. Hematopoietic defects in PDGF-deficient mice have been reported but appear to be secondary to cardiovascular and placental abnormalities. Nevertheless, PDGF acts directly on several hematopoietic cell types in vitro, such as megakaryocytes, platelets, activated macrophages and, possibly, certain lymphocyte subsets and eosinophils. The relevance of these observations for normal human hematopoiesis remains to be established. PMID:22432087

  7. Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression.

    Science.gov (United States)

    Haile, C N; Murrough, J W; Iosifescu, D V; Chang, L C; Al Jurdi, R K; Foulkes, A; Iqbal, S; Mahoney, J J; De La Garza, R; Charney, D S; Newton, T F; Mathew, S J

    2014-02-01

    Ketamine produces rapid antidepressant effects in treatment-resistant depression (TRD), but the magnitude of response varies considerably between individual patients. Brain-derived neurotrophic factor (BDNF) has been investigated as a biomarker of treatment response in depression and has been implicated in the mechanism of action of ketamine. We evaluated plasma BDNF and associations with symptoms in 22 patients with TRD enrolled in a randomized controlled trial of ketamine compared to an anaesthetic control (midazolam). Ketamine significantly increased plasma BDNF levels in responders compared to non-responders 240 min post-infusion, and Montgomery-Åsberg Depression Rating Scale (MADRS) scores were negatively correlated with BDNF (r=-0.701, p = 0.008). Plasma BDNF levels at 240 min post-infusion were highly negatively associated with MADRS scores at 240 min (r = -0.897, p=.002), 24 h (r = -0.791, p = 0.038), 48 h (r = -0.944, p = 0.001) and 72 h (r = -0.977, p = 0.010). No associations with BDNF were found for patients receiving midazolam. These data support plasma BDNF as a peripheral biomarker relevant to ketamine antidepressant response.

  8. Pro-region engineering for improved yeast display and secretion of brain derived neurotrophic factor.

    Science.gov (United States)

    Burns, Michael L; Malott, Thomas M; Metcalf, Kevin J; Puguh, Arthya; Chan, Jonah R; Shusta, Eric V

    2016-03-01

    Brain derived neurotrophic factor (BDNF) is a promising therapeutic candidate for a variety of neurological diseases. However, it is difficult to produce as a recombinant protein. In its native mammalian context, BDNF is first produced as a pro-protein with subsequent proteolytic removal of the pro-region to yield mature BDNF protein. Therefore, in an attempt to improve yeast as a host for heterologous BDNF production, the BDNF pro-region was first evaluated for its effects on BDNF surface display and secretion. Addition of the wild-type pro-region to yeast BDNF production constructs improved BDNF folding both as a surface-displayed and secreted protein in terms of binding its natural receptors TrkB and p75, but titers remained low. Looking to further enhance the chaperone-like functions provided by the pro-region, two rounds of directed evolution were performed, yielding mutated pro-regions that further improved the display and secretion properties of BDNF. Subsequent optimization of the protease recognition site was used to control whether the produced protein was in pro- or mature BDNF forms. Taken together, we have demonstrated an effective strategy for improving BDNF compatibility with yeast protein engineering and secretion platforms.

  9. TrkB-Mediated Neuroprotective and Antihypoxic Properties of Brain-Derived Neurotrophic Factor.

    Science.gov (United States)

    Vedunova, Maria V; Mishchenko, Tatiana A; Mitroshina, Elena V; Mukhina, Irina V

    2015-01-01

    The neuroprotective and antihypoxic effects of brain-derived neurotrophic factor (BDNF) on dissociated hippocampal cultures in a hypoxia model were investigated. These experiments demonstrate that 10 minutes of normobaric hypoxia increased the number of dead cells in primary culture, whereas a preventive application of BDNF increased the number of viable cells. Spontaneous bioelectrical and calcium activity in neural networks was analyzed using multielectrode arrays and functional intravital calcium imaging. The results indicate that BDNF affects the functional parameters of neuronal networks in dissociated hippocampal cultures over the 7-day posthypoxic period. In addition, the effects of k252a, an antagonist of tropomyosin-related kinase B (TrkB), on functional bioelectrical activity during and after acute hypoxia were investigated. It was shown that the protective effects of BDNF are associated with binding to the TrkB receptor. Finally, intravital fluorescent mRNA probes were used to study the role of NF-κB1 in the protective effects of BDNF. Our experiments revealed that BDNF application stimulates NF-κB1 mRNA synthesis in primary dissociated hippocampal cells under normal conditions but not in hypoxic state.

  10. Brain-derived neurotrophic factor into adult neocortex strengthens a taste aversion memory.

    Science.gov (United States)

    Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F; Escobar, Martha L

    2016-01-15

    Nowadays, it is known that brain derived neurotrophic-factor (BDNF) is a protein critically involved in regulating long-term memory related mechanisms. Previous studies from our group in the insular cortex (IC), a brain structure of the temporal lobe implicated in acquisition, consolidation and retention of conditioned taste aversion (CTA), demonstrated that BDNF is essential for CTA consolidation. Recent studies show that BDNF-TrkB signaling is able to mediate the enhancement of memory. However, whether BDNF into neocortex is able to enhance aversive memories remains unexplored. In the present work, we administrated BDNF in a concentration capable of inducing in vivo neocortical LTP, into the IC immediately after CTA acquisition in two different conditions: a "strong-CTA" induced by 0.2M lithium chloride i.p. as unconditioned stimulus, and a "weak-CTA" induced by 0.1M lithium chloride i.p. Our results show that infusion of BDNF into the IC converts a weak CTA into a strong one, in a TrkB receptor-dependent manner. The present data suggest that BDNF into the adult insular cortex is sufficient to increase an aversive memory-trace.

  11. Directed evolution of brain-derived neurotrophic factor for improved folding and expression in Saccharomyces cerevisiae.

    Science.gov (United States)

    Burns, Michael L; Malott, Thomas M; Metcalf, Kevin J; Hackel, Benjamin J; Chan, Jonah R; Shusta, Eric V

    2014-09-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in nervous system function and has therapeutic potential. Microbial production of BDNF has resulted in a low-fidelity protein product, often in the form of large, insoluble aggregates incapable of binding to cognate TrkB or p75 receptors. In this study, employing Saccharomyces cerevisiae display and secretion systems, it was found that BDNF was poorly expressed and partially inactive on the yeast surface and that BDNF was secreted at low levels in the form of disulfide-bonded aggregates. Thus, for the purpose of increasing the compatibility of yeast as an expression host for BDNF, directed-evolution approaches were employed to improve BDNF folding and expression levels. Yeast surface display was combined with two rounds of directed evolution employing random mutagenesis and shuffling to identify BDNF mutants that had 5-fold improvements in expression, 4-fold increases in specific TrkB binding activity, and restored p75 binding activity, both as displayed proteins and as secreted proteins. Secreted BDNF mutants were found largely in the form of soluble homodimers that could stimulate TrkB phosphorylation in transfected PC12 cells. Site-directed mutagenesis studies indicated that a particularly important mutational class involved the introduction of cysteines proximal to the native cysteines that participate in the BDNF cysteine knot architecture. Taken together, these findings show that yeast is now a viable alternative for both the production and the engineering of BDNF.

  12. Brain-derived neurotrophic factor signaling rewrites the glucocorticoid transcriptome via glucocorticoid receptor phosphorylation.

    Science.gov (United States)

    Lambert, W Marcus; Xu, Chong-Feng; Neubert, Thomas A; Chao, Moses V; Garabedian, Michael J; Jeanneteau, Freddy D

    2013-09-01

    Abnormal glucocorticoid and neurotrophin signaling has been implicated in numerous psychiatric disorders. However, the impact of neurotrophic signaling on glucocorticoid receptor (GR)-dependent gene expression is not understood. We therefore examined the impact of brain-derived neurotrophic factor (BDNF) signaling on GR transcriptional regulatory function by gene expression profiling in primary rat cortical neurons stimulated with the selective GR agonist dexamethasone (Dex) and BDNF, alone or in combination. Simultaneous treatment with BDNF and Dex elicited a unique set of GR-responsive genes associated with neuronal growth and differentiation and also enhanced the induction of a large number of Dex-sensitive genes. BDNF via its receptor TrkB enhanced the transcriptional activity of a synthetic GR reporter, suggesting a direct effect of BDNF signaling on GR function. Indeed, BDNF treatment induces the phosphorylation of GR at serine 155 (S155) and serine 287 (S287). Expression of a nonphosphorylatable mutant (GR S155A/S287A) impaired the induction of a subset of BDNF- and Dex-regulated genes. Mechanistically, BDNF-induced GR phosphorylation increased GR occupancy and cofactor recruitment at the promoter of a BDNF-enhanced gene. GR phosphorylation in vivo is sensitive to changes in the levels of BDNF and TrkB as well as stress. Therefore, BDNF signaling specifies and amplifies the GR transcriptome through a coordinated GR phosphorylation-dependent detection mechanism.

  13. Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons.

    Science.gov (United States)

    Murphy, D D; Cole, N B; Segal, M

    1998-09-15

    Dendritic spines are of major importance in information processing and memory formation in central neurons. Estradiol has been shown to induce an increase of dendritic spine density on hippocampal neurons in vivo and in vitro. The neurotrophin brain-derived neurotrophic factor (BDNF) recently has been implicated in neuronal maturation, plasticity, and regulation of GABAergic interneurons. We now demonstrate that estradiol down-regulates BDNF in cultured hippocampal neurons to 40% of control values within 24 hr of exposure. This, in turn, decreases inhibition and increases excitatory tone in pyramidal neurons, leading to a 2-fold increase in dendritic spine density. Exogenous BDNF blocks the effects of estradiol on spine formation, and BDNF depletion with a selective antisense oligonucleotide mimics the effects of estradiol. Addition of BDNF antibodies also increases spine density, and diazepam, which facilitates GABAergic neurotransmission, blocks estradiol-induced spine formation. These observations demonstrate a functional link between estradiol, BDNF as a potent regulator of GABAergic interneurons, and activity-dependent formation of dendritic spines in hippocampal neurons.

  14. Effect of recombinant platelet-derived growth factor (Regranex) on wound closure in genetically diabetic mice.

    Science.gov (United States)

    Chan, Rodney K; Liu, Perry H; Pietramaggiori, Giorgio; Ibrahim, Shahrul I; Hechtman, Herbert B; Orgill, Dennis P

    2006-01-01

    Burns, especially those involving large surface areas, represent a complex wound healing problem. Platelet-derived growth factor (PDGF) is released by activated platelets to recruit inflammatory cells toward the wound bed. It has effects on promoting angiogenesis and granulation tissue formation. However, the effectiveness of topical PDGF on wound closure is variable, ranging from little improvement observed in pig models to dramatic improvement reported in a diabetic mouse model. Here, we sought to determine the effectiveness of commercially sold PDGF-BB (Regranex) on wound closure in genetically diabetic mice. C57BL/KsJ db+/db+ mice and its host strain bearing dorsal 1.5-cm wounds were divided into groups (n = 8 in each group) receiving topical application of either Regranex (10 microg/wound) or vehicle for 5 consecutive days after wounding. The rate of wound closure was analyzed using computerized planimetry. The amount of granulation tissue was determined histologically. Our data indicate that diabetic mice exhibit a significant delay in wound closure when compared with their host strain. Topical application of Regranex did not improve the time to wound closure but did significantly increase the amount of granulation tissue. Our current study using commercially available Regranex failed to reproduce the previously reported finding that PDGF improved wound closure in healing impaired genetically diabetic mice.

  15. Low-level laser therapy promotes dendrite growth via upregulating brain-derived neurotrophic factor expression

    Science.gov (United States)

    Meng, Chengbo; He, Zhiyong; Xing, Da

    2014-09-01

    Downregulation of brain-derived neurotrophic factor (BDNF) in the hippocampus occurs early in the progression of Alzheimer's disease (AD). Since BDNF plays a critical role in neuronal survival and dendrite growth, BDNF upregulation may contribute to rescue dendrite atrophy and cell loss in AD. Low-level laser therapy (LLLT) has been demonstrated to regulate neuronal function both in vitro and in vivo. In the present study, we found that LLLT rescued neurons loss and dendritic atrophy via the increase of both BDNF mRNA and protein expression. In addition, dendrite growth was improved after LLLT, characterized by upregulation of PSD95 expression, and the increase in length, branching, and spine density of dendrites in hippocampal neurons. Together, these studies suggest that upregulation of BDNF with LLLT can ameliorate Aβ-induced neurons loss and dendritic atrophy, thus identifying a novel pathway by which LLLT protects against Aβ-induced neurotoxicity. Our research may provide a feasible therapeutic approach to control the progression of Alzheimer's disease.

  16. Oncogenic human papillomaviruses activate the tumor-associated lens epithelial-derived growth factor (LEDGF gene.

    Directory of Open Access Journals (Sweden)

    Jenny Leitz

    2014-03-01

    Full Text Available The expression of the human papillomavirus (HPV E6/E7 oncogenes is crucial for HPV-induced malignant cell transformation. The identification of cellular targets attacked by the HPV oncogenes is critical for our understanding of the molecular mechanisms of HPV-associated carcinogenesis and may open novel therapeutic opportunities. Here, we identify the Lens Epithelial-Derived Growth Factor (LEDGF gene as a novel cellular target gene for the HPV oncogenes. Elevated LEDGF expression has been recently linked to human carcinogenesis and can protect tumor cells towards different forms of cellular stress. We show that intracellular LEDGF mRNA and protein levels in HPV-positive cancer cells are critically dependent on the maintenance of viral oncogene expression. Ectopic E6/E7 expression stimulates LEDGF transcription in primary keratinocytes, at least in part via activation of the LEDGF promoter. Repression of endogenous LEDGF expression by RNA interference results in an increased sensitivity of HPV-positive cancer cells towards genotoxic agents. Immunohistochemical analyses of cervical tissue specimens reveal a highly significant increase of LEDGF protein levels in HPV-positive lesions compared to histologically normal cervical epithelium. Taken together, these results indicate that the E6/E7-dependent maintenance of intracellular LEDGF expression is critical for protecting HPV-positive cancer cells against various forms of cellular stress, including DNA damage. This could support tumor cell survival and contribute to the therapeutic resistance of cervical cancers towards genotoxic treatment strategies in the clinic.

  17. Oncogenic Human Papillomaviruses Activate the Tumor-Associated Lens Epithelial-Derived Growth Factor (LEDGF) Gene

    Science.gov (United States)

    Leitz, Jenny; Reuschenbach, Miriam; Lohrey, Claudia; Honegger, Anja; Accardi, Rosita; Tommasino, Massimo; Llano, Manuel; von Knebel Doeberitz, Magnus; Hoppe-Seyler, Karin; Hoppe-Seyler, Felix

    2014-01-01

    The expression of the human papillomavirus (HPV) E6/E7 oncogenes is crucial for HPV-induced malignant cell transformation. The identification of cellular targets attacked by the HPV oncogenes is critical for our understanding of the molecular mechanisms of HPV-associated carcinogenesis and may open novel therapeutic opportunities. Here, we identify the Lens Epithelial-Derived Growth Factor (LEDGF) gene as a novel cellular target gene for the HPV oncogenes. Elevated LEDGF expression has been recently linked to human carcinogenesis and can protect tumor cells towards different forms of cellular stress. We show that intracellular LEDGF mRNA and protein levels in HPV-positive cancer cells are critically dependent on the maintenance of viral oncogene expression. Ectopic E6/E7 expression stimulates LEDGF transcription in primary keratinocytes, at least in part via activation of the LEDGF promoter. Repression of endogenous LEDGF expression by RNA interference results in an increased sensitivity of HPV-positive cancer cells towards genotoxic agents. Immunohistochemical analyses of cervical tissue specimens reveal a highly significant increase of LEDGF protein levels in HPV-positive lesions compared to histologically normal cervical epithelium. Taken together, these results indicate that the E6/E7-dependent maintenance of intracellular LEDGF expression is critical for protecting HPV-positive cancer cells against various forms of cellular stress, including DNA damage. This could support tumor cell survival and contribute to the therapeutic resistance of cervical cancers towards genotoxic treatment strategies in the clinic. PMID:24604027

  18. Brain-derived neurotrophic factor stimulates energy metabolism in developing cortical neurons.

    Science.gov (United States)

    Burkhalter, Julia; Fiumelli, Hubert; Allaman, Igor; Chatton, Jean-Yves; Martin, Jean-Luc

    2003-09-10

    Brain-derived neurotrophic factor (BDNF) promotes the biochemical and morphological differentiation of selective populations of neurons during development. In this study we examined the energy requirements associated with the effects of BDNF on neuronal differentiation. Because glucose is the preferred energy substrate in the brain, the effect of BDNF on glucose utilization was investigated in developing cortical neurons via biochemical and imaging studies. Results revealed that BDNF increases glucose utilization and the expression of the neuronal glucose transporter GLUT3. Stimulation of glucose utilization by BDNF was shown to result from the activation of Na+/K+-ATPase via an increase in Na+ influx that is mediated, at least in part, by the stimulation of Na+-dependent amino acid transport. The increased Na+-dependent amino acid uptake by BDNF is followed by an enhancement of overall protein synthesis associated with the differentiation of cortical neurons. Together, these data demonstrate the ability of BDNF to stimulate glucose utilization in response to an enhanced energy demand resulting from increases in amino acid uptake and protein synthesis associated with the promotion of neuronal differentiation by BDNF.

  19. Effects of pigment epithelium derived factor (PEDF) on malignant peripheral nerve sheath tumours (MPNSTs).

    Science.gov (United States)

    Demestre, Maria; Terzi, Menderes Yusuf; Mautner, Victor; Vajkoczy, Peter; Kurtz, Andreas; Piña, Ana Luisa

    2013-12-01

    Neurofibromatosis type 1 (NF1) is an inherited genetic disease affecting 1 in 3,500 individuals. A prominent feature of NF1 is the formation of benign tumours of the peripheral nerve sheath (neurofibromas). However, these can become malignant and form highly metastatic malignant peripheral nerve sheath tumours (MPNST), which are usually fatal despite aggressive surgery, chemotherapy, and radiotherapy. Recent studies have shown that pigment epithelium-derived factor (PEDF) can induce differentiation and inhibit angiogenesis in several kinds of tumours. The present study was designed to determine the in vitro and in vivo effects of PEDF on MPNST angiogenesis and tumour growth. PEDF inhibited proliferation and augmented apoptosis in S462 MPNST cells after 48 h of treatment in culture. In xenografts of S462 MPNST cells in athymic nude mice, PEDF suppressed MPNST tumour burden, due mainly to inhibition of angiogenesis. These results demonstrate for the first time inhibitory effects of PEDF on the growth of human MPNST via induction of anti-angiogenesis and apoptosis. Our results suggest that PEDF could be a novel approach for future therapeutic purposes against MPNST.

  20. Role of Pigment Epithelium-Derived Factor in Stem/Progenitor Cell-Associated Neovascularization

    Directory of Open Access Journals (Sweden)

    Jung-Tung Liu

    2012-01-01

    Full Text Available Pigment epithelium-derived factor (PEDF was first identified in retinal pigment epithelium cells. It is an endogenously produced protein that is widely expressed throughout the human body such as in the eyes, liver, heart, and adipose tissue; it exhibits multiple and varied biological activities. PEDF is a multifunctional protein with antiangiogenic, antitumorigenic, antioxidant, anti-inflammatory, antithrombotic, neurotrophic, and neuroprotective properties. More recently, PEDF has been shown to be the most potent inhibitor of stem/progenitor cell-associated neovascularization. Neovascularization is a complex process regulated by a large, interacting network of molecules from stem/progenitor cells. PEDF is also involved in the pathogenesis of angiogenic eye disease, tumor growth, and cardiovascular disease. Novel antiangiogenic agents with tolerable side effects are desired for the treatment of patients with various diseases. Here, we review the value of PEDF as an important endogenous antiangiogenic molecule; we focus on the recently identified role of PEDF as a possible new target molecule to influence stem/progenitor cell-related neovascularization.

  1. Brain-derived Neurotrophic Factor Promotes the Migration of Olfactory Ensheathing Cells Through TRPC Channels.

    Science.gov (United States)

    Wang, Ying; Teng, Hong-Lin; Gao, Yuan; Zhang, Fan; Ding, Yu-Qiang; Huang, Zhi-Hui

    2016-12-01

    Olfactory ensheathing cells (OECs) are a unique type of glial cells with axonal growth-promoting properties in the olfactory system. Organized migration of OECs is essential for neural regeneration and olfactory development. However, the molecular mechanism of OEC migration remains unclear. In the present study, we examined the effects of brain-derived neurotrophic factor (BDNF) on OEC migration. Initially, the "scratch" migration assay, the inverted coverslip and Boyden chamber migration assays showed that BDNF could promote the migration of primary cultured OECs. Furthermore, BDNF gradient attracted the migration of OECs in single-cell migration assays. Mechanistically, TrkB receptor expressed in OECs mediated BDNF-induced OEC migration, and BDNF triggered calcium signals in OECs. Finally, transient receptor potential cation channels (TRPCs) highly expressed in OECs were responsible for BDNF-induced calcium signals, and required for BDNF-induced OEC migration. Taken together, these results demonstrate that BDNF promotes the migration of cultured OECs and an unexpected finding is that TRPCs are required for BDNF-induced OEC migration. GLIA 2016;64:2154-2165.

  2. Controlled delivery of platelet-derived growth factor-BB from injectable microsphere/hydrogel composites.

    Science.gov (United States)

    Wu, Hua; Liu, Jiaoyan; Wu, Jingjing; Wan, Ying; Chen, Yun

    2016-12-01

    Platelet-derived growth factor-BB (PGDF-BB) loaded gelatin microspheres with an average size of about 2μm was incorporated into chitosan/silk fibroin/glycerophosphate (GP) solutions to prepare composites. The formulated composite solutions were able to form into hydrogels in a temperature range between 32 and 37°C at a pH of ca.7. They had good fluidity at 25°C and showed shear-thinning features at both 25 and 37°C, revealing that they are injectable at room temperature. Elastic modulus of some composites at 37°C was about 10-fold higher than that of chitosan/GP gel, confirming that these composites behave like mechanically strong gels. Optimal composites showed abilities to administrate PDGF-BB release in an approximately linear manner up to 5 weeks. The PDGF-BB release could be regulated by the PDGF-BB load and the silk fibroin content in the composites in an individual or cooperative way. In vivo degradation of composites demonstrated that some of them had markedly enhanced degradation endurance as compared to the chitosan/GP gel. PDGF-BB-stimulated DNA synthesis in Balb/c 3T3 fibroblasts and PDGF-BB-induced cell migration suggested that the bioactivity of released PDGF-BB was well retained.

  3. Serum brain-derived neurotrophic factor in patients with trauma psychopathology.

    Science.gov (United States)

    Hauck, Simone; Kapczinski, Flávio; Roesler, Rafael; de Moura Silveira, Erico; Magalhães, Pedro V; Kruel, Letícia Rosito Pinto; Schestatsky, Sidnei Samuel; Ceitlin, Lúcia Helena Freitas

    2010-04-16

    Brain-derived neurotrophic factor (BDNF) has an important role in learning, motivation and regulation of mood. The aim of this study was to investigate levels of serum BDNF in patients with trauma psychopathology (acute and post-traumatic stress disorder) when compared to age and gender matched controls. A consecutive sample of 34 patients was evaluated regarding socio-demographic and clinical variables by means of a standard protocol, Davidson Trauma Scale, Beck Depression Inventory, Clinical Global Impression and the Global Assessment of Functioning. BDNF serum levels were measured right after the intake interview. Patients had higher BDNF levels than controls. Those levels, however, were higher right after the traumatic event, decreasing over time. When two groups of patients (recent and remote trauma) were investigated in separate, the recent trauma group (less than 1year since the traumatic event) had higher BDNF than controls, but this effect was not detected in the remote trauma group. The recent and remote trauma groups had different BDNF levels. Those findings persisted, even controlling for symptom severity, use of psychotropic medication, and history of psychiatric disease. As far as we know this is the first report of elevated serum BDNF levels in patients with recent trauma. Based in animal models that implicate BDNF in memory formation and consolidation, higher BDNF in recent PTSD could be related to memory and learning disruption central in PTSD psychopathology. Copyright 2010 Elsevier Inc. All rights reserved.

  4. A role for platelet-derived growth factor-BB in rat postpneumonectomy compensatory lung growth.

    Science.gov (United States)

    Yuan, Shizeng; Hannam, Vicky; Belcastro, Rosetta; Cartel, Nicholas; Cabacungan, Judy; Wang, Jinxia; Diambomba, Yenge; Johnstone, Leslie; Post, Martin; Tanswell, A Keith

    2002-07-01

    Unilateral pneumonectomy leads to compensatory growth in the residual lung, the mediators of which are largely unknown. We hypothesized, based on its other known roles in lung cell growth, that platelet-derived growth factor (PDGF)-BB would be an essential mediator of postpneumonectomy compensatory lung growth. Left-sided pneumonectomies were performed on 21-d-old rats, for comparison with sham-operated or unoperated control animals. Body weights were not different between groups. Right lung weights and DNA content were significantly increased (p < 0.05), compared with controls, by 10 d after pneumonectomy. The rate of DNA synthesis was maximal on d 5 postpneumonectomy. Total right lung PDGF-B mRNA and PDGF-BB protein increased after pneumonectomy, but were apparently tightly regulated, relative to total right lung beta-actin mRNA and protein content, respectively. However, PDGF-BB expression after pneumonectomy was apparently not purely constitutive, in that daily i.p. injections of a truncated soluble PDGF beta-receptor both reduced activation of the native PDGF beta-receptor, and attenuated increased lung DNA synthesis on d 3 after pneumonectomy. These findings are consistent with a critical role for PDGF-BB in postpneumonectomy lung growth.

  5. Platelet-derived growth factor-BB-mediated glycosaminoglycan synthesis is transduced through Akt.

    Science.gov (United States)

    Cartel, Nicholas J; Wang, Jinxia; Post, Martin

    2002-04-01

    Previously we have demonstrated that the phosphoinositide 3-kinase (PI-3K) signal-transduction pathway mediates platelet-derived growth factor (PDGF)-BB-induced glycosaminoglycan (GAG) synthesis in fetal lung fibroblasts. In the present study we further investigated the signal-transduction pathway(s) that results in PDGF-BB-induced GAG synthesis. Over-expression of a soluble PDGF beta-receptor as well as a mutated form of the beta-receptor, unable to bind PI-3K, diminished GAG synthesis in fetal lung fibroblasts subsequent to PDGF-BB stimulation. The PI-3K inhibitor wortmannin blocked PDGF-BB-induced Akt activity as well as significantly diminishing PDGF-BB-mediated GAG synthesis. Expression of dominant-negative PI-3K also abrogated Akt activity and GAG synthesis. Furthermore, expression of dominant-negative Akt abrogated endogenous Akt activity, Rab3D phosphorylation and GAG synthesis, whereas expression of constitutively activated Akt stimulated Rab3D phosphorylation and GAG synthesis in the absence of PDGF-BB. Over-expression of wild-type PTEN (phosphatase and tensin homologue deleted in chromosome 10) inhibited Akt activity and concomitantly attenuated GAG synthesis in fibroblasts stimulated with PDGF-BB. These data suggest that Akt is an integral protein involved in PDGF-BB-mediated GAG regulation in fetal lung fibroblasts.

  6. Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression.

    Science.gov (United States)

    Chen, Hao-Hao; Zhang, Ning; Li, Wei-Yun; Fang, Ma-Rong; Zhang, Hui; Fang, Yuan-Shu; Ding, Ming-Xing; Fu, Xiao-Yan

    2015-09-01

    Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor (BDNF). In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. A BDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippocampus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open field test in these rats as well. These findings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.

  7. Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression

    Directory of Open Access Journals (Sweden)

    Hao-hao Chen

    2015-01-01

    Full Text Available Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor (BDNF. In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. A BDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippocampus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open field test in these rats as well. These findings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.

  8. Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression

    Institute of Scientific and Technical Information of China (English)

    Hao-hao Chen; Ning Zhang; Wei-yun Li; Ma-rong Fang; Hui Zhang; Yuan-shu Fang; Ming-xing Ding; Xiao-yan Fu

    2015-01-01

    Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor (BDNF). In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. ABDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippo-campus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open ifeld test in these rats as well. These ifndings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.

  9. AMPA receptor-induced local brain-derived neurotrophic factor signaling mediates motor recovery after stroke.

    Science.gov (United States)

    Clarkson, Andrew N; Overman, Justine J; Zhong, Sheng; Mueller, Rudolf; Lynch, Gary; Carmichael, S Thomas

    2011-03-09

    Stroke is the leading cause of adult disability. Recovery after stroke shares similar molecular and cellular properties with learning and memory. A main component of learning-induced plasticity involves signaling through AMPA receptors (AMPARs). We systematically tested the role of AMPAR function in motor recovery in a mouse model of focal stroke. AMPAR function controls functional recovery beginning 5 d after the stroke. Positive allosteric modulators of AMPARs enhance recovery of limb control when administered after a delay from the stroke. Conversely, AMPAR antagonists impair motor recovery. The contributions of AMPARs to recovery are mediated by release of brain-derived neurotrophic factor (BDNF) in periinfarct cortex, as blocking local BDNF function in periinfarct cortex blocks AMPAR-mediated recovery and prevents the normal pattern of motor recovery. In contrast to a delayed AMPAR role in motor recovery, early administration of AMPAR agonists after stroke increases stroke damage. These findings indicate that the role of glutamate signaling through the AMPAR changes over time in stroke: early potentiation of AMPAR signaling worsens stroke damage, whereas later potentiation of the same signaling system improves functional recovery.

  10. Protective role of a novel human erythrocyte-derived depressing factor on blood vessels in rats

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The protective role of a human erythrocyte-derived depressing factor (EDDF) on blood vessels was evaluated. The experiments were carried out on 25male Wistar rats aged 6-8 weeks, which were divided into control (n = 8), calcium overload (n = 8) and NG-L-nitro-arginine hypertensive model groups (L-NNA,n = 9), respectively. The isolated vascular ring perfusion assay, two-photon laser scanning fluorescence microscopy (TPM) and transmitted electron microscope were used to examine the effect of EDDF on vascular function and ultrastructure. Results showed that the contractile response of calcium overload rats and L-NNA rats to phenylephrine (PE) was significantly enhanced compared with that of the control (P < 0.05), and EDDF (10-3 g @mL-1) remarkably decreased the vascular contractile response of control's and calcium overload rats (P < 0.05),while EDDF had no effect on that of L-NNA rats. EDDF also alleviated the ultrastructural lesion of aorta VSMC in calcium overload rats by easing the abnormal in the nucleus, mitochondrion and other organell. It is concluded that EDDF could efficiently protect blood vessels against injury by influencing Ca2+ transport and ameliorating the lesion of VSMC, and further supported the hypothesis that the NO-cGMP pathway might contribute to the vasodilation and partially antihypertensive mechanism of EDDF.``

  11. Label-free aptasensor for platelet-derived growth factor (PDGF) protein

    Energy Technology Data Exchange (ETDEWEB)

    Degefa, Tesfaye Hailu [Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701 (Korea, Republic of); Kwak, Juhyoun [Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701 (Korea, Republic of)], E-mail: Juhyoun_Kwak@kaist.ac.kr

    2008-04-21

    A label-free aptasensor for platelet-derived growth factor (PDGF) protein is reported. The aptasensor uses mixed self-assembled monolayers (SAMs) composed of a thiol-modified PDGF binding aptamer and 6-mercaptohexanol (MCH) on a gold electrode. The SAMs were characterized by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV) before and after binding of the protein using [Fe(CN){sub 6}]{sup 3-/4-}, a redox marker ion as an indicator for the formation of a protein-aptamer complex. The CVs at the PDGF modified electrode showed significant differences, such as changes in the peak currents and peak-to-peak separation, before and after binding of the target protein. The EIS spectra, in the form of Nyquist plots, were analyzed with a Randles circuit while the electron transfer resistance R{sub ct} was used to monitor the binding of the target protein. The results showed that, without any modification to the aptamer, the target protein can be recognized effectively at the PDGF binding aptamer SAMs at the electrode surface. Control experiments using non-binding oligonucleotides assembled at the electrode surfaces also confirmed the results and showed that there was no formation of an aptamer-protein complex. The DPV signal at the aptamer functionalized electrode showed a linearly decreased marker ion peak current in a protein concentrations range of 1-40 nM. Thus, label-free detection of PDGF protein at an aptamer modified electrode has been demonstrated.

  12. Serum concentrations of brain-derived neurotrophic factor and mental disorders in imprisoned women

    Directory of Open Access Journals (Sweden)

    Renata M. Dotta-Panichi

    2015-06-01

    Full Text Available Objective:Mental disorders and early trauma are highly prevalent in female inmates. Brain-derived neurotrophic factor (BDNF plays an important role in learning, memory processes, and mood regulation. The aim of this study was to evaluate the relationship between serum BDNF levels and mental disorders among imprisoned women as compared with age- and education-matched controls.Methods:A consecutively recruited sample of 18 female prisoners with mental disorders was assessed for sociodemographic, criminal, and clinical variables using standardized instruments, the Mini International Neuropsychiatric Interview Plus (MINI Plus, and serum BDNF levels.Results:High rates of childhood sexual abuse and posttraumatic stress disorder (PTSD were found in the group of forensic patients. Serum BDNF levels in the forensic group did not differ from those of healthy controls, and were significantly higher when compared with those of women with mental disorders hospitalized in a general hospital.Conclusion:Elevated serum BDNF levels were found in imprisoned women. The results of this study may suggest neurobiological mechanisms similar to those seen in previous clinical and preclinical studies showing the involvement of BDNF in the pathophysiology of PTSD.

  13. Platelet-derived growth factor receptor alpha in glioma: a bad seed

    Institute of Scientific and Technical Information of China (English)

    Kun-Wei Liu; Bo Hu; Shi-Yuan Cheng

    2011-01-01

    Recent collaborative,large-scale genomic profiling of the most common and aggressive brain tumor glioblastoma multiforme(GBM) has significantly advanced our understanding of this disease.The gene encoding platelet-derived growth factor receptor alpha (PDGFRα) was identified as the third of the top 11 amplified genes in clinical GBM specimens.The important roles of PDGFRα signaling during normal brain development also implicate the possible pathologic consequences of PDGFRα over-activation in glioma.Although the initial clinical trials using PDGFR kinase inhibitors have been predominantly disappointing,diagnostic and treatment modalities involving genomic profiling and personalized medicine are expected to improve the therapy targeting PDGFRα signaling.In this review,we discuss the roles of PDGFRα signaling during development of the normal central nervous system (CNS) and in pathologic conditions such as malignant glioma.We further compare various animal models of PDGF-induced gliomagenesis and their potential as a novel platform of pre-clinical drug testing.We then summarize our recent publication and how these findings will likely impact treatments for gliomas driven by PDGFRα overexpression.A better understanding of PDGFRα signaling in glioma and their microenvironment,through the use of human or mouse models,is necessary to design a more effective therapeutic strategy against gliomas harboring the aberrant PDGFRα signaling.

  14. Anatomical evidence for transsynaptic influences of estrogen on brain-derived neurotrophic factor expression.

    Science.gov (United States)

    Blurton-Jones, M; Kuan, P N; Tuszynski, M H

    2004-01-12

    Several studies have demonstrated that estrogen modulates brain-derived neurotrophic factor (BDNF) mRNA and protein within the adult hippocampus and cortex. However, mechanisms underlying this regulation are unknown. Although an estrogen response element (ERE)-like sequence has been identified within the BDNF gene, such a classical mechanism of estrogen-induced transcriptional activation requires the colocalized expression of estrogen receptors within cells that produce BDNF. Developmental studies have demonstrated such a relationship, but to date no studies have examined colocalization of estrogen receptors and BDNF within the adult brain. By utilizing double-label immunohistochemistry for BDNF, estrogen receptor-alpha (ER-alpha), and estrogen receptor-beta (ER-beta), we found only sparse colocalization between ER-alpha and BDNF in the hypothalamus, amygdala, prelimbic cortex, and ventral hippocampus. Furthermore, ER-beta and BDNF do not colocalize in any brain region. Given the recent finding that cortical ER-beta is almost exclusively localized to parvalbumin-immunoreactive GABAergic neurons, we performed BDNF/parvalbumin double labeling and discovered that axons from cortical ER-beta-expressing inhibitory neurons terminate on BDNF-immunoreactive pyramidal cells. Collectively, these findings support a potential transsynaptic relationship between estrogen state and cortical BDNF: By directly modulating GABAergic interneurons, estrogen may indirectly influence the activity and expression of BDNF-producing cortical neurons.

  15. Oncogenic human papillomaviruses activate the tumor-associated lens epithelial-derived growth factor (LEDGF) gene.

    Science.gov (United States)

    Leitz, Jenny; Reuschenbach, Miriam; Lohrey, Claudia; Honegger, Anja; Accardi, Rosita; Tommasino, Massimo; Llano, Manuel; von Knebel Doeberitz, Magnus; Hoppe-Seyler, Karin; Hoppe-Seyler, Felix

    2014-03-01

    The expression of the human papillomavirus (HPV) E6/E7 oncogenes is crucial for HPV-induced malignant cell transformation. The identification of cellular targets attacked by the HPV oncogenes is critical for our understanding of the molecular mechanisms of HPV-associated carcinogenesis and may open novel therapeutic opportunities. Here, we identify the Lens Epithelial-Derived Growth Factor (LEDGF) gene as a novel cellular target gene for the HPV oncogenes. Elevated LEDGF expression has been recently linked to human carcinogenesis and can protect tumor cells towards different forms of cellular stress. We show that intracellular LEDGF mRNA and protein levels in HPV-positive cancer cells are critically dependent on the maintenance of viral oncogene expression. Ectopic E6/E7 expression stimulates LEDGF transcription in primary keratinocytes, at least in part via activation of the LEDGF promoter. Repression of endogenous LEDGF expression by RNA interference results in an increased sensitivity of HPV-positive cancer cells towards genotoxic agents. Immunohistochemical analyses of cervical tissue specimens reveal a highly significant increase of LEDGF protein levels in HPV-positive lesions compared to histologically normal cervical epithelium. Taken together, these results indicate that the E6/E7-dependent maintenance of intracellular LEDGF expression is critical for protecting HPV-positive cancer cells against various forms of cellular stress, including DNA damage. This could support tumor cell survival and contribute to the therapeutic resistance of cervical cancers towards genotoxic treatment strategies in the clinic.

  16. Serum Brain-Derived Neurotrophic Factor Levels in