Sample records for mage a9 expression

  1. Contrary melanoma-associated antigen-A expression at the tumor front and center: A comparative analysis of stage I and IV head and neck squamous cell carcinoma

    PubMed Central

    Hartmann, Stefan; Brisam, Muna; Rauthe, Stephan; Driemel, Oliver; Brands, Roman C.; Rosenwald, Andreas; Kübler, Alexander C.; Müller-Richter, Urs D. A.

    2016-01-01

    There is a growing body of evidence indicating that several melanoma-associated antigen-A (MAGE-A) subgroups contribute to the malignancy of head and neck cancer. The present study retrospectively analyzed the expression of all known MAGE-A subgroups in the tumor front and center of 38 head and neck cancer patients (Union for International Cancer Control stage I or IV) by immunohistochemistry. MAGE-A1, -A6, -A8, -A9 and -A11 were expressed at significantly higher levels at the tumor front of stage IV specimens compared with the tumor front of stage I specimens. In stage I cancer, the tumor center and front ratio (C/F ratio) for each subgroup was >1.0. In stage IV cancer, the C/F ratio was <1.0 in 9/11 subgroups. The most significant change in the expression pattern was observed for MAGE-A11. These results indicated that there is a marked alteration and shift to the invasive front of almost all MAGE-A subgroups, but particularly MAGE-A11, during the progression of head and neck squamous cell carcinoma. PMID:27703530

  2. Quantitative Expression and Immunogenicity of MAGE-3 and -6 in Upper Aerodigestive Tract Cancer

    PubMed Central

    Andrade Filho, Pedro A.; López-Albaitero, Andrés; Xi, Liqiang; Gooding, William; Godfrey, Tony; Ferris, Robert L.

    2009-01-01

    The MAGE antigens are frequently expressed cancer vaccine targets. However, quantitative analysis of MAGE expression in upper aero-digestive tract (UADT) tumor cells and its association with T cell recognition has not been performed, hindering the selection of appropriate candidates for MAGE specific immunotherapy. Using quantitative RT-PCR (QRT-PCR), we evaluated the expression of MAGE-3/6 in 65 UADT cancers, 48 normal samples from tumor matched sites and 7 HLA-A*0201+squamous cell carcinoma of the head and neck (SCCHN) cell lines. Expression results were confirmed using western blot. HLA-A*0201:MAGE-3(271–279) specific cytotoxic T lymphocytes (MAGE-CTL) from SCCHN patients and healthy donors showed that MAGE-3/6 expression was highly associated with CTL recognition in vitro. Based on MAGE-3/6 expression we could identify 31 (47%) of the 65 UADT tumors which appeared to express MAGE-3/6 at levels that correlated with efficient CTL recognition. To confirm that the level of MAGE-3 expression was responsible for CTL recognition, two MAGE-3/6 mRNAhigh SCCHN cell lines, PCI-13 and PCI-30, were subjected to MAGE-3/6 specific knockdown. RNAi–transfected cells showed that MAGE expression, and MAGE-CTL recognition, were significantly reduced. Furthermore, treatment of cells expressing low MAGE-3/6 mRNA with a demethylating agent, 5-aza-2'-deoxycytidine (DAC), increased the expression of MAGE-3/6 and CTL recognition. Thus, using QRT-PCR UADT cancers frequently express MAGE-3/6 at levels sufficient for CTL recognition, supporting the use of a QRT-PCR based assay for the selection of candidates likely to respond to MAGE-3/6 immunotherapy. Demethylating agents could increase the number of patients amenable for targeting epigenetically modified tumor antigens in vaccine trials. PMID:19610063

  3. Quantitative expression and immunogenicity of MAGE-3 and -6 in upper aerodigestive tract cancer.

    PubMed

    Filho, Pedro A Andrade; López-Albaitero, Andrés; Xi, Liqiang; Gooding, William; Godfrey, Tony; Ferris, Robert L

    2009-10-15

    The MAGE antigens are frequently expressed cancer vaccine targets. However, quantitative analysis of MAGE expression in upper aerodigestive tract (UADT) tumor cells and its association with T-cell recognition has not been performed, hindering the selection of appropriate candidates for MAGE-specific immunotherapy. Using quantitative RT-PCR (QRT-PCR), we evaluated the expression of MAGE-3/6 in 65 UADT cancers, 48 normal samples from tumor matched sites and 7 HLA-A*0201+ squamous cell carcinoma of the head and neck (SCCHN) cell lines. Expression results were confirmed using Western blot. HLA-A*0201:MAGE-3- (271-279) specific cytotoxic T lymphocytes (MAGE-CTL) from SCCHN patients and healthy donors showed that MAGE-3/6 expression was highly associated with CTL recognition in vitro. On the basis of the MAGE-3/6 expression, we could identify 31 (47%) of the 65 UADT tumors, which appeared to express MAGE-3/6 at levels that correlated with efficient CTL recognition. To confirm that the level of MAGE-3 expression was responsible for CTL recognition, 2 MAGE-3/6 mRNA(high) SCCHN cell lines, PCI-13 and PCI-30, were subjected to MAGE-3/6-specific knockdown. RNAi-transfected cells showed that MAGE expression and MAGE-CTL recognition were significantly reduced. Furthermore, treatment of cells expressing low MAGE-3/6 mRNA with a demethylating agent, 5-aza-2'-deoxycytidine (DAC), increased the expression of MAGE-3/6 and CTL recognition. Thus, using QRT-PCR UADT cancers frequently express MAGE-3/6 at levels sufficient for CTL recognition, supporting the use of a QRT-PCR-based assay for the selection of candidates likely to respond to MAGE-3/6 immunotherapy. Demethylating agents could increase the number of patients amenable for targeting epigenetically modified tumor antigens in vaccine trials.

  4. Expression of cancer-testis antigens MAGE-A4 and MAGE-C1 in oral squamous cell carcinoma.

    PubMed

    Montoro, José Raphael de Moura Campos; Mamede, Rui Celso Martins; Neder Serafini, Luciano; Saggioro, Fabiano Pinto; Figueiredo, David Livingstone Alves; Silva, Wilson Araújo da; Jungbluth, Achim A; Spagnoli, Giulio Cesare; Zago, Marco Antônio

    2012-08-01

    Tumor markers are genes or their products expressed exclusively or preferentially in tumor cells and cancer-testis antigens (CTAs) form a group of genes with a typical expression pattern expressed in a variety of malignant neoplasms. CTAs are considered potential targets for cancer vaccines. It is possible that the CTA MAGE-A4 (melanoma antigen) and MAGE-C1 are expressed in carcinoma of the oral cavity and are related with survival. This study involved immunohistochemical analysis of 23 patients with oral squamous cell carcinoma (SCC) and was carried out using antibodies for MAGE-A4 and MAGE-C1. Fisher's exact test and log-rank test were used to evaluate the results. The expression of the MAGE-A4 and MAGE-C1 were 56.5% and 47.8% without statistical difference in studied variables and survival. The expression of at least 1 CTA was present in 78.3% of the patients, however, without correlation with clinicopathologic variables and survival. Copyright © 2011 Wiley Periodicals, Inc.

  5. Necdin interacts with the Msx2 homeodomain protein via MAGE-D1 to promote myogenic differentiation of C2C12 cells.

    PubMed

    Kuwajima, Takaaki; Taniura, Hideo; Nishimura, Isao; Yoshikawa, Kazuaki

    2004-09-24

    Necdin is a potent growth suppressor that is expressed predominantly in postmitotic cells such as neurons and skeletal muscle cells. Necdin shows a significant homology to MAGE (melanoma antigen) family proteins, all of which contain a large homology domain. MAGE-D1 (NRAGE, Dlxin-1) interacts with the Dlx/Msx family homeodomain proteins via an interspersed hexapeptide repeat domain distinct from the homology domain. Here we report that necdin associates with the Msx homeodomain proteins via MAGE-D1 to modulate their function. In vitro binding and co-immunoprecipitation analyses revealed that MAGE-D1 directly interacted with necdin via the homology domain and Msx1 (or Msx2) via the repeat domain. A ternary complex of necdin, MAGE-D1, and Msx2 was formed in vitro, and an endogenous complex containing these three proteins was detected in differentiating embryonal carcinoma cells. Co-expression of necdin and MAGE-D1 released Msx-dependent transcriptional repression. C2C12 myoblast cells that were stably transfected with Msx2 cDNA showed a marked reduction in myogenic differentiation, and co-expression of necdin and MAGE-D1 canceled the Msx2-dependent repression. These results suggest that necdin and MAGE-D1 cooperate to modulate the function of Dlx/Msx homeodomain proteins in cellular differentiation. Copyright 2004 American Society for Biochemistry and Molecular Biology, Inc.

  6. Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel

    PubMed Central

    Kyogoku, Noriaki; Ikeda, Hiroaki; Tsuchikawa, Takahiro; Abiko, Takehiro; Fujiwara, Aki; Maki, Takehiro; Yamamura, Yoshiyuki; Ichinokawa, Masaomi; Tanaka, Kimitaka; Imai, Naoko; Miyahara, Yoshihiro; Kageyama, Shinichi; Shiku, Hiroshi; Hirano, Satoshi

    2016-01-01

    A phase I+II clinical trial of vaccination with MAGE-A4 protein complexed with cholesteryl pullulan melanoma antigen gene-A4 nanogel (CHP-MAGE-A4) is currently underway in patients with MAGE-A4-expressing cancer. In the present study, the primary phase I endpoint was to test the safety of the administration of 300 µg CHP-MAGE-A4 with and without OK-432. Another aim of the study was to clarify the details of the specific humoral immune response to vaccination. The 9 patients enrolled for phase I were vaccinated 6 times, once every 2 weeks: 3 patients with 100 µg and 3 patients with 300 µg CHP-MAGE-A4, and 3 patients with 300 µg CHP-MAGE-A4 plus 0.5 clinical units of OK-432. Toxicities were assessed using Common Terminology Criteria for Adverse Events v3.0. Clinical response was evaluated by modified Response Evaluation Criteria in Solid Tumours. Immunological monitoring of anti-MAGE-A4-specific antibodies was performed by ELISA of pre- and post-vaccination patient sera. The 6 vaccinations produced no severe adverse events. Stable disease was assessed in 4/9 patients. Anti-MAGE-A4 total immunoglobulin (Ig)G titers increased in 7/9 patients. Efficacious anti-MAGE-A4 IgG1, 2 and 3 antibody responses were observed in 7/9 patients. Among them, positive conversions to T helper 2 (Th2)-type antibody responses (IgG4 and IgE) were observed after frequent vaccination in 4/7 patients. The Th2 conversion was possibly associated with undesirable clinical observations, including progressive disease and the appearance of a new relapse lesion. The present study suggested that frequent vaccinations activated a Th2-dominant status in the cancer patients. The identification of a time-dependent IgG subclass and IgE antibody production during vaccination protocols may be a useful surrogate marker indicating a potentially undesirable change of the immunological environment for an effective antitumor immune response in cancer patients. PMID:28105158

  7. Induction of antigen-specific cytotoxic T-cell response by dendritic cells generated from ecto-mesenchymal stem cells infected with an adenovirus containing the MAGE-D4a gene.

    PubMed

    Hu, Shijie; Li, Bing; Shen, Xuefeng; Zhang, Rui; Gao, Dakuan; Guo, Qingdong; Jin, Yan; Fei, Zhou

    2016-04-01

    The present study aimed to investigate the feasibility of using ecto-mesenchymal stem cell (EMSC)-derived dendritic cells (DCs) for glioma immunotherapy following infection by a recombinant adenovirus containing the melanoma-associated antigen D4a (MAGE-D4a) gene. The ex vivo cultured EMSCs were infected by the adenoviral plasmid containing MAGE-D4a (pAd/MAGE-D4a). Efficiency of transfection was evaluated through the detection of green fluorescent protein-marked MAGE-D4a. The MAGE-EMSCs were induced to differentiate into DCs, termed as MAGE-EMSCs-DCs. The morphology was subsequently analyzed under a microscope, and methyl thiazolyl tetrazolium (MTT) and interferon-γ (IFN-γ) assays were performed to analyze the cytotoxicity of the MAGE-EMSC-DCs on the human glioma U251 cell line. Following purification by magnetic-activated cell sorting, the EMSCs grew into swirls, with a long spindle shape and were fibroblast-like. The gene transfected with recombinant adenovirus vectors maintained high and stable expression levels of MAGE-D4a, and its efficiency was increased in a multiplicity of infection-dependent manner. The results of the MTT assay indicated that the T cells, primed by the recombinant MAGE-D4a-infected EMSC-DCs in vitro , recognized MAGE-D4a-expressing tumor cell lines in a human leukocyte antigen class I-restricted manner, and evoked a higher cytotoxic T cell (CTL) response. The CTL response induced by the MAGE-EMSC-DCs, co-cultured with the U251 cells for 24 h, produced 765.0 pg/ml IFN-γ, which was significantly greater when compared to the control wells. T lymphocytes stimulated by MAGE-EMSC-DCs evoke a higher CTL response to human glioma cell lines, and may serve as a promising therapeutic modality for the treatment of MAGE-D4a-expressing glioma.

  8. Expression of cancer/testis antigens in salivary gland carcinomas with reference to MAGE-A and NY-ESO-1 expression in adenoid cystic carcinoma.

    PubMed

    Beppu, Shintaro; Ito, Yohei; Fujii, Kana; Saida, Kosuke; Takino, Hisashi; Masaki, Ayako; Murase, Takayuki; Kusafuka, Kimihide; Iida, Yoshiyuki; Onitsuka, Tetsuro; Yatabe, Yasushi; Hanai, Nobuhiro; Hasegawa, Yasuhisa; Ijichi, Kei; Murakami, Shingo; Inagaki, Hiroshi

    2017-08-01

    Cancer/testis antigens (CTAs) are detected in cancer cells but not in healthy normal tissues, with the exception of gametogenic tissues. CTAs are highly immunogenic proteins, and thus represent ideal targets for cytotoxic T-lymphocyte-mediated specific immune therapy. The aim of this study was to screen CTA expression in various types of salivary gland carcinoma and to clarify clinicopathological significance of MAGE-A and NY-ESO-1 expression in adenoid cystic carcinomas (AdCCs) of the salivary gland, which is one of the most common salivary gland carcinomas, and usually has a fatal outcome. We used immunohistochemistry to examine the expression of four CTAs (MAGE-A, NY-ESO-1, CT7, and GAGE7) in various types of salivary gland carcinoma (n = 95). When carcinoma cases were divided into low-grade and intermediate/high-grade types, NY-ESO-1 and CT7 were expressed more frequently in intermediate/high-grade carcinomas. We then focused on MAGE-A and NY-ESO-1 expression in a large cohort of adenoid cystic carcinomas (AdCCs) (n = 46). MAGE-A and NY-ESO-1 were frequently expressed in AdCC; specifically, MAGE-A was expressed in >60% of the AdCC cases. MAGE-A expression and tumour site (minor salivary gland) were identified as independent risk factors for locoregional tumour recurrence. These findings suggest that CTAs may be expressed in a variety of salivary gland carcinomas, especially in those with higher histological grades. In addition, MAGE-A, which is frequently expressed in AdCC cases, may be a useful prognostic factor for poorer locoregional recurrence-free survival. © 2017 John Wiley & Sons Ltd.

  9. MAGE-A inhibits apoptosis in proliferating myeloma cells through repression of Bax and maintenance of survivin.

    PubMed

    Nardiello, Tricia; Jungbluth, Achim A; Mei, Anna; Diliberto, Maurizio; Huang, Xiangao; Dabrowski, Ania; Andrade, Valéria C C; Wasserstrum, Rebecca; Ely, Scott; Niesvizky, Ruben; Pearse, Roger; Coleman, Morton; Jayabalan, David S; Bhardwaj, Nina; Old, Lloyd J; Chen-Kiang, Selina; Cho, Hearn Jay

    2011-07-01

    The type I Melanoma Antigen GEnes (MAGEs) are commonly expressed in cancers, fueling speculation that they may be therapeutic targets with oncogenic potential. They form complexes with RING domain proteins that have E3 ubiquitin ligase activity and promote p53 degradation. MAGE-A3 was detected in tumor specimens from patients with multiple myeloma and its expression correlated with higher frequencies of Ki-67(+) malignant cells. In this report, we examine the mechanistic role of MAGE-A in promoting survival of proliferating multiple myeloma cells. The impact of MAGE-A3 expression on survival and proliferation in vivo was examined by immunohistochemical analysis in an independent set of tumor specimens segregated into two groups: newly diagnosed, untreated patients and patients who had relapsed after chemotherapy. The mechanisms of MAGE-A3 activity were investigated in vitro by silencing its expression by short hairpin RNA interference in myeloma cell lines and primary cells and assessing the resultant effects on proliferation and apoptosis. MAGE-A3 was detected in a significantly higher percentage of relapsed patients compared with newly diagnosed, establishing a novel correlation with progression of disease. Silencing of MAGE-A showed that it was dispensable for cell cycling, but was required for survival of proliferating myeloma cells. Loss of MAGE-A led to apoptosis mediated by p53-dependent activation of proapoptotic Bax expression and by reduction of survivin expression through both p53-dependent and -independent mechanisms. These data support a role for MAGE-A in the pathogenesis and progression of multiple myeloma by inhibiting apoptosis in proliferating myeloma cells through two novel mechanisms.

  10. MAGE-A inhibits apoptosis in proliferating myeloma cells through repression of Bax and maintenance of survivin

    PubMed Central

    Nardiello, Tricia; Jungbluth, Achim A.; Mei, Anna; DiLiberto, Maurizio; Huang, Xiangao; Dabrowski, Ania; Andrade, Valéria C. C.; Wasserstrum, Rebecca; Ely, Scott; Niesvizky, Ruben; Pearse, Roger; Coleman, Morton; Jayabalan, David S.; Bhardwaj, Nina; Old, Lloyd J.; Chen-Kiang, Selina; Cho, Hearn Jay

    2011-01-01

    Purpose The type I Melanoma Antigen GEnes (MAGEs) are commonly expressed in cancers, fueling speculation that they may be therapeutic targets with oncogenic potential. They form complexes with RING domain proteins that have E3 ubiquitin ligase activity and promote p53 degradation. MAGE-A3 was detected in tumor specimens from patients with multiple myeloma and its expression correlated with higher frequencies of Ki-67+ malignant cells. In this report, we examine the mechanistic role of MAGE-A in promoting survival of proliferating multiple myeloma cells. Experimental Design The impact of MAGE-A3 expression on survival and proliferation in vivo was examined by immunohistochemical analysis in an independent set of tumor specimens segregated into two groups; newly diagnosed, untreated patients and patients who had relapsed after chemotherapy. The mechanisms of MAGE-A3 activity were investigated in vitro by silencing its expression by shRNA interference in myeloma cell lines and primary cells and assessing the resultant effects on proliferation and apoptosis. Results MAGE-A3 was detected in a significantly higher percentage of relapsed patients compared to newly diagnosed, establishing a novel correlation with progression of disease. Silencing of MAGE-A demonstrated that it was dispensable for cell cycling, but was required for survival of proliferating myeloma cells. Loss of MAGE-A led to apoptosis mediated by p53-dependent activation of pro-apoptotic Bax expression and by reduction of survivin expression through both p53-dependent and independent mechanisms. Conclusions These data support a role for MAGE-A in the pathogenesis and progression of multiple myeloma by inhibiting apoptosis in proliferating myeloma cells through two novel mechanisms. PMID:21565982

  11. Single mage gene in the chicken genome encodes CMage, a protein with functional similarities to mammalian type II Mage proteins.

    PubMed

    López-Sánchez, Noelia; González-Fernández, Zaira; Niinobe, Michio; Yoshikawa, Kazuaki; Frade, José María

    2007-07-18

    In mammals, the type II melanoma antigen (Mage) protein family is constituted by at least 10 closely related members that are expressed in different tissues, including the nervous system. These proteins are believed to regulate cell cycle withdrawal, neuronal differentiation, and apoptosis. However, the analysis of their specific function has been complicated by functional redundancy. In accordance with previous studies in teleosts and Drosophila, we present evidence that only one mage gene exists in genomes from protists, fungi, plants, nematodes, insects, and nonmammalian vertebrates. We have identified the chicken mage gene and cloned the cDNA encoding the chick Mage protein (CMage). CMage shares close homology with the type II Mage protein family, and, as previously shown for the type II Mage proteins Necdin and Mage-G1, it can interact with the transcription factor E2F-1. CMage is expressed in specific regions of the developing nervous system including the retinal ganglion cell layer, the ventral horn of the spinal cord, and the dorsal root ganglia, coinciding with the expression of the neurotrophin receptor p75 (p75(NTR)) in these regions. We show that the intracellular domain of p75(NTR) can interact with both CMage and Necdin, thus preventing the binding of the latter proteins to the transcription factor E2F-1, and facilitating the proapoptotic activity of E2F-1 in N1E-115 differentiating neurons. The presence of a single mage gene in the chicken genome, together with the close functional resemblance between CMage and Necdin, makes this species ideal to further analyze signal transduction through type II Mage proteins.

  12. Expression of MAGE--A restricted to testis and ovary or to various cancers in dogs.

    PubMed

    Chen, Yin-Chu; Hsu, Wei-Li; Chiu, Cheng-Yang; Liao, Jiunn-Wang; Chang, Chao-Chin; Chang, Shih-Chieh

    2013-05-15

    Expression of MAGE-A protein, a family of cancer/testis antigens, was investigated in normal and neoplastic canine tissues. Immunohistochemical analysis of cross-reactions between a mouse anti-human MAGE-A proteins including MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 monoclonal antibody and canine proteins, showed positive immunoreactivity only in testicular spermatogonia and spermatocytes, and ovary oocytes. The immunoreaction was negative in all other tissues tested, including normal tissues of the skin, gingiva, muscle, adipose, connective, salivary gland, lymph node, intestinal mucosa, mammary gland, liver, cartilage, oviduct, endometrium, cerebrum and cerebellum. Use of a scoring system in the investigated tumors showed positive immunoreactivity in 75% (21/28) of melanomas including oral, cutaneous, eyelid, and interdigital melanomas; in 68.7% (22/32) of oral and nasal tumors; in 52.5% (21/40) discrete round cell tumors; and in 40.5% (15/37) of soft tissue sarcomas. Different tumor types also showed large difference in percentage of MAGE-A expression. Although oral squamous cell carcinomas, multicentric lymphomas and extraosseous osteosarcomas showed no expression, overexpression occurred in oral melanomas (81.82%, 18/21), malignant nasal tumors (100%, 3/3) and in transmissible venereal tumors (100%, 10/10). Based on the characteristic expression of MAGE-A in canine germ cells and in various neoplasms, MAGE-A has potential use as an indicator of malignancy but is probably unsuitable for strictly diagnostic purposes (i.e., diagnosis of tumor type). Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Expression and clinical significance of MAGE and NY-ESO-1 cancer-testis antigens in adenoid cystic carcinoma of the head and neck.

    PubMed

    Veit, Johannes A; Heine, Daniela; Thierauf, Julia; Lennerz, Jochen; Shetty, Subasch; Schuler, Patrick J; Whiteside, Theresa; Beutner, Dirk; Meyer, Moritz; Grünewald, Inga; Ritter, Gerd; Gnjatic, Sacha; Sikora, Andrew G; Hoffmann, Thomas K; Laban, Simon

    2016-07-01

    Adenoid cystic carcinoma (ACC) of the head and neck is a rare but highly malignant tumor. Cancer-testis antigens (CTAs) represent an immunogenic family of cancer-specific proteins and thus represent an attractive target for immunotherapy. Eighty-four cases of ACC were identified, the CTAs pan-Melanoma antigen (pan-MAGE; M3H67) and New York esophageal squamous cell carcinoma (NY-ESO-1; E978) were detected immunohistochemically (IHC) and correlated with clinical data. Expression of NY-ESO-1 was found in 48 of 84 patients (57.1%) and of pan-MAGE in 28 of 84 patients (31.2%). Median overall survival (OS) in NY-ESO-1 positive versus negative patients was 130.8 and 282.0 months (p = .223), respectively. OS in pan-MAGE positive versus negative patients was 105.3 and 190.5 months, respectively (p = .096). Patients expressing both NY-ESO-1 and pan-MAGE simultaneously had significantly reduced OS with a median of 90.5 months compared with 282.0 months in negative patients (p = .047). A significant fraction of patients with ACC show expression of the CTAs NY-ESO-1 and/or pan-MAGE with promising immunotherapeutic implications. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1008-1016, 2016. © 2016 Wiley Periodicals, Inc.

  14. Importing MAGE-ML format microarray data into BioConductor.

    PubMed

    Durinck, Steffen; Allemeersch, Joke; Carey, Vincent J; Moreau, Yves; De Moor, Bart

    2004-12-12

    The microarray gene expression markup language (MAGE-ML) is a widely used XML (eXtensible Markup Language) standard for describing and exchanging information about microarray experiments. It can describe microarray designs, microarray experiment designs, gene expression data and data analysis results. We describe RMAGEML, a new Bioconductor package that provides a link between cDNA microarray data stored in MAGE-ML format and the Bioconductor framework for preprocessing, visualization and analysis of microarray experiments. http://www.bioconductor.org. Open Source.

  15. MAGE-A1 promotes melanoma proliferation and migration through C-JUN activation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Dong; The 309th Hospital of China People's Liberation Army, Beijing 100091; Wang, Junyun

    2016-05-13

    MAGE-A1 belongs to the chromosome X-clustered genes of cancer-testis antigen family and is normally expressed in the human germ line but is also overexpressed in various tumors. Previous studies of MAGE-A1 in melanoma mainly focused on methylation changes or its role in immunotherapy, however, its biological functions in melanoma have remained unknown. In order to determine the role of MAGE-A1 in melanoma growth and metastasis, we manipulated melanoma cell lines with overexpression and knockdown of MAGE-A1. Integration of cell proliferation assays, transwell migration and invasion assays, and RNA-Seq analysis revealed that up-regulation of MAGE-A1 dramatically promoted proliferation, migration, and invasionmore » of human melanoma cell lines in vitro, while down-regulation of MAGE-A1 inhibited those characteristics associated with tumor cells. Furthermore, transcriptome sequencing revealed that MAGE-A1 exerts its tumor promoting activity by activating p-C-JUN directly or through ERK-MAPK signaling pathways. Based on our findings, we propose that MAGE-A1 may be a potential therapeutic target for melanoma patients. - Highlights: • MAGE-A1 promotes proliferation and clone formation in melanoma cell lines. • MAGE-A1 enhances tumor cell migration and invasion in melanoma cell lines. • Network including C-JUN, IL8, and ARHGAP29 play critical role in malignant melanoma. • Oncogenic MAGE-A1 increases p-C-JUN levels, possibly via ERK-MAPK signaling pathway.« less

  16. Systems Genetic Analysis of Osteoblast-Lineage Cells

    PubMed Central

    Calabrese, Gina; Bennett, Brian J.; Orozco, Luz; Kang, Hyun M.; Eskin, Eleazar; Dombret, Carlos; De Backer, Olivier; Lusis, Aldons J.; Farber, Charles R.

    2012-01-01

    The osteoblast-lineage consists of cells at various stages of maturation that are essential for skeletal development, growth, and maintenance. Over the past decade, many of the signaling cascades that regulate this lineage have been elucidated; however, little is known of the networks that coordinate, modulate, and transmit these signals. Here, we identify a gene network specific to the osteoblast-lineage through the reconstruction of a bone co-expression network using microarray profiles collected on 96 Hybrid Mouse Diversity Panel (HMDP) inbred strains. Of the 21 modules that comprised the bone network, module 9 (M9) contained genes that were highly correlated with prototypical osteoblast maker genes and were more highly expressed in osteoblasts relative to other bone cells. In addition, the M9 contained many of the key genes that define the osteoblast-lineage, which together suggested that it was specific to this lineage. To use the M9 to identify novel osteoblast genes and highlight its biological relevance, we knocked-down the expression of its two most connected “hub” genes, Maged1 and Pard6g. Their perturbation altered both osteoblast proliferation and differentiation. Furthermore, we demonstrated the mice deficient in Maged1 had decreased bone mineral density (BMD). It was also discovered that a local expression quantitative trait locus (eQTL) regulating the Wnt signaling antagonist Sfrp1 was a key driver of the M9. We also show that the M9 is associated with BMD in the HMDP and is enriched for genes implicated in the regulation of human BMD through genome-wide association studies. In conclusion, we have identified a physiologically relevant gene network and used it to discover novel genes and regulatory mechanisms involved in the function of osteoblast-lineage cells. Our results highlight the power of harnessing natural genetic variation to generate co-expression networks that can be used to gain insight into the function of specific cell-types. PMID:23300464

  17. Uptake routes of tumor-antigen MAGE-A3 by dendritic cells determine priming of naïve T-cell subtypes.

    PubMed

    Moeller, Ines; Spagnoli, Giulio C; Finke, Jürgen; Veelken, Hendrik; Houet, Leonora

    2012-11-01

    Induction of tumor-antigen-specific T cells in active cancer immunotherapy is generally difficult due to the very low anti-tumoral precursor cytotoxic T cells. By improving tumor-antigen uptake and presentation by dendritic cells (DCs), this problem can be overcome. Focusing on MAGE-A3 protein, frequently expressed in many types of tumors, we analyzed different DC-uptake routes after additional coating the recombinant MAGE-A3 protein with either a specific monoclonal antibody or an immune complex formulation. Opsonization of the protein with antibody resulted in increased DC-uptake compared to the uncoated rhMAGE-A3 protein. This was partly due to Fcγ receptor-dependent internalization. However, unspecific antigen internalization via macropinocytosis also played a role. When analyzing DC-uptake of MAGE-A3 antigen expressed in multiple myeloma cell line U266, pretreatment with proteasome inhibitor bortezomib resulted in increased apoptosis compared to γ-irradiation. Bortezomib-mediated immunogenic apoptosis, characterized by elevated surface expression of hsp90, triggered higher phagocytosis of U266 cells by DCs involving specific DC-derived receptors. We further investigated the impact of antigen delivery on T-cell priming. Induction of CD8(+) T-cell response was favored by stimulating naïve T cells with either antibody-opsonized MAGE-A3 protein or with the bortezomib-pretreated U266 cells, indicating that receptor-mediated uptake favors cross-presentation of antigens. In contrast, CD4(+) T cells were preferentially induced after stimulation with the uncoated protein or protein in the immune complex, both antigen formulations were preferentially internalized by DCs via macropinocytosis. In summary, receptor-mediated DC-uptake mechanisms favored the induction of CD8(+) T cells, relevant for clinical anti-tumor response.

  18. Cellular immune responses against CT7 (MAGE-C1) and humoral responses against other cancer-testis antigens in multiple myeloma patients

    PubMed Central

    Lendvai, Nikoletta; Gnjatic, Sacha; Ritter, Erika; Mangone, Michael; Austin, Wayne; Reyner, Karina; Jayabalan, David; Niesvizky, Ruben; Jagannath, Sundar; Bhardwaj, Nina; Chen-Kiang, Selina; Old, Lloyd J.

    2010-01-01

    The type I melanoma antigen gene (MAGE) proteins CT7 (MAGE-C1) and MAGE-A3 are commonly expressed in multiple myeloma (MM), and their expression correlates with increased plasma cell proliferation and poor clinical outcome. They belong to the cancer-testis antigen (CTAg) group of tumor-associated proteins, some of which elicit spontaneous immune responses in cancer patients. CT7 and MAGE-A3 are promising antigenic targets for therapeutic tumor vaccines in myeloma; therefore, it is critical to determine if they are immunogenic in MM patients. We analyzed cellular and humoral immune responses against CTAgs in patients with plasma cell dyscrasias: MM, monoclonal gammopathy of undetermined significance (MGUS), and Waldenström's macroglobulinemia (WM). Bone marrow lymphocytes from two of four untreated MM patients exhibited CT7-specific cellular immune responses as measured by an autologous cellular immunity assay, the first such immune response to CT7 to be reported in cancer patients. Sera from 24 patients were screened by ELISA for humoral immune responses to CTAgs. Two patients with MM demonstrated positive titers, one for MAGE-A1 and the other for SSX1. These data demonstrate that CTAgs, particularly CT7, are immunogenic in MM patients and merit further exploration as targets of immunological therapy in MM. PMID:20108890

  19. Cellular immune responses against CT7 (MAGE-C1) and humoral responses against other cancer-testis antigens in multiple myeloma patients.

    PubMed

    Lendvai, Nikoletta; Gnjatic, Sacha; Ritter, Erika; Mangone, Michael; Austin, Wayne; Reyner, Karina; Jayabalan, David; Niesvizky, Ruben; Jagannath, Sundar; Bhardwaj, Nina; Chen-Kiang, Selina; Old, Lloyd J; Cho, Hearn Jay

    2010-01-29

    The type I melanoma antigen gene (MAGE) proteins CT7 (MAGE-C1) and MAGE-A3 are commonly expressed in multiple myeloma (MM), and their expression correlates with increased plasma cell proliferation and poor clinical outcome. They belong to the cancer-testis antigen (CTAg) group of tumor-associated proteins, some of which elicit spontaneous immune responses in cancer patients. CT7 and MAGE-A3 are promising antigenic targets for therapeutic tumor vaccines in myeloma; therefore, it is critical to determine if they are immunogenic in MM patients. We analyzed cellular and humoral immune responses against CTAgs in patients with plasma cell dyscrasias: MM, monoclonal gammopathy of undetermined significance (MGUS), and Waldenström's macroglobulinemia (WM). Bone marrow lymphocytes from two of four untreated MM patients exhibited CT7-specific cellular immune responses as measured by an autologous cellular immunity assay, the first such immune response to CT7 to be reported in cancer patients. Sera from 24 patients were screened by ELISA for humoral immune responses to CTAgs. Two patients with MM demonstrated positive titers, one for MAGE-A1 and the other for SSX1. These data demonstrate that CTAgs, particularly CT7, are immunogenic in MM patients and merit further exploration as targets of immunological therapy in MM.

  20. The antitumor immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70/SEA complex protein vaccine following different administration routes.

    PubMed

    Ge, Wei; Hu, Pei-Zhen; Huang, Yang; Wang, Xiao-Ming; Zhang, Xiu-Min; Sun, Yu-Jing; Li, Zeng-Shan; Si, Shao-Yan; Sui, Yan-Fang

    2009-10-01

    Our previous study showed that nanoemulsion-encapsulated MAGE1-HSP70/SEA (MHS) complex protein vaccine elicited MAGE-1 specific immune response and antitumor effects against MAGE-1-expressing tumor and nanoemulsion is a useful vehicle with possible important implications for cancer biotherapy. The purpose of this study was to compare the immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70 and SEA as NE(MHS) vaccine following different administration routes and to find out the new and effective immune routes. Nanoemulsion vaccine was prepared using magnetic ultrasound methods. C57BL/6 mice were immunized with NE(MHS) via po., i.v., s.c. or i.p., besides mice s.c. injected with PBS or NE(-) as control. The cellular immunocompetence was detected by ELISpot assay and LDH release assay. The therapeutic and tumor challenge assay were also examined. The results showed that the immune responses against MAGE-1 expressing murine tumors elicited by NE(MHS) via 4 different routes were approximately similar and were all stronger than that elicited by PBS or NE(-), suggesting that this novel nanoemulsion carrier can exert potent antitumor immunity against antigens encapsulated in it. Especially, the present results indicated that nanoemulsion vaccine adapted to administration via different routes including peroral, and may have broader applications in the future.

  1. Gain in Transcriptional Activity by Primate-specific Coevolution of Melanoma Antigen-A11 and Its Interaction Site in Androgen Receptor*

    PubMed Central

    Liu, Qiang; Su, Shifeng; Blackwelder, Amanda J.; Minges, John T.; Wilson, Elizabeth M.

    2011-01-01

    Male sex development and growth occur in response to high affinity androgen binding to the androgen receptor (AR). In contrast to complete amino acid sequence conservation in the AR DNA and ligand binding domains among mammals, a primate-specific difference in the AR NH2-terminal region that regulates the NH2- and carboxyl-terminal (N/C) interaction enables direct binding to melanoma antigen-A11 (MAGE-11), an AR coregulator that is also primate-specific. Human, mouse, and rat AR share the same NH2-terminal 23FQNLF27 sequence that mediates the androgen-dependent N/C interaction. However, the mouse and rat AR FXXLF motif is flanked by Ala33 that evolved to Val33 in primates. Human AR Val33 was required to interact directly with MAGE-11 and for the inhibitory effect of the AR N/C interaction on activation function 2 that was relieved by MAGE-11. The functional importance of MAGE-11 was indicated by decreased human AR regulation of an androgen-dependent endogenous gene using lentivirus short hairpin RNAs and by the greater transcriptional strength of human compared with mouse AR. MAGE-11 increased progesterone and glucocorticoid receptor activity independently of binding an FXXLF motif by interacting with p300 and p160 coactivators. We conclude that the coevolution of the AR NH2-terminal sequence and MAGE-11 expression among primates provides increased regulatory control over activation domain dominance. Primate-specific expression of MAGE-11 results in greater steroid receptor transcriptional activity through direct interactions with the human AR FXXLF motif region and indirectly through steroid receptor-associated p300 and p160 coactivators. PMID:21730049

  2. CD8+ TIL recruitment may revert the association of MAGE A3 with aggressive features in thyroid tumors.

    PubMed

    Martins, Mariana Bonjiorno; Marcello, Marjory Alana; Batista, Fernando de Assis; Cunha, Lucas Leite; Morari, Elaine Cristina; Soares, Fernando Augusto; Vassallo, José; Ward, Laura Sterian

    2014-01-01

    We aimed to investigate a possible role of MAGE A3 and its associations with infiltrated immune cells in thyroid malignancy, analyzing their utility as a diagnostic and prognostic marker. We studied 195 malignant tissues: 154 PTCs and 41 FTCs; 102 benign tissues: 51 follicular adenomas and 51 goiter and 17 normal thyroid tissues. MAGE A3 and immune cell markers (CD4 and CD8) were evaluated using immunohistochemistry and compared with clinical pathological features. The semiquantitative analysis and ACIS III analysis showed similar results. MAGE A3 was expressed in more malignant than in benign lesions (P < 0.0001), also helping to discriminate follicular-patterned lesions. It was also higher in tumors in which there was extrathyroidal invasion (P = 0.0206) and in patients with stage II disease (P = 0.0107). MAGE A3+ tumors were more likely to present CD8+ TIL (P = 0.0346), and these tumors were associated with less aggressive features, that is, extrathyroidal invasion and small size. There was a trend of MAGE A3+ CD8+ tumors to evolve free of disease. We demonstrated that MAGE A3 and CD8+ TIL infiltration may play an important role in malignant thyroid nodules, presenting an interesting perspective for new researches on DTC immunotherapy.

  3. RDFBuilder: a tool to automatically build RDF-based interfaces for MAGE-OM microarray data sources.

    PubMed

    Anguita, Alberto; Martin, Luis; Garcia-Remesal, Miguel; Maojo, Victor

    2013-07-01

    This paper presents RDFBuilder, a tool that enables RDF-based access to MAGE-ML-compliant microarray databases. We have developed a system that automatically transforms the MAGE-OM model and microarray data stored in the ArrayExpress database into RDF format. Additionally, the system automatically enables a SPARQL endpoint. This allows users to execute SPARQL queries for retrieving microarray data, either from specific experiments or from more than one experiment at a time. Our system optimizes response times by caching and reusing information from previous queries. In this paper, we describe our methods for achieving this transformation. We show that our approach is complementary to other existing initiatives, such as Bio2RDF, for accessing and retrieving data from the ArrayExpress database. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. The role of pleural fluid MAGE RT-nested PCR in the diagnosis of malignant pleural effusion.

    PubMed

    Jeon, Eun Ju; Park, Hye Kyeong; Jeon, Kyeongman; Koh, Won-Jung; Suh, Gee Young; Chung, Man Pyo; Kim, Hojoong; Kwon, O Jung; Ki, Chang-Seok; Kim, Jong-Won; Shim, Young Mog; Um, Sang-Won

    2012-11-01

      Melanoma antigen (MAGE) genes are expressed in tumor cells, the testis and the placenta. The purpose of this prospective study was to investigate the sensitivity, specificity, and accuracy of the carcinoembryonic antigen (CEA), MAGE reverse transcriptase-nested polymerase chain reaction (RT-nested PCR), and cytology of pleural fluid in the diagnosis of malignant pleural effusion.   Patients in whom unilateral pleural effusion was identified on chest radiography from January to December 2009 were included in the study. MAGE genes were analyzed by RT-nested PCR using MAGE A1-6 common primers.   Of 81 enrolled patients, 46 were diagnosed as malignant pleural effusion, and 24 were diagnosed as benign pleural effusion. The diagnoses of 11 patients were not confirmed in this study. The diagnostic sensitivity, specificity, and accuracy of MAGE RT-nested PCR were 61.4%, 95.7%, and 73.1%, respectively. The diagnostic sensitivities of cytology and CEA (>5 ng/mL) were 61.4% and 75.0%, respectively. Among 17 patients with negative cytology who had malignant pleural effusion, 12 and 10 patients were positive for CEA (>5.0 ng/mL) and MAGE RT-nested PCR, respectively. However, of five patients with malignant pleural effusion that was not recognized by cytology and CEA, MAGE RT-nested PCR correctly predicted a malignant etiology in only one additional patient (20%).   MAGE RT-nested PCR seems to add little on the combination of conventional methods in the diagnosis of malignant effusion. © 2012 Tianjin Lung Cancer Institute and Wiley Publishing Asia Pty. Ltd.

  5. Intratumoral Heterogeneity of MAGE-C1/CT7 and MAGE-C2/CT10 Expression in Mucosal Melanoma.

    PubMed

    Curioni-Fontecedro, A; Pitocco, R; Schoenewolf, N L; Holzmann, D; Soldini, D; Dummer, R; Calvieri, S; Moch, H; Mihic-Probst, D; Fitsche, A

    2015-01-01

    Mucosal melanoma is a rare disease, which differs from its cutaneous counterpart genetically and for its clinical behaviour. Moreover this is a heterogeneous disease based on the tissue of origin. As CT7 and CT10 are highly expressed in cutaneous melanoma and are immunogenic in this disease, we analysed their expression throughout the different subtypes of mucosal melanoma and tumor development. We detected a frequent expression of CT7 in primaries and corresponding metastases (55%) as well as for CT10 (30%). This expression resulted to be heterogeneous in the same tumor specimen and moreover influenced by the tissue of origin. Our results support the role of these antigens in immunotherapy for mucosal melanoma.

  6. Intratumoral Heterogeneity of MAGE-C1/CT7 and MAGE-C2/CT10 Expression in Mucosal Melanoma

    PubMed Central

    Curioni-Fontecedro, A.; Pitocco, R.; Schoenewolf, N. L.; Holzmann, D.; Soldini, D.; Dummer, R.; Calvieri, S.; Moch, H.; Mihic-Probst, D.; Fitsche, A.

    2015-01-01

    Mucosal melanoma is a rare disease, which differs from its cutaneous counterpart genetically and for its clinical behaviour. Moreover this is a heterogeneous disease based on the tissue of origin. As CT7 and CT10 are highly expressed in cutaneous melanoma and are immunogenic in this disease, we analysed their expression throughout the different subtypes of mucosal melanoma and tumor development. We detected a frequent expression of CT7 in primaries and corresponding metastases (55%) as well as for CT10 (30%). This expression resulted to be heterogeneous in the same tumor specimen and moreover influenced by the tissue of origin. Our results support the role of these antigens in immunotherapy for mucosal melanoma. PMID:26161400

  7. Exposure to Violence during Adolescence as a Predictor of Perceived Stress Trajectories in Emerging Adulthood

    PubMed Central

    Heinze, Justin E.; Stoddard, Sarah A.; Aiyer, Sophie M.; Eisman, Andria B.; Zimmerman, Marc A.

    2017-01-01

    Early exposure to violence during adolescence is related to negative psycho-social outcomes later in life. In the present study, we examined the influence of cumulative exposure to violence during adolescence and trajectories of perceived stress in emerging adulthood in a sample of at-risk urban youth (N = 850; 80.1% African American; 50% female). Growth curve modeling indicated an overall decrease in reported stress as individuals aged. Baseline levels of violence exposure (Mage = 14.9) were associated with higher perceived stress levels in emerging adulthood (Mage = 20.1), but also slightly more negative perceived stress slopes from adolescence into emerging adulthood (Mage = 15.9–22.1). Individuals reporting increased violence exposure over time during adolescence also reported higher perceived stress levels in emerging adulthood (Mage = 20.1). Associations held after controlling for demographics and baseline functioning variables. The results suggest that violence exposure may disrupt normative adaptation to daily stressors in emerging adulthood. PMID:28966425

  8. Predictive and prognostic effect of CD133 and cancer-testis antigens in stage Ib-IIIA non-small cell lung cancer.

    PubMed

    Su, Chunxia; Xu, Ying; Li, Xuefei; Ren, Shengxiang; Zhao, Chao; Hou, Likun; Ye, Zhiwei; Zhou, Caicun

    2015-01-01

    CD133 and cancer-testis antigens (CTAs) may be potential predicted markers of adjuvant chemotherapy or immune therapy, and they may be the independent prognostic factor of NSCLC. Nowadays, there is still no predictive biomarker identified for the use of adjuvant chemotherapy in non-small cell lung cancer (NSCLC) patients. To clarify the role of CD133 and CTAs as a predictive marker for adjuvant chemotherapy or prognostic factors of overall survival, we performed a retrospective study in 159 stage Ib-IIIA NSCLC patients receiving adjuvant chemotherapy or observe from April 2003 to March 2004 in our institute. Clinical data and gene anaylisis results were collected, while CD133 and three CTAs (MAGE-A4, NY-ESO-1, MAGE-A10) were determined according to their monoclonal antibodies such as CD133, 57B, D8.38 and 3GA11 by immunohistochemistry. All CTAs were more frequently expressed in squamous cell carcinoma (SCC) (50.0%, 26.9%, 34.6%) than in adenocarcinoma (16.2%, 16.2%, 16.2%). CD133 was more frequently found in patients with adenocarcinoma (P=0.044). Negative expression of CD133 was associated with a significantly longer overall survival compared to positive expression of CD133 (62.5 vs. 48.5 months, P=0.035). When combined with MAGEA4, NY-ESO-1or MAGE-A10, patients' OS showed significantly difference among different combination. (CD133-MAGEA4-/CD133-MAGEA4+/CD133+MAGEA4-/CD133+MAGEA4+: 65.6 months vs.51.5 months vs.32.2 months vs.19.8 months, P=0.000, CD133-NY-ESO-1-/ CD133+NY-ESO-1-/CD133-NY-ESO-1+/ CD133+NY-ESO-1+: 57.8 months vs. 55.7 months vs. 44.6 months vs. 28.5 months, P=0.000, CD133-MAGEA10-/CD133+ MAGEA10-/CD133-MAGEA10-/CD133+MAGEA10+: 66.2 months vs. 57.2 months vs. 48.8 months vs. 41.4 months, P=0.001). There is no difference between patients received adjuvant chemotherapy or not, but subgroup analysis showed that the patients with CD133+NY-ESO-1+ expression who received chemotherapy will survive longer than not receive adjuvant chemotherapy (received vs. not received, 52.1 vs. 27.1 months, P=0.020). In the subgroup with EGFR mutation/ALK translocation/Ros1 translocation/Ret fusion, the trend remained but without a statistically significant difference. Multivariate COX regression analysis showed that stage, CD133, CD133-MAGEA4- and CD133-NY-ESO-1- are independent prognostic factors. In conclusion, CTAs (MAGE-A4, NY-ESO-1, MAGE-A10) were more likely expressed in patients with squamous cell carcinoma and when CTAs combined with CD133, they can be better prognostic factors. Patients with CD133+NY-ESO-1+ expression may survive longer when treated with adjuvant chemotherapy, which indicates that the CD133 and CTAs might be a potential marker to guide adjuvant chemotherapy in this population.

  9. Prospective assessment of a gene signature potentially predictive of clinical benefit in metastatic melanoma patients following MAGE-A3 immunotherapeutic (PREDICT).

    PubMed

    Saiag, P; Gutzmer, R; Ascierto, P A; Maio, M; Grob, J-J; Murawa, P; Dreno, B; Ross, M; Weber, J; Hauschild, A; Rutkowski, P; Testori, A; Levchenko, E; Enk, A; Misery, L; Vanden Abeele, C; Vojtek, I; Peeters, O; Brichard, V G; Therasse, P

    2016-10-01

    Genomic profiling of tumor tissue may aid in identifying predictive or prognostic gene signatures (GS) in some cancers. Retrospective gene expression profiling of melanoma and non-small-cell lung cancer led to the characterization of a GS associated with clinical benefit, including improved overall survival (OS), following immunization with the MAGE-A3 immunotherapeutic. The goal of the present study was to prospectively evaluate the predictive value of the previously characterized GS. An open-label prospective phase II trial ('PREDICT') in patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma. Of 123 subjects who received the MAGE-A3 immunotherapeutic, 71 (58.7%) displayed the predictive GS (GS+). The 1-year OS rate was 83.1%/83.3% in the GS+/GS- populations. The rate of progression-free survival at 12 months was 5.8%/4.1% in GS+/GS- patients. The median time-to-treatment failure was 2.7/2.4 months (GS+/GS-). There was one complete response (GS-) and two partial responses (GS+). The MAGE-A3 immunotherapeutic was similarly immunogenic in both populations and had a clinically acceptable safety profile. Treatment of patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma with the MAGE-A3 immunotherapeutic demonstrated an overall 1-year OS rate of 83.5%. GS- and GS+ patients had similar 1-year OS rates, indicating that in this study, GS was not predictive of outcome. Unexpectedly, the objective response rate was lower in this study than in other studies carried out in the same setting with the MAGE-A3 immunotherapeutic. Investigation of a GS to predict clinical benefit to adjuvant MAGE-A3 immunotherapeutic treatment is ongoing in another melanoma study.This study is registered at www.clinicatrials.gov NCT00942162. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

  10. MODEST: a web-based design tool for oligonucleotide-mediated genome engineering and recombineering

    PubMed Central

    Bonde, Mads T.; Klausen, Michael S.; Anderson, Mads V.; Wallin, Annika I.N.; Wang, Harris H.; Sommer, Morten O.A.

    2014-01-01

    Recombineering and multiplex automated genome engineering (MAGE) offer the possibility to rapidly modify multiple genomic or plasmid sites at high efficiencies. This enables efficient creation of genetic variants including both single mutants with specifically targeted modifications as well as combinatorial cell libraries. Manual design of oligonucleotides for these approaches can be tedious, time-consuming, and may not be practical for larger projects targeting many genomic sites. At present, the change from a desired phenotype (e.g. altered expression of a specific protein) to a designed MAGE oligo, which confers the corresponding genetic change, is performed manually. To address these challenges, we have developed the MAGE Oligo Design Tool (MODEST). This web-based tool allows designing of MAGE oligos for (i) tuning translation rates by modifying the ribosomal binding site, (ii) generating translational gene knockouts and (iii) introducing other coding or non-coding mutations, including amino acid substitutions, insertions, deletions and point mutations. The tool automatically designs oligos based on desired genotypic or phenotypic changes defined by the user, which can be used for high efficiency recombineering and MAGE. MODEST is available for free and is open to all users at http://modest.biosustain.dtu.dk. PMID:24838561

  11. Combination of PDT and a DNA demethylating agent produces anti-tumor immune response in a mouse tumor model

    NASA Astrophysics Data System (ADS)

    Mroz, Pawel; Hamblin, Michael R.

    2009-06-01

    Epigenetic mechanisms, which involve DNA methylation and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. However, these changes must be actively maintained after each cell division rendering them a promising target for pharmacologic inhibition. DNA methyltransferase inhibitors like 5-aza-deoxycytidine (5-aza-dC) induce and/or up-regulate the expression of MAGE-type antigens in human and mice cancer cells. Photodynamic therapy (PDT) has been shown to be an effective locally ablative anti-cancer treatment that has the additional advantage of stimulating tumor-directed immune response. We studied the effects of a new therapy that combined the demethylating agent 5-aza-dC with PDT in the breast cancer model 4T1 syngenic to immunocompetent BALB/c mice. PDT was used as a locally ablating tumor treatment that is capable of eliciting strong and tumor directed immune response while 5-aza-dC pretreatment was used promote de novo induction of the expression of P1A.protein. This is the mouse homolog of human MAGE family antigens and is reported to function as a tumor rejection antigen in certain mouse tumors. This strategy led to an increase in PDT-mediated immune response and better treatment outcome. These results strongly suggest that the MAGE family antigens are important target for PDT mediated immune response but that their expression can be silenced by epigenetic mechanisms. Therefore the possibility that PDT can be combined with epigenetic strategies to elicit anti-tumor immunity in MAGE-positive tumor models is highly clinically significant and should be studied in detail.

  12. Family factors that characterize adolescents with severe obesity and their role in weight loss surgery outcomes

    PubMed Central

    Zeller, Meg H.; Hunsaker, Sanita; Mikhail, Carmen; Reiter-Purtill, Jennifer; McCullough, Mary Beth; Garland, Beth; Austin, Heather; Washington, Gia; Baughcum, Amy; Rofey, Dana; Smith, Kevin

    2016-01-01

    Objective To comprehensively assess family characteristics of adolescents with severe obesity and whether family factors impact weight loss outcomes following weight loss surgery (WLS). Methods Multi-site prospective data from 138 adolescents undergoing WLS and primary caregivers (Adolescent Mage=16.9; MBMI= 51.5 kg/m2; Caregiver: Mage=44.5; 93% female) and 83 non-surgical comparators (NSComp: Adolescent: Mage=16.1; MBMI= 46.9 kg/m2; Caregiver: Mage=43.9; 94% female) were collected using standardized measures at pre-surgery/baseline, 1- and 2-years. Results The majority (77.3%) of caregivers were obese, with rates of caregiver WLS significantly higher in the WLS (23.8%) versus NSComp group (3.7%, p<.001). Family dysfunction was prevalent (≈1 in every 2–3 families), with rates higher for NSComp than the WLS group. For the WLS group, pre-operative family factors (i.e., caregiver BMI or WLS history, dysfunction, social support) were not significant predictors of adolescent weight loss at 1- and 2-years post-operatively, although change in family functioning over time emerged as a significant correlate of percent weight loss. Conclusions Rates of severe obesity in caregivers as well as family dysfunction were clinically noteworthy, although not related to adolescent weight loss success following WLS. However, change in family communication and emotional climate over time emerged as potential targets to optimize weight loss outcomes. PMID:27753228

  13. Applying new Magee equations for predicting the Oncotype Dx recurrence score.

    PubMed

    Sughayer, Maher; Alaaraj, Rolla; Alsughayer, Ahmad

    2018-04-24

    Breast cancer is one of the most prevalent cancers in women. Oncotype Dx is a multi-gene assay frequently used to predict the recurrence risk for estrogen receptor-positive early breast cancer, with values < 18 considered low risk; ≥ 18 and ≤ 30, intermediate risk; and > 30, high risk. Patients at a high risk for recurrence are more likely to benefit from chemotherapy treatment. In this study, clinicopathological parameters for 37 cases of early breast cancer with available Oncotype Dx results were used to estimate the recurrence score using the three new Magee equations. Correlation studies with Oncotype Dx results were performed. Applying the same cutoff points as Oncotype Dx, patients were categorized into low-, intermediate- and high-risk groups according to their estimated recurrence scores. Pearson correlation coefficient (R) values between estimated and actual recurrence score were 0.73, 0.66, and 0.70 for Magee equations 1, 2 and 3, respectively. The concordance values between actual and estimated recurrence scores were 57.6%, 52.9%, and 57.6% for Magee equations 1, 2 and 3, respectively. Using standard pathologic measures and immunohistochemistry scores in these three linear Magee equations, most low and high recurrence risk cases can be predicted with a strong positive correlation coefficient, high concordance and negligible two-step discordance. Magee equations are user-friendly and can be used to predict the recurrence score in early breast cancer cases.

  14. Methionine Deprivation Induces a Targetable Vulnerability in Triple-negative Breast Cancer Cells by Enhancing TRAIL Receptor-2 Expression

    PubMed Central

    Strekalova, Elena; Malin, Dmitry; Good, David M.; Cryns, Vincent L.

    2015-01-01

    Purpose Many neoplasms are vulnerable to methionine deficiency by mechanisms that are poorly understood. Because gene profiling studies have revealed that methionine depletion increases TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) mRNA, we postulated that methionine stress sensitizes breast cancer cells to proapoptotic TRAIL-R2 agonists. Experimental Design Human triple (ER/PR/HER2)-negative breast carcinoma cell lines were cultured in control or methionine-free media. The effects of methionine depletion on TRAIL receptor expression and sensitivity to chemotherapy or a humanized agonistic TRAIL-R2 monoclonal antibody (lexatumumab) were determined. The melanoma-associated antigen MAGED2 was silenced to delineate its functional role in sensitizing TNBC cells to methionine stress. An orthotopic TNBC model was utilized to evaluate the effects of dietary methionine deficiency, lexatumumab or the combination. Results Methionine depletion sensitized TNBC cells to lexatumumab-induced caspase activation and apoptosis by increasing TRAIL-R2 mRNA and cell surface expression. MCF-10A cells transformed by oncogenic H-Ras, but not untransformed cells, and matrix-detached TNBC cells were highly sensitive to the combination of lexatumumab and methionine depletion. Proteomics analyses revealed that MAGED2, which has been reported to reduce TRAIL-R2 expression, was suppressed by methionine stress. Silencing MAGED2 recapitulated features of methionine deprivation, including enhanced mRNA and cell surface expression of TRAIL receptors and increased sensitivity to TRAIL receptor agonists. Dietary methionine deprivation enhanced the antitumor effects of lexatumumab in an orthotopic metastatic TNBC model. Conclusion Methionine depletion exposes a targetable defect in TNBC cells by increasing TRAIL-R2 expression. Our findings provide the foundation for a clinical trial combining dietary methionine restriction and TRAIL-R2 agonists. PMID:25724522

  15. Admission glycemic variability correlates with in-hospital outcomes in diabetic patients with non-ST segment elevation acute coronary syndrome undergoing percutaneous coronary intervention

    PubMed Central

    Su, Gong; Zhang, Tao; Yang, Hongxia; Dai, Wenlong; Tian, Lei; Tao, Hong; Wang, Tao; Mi, Shuhua

    2018-01-01

    Objective The aim of this study is to evaluate the effects of admission glycemic variability (AGV) on in-hospital outcomes in diabetic patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). Methods We studied 759 diabetic patients with NSTE-ACS undergoing PCI. AGV was accessed based on the mean amplitude of glycemic excursions (MAGEs) in the first 24 hours after admission. Primary outcome was a composite of in-hospital events, all-cause mortality, new-onset myocardial infarction, acute heart failure, and stroke. Secondary outcomes were each of these considered separately. Predictive effects of AGV on the in-hospital outcomes in patients were analyzed. Results Patients with high MAGE levels had significantly higher incidence of total outcomes (9.9% vs. 4.8%, p=0.009) and all-cause mortality (2.3% vs. 0.4%, p=0.023) than those with low MAGE levels during hospitalization. Multivariable analysis revealed that AGV was significantly associated with incidence of in-hospital outcomes (Odds ratio=2.024, 95% CI 1.105-3.704, p=0.022) but hemoglobin A1c (HbA1c) was not. In the receiver-operating characteristic curve analysis for MAGE and HbA1c in predicting in-hospital outcomes, the area under the curve for MAGE (0.608, p=0.012) was superior to that for HbA1c (0.556, p=0.193). Conclusion High AGV levels may be closely correlated with increased in-hospital poor outcomes in diabetic patients with NSTE-ACS following PCI. PMID:29848920

  16. Emergent Rules for Codon Choice Elucidated by Editing Rare Arginine Codons in Escherichia coli

    DTIC Science & Technology

    2016-09-20

    alternative codons are more likely to be viable. To evaluate synonymous and nonsynonymous alternatives to essential AGRs further, we imple- mented a CRISPR ... Crispr -assisted MAGE). First, we designed oligos that changed not only the target AGR codon to NNN but also made several synonymous changes at least 50...nt downstream that would disrupt a 20-bp CRISPR target lo- cus. MAGE was used to replace each AGR with NNN in parallel, and CRISPR /cas9 was used to

  17. Up-Regulation of Follistatin-Like 1 By the Androgen Receptor and Melanoma Antigen-A11 in Prostate Cancer.

    PubMed

    Su, Shifeng; Parris, Amanda B; Grossman, Gail; Mohler, James L; Wang, Zengjun; Wilson, Elizabeth M

    2017-04-01

    High affinity androgen binding to the androgen receptor (AR) activates genes required for male sex differentiation and promotes the development and progression of prostate cancer. Human AR transcriptional activity involves interactions with coregulatory proteins that include primate-specific melanoma antigen-A11 (MAGE-A11), a coactivator that increases AR transcriptional activity during prostate cancer progression to castration-resistant/recurrent prostate cancer (CRPC). Microarray analysis and quantitative RT-PCR were performed to identify androgen-regulated MAGE-A11-dependent genes in LAPC-4 prostate cancer cells after lentivirus shRNA knockdown of MAGE-A11. Chromatin immunoprecipitation was used to assess androgen-dependent AR recruitment, and immunocytochemistry to localize an androgen-dependent protein in prostate cancer cells and tissue and in the CWR22 human prostate cancer xenograft. Microarray analysis of androgen-treated LAPC-4 prostate cancer cells indicated follistatin-like 1 (FSTL1) is up-regulated by MAGE-A11. Androgen-dependent up-regulation of FSTL1 was inhibited in LAPC-4 cells by lentivirus shRNA knockdown of AR or MAGE-A11. Chromatin immunoprecipitation demonstrated AR recruitment to intron 10 of the FSTL1 gene that contains a classical consensus androgen response element. Increased levels of FSTL1 protein in LAPC-4 cells correlated with higher levels of MAGE-A11 relative to other prostate cancer cells. FSTL1 mRNA levels increased in CRPC and castration-recurrent CWR22 xenografts in association with predominantly nuclear FSTL1. Increased nuclear localization of FSTL1 in prostate cancer was suggested by predominantly cytoplasmic FSTL1 in benign prostate epithelial cells and predominantly nuclear FSTL1 in epithelial cells in CRPC tissue and the castration-recurrent CWR22 xenograft. AR expression studies showed nuclear colocalization of AR and endogenous FSTL1 in response to androgen. AR and MAGE-A11 cooperate in the up-regulation of FSTL1 to promote growth and progression of CRPC. Prostate 77:505-516, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. The XBabelPhish MAGE-ML and XML translator.

    PubMed

    Maier, Don; Wymore, Farrell; Sherlock, Gavin; Ball, Catherine A

    2008-01-18

    MAGE-ML has been promoted as a standard format for describing microarray experiments and the data they produce. Two characteristics of the MAGE-ML format compromise its use as a universal standard: First, MAGE-ML files are exceptionally large - too large to be easily read by most people, and often too large to be read by most software programs. Second, the MAGE-ML standard permits many ways of representing the same information. As a result, different producers of MAGE-ML create different documents describing the same experiment and its data. Recognizing all the variants is an unwieldy software engineering task, resulting in software packages that can read and process MAGE-ML from some, but not all producers. This Tower of MAGE-ML Babel bars the unencumbered exchange of microarray experiment descriptions couched in MAGE-ML. We have developed XBabelPhish - an XQuery-based technology for translating one MAGE-ML variant into another. XBabelPhish's use is not restricted to translating MAGE-ML documents. It can transform XML files independent of their DTD, XML schema, or semantic content. Moreover, it is designed to work on very large (> 200 Mb.) files, which are common in the world of MAGE-ML. XBabelPhish provides a way to inter-translate MAGE-ML variants for improved interchange of microarray experiment information. More generally, it can be used to transform most XML files, including very large ones that exceed the capacity of most XML tools.

  19. Transcriptome analysis to identify genes for peptides and proteins involved in immunity and reproduction from male accessory glands and ejaculatory duct of Bactrocera dorsalis.

    PubMed

    Wei, Dong; Tian, Chuan-Bei; Liu, Shi-Huo; Wang, Tao; Smagghe, Guy; Jia, Fu-Xian; Dou, Wei; Wang, Jin-Jun

    2016-06-01

    In the male reproductive system of insects, the male accessory glands and ejaculatory duct (MAG/ED) are important organs and their primary function is to enhance the fertility of spermatozoa. Proteins secreted by the MAG/ED are also known to induce post-mating changes and immunity responses in the female insect. To understand the gene expression profile in the MAG/ED of the oriental fruit fly Bactrocera dorsalis (Hendel), that is an important pest in fruits, we performed an Illumina-based deep sequencing of mRNA. This yielded 54,577,630 clean reads corresponding to 4.91Gb total nucleotides that were assembled and clustered to 30,669 unigenes (average 645bp). Among them, 20,419 unigenes were functionally annotated to known proteins/peptides in Gene Orthology, Clusters of Orthologous Groups, Kyoto Encyclopedia of Genes and Genomes pathway databases. Typically, many genes were involved in immunity and these included microbial recognition proteins and antimicrobial peptides. Subsequently, the inducible expression of these immunity-related genes was confirmed by qRT-PCR analysis when insects were challenged with immunity-inducible factors, suggesting their function in guaranteeing fertilization success. Besides, we identified some important reproductive genes such as juvenile hormone- and ecdysteroid-related genes in this de novo assembly. In conclusion, this transcriptomic sequencing of B. dorsalis MAG/ED provides insights to facilitate further functional research of reproduction, immunity and molecular evolution of reproductive proteins in this important agricultural pest. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. [Prognostic significance of mean amplitude of glycemic excursion in patients with severe burn].

    PubMed

    Zang, Z D; Yan, Z; Hui, J J; Yan, J; Chen, H Y

    2016-01-01

    To retrospectively analyze the prognostic significance of mean amplitude of glycemic excursion (MAGE) in patients with severe burn. A study involving 76 patients with severe burn admitted into Department of Burns of the Third People's Hospital of Wuxi City from January 2011 to August 2014, conforming to the inclusion criteria was conducted. Data of their demography, injury, and treatment were collected. Blood glucose level of patients was measured during the first 72 h after admission, and MAGE was calculated. (1) The patients were divided into survival group (n=46) and death group (n=30) according to the outcome within post injury day (PID) 90. The MAGE level of patients was compared between two groups. (2) The patients were divided into 3 groups by tertiles of MAGE within 72 h after admission, with 26 cases in low tertile group (MAGE<3.3 mmol/L), 27 cases in middle tertile group (with MAGE from 3.3 to 5.5 mmol/L), 23 cases in high tertile group (MAGE>5.5 mmol/L). The surviving curve was drawn using the Kaplan-Meier method to compare survival rates and surviving time of patients among the 3 groups within PID 90. Data were processed with t test, one-way analysis of variance, LSD test, chi-square test, and Fisher's exact test. The surviving curve was analyzed by the Log-rank test. Correlation was analyzed between demography, acute physiology and chronic health evaluation Ⅱ score, injury, treatment, sepsis, length of ICU stay, MAGE and death of patients using the univariate and multivariate Cox regression analysis. Receiver operating characteristic (ROC) curve of MAGE was drawn to predict death for 76 patients. Within 72 h after admission, the MAGE of patients in death group was (6.0±1.4) mmol/L, which was significantly higher than that in survival group [(3.5±1.2) mmol/L, t=9.219, P=0.004]. The survival rates of patients in low tertile, middle tertile, and high tertile groups within PID 90 were respectively 88.5% (23/26), 59.3% (16/27), and 30.4% (7/23), with significant differences among 3 groups (χ(2)=18.073, P<0.001). The surviving time of patients in low tertile group [(83±21) d] was significantly longer than that of middle tertile group [(63±34) d, P<0.05]. The surviving time of patients was longer in low tertile and middle tertile groups than in high tertile group [(46±37) d, with P values below 0.05]. Total burn area, sepsis, blood purification, and MAGE were independent risk factors of death (with hazard ratio respectively 4.324, 1.591, 1.886, 2.047; 95% confidence interval respectively 2.978-6.119, 1.005-1.657, 1.614-2.408, 1.852-3.161; P<0.05 or P<0.01). The area under the ROC curve of MAGE for predicting death for 76 patients was 0.870 (with 95% confidence interval 0.786-0.966, P<0.001), and 4.7 mmol/L was chosen as the optimal threshold value, with sensitivity of 86.7% and specificity of 89.1%. The increase of MAGE in patients with severe burn is significantly associated with poor prognosis; controlling the glucose level fluctuation guided by measuring MAGE may be helpful in reducing mortality of patients.

  1. Hypoglycemia and blood glucose fluctuations in the application of a sensor-augmented insulin pump.

    PubMed

    Luo, Pei; Cheng, Qianpeng; Chen, Bin; Li, Yang; Wu, Jinxiao; Zhang, Xingguang; Jiao, Xiumin; Zhao, Jing; Lv, Xiaofeng

    2013-12-01

    The purpose of this study was to understand the effect of sensor-augmented insulin pump (SAP) use on hypoglycemia and blood glucose (BG) fluctuations. Sixty patients with type 2 diabetes mellitus were randomly assigned to three groups of treatment with SAP, continuous subcutaneous insulin infusion (CSII), or multiple daily injection (MDI) therapy for 6 days. Parameters of glycemic control that were determined included mean BG concentration (MBG), SD of BG (SDBG), mean amplitude of glycemic excursions (MAGE), absolute means of daily differences (MODD), 24-h area under the curve at 10 h (AUC10), 24-h area under the curve at 3.9 h (AUC3.9), and Low Blood Glucose Index (LBGI). No significant differences were observed among the three groups in terms of MBG, SDBG, MAGE, or MODD at the beginning of treatment. The MBG, SDBG, MAGE, MODD, and total AUC10 of the SAP group improved over the 4 days of the intervention compared with the CSII and MDI groups; however, no significant differences were observed among the three groups in terms of total AUC3.9 and LBGI. Compared with CSII and MDI therapy, SAP therapy was able to rapidly lower mean BG and reduce BG level fluctuations with no increased risks of hypoglycemia.

  2. Methionine Deprivation Induces a Targetable Vulnerability in Triple-Negative Breast Cancer Cells by Enhancing TRAIL Receptor-2 Expression.

    PubMed

    Strekalova, Elena; Malin, Dmitry; Good, David M; Cryns, Vincent L

    2015-06-15

    Many neoplasms are vulnerable to methionine deficiency by mechanisms that are poorly understood. Because gene profiling studies have revealed that methionine depletion increases TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) mRNA, we postulated that methionine stress sensitizes breast cancer cells to proapoptotic TRAIL-R2 agonists. Human triple (ER/PR/HER2)-negative breast carcinoma cell lines were cultured in control or methionine-free media. The effects of methionine depletion on TRAIL receptor expression and sensitivity to chemotherapy or a humanized agonistic TRAIL-R2 monoclonal antibody (lexatumumab) were determined. The melanoma-associated antigen MAGED2 was silenced to delineate its functional role in sensitizing TNBC cells to methionine stress. An orthotopic TNBC model was utilized to evaluate the effects of dietary methionine deficiency, lexatumumab, or the combination. Methionine depletion sensitized TNBC cells to lexatumumab-induced caspase activation and apoptosis by increasing TRAIL-R2 mRNA and cell surface expression. MCF-10A cells transformed by oncogenic H-Ras, but not untransformed cells, and matrix-detached TNBC cells were highly sensitive to the combination of lexatumumab and methionine depletion. Proteomics analyses revealed that MAGED2, which has been reported to reduce TRAIL-R2 expression, was suppressed by methionine stress. Silencing MAGED2 recapitulated features of methionine deprivation, including enhanced mRNA and cell surface expression of TRAIL receptors and increased sensitivity to TRAIL receptor agonists. Dietary methionine deprivation enhanced the antitumor effects of lexatumumab in an orthotopic metastatic TNBC model. Methionine depletion exposes a targetable defect in TNBC cells by increasing TRAIL-R2 expression. Our findings provide the foundation for a clinical trial combining dietary methionine restriction and TRAIL-R2 agonists. Clin Cancer Res; 21(12); 2780-91. ©2015 AACR. ©2015 American Association for Cancer Research.

  3. Spontaneous CD4+ and CD8+ T-cell responses directed against cancer testis antigens are present in the peripheral blood of testicular cancer patients.

    PubMed

    Pearce, Hayden; Hutton, Paul; Chaudhri, Shalini; Porfiri, Emilio; Patel, Prashant; Viney, Richard; Moss, Paul

    2017-07-01

    Cancer/testis antigen (CTAg) expression is restricted to spermatogenic cells in an immune-privileged site within the testis. However, these proteins are expressed aberrantly by malignant cells and T-cell responses against CTAgs develop in many cancer patients. We investigated the prevalence, magnitude and phenotype of CTAg-specific T cells in the blood of patients with testicular germ cell tumors (TGCTs). CD8 + and CD4 + T-cell responses against MAGE-A family antigens were present in 44% (20/45) of patients' samples assayed by ex vivo IFN-γ ELISPOT. The presence of MAGE-specific CD8 + T cells was further determined following short-term in vitro expansion through the use of pMHC-I multimers containing known immunogenic peptides. Longitudinal analysis revealed that the frequency of MAGE-specific T cells decreased by 89% following orchidectomy suggesting that persistence of tumor antigen is required to sustain CTAg-specific T-cell immunity. Notably, this decrease correlated with a decline in the global effector/memory T-cell pool following treatment. Spontaneous T-cell immunity against CTAg proteins therefore develops in many patients with testicular cancer and may play an important role in the excellent clinical outcome of patients with this tumor subtype. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Hyperglycemia and glycemic variability are associated with the severity of sepsis in nondiabetic subjects.

    PubMed

    Preechasuk, Lukana; Suwansaksri, Nattakarn; Ipichart, Nantawan; Vannasaeng, Sathit; Permpikul, Chairat; Sriwijitkamol, Apiradee

    2017-04-01

    The purpose was to compare glucose variability (GV) obtained via continuous glucose monitoring between nondiabetic sepsis patients and healthy subjects and to seek associations between GV and sepsis severity in nondiabetic sepsis patients. Nondiabetic sepsis inpatients and healthy controls received a 72-hour continuous glucose monitoring (iPro2, Medtronic) postadmission and post-oral glucose tolerance test, respectively. The mean glucose level (MGL) along with GV represented by standard deviation (SD) and the mean amplitude of glycemic excursion (MAGE) were calculated at 24 and 72 hours. Sepsis severity was evaluated with the Sepsis-related Organ Failure Assessment Score (SOFA). MGL and GV in patients with SOFA ≥9 and <9 were compared. Thirty nondiabetic sepsis and 10 healthy subjects were recruited. No differences were found between groups except for higher patient age in sepsis patients. The MGL and MAGE 72h of sepsis patients were significantly higher than those of healthy subjects. MGL and GV 24h were higher in patients with SOFA ≥9 than in patients with SOFA <9 (MGL 24h 195±17 vs 139±27, P<.001; SD 24h 32 [28, 36] vs 19 [5, 58], P=.02; and MAGE 24h 94 [58, 153] vs 54 [16, 179], P=.01). Nondiabetic sepsis patients had higher MGL and GV values than healthy subjects. MGL and GV 24h were associated with sepsis severity. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Motor functioning, exploration, visuospatial cognition and language development in preschool children with autism.

    PubMed

    Hellendoorn, Annika; Wijnroks, Lex; van Daalen, Emma; Dietz, Claudine; Buitelaar, Jan K; Leseman, Paul

    2015-04-01

    In order to understand typical and atypical developmental trajectories it is important to assess how strengths or weaknesses in one domain may be affecting performance in other domains. This study examined longitudinal relations between early fine motor functioning, visuospatial cognition, exploration, and language development in preschool children with ASD and children with other developmental delays/disorders. The ASD group included 63 children at T1 (Mage = 27.10 months, SD = 8.71) and 46 children at T2 (Mage = 45.85 months, SD = 7.16). The DD group consisted of 269 children at T1 (Mage = 17.99 months, SD = 5.59), and 121 children at T2 (Mag e= 43.51 months, SD = 3.81). A subgroup nested within the total sample was randomly selected and studied in-depth on exploratory behavior. This group consisted of 50 children, 21 children with ASD (Mage = 27.57, SD = 7.09) and 29 children with DD (Mage = 24.03 months, SD = 6.42). Fine motor functioning predicted language in both groups. Fine motor functioning was related to visuospatial cognition in both groups and related to object exploration, spatial exploration, and social orientation during exploration only in the ASD group. Visuospatial cognition and all exploration measures were related to both receptive and expressive language in both groups. The findings are in line with the embodied cognition theory, which suggests that cognition emerges from and is grounded in the bodily interactions of an agent with the environment. This study emphasizes the need for researchers and clinicians to consider cognition as emergent from multiple interacting systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Not all great minds think alike: systematic and intuitive cognitive styles.

    PubMed

    Sagiv, Lilach; Amit, Adi; Ein-Gar, Danit; Arieli, Sharon

    2014-10-01

    Individuals process information and make decisions in different ways. Some plan carefully and analyze information systematically, whereas others follow their instincts and do what "feels right." We aimed to deepen our understanding of the meaning of the intuitive versus systematic cognitive styles. Study 1 (N = 130, 39% female, M(age)  = 24) compared cognitive styles of arts, accounting, and mathematics students. Cognitive styles were associated with values (Study 2: N = 154, 123, 78; female = 59%, 49%, 85.9%; M(age)  = 22, 23, 27) and traits (Study 3: N = 77, 140, 151; female = 59%, 66%, 46%; M(age)  = 22, 25, 23), and they interacted with experience in predicting performance (Study 4: N = 63, 48% female, M(age)  = 23; Study 5: N = 44, 39% female, M(age)  = 23). All participants were Caucasian Israeli students. The systematic style was most frequent among accountants, and the intuitive style was most frequent among artists, validating the meaning of the styles. Systematic style was positively correlated with Conscientiousness and with security values and negatively correlated with stimulation values. The intuitive style had the opposite pattern and was also positively correlated with Extraversion. Experience improved rule-based performance among systematic individuals but had no effect on intuitive ones. Cognitive style is consistent with other personal attributes (traits and values), with implications for decision making and task performance. © 2013 Wiley Periodicals, Inc.

  7. Measuring adjustment in Japanese juvenile delinquents with learning disabilities using Japanese version of Kaufman Assessment Battery for Children II.

    PubMed

    Kumagami, Takashi; Kumagai, Keiko

    2014-10-01

    The aim of this study was to create a profile of the cognitive and academic abilities of juvenile delinquents (JD) in Japan using the newly validated Japanese version of the Kaufman Assessment Battery for Children, Second Edition (KABC-II-J). We administered the KABC-II-J to 22 JD (Mage  = 15.9 years, standard deviation [SD] = 1.4), 28 typically developing high school students (Mage  = 16.0 years, SD = 0.08), and (as controls) 12 special education students (Mage  = 16.9, SD = 0.83) with mild intellectual disabilities. We observed significant differences between JD and typically developing students on learning index of the Mental Process Index, and the vocabulary, reading, writing, and mathematics indices on the Achievement Index. JD had lower scores than did typically developing high school students. Fourteen JD had a 1 SD discrepancy (43%) in scores on these indices. These cases were suspected of having learning disabilities. The KABC-II-J is a suitable means of assessing academic and cognitive problems in JD; professionals working in the field of juvenile delinquency should recognize that offenders might have severe academic delays and learning disabilities. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

  8. Prevalence of Novel MAGED2 Mutations in Antenatal Bartter Syndrome.

    PubMed

    Legrand, Anne; Treard, Cyrielle; Roncelin, Isabelle; Dreux, Sophie; Bertholet-Thomas, Aurélia; Broux, Françoise; Bruno, Daniele; Decramer, Stéphane; Deschenes, Georges; Djeddi, Djamal; Guigonis, Vincent; Jay, Nadine; Khalifeh, Tackwa; Llanas, Brigitte; Morin, Denis; Morin, Gilles; Nobili, François; Pietrement, Christine; Ryckewaert, Amélie; Salomon, Rémi; Vrillon, Isabelle; Blanchard, Anne; Vargas-Poussou, Rosa

    2018-02-07

    Mutations in the MAGED2 gene, located on the X chromosome, have been recently detected in males with a transient form of antenatal Bartter syndrome or with idiopathic polyhydramnios. The aim of this study is to analyze the proportion of the population with mutations in this gene in a French cohort of patients with antenatal Bartter syndrome. The French cohort of patients with antenatal Bartter syndrome encompasses 171 families. Mutations in genes responsible for types 1-4 have been detected in 75% of cases. In patients without identified genetic cause ( n =42), transient antenatal Bartter syndrome was reported in 12 cases. We analyzed the MAGED2 gene in the entire cohort of negative cases by Sanger sequencing and retrospectively collected clinical data regarding pregnancy as well as the postnatal outcome for positive cases. We detected mutations in MAGED2 in 17 patients, including the 12 with transient antenatal Bartter syndrome, from 16 families. Fifteen different mutations were detected (one whole deletion, three frameshift, three splicing, three nonsense, two inframe deletions, and three missense); 13 of these mutations had not been previously described. Interestingly, two patients are females; in one of these patients our data are consistent with selective inactivation of chromosome X explaining the severity. The phenotypic presentation in our patients was variable and less severe than that of the originally described cases. MAGED2 mutations explained 9% of cases of antenatal Bartter syndrome in a French cohort, and accounted for 38% of patients without other characterized mutations and for 44% of male probands of negative cases. Our study confirmed previously published data and showed that females can be affected. As a result, this gene must be included in the screening of the most severe clinical form of Bartter syndrome. Copyright © 2018 by the American Society of Nephrology.

  9. Loss of Maged1 results in obesity, deficits of social interactions, impaired sexual behavior and severe alteration of mature oxytocin production in the hypothalamus.

    PubMed

    Dombret, Carlos; Nguyen, Tuan; Schakman, Olivier; Michaud, Jacques L; Hardin-Pouzet, Hélène; Bertrand, Mathieu J M; De Backer, Olivier

    2012-11-01

    MAGED1, NECDIN and MAGEL2 are members of the MAGE gene family. The latter two of these genes have been involved in Prader-Willi syndrome (PWS), which includes hyperphagia, repetitive and compulsive behaviors, and cognitive impairment. Here, we show that Maged1-deficient mice develop progressive obesity associated with hyperphagia and reduced motor activity. Loss of Maged1 also results in a complex behavioral syndrome that includes reduced social interactions and memory, deficient sexual behavior, as well as increased anxiety and self-grooming. Oxytocin (OT), which is produced in the hypothalamus, can act as a neurotransmitter that reduces anxiety, promotes social behaviors and regulates food intake. Growing evidences indicate that OT is involved in autism. We found that Maged1 mutants showed a severe reduction in the levels of mature OT, but not of its precursors, in the hypothalamus. Moreover, the administration of OT rescued the deficit in social memory of these mice. We conclude that Maged1 is required for OT processing or stability. A decrease in mature OT levels in Maged1 mutants affects social interactions and possibly other behavioral processes. Our observations suggest that, in human, MAGED1 could play a role in autism or cause a neurodevelopmental condition that is reminiscent of the PWS.

  10. Arousing "gentle passions" in young adolescents: Sustained experimental effects of value affirmations on prosocial feelings and behaviors.

    PubMed

    Thomaes, Sander; Bushman, Brad J; de Castro, Bram Orobio; Reijntjes, Albert

    2012-01-01

    When people reflect on their important values, they may become more attuned to the needs of others. Two longitudinal field experiments examined whether a subtle value-affirmation manipulation can initiate relatively enduring increases in young adolescents' prosocial feelings (Study 1; Mage = 12.9) and prosocial behaviors (Study 2; Mage = 12.9). Participants completed a brief writing exercise that affirmed the values they deemed either most important (value-affirmation group) or unimportant (control group). As predicted, the value affirmation, coupled with a booster affirmation 6 weeks later, caused increases in prosocial feelings and behaviors over the 3-month study period. Antisocial students who were value-affirmed showed especially strong increases in prosocial behavior. These results suggest that "gentle passions" can be aroused in youth by cost- and time-efficient means. The practical utility of value affirmations will need to be evaluated in future work.

  11. 76 FR 66726 - Government-Owned Inventions; Availability for Licensing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-27

    ...-A12 peptide antigens. The TCRs recognize these antigens in the context of major histocompatibility... proteins to mediate tumor growth and spreading. The MAGE-A proteins are some of the most widely expressed... adapted to the depletion of hormones and continue to grow. Abnormal androgen receptor signaling is known...

  12. Effects of acarbose versus glibenclamide on glycemic excursion and oxidative stress in type 2 diabetic patients inadequately controlled by metformin: a 24-week, randomized, open-label, parallel-group comparison.

    PubMed

    Wang, Jun-Sing; Lin, Shi-Dou; Lee, Wen-Jane; Su, Shih-Li; Lee, I-Te; Tu, Shih-Te; Tseng, Yao-Hsien; Lin, Shih-Yi; Sheu, Wayne Huey-Herng

    2011-12-01

    Glycemic excursion is significantly associated with oxidative stress, which plays a role in the development of chronic complications in type 2 diabetes mellitus (T2DM). Acarbose has been reported to reduce cardiovascular risk in patients with impaired glucose tolerance and T2DM. We hypothesize that treatment with acarbose could attenuate glycemic excursions and reduce oxidative stress in patients with T2DM. This study aimed to evaluate the effects of acarbose versus glibenclamide on mean amplitude of glycemic excursions (MAGE) and oxidative stress in patients with T2DM who are insufficiently controlled by metformin. T2DM outpatients aged 30 to 70 years who were taking single or dual oral antidiabetic drugs for ≥3 months and had a glycosylated hemoglobin (HbA(1c)) value between 7.0% and 11.0% were eligible. Patients were treated with metformin monotherapy (1500 mg daily) for 8 weeks, followed by randomization to either acarbose or glibenclamide add-on for 16 weeks. The dosage of acarbose and glibenclamide was 50 mg TID and 2.5 mg TID, respectively, for the first 4 weeks. In the following 12 weeks, the dosage was doubled in both groups. Continuous glucose monitoring (CGM) for 72 hours and a meal tolerance test (MTT) after a 10-hour overnight fast were conducted before randomization and at the end of study. MAGE was calculated from CGM data. β-cell response to postprandial glucose increments was assessed by the ratio between incremental AUC of insulin and glucose during MTT. Oxidative stress was estimated by plasma oxidized LDL (ox-LDL) and urinary excretion rates of 8-iso prostaglandin F(2α) (8-iso PGF(2α)). The primary outcomes included changes in MAGE, plasma ox-LDL, and urinary excretion of 8-iso PGF(2α). Adverse events, including hypoglycemia, were recorded. A total of 55 patients were randomized (mean age, 54 years; males, 47%; mean body mass index, 25.9 kg/m(2); mean duration of diabetes, 6.9 years; mean HbA(1c), 8.3%) and 51 patients completed this study (acarbose, n = 28; glibenclamide, n = 23). HbA(1c) decreased significantly in both treatment groups (acarbose: 8.2 [0.8]% to 7.5 [0.8]% [P < 0.001]; glibenclamide: 8.6 [1.6]% to 7.4 [1.2]% [P < 0.001]). MAGE did not change significantly in glibenclamide-treated patients (6.2 [2.8] mmol/L to 6.3 [2.3] mmol/L; P = 0.82), whereas ox-LDL (242.4 [180.9] ng/mL to 470.7 [247.3] ng/mL; P = 0.004) and urinary excretion of 8-iso PGF(2α) (121.6 [39.6] pmol/mmol creatinine to 152.5 [41.8] pmol/mmol creatinine; P = 0.03) increased significantly. Acarbose decreased MAGE (5.6 [1.5] mmol/L to 4.0 [1.4] mmol/L; P < 0.001) without significant change in ox-LDL levels (254.4 [269.1] ng/mL to 298.5 [249.8) ng/mL; P = 0.62) or 8-iso PGF(2α) excretion rates (117.9 [58.1] pmol/mmol creatinine to 137.8 [64.4] pmol/mmol creatinine; P = 0.12). Body weight and serum triglycerides (fasting and 2-hour postprandial) decreased (all, P < 0.01) and serum adiponectin increased (P < 0.05) after treatment with acarbose, whereas HDL-C decreased (P < 0.01) after treatment with glibenclamide. β-cell response to postprandial glucose increments was negatively correlated with MAGE (r = 0.570, P < 0.001) and improved significantly with acarbose (35.6 [32.2] pmol/mmol to 56.4 [43.7] pmol/mmol; P = 0.001) but not with glibenclamide (27.9 [17.6] pmol/mmol to 36.5 [24.2] pmol/mmol; P = 0.12). In this select population of adult Taiwanese patients with T2DM who were inadequately controlled by metformin, add-on acarbose or glibenclamide significantly reduced HbA(1c). However, treatment with acarbose decreased MAGE, body weight, and serum triglyceride and increased serum adiponectin without significant effect on oxidative stress. Treatment with glibenclamide had no statistically significant effect on MAGE but increased oxidative stress and decreased HDL-C. ClinicalTrials.gov identifier: NCT00417729. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

  13. Open Skies Project Computational Fluid Dynamic Analysis

    DTIC Science & Technology

    1994-03-01

    109 -. -_ _ 9 . CONCLUSIONSI1 f 10. LIST OF REFERENCES _________ ___________112 APPENDIX A: Transition Prediction __________________116 B...Behind the Open Skies Plate 20 8. VSAERO Results on the Alternate Fairing 21 9 . Centerline Cp Comparisons 22 10. VSAERO Wing Effects Study Centerline C...problems. The assistance Mrs. Mary Ann Mages, at Kirtland Supercomputer Center ( PL /SCPR) gave by setting a precedent for supercomputer account

  14. Epigenetic Control of Tamoxifen-Resistant Breast Cancer

    DTIC Science & Technology

    2014-03-01

    had decreases in expression in TMX2-11 and TMX2-28, however neither was significant (Figure 2A & B, Williams et al . 2014). Treatment with 5- Aza...expression!of!MAGED1!in!TMX2?28,!however!a!significant!decrease!in!methylation!was! observed!in!both!TMX2?11!and!TMX2?28!(see!Williams! et ! al !2014...treated with the methylating agent, S- adenosylmethionine (SAM) using the protocol described in Pakneshan et al (2004) in an attempt to replicate

  15. Test-retest reliability of a continuous glucose monitoring system in individuals with type 2 diabetes.

    PubMed

    Terada, Tasuku; Loehr, Sarah; Guigard, Emmanuel; McCargar, Linda J; Bell, Gordon J; Senior, Peter; Boulé, Normand G

    2014-08-01

    This study determined the test-retest reliability of a continuous glucose monitoring system (CGMS) (iPro™2; Medtronic, Northridge, CA) under standardized conditions in individuals with type 2 diabetes (T2D). Fourteen individuals with T2D spent two nonconsecutive days in a calorimetry unit. On both days, meals, medication, and exercise were standardized. Glucose concentrations were measured continuously by CGMS, from which daily mean glucose concentration (GLU(mean)), time spent in hyperglycemia (t(>10.0 mmol/L)), and meal, exercise, and nocturnal mean glucose concentrations, as well as glycemic variability (SD(w), percentage coefficient of variation [%cv(w)], mean amplitude of glycemic excursions [MAGEc, MAGE(ave), and MAGE(abs.gos)], and continuous overlapping net glycemic action [CONGA(n)]) were estimated. Absolute and relative reliabilities were investigated using coefficient of variation (CV) and intraclass correlation, respectively. Relative reliability ranged from 0.77 to 0.95 (P<0.05) for GLU(mean) and meal, exercise, and nocturnal glycemia with CV ranging from 3.9% to 11.7%. Despite significant relative reliability (R=0.93; P<0.01), t(>10.0 mmol/L) showed larger CV (54.7%). Among the different glycemic variability measures, a significant between-day difference was observed in MAGEc, MAGE(ave), CONGA6, and CONGA12. The remaining measures (i.e., SD(w), %cv(w), MAGE(abs.gos), and CONGA1-4) indicated no between-day differences and significant relative reliability. In individuals with T2D, CGMS-estimated glycemic profiles were characterized by high relative and absolute reliability for both daily and shorter-term measurements as represented by GLUmean and meal, exercise, and nocturnal glycemia. Among the different methods to calculate glycemic variability, our results showed SD(w), %cv(w), MAGE(abs.gos), and CONGAn with n ≤ 4 were reliable measures. These results suggest the usefulness of CGMS in clinical trials utilizing repeated measured.

  16. Mage: A Tool for Developing Interactive Instructional Graphics

    ERIC Educational Resources Information Center

    Pavkovic, Stephen F.

    2005-01-01

    Mage is a graphics program developed for visualization of three-dimensional structures of proteins and other macromolecules. An application of the Mage program is reported here for developing interactive instructional graphics files (kinemages) of much smaller scale. Examples are given illustrating features of VSEPR models, permanent dipoles,…

  17. Safety and immunogenicity of MAGE-A3 cancer immunotherapeutic with dacarbazine in patients with MAGE-A3-positive metastatic cutaneous melanoma: an open phase I/II study with a first assessment of a predictive gene signature.

    PubMed

    Grob, Jean-Jacques; Mortier, Laurent; D'Hondt, Lionel; Grange, Florent; Baurain, Jean Francois; Dréno, Brigitte; Lebbe, Céleste; Robert, Caroline; Dompmartin, Anne; Neyns, Bart; Gillet, Marc; Louahed, Jamila; Jarnjak, Silvija; Lehmann, Frédéric F

    2017-01-01

    We assessed safety, immunogenicity and clinical activity of recombinant MAGE-A3 antigen combined with AS15 immunostimulant (MAGE-A3 immunotherapeutic) in association with dacarbazine in patients with metastatic melanoma. In this open-label, phase I/II, uncontrolled multicentre trial conducted in Belgium and France, patients with MAGE-A3-positive melanoma received up to 24 doses of MAGE-A3 immunotherapeutic (four cycles) coadministered with eight doses of dacarbazine. Adverse events (AE) were recorded until 31 days postvaccination, and serious AEs (SAE), until 30 days following the last dose. MAGE-A3-specific antibodies were measured by ELISA. Clinical activity of MAGE-A3 immunotherapeutic was assessed in patients positive/negative for previously identified gene signature (GS) associated with clinical outcome. Forty-eight patients were enrolled and treated (32 GS+, 15 GS-, 1 unknown GS status); two patients completed the study. All patients reported AEs, the most common were 'general disorders and administration site conditions' (94%). Treatment-related AEs were reported by 85% of patients; the most common was pain at injection site (38%). Sixteen SAEs were reported by 21% of patients; two were considered as treatment related (neutropenia and thrombocytopenia; grade 4). Postdose 4, all patients were seropositive for MAGE-A3-specific antibodies, with a geometric mean titre of 2778.7 ELISA units (EU)/mL (95% CI 1638.3 to 4712.8). One complete and three partial responses were reported (only in GS+ patients). Median overall survival was 11.4 months for GS+ and 5.3 months for GS- patients. Although this trial shows poor results compared with the new results with checkpoint inhibitors, it gives an interesting insight in rapidly developing fields like combinations of immunotherapy and chemotherapy, new generation vaccines and the use of gene profile as a predictive marker. NCT00849875.

  18. Cancer-testis antigen expression is shared between epithelial ovarian cancer tumors.

    PubMed

    Garcia-Soto, Arlene E; Schreiber, Taylor; Strbo, Natasa; Ganjei-Azar, Parvin; Miao, Feng; Koru-Sengul, Tulay; Simpkins, Fiona; Nieves-Neira, Wilberto; Lucci, Joseph; Podack, Eckhard R

    2017-06-01

    Cancer-testis (CT) antigens have been proposed as potential targets for cancer immunotherapy. Our objective was to evaluate the expression of a panel of CT antigens in epithelial ovarian cancer (EOC) tumor specimens, and to determine if antigen sharing occurs between tumors. RNA was isolated from EOC tumor specimens, EOC cell lines and benign ovarian tissue specimens. Real time-PCR analysis was performed to determine the expression level of 20 CT antigens. A total of 62 EOC specimens, 8 ovarian cancer cell lines and 3 benign ovarian tissues were evaluated for CT antigen expression. The majority of the specimens were: high grade (62%), serous (68%) and advanced stage (74%). 58 (95%) of the EOC tumors analyzed expressed at least one of the CT antigens evaluated. The mean number of CT antigen expressed was 4.5 (0-17). The most frequently expressed CT antigen was MAGE A4 (65%). Antigen sharing analysis showed the following: 9 tumors shared only one antigen with 62% of the evaluated specimens, while 37 tumors shared 4 or more antigens with 82%. 5 tumors expressed over 10 CT antigens, which were shared with 90% of the tumor panel. CT antigens are expressed in 95% of EOC tumor specimens. However, not a single antigen was universally expressed across all samples. The degree of antigen sharing between tumors increased with the total number of antigens expressed. These data suggest a multi-epitope approach for development of immunotherapy for ovarian cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Automated electrotransformation of Escherichia coli on a digital microfluidic platform using bioactivated magnetic beads.

    PubMed

    Moore, J A; Nemat-Gorgani, M; Madison, A C; Sandahl, M A; Punnamaraju, S; Eckhardt, A E; Pollack, M G; Vigneault, F; Church, G M; Fair, R B; Horowitz, M A; Griffin, P B

    2017-01-01

    This paper reports on the use of a digital microfluidic platform to perform multiplex automated genetic engineering (MAGE) cycles on droplets containing Escherichia coli cells. Bioactivated magnetic beads were employed for cell binding, washing, and media exchange in the preparation of electrocompetent cells in the electrowetting-on-dieletric (EWoD) platform. On-cartridge electroporation was used to deliver oligonucleotides into the cells. In addition to the optimization of a magnetic bead-based benchtop protocol for generating and transforming electrocompetent E. coli cells, we report on the implementation of this protocol in a fully automated digital microfluidic platform. Bead-based media exchange and electroporation pulse conditions were optimized on benchtop for transformation frequency to provide initial parameters for microfluidic device trials. Benchtop experiments comparing electrotransformation of free and bead-bound cells are presented. Our results suggest that dielectric shielding intrinsic to bead-bound cells significantly reduces electroporation field exposure efficiency. However, high transformation frequency can be maintained in the presence of magnetic beads through the application of more intense electroporation pulses. As a proof of concept, MAGE cycles were successfully performed on a commercial EWoD cartridge using variations of the optimal magnetic bead-based preparation procedure and pulse conditions determined by the benchtop results. Transformation frequencies up to 22% were achieved on benchtop; this frequency was matched within 1% (21%) by MAGE cycles on the microfluidic device. However, typical frequencies on the device remain lower, averaging 9% with a standard deviation of 9%. The presented results demonstrate the potential of digital microfluidics to perform complex and automated genetic engineering protocols.

  20. Automated electrotransformation of Escherichia coli on a digital microfluidic platform using bioactivated magnetic beads

    PubMed Central

    Moore, J. A.; Nemat-Gorgani, M.; Madison, A. C.; Punnamaraju, S.; Eckhardt, A. E.; Pollack, M. G.; Church, G. M.; Fair, R. B.; Horowitz, M. A.; Griffin, P. B.

    2017-01-01

    This paper reports on the use of a digital microfluidic platform to perform multiplex automated genetic engineering (MAGE) cycles on droplets containing Escherichia coli cells. Bioactivated magnetic beads were employed for cell binding, washing, and media exchange in the preparation of electrocompetent cells in the electrowetting-on-dieletric (EWoD) platform. On-cartridge electroporation was used to deliver oligonucleotides into the cells. In addition to the optimization of a magnetic bead-based benchtop protocol for generating and transforming electrocompetent E. coli cells, we report on the implementation of this protocol in a fully automated digital microfluidic platform. Bead-based media exchange and electroporation pulse conditions were optimized on benchtop for transformation frequency to provide initial parameters for microfluidic device trials. Benchtop experiments comparing electrotransformation of free and bead-bound cells are presented. Our results suggest that dielectric shielding intrinsic to bead-bound cells significantly reduces electroporation field exposure efficiency. However, high transformation frequency can be maintained in the presence of magnetic beads through the application of more intense electroporation pulses. As a proof of concept, MAGE cycles were successfully performed on a commercial EWoD cartridge using variations of the optimal magnetic bead-based preparation procedure and pulse conditions determined by the benchtop results. Transformation frequencies up to 22% were achieved on benchtop; this frequency was matched within 1% (21%) by MAGE cycles on the microfluidic device. However, typical frequencies on the device remain lower, averaging 9% with a standard deviation of 9%. The presented results demonstrate the potential of digital microfluidics to perform complex and automated genetic engineering protocols. PMID:28191268

  1. Recent advances and versatility of MAGE towards industrial applications.

    PubMed

    Singh, Vijai; Braddick, Darren

    2015-12-01

    The genome engineering toolkit has expanded significantly in recent years, allowing us to study the functions of genes in cellular networks and assist in over-production of proteins, drugs, chemicals and biofuels. Multiplex automated genome engineering (MAGE) has been recently developed and gained more scientific interest towards strain engineering. MAGE is a simple, rapid and efficient tool for manipulating genes simultaneously in multiple loci, assigning genetic codes and integrating non-natural amino acids. MAGE can be further expanded towards the engineering of fast, robust and over-producing strains for chemicals, drugs and biofuels at industrial scales.

  2. The Interplay of Students’ School Engagement, School Self-Concept and Motivational Relations during Adolescence

    PubMed Central

    Bakadorova, Olga; Raufelder, Diana

    2017-01-01

    Existing literature evidences the association between adolescents’ school self-concept and engagement, both concepts being related to students’ perception of teachers and peers as motivators. However, few longitudinal studies explore the interplay of these factors. The present study aims to close this gap, applying latent cross-lagged panel design to two-wave data from German adolescent students [1088 8th grade students at T1 (Mage = 13.7, SD = 0.53; 53.9% girls) and 845 9th grade students at T2 (Mage = 14.86; SD = 0.57; 55% girls) from the initial sample]. Besides direct effects, three cross-lagged over-time paths were found to be significant: students’ perception of peers as positive motivators (PPMs) at the beginning of 8th grade (T1) positively predicts their behavioral school engagement at the end of 9th grade (T2), as well as emotional school engagement at the beginning of 8th grade positively predicts students’ perception of PPMs 1.5 years later. Furthermore, behavioral school engagement at T1 functions as a predictor of a student’s school self-concept at T2. PMID:29321754

  3. An object model and database for functional genomics.

    PubMed

    Jones, Andrew; Hunt, Ela; Wastling, Jonathan M; Pizarro, Angel; Stoeckert, Christian J

    2004-07-10

    Large-scale functional genomics analysis is now feasible and presents significant challenges in data analysis, storage and querying. Data standards are required to enable the development of public data repositories and to improve data sharing. There is an established data format for microarrays (microarray gene expression markup language, MAGE-ML) and a draft standard for proteomics (PEDRo). We believe that all types of functional genomics experiments should be annotated in a consistent manner, and we hope to open up new ways of comparing multiple datasets used in functional genomics. We have created a functional genomics experiment object model (FGE-OM), developed from the microarray model, MAGE-OM and two models for proteomics, PEDRo and our own model (Gla-PSI-Glasgow Proposal for the Proteomics Standards Initiative). FGE-OM comprises three namespaces representing (i) the parts of the model common to all functional genomics experiments; (ii) microarray-specific components; and (iii) proteomics-specific components. We believe that FGE-OM should initiate discussion about the contents and structure of the next version of MAGE and the future of proteomics standards. A prototype database called RNA And Protein Abundance Database (RAPAD), based on FGE-OM, has been implemented and populated with data from microbial pathogenesis. FGE-OM and the RAPAD schema are available from http://www.gusdb.org/fge.html, along with a set of more detailed diagrams. RAPAD can be accessed by registration at the site.

  4. Self-Concept Clarity in Adolescents and Parents: A Six-Wave Longitudinal and Multi-Informant Study on Development and Intergenerational Transmission.

    PubMed

    Crocetti, Elisabetta; Rubini, Monica; Branje, Susan; Koot, Hans M; Meeus, Wim

    2016-10-01

    The purpose of this study was twofold: (a) to disentangle patterns of change and stability in self-concept clarity (SCC) in adolescents and in their parents and (b) to examine processes of intergenerational transmission of SCC in families with adolescents. Participants were 497 Dutch families including the father (baseline Mage  = 46.74), the mother (baseline Mage  = 44.41), and their adolescent child (56.9% males; baseline Mage  = 13.03). Each family member completed the SCC scale for six waves, with a one-year interval between each wave. Latent growth curve analyses indicated that adolescent boys reported higher SCC than girls. Furthermore, fathers and mothers reported higher SCC than their children, and it increased over time. Indices of SCC rank-order stability were high and increased from T1 to T2, T2 to T3, etc., for each family member, especially for adolescents. Multivariate latent growth curve analyses and cross-lagged models highlighted a unidirectional transmission process, with fathers' and mothers' SCC influencing adolescents' SCC. This result was not moderated by adolescent gender. These findings indicate that self-concept clarity is transmitted from parents to children. © 2015 Wiley Periodicals, Inc.

  5. Safety and immunogenicity of MAGE-A3 cancer immunotherapeutic with dacarbazine in patients with MAGE-A3-positive metastatic cutaneous melanoma: an open phase I/II study with a first assessment of a predictive gene signature

    PubMed Central

    Grob, Jean-Jacques; Mortier, Laurent; D’Hondt, Lionel; Grange, Florent; Baurain, Jean Francois; Dréno, Brigitte; Lebbe, Céleste; Robert, Caroline; Dompmartin, Anne; Neyns, Bart; Gillet, Marc; Louahed, Jamila; Jarnjak, Silvija; Lehmann, Frédéric F

    2017-01-01

    Background We assessed safety, immunogenicity and clinical activity of recombinant MAGE-A3 antigen combined with AS15 immunostimulant (MAGE-A3 immunotherapeutic) in association with dacarbazine in patients with metastatic melanoma. Methods In this open-label, phase I/II, uncontrolled multicentre trial conducted in Belgium and France, patients with MAGE-A3-positive melanoma received up to 24 doses of MAGE-A3 immunotherapeutic (four cycles) coadministered with eight doses of dacarbazine. Adverse events (AE) were recorded until 31 days postvaccination, and serious AEs (SAE), until 30 days following the last dose. MAGE-A3-specific antibodies were measured by ELISA. Clinical activity of MAGE-A3 immunotherapeutic was assessed in patients positive/negative for previously identified gene signature (GS) associated with clinical outcome. Results Forty-eight patients were enrolled and treated (32 GS+, 15 GS−, 1 unknown GS status); two patients completed the study. All patients reported AEs, the most common were ‘general disorders and administration site conditions’ (94%). Treatment-related AEs were reported by 85% of patients; the most common was pain at injection site (38%). Sixteen SAEs were reported by 21% of patients; two were considered as treatment related (neutropenia and thrombocytopenia; grade 4). Postdose 4, all patients were seropositive for MAGE-A3-specific antibodies, with a geometric mean titre of 2778.7 ELISA units (EU)/mL (95% CI 1638.3 to 4712.8). One complete and three partial responses were reported (only in GS+ patients). Median overall survival was 11.4 months for GS+ and 5.3 months for GS− patients. Conclusion Although this trial shows poor results compared with the new results with checkpoint inhibitors, it gives an interesting insight in rapidly developing fields like combinations of immunotherapy and chemotherapy, new generation vaccines and the use of gene profile as a predictive marker. Trial registration number NCT00849875. PMID:29177094

  6. Merlin: Computer-Aided Oligonucleotide Design for Large Scale Genome Engineering with MAGE.

    PubMed

    Quintin, Michael; Ma, Natalie J; Ahmed, Samir; Bhatia, Swapnil; Lewis, Aaron; Isaacs, Farren J; Densmore, Douglas

    2016-06-17

    Genome engineering technologies now enable precise manipulation of organism genotype, but can be limited in scalability by their design requirements. Here we describe Merlin ( http://merlincad.org ), an open-source web-based tool to assist biologists in designing experiments using multiplex automated genome engineering (MAGE). Merlin provides methods to generate pools of single-stranded DNA oligonucleotides (oligos) for MAGE experiments by performing free energy calculation and BLAST scoring on a sliding window spanning the targeted site. These oligos are designed not only to improve recombination efficiency, but also to minimize off-target interactions. The application further assists experiment planning by reporting predicted allelic replacement rates after multiple MAGE cycles, and enables rapid result validation by generating primer sequences for multiplexed allele-specific colony PCR. Here we describe the Merlin oligo and primer design procedures and validate their functionality compared to OptMAGE by eliminating seven AvrII restriction sites from the Escherichia coli genome.

  7. Dual roles of brain serine hydrolase KIAA1363 in ether lipid metabolism and organophosphate detoxification

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nomura, Daniel K.; Fujioka, Kazutoshi; Issa, Roger S.

    2008-04-01

    Serine hydrolase KIAA1363 is an acetyl monoalkylglycerol ether (AcMAGE) hydrolase involved in tumor cell invasiveness. It is also an organophosphate (OP) insecticide-detoxifying enzyme. The key to understanding these dual properties was the use of KIAA1363 +/+ (wildtype) and -/- (gene deficient) mice to define the role of this enzyme in brain and other tissues and its effectiveness in vivo in reducing OP toxicity. KIAA1363 was the primary AcMAGE hydrolase in brain, lung, heart and kidney and was highly sensitive to inactivation by chlorpyrifos oxon (CPO) (IC{sub 50} 2 nM) [the bioactivated metabolite of the major insecticide chlorpyrifos (CPF)]. Although theremore » was no difference in hydrolysis product monoalkylglycerol ether (MAGE) levels in +/+ and -/- mouse brains in vivo, isopropyl dodecylfluorophosphonate (30 mg/kg) and CPF (100 mg/kg) resulted in 23-51% decrease in brain MAGE levels consistent with inhibition of AcMAGE hydrolase activity. On incubating +/+ and -/- brain membranes with AcMAGE and cytidine-5'-diphosphocholine, the absence of KIAA1363 activity dramatically increased de novo formation of platelet-activating factor (PAF) and lyso-PAF, signifying that metabolically-stabilized AcMAGE can be converted to this bioactive lipid in brain. On considering detoxification, KIAA1363 -/- mice were significantly more sensitive than +/+ mice to ip-administered CPF (100 mg/kg) and parathion (10 mg/kg) with increased tremoring and mortality that correlated for CPF with greater brain acetylcholinesterase inhibition. Docking AcMAGE and CPO in a KIAA1363 active site model showed similar positioning of their acetyl and trichloropyridinyl moieties, respectively. This study establishes the relevance of KIAA1363 in ether lipid metabolism and OP detoxification.« less

  8. A novel electrochemical immunosensor based on ITO modified by carboxyl-ended silane agent for ultrasensitive detection of MAGE-1 in human serum.

    PubMed

    Gündoğdu, Aslı; Aydın, Elif Burcu; Sezgintürk, Mustafa Kemal

    2017-11-15

    A new, low-cost electrochemical immunosensor was developed for rapid detection of Melanoma-associated antigen 1 (MAGE-1), a cancer biomarker. The fabrication procedure of immunosensor was based on the covalent immobilization of anti-MAGE-1, biorecognition molecule, on ITO electrode by carboxyethylsilanetriol (CTES) monolayer. The biosensing MAGE-1 antigen was monitored by using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) technique. Apart from these techniques, single frequency impedance (SFI) was used for investigation of antibody-antigen interactions. Scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) were utilized for characterization of the proposed biosensor. To fabricate highly sensitive, good stability immunosensor, some parameters were optimized. Under optimal conditions, the developed electrochemical immunosensor for MAGE-1 exhibited a dynamic range of 4 fg/mL and 200 fg/mL with a low detection limit of 1.30 fg/mL. It had acceptable repeatability (5.05%, n = 20) and good storage stability (3.58% loss after 10 weeks). Moreover, this electrochemical immunosensor has been successfully applied to the determination of MAGE-1 in human serum samples. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Xp11.22 deletions encompassing CENPVL1, CENPVL2, MAGED1 and GSPT2 as a cause of syndromic X-linked intellectual disability.

    PubMed

    Grau, Christina; Starkovich, Molly; Azamian, Mahshid S; Xia, Fan; Cheung, Sau Wai; Evans, Patricia; Henderson, Alex; Lalani, Seema R; Scott, Daryl A

    2017-01-01

    By searching a clinical database of over 60,000 individuals referred for array-based CNV analyses and online resources, we identified four males from three families with intellectual disability, developmental delay, hypotonia, joint hypermobility and relative macrocephaly who carried small, overlapping deletions of Xp11.22. The maximum region of overlap between their deletions spanned ~430 kb and included two pseudogenes, CENPVL1 and CENPVL2, whose functions are not known, and two protein coding genes-the G1 to S phase transition 2 gene (GSPT2) and the MAGE family member D1 gene (MAGED1). Deletions of this ~430 kb region have not been previously implicated in human disease. Duplications of GSPT2 have been documented in individuals with intellectual disability, but the phenotypic consequences of a loss of GSPT2 function have not been elucidated in humans or mouse models. Changes in MAGED1 have not been associated with intellectual disability in humans, but loss of MAGED1 function is associated with neurocognitive and neurobehavioral phenotypes in mice. In all cases, the Xp11.22 deletion was inherited from an unaffected mother. Studies performed on DNA from one of these mothers did not show evidence of skewed X-inactivation. These results suggest that deletions of an ~430 kb region on chromosome Xp11.22 that encompass CENPVL1, CENPVL2, GSPT2 and MAGED1 cause a distinct X-linked syndrome characterized by intellectual disability, developmental delay, hypotonia, joint hypermobility and relative macrocephaly. Loss of GSPT2 and/or MAGED1 function may contribute to the intellectual disability and developmental delay seen in males with these deletions.

  10. Curcumin improves the therapeutic efficacy of Listeria(at)-Mage-b vaccine in correlation with improved T-cell responses in blood of a triple-negative breast cancer model 4T1.

    PubMed

    Singh, Manisha; Ramos, Ilyssa; Asafu-Adjei, Denise; Quispe-Tintaya, Wilber; Chandra, Dinesh; Jahangir, Arthee; Zang, Xingxing; Aggarwal, Bharat B; Gravekamp, Claudia

    2013-08-01

    Success of cancer vaccination is strongly hampered by immune suppression in the tumor microenvironment (TME). Interleukin (IL)-6 is particularly and highly produced by triple-negative breast cancer (TNBC) cells, and has been considered as an important contributor to immune suppression in the TME. Therefore, we hypothesized that IL-6 reduction may improve efficacy of vaccination against TNBC cancer through improved T-cell responses. To prove this hypothesis, we investigated the effect of curcumin, an inhibitor of IL-6 production, on vaccination of a highly attenuated Listeria monocytogenes (Listeria(at)), encoding tumor-associated antigens (TAA) Mage-b in a TNBC model 4T1. Two therapeutic vaccination strategies with Listeria(at)-Mage-b and curcumin were tested. The first immunization strategy involved all Listeria(at)-Mage-b vaccinations and curcumin after tumor development. As curcumin has been consumed all over the world, the second immunization strategy involved curcumin before and all therapeutic vaccinations with Listeria(at)-Mage-b after tumor development. Here, we demonstrate that curcumin significantly improves therapeutic efficacy of Listeria(at)-Mage-b with both immunization strategies particularly against metastases in a TNBC model (4T1). The combination therapy was slightly but significantly more effective against the metastases when curcumin was administered before compared to after tumor development. With curcumin before tumor development in the combination therapy, the production of IL-6 was significantly decreased and IL-12 increased by myeloid-derived suppressor cells (MDSC), in correlation with improved CD4 and CD8 T-cell responses in blood. Our study suggests that curcumin improves the efficacy of Listeria(at)-Mage-b vaccine against metastases in TNBC model 4T1 through reversal of tumor-induced immune suppression.

  11. Development of Teleological Explanations in Peruvian Quechua-Speaking and U.S. English-Speaking Preschoolers and Adults.

    PubMed

    Sánchez Tapia, Ingrid; Gelman, Susan A; Hollander, Michelle A; Manczak, Erika M; Mannheim, Bruce; Escalante, Carmen

    2016-05-01

    Teleological reasoning involves the assumption that entities exist for a purpose (giraffes have long necks for reaching leaves). This study examines how teleological reasoning relates to cultural context, by studying teleological reasoning in 61 Quechua-speaking Peruvian preschoolers (Mage  = 5.3 years) and adults in an indigenous community, compared to 72 English-speaking U.S. preschoolers (Mage  = 4.9 years) and university students. Data were responses to open-ended "why" questions ("Why is that mountain tall?"). Teleological explanations about nonliving natural kinds were more frequent for children than adults, and for Quechua than U.S. However, changes with age were importantly distinct from differences corresponding to cultural variation. Developmental and cultural differences in teleological explanations may reflect causal analysis of the features under consideration. © 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.

  12. Grammatical morphology in school-age children with and without language impairment: a discriminant function analysis.

    PubMed

    Moyle, Maura Jones; Karasinski, Courtney; Ellis Weismer, Susan; Gorman, Brenda K

    2011-10-01

    The purpose of this study was to test Bedore and Leonard's (1998) proposal that a verb morpheme composite may hold promise as a clinical marker for specific language impairment (SLI) in English speakers and serve as an accurate basis for the classification of children with and without SLI beyond the preschool level. The language transcripts of 50 school-age children with SLI (M(age) = 7;9 [years;months]) and 50 age-matched typically developing peers (M(age) = 7;9) were analyzed. Following the Bedore and Leonard (1998) procedure, 3 variables were measured: a finite verb morpheme composite, a noun morpheme composite, and mean length of utterance in morphemes (MLU(m)). Overall findings indicated that neither grammatical morpheme composite alone adequately discriminated the groups at this developmental level. However, combining the verb and noun grammatical morpheme composite measures with MLU(m) resulted in good discriminant accuracy in classifying subgroups of the youngest children with and without SLI in the school-age sample. Verb morphology alone is not a useful clinical marker of SLI in school-age children. Potential explanations for these findings and ideas for future research are discussed.

  13. Developmental outcomes of toddlers of young Latina mothers: Cultural, family, and parenting factors.

    PubMed

    Grau, Josefina M; Duran, Petra A; Castellanos, Patricia; Smith, Erin N; Silberman, Stephanie G; Wood, Lauren E

    2015-11-01

    Children of adolescent mothers are at risk for poor developmental outcomes. This study is among the first to examine how cultural, family, and parenting factors prospectively predict the cognitive and language development of children of young Latina mothers (N=170; Mage=17.9 years). Mothers were interviewed and observed interacting with their children at 18 months (W1). Children were tested at 18 (W1) and 24 (W2) months. Mothers' cultural orientation (W1) was related to aspects of the childrearing environment (W1), which in turn had implications for the children's development (W2). Specifically, a stronger orientation toward American culture was related to higher mother-reported engagement in parenting by their own mothers (grandmothers), which in turn predicted stronger gains in cognitive and expressive language functioning from W1 to W2. A stronger Latino orientation related to the display of more directiveness and greater mother-reported engagement by the children's biological fathers; directiveness, in turn, predicted fewer gains in cognitive functioning only when father engagement was low and did not predict expressive language development. Finally, mothers' display of more positive affect, a stronger American orientation, and higher grandmother engagement uniquely predicted gains in W2 expressive language functioning. Implications for intervention are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Developmental Outcomes of Toddlers of Young Latina Mothers: Cultural, Family, and Parenting Factors

    PubMed Central

    Grau, Josefina M.; Duran, Petra A.; Castellanos, Patricia; Smith, Erin N.; Silberman, Stephanie G.; Wood, Lauren

    2015-01-01

    Children of adolescent mothers are at risk for poor developmental outcomes. This study is among the first to examine how cultural, family, and parenting factors prospectively predict the cognitive and language development of children of young Latina mothers (N=170; Mage = 17.9 years). Mothers were interviewed and observed interacting with their children at 18 months (W1). Children were tested at 18 (W1) and 24 (W2) months. Mothers’ cultural orientation (W1) was related to aspects of the childrearing environment (W1), which in turn had implications for the children's development (W2). Specifically, a stronger orientation toward American culture was related to higher mother-reported engagement in parenting by their own mothers (grandmothers), which in turn predicted stronger gains in cognitive and expressive language functioning from W1 to W2. A stronger Latino orientation related to the display of more directiveness and greater mother-reported engagement by the children's biological fathers; directiveness, in turn, predicted fewer gains in cognitive functioning only when father engagement was low and did not predict expressive language development. Finally, mothers’ display of more positive affect, a stronger American orientation, and higher grandmother engagement uniquely predicted gains in W2 expressive language functioning. Implications for intervention are discussed. PMID:26454205

  15. Cardiorespiratory and Biomechanical Responses to Simulated Recreational Horseback Riding in Healthy Children

    ERIC Educational Resources Information Center

    Rigby, Brandon R.; Papadakis, Zacharias; Bane, Annie A.; Park, Jin K.; Grandjean, Peter W.

    2015-01-01

    Purpose: The purpose of this study was to determine the reliability of cardiorespiratory and pelvic kinematic responses to simulated horseback riding (SHBR) and to characterize responses to SHBR relative to walking in apparently healthy children. Method: Fifteen healthy children (Mage = 9.5 ± 2.6 years) completed SHBR on a commercially available…

  16. Facial emotion expression recognition by children at familial risk for depression: High risk boys are oversensitive to sadness

    PubMed Central

    Lopez-Duran, Nestor L.; Kuhlman, Kate R.; George, Charles; Kovacs, Maria

    2012-01-01

    In the present study we examined perceptual sensitivity to facial expressions of sadness among children at familial-risk for depression (N = 64) and low-risk peers (N = 40) between the ages 7 and 13(Mage = 9.51; SD = 2.27). Participants were presented with pictures of facial expressions that varied in emotional intensity from neutral to full-intensity sadness or anger (i.e., emotion recognition), or pictures of faces morphing from anger to sadness (emotion discrimination). After each picture was presented, children indicated whether the face showed a specific emotion (i.e., sadness, anger) or no emotion at all (neutral). In the emotion recognition task, boys (but not girls) at familial-risk for depression identified sadness at significantly lower levels of emotional intensity than did their low-risk peers. The high and low-risk groups did not differ with regard to identification of anger. In the emotion discrimination task, both groups displayed over-identification of sadness in ambiguous mixed faces but high-risk youth were less likely to show this labeling bias than their peers. Our findings are consistent with the hypothesis that enhanced perceptual sensitivity to subtle traces of sadness in facial expressions may be a potential mechanism of risk among boys at familial-risk for depression. This enhanced perceptual sensitivity does not appear to be due to biases in the labeling of ambiguous faces. PMID:23106941

  17. CEBS object model for systems biology data, SysBio-OM.

    PubMed

    Xirasagar, Sandhya; Gustafson, Scott; Merrick, B Alex; Tomer, Kenneth B; Stasiewicz, Stanley; Chan, Denny D; Yost, Kenneth J; Yates, John R; Sumner, Susan; Xiao, Nianqing; Waters, Michael D

    2004-09-01

    To promote a systems biology approach to understanding the biological effects of environmental stressors, the Chemical Effects in Biological Systems (CEBS) knowledge base is being developed to house data from multiple complex data streams in a systems friendly manner that will accommodate extensive querying from users. Unified data representation via a single object model will greatly aid in integrating data storage and management, and facilitate reuse of software to analyze and display data resulting from diverse differential expression or differential profile technologies. Data streams include, but are not limited to, gene expression analysis (transcriptomics), protein expression and protein-protein interaction analysis (proteomics) and changes in low molecular weight metabolite levels (metabolomics). To enable the integration of microarray gene expression, proteomics and metabolomics data in the CEBS system, we designed an object model, Systems Biology Object Model (SysBio-OM). The model is comprehensive and leverages other open source efforts, namely the MicroArray Gene Expression Object Model (MAGE-OM) and the Proteomics Experiment Data Repository (PEDRo) object model. SysBio-OM is designed by extending MAGE-OM to represent protein expression data elements (including those from PEDRo), protein-protein interaction and metabolomics data. SysBio-OM promotes the standardization of data representation and data quality by facilitating the capture of the minimum annotation required for an experiment. Such standardization refines the accuracy of data mining and interpretation. The open source SysBio-OM model, which can be implemented on varied computing platforms is presented here. A universal modeling language depiction of the entire SysBio-OM is available at http://cebs.niehs.nih.gov/SysBioOM/. The Rational Rose object model package is distributed under an open source license that permits unrestricted academic and commercial use and is available at http://cebs.niehs.nih.gov/cebsdownloads. The database and interface are being built to implement the model and will be available for public use at http://cebs.niehs.nih.gov.

  18. Neuropsychological Profiles of Written Expression Learning Disabilities Determined by Concordance-Discordance Model Criteria.

    PubMed

    Fenwick, Melanie E; Kubas, Hanna A; Witzke, Justin W; Fitzer, Kim R; Miller, Daniel C; Maricle, Denise E; Harrison, Gina L; Macoun, Sarah J; Hale, James B

    2016-01-01

    Children with specific learning disabilities (SLD) have disparate neuropsychological processing deficits that interfere with academic achievement in spelling, writing fluency, and/or written expression (WE). Although there are multiple potential causes of WE SLD, there is a paucity of research exploring this critical academic skill from a neuropsychological perspective. This study examined the neuropsychological profiles of WE SLD subtypes defined using the concordance-discordance model (C-DM) of SLD identification. Participants were drawn from a sample of 283 children (194 boys, 89 girls) aged 6 years to 16 years old (M(age) = 9.58 years, SD = 2.29 years) referred for comprehensive neuropsychological evaluations in school settings and subsequently selected based on C-DM determined spelling, writing fluency, and WE SLD. WE SLD subtypes differed on several psychomotor, memory, and executive function measures (F range = 2.48-5.07, p range = .049 to <.001), suggesting that these children exhibit distinct patterns of neuropsychological processing strengths and weaknesses. Findings have relevance for differential diagnosis of WE subtypes, discriminating WE SLD subtypes from low WE achievement, and developing differentiated evidence-based instruction and intervention for children with WE SLD. Limitations and future research will be addressed.

  19. Direct molecular mimicry enables off-target cardiovascular toxicity by an enhanced affinity TCR designed for cancer immunotherapy.

    PubMed

    Raman, Marine C C; Rizkallah, Pierre J; Simmons, Ruth; Donnellan, Zoe; Dukes, Joseph; Bossi, Giovanna; Le Provost, Gabrielle S; Todorov, Penio; Baston, Emma; Hickman, Emma; Mahon, Tara; Hassan, Namir; Vuidepot, Annelise; Sami, Malkit; Cole, David K; Jakobsen, Bent K

    2016-01-13

    Natural T-cell responses generally lack the potency to eradicate cancer. Enhanced affinity T-cell receptors (TCRs) provide an ideal approach to target cancer cells, with emerging clinical data showing significant promise. Nevertheless, the risk of off target reactivity remains a key concern, as exemplified in a recent clinical report describing fatal cardiac toxicity, following administration of MAGE-A3 specific TCR-engineered T-cells, mediated through cross-reactivity with an unrelated epitope from the Titin protein presented on cardiac tissue. Here, we investigated the structural mechanism enabling TCR cross-recognition of MAGE-A3 and Titin, and applied the resulting data to rationally design mutants with improved antigen discrimination, providing a proof-of-concept strategy for altering the fine specificity of a TCR towards an intended target antigen. This study represents the first example of direct molecular mimicry leading to clinically relevant fatal toxicity, mediated by a modified enhanced affinity TCR designed for cancer immunotherapy. Furthermore, these data demonstrate that self-antigens that are expressed at high levels on healthy tissue should be treated with extreme caution when designing immuno-therapeutics.

  20. Main and interactive effects of a nonclinical panic attack history and distress tolerance in relation to PTSD symptom severity.

    PubMed

    Marshall-Berenz, Erin C; Vujanovic, Anka A; Zvolensky, Michael J

    2011-03-01

    The current study investigated the main and interactive effects of a nonclinical panic attack history and distress tolerance in relation to PTSD symptoms. The sample consisted of 91 adults (62.6% women; M(age)=23.45, SD=9.56) who met DSM-IV criteria for trauma exposure, 53.8% of whom met criteria for a recent (past 2 years) history of nonclinical panic attacks. Results indicated that distress tolerance, as measured by the Distress Tolerance Scale (Simons & Gaher, 2005), was significantly related to all PTSD symptom clusters, and a nonclinical panic attack history was significantly related to PTSD re-experiencing and hyperarousal symptoms. The interaction of a nonclinical panic attack history and distress tolerance significantly predicted unique variance in only PTSD hyperarousal symptoms. Implications and future directions are discussed for the role of nonclinical panic attacks and distress tolerance in PTSD symptom expression. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Transactional Links between Teacher-Child Relationship Quality and Perceived versus Sociometric Popularity: A Three-Wave Longitudinal Study

    ERIC Educational Resources Information Center

    De Laet, Steven; Doumen, Sarah; Vervoort, Eleonora; Colpin, Hilde; Van Leeuwen, Karla; Goossens, Luc; Verschueren, Karine

    2014-01-01

    This study examined how peer relationships (i.e., sociometric and perceived popularity) and teacher--child relationships (i.e., support and conflict) impact one another throughout late childhood. The sample included 586 children (46% boys), followed annually from Grades 4 to 6 (Mage.wave1 = 9.26 years). Autoregressive cross-lagged modeling was…

  2. Children’s Sympathy for Peers Who Are the Targets of Peer Aggression

    PubMed Central

    Leff, Stephen S.

    2014-01-01

    Although a goal of many aggression intervention programs is to increase children’s concern (often termed sympathy or empathy) for their peers as a means of ultimately reducing aggressive behavior, there are no measures specifically of children’s concern for peers who are the targets of peer aggression. A participatory action research (PAR) model was used to create a culturally-sensitive measure of urban African American children’s sympathy for peers who are the targets of physical aggression, relational or social aggression, verbal aggression, and property damage. In Study 1, 40 children (Mage =9.71 years; 47.5 % female) were interviewed about the types of incidents that lead them to feel sympathy for a peer. Based upon these findings, the 15-item Peer Sympathy Scale (PSS) was developed. In Study 2, the PSS was administered to 517 children (Mage=9.82 years; 47.4 % female) to examine the psychometric properties of the measure and to explore the association between children’s sympathy for their peers and their social behavior. Greater sympathy was associated with less overt and relational aggression according to both peer and teacher reports as well as with less oppositional-defiant behavior according to teacher reports. The clinical utility of the PSS as an outcome assessment tool for social skills intervention programs is discussed. PMID:22556114

  3. Examining the components of children's peer liking as antecedents of school adjustment.

    PubMed

    Betts, Lucy R; Rotenberg, Ken J; Trueman, Mark; Stiller, James

    2012-06-01

    Children's social interactions with their peers influence their psychosocial adjustment; consequently, the relationship between class-wide peer liking, same-gender peer liking, and school adjustment was explored in two age groups. Peer liking was analysed using the social relations model (SRM). In Study 1, 205 children (103 female and 102 male, M(age) = 7.15, SD= 7 months) completed measures of peer liking and school adjustment, and teachers completed the Short-Form Teacher Rating Scale of School Adjustment (Short-Form TRSSA). In Study 2, 197 children (98 female and 90 male, M(age) = 9.87, SD= 5.9 months) completed measures of peer liking and school adjustment. Both studies yielded evidence of reciprocal liking and individual differences in the ratings of liking awarded to, and elicited from, both peer groups. Multigroup path analysis, with groups created according to gender, revealed that elements of liking predicted different aspects of school adjustment with some variation according to age and gender. Together, these findings suggest that the SRM can be used to examine peer liking and underscore the importance of children's peers for school adjustment. © 2011 The British Psychological Society.

  4. What Is Engagement? Proactivity as the Missing Link in the HEXACO Model of Personality.

    PubMed

    de Vries, Reinout E; Wawoe, Kilian W; Holtrop, Djurre

    2016-04-01

    We tested the hypothesis that proactivity represents the engagement vector in the HEXACO model of personality. Questionnaire data were obtained in five studies, three of which consisted (mostly) of students: Study 1 (N = 188, Mage  = 20.0, 89.4% women), Study 3 (N = 315, Mage  = 20.4, 80.6% women), and Study 4 (N = 309 self-ratings, Mage  = 20.0, 78.3% women; N = 307 other-ratings, Mage  = 24.5, 62.2% women). Participants in the other two studies came from an ISO-certified representative community panel: Study 2 (N = 525, Mage  = 51.2, 52.0% women) and Study 5 (N = 736, Mage  = 42.2, 48.0% women). Proactive Personality and Proactivity were positively related to Extraversion, Conscientiousness, and Openness to Experience, but only weakly related or unrelated to Honesty-Humility, Emotionality, and Agreeableness, supporting the alignment of Proactive Personality/Proactivity with the hypothesized HEXACO engagement vector. Additionally, Proactivity explained incremental variance in self-rated job performance on top of the HEXACO facets that were most closely associated with Proactive Personality/Proactivity, that is, Social Boldness (an Extraversion facet), Diligence (a Conscientiousness facet), and Creativity (an Openness to Experience facet), but not in entrepreneurship and intrapreneurship. Proactivity is the missing engagement link in the HEXACO model of personality. The results are discussed in light of higher-order factors (e.g., general factor of personality and Alpha and Beta) of personality and bandwidth-fidelity controversies. © 2014 Wiley Periodicals, Inc.

  5. Interactions between the Nse3 and Nse4 Components of the SMC5-6 Complex Identify Evolutionarily Conserved Interactions between MAGE and EID Families

    PubMed Central

    Kozakova, Lucie; Liao, Chunyan; Guerineau, Marc; Colnaghi, Rita; Vidot, Susanne; Marek, Jaromir; Bathula, Sreenivas R.; Lehmann, Alan R.; Palecek, Jan

    2011-01-01

    Background The SMC5-6 protein complex is involved in the cellular response to DNA damage. It is composed of 6–8 polypeptides, of which Nse1, Nse3 and Nse4 form a tight sub-complex. MAGEG1, the mammalian ortholog of Nse3, is the founding member of the MAGE (melanoma-associated antigen) protein family and Nse4 is related to the EID (E1A-like inhibitor of differentiation) family of transcriptional repressors. Methodology/Principal Findings Using site-directed mutagenesis, protein-protein interaction analyses and molecular modelling, we have identified a conserved hydrophobic surface on the C-terminal domain of Nse3 that interacts with Nse4 and identified residues in its N-terminal domain that are essential for interaction with Nse1. We show that these interactions are conserved in the human orthologs. Furthermore, interaction of MAGEG1, the mammalian ortholog of Nse3, with NSE4b, one of the mammalian orthologs of Nse4, results in transcriptional co-activation of the nuclear receptor, steroidogenic factor 1 (SF1). In an examination of the evolutionary conservation of the Nse3-Nse4 interactions, we find that several MAGE proteins can interact with at least one of the NSE4/EID proteins. Conclusions/Significance We have found that, despite the evolutionary diversification of the MAGE family, the characteristic hydrophobic surface shared by all MAGE proteins from yeast to humans mediates its binding to NSE4/EID proteins. Our work provides new insights into the interactions, evolution and functions of the enigmatic MAGE proteins. PMID:21364888

  6. ArrayExpress update--trends in database growth and links to data analysis tools.

    PubMed

    Rustici, Gabriella; Kolesnikov, Nikolay; Brandizi, Marco; Burdett, Tony; Dylag, Miroslaw; Emam, Ibrahim; Farne, Anna; Hastings, Emma; Ison, Jon; Keays, Maria; Kurbatova, Natalja; Malone, James; Mani, Roby; Mupo, Annalisa; Pedro Pereira, Rui; Pilicheva, Ekaterina; Rung, Johan; Sharma, Anjan; Tang, Y Amy; Ternent, Tobias; Tikhonov, Andrew; Welter, Danielle; Williams, Eleanor; Brazma, Alvis; Parkinson, Helen; Sarkans, Ugis

    2013-01-01

    The ArrayExpress Archive of Functional Genomics Data (http://www.ebi.ac.uk/arrayexpress) is one of three international functional genomics public data repositories, alongside the Gene Expression Omnibus at NCBI and the DDBJ Omics Archive, supporting peer-reviewed publications. It accepts data generated by sequencing or array-based technologies and currently contains data from almost a million assays, from over 30 000 experiments. The proportion of sequencing-based submissions has grown significantly over the last 2 years and has reached, in 2012, 15% of all new data. All data are available from ArrayExpress in MAGE-TAB format, which allows robust linking to data analysis and visualization tools, including Bioconductor and GenomeSpace. Additionally, R objects, for microarray data, and binary alignment format files, for sequencing data, have been generated for a significant proportion of ArrayExpress data.

  7. [Clinical study of the influence of daily sedation interruption on fluctuation of blood glucose level and mortality of critical patients with multiple trauma].

    PubMed

    Li, Yong; Jin, Zhaochen; Cai, Yan; Ji, Musen; Kong, Xianru; Liu, Jing; Yang, Hongfeng; Wang, Chenglong

    2014-04-01

    To assess the influence of a protocol of routine daily interruption of sedation on fluctuation of blood glucose level and mortality of critical patients with multiple trauma. A prospective study involving 68 critical patients with multiple trauma admitted to intensive care unit (ICU) was performed. Finger blood glucose level was measured after the implementation of daily interruption of sedation, and the results were recorded every 2 hours during the first 24 hours. Mean (MEAN), standard deviation (SD) and coefficient of variability (CV) of blood glucose level, glycemic liability index (GLI), mean amplitude of glycemic excursion (MAGE) and largest amplitude of glycemic excursions (LAGE) were calculated respectively, and 30-day mortality was recorded. The patients under study were divided into four groups according to the median values of MEAN and GLI, group A with patients of low MEAN+low GLI (n=34), group B with patients of low MEAN+high GLI (n=14), group C with patients of high MEAN+low GLI (n=12), and group D with patients of high MEAN+high GLI (n=8). Glucose levels, their range of fluctuation, and the prognosis were compared among groups. Five of the 68 patients died, with a gross mortality rate of 7.4%. Group analysis demonstrated that the patients in group A had the best prognosis with the 30-day mortality rate of 0 (0/34), while that of the group D was worst with the 30-day mortality rate of 37.5% (3/8). The MEAN levels of glucose were relatively lower in groups A and B (6.7±1.3 mmol/L, 7.6±0.8 mmol/L) and higher in groups C and D (9.3±1.4 mmol/L, 10.7±1.3 mmol/L). Indicators of glucose level fluctuation, including SD, CV, GLI, LAGE, and MAGE, were lower in groups A and C (SD: 1.6±0.4 mmol/L, 1.7±0.6 mmol/L; CV: 0.2±0.1, 0.2±0.1; GLI: 26.5±19.5, 40.1±17.6; LAGE: 4.6±2.3 mmol/L, 6.5±1.9 mmol/L; MAGE: 2.7±0.8 mmol/L, 3.1±0.80 mmol/L), and higher in groups B and D (SD: 2.9±0.7 mmol/L, 3.9±0.8 mmol/L; CV: 0.4±0.1, 0.4±0.1; GLI: 120.5±33.2, 184.6±98.4; LAGE: 9.5±2.0 mmol/L, 12.7±4.0 mmol/L; MAGE: 6.2±1.2 mmol/L, 7.6±1.8 mmol/L). The incidence of hypoglycemia was highest in group D [5.8% (6/104)], followed by that of group B [1.6% (3/182)], while that of groups A and C was lower [0.9% (4/442), 0.1% (2/256)]. The incidence of hyperglycemia were highest in groups C and D [67.3% (105/156), 69.2% (72/104)], and it was followed by that of group B [33.5% (61/182)], and that of group A was the lowest [15.4% (68/442)]. The duration of mechanical ventilation [(3.4±3.3) days], the incidence of multiple organ failure (MOF, 44.1%, 15/34), rate of continuous renal replacement therapy (CRRT, 11.8%, 4/34), and day in ICU [(5.1±3.9) days] were shortest and lowest in group A, and highest and longest in group D [(9.4±5.2) days, 87.5% (7/8), 75.0% (4/8), (10.3±7.4) days]. Daily interruption of sedation can reduce fluctuation of blood glucose level in critical patients with multiple trauma, and improve patients' outcome.

  8. The initial glycemic variability is associated with early neurological deterioration in diabetic patients with acute ischemic stroke.

    PubMed

    Hui, Jiaojie; Zhang, Jianping; Mao, Xuqiang; Li, Zaiwang; Li, Xinxin; Wang, Fengyun; Wang, Tao; Yuan, Qingfang; Wang, Sunwei; Pu, Mengjia; Xi, Guangjun

    2018-06-05

    The association between glycemic variability and early neurological deterioration (END) in acute ischemic stroke remains unclear. This study attempted to explore whether initial glycemic variability increases END in diabetic patients with acute ischemic stroke. We enrolled type 2 diabetic patients undergoing acute ischemic stroke from November 2015 to November 2016. A total of 336 patients within 72 h from stroke onset were included. The serum glucose levels were checked four times per day during the initial 3 hospital days. The standard deviation of blood glucose (SDBG) values and the mean amplitude of glycemic excursions (MAGE) were calculated for glycemic variability. END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) ≥ 2 points between hospital days 0 and 5. The frequencies of END and HbA1c were significantly different in subjects grouped according to tertiles of MAGE (9.09, 12.07 and 50.00%, p < 0.001 for END; 7.36 ± 1.91, 7.83 ± 1.93 and 8.56 ± 1.79, p < 0.001 for HbA1c). Compared to patients without END, patients with END had significantly higher HbA1c levels (8.30 ± 1.92 vs 7.80 ± 1.93, p = 0.043), increased SDBG (3.42 ± 1.14 vs 2.60 ± 0.96, p < 0.001), and increased MAGE (6.46 ± 2.09 vs 4.59 ± 1.91, p < 0.001). In a multivariable logistic regression, stroke etiology (OR 0.675; 95% CI 0.485-0.940, p = 0.020), baseline NIHSS (OR 1.086; 95% CI 1.004-1.175, p = 0.040), and MAGE (OR 1.479; 95% CI 1.162-1.882, p = 0.001) were significantly associated with END. Initial glycemic variability is associated with END in diabetic patients with acute ischemic stroke.

  9. Hair penalties: the negative influence of Afrocentric hair on ratings of Black women’s dominance and professionalism

    PubMed Central

    Opie, Tina R.; Phillips, Katherine W.

    2015-01-01

    Purpose: Women are penalized if they do not behave in a stereotype-congruent manner (Heilman, 1983, 2001; Eagly and Carli, 2007). For example, because women are not expected to be agentic they incur an “agency penalty” for expressing anger, dominance or assertiveness (Rudman, 1998; Rudman and Glick, 1999, 2001; Eagly and Karau, 2002; Rudman and Fairchild, 2004; Brescoll and Uhlmann, 2008; Livingston et al., 2012). Yet, all women are not equally penalized (Livingston et al., 2012). We make a novel contribution by examining how both White and Black evaluators respond to displays of Black women’s dominance, in this case, whether Black women choose to wear Afrocentric or Eurocentric hairstyles. Design/methodology/approach: We conducted three experimental studies to examine the influence of target hairstyle and participant race on ratings of the target’s professionalism (Studies 1, 2, and 3) and dominance (Study 2). Study 1 was an online experimental study with 200 participants (112 females, 87 males, 1 missing gender; 160 Whites, 19 Blacks, 11 Latinos, 7 Asian Americans and 3 who identify as “other”; Mage = 35.5, SD = 11.4). Study 2 was an online experimental study with 510 participants (276 women, 234 males; 256 Blacks, 254 Whites; Mage = 41.25 years, SD = 12.21). Study 3 was an online experimental study with 291 participants (141 Blacks, 150 Whites, Mage = 47.5 years, SD = 11.66). Findings: Black, as compared to White, evaluators gave higher agency penalties to Black employment candidates when they donned Afrocentric versus Eurocentric hair, rating them as more dominant and less professional. Implications: The present research illustrates the significance of considering both target and evaluator race when examining the influence of agency, and specifically dominance, on ratings of professionalism. PMID:26379612

  10. ETV VR/VS Magee Scientific Model AE33 Aethalometer

    EPA Science Inventory

    The objective of the ETV AMS Center is to verify the performance characteristics of environmental monitoring technologies for air, water, and soil. This report provides results for the verification testing of the Magee Scientific Model AE33 Aethalometer.

  11. Direct molecular mimicry enables off-target cardiovascular toxicity by an enhanced affinity TCR designed for cancer immunotherapy

    PubMed Central

    Raman, Marine C C; Rizkallah, Pierre J; Simmons, Ruth; Donnellan, Zoe; Dukes, Joseph; Bossi, Giovanna; Le Provost, Gabrielle S; Todorov, Penio; Baston, Emma; Hickman, Emma; Mahon, Tara; Hassan, Namir; Vuidepot, Annelise; Sami, Malkit; Cole, David K; Jakobsen, Bent K.

    2016-01-01

    Natural T-cell responses generally lack the potency to eradicate cancer. Enhanced affinity T-cell receptors (TCRs) provide an ideal approach to target cancer cells, with emerging clinical data showing significant promise. Nevertheless, the risk of off target reactivity remains a key concern, as exemplified in a recent clinical report describing fatal cardiac toxicity, following administration of MAGE-A3 specific TCR-engineered T-cells, mediated through cross-reactivity with an unrelated epitope from the Titin protein presented on cardiac tissue. Here, we investigated the structural mechanism enabling TCR cross-recognition of MAGE-A3 and Titin, and applied the resulting data to rationally design mutants with improved antigen discrimination, providing a proof-of-concept strategy for altering the fine specificity of a TCR towards an intended target antigen. This study represents the first example of direct molecular mimicry leading to clinically relevant fatal toxicity, mediated by a modified enhanced affinity TCR designed for cancer immunotherapy. Furthermore, these data demonstrate that self-antigens that are expressed at high levels on healthy tissue should be treated with extreme caution when designing immuno-therapeutics. PMID:26758806

  12. VoxelMages: a general-purpose graphical interface for designing geometries and processing DICOM images for PENELOPE.

    PubMed

    Giménez-Alventosa, V; Ballester, F; Vijande, J

    2016-12-01

    The design and construction of geometries for Monte Carlo calculations is an error-prone, time-consuming, and complex step in simulations describing particle interactions and transport in the field of medical physics. The software VoxelMages has been developed to help the user in this task. It allows to design complex geometries and to process DICOM image files for simulations with the general-purpose Monte Carlo code PENELOPE in an easy and straightforward way. VoxelMages also allows to import DICOM-RT structure contour information as delivered by a treatment planning system. Its main characteristics, usage and performance benchmarking are described in detail. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. SSX2-4 expression in early-stage non-small cell lung cancer.

    PubMed

    Greve, K B V; Pøhl, M; Olsen, K E; Nielsen, O; Ditzel, H J; Gjerstorff, M F

    2014-05-01

    The expression of cancer/testis antigens SSX2, SSX3, and SSX4 in non-small cell lung cancers (NSCLC) was examined, since they are considered promising targets for cancer immunotherapy due to their immunogenicity and testis-restricted normal tissue expression. We characterized three SSX antibodies and performed immunohistochemical staining of 25 different normal tissues and 143 NSCLCs. The antibodies differed in binding to two distinctive splice variants of SSX2 that exhibited different subcellular staining patterns, suggesting that the two splice variants display different functions. SSX2-4 expression was only detected in 5 of 143 early-stage NSCLCs, which is rare compared to other cancer/testis antigens (e.g. MAGE-A and GAGE). However, further studies are needed to determine whether SSX can be used as a prognostic or predictive biomarker in NSCLC. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Loneliness and the social monitoring system: Emotion recognition and eye gaze in a real-life conversation.

    PubMed

    Lodder, Gerine M A; Scholte, Ron H J; Goossens, Luc; Engels, Rutger C M E; Verhagen, Maaike

    2016-02-01

    Based on the belongingness regulation theory (Gardner et al., 2005, Pers. Soc. Psychol. Bull., 31, 1549), this study focuses on the relationship between loneliness and social monitoring. Specifically, we examined whether loneliness relates to performance on three emotion recognition tasks and whether lonely individuals show increased gazing towards their conversation partner's faces in a real-life conversation. Study 1 examined 170 college students (Mage = 19.26; SD = 1.21) who completed an emotion recognition task with dynamic stimuli (morph task) and a micro(-emotion) expression recognition task. Study 2 examined 130 college students (Mage = 19.33; SD = 2.00) who completed the Reading the Mind in the Eyes Test and who had a conversation with an unfamiliar peer while their gaze direction was videotaped. In both studies, loneliness was measured using the UCLA Loneliness Scale version 3 (Russell, 1996, J. Pers. Assess., 66, 20). The results showed that loneliness was unrelated to emotion recognition on all emotion recognition tasks, but that it was related to increased gaze towards their conversation partner's faces. Implications for the belongingness regulation system of lonely individuals are discussed. © 2015 The British Psychological Society.

  15. Automatic segmentation of the hippocampus for preterm neonates from early-in-life to term-equivalent age.

    PubMed

    Guo, Ting; Winterburn, Julie L; Pipitone, Jon; Duerden, Emma G; Park, Min Tae M; Chau, Vann; Poskitt, Kenneth J; Grunau, Ruth E; Synnes, Anne; Miller, Steven P; Mallar Chakravarty, M

    2015-01-01

    The hippocampus, a medial temporal lobe structure central to learning and memory, is particularly vulnerable in preterm-born neonates. To date, segmentation of the hippocampus for preterm-born neonates has not yet been performed early-in-life (shortly after birth when clinically stable). The present study focuses on the development and validation of an automatic segmentation protocol that is based on the MAGeT-Brain (Multiple Automatically Generated Templates) algorithm to delineate the hippocampi of preterm neonates on their brain MRIs acquired at not only term-equivalent age but also early-in-life. First, we present a three-step manual segmentation protocol to delineate the hippocampus for preterm neonates and apply this protocol on 22 early-in-life and 22 term images. These manual segmentations are considered the gold standard in assessing the automatic segmentations. MAGeT-Brain, automatic hippocampal segmentation pipeline, requires only a small number of input atlases and reduces the registration and resampling errors by employing an intermediate template library. We assess the segmentation accuracy of MAGeT-Brain in three validation studies, evaluate the hippocampal growth from early-in-life to term-equivalent age, and study the effect of preterm birth on the hippocampal volume. The first experiment thoroughly validates MAGeT-Brain segmentation in three sets of 10-fold Monte Carlo cross-validation (MCCV) analyses with 187 different groups of input atlases and templates. The second experiment segments the neonatal hippocampi on 168 early-in-life and 154 term images and evaluates the hippocampal growth rate of 125 infants from early-in-life to term-equivalent age. The third experiment analyzes the effect of gestational age (GA) at birth on the average hippocampal volume at early-in-life and term-equivalent age using linear regression. The final segmentations demonstrate that MAGeT-Brain consistently provides accurate segmentations in comparison to manually derived gold standards (mean Dice's Kappa > 0.79 and Euclidean distance <1.3 mm between centroids). Using this method, we demonstrate that the average volume of the hippocampus is significantly different (p < 0.0001) in early-in-life (621.8 mm(3)) and term-equivalent age (958.8 mm(3)). Using these differences, we generalize the hippocampal growth rate to 38.3 ± 11.7 mm(3)/week and 40.5 ± 12.9 mm(3)/week for the left and right hippocampi respectively. Not surprisingly, younger gestational age at birth is associated with smaller volumes of the hippocampi (p = 0.001). MAGeT-Brain is capable of segmenting hippocampi accurately in preterm neonates, even at early-in-life. Hippocampal asymmetry with a larger right side is demonstrated on early-in-life images, suggesting that this phenomenon has its onset in the 3rd trimester of gestation. Hippocampal volume assessed at the time of early-in-life and term-equivalent age is linearly associated with GA at birth, whereby smaller volumes are associated with earlier birth.

  16. Automatic segmentation of the hippocampus for preterm neonates from early-in-life to term-equivalent age

    PubMed Central

    Guo, Ting; Winterburn, Julie L.; Pipitone, Jon; Duerden, Emma G.; Park, Min Tae M.; Chau, Vann; Poskitt, Kenneth J.; Grunau, Ruth E.; Synnes, Anne; Miller, Steven P.; Mallar Chakravarty, M.

    2015-01-01

    Introduction The hippocampus, a medial temporal lobe structure central to learning and memory, is particularly vulnerable in preterm-born neonates. To date, segmentation of the hippocampus for preterm-born neonates has not yet been performed early-in-life (shortly after birth when clinically stable). The present study focuses on the development and validation of an automatic segmentation protocol that is based on the MAGeT-Brain (Multiple Automatically Generated Templates) algorithm to delineate the hippocampi of preterm neonates on their brain MRIs acquired at not only term-equivalent age but also early-in-life. Methods First, we present a three-step manual segmentation protocol to delineate the hippocampus for preterm neonates and apply this protocol on 22 early-in-life and 22 term images. These manual segmentations are considered the gold standard in assessing the automatic segmentations. MAGeT-Brain, automatic hippocampal segmentation pipeline, requires only a small number of input atlases and reduces the registration and resampling errors by employing an intermediate template library. We assess the segmentation accuracy of MAGeT-Brain in three validation studies, evaluate the hippocampal growth from early-in-life to term-equivalent age, and study the effect of preterm birth on the hippocampal volume. The first experiment thoroughly validates MAGeT-Brain segmentation in three sets of 10-fold Monte Carlo cross-validation (MCCV) analyses with 187 different groups of input atlases and templates. The second experiment segments the neonatal hippocampi on 168 early-in-life and 154 term images and evaluates the hippocampal growth rate of 125 infants from early-in-life to term-equivalent age. The third experiment analyzes the effect of gestational age (GA) at birth on the average hippocampal volume at early-in-life and term-equivalent age using linear regression. Results The final segmentations demonstrate that MAGeT-Brain consistently provides accurate segmentations in comparison to manually derived gold standards (mean Dice's Kappa > 0.79 and Euclidean distance <1.3 mm between centroids). Using this method, we demonstrate that the average volume of the hippocampus is significantly different (p < 0.0001) in early-in-life (621.8 mm3) and term-equivalent age (958.8 mm3). Using these differences, we generalize the hippocampal growth rate to 38.3 ± 11.7 mm3/week and 40.5 ± 12.9 mm3/week for the left and right hippocampi respectively. Not surprisingly, younger gestational age at birth is associated with smaller volumes of the hippocampi (p = 0.001). Conclusions MAGeT-Brain is capable of segmenting hippocampi accurately in preterm neonates, even at early-in-life. Hippocampal asymmetry with a larger right side is demonstrated on early-in-life images, suggesting that this phenomenon has its onset in the 3rd trimester of gestation. Hippocampal volume assessed at the time of early-in-life and term-equivalent age is linearly associated with GA at birth, whereby smaller volumes are associated with earlier birth. PMID:26740912

  17. A New Black Carbon Sensor for Dense Air Quality Monitoring Networks

    PubMed Central

    Caubel, Julien J.; Cados, Troy E.; Kirchstetter, Thomas W.

    2018-01-01

    Low-cost air pollution sensors are emerging and increasingly being deployed in densely distributed wireless networks that provide more spatial resolution than is typical in traditional monitoring of ambient air quality. However, a low-cost option to measure black carbon (BC)—a major component of particulate matter pollution associated with adverse human health risks—is missing. This paper presents a new BC sensor designed to fill this gap, the Aerosol Black Carbon Detector (ABCD), which incorporates a compact weatherproof enclosure, solar-powered rechargeable battery, and cellular communication to enable long-term, remote operation. This paper also demonstrates a data processing methodology that reduces the ABCD’s sensitivity to ambient temperature fluctuations, and therefore improves measurement performance in unconditioned operating environments (e.g., outdoors). A fleet of over 100 ABCDs was operated outdoors in collocation with a commercial BC instrument (Magee Scientific, Model AE33) housed inside a regulatory air quality monitoring station. The measurement performance of the 105 ABCDs is comparable to the AE33. The fleet-average precision and accuracy, expressed in terms of mean absolute percentage error, are 9.2 ± 0.8% (relative to the fleet average data) and 24.6 ± 0.9% (relative to the AE33 data), respectively (fleet-average ± 90% confidence interval). PMID:29494528

  18. A New Black Carbon Sensor for Dense Air Quality Monitoring Networks.

    PubMed

    Caubel, Julien J; Cados, Troy E; Kirchstetter, Thomas W

    2018-03-01

    Low-cost air pollution sensors are emerging and increasingly being deployed in densely distributed wireless networks that provide more spatial resolution than is typical in traditional monitoring of ambient air quality. However, a low-cost option to measure black carbon (BC)-a major component of particulate matter pollution associated with adverse human health risks-is missing. This paper presents a new BC sensor designed to fill this gap, the Aerosol Black Carbon Detector (ABCD), which incorporates a compact weatherproof enclosure, solar-powered rechargeable battery, and cellular communication to enable long-term, remote operation. This paper also demonstrates a data processing methodology that reduces the ABCD's sensitivity to ambient temperature fluctuations, and therefore improves measurement performance in unconditioned operating environments (e.g., outdoors). A fleet of over 100 ABCDs was operated outdoors in collocation with a commercial BC instrument (Magee Scientific, Model AE33) housed inside a regulatory air quality monitoring station. The measurement performance of the 105 ABCDs is comparable to the AE33. The fleet-average precision and accuracy, expressed in terms of mean absolute percentage error, are 9.2 ± 0.8% (relative to the fleet average data) and 24.6 ± 0.9% (relative to the AE33 data), respectively (fleet-average ± 90% confidence interval).

  19. Peripheral Nerve Repair and Prevention of Neuroma Formation

    DTIC Science & Technology

    2014-09-01

    Magee1), ADRB3, β arrestin, Patched 1 (Ptch1) and 2, desert hedgehog (Dhh), smoothen (Smo), Src kinase, and UCP1. (Months 6-36) c. We will also use the...antibody. Figure 9. Representative photomicrographs of desert hedgehog staining in perineurial fibroblasts. A.) C57/BL6 mouse nerve was isolated 3...days after BMP2 induction stained with desert hedgehog (red) and NF (green). P. perineurium; E. endoneurium. Note that the mouse nerve, unlike the

  20. Expressive inhibition in response to stress: implications for emotional processing following trauma.

    PubMed

    Clapp, Joshua D; Patton, Samantha C; Beck, J Gayle

    2015-01-01

    Expressive inhibition--the willful restriction of expressed emotion--is documented in individuals reporting trauma-related distress, but its impact on global affective functioning remains unclear. Theoretical models propose that chronic activation of negative emotion and deliberate restriction of affect operate synergistically to produce trauma-related emotional deficits. The current project examined the impact of these factors on subjective experience and physiological activation following exposure to an analog trauma. University students (N=192; Mage=20, 57% female, 42% White/Non-Hispanic) viewed a graphic film depicting scenes of a televised suicide. Participants then viewed either a sadness- or humor-eliciting film under instructions to inhibit [nsadness=45, nhumor=52] or naturally express emotion [nsadness=48, nhumor=47]. Expressive inhibition was associated with restricted amusement specifically among participants viewing the humor film. Inhibition also produced attenuated sympathetic and parasympathetic recovery, irrespective of film assignment. Evidence of disruptions in emotional processing supports models identifying inhibition as a possible mechanism in post-trauma affect dysregulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Expressive inhibition in response to stress: Implications for emotional processing following trauma

    PubMed Central

    Clapp, Joshua D.; Patton, Samantha C.; Beck, J. Gayle

    2015-01-01

    Expressive inhibition - the willful restriction of expressed emotion - is documented in individuals reporting trauma-related distress, but its impact on global affective functioning remains unclear. Theoretical models propose that chronic activation of negative emotion and deliberate restriction of affect operate synergistically to produce trauma-related emotional deficits. The current project examined the impact of these factors on subjective experience and physiological activation following exposure to an analog trauma. University students (N = 192; Mage = 20, 57% female, 42% White/Non-Hispanic) viewed a graphic film depicting scenes of a televised suicide. Participants then viewed either a sadness- or humor-eliciting film under instructions to inhibit [nsadness = 45, nhumor = 52] or naturally express emotion [nsadness = 48, nhumor = 47]. Expressive inhibition was associated with restricted amusement specifically among participants viewing the humor film. Inhibition also produced attenuated sympathetic and parasympathetic recovery, irrespective of film assignment. Evidence of disruptions in emotional processing supports models identifying inhibition as a possible mechanism in post-trauma affect dysregulation. PMID:25576773

  2. 78 FR 72010 - Establishment of Class E Airspace; Magee, MS

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-02

    ... safety and airspace management of Instrument Flight Rules (IFR) operations within the National Airspace System. This action also updates the geographic coordinates of the airport. DATES: Effective 0901 UTC.... Subsequent to publication, the FAA found an error in the geographic coordinates of Magee Municipal Airport...

  3. Emotion Recognition and Perspective Taking: A Comparison between Typical and Incarcerated Male Adolescents

    PubMed Central

    Morosan, Larisa; Badoud, Deborah; Zaharia, Alexandra; Brosch, Tobias; Eliez, Stephan; Bateman, Anthony; Heller, Patrick; Debbané, Martin

    2017-01-01

    Background Previous research suggests that antisocial individuals present impairment in social cognitive processing, more specifically in emotion recognition (ER) and perspective taking (PT). The first aim of the present study was to investigate the recognition of a wide range of emotional expressions and visual PT capacities in a group of incarcerated male adolescents in comparison to a matched group of community adolescents. Secondly, we sought to explore the relationship between these two mechanisms in relation to psychopathic traits. Methods Forty-five male adolescents (22 incarcerated adolescents (Mage = 16.52, SD = 0.96) and 23 community adolescents (Mage = 16.43, SD = 1.41)) participated in the study. ER abilities were measured using a dynamic and multimodal task that requires the participants to watch short videos in which trained actors express 14 emotions. PT capacities were examined using a task recognized and proven to be sensitive to adolescent development, where participants had to follow the directions of another person whilst taking into consideration his perspective. Results We found a main effect of group on emotion recognition scores. In comparison to the community adolescents, the incarcerated adolescents presented lower recognition of three emotions: interest, anxiety and amusement. Analyses also revealed significant impairments in PT capacities in incarcerated adolescents. In addition, incarcerated adolescents’ PT scores were uniquely correlated to their scores on recognition of interest. Conclusions The results corroborate previously reported impairments in ER and PT capacities, in the incarcerated adolescents. The study also indicates an association between impairments in the recognition of interest and impairments in PT. PMID:28122048

  4. 78 FR 48080 - Proposed Establishment of Class E Airspace; Magee, MS

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-07

    ...) Global Positioning System (GPS) Standard Instrument Approach Procedure (SIAP) serving Magee Municipal...) operations within the National Airspace System. DATES: Comments must be received on or before September 23... No. 13-ASO-8) and be submitted in triplicate to the Docket Management System (see ADDRESSES section...

  5. Prognostic value of early in-hospital glycemic excursion in elderly patients with acute myocardial infarction.

    PubMed

    Su, Gong; Mi, Shu-hua; Li, Zhao; Tao, Hong; Yang, Hong-xia; Zheng, Hong

    2013-02-11

    Acute phase hyperglycemia has been associated with increased mortality in patients with acute myocardial infarction (AMI). However, the predictive value of glycemic excursion for adverse outcome in elderly AMI patients is not clear. The aim of this study is to investigate the prognostic value of early in-hospital glycemic excursion and hemoglobin A1c (HbA1c) for one-year major adverse cardiac event (MACE) in elderly patients with AMI. We studied 186 elderly AMI patients, whose clinical data were collected and the Global Registry of Acute Coronary Events (GRACE) risk score were calculated on admission. The fluctuations of blood glucose in patients were measured by a continuous glucose monitoring system (CGMS) for 72 hours. Participants were grouped into tertiles of mean amplitude of glycemic excursions (MAGE) and grouped into HbA1c levels (as ≥6.5% or <6.5%). The MACE of patients, including new-onset myocardial infarction, acute heart failure and cardiac death, was documented during one year follow-up. The relationship of MAGE and HbA1c to the incidence of MACE in elderly AMI patients was analyzed. In all participants, a higher MAGE level was associated with the higher GRACE score (r = 0.335, p < 0.001). The rate of MACE by MAGE tertiles (>3.94 mmol/L, 2.55-3.94 mmol/L or <2.55 mmol/L) was 30.2% vs. 14.8% vs. 8.1%, respectively (p = 0.004); by HbA1c category (≥6.5% vs. <6.5%) was 22.7% vs. 14.4%, respectively (p = 0.148). Elderly AMI patients with a higher MAGE level had a significantly higher cardiac mortality. In multivariable analysis, high MAGE level was significantly associated with incidence of MACE (HR 3.107, 95% CI 1.190-8.117, p = 0.021) even after adjusting for GRACE risk score, but HbA1c was not. The early in-hospital intraday glycemic excursion may be an important predictor of mortality and MACE even stronger than HbA1c in elderly patients after AMI.

  6. An Evaluation of the Experimental Anthropology Program at Magee Secondary School, During the Spring Semester of 1971.

    ERIC Educational Resources Information Center

    Clinton, A.; And Others

    An evaluation of an experimental anthropology program which was introduced to students at the Magee Secondary School is presented. The purpose of the course, a detailed course outline, and the rationale and basic generalizations of Anthropology 11E are included. A listing of required and suggested course readings as well as student reaction to the…

  7. Patient-Reported Geriatric Symptoms as Risk Factors for Hospitalization and Emergency Department Visits

    PubMed Central

    Chandra, Anupam; Crane, Sarah J; Tung, Ericka E; Hanson, Gregory J; North, Frederick; Cha, Stephen S; Takahashi, Paul Y

    2015-01-01

    There is an urgent need to identify predictors of adverse outcomes and increased health care utilization in the elderly. The Mayo Ambulatory Geriatric Evaluation (MAGE) is a symptom questionnaire that was completed by patients aged 65 years and older during office visits to Primary Care Internal Medicine at Mayo Clinic in Rochester, MN. It was introduced to improve screening for geriatric conditions. We conducted this study to explore the relationship between self-reported geriatric symptoms and hospitalization and emergency department (ED) visits within 1 year of completing the survey. This was a retrospective cohort study of patients who completed the MAGE from April 2008 to December 2010. The primary outcome was an ED visit or hospitalization within 1 year. Predictors included responses to individual questions in the MAGE. Data were obtained from the electronic medical record and administrative records. Logistic regression analyses were performed from significant univariate factors to determine predictors in a multivariable setting. A weighted scoring system was created based upon the odds ratios derived from a bootstrap process. The sensitivity, specificity, and AUC were calculated using this scoring system. The MAGE survey was completed by 7738 patients. The average age was 76.2 ± 7.68 years and 57% were women. Advanced age, a self-report of worse health, history of 2 or more falls, weight loss, and depressed mood were significantly associated with hospitalization or ED visits within 1 year. A score equal to or greater than 2 had a sensitivity of 0.74 and specificity of 0.45. The calculated AUC was 0.60. The MAGE questionnaire, which was completed by patients at an outpatient visit to screen for common geriatric issues, could also be used to assess risk for ED visits and hospitalization within 1 year. PMID:26029477

  8. Anxiety, depression, and HIV symptoms among persons living with HIV/AIDS: the role of hazardous drinking.

    PubMed

    Garey, Lorra; Bakhshaie, Jafar; Sharp, Carla; Neighbors, Clayton; Zvolensky, Michael J; Gonzalez, Adam

    2015-01-01

    Hazardous drinking is common among persons living with HIV/AIDS (PLWHA) and associated with numerous negative health consequences. Despite the well-established negative effects of hazardous drinking among PLWHA, scholarly work has neglected to explore the role of such drinking in regard to anxiety/depressive symptoms and HIV symptom expression. The current study investigated associations between hazardous drinking and anxiety/depressive symptoms and HIV symptoms among PLWHA. Participants (n = 94; 88.3% male; Mage = 48.55; SD = 9.15) included PLWHA recruited from AIDS service organizations in the northeast. Hazardous drinking was significantly associated with anxiety/depressive symptoms and HIV symptom expression above and beyond the variance accounted for by sex, race, recruitment site, and CD4 T-Cell count, as well as other cognitive-affective variables (emotion dysregulation, distress intolerance, and anxiety sensitivity). The present results provide empirical support that hazardous drinking is indeed related to depressive and anxiety symptoms as well as HIV symptom distress and that this effect is not attributable to other factors commonly related to both alcohol use problems and emotional distress among PLWHA. Results highlight the importance of alcohol interventions for excessive drinking specifically tailored for PLWHA to facilitate better mental and physical health adjustment.

  9. Distinct impacts of sleep-disordered breathing on glycemic variability in patients with and without diabetes mellitus

    PubMed Central

    Nakata, Kei; Tanno, Masaya; Ohnishi, Hirofumi; Yano, Toshiyuki; Muranaka, Atsuko; Sato, Tatsuya; Oshima, Hiroto; Tatekoshi, Yuki; Mizuno, Masashi; Abe, Koki; Miura, Tetsuji

    2017-01-01

    Background Sleep-disordered breathing (SDB) is highly prevalent in patients with diabetes mellitus (DM) and heart failure (HF) and contributes to poor cardiovascular outcomes. Enlarged glycemic variability (GV) is a risk factor of cardiac events independently of average blood glucose level, but the influence of SDB on GV is uncertain. In this study, we examined whether the impact of SDB on GV is modified by the presence of DM with or without HF. Methods and results Two hundred three patients (67.5±14.1 [SD] years old, 132 males) who were admitted to our institute for examination or treatment of DM and/or HF underwent continuous glucose monitoring and polysomnography. Both HbA1c (8.0±2.0 vs. 5.7±0.4%) and mean amplitude of glycemic excursion (MAGE, median: 95.5 vs. 63.5 mg/dl) were significantly higher in a DM group (n = 100) than in a non-DM group (n = 103), but apnea-hypopnea index (AHI: 29.0±22.7 vs. 29.3±21.5) was similar in the two groups. AHI was correlated with log MAGE in the non-DM group but not in the DM group, and multivariate regression analysis revealed that AHI was an independent variable for log MAGE in the non-DM group but not in the DM group. We then divided the non-DM patients into two subgroups according to BNP level (100 pg/ml). AHI was positively correlated with log MAGE (r = 0.74, p<0.001) in the non-DM low-BNP subgroup, but such a correlation was not found in the non-DM high-BNP subgroup. Continuous positive airway pressure (CPAP) reduced MAGE from 75.3 to 53.0 mg/dl in the non-DM group but did not reduce MAGE in the DM group. Conclusion Severity of SDB was associated with higher GV, but DM as well as HF diminished the contribution of SDB to GV. Treatment with CPAP was effective for reduction of GV only in patients without DM. PMID:29261679

  10. Strong genetic contribution to peer relationship difficulties at school entry: findings from a longitudinal twin study.

    PubMed

    Boivin, Michel; Brendgen, Mara; Vitaro, Frank; Dionne, Ginette; Girard, Alain; Pérusse, Daniel; Tremblay, Richard E

    2013-01-01

    This study assessed the genetic and environmental contributions to peer difficulties in the early school years. Twins' peer difficulties were assessed longitudinally in kindergarten (796 twins, Mage = 6.1 years), Grade 1 (948 twins, Mage = 7.1 years), and Grade 4 (868 twins, Mage = 10 years) through multiple informants. The multivariate results revealed that genetic factors accounted for a strong part of both yearly and stable peer difficulties. At the univariate level, the genetic contributions emerged progressively, as did a growing consensus among informants with respect to those who experienced peer difficulties. These results underline the need to intervene early and persistently, and to target the child and the peer context to prevent peer difficulties and their consequences. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

  11. Effect of a 16-Week Yoga Program on Blood Pressure in Healthy College Students

    ERIC Educational Resources Information Center

    Nelson, Debra; Reed, Justy; Buck, Sarah M.

    2014-01-01

    The purpose of this study was to examine the effect of a 16-week yoga program on blood pressure (BP) in healthy college students. Twenty-five students (Mage = 28.24, SD = 10.64) participated in yoga class twice per week for 16 weeks. Thirty-one students (Mage = 28.77, SD = 7.23) attended a lecture (control condition) at approximately the same time…

  12. Human Neoplasms Elicit Multiple Specific Immune Responses in the Autologous Host

    NASA Astrophysics Data System (ADS)

    Sahin, Ugur; Tureci, Ozlem; Schmitt, Holger; Cochlovius, Bjorn; Johannes, Thomas; Schmits, Rudolf; Stenner, Frank; Luo, Guorong; Schobert, Ingrid; Pfreundschuh, Michael

    1995-12-01

    Expression of cDNA libraries from human melanoma, renal cancer, astrocytoma, and Hodgkin disease in Escherichia coli and screening for clones reactive with high-titer IgG antibodies in autologous patient serum lead to the discovery of at least four antigens with a restricted expression pattern in each tumor. Besides antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase, numerous additional antigens that were overexpressed or specifically expressed in tumors of the same type were identified. Sequence analyses suggest that many of these molecules, besides being the target of a specific immune response, might be of relevance for tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be readily defined at the molecular level by the serological analysis of autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.

  13. "If It Helps, I'll Carry On": Factors Supporting the Participation of Native and Immigrant Youth in Belgium and Germany.

    PubMed

    Born, Michel; Marzana, Daniela; Alfieri, Sara; Gavray, Claire

    2015-01-01

    In this article we propose looking into some factors for Civic Participation and the intention to continue to participate among local (Study I) and immigrant (Study II) young people living in Belgium and Germany. In Study I, 1,079 young people (M(age) = 19.23, 44.9% males) completed a self-report questionnaire asking about their Civic Participation. Multiple linear regressions reveal (a) evidence of a pool of variables significantly linked to Civic Participation: Institutional Trust, Collective-Efficacy, Parents' and Peers' Support, Political Interest, Motivations and (b) that Civic Participation, along with the mediation of the Participation's Efficacy, explains the Intention to Continue to Participate. An explanatory model was constructed on participation and the Intention to Continue to Participate on behalf of the native youth. This model is invariant between the two countries. In Study II, 276 young Turkish immigrants (M(age) = 20.80, 49.3% males) recruited in Belgium and Germany filled out the same questionnaire as in Study I. The same analysis was conducted as for Study I, and they provided the same results as the native group, highlighting the invariance of the model between natives and immigrants. Applicative repercussions are discussed.

  14. Effect of Linagliptin Versus Metformin on Glycemic Variability in Patients with Impaired Glucose Tolerance.

    PubMed

    González-Heredia, Tonatiuh; Hernández-Corona, Diana M; González-Ortiz, Manuel; Martínez-Abundis, Esperanza

    2017-08-01

    Impaired glucose tolerance (IGT) and glycemic variability may be associated with increased risk of micro- and macrovascular complications. The aim of this study was to assess the effect of linagliptin versus metformin on glycemic variability in patients with IGT. A randomized, double-blind clinical trial with parallel groups was carried out in 16 adult patients with IGT, overweight or obesity. All patients signed an informed consent. The therapies were randomly assigned: (a) metformin 500 mg bid (n = 8) or (b) linagliptin 5 mg a.m. and placebo p.m. (n = 8), both for 90 days. At the beginning of the trial and 3 months later, fasting glucose, glycated hemoglobin A1c, oral glucose tolerance test (OGTT), and glycemic variability [area under the curve (AUC) of glucose, mean amplitude of glycemic excursion (MAGE), standard deviation (SD) of glucose, coefficient of variation (CV) of glucose, and mean blood glucose (MBG)] were measured. Mann-Whitney U, Wilcoxon, and Fisher exact tests were used for statistical analyses. Both groups were similar in basal characteristics. After linagliptin administration, a significant decrease in glucose levels at 120 min of OGTT (9.0 ± 0.9 vs. 6.9 ± 2.2 mmol/L, P = 0.012) was observed. Glycemic variability showed a similar behavior and there were no significant differences in the AUC, MAGE, SD of glucose, CV of glucose, and MBG between groups. Linagliptin administration resulted in better glycemic control according to the decrease of glucose levels by the OGTT at 120 min in patients with IGT. Meanwhile, glycemic variability was not modified in any of the study groups.

  15. The MGED Ontology: a resource for semantics-based description of microarray experiments.

    PubMed

    Whetzel, Patricia L; Parkinson, Helen; Causton, Helen C; Fan, Liju; Fostel, Jennifer; Fragoso, Gilberto; Game, Laurence; Heiskanen, Mervi; Morrison, Norman; Rocca-Serra, Philippe; Sansone, Susanna-Assunta; Taylor, Chris; White, Joseph; Stoeckert, Christian J

    2006-04-01

    The generation of large amounts of microarray data and the need to share these data bring challenges for both data management and annotation and highlights the need for standards. MIAME specifies the minimum information needed to describe a microarray experiment and the Microarray Gene Expression Object Model (MAGE-OM) and resulting MAGE-ML provide a mechanism to standardize data representation for data exchange, however a common terminology for data annotation is needed to support these standards. Here we describe the MGED Ontology (MO) developed by the Ontology Working Group of the Microarray Gene Expression Data (MGED) Society. The MO provides terms for annotating all aspects of a microarray experiment from the design of the experiment and array layout, through to the preparation of the biological sample and the protocols used to hybridize the RNA and analyze the data. The MO was developed to provide terms for annotating experiments in line with the MIAME guidelines, i.e. to provide the semantics to describe a microarray experiment according to the concepts specified in MIAME. The MO does not attempt to incorporate terms from existing ontologies, e.g. those that deal with anatomical parts or developmental stages terms, but provides a framework to reference terms in other ontologies and therefore facilitates the use of ontologies in microarray data annotation. The MGED Ontology version.1.2.0 is available as a file in both DAML and OWL formats at http://mged.sourceforge.net/ontologies/index.php. Release notes and annotation examples are provided. The MO is also provided via the NCICB's Enterprise Vocabulary System (http://nciterms.nci.nih.gov/NCIBrowser/Dictionary.do). Stoeckrt@pcbi.upenn.edu Supplementary data are available at Bioinformatics online.

  16. The roles of values, behavior, and value-behavior fit in the relation of agency and communion to well-being.

    PubMed

    Buchanan, Kathryn; Bardi, Anat

    2015-06-01

    Four studies examined whether agency and communion values, behaviors, or an interaction between values and behaviors (value-behavior fit) would predict well-being. In addition, Study 2 examined whether agency and communion goals, behaviors, or goal-behavior fit would predict well-being. In all four studies, participants completed online questionnaires containing measures of agency and communion values, behaviors, and well-being. In Studies 1 and 4, participants were recruited from the general population (respectively, N = 371, Mage  = 37.49, and N = 133, Mage  = 36.59). In Studies 2 and 3, participants were undergraduate students (respectively, N = 239, Mage  = 20.8, and N = 242, Mage  = 21.6). All four studies consistently found that agency and communion behaviors were significantly positively correlated with both subjective and psychological well-being. There was no strong indication that either values were directly associated with well-being. Neither was there any indication that well-being was predicted by value-behavior fit. The implications of these findings for theory and improving well-being are discussed. © 2014 Wiley Periodicals, Inc.

  17. The relationship between help-seeking attitudes and masculine norms among monozygotic male twins discordant for sexual orientation.

    PubMed

    Sánchez, Francisco J; Bocklandt, Sven; Vilain, Eric

    2013-01-01

    In general, heterosexual men are less favorable to asking for help compared to women and gay men. This can be problematic if a man avoids professional help when he is experiencing significant psychological distress. Yet, it is unclear to what degree such attitudes among men are due to innate differences or social environments. Studying twins provides one avenue for teasing apart these relationships. We recruited 38 pairs of monozygotic male twins (Mage = 35.87 years, SD = 9.52) raised together and who were discordant for sexual orientation. They completed measures of psychological distress (Symptom Checklist-90-Revised), positive attitudes toward psychological help-seeking behavior, and emphasis with fulfilling traditional masculine norms. Contrary to predictions, the heterosexual twins expressed more symptoms of specific distress-hostility (r = .30), paranoid ideation (r = .26), and psychoticism (r = .24)-than their gay cotwins. As predicted, heterosexual men were less favorable to seeking help (r = .25) and expressed greater emphasis on masculine norms (r = .26) than their cotwins. Within each group of men, unique aspects of masculine norms were significantly related to attitudes toward psychological help-seeking behavior. The findings lend credence to the hypothesis that social environments influence attitudes and behaviors that are stereotypically masculine and potentially detrimental to men's health. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  18. Pyroxenes in Serra de Mage - Cooling history in comparison with Moama and Moore County

    NASA Technical Reports Server (NTRS)

    Harlow, G. E.; Prinz, M.; Nehru, C. E.; Taylor, G. J.; Keil, K.

    1979-01-01

    Thin sections and single grains of pyroxenes from the Serra de Mage feldspar cumulate eucrites were studied by X-ray crystallography, electron microprobe and optical techniques. It was concluded that the pyroxene crystallized as pigeonite. On cooling augite was exsolved along (001) and inverted to hypersthene, with exsolution of (100) augite from hypersthene during continued slow cooling. The estimated original bulk composition of the pigeonite pyroxene is Wo10En51Fs39. The compositional data, textural relations, and existence of P2 sub 1 ca hypersthene suggest very low cooling (about 0.0004 deg C/year) below 800 deg. The Serra de Mage augite lamellae were found to be as thick or thicker than those of Moore County and Moama meteorites.

  19. Associations Between Maternal Mental Health and Well-being and Physical Activity and Sedentary Behavior in Children.

    PubMed

    Maher, Jaclyn P; Ra, Chaelin; OʼConnor, Sydney G; Belcher, Britni R; Leventhal, Adam; Margolin, Gayla; Dunton, Genevieve F

    This study assessed whether aspects of maternal mental health and well-being were associated with objective monitor-based measures of child's physical activity (PA) and sedentary behavior (SB) and the extent to which household structure (i.e., single- vs multigenerational/dual-parent) and maternal employment (i.e., full-time vs not full-time) moderated those associations. Dyads (N = 191) of mothers and their 8- to 12-year-old children participated in the baseline wave of the Mother's and Their Children's Health study. Mothers (Mage = 40.9 yr [SD = 6.1]; 49% Hispanic) completed a battery of questionnaires to assess maternal mental health and well-being (i.e., self-esteem, life satisfaction, depressive symptoms, anxiety, perceived stress, parenting stress, financial stress, and life events stress). Children (Mage = 9.6 yr [SD = 0.9]; 54% Hispanic; 51% girls) wore an accelerometer across 1 week during waking hours to objectively measure moderate-to-vigorous PA (MVPA) and SB. In single-parent families (n = 47), but not multigenerational/dual-parent families, mothers' parenting stress was negatively associated with child's MVPA (β = -.34, p = .02). In corrected analyses, all other aspects of maternal mental health and well-being were not related to children's activity patterns. Parenting stress was the only maternal mental health variable associated with objective monitor-based measures of child's PA after adjusting for multiple comparisons. Results indicated weaker associations between maternal mental health and well-being and child's MVPA and SB than previously identified using subjective measures of behavior. Study findings support the need to use objective measurements of child's activity patterns to minimize potential confounding because of maternal report in evaluating child's PA and SB.

  20. Association of glycaemic variability evaluated by continuous glucose monitoring with diabetic peripheral neuropathy in type 2 diabetic patients.

    PubMed

    Hu, Yu-Ming; Zhao, Li-Hua; Zhang, Xiu-Lin; Cai, Hong-Li; Huang, Hai-Yan; Xu, Feng; Chen, Tong; Wang, Xue-Qin; Guo, Ai-Song; Li, Jian-An; Su, Jian-Bin

    2018-05-01

    Diabetic peripheral neuropathy (DPN), a common microvascular complication of diabetes, is linked to glycaemic derangements. Glycaemic variability, as a pattern of glycaemic derangements, is a key risk factor for diabetic complications. We investigated the association of glycaemic variability with DPN in a large-scale sample of type 2 diabetic patients. In this cross-sectional study, we enrolled 982 type 2 diabetic patients who were screened for DPN and monitored by a continuous glucose monitoring (CGM) system between February 2011 and January 2017. Multiple glycaemic variability parameters, including the mean amplitude of glycaemic excursions (MAGE), mean of daily differences (MODD), standard deviation of glucose (SD), and 24-h mean glucose (24-h MG), were calculated from glucose profiles obtained from CGM. Other possible risks for DPN were also examined. Of the recruited type 2 diabetic patients, 20.1% (n = 197) presented with DPN, and these patients also had a higher MAGE, MODD, SD, and 24-h MG than patients without DPN (p < 0.001). Using univariate and multiple logistic regression analyses, MAGE and conventional risks including diabetic duration, HOMA-IR, and hemoglobin A1c (HbA1c) were found to be independent contributors to DPN, and the corresponding odds ratios (95% confidence interval) were 4.57 (3.48-6.01), 1.10 (1.03-1.17), 1.24 (1.09-1.41), and 1.33 (1.15-1.53), respectively. Receiver operating characteristic analysis indicated that the optimal MAGE cutoff value for predicting DPN was 4.60 mmol/L; the corresponding sensitivity was 64.47%, and the specificity was 75.54%. In addition to conventional risks including diabetic duration, HOMA-IR and HbA1c, increased glycaemic variability assessed by MAGE is a significant independent contributor to DPN in type 2 diabetic patients.

  1. Using Digital Health Technologies to Understand the Association Between Movement Behaviors and Interstitial Glucose: Exploratory Analysis

    PubMed Central

    Whelan, Maxine E; Sanders, James P; Sherar, Lauren B; Esliger, Dale W

    2018-01-01

    Background Acute reductions in postprandial glucose excursions because of movement behaviors have been demonstrated in experimental studies but less so in free-living settings. Objective The objective of this study was to explore the nature of the acute stimulus-response model between accelerometer-assessed physical activity, sedentary time, and glucose variability over 13 days in nondiabetic adults. Methods This study measured physical activity, sedentary time, and interstitial glucose continuously over 13 days in 29 participants (mean age in years: 44.9 [SD 9.1]; female: 59%, 17/29; white: 90%, 26/29; mean body mass index: 25.3 [SD 4.1]) as part of the Sensing Interstitial Glucose to Nudge Active Lifestyles (SIGNAL) research program. Daily minutes spent sedentary, in light activity, and moderate to vigorous physical activity were associated with daily mean glucose, SD of glucose, and mean amplitude of glycemic excursions (MAGE) using generalized estimating equations. Results After adjustment for covariates, sedentary time in minutes was positively associated with a higher daily mean glucose (mmol/L; beta=0.0007; 95% CI 0.00030-0.00103; P<.001), SD of glucose (mmol/L; beta=0.0006; 95% CI 0.00037-0.00081; P<.001), and MAGE (mmol/L; beta=0.002; 95% CI 0.00131-0.00273; P<.001) for those of a lower fitness. Additionally, light activity was inversely associated with mean glucose (mmol/L; beta=−0.0004; 95% CI −0.00078 to −0.00006; P=.02), SD of glucose (mmol/L; beta=−0.0006; 95% CI −0.00085 to −0.00039; P<.001), and MAGE (mmol/L; beta=−0.002; 95% CI −0.00285 to −0.00146; P<.001) for those of a lower fitness. Moderate to vigorous physical activity was only inversely associated with mean glucose (mmol/L; beta=−0.002; 95% CI −0.00250 to −0.00058; P=.002). Conclusions Evidence of an acute stimulus-response model was observed between sedentary time, physical activity, and glucose variability in low fitness individuals, with sedentary time and light activity conferring the most consistent changes in glucose variability. Further work is required to investigate the coupling of movement behaviors and glucose responses in larger samples and whether providing these rich data sources as feedback could induce lifestyle behavior change. PMID:29724703

  2. Using three-phase theory-based formative research to explore healthy eating in Australian truck drivers.

    PubMed

    Vayro, Caitlin; Hamilton, Kyra

    2016-03-01

    In Australia, fruit and vegetable consumption is lower than recommended while discretionary foods (i.e., foods high in fat, sugar, and salt) are eaten in excess. Long-haul truck drivers are a group at risk of unhealthy eating but have received limited attention in the health literature. We aimed to examine long-haul truck drivers eating decisions in order to develop theory-based and empirically-driven health messages to improve their healthy food choices. Drawing on the Theory of Planned Behavior, three-phased formative research was conducted using self-report surveys. Phase 1 (N = 30, Mage = 39.53, SDage = 10.72) identified modal salient beliefs about fruit and vegetable (FV) intake and limiting discretionary choices (DC). There were nine behavioral and seven normative beliefs elicited for both FV and DC; while nine and five control beliefs were elicited for FV and DC, respectively. Phase 2 (N = 148, Mage = 44.23, SDage = 12.08) adopted a prospective design with one week follow-up to examine the predictors of FV and DC intention and behavior. A variety of behavioral and control beliefs were predictive of FV and DC intention and behavior. Normative beliefs were predictive of FV intention and behavior and DC intention only. Phase 3 (N = 20, Mage = 46.9, SDage = 12.85) elicited the reasons why each belief is held/solutions to negative beliefs, that could be used as health messages. In total, 40 reasons/solutions were identified: 26 for FV and 14 for DC. In summary, we found that specific behavioral, normative and control beliefs influenced FV and DC eating decisions. These results have implications for truck driver's health and provide formative research to inform future interventions to improve the food choices of a unique group who are at risk of unhealthy eating behaviors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. “They Were Just Making Jokes”: Ethnic/Racial Teasing and Discrimination Among Adolescents

    PubMed Central

    Douglass, Sara; Mirpuri, Sheena; English, Devin; Yip, Tiffany

    2015-01-01

    Objectives The effects of peer-based discrimination are especially harmful for adolescents given the heightened role of social feedback during this period. The current study aimed to understand the unique expressions of discrimination that adolescents experience between close peers and friends, as well as the daily influence of such experiences. Method Study 1 included semistructured interviews (10 interviews, 2 focus groups; Mage = 17.3) with an ethnic/racially diverse sample of adolescence. Study 2 (n = 79; Mage = 15.72) used a 21-day daily diary study with a different sample of ethnic/racially diverse adolescents. Results Study 1 found that, among close peers and friends, adolescents experienced “ethnic/racial teasing,” a unique form of discrimination characterized by humor. Additionally, adolescents consistently dismissed the negative messages as innocuous based on the supposedly humorous nature of such interactions. Study 2 found that when adolescents were targeted for ethnic/racial teasing, individuals who were already anxious experienced increased daily anxiety, and that increases in social anxiety persisted across days. Conclusions The current study suggests that among peers, ethnic/racial teasing is a common way that adolescents interact around ethnicity/race. Further, this study points to the complexity of these experiences; though they were largely considered normative and harmless, they also had negative psychological effects for some adolescents. Implications for our conceptual understanding of discrimination and teasing during adolescence are discussed. PMID:26009942

  4. "They were just making jokes": Ethnic/racial teasing and discrimination among adolescents.

    PubMed

    Douglass, Sara; Mirpuri, Sheena; English, Devin; Yip, Tiffany

    2016-01-01

    The effects of peer-based discrimination are especially harmful for adolescents given the heightened role of social feedback during this period. The current study aimed to understand the unique expressions of discrimination that adolescents experience between close peers and friends, as well as the daily influence of such experiences. Study 1 included semistructured interviews (10 interviews, 2 focus groups; Mage = 17.3) with an ethnic/racially diverse sample of adolescence. Study 2 (n = 79; Mage = 15.72) used a 21-day daily diary study with a different sample of ethnic/racially diverse adolescents. Study 1 found that, among close peers and friends, adolescents experienced "ethnic/racial teasing," a unique form of discrimination characterized by humor. Additionally, adolescents consistently dismissed the negative messages as innocuous based on the supposedly humorous nature of such interactions. Study 2 found that when adolescents were targeted for ethnic/racial teasing, individuals who were already anxious experienced increased daily anxiety, and that increases in social anxiety persisted across days. The current study suggests that among peers, ethnic/racial teasing is a common way that adolescents interact around ethnicity/race. Further, this study points to the complexity of these experiences; though they were largely considered normative and harmless, they also had negative psychological effects for some adolescents. Implications for our conceptual understanding of discrimination and teasing during adolescence are discussed. (c) 2016 APA, all rights reserved).

  5. A randomized controlled trial to compare the effects of sulphonylurea gliclazide MR (modified release) and the DPP-4 inhibitor vildagliptin on glycemic variability and control measured by continuous glucose monitoring (CGM) in Brazilian women with type 2 diabetes.

    PubMed

    Vianna, Andre Gustavo Daher; Lacerda, Claudio Silva; Pechmann, Luciana Muniz; Polesel, Michelle Garcia; Marino, Emerson Cestari; Faria-Neto, Jose Rocha

    2018-05-01

    This study aims to evaluate whether there is a difference between the effects of vildagliptin and gliclazide MR (modified release) on glycemic variability (GV) in women with type 2 diabetes (T2DM) as evaluated by continuous glucose monitoring (CGM). An open-label, randomized study was conducted in T2DM women on steady-dose metformin monotherapy which were treated with 50 mg vildagliptin twice daily or 60-120 mg of gliclazide MR once daily. CGM and GV indices calculation were performed at baseline and after 24 weeks. In total, 42 patients (age: 61.9 ± 5.9 years, baseline glycated hemoglobin (HbA1c): 7.3 ± 0.56) were selected and 37 completed the 24-week protocol. Vildagliptin and gliclazide MR reduced GV, as measured by the mean amplitude of glycemic excursions (MAGE, p = 0.007 and 0.034, respectively). The difference between the groups did not reach statistical significance. Vildagliptin also significantly decreased the standard deviation of the mean glucose (SD) and the mean of the daily differences (MODD) (p = 0.007 and 0.030). Vildagliptin and gliclazide MR similarly reduced the MAGE in women with T2DM after 24 weeks of treatment. Further studies are required to attest differences between vildagliptin and gliclazide MR regarding glycemic variability. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Longitudinal Predictors of Vocabulary Knowledge in Turkish Children: The Role of Maternal Warmth, Inductive Reasoning, and Children's Inhibitory Control

    ERIC Educational Resources Information Center

    Ekerim, Muge; Selcuk, Bilge

    2018-01-01

    Research Findings: The present study investigated the social and cognitive precursors of vocabulary knowledge in 239 Turkish preschoolers both concurrently (Time 1 [T1] Mage = 53.29 months, SD = 10.19) and subsequently 1 year later (Time 2 [T2] Mage = 65.40 months, SD = 10.55). We examined the role of parenting behaviors by focusing on emotional…

  7. iMAGE cloud: medical image processing as a service for regional healthcare in a hybrid cloud environment.

    PubMed

    Liu, Li; Chen, Weiping; Nie, Min; Zhang, Fengjuan; Wang, Yu; He, Ailing; Wang, Xiaonan; Yan, Gen

    2016-11-01

    To handle the emergence of the regional healthcare ecosystem, physicians and surgeons in various departments and healthcare institutions must process medical images securely, conveniently, and efficiently, and must integrate them with electronic medical records (EMRs). In this manuscript, we propose a software as a service (SaaS) cloud called the iMAGE cloud. A three-layer hybrid cloud was created to provide medical image processing services in the smart city of Wuxi, China, in April 2015. In the first step, medical images and EMR data were received and integrated via the hybrid regional healthcare network. Then, traditional and advanced image processing functions were proposed and computed in a unified manner in the high-performance cloud units. Finally, the image processing results were delivered to regional users using the virtual desktop infrastructure (VDI) technology. Security infrastructure was also taken into consideration. Integrated information query and many advanced medical image processing functions-such as coronary extraction, pulmonary reconstruction, vascular extraction, intelligent detection of pulmonary nodules, image fusion, and 3D printing-were available to local physicians and surgeons in various departments and healthcare institutions. Implementation results indicate that the iMAGE cloud can provide convenient, efficient, compatible, and secure medical image processing services in regional healthcare networks. The iMAGE cloud has been proven to be valuable in applications in the regional healthcare system, and it could have a promising future in the healthcare system worldwide.

  8. Immunomodulatory action of SGI-110, a hypomethylating agent, in acute myeloid leukemia cells

    PubMed Central

    Srivastava, Pragya; Paluch, Benjamin E.; Matsuzaki, Junko; James, Smitha R.; Collamat-Lai, Golda; Karbach, Julia; Nemeth, Michael J.; Taverna, Pietro; Karpf, Adam R.; Griffiths, Elizabeth A.

    2017-01-01

    The mechanism of clinical action for the FDA approved hypomethylating drugs azacitidine and decitabine remains unresolved and in this context the potential immunomodulatory effect of these agents on leukemic cells is an area of active investigation. Induced expression of methylated Cancer Testis Antigen (CTA) genes has been demonstrated in leukemic cell lines following exposure to hypomethylating drugs in vitro. SGI-110 is a novel hypomethylating dinucleotide with prolonged in vivo exposure and clinical activity in patients with MDS and AML. We demonstrate that this agent, like decitabine, produces robust re-expression of the CTAs NY-ESO-1 and MAGE-A, both in vitro and in leukemia-bearing AML xenografts. Upregulation of these genes in vitro was sufficient to induce cytotoxicity by HLA-compatible CD8+ T-cells specific for NY-ESO-1, a well-recognized and immunogenic CTA. Additionally, exposure to SGI-110 enhances MHC class I and co-stimulatory molecule expression, potentially contributing to recognition of CTAs. SGI-110, like the parent compound decitabine, induces expression of CTAs and might modulate immune recognition of myeloid malignancy. PMID:25260825

  9. Programming cells by multiplex genome engineering and accelerated evolution.

    PubMed

    Wang, Harris H; Isaacs, Farren J; Carr, Peter A; Sun, Zachary Z; Xu, George; Forest, Craig R; Church, George M

    2009-08-13

    The breadth of genomic diversity found among organisms in nature allows populations to adapt to diverse environments. However, genomic diversity is difficult to generate in the laboratory and new phenotypes do not easily arise on practical timescales. Although in vitro and directed evolution methods have created genetic variants with usefully altered phenotypes, these methods are limited to laborious and serial manipulation of single genes and are not used for parallel and continuous directed evolution of gene networks or genomes. Here, we describe multiplex automated genome engineering (MAGE) for large-scale programming and evolution of cells. MAGE simultaneously targets many locations on the chromosome for modification in a single cell or across a population of cells, thus producing combinatorial genomic diversity. Because the process is cyclical and scalable, we constructed prototype devices that automate the MAGE technology to facilitate rapid and continuous generation of a diverse set of genetic changes (mismatches, insertions, deletions). We applied MAGE to optimize the 1-deoxy-D-xylulose-5-phosphate (DXP) biosynthesis pathway in Escherichia coli to overproduce the industrially important isoprenoid lycopene. Twenty-four genetic components in the DXP pathway were modified simultaneously using a complex pool of synthetic DNA, creating over 4.3 billion combinatorial genomic variants per day. We isolated variants with more than fivefold increase in lycopene production within 3 days, a significant improvement over existing metabolic engineering techniques. Our multiplex approach embraces engineering in the context of evolution by expediting the design and evolution of organisms with new and improved properties.

  10. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial

    PubMed Central

    Escudier, Bernard; Dorval, Thierry; Chaput, Nathalie; André, Fabrice; Caby, Marie-Pierre; Novault, Sophie; Flament, Caroline; Leboulaire, Christophe; Borg, Christophe; Amigorena, Sebastian; Boccaccio, Catherine; Bonnerot, Christian; Dhellin, Olivier; Movassagh, Mojgan; Piperno, Sophie; Robert, Caroline; Serra, Vincent; Valente, Nancy; Le Pecq, Jean-Bernard; Spatz, Alain; Lantz, Olivier; Tursz, Thomas; Angevin, Eric; Zitvogel, Laurence

    2005-01-01

    Background DC derived-exosomes are nanomeric vesicles harboring functional MHC/peptide complexes capable of promoting T cell immune responses and tumor rejection. Here we report the feasability and safety of the first Phase I clinical trial using autologous exosomes pulsed with MAGE 3 peptides for the immunization of stage III/IV melanoma patients. Secondary endpoints were the monitoring of T cell responses and the clinical outcome. Patients and methods Exosomes were purified from day 7 autologous monocyte derived-DC cultures. Fifteen patients fullfilling the inclusion criteria (stage IIIB and IV, HLA-A1+, or -B35+ and HLA-DPO4+ leukocyte phenotype, tumor expressing MAGE3 antigen) were enrolled from 2000 to 2002 and received four exosome vaccinations. Two dose levels of either MHC class II molecules (0.13 versus 0.40 × 1014 molecules) or peptides (10 versus 100 μg/ml) were tested. Evaluations were performed before and 2 weeks after immunization. A continuation treatment was performed in 4 cases of non progression. Results The GMP process allowed to harvest about 5 × 1014 exosomal MHC class II molecules allowing inclusion of all 15 patients. There was no grade II toxicity and the maximal tolerated dose was not achieved. One patient exhibited a partial response according to the RECIST criteria. This HLA-B35+/A2+ patient vaccinated with A1/B35 defined CTL epitopes developed halo of depigmentation around naevi, a MART1-specific HLA-A2 restricted T cell response in the tumor bed associated with progressive loss of HLA-A2 and HLA-BC molecules on tumor cells during therapy with exosomes. In addition, one minor, two stable and one mixed responses were observed in skin and lymph node sites. MAGE3 specific CD4+ and CD8+ T cell responses could not be detected in peripheral blood. Conclusion The first exosome Phase I trial highlighted the feasibility of large scale exosome production and the safety of exosome administration. PMID:15740633

  11. A role for NRAGE in NF-κB activation through the non-canonical BMP pathway

    PubMed Central

    2010-01-01

    Background Previous studies have linked neurotrophin receptor-interacting MAGE protein to the bone morphogenic protein signaling pathway and its effect on p38 mediated apoptosis of neural progenitor cells via the XIAP-Tak1-Tab1 complex. Its effect on NF-κB has yet to be explored. Results Herein we report that NRAGE, via the same XIAP-Tak1-Tab1 complex, is required for the phosphorylation of IKK -α/β and subsequent transcriptional activation of the p65 subunit of NF-κB. Ablation of endogenous NRAGE by siRNA inhibited NF-κB pathway activation, while ablation of Tak1 and Tab1 by morpholino inhibited overexpression of NRAGE from activating NF-κB. Finally, cytokine profiling of an NRAGE over-expressing stable line revealed the expression of macrophage migration inhibitory factor. Conclusion Modulation of NRAGE expression revealed novel roles in regulating NF-κB activity in the non-canonical bone morphogenic protein signaling pathway. The expression of macrophage migration inhibitory factor by bone morphogenic protein -4 reveals novel crosstalk between an immune cytokine and a developmental pathway. PMID:20100315

  12. The Predictive Validity of Four Intelligence Tests for School Grades: A Small Sample Longitudinal Study

    PubMed Central

    Gygi, Jasmin T.; Hagmann-von Arx, Priska; Schweizer, Florine; Grob, Alexander

    2017-01-01

    Intelligence is considered the strongest single predictor of scholastic achievement. However, little is known regarding the predictive validity of well-established intelligence tests for school grades. We analyzed the predictive validity of four widely used intelligence tests in German-speaking countries: The Intelligence and Development Scales (IDS), the Reynolds Intellectual Assessment Scales (RIAS), the Snijders-Oomen Nonverbal Intelligence Test (SON-R 6-40), and the Wechsler Intelligence Scale for Children (WISC-IV), which were individually administered to 103 children (Mage = 9.17 years) enrolled in regular school. School grades were collected longitudinally after 3 years (averaged school grades, mathematics, and language) and were available for 54 children (Mage = 11.77 years). All four tests significantly predicted averaged school grades. Furthermore, the IDS and the RIAS predicted both mathematics and language, while the SON-R 6-40 predicted mathematics. The WISC-IV showed no significant association with longitudinal scholastic achievement when mathematics and language were analyzed separately. The results revealed the predictive validity of currently used intelligence tests for longitudinal scholastic achievement in German-speaking countries and support their use in psychological practice, in particular for predicting averaged school grades. However, this conclusion has to be considered as preliminary due to the small sample of children observed. PMID:28348543

  13. Possible involvement of loss of imprinting in immortalization of human fibroblasts.

    PubMed

    Okamura, Kotaro; Ohno, Maki; Tsutsui, Takeki

    2011-04-01

    Disruption of the normal pattern of parental origin-specific gene expression is referred to as loss of imprinting (LOI), which is common in various cancers. To investigate a possible role of LOI in the early stage of human cell transformation, we studied LOI in 18 human fibroblast cell lines immortalized spontaneously, by viral oncogenes, by chemical or physical carcinogens, or by infection with a retrovirus vector encoding the human telomerase catalytic subunit, hTERT cDNA. LOI was observed in all the 18 immortal cell lines. The gene most commonly exhibiting LOI was NDN which displayed LOI in 15 of the 18 cell lines (83%). The other genes exhibiting LOI at high frequencies were PEG3 (50%), MAGE-L2 (61%) and ZNF 127 (50%). Expression of NDN that was lost in the immortal cell lines was restored by treatment with 5-aza-2'-deoxycytidine. The ratio of histone H3 lysine 9 methylation to histone H3 lysine 4 methylation of the chromatin containing the NDN promoter in the immortal WI-38VA13 cells was greater than that in the parental cells, suggesting chromatin structure-mediated regulation of NDN expression. We previously demonstrated that inactivation of the p16INK4a/pRb pathway is necessary for immortalization of human cells. Human fibroblasts in the pre-crisis phase and cells with an extended lifespan that eventually senesce, both of which have the normal p16INK4a/pRb pathway, did not show LOI at any imprinted gene examined. Although it is not clear if LOI plays a causal role in immortalization of human cells or is merely coincidental, these findings indicate a possible involvement of LOI in immortalization of human cells or a common mechanism involved in both processes.

  14. First Attempt of Glycidol-to-Monoalkyl Glyceryl Ethers Conversion by Acid Heterogeneous Catalysis: Synthesis and Simplified Sustainability Assessment.

    PubMed

    Ricciardi, Maria; Passarini, Fabrizio; Capacchione, Carmine; Proto, Antonio; Barrault, Joel; Cucciniello, Raffaele; Cespi, Daniele

    2018-04-14

    The selective preparation of monoalkylglyceryl ethers (MAGEs) is a task for researchers owing to their broad range of applications. In this work, green feedstocks such as glycidol and alcohols were used to prepare MAGEs under mild reaction conditions (80 °C, 3 h, 0.5 mol % catalyst) in the presence of acid heterogeneous catalysts. Nafion shows the best performances in terms of conversion and selectivity to MAGES and also high stability. A comparison of the environmental performances with the most consolidated pathway from glycerol has shown that the usage of glycidol (recovered as a value-added product from Epicerol process) and Nafion leads to a lower impact on ecosystems. In addition, results achieved from a simplified socio-economic analysis show that the innovative route here proposed has potential (at the laboratory scale) of enhancing potential gains and of reducing the social implications resulting from externalities associated with environmental impacts (e.g., CO 2 equivalents). © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Individual differences in the components of children's and adults' information processing for simple symbolic and non-symbolic numeric decisions.

    PubMed

    Thompson, Clarissa A; Ratcliff, Roger; McKoon, Gail

    2016-10-01

    How do speed and accuracy trade off, and what components of information processing develop as children and adults make simple numeric comparisons? Data from symbolic and non-symbolic number tasks were collected from 19 first graders (Mage=7.12 years), 26 second/third graders (Mage=8.20 years), 27 fourth/fifth graders (Mage=10.46 years), and 19 seventh/eighth graders (Mage=13.22 years). The non-symbolic task asked children to decide whether an array of asterisks had a larger or smaller number than 50, and the symbolic task asked whether a two-digit number was greater than or less than 50. We used a diffusion model analysis to estimate components of processing in tasks from accuracy, correct and error response times, and response time (RT) distributions. Participants who were accurate on one task were accurate on the other task, and participants who made fast decisions on one task made fast decisions on the other task. Older participants extracted a higher quality of information from the stimulus arrays, were more willing to make a decision, and were faster at encoding, transforming the stimulus representation, and executing their responses. Individual participants' accuracy and RTs were uncorrelated. Drift rate and boundary settings were significantly related across tasks, but they were unrelated to each other. Accuracy was mainly determined by drift rate, and RT was mainly determined by boundary separation. We concluded that RT and accuracy operate largely independently. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Cross-Cultural Invariance of the Mental Toughness Inventory Among Australian, Chinese, and Malaysian Athletes: A Bayesian Estimation Approach.

    PubMed

    Gucciardi, Daniel F; Zhang, Chun-Qing; Ponnusamy, Vellapandian; Si, Gangyan; Stenling, Andreas

    2016-04-01

    The aims of this study were to assess the cross-cultural invariance of athletes' self-reports of mental toughness and to introduce and illustrate the application of approximate measurement invariance using Bayesian estimation for sport and exercise psychology scholars. Athletes from Australia (n = 353, Mage = 19.13, SD = 3.27, men = 161), China (n = 254, Mage = 17.82, SD = 2.28, men = 138), and Malaysia (n = 341, Mage = 19.13, SD = 3.27, men = 200) provided a cross-sectional snapshot of their mental toughness. The cross-cultural invariance of the mental toughness inventory in terms of (a) the factor structure (configural invariance), (b) factor loadings (metric invariance), and (c) item intercepts (scalar invariance) was tested using an approximate measurement framework with Bayesian estimation. Results indicated that approximate metric and scalar invariance was established. From a methodological standpoint, this study demonstrated the usefulness and flexibility of Bayesian estimation for single-sample and multigroup analyses of measurement instruments. Substantively, the current findings suggest that the measurement of mental toughness requires cultural adjustments to better capture the contextually salient (emic) aspects of this concept.

  17. Glycemic excursions are positively associated with changes in duration of asymptomatic hypoglycemia after treatment intensification in patients with type 2 diabetes.

    PubMed

    Wang, Jun-Sing; Lee, I-Te; Lee, Wen-Jane; Lin, Shi-Dou; Su, Shih-Li; Tu, Shih-Te; Tseng, Yao-Hsien; Lin, Shih-Yi; Sheu, Wayne Huey-Herng

    2016-03-01

    The aim of this study was to examine the association between glycemic excursions and duration of hypoglycemia after treatment intensification in patients with type 2 diabetes (T2D). Patients with T2D on oral anti-diabetes drug (OAD) with glycated hemoglobin (HbA1c) of 7.0-11.0% were switched to metformin monotherapy (500 mg thrice daily) for 8 weeks, followed by randomization to either glibenclamide or acarbose as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring (CGM) before randomization and at the end of study. Hypoglycemia was defined as sensor glucose level of less than 60 mg/dl in two or more consecutive readings from CGM. A total of 50 patients (mean age 53.5 ± 8.2 years, male 48%, mean baseline HbA1c 8.4 ± 1.2%) were analyzed. Duration of hypoglycemia significantly increased after treatment with glibenclamide (from 5.5 ± 13.8 to 18.8 ± 35.8 min/day, p=0.041), but not with acarbose (from 2.9 ± 10.9 to 14.7 ± 41.9 min/day, p=0.114). Post treatment MAGE was positively associated with change from baseline in duration of hypoglycemia after treatment with either glibenclamide (β coefficient 0.345, p=0.036) or acarbose (β coefficient 0.674, p=0.046). The association remained significant after multivariate adjustment (p<0.05 for all models). Post treatment glycemic excursions are associated with changes in duration of hypoglycemia after treatment intensification with OAD in patients with T2D. Glycemic excursions should be an important treatment target for T2D to reduce the risk of hypoglycemia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. The Smc5/Smc6/MAGE Complex Confers Resistance to Caffeine and Genotoxic Stress in Drosophila melanogaster

    PubMed Central

    Li, Xiao; Zhuo, Ran; Tiong, Stanley; Di Cara, Francesca; King-Jones, Kirst; Hughes, Sarah C.; Campbell, Shelagh D.; Wevrick, Rachel

    2013-01-01

    The SMC5/6 protein complex consists of the Smc5, Smc6 and Non-Smc-Element (Nse) proteins and is important for genome stability in many species. To identify novel components in the DNA repair pathway, we carried out a genetic screen to identify mutations that confer reduced resistance to the genotoxic effects of caffeine, which inhibits the ATM and ATR DNA damage response proteins. This approach identified inactivating mutations in CG5524 and MAGE, homologs of genes encoding Smc6 and Nse3 in yeasts. The fact that Smc5 mutants are also caffeine-sensitive and that Mage physically interacts with Drosophila homologs of Nse proteins suggests that the structure of the Smc5/6 complex is conserved in Drosophila. Although Smc5/6 proteins are required for viability in S. cerevisiae, they are not essential under normal circumstances in Drosophila. However, flies carrying mutations in Smc5, Smc6 and MAGE are hypersensitive to genotoxic agents such as ionizing radiation, camptothecin, hydroxyurea and MMS, consistent with the Smc5/6 complex serving a conserved role in genome stability. We also show that mutant flies are not compromised for pre-mitotic cell cycle checkpoint responses. Rather, caffeine-induced apoptosis in these mutants is exacerbated by inhibition of ATM or ATR checkpoint kinases but suppressed by Rad51 depletion, suggesting a functional interaction involving homologous DNA repair pathways that deserves further scrutiny. Our insights into the SMC5/6 complex provide new challenges for understanding the role of this enigmatic chromatin factor in multi-cellular organisms. PMID:23555814

  19. Familial Aggregation of Insomnia.

    PubMed

    Jarrin, Denise C; Morin, Charles M; Rochefort, Amélie; Ivers, Hans; Dauvilliers, Yves A; Savard, Josée; LeBlanc, Mélanie; Merette, Chantal

    2017-02-01

    There is little information about familial aggregation of insomnia; however, this type of information is important to (1) improve our understanding of insomnia risk factors and (2) to design more effective treatment and prevention programs. This study aimed to investigate evidence of familial aggregation of insomnia among first-degree relatives of probands with and without insomnia. Cases (n = 134) and controls (n = 145) enrolled in a larger epidemiological study were solicited to invite their first-degree relatives and spouses to complete a standardized sleep/insomnia survey. In total, 371 first-degree relatives (Mage = 51.9 years, SD = 18.0; 34.3% male) and 138 spouses (Mage = 55.5 years, SD = 12.2; 68.1% male) completed the survey assessing the nature, severity, and frequency of sleep disturbances. The dependent variable was insomnia in first-degree relatives and spouses. Familial aggregation was claimed if the risk of insomnia was significantly higher in the exposed (relatives of cases) compared to the unexposed cohort (relatives of controls). The risk of insomnia was also compared between spouses in the exposed (spouses of cases) and unexposed cohort (spouses of controls). The risk of insomnia in exposed and unexposed biological relatives was 18.6% and 10.4%, respectively, yielding a relative risk (RR) of 1.80 (p = .04) after controlling for age and sex. The risk of insomnia in exposed and unexposed spouses was 9.1% and 4.2%, respectively; however, corresponding RR of 2.13 (p = .28) did not differ significantly. Results demonstrate evidence of strong familial aggregation of insomnia. Additional research is warranted to further clarify and disentangle the relative contribution of genetic and environmental factors in insomnia. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  20. A pilot study of the effects of RightStart instruction on early numeracy skills of children with specific language impairment.

    PubMed

    Mononen, Riikka; Aunio, Pirjo; Koponen, Tuire

    2014-05-01

    This pilot study investigated the effects of an early numeracy program, RightStart Mathematics (RS), on Finnish kindergartners with specific language impairment (SLI). The study applied a pre-test-instruction-post-test design. The children with SLI (n=9, Mage=82.11 months) received RS instruction two to three times a week for 40 min over seven months, which replaced their business-as-usual mathematics instruction. Mathematical skill development among children with SLI was examined at the individual and group levels, and compared to the performance of normal language-achieving age peers (n=32, Mage=74.16 months) who received business-as-usual kindergarten mathematics instruction. The children with SLI began kindergarten with significantly weaker early numeracy skills compared to their peers. Immediately after the instruction phase, there was no significant difference between the groups in counting skills. In Grade 1, the children with SLI performed similarly to their peers in addition and subtraction skills (accuracy) and multi-digit number comparison, but showed weaker skills in arithmetical reasoning and in matching spoken and printed multi-digit numbers. Our pilot study showed encouraging signs that the early numeracy skills of children with SLI can be improved successfully in a kindergarten small-classroom setting with systematic instruction emphasizing visualization. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Reconstruction of Mouse Testicular Cellular Microenvironments in Long-Term Seminiferous Tubule Culture

    PubMed Central

    Mäkelä, Juho-Antti; Toppari, Jorma; Rivero-Müller, Adolfo; Ventelä, Sami

    2014-01-01

    Research on spermatogonia is hampered by complex architecture of the seminiferous tubule, poor viability of testicular tissue ex vivo and lack of physiologically relevant long-term culture systems. Therefore there is a need for an in vitro model that would enable long term survival and propagation of spermatogonia. We aimed at the most simplified approach to enable all different cell types within the seminiferous tubules to contribute to the creation of a niche for spermatogonia. In the present study we describe the establishment of a co-culture of mouse testicular cells that is based on proliferative and migratory activity of seminiferous tubule cells and does not involve separation, purification or differential plating of individual cell populations. The co-culture is composed of the constituents of testicular stem cell niche: Sertoli cells [identified by expression of Wilm's tumour antigen 1 (WT1) and secretion of glial cell line-derived neurotrophic factor, GDNF], peritubular myoid cells (expressing alpha smooth muscle actin, αSMA) and spermatogonia [expressing MAGE-B4, PLZF (promyelocytic leukaemia zinc finger), LIN28, Gpr125 (G protein-coupled receptor 125), CD9, c-Kit and Nanog], and can be maintained for at least five weeks. GDNF was found in the medium at a sufficient concentration to support proliferating spermatogonial stem cells (SSCs) that were able to start spermatogenic differentiation after transplantation to an experimentally sterile recipient testis. Gdnf mRNA levels were elevated by follicle-stimulating hormone (FSH) which shows that the Sertoli cells in the co-culture respond to physiological stimuli. After approximately 2–4 weeks of culture a spontaneous formation of cord-like structures was monitored. These structures can be more than 10 mm in length and branch. They are formed by peritubular myoid cells, Sertoli cells, fibroblasts and spermatogonia as assessed by gene expression profiling. In conclusion, we have managed to establish in vitro conditions that allow spontaneous reconstruction of testicular cellular microenvironments. PMID:24619130

  2. Performing label-fusion-based segmentation using multiple automatically generated templates.

    PubMed

    Chakravarty, M Mallar; Steadman, Patrick; van Eede, Matthijs C; Calcott, Rebecca D; Gu, Victoria; Shaw, Philip; Raznahan, Armin; Collins, D Louis; Lerch, Jason P

    2013-10-01

    Classically, model-based segmentation procedures match magnetic resonance imaging (MRI) volumes to an expertly labeled atlas using nonlinear registration. The accuracy of these techniques are limited due to atlas biases, misregistration, and resampling error. Multi-atlas-based approaches are used as a remedy and involve matching each subject to a number of manually labeled templates. This approach yields numerous independent segmentations that are fused using a voxel-by-voxel label-voting procedure. In this article, we demonstrate how the multi-atlas approach can be extended to work with input atlases that are unique and extremely time consuming to construct by generating a library of multiple automatically generated templates of different brains (MAGeT Brain). We demonstrate the efficacy of our method for the mouse and human using two different nonlinear registration algorithms (ANIMAL and ANTs). The input atlases consist a high-resolution mouse brain atlas and an atlas of the human basal ganglia and thalamus derived from serial histological data. MAGeT Brain segmentation improves the identification of the mouse anterior commissure (mean Dice Kappa values (κ = 0.801), but may be encountering a ceiling effect for hippocampal segmentations. Applying MAGeT Brain to human subcortical structures improves segmentation accuracy for all structures compared to regular model-based techniques (κ = 0.845, 0.752, and 0.861 for the striatum, globus pallidus, and thalamus, respectively). Experiments performed with three manually derived input templates suggest that MAGeT Brain can approach or exceed the accuracy of multi-atlas label-fusion segmentation (κ = 0.894, 0.815, and 0.895 for the striatum, globus pallidus, and thalamus, respectively). Copyright © 2012 Wiley Periodicals, Inc.

  3. Reproductive health rights and survival: The voices of mothers experiencing homelessness.

    PubMed

    Cronley, Courtney; Hohn, Kris; Nahar, Shamsun

    2018-03-01

    Women experiencing homelessness report higher rates of reproductive health-related traumas, including unplanned pregnancy, miscarriage, and abortion than their non-homeless peers. Using phenomenological hermeneutic methods, we sought to understand the reproductive health histories of women currently experiencing homelessness (N = 20, 25-61 years old, Mage = 38.33, SDage = 9.33) analyzing data collected between June 2014 and July 2015 in north central Texas. Three key themes highlight the essence of the women's experiences: (1) unexpected pregnancy-pregnancy just happened, (2) loss of reproductive health rights-I was broken, and (3) resilience-giving back and looking forward to good things. Many of the women became mothers through unexpected pregnancies, and overnight found that their lives were transformed irrevocably. Often unexpected pregnancy was the result or cause of a lack of ownership over their reproductive health and led to prolonged health-related traumas. Over time, though, many of the women whom we interviewed re-expressed resilience through social support, housing assistance, and a sense of giving back to society. Results indicate that reproductive health care providers require training to identify the relationship among unexpected pregnancy, reproductive health-related traumas, and housing insecurity. Providers can help preserve women's reproductive health rights through education and empowerment.

  4. Egfl6 is involved in zebrafish notochord development.

    PubMed

    Wang, Xueqian; Wang, Xin; Yuan, Wei; Chai, Renjie; Liu, Dong

    2015-08-01

    The epidermal growth factor (EGF) repeat motif defines a superfamily of diverse protein involved in regulating a variety of cellular and physiological processes, such as cell cycle, cell adhesion, proliferation, migration, and neural development. Egfl6, an EGF protein, also named MAGE was first cloned in human tissue. Up to date, the study of zebrafish Egfl6 expression pattern and functional analysis of Egfl6 involved in embryonic development of vertebrate in vivo is thus far lacking. Here we reported that Egfl6 was involved in zebrafish notochord development. It was shown that Egfl6 mRNA was expressed in zebrafish, developing somites, fin epidermis, pharyngeal arches, and hindbrain region. Particularly the secreted Egfl6 protein was significantly accumulated in notochord. Loss of Egfl6 function in zebrafish embryos resulted in curved body with distorted notochord in the posterior trunk. It was observed that expression of all Notch ligand and receptors in notochord of 28 hpf Egfl6 morphants was not affected, except notch2, which was up-regulated. We found that inhibition of Notch signaling by DAPT efficiently rescued notochord developmental defect of Egfl6 deficiency embryos.

  5. Socio-motivational moderators—two sides of the same coin? Testing the potential buffering role of socio-motivational relationships on achievement drive and test anxiety among German and Canadian secondary school students

    PubMed Central

    Hoferichter, Frances; Raufelder, Diana; Eid, Michael

    2015-01-01

    The current cross-national study investigates the potential buffering role of socio-motivational relationships for the association of achievement drive (AD) and test anxiety (TX) in secondary school students from Canada and Germany. One thousand and eighty-eight students (54% girls, Mage = 13.71, SD = 0.53, age span 12–15 years) from the state of Brandenburg and 389 students from Quebéc (55.9% girls, Mage = 13.43, SD = 0.82, age span 12–16 years) were asked about their socio-motivational relationships with their teachers and peers, their drive for achievement, and TX. Multigroup latent moderated structural equations were conducted to test for the moderator role of socio-motivational relationships that would buffer feelings of TX related to the drive for achievement. The analyses revealed the two-sided role socio-motivational relationships can have for students with different levels of AD; intensifying or mitigating feelings of TX. Thereby, the results of this study extend the buffering hypothesis by Cohen and Wills (1985). Cross-national differences between Canada and Germany were found concerning the studied moderators on the association of AD and TX: While for German students teacher–student relationships acted as moderator, for Canadian students student–student relationships and teachers acting as positive motivators displayed a moderator role. PMID:26583000

  6. Worldview implications of believing in free will and/or determinism: politics, morality, and punitiveness.

    PubMed

    Carey, Jasmine M; Paulhus, Delroy L

    2013-04-01

    We used the FAD-Plus to investigate the association of free will belief (FWB) with political orientation, moral attitudes, and punitiveness. Other goals included (a) confirming the independence of believing in free will and determinism and (b) contrasting scientific determinism with fatalistic determinism. Three studies were conducted via online questionnaires. Studies 1 and 3 recruited undergraduate students: Study 1, N = 220, M(age) = 20.96; Study 3, N = 161, M(age) = 20.2. Study 2 participants were recruited from a broader community sample: N = 253, M(age) = 34.29. Studies 1 and 2 found that FWB is associated with traditional conservative attitudes, including authoritarianism, religiosity, and belief in a just world. Study 2 replicated this pattern but narrowed the religiosity link to the intrinsic style. In Study 3, FWB was associated with binding moral foundations and retributive punishment of hypothetical criminals. Belief in free will is associated with a conservative worldview, including such facets as authoritarianism, religiosity, punitiveness, and moralistic standards for judging self and others. The common element appears to be a strong sense of personal responsibility. Evidence for distinct correlates of scientific and fatalistic determinism reinforces the need for treating them separately. © 2012 Wiley Periodicals, Inc.

  7. Emotional expressivity and emotion regulation: Relation to academic functioning among elementary school children.

    PubMed

    Kwon, Kyongboon; Hanrahan, Amanda R; Kupzyk, Kevin A

    2017-03-01

    We examined emotional expressivity (i.e., happiness, sadness, and anger) and emotion regulation (regulation of exuberance, sadness, and anger) as they relate to academic functioning (motivation, engagement, and achievement). Also, we tested the premise that emotional expressivity and emotion regulation are indirectly associated with achievement through academic motivation and engagement. Participants included 417 elementary school students (Mage = 10 years; 52% female; 60% Black) and their teachers from a Midwestern metropolitan area. We used child and teacher questionnaires, and data were analyzed with structural equation modeling. Regarding emotionality, happiness was positively associated with multiple aspects of academic functioning whereas an inverse association was found for anger; sadness was not associated with academic functioning. Also, happiness and anger were indirectly related to achievement through academic engagement. Emotion regulation was positively associated with multiple aspects of academic functioning; it was also indirectly associated with achievement through engagement. Implications are discussed regarding how social and emotional learning programs in schools can further benefit from research on children's emotions. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  8. Efficacy of a New Medical Information system, Ubiquitous Healthcare Service with Voice Inception Technique in Elderly Diabetic Patients.

    PubMed

    Kim, Kyoung Min; Park, Kyeong Seon; Lee, Hyun Ju; Lee, Yun Hee; Bae, Ji Seon; Lee, Young Joon; Choi, Sung Hee; Jang, Hak Chul; Lim, Soo

    2015-12-11

    We have demonstrated previously that an individualized health management system using advanced medical information technology, named ubiquitous (u)-healthcare, was helpful in achieving better glycemic control than routine care. Recently, we generated a new u-healthcare system using a voice inception technique for elderly diabetic patients to communicate information about their glucose control, physical activity, and diet more easily. In a randomized clinical trial, 70 diabetic patients aged 60-85 years were assigned randomly to a standard care group or u-healthcare group for 6 months. The primary end points were the changes in glycated hemoglobin (HbA1c) and glucose fluctuation assessed by the mean amplitude glycemic excursion (MAGE). Changes in body weight, lifestyle, and knowledge about diabetes were also investigated. After 6 months, the HbA1c levels decreased significantly in the u-healthcare group (from 8.6 ± 1.0% to 7.5 ± 0.6%) compared with the standard care group (from 8.7 ± 0.9% to 8.2 ± 1.1%, P < 0.01). The MAGE decreased more in the u-healthcare group than in the standard care group. Systolic blood pressure and body weight decreased and liver functions improved in the u-healthcare group, but not in the standard care group. The u-healthcare system with voice inception technique was effective in achieving glycemic control without hypoglycemia in elderly diabetic patients (Clinicaltrials.gov: NCT01891474).

  9. Source personality and persuasiveness: big five predispositions to being persuasive and the role of message involvement.

    PubMed

    Oreg, Shaul; Sverdlik, Noga

    2014-06-01

    In the present studies we incorporate a Person × Situation perspective into the study of the persuasion source. Specifically, we aimed to identify the personality characteristics of the persuasive individual and test the moderating role of target and source involvement. In three studies we found support for hypothesized relationships between source persuasiveness and Extraversion, Neuroticism, and Openness to Experience, and evidence for a moderating effect of involvement. In a preliminary study (N = 66, M(age)  = 22.7, 64% female), we demonstrated expected differences in the personality ratings assigned to a hypothetical persuasive versus nonpersuasive individual. In Study 1 (N = 95, M(age)  = 24.1, 62% female), through sets of two-person debates, we showed that source Extraversion and Openness to Experience were positively, and Neuroticism negatively, associated with source persuasiveness. In Study 2 (N = 148, M(age)  = 24.3, 61% female), we manipulated the level of involvement and mostly replicated the results from Study 1, but, corresponding with our predictions, only when involvement was low. Our findings demonstrate the relevance of an interactionist approach to the study of persuasion, highlighting the role of personality in the study of the persuasion source. © 2013 Wiley Periodicals, Inc.

  10. A novel dual-marker expression panel for easy and accurate risk stratification of patients with gastric cancer.

    PubMed

    Kanda, Mitsuro; Murotani, Kenta; Tanaka, Haruyoshi; Miwa, Takashi; Umeda, Shinichi; Tanaka, Chie; Kobayashi, Daisuke; Hayashi, Masamichi; Hattori, Norifumi; Suenaga, Masaya; Yamada, Suguru; Nakayama, Goro; Fujiwara, Michitaka; Kodera, Yasuhiro

    2018-05-07

    Development of specific biomarkers is necessary for individualized management of patients with gastric cancer. The aim of this study was to design a simple expression panel comprising novel molecular markers for precise risk stratification. Patients (n = 200) who underwent gastrectomy for gastric cancer were randomly assigned into learning and validation sets. Tissue mRNA expression levels of 15 candidate molecular markers were determined using quantitative PCR analysis. A dual-marker expression panel was created according to concordance index (C-index) values of overall survival for all 105 combinations of two markers in the learning set. The reproducibility and clinical significance of the dual-marker expression panel were evaluated in the validation set. The patient characteristics of the learning and validation sets were well balanced. The C-index values of combinations were significantly higher compared with those of single markers. The panel with the highest C-index (0.718) of the learning set comprised SYT8 and MAGED2, which clearly stratified patients into low-, intermediate-, and high-risk groups. The reproducibility of the panel was demonstrated in the validation set. High expression scores were significantly associated with larger tumor size, vascular invasion, lymph node metastasis, peritoneal metastasis, and advanced disease. The dual-marker expression panel provides a simple tool that clearly stratifies patients with gastric cancer into low-, intermediate-, and high risk after gastrectomy. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  11. Transient overexpression of DNA adenine methylase enables efficient and mobile genome engineering with reduced off-target effects

    PubMed Central

    Lennen, Rebecca M.; Nilsson Wallin, Annika I.; Pedersen, Margit; Bonde, Mads; Luo, Hao; Herrgård, Markus J.; Sommer, Morten O. A.

    2016-01-01

    Homologous recombination of single-stranded oligonucleotides is a highly efficient process for introducing precise mutations into the genome of E. coli and other organisms when mismatch repair (MMR) is disabled. This can result in the rapid accumulation of off-target mutations that can mask desired phenotypes, especially when selections need to be employed following the generation of combinatorial libraries. While the use of inducible mutator phenotypes or other MMR evasion tactics have proven useful, reported methods either require non-mobile genetic modifications or costly oligonucleotides that also result in reduced efficiencies of replacement. Therefore a new system was developed, Transient Mutator Multiplex Automated Genome Engineering (TM-MAGE), that solves problems encountered in other methods for oligonucleotide-mediated recombination. TM-MAGE enables nearly equivalent efficiencies of allelic replacement to the use of strains with fully disabled MMR and with an approximately 12- to 33-fold lower off-target mutation rate. Furthermore, growth temperatures are not restricted and a version of the plasmid can be readily removed by sucrose counterselection. TM-MAGE was used to combinatorially reconstruct mutations found in evolved salt-tolerant strains, enabling the identification of causative mutations and isolation of strains with up to 75% increases in growth rate and greatly reduced lag times in 0.6 M NaCl. PMID:26496947

  12. To study or to sleep? The academic costs of extra studying at the expense of sleep.

    PubMed

    Gillen-O'Neel, Cari; Huynh, Virginia W; Fuligni, Andrew J

    2013-01-01

    This longitudinal study examined how nightly variations in adolescents' study and sleep time are associated with academic problems on the following day. Participants (N = 535, 9th grade M(age) = 14.88) completed daily diaries every day for 14 days in 9th, 10th, and 12th grades. Results suggest that regardless of how much a student generally studies each day, if that student sacrifices sleep time to study more than usual, he or she will have more trouble understanding material taught in class and be more likely to struggle on an assignment or test the following day. Because students are increasingly likely to sacrifice sleep time for studying in the latter years of high school, this negative dynamic becomes increasingly prevalent over time. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

  13. Does Anger Regulation Mediate the Discrimination-Mental Health Link among Mexican-Origin Adolescents? A Longitudinal Mediation Analysis Using Multilevel Modeling

    PubMed Central

    Park, Irene J. K.; Wang, Lijuan; Williams, David R.; Alegría, Margarita

    2016-01-01

    Although prior research has consistently documented the association between racial/ethnic discrimination and poor mental health outcomes, the mechanisms that underlie this link are still unclear. The present three-wave longitudinal study tested the mediating role of anger regulation in the discrimination—mental health link among 269 Mexican-origin adolescents (Mage = 14.1 years, SD = 1.6; 57% girls), 12 – 17 years old. Three competing anger regulation variables were tested as potential mediators: outward anger expression, anger suppression, and anger control. Longitudinal mediation analyses were conducted using multilevel modeling that disaggregated within-person effects from between-person effects. Results indicated that outward anger expression was a significant mediator; anger suppression and anger control were not significant mediators. Within a given individual, greater racial/ethnic discrimination was associated with more frequent outward anger expression. In turn, more frequent outward anger expression was associated with higher levels of anxiety and depression at a given time point. Gender, age, and nativity status were not significant moderators of the hypothesized mediation models. By identifying outward anger expression as an explanatory mechanism in the discrimination-distress link among Latino youths, this study points to a malleable target for prevention and intervention efforts aimed at mitigating the detrimental impact of racism on Latino youths’ mental health during the developmentally critical period of adolescence. PMID:27893238

  14. Improvements of ambient hyperglycemia and glycemic variability are associated with reduction in oxidative stress for patients with type 2 diabetes.

    PubMed

    Ohara, Makoto; Nagaike, Hiroe; Goto, Satoshi; Fukase, Ayako; Tanabe, Yuki; Tomoyasu, Masako; Yamamoto, Takeshi; Hayashi, Toshiyuki; Fukui, Tomoyasu; Hirano, Tsutomu

    2018-05-01

    We aimed to evaluate which parameters of improvement in glucose metabolism reduce oxidative stress for patients with Type 2 diabetes mellitus (T2DM). Sixty-seven outpatients with T2DM underwent 72 h of continuous glucose monitoring (CGM) and were measured for oxidative stress before and after a 24-week intervention with the following targets: fasting plasma glucose (FPG), <130 mg/dl; postprandial plasma glucose (PPG), <180 mg/dl; and glycated hemoglobin (HbA1c), <7% (53 mmol/mol). The mean glucose level (MGL), mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), percentage coefficient of variation for glucose (%CV) and area under the postprandial plasma glucose curve (AUC PP ) were calculated from the CGM data. Oxidative stress was estimated using the diacron-reactive oxygen metabolites (d-ROMs) test. Finally, the association between the improvements in glucose metabolism and oxidative stress was evaluated. FPG, MGL, HbA1c, MAGE, MODD, %CV, AUC PP , and d-ROMs significantly improved after 24 weeks of intervention. The change in d-ROMs was significantly correlated with that in FPG (r = 0.414), MGL (r = 0.402), HbA1c (r = 0.271), MAGE (r = 0.457), MODD (r = 0.371), and AUC PP (r = 0.352). The correlation of the change in d-ROMs with that in FPG, MAGE, and MODD and the use of glucose-like peptide 1 receptor agonists and statins remained significant after adjustment for other markers of diabetes control (multiple R 2 = 0.406). Improvements in glucose metabolism, including FPG and daily and day-to-day glucose variability, were all correlated with reduced oxidative stress for patients with T2DM. Published by Elsevier B.V.

  15. Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM): Crossover pilot study (J-VICTORIA study)

    PubMed Central

    2012-01-01

    Background No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters. Methods Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1) mean (± standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood glucose level and time, 5) increase in blood glucose level after each meal, 6) area under the curve (AUC) for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7) area over the curve (AOC) for daily blood glucose level <70 mg/dL. Plasma glycosylated hemoglobin (HbA1c), glycoalbumin (GA), 1,5-anhydroglucitol (1,5AG), immunoreactive insulin (IRI), C-peptide immunoreactivity (CPR), brain natriuretic peptide (BNP), and plasminogen activator inhibitor-1 (PAI-1) levels, and urinary CPR levels, were measured. Results The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012). In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015), the AUC (≥180 mg/dL) within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 μg/day; p = 0.008) than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin. Conclusions CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and sitagliptin. Trial registration UMIN000007687 PMID:22867630

  16. LA-iMageS: a software for elemental distribution bioimaging using LA-ICP-MS data.

    PubMed

    López-Fernández, Hugo; de S Pessôa, Gustavo; Arruda, Marco A Z; Capelo-Martínez, José L; Fdez-Riverola, Florentino; Glez-Peña, Daniel; Reboiro-Jato, Miguel

    2016-01-01

    The spatial distribution of chemical elements in different types of samples is an important field in several research areas such as biology, paleontology or biomedicine, among others. Elemental distribution imaging by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is an effective technique for qualitative and quantitative imaging due to its high spatial resolution and sensitivity. By applying this technique, vast amounts of raw data are generated to obtain high-quality images, essentially making the use of specific LA-ICP-MS imaging software that can process such data absolutely mandatory. Since existing solutions are usually commercial or hard-to-use for average users, this work introduces LA-iMageS, an open-source, free-to-use multiplatform application for fast and automatic generation of high-quality elemental distribution bioimages from LA-ICP-MS data in the PerkinElmer Elan XL format, whose results can be directly exported to external applications for further analysis. A key strength of LA-iMageS is its substantial added value for users, with particular regard to the customization of the elemental distribution bioimages, which allows, among other features, the ability to change color maps, increase image resolution or toggle between 2D and 3D visualizations.

  17. Integrated multigene expression panel to prognosticate patients with gastric cancer.

    PubMed

    Kanda, Mitsuro; Murotani, Kenta; Tanaka, Haruyoshi; Miwa, Takashi; Umeda, Shinichi; Tanaka, Chie; Kobayashi, Daisuke; Hayashi, Masamichi; Hattori, Norifumi; Suenaga, Masaya; Yamada, Suguru; Nakayama, Goro; Fujiwara, Michitaka; Kodera, Yasuhiro

    2018-04-10

    Most of the proposed individual markers had limited clinical utility due to the inherent biological and genetic heterogeneity of gastric cancer. We aimed to build a new molecular-based model to predict prognosis in patients with gastric cancer. A total of 200 patients who underwent gastric resection for gastric cancer were divided into learning and validation cohorts using a table of random numbers in a 1:1 ratio. In the learning cohort, mRNA expression levels of 15 molecular markers in gastric tissues were analyzed and concordance index (C-index) values of all single and combinations of the 15 candidate markers for overall survival were calculated. The multigene expression panel was designed according to C-index values and the subpopulation index. Expression scores were determined with weighting according to the coefficient of each constituent. The reproducibility of the panel was evaluated in the validation cohort. C-index values of the 15 single candidate markers ranged from 0.506-0.653. Among 32,767 combinations, the optimal and balanced expression panel comprised four constituents ( MAGED2, SYT8, BTG1 , and FAM46 ) and the C-index value was 0.793. Using this panel, patients were provisionally categorized with scores of 1-3, and clearly stratified into favorable, intermediate, and poor overall survival groups. In the validation cohort, both overall and disease-free survival rates decreased incrementally with increasing expression scores. Multivariate analysis revealed that the expression score was an independent prognostic factor for overall survival after curative gastrectomy. We developed an integrated multigene expression panel that simply and accurately stratified risk of patients with gastric cancer.

  18. Necdin, a Prader-Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development.

    PubMed

    Miller, Nichol L G; Wevrick, Rachel; Mellon, Pamela L

    2009-01-15

    Prader-Willi syndrome (PWS) is a complex genetic disorder characterized by hyperphagia, obesity and hypogonadotrophic hypogonadism, all highly suggestive of hypothalamic dysfunction. The NDN gene, encoding the MAGE family protein, necdin, maps to the PWS chromosome region and is highly expressed in mature hypothalamic neurons. Adult mice lacking necdin have reduced numbers of gonadotropin-releasing hormone (GnRH) neurons, but the mechanism for this reduction is unknown. Herein, we show that, although necdin is not expressed in an immature, migratory GnRH neuronal cell line (GN11), high levels are present in a mature GnRH neuronal cell line (GT1-7). Furthermore, overexpression of necdin activates GnRH transcription through cis elements bound by the homeodomain repressor Msx that are located in the enhancer and promoter of the GnRH gene, and knock-down of necdin expression reduces GnRH gene expression. In fact, overexpression of Necdin relieves Msx repression of GnRH transcription through these elements and necdin co-immunoprecipitates with Msx from GnRH neuronal cells, indicating that necdin may activate GnRH gene expression by preventing repression of GnRH gene expression by Msx. Finally, necdin is necessary for generation of the full complement of GnRH neurons during mouse development and extension of GnRH axons to the median eminence. Together, these results indicate that lack of necdin during development likely contributes to the hypogonadotrophic hypogonadal phenotype in individuals with PWS.

  19. Necdin, a Prader–Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development

    PubMed Central

    Miller, Nichol L.G.; Wevrick, Rachel; Mellon, Pamela L.

    2009-01-01

    Prader–Willi syndrome (PWS) is a complex genetic disorder characterized by hyperphagia, obesity and hypogonadotrophic hypogonadism, all highly suggestive of hypothalamic dysfunction. The NDN gene, encoding the MAGE family protein, necdin, maps to the PWS chromosome region and is highly expressed in mature hypothalamic neurons. Adult mice lacking necdin have reduced numbers of gonadotropin-releasing hormone (GnRH) neurons, but the mechanism for this reduction is unknown. Herein, we show that, although necdin is not expressed in an immature, migratory GnRH neuronal cell line (GN11), high levels are present in a mature GnRH neuronal cell line (GT1-7). Furthermore, overexpression of necdin activates GnRH transcription through cis elements bound by the homeodomain repressor Msx that are located in the enhancer and promoter of the GnRH gene, and knock-down of necdin expression reduces GnRH gene expression. In fact, overexpression of Necdin relieves Msx repression of GnRH transcription through these elements and necdin co-immunoprecipitates with Msx from GnRH neuronal cells, indicating that necdin may activate GnRH gene expression by preventing repression of GnRH gene expression by Msx. Finally, necdin is necessary for generation of the full complement of GnRH neurons during mouse development and extension of GnRH axons to the median eminence. Together, these results indicate that lack of necdin during development likely contributes to the hypogonadotrophic hypogonadal phenotype in individuals with PWS. PMID:18930956

  20. Auditory habituation to simple tones: reduced evidence for habituation in children compared to adults

    PubMed Central

    Muenssinger, Jana; Stingl, Krunoslav T.; Matuz, Tamara; Binder, Gerhard; Ehehalt, Stefan; Preissl, Hubert

    2013-01-01

    Habituation—the response decrement to repetitively presented stimulation—is a basic cognitive capability and suited to investigate development and integrity of the human brain. To evaluate the developmental process of auditory habituation, the current study used magnetoencephalography (MEG) to investigate auditory habituation, dishabituation and stimulus specificity in children and adults and compared the results between age groups. Twenty-nine children (Mage = 9.69 years, SD ± 0.47) and 14 adults (Mage = 29.29 years, SD ± 3.47) participated in the study and passively listened to a habituation paradigm consisting of 100 trains of tones which were composed of five 500 Hz tones, one 750 Hz tone (dishabituator) and another two 500 Hz tones, respectively while focusing their attention on a silent movie. Adults showed the expected habituation and stimulus specificity within-trains while no response decrement was found between trains. Sensory adaptation or fatigue as a source for response decrement in adults is unlikely due to the strong reaction to the dishabituator (stimulus specificity) and strong mismatch negativity (MMN) responses. However, in children neither habituation nor dishabituation or stimulus specificity could be found within-trains, response decrement was found across trains. It can be speculated that the differences between children and adults are linked to differences in stimulus processing due to attentional processes. This study shows developmental differences in task-related brain activation and discusses the possible influence of broader concepts such as attention, which should be taken into account when comparing performance in an identical task between age groups. PMID:23882207

  1. Role-Playing and Real-Time Strategy Games Associated with Greater Probability of Internet Gaming Disorder.

    PubMed

    Eichenbaum, Adam; Kattner, Florian; Bradford, Daniel; Gentile, Douglas A; Green, C Shawn

    2015-08-01

    Research indicates that a small subset of those who routinely play video games show signs of pathological habits, with side effects ranging from mild (e.g., being late) to quite severe (e.g., losing a job). However, it is still not clear whether individual types, or genres, of games are most strongly associated with Internet gaming disorder (IGD). A sample of 4,744 University of Wisconsin-Madison undergraduates (Mage=18.9 years; SD=1.9 years; 60.5% female) completed questionnaires on general video game playing habits and on symptoms of IGD. Consistent with previous reports: 5.9-10.8% (depending on classification criteria) of individuals who played video games show signs of pathological play. Furthermore, real-time strategy and role-playing video games were more strongly associated with pathological play, compared with action and other games (e.g., phone games). The current investigation adds support to the idea that not all video games are equal. Instead, certain genres of video games, specifically real-time strategy and role-playing/fantasy games, are disproportionately associated with IGD symptoms.

  2. The influence of spelling ability on handwriting production: children with and without dyslexia.

    PubMed

    Sumner, Emma; Connelly, Vincent; Barnett, Anna L

    2014-09-01

    Current models of writing do not sufficiently address the complex relationship between the 2 transcription skills: spelling and handwriting. For children with dyslexia and beginning writers, it is conceivable that spelling ability will influence rate of handwriting production. Our aim in this study was to examine execution speed and temporal characteristics of handwriting when completing sentence-copying tasks that are free from composing demands and to determine the predictive value of spelling, pausing, and motor skill on handwriting production. Thirty-one children with dyslexia (Mage = 9 years 4 months) were compared with age-matched and spelling-ability matched children (Mage = 6 years 6 months). A digital writing tablet and Eye and Pen software were used to analyze handwriting. Children with dyslexia were able to execute handwriting at the same speed as the age-matched peers. However, they wrote less overall and paused more frequently while writing, especially within words. Combined spelling ability and within-word pausing accounted for over 76% of the variance in handwriting production of children with dyslexia, demonstrating that productivity relies on spelling capabilities. Motor skill did not significantly predict any additional variance in handwriting production. Reading ability predicted performance of the age-matched group, and pausing predicted performance for the spelling-ability group. The findings from the digital writing tablet highlight the interactive relationship between the transcription skills and how, if spelling is not fully automatized, it can constrain the rate of handwriting production. Practical implications are also addressed, emphasizing the need for more consideration to be given to what common handwriting tasks are assessing as a whole.

  3. School and Peer Influences on the Academic Outcomes of African American Adolescents

    PubMed Central

    Estrada-Martinez, Lorena; Colin, Rosa J.; Jones, Brittni D.

    2015-01-01

    Little scholarship explores how adolescents’ beliefs about school and peers influence the academic outcomes of African American boys and girls. The sample included 612 African American boys (N=307, Mage=16.84) and girls (N=305, Mage=16.79). Latent class analysis (LCA) revealed unique patterns for African American boys and girls. Findings indicate that for African American boys, school attachment was protective, despite having peers who endorsed negative achievement values. Furthermore, socio-economic (SES) status was associated with higher grade point averages (GPA) for African American girls. Overall, these findings underscore the unique role of school, peer, and gendered experiences in lives of African American adolescents. PMID:26277404

  4. A fisheye viewer for microarray-based gene expression data

    PubMed Central

    Wu, Min; Thao, Cheng; Mu, Xiangming; Munson, Ethan V

    2006-01-01

    Background Microarray has been widely used to measure the relative amounts of every mRNA transcript from the genome in a single scan. Biologists have been accustomed to reading their experimental data directly from tables. However, microarray data are quite large and are stored in a series of files in a machine-readable format, so direct reading of the full data set is not feasible. The challenge is to design a user interface that allows biologists to usefully view large tables of raw microarray-based gene expression data. This paper presents one such interface – an electronic table (E-table) that uses fisheye distortion technology. Results The Fisheye Viewer for microarray-based gene expression data has been successfully developed to view MIAME data stored in the MAGE-ML format. The viewer can be downloaded from the project web site . The fisheye viewer was implemented in Java so that it could run on multiple platforms. We implemented the E-table by adapting JTable, a default table implementation in the Java Swing user interface library. Fisheye views use variable magnification to balance magnification for easy viewing and compression for maximizing the amount of data on the screen. Conclusion This Fisheye Viewer is a lightweight but useful tool for biologists to quickly overview the raw microarray-based gene expression data in an E-table. PMID:17038193

  5. Glycemic excursions are positively associated with HbA1c reduction from baseline after treatment with acarbose in patients with type 2 diabetes on metformin monotherapy.

    PubMed

    Wang, Jun-Sing; Lee, I-Te; Lee, Wen-Jane; Lin, Shi-Dou; Su, Shih-Li; Tu, Shih-Te; Tseng, Yao-Hsien; Lin, Shih-Yi; Sheu, Wayne Huey-Herng

    2017-03-01

    The aim of the present study was to examine the association between glycemic excursions before treatment and HbA1c reduction after treatment intensification with acarbose or glibenclamide in patients with type 2 diabetes (T2D). Patients receiving single or dual oral antidiabetic drug treatment with an HbA1c of 7.0-11.0 % (53-97 mmol/mol) were switched to metformin monotherapy (500 mg, t.i.d.) for 8 weeks, followed by randomization to either acarbose (100 mg, t.i.d.) or glibenclamide (5 mg, t.i.d.) as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring. Treatment efficacy was evaluated as relative HbA1c reduction (%), calculated as (baseline HbA1c - post-treatment HbA1c)/baseline HbA1c × 100. Fifty patients (mean [±SD] age 53.5 ± 8.2 years, 48 % men, mean baseline HbA1c 8.4 ± 1.2 %) were analyzed. Baseline MAGE was positively correlated with relative HbA1c reduction from baseline in patients treated with acarbose (r = 0.421, P = 0.029) but not glibenclamide (r = 0.052, P = 0.813). Linear regression analysis revealed that the association between baseline MAGE and relative HbA1c reduction from baseline (β = 0.125, P = 0.029) in patients treated with acarbose remained significant after adjustment for several confounders (P < 0.05 for all models). In patients with T2D on metformin monotherapy, baseline MAGE was positively correlated with relative HbA1c reduction from baseline after treatment with acarbose, but not glibenclamide. These findings highlight the importance of glycemic excursions in individualized treatment for patients with T2D. © 2016 Ruijin Hospital, Shanghai JiaoTong University School of Medicine (SJTU), Chinese Society of Endocrinology and Chinese Endocrinologist Association and John Wiley & Sons Australia, Ltd.

  6. Validation of the social appearance anxiety scale in female eating disorder patients.

    PubMed

    Claes, Laurence; Hart, Trevor A; Smits, Dirk; Van den Eynde, Frederique; Mueller, Astrid; Mitchell, James E

    2012-09-01

    In the present study, we investigated the psychometric properties of the Social Appearance Anxiety Scale (SAAS) in a sample of 60 female eating disorder patients (M(age) = 27.82, SD = 9.76). The SAAS was developed to assess anxiety about being negatively evaluated for one's appearance. All patients completed the SAAS, the Eating Disorder Inventory-2, the Physical Health Questionnaire-9 Depression and the Dimensional Assessment of Personality Psychopathology. The SAAS demonstrated a one-factor structure and a high internal consistency. The SAAS was significantly positive in relation to body mass index, drive for thinness and body dissatisfaction. Concerning personality dimensions, the SAAS was positively related to emotional problems (e.g. depression, anxiety) and interpersonal problems (e.g. suspiciousness, submissiveness). Findings suggest that the SAAS is a psychometrically sound instrument to assess anxiety about being negatively evaluated about one's appearance in a sample of eating disorder patients. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.

  7. Risky business: is pubic hair removal by women associated with body image and sexual health?

    PubMed

    Grossman, Stephanie L; Annunziato, Rachel A

    2018-04-30

    Background: Body hair removal is a behaviour that has become normative among women in Westernised cultures, and is presented by the media as the feminine ideal, despite being painful and a potential cause of infection. Of concern, removal may be part of a more global pattern of appearance dissatisfaction and risky sexual behaviour. The aim of the present study was to examine the relationships among pubic hair removal, body image and sexual health indicators. Methods: Women (n=264; Mage=33.82, s.d.=11.13, range=18-66) completed self-report questionnaires assessing these constructs, including an assessment of body hair removal practices. Results: Greater appearance concerns (as measured by thin-ideal internalisation, appearance investment and self-objectification) and sexual health indicators (i.e. less condom use self-efficacy when a partner disapproves of condom use) all predicted greater importance of reasons for pubic hair removal (R2=0.315, F(8184)=9.97, P<0.001), controlling for age groups. Additionally, women who removed a greater amount of hair reported more thin-ideal internalisation and appearance investment than those who removed less hair. Conclusions: Women who express stronger reasoning for pubic hair removal, and remove a larger amount of it, may endorse problematic beliefs and behaviours particularly related to appearance concerns. It is important for practitioners to consider this practice as distinct from grooming and to be aware of its association with a broader array of risky beliefs and behaviours that can compromise women's well-being.

  8. Effects of vildagliptin versus saxagliptin on daily acute glucose fluctuations in Chinese patients with T2DM inadequately controlled with a combination of metformin and sulfonylurea.

    PubMed

    Xiaoyan, Chen; Jing, Wang; Xiaochun, Huang; Yuyu, Tan; Shunyou, Deng; Yingyu, Fu

    2016-06-01

    Objective The present study aimed to compare the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitors vildagliptin and saxagliptin on 24 hour acute glucose fluctuations in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with a combination of metformin and sulfonylurea. Research design and methods This was a 24 week, prospective, randomized, open-label, active-controlled study. Patients (N = 73) with T2DM who had inadequate glycemic control (HbA1c 7.0%-10.0%) with a stable dosage of metformin plus gliclazide for more than 3 months were randomized to receive either vildagliptin 50 mg twice daily (BID, n = 37) or saxagliptin 5 mg once daily (QD, n = 36). Change in mean amplitude of glycemic excursions (MAGE) was assessed at the end of 24 weeks. Results At baseline, the mean (±SD) age was 62.9 ± 6.55 years, disease duration was 7.0 ± 2.33 years, and HbA1c was 8.4 ± 0.68%. After 24 weeks of treatment, the MAGE decreased from 5.81 ± 1.16 mmol/L to 4.06 ± 0.86 mmol/L (p<0.001) in the vildagliptin group and from 5.66 ± 1.14 mmol/L to 4.79 ± 1.25 mmol/L (p = 0.003) in the saxagliptin group. The mean change in MAGE in the vildagliptin group was significantly greater than that in the saxagliptin group (1.74 ± 0.48 mmol/L vs. 0.87 ± 0.40 mmol/L, p<0.001). The mean change in HbA1c, from baseline to the study endpoint, in the vildagliptin and saxagliptin groups, was 1.22 ± 0.40% and 1.07 ± 0.36%, respectively, with no significant difference between the groups (p = 0.091). The overall safety and tolerability of vildagliptin and saxagliptin were similar. The limitations of the study were a small number of patients and open-label administration of the study drug. Conclusion Vildagliptin produced a significantly greater reduction in acute glucose fluctuations compared with saxagliptin when added to a dual combination of metformin and sulfonylurea in Chinese patients with T2DM. Chinese clinical trial registration number ChiCTR-TRC-13003858.

  9. Effects of communication skills on stress responses while speaking Japanese and English.

    PubMed

    Hirokawa, Kumi; Yagi, Akihiro; Miyata, Yo

    2008-08-01

    The present study was conducted to examine the effects of communication skills on stress responses, such as physiological (blink and heart rate), emotional (state of anxiety and mood), and behavioral responses (smiling and expressing an opinion) in stressful communication situations, specifically answering questions and giving a speech in Japanese and English. Participants were 32 students (16 men and 16 women; Mage = 19.5 yr., SD = 1.3) attending a Japanese university. A high communication skills group was selected from the upper tertile scores of the Social Skills Inventory, and a low communication skills group was selected from the lower tertile scores. Analysis indicated that individuals who had high communication skills performed without heart-rate increase and with more positive attitude during stressful communication tasks. Individuals who had low communication skills displayed higher anxiety prior to the experiment than those who had high communication skills.

  10. Investigating correlates of synthetic marijuana and Salvia use in light and intermittent smokers and college students in a predominantly Hispanic sample.

    PubMed

    Gutierrez, Kevin M; Cooper, Theodore V

    2014-12-01

    Few studies have examined correlates related to the use of synthetic cannabinoids (e.g., Spice, K2) and Salvia divinorum. Two studies were conducted to investigate whether demographic, smoking-related, and substance-related variables were associated with the use of synthetic cannabinoids and Salvia. In Study 1, 185 participants (50% female; 83% Hispanic; Mage = 32 years; SD = 13.68) were recruited from a local health clinic and a university on the U.S./Mexico border for a smoking-cessation study targeting light and intermittent smokers. In Study 2, 675 participants (62.4% female; 89.1% Hispanic; Mage = 21.0, SD = 8.56) were recruited from a university on the U.S./Mexico border for an online study. In Study 1, 10% of the sample indicated they had ever used either synthetic cannabinoids or Salvia in their lifetime. Being male and dual/multiple use of tobacco products were significantly associated with having ever used synthetic cannabinoids or Salvia. In Study 2, 9%, 5%, and 3% of the sample indicated lifetime, past-year, and past 30-day use of synthetic cannabinoids, respectively. Five percent, 2%, and 1% of the sample indicated lifetime, past-year, and past 30-day use of Salvia, respectively. Logistic regression analyses revealed that past 30-day marijuana use and past 30-day ecstasy use were significantly associated with use of synthetic cannabinoids and Salvia in one's lifetime. These findings suggest that the assessment of synthetic marijuana and Salvia use is warranted in studies of other addictive behaviors, particularly among current marijuana and ecstasy users. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  11. Empathy scores in medical school and ratings of empathic behavior in residency training 3 years later.

    PubMed

    Hojat, Mohammadreza; Mangione, Salvatore; Nasca, Thomas J; Gonnella, Joseph S; Magee, Mike

    2005-12-01

    The authors designed the present study to examine the association between individuals' scores on the Jefferson Scale of Physician Empathy (JSPE; M. Hojat, J. S. Gonnella, S. Mangione, T. J. Nasca, & M. Magee, 2003; M. Hojat, J. S. Gonnella, T. J. Nasca, S. Mangione, M. Vergare, & M. Magee, 2002; M. Hojat, S. Mangione, T. J. Nasca, M. J. M. Cohen, J. S. Gonnella, J. B. Erdmann, J. J. Veloski, & M. Magee, 2001), a self-report empathy scale, during medical school and ratings of their empathic behavior made by directors of their residency training programs 3 years later. Participants were 106 physicians. The authors examined the relationships between scores on the JSPE (with 20 Likert-type items) at the beginning of the students' 3rd year of medical school and ratings of their empathic behavior made by directors of their residency training programs. Top scorers on the JSPE in medical school, compared to Bottom scorers, obtained a significantly higher average rating of empathic behavior in residency 3 years later (p < .05, effect size = 0.50). The findings support the long-term predictive validity of the self-report empathy scale, JSPE, despite different methods of evaluations (self-report and supervisors' ratings) and despite a time interval between evaluations (3 years). Because empathy is relevant to prosocial and helping behavior, it is important for investigators to further enhance our understanding of its correlates and outcomes among health professionals.

  12. A diabetes-specific enteral formula improves glycemic variability in patients with type 2 diabetes.

    PubMed

    Alish, Carolyn J; Garvey, W Timothy; Maki, Kevin C; Sacks, Gordon S; Hustead, Deborah S; Hegazi, Refaat A; Mustad, Vikkie A

    2010-06-01

    Well-controlled studies have demonstrated that inpatient hyperglycemia is an indicator of poor clinical outcomes, but the use of diabetes-specific enteral formulas in hospitalized patients remains a topic of great debate. In two different protocols, postprandial glycemia and insulinemia were measured in 22 subjects with diabetes fed a diabetes-specific or standard formula (protocol 1). Continuous glucose monitoring was used to assess glucose levels in 12 enterally fed patients with diabetes receiving the standard formula followed by the diabetes-specific formula continuously for 5 days each (protocol 2). End points included postprandial glycemia and insulinemia, glycemic variability (mean amplitude of glycemic excursions [MAGE]), mean glucose, and insulin use. In the postprandial response protocol, the diabetes-specific formula resulted in lower positive areas under the postprandial curve (P < 0.001) and peak glucose (P < 0.001) and insulin (P = 0.017) levels. In the protocol using continuous glucose monitoring, glycemic variability (as measured by MAGE) was lower with continuous administration of the diabetes-specific than the standard formula (64.6 +/- 6.8 mg/dL vs. 110.6 +/-15.3 mg/dL, P = 0.003). Also, administration of the diabetes-specific formula resulted in lower mean glucose concentrations during feeding (171.1 +/- 16.1 vs. 202.1 +/- 17.4 mg/dL, P = 0.024) and insulin requirements (7.8 +/- 2.3 vs. 10.9 +/- 3.3 units/day, P = 0.039) than the standard formula. Relative to the standard formula, the diabetes-specific formula reduced postprandial glycemia, mean glucose, glycemic variability, and short-acting insulin requirements. These results suggest potential clinical usefulness of a diabetes-specific enteral formula for minimizing glycemic excursions in hospitalized patients.

  13. Pathways to social anxiety: the role of reinforcement sensitivities and emotion regulation.

    PubMed

    O'Connor, Elodie J; Staiger, Petra K; Kambouropoulos, Nicolas; Smillie, Luke D

    2014-12-30

    Past research has demonstrated a strong relationship between threat sensitivity and social anxiety; however, the relationship between reward sensitivity and social anxiety is less clear. Further, the role that emotion regulation (ER) may play in the expression of social anxiety disorder (SAD) is rarely considered. The current study tested whether two emotion regulation strategies (emotional suppression and cognitive reappraisal) mediated associations between threat sensitivity and reward sensitivity and social anxiety in a community sample (402 adults, 78% female; Mage=32.49, S.D.age=11.53). Path analyses indicated that low reappraisal mediated the relationship between high threat sensitivity and high social anxiety; and both low reappraisal and high suppression mediated the relationship between low reward sensitivity and high social anxiety. These results highlight the potential role that emotion regulation plays in the relationship between trait motivation and social anxiety. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Perinatal Parenting Stress, Anxiety, and Depression Outcomes in First-Time Mothers and Fathers: A 3- to 6-Months Postpartum Follow-Up Study

    PubMed Central

    Vismara, Laura; Rollè, Luca; Agostini, Francesca; Sechi, Cristina; Fenaroli, Valentina; Molgora, Sara; Neri, Erica; Prino, Laura E.; Odorisio, Flaminia; Trovato, Annamaria; Polizzi, Concetta; Brustia, Piera; Lucarelli, Loredana; Monti, Fiorella; Saita, Emanuela; Tambelli, Renata

    2016-01-01

    Objective: Although there is an established link between parenting stress, postnatal depression, and anxiety, no study has yet investigated this link in first-time parental couples. The specific aims of this study were 1) to investigate whether there were any differences between first-time fathers’ and mothers’ postnatal parenting stress, anxiety, and depression symptoms and to see their evolution between three and 6 months after their child’s birth; and 2) to explore how each parent’s parenting stress and anxiety levels and the anxiety levels and depressive symptoms of their partners contributed to parental postnatal depression. Method: The sample included 362 parents (181 couples; mothers’ MAge = 35.03, SD = 4.7; fathers’ MAge = 37.9, SD = 5.6) of healthy babies. At three (T1) and 6 months (T2) postpartum, both parents filled out, in a counterbalanced order, the Parenting Stress Index-Short Form, the Edinburgh Postnatal Depression Scale, and the State-Trait Anxiety Inventory. Results: The analyses showed that compared to fathers, mothers reported higher scores on postpartum anxiety, depression, and parenting stress. The scores for all measures for both mothers and fathers decreased from T1 to T2. However, a path analysis suggested that the persistence of both maternal and paternal postnatal depression was directly influenced by the parent’s own levels of anxiety and parenting stress and by the presence of depression in his/her partner. Discussion: This study highlights the relevant impact and effects of both maternal and paternal stress, anxiety, and depression symptoms during the transition to parenthood. Therefore, to provide efficacious, targeted, early interventions, perinatal screening should be directed at both parents. PMID:27445906

  15. Preschoolers’ Genetic, Physiological, and Behavioral Sensitivity Factors Moderate Links Between Parenting Stress and Child Internalizing, Externalizing, and Sleep Problems

    PubMed Central

    Davis, Molly; Thomassin, Kristel; Bilms, Joanie; Suveg, Cynthia; Shaffer, Anne; Beach, Steven R. H.

    2017-01-01

    This study examined three potential moderators of the relations between maternal parenting stress and preschoolers’ adjustment problems: a genetic polymorphism - the short allele of the serotonin transporter (5-HTTLPR, ss/sl allele) gene, a physiological indicator - children’s baseline respiratory sinus arrhythmia (RSA), and a behavioral indicator - mothers’ reports of children’s negative emotionality. A total of 108 mothers (Mage = 30.68 years, SDage = 6.06) reported on their parenting stress as well as their preschoolers’ (Mage = 3.50 years, SDage = .51, 61% boys) negative emotionality and internalizing, externalizing, and sleep problems. Results indicated that the genetic sensitivity variable functioned according to a differential susceptibility model; however, the results involving physiological and behavioral sensitivity factors were most consistent with a diathesis-stress framework. Implications for prevention and intervention efforts to counter the effects of parenting stress are discussed. PMID:28295263

  16. Genetics Home Reference: Kleefstra syndrome

    MedlinePlus

    ... PubMed Kleefstra T, Brunner HG, Amiel J, Oudakker AR, Nillesen WM, Magee A, Geneviève D, Cormier-Daire ... PubMed Kleefstra T, Smidt M, Banning MJ, Oudakker AR, Van Esch H, de Brouwer AP, Nillesen W, ...

  17. The Model Human Processor and the Older Adult: Parameter Estimation and Validation Within a Mobile Phone Task

    PubMed Central

    Jastrzembski, Tiffany S.; Charness, Neil

    2009-01-01

    The authors estimate weighted mean values for nine information processing parameters for older adults using the Card, Moran, and Newell (1983) Model Human Processor model. The authors validate a subset of these parameters by modeling two mobile phone tasks using two different phones and comparing model predictions to a sample of younger (N = 20; Mage = 20) and older (N = 20; Mage = 69) adults. Older adult models fit keystroke-level performance at the aggregate grain of analysis extremely well (R = 0.99) and produced equivalent fits to previously validated younger adult models. Critical path analyses highlighted points of poor design as a function of cognitive workload, hardware/software design, and user characteristics. The findings demonstrate that estimated older adult information processing parameters are valid for modeling purposes, can help designers understand age-related performance using existing interfaces, and may support the development of age-sensitive technologies. PMID:18194048

  18. Quantifying deficits in the perception of fear and anger in morphed facial expressions after bilateral amygdala damage.

    PubMed

    Graham, Reiko; Devinsky, Orrin; Labar, Kevin S

    2007-01-07

    Amygdala damage has been associated with impairments in perceiving facial expressions of fear. However, deficits in perceiving other emotions, such as anger, and deficits in perceiving emotion blends have not been definitively established. One possibility is that methods used to index expression perception are susceptible to heuristic use, which may obscure impairments. To examine this, we adapted a task used to examine categorical perception of morphed facial expressions [Etcoff, N. L., & Magee, J. J. (1992). Categorical perception of facial expressions. Cognition, 44(3), 227-240]. In one version of the task, expressions were categorized with unlimited time constraints. In the other, expressions were presented with limited exposure durations to tap more automatic aspects of processing. Three morph progressions were employed: neutral to anger, neutral to fear, and fear to anger. Both tasks were administered to a participant with bilateral amygdala damage (S.P.), age- and education-matched controls, and young controls. The second task was also administered to unilateral temporal lobectomy patients. In the first version, S.P. showed impairments relative to normal controls on the neutral-to-anger and fear-to-anger morphs, but not on the neutral-to-fear morph. However, reaction times suggested that speed-accuracy tradeoffs could account for results. In the second version, S.P. showed impairments on all morph types relative to all other subject groups. A third experiment showed that this deficit did not extend to the perception of morphed identities. These results imply that when heuristics use is discouraged on tasks utilizing subtle emotion transitions, deficits in the perception of anger and anger/fear blends, as well as fear, are evident with bilateral amygdala damage.

  19. NASA/University Joint Venture (JOVE) Program

    NASA Technical Reports Server (NTRS)

    Magee-Sauer, Karen P.

    1999-01-01

    Hale-Bopp observations at the NASA IRTF concluded in September 1997. For the post Hale-Bopp period, telescope time was awarded to study comet Giacobini-Zinner in October 1998 at the NASA IRTF. A total of 6 nights were awarded to our team to study the comet where 2 of those 6 nights were awarded to Magee-Sauer as the principal investigator. Other observing trips were awarded to study YSOs (October 1998) and Mars (spring 1999) were Magee-Sauer was a co-investigator. An observing run from July 4 -7 1999 included study of Mars and YSOS. Our group has started to use the NIRSPEC instrument on the Keck II telescope. In collaboration with the development team from UCLA, we obtained images of comet Lee in August 1999. Telescope proposals are submitted each semester for targeted comet observations when a comet is bright enough to observe.

  20. Parental Cultural Socialization of Mexican American Adolescents’ Family Obligation Values and Behaviors

    PubMed Central

    Tsai, Kim M.; Telzer, Eva H.; Gonzales, Nancy A.; Fuligni, Andrew J.

    2015-01-01

    The current study examined how parents’ cultural socialization efforts contribute to adolescents’ family obligation values and behaviors and how these processes may depend upon the relational climate at home. Utilizing survey and daily diary methodologies, 428 Mexican American adolescents (50% males; MAge=15 years) and their parents (83% mothers; MAge=42 years) participated in the study. Adolescents reported on their family obligation values and engagement in family assistance tasks across 14 days. Parents reported on their cultural socialization practices. Results indicated that parental cultural socialization was associated with adolescents’ family obligation values and behaviors when parent-child relationships were low in conflict and high in support. Findings suggest that the transmission of cultural values and practices is best facilitated through positive parent-child relationships. PMID:25726966

  1. Adolescent Controversial Status Brokers: A Double-Edged Sword

    PubMed Central

    Borowski, Sarah; Zeman, Janice; Carboni, Inga; Gilman, Rich; Thrash, Todd

    2016-01-01

    Using a 3-wave longitudinal, multidimensional approach, this study investigated the influence of social network position and social status on psychosocial outcomes of 440 youth (45.1% girls; Mage = 16.1; 90.9% Caucasian) over 26 months, focusing on the controversial status classification (i.e., youth who are both highly liked and disliked by their peers). Brokerage (i.e., the degree to which a person has relationships with peers who do not have a direct relationship with each other) was examined in conjunction with sociometric status to explain potential heterogeneity of outcomes for controversial status youth. Adolescents completed peer nominations and self-reports of adjustment. Results demonstrated that brokerage related to poorer psychosocial outcomes for controversial than average status youth. Brokerage appears to add predictive value to youths’ adjustment beyond traditional sociometric classifications, especially for controversial status youth. PMID:27428447

  2. MAGE (M-file/Mif Automatic GEnerator): A graphical interface tool for automatic generation of Object Oriented Micromagnetic Framework configuration files and Matlab scripts for results analysis

    NASA Astrophysics Data System (ADS)

    Chęciński, Jakub; Frankowski, Marek

    2016-10-01

    We present a tool for fully-automated generation of both simulations configuration files (Mif) and Matlab scripts for automated data analysis, dedicated for Object Oriented Micromagnetic Framework (OOMMF). We introduce extended graphical user interface (GUI) that allows for fast, error-proof and easy creation of Mifs, without any programming skills usually required for manual Mif writing necessary. With MAGE we provide OOMMF extensions for complementing it by mangetoresistance and spin-transfer-torque calculations, as well as local magnetization data selection for output. Our software allows for creation of advanced simulations conditions like simultaneous parameters sweeps and synchronic excitation application. Furthermore, since output of such simulation could be long and complicated we provide another GUI allowing for automated creation of Matlab scripts suitable for analysis of such data with Fourier and wavelet transforms as well as user-defined operations.

  3. Cancer testis antigens and NY-BR-1 expression in primary breast cancer: prognostic and therapeutic implications.

    PubMed

    Balafoutas, Dimitrios; zur Hausen, Axel; Mayer, Sebastian; Hirschfeld, Marc; Jaeger, Markus; Denschlag, Dominik; Gitsch, Gerald; Jungbluth, Achim; Stickeler, Elmar

    2013-06-03

    Cancer-testis antigens (CTA) comprise a family of proteins, which are physiologically expressed in adult human tissues solely in testicular germ cells and occasionally placenta. However, CTA expression has been reported in various malignancies. CTAs have been identified by their ability to elicit autologous cellular and or serological immune responses, and are considered potential targets for cancer immunotherapy. The breast differentiation antigen NY-BR-1, expressed specifically in normal and malignant breast tissue, has also immunogenic properties. Here we evaluated the expression patterns of CTAs and NY-BR-1 in breast cancer in correlation to clinico-pathological parameters in order to determine their possible impact as prognostic factors. The reactivity pattern of various mAbs (6C1, MA454, M3H67, 57B, E978, GAGE #26 and NY-BR-1 #5) were assessed by immunohistochemistry in a tissue micro array series of 210 randomly selected primary invasive breast cancers in order to study the diversity of different CTAs (e.g. MAGE-A, NY-ESO-1, GAGE) and NY-BR-1. These expression data were correlated to clinico-pathological parameters and outcome data including disease-free and overall survival. Expression of at least one CTA was detectable in the cytoplasm of tumor cells in 37.2% of the cases. NY-BR-1 expression was found in 46.6% of tumors, respectively. Overall, CTA expression seemed to be linked to adverse prognosis and M3H67 immunoreactivity specifically was significantly correlated to shorter overall and disease-free survival (p=0.000 and 0.024, respectively). Our findings suggest that M3H67 immunoreactivity could serve as potential prognostic marker in primary breast cancer patients. The exclusive expression of CTAs in tumor tissues as well as the frequent expression of NY-BR-1 could define new targets for specific breast cancer therapies.

  4. Do single-use medical devices containing biopolymers reduce the environmental impacts of surgical procedures compared with their plastic equivalents?

    PubMed

    Unger, Scott R; Hottle, Troy A; Hobbs, Shakira R; Thiel, Cassandra L; Campion, Nicole; Bilec, Melissa M; Landis, Amy E

    2017-01-01

    Background While petroleum-based plastics are extensively used in health care, recent developments in biopolymer manufacturing have created new opportunities for increased integration of biopolymers into medical products, devices and services. This study compared the environmental impacts of single-use disposable devices with increased biopolymer content versus typically manufactured devices in hysterectomy. Methods A comparative life cycle assessment of single-use disposable medical products containing plastic(s) versus the same single-use medical devices with biopolymers substituted for plastic(s) at Magee-Women's Hospital (Magee) in Pittsburgh, PA and the products used in four types of hysterectomies that contained plastics potentially suitable for biopolymer substitution. Magee is a 360-bed teaching hospital, which performs approximately 1400 hysterectomies annually. Results There are life cycle environmental impact tradeoffs when substituting biopolymers for petroplastics in procedures such as hysterectomies. The substitution of biopolymers for petroleum-based plastics increased smog-related impacts by approximately 900% for laparoscopic and robotic hysterectomies, and increased ozone depletion-related impacts by approximately 125% for laparoscopic and robotic hysterectomies. Conversely, biopolymers reduced life cycle human health impacts, acidification and cumulative energy demand for the four hysterectomy procedures. The integration of biopolymers into medical products is correlated with reductions in carcinogenic impacts, non-carcinogenic impacts and respiratory effects. However, the significant agricultural inputs associated with manufacturing biopolymers exacerbate environmental impacts of products and devices made using biopolymers. Conclusions The integration of biopolymers into medical products is correlated with reductions in carcinogenic impacts, non-carcinogenic impacts and respiratory effects; however, the significant agricultural inputs associated with manufacturing biopolymers exacerbate environmental impacts.

  5. 5-HTTLPR Expression Outside the Skin: An Experimental Test of the Emotional Reactivity Hypothesis in Children.

    PubMed

    Weeland, Joyce; Slagt, Meike; Brummelman, Eddie; Matthys, Walter; de Castro, Bram Orobio; Overbeek, Geertjan

    2015-01-01

    There is increasing evidence that variation in the promoter region of the serotonin transporter gene SLC6A4 (i.e., the 5-HTTLPR polymorphism) moderates the impact of environmental stressors on child psychopathology. Emotional reactivity -the intensity of an individual's response to other's emotions- has been put forward as a possible mechanism underlying these gene-by-environment interactions (i.e., G×E). Compared to children homozygous for the L-allele (LL-genotypes), children carrying an S-allele (SS/SL-genotypes), specifically when they have been frequently exposed to negative emotions in the family environment, might be more emotionally reactive and therefore more susceptible to affective environmental stressors. However, the association between 5-HTTLPR and emotional reactivity in children has not yet been empirically tested. Therefore, the goal of this study was to test this association in a large-scale experiment. Children (N = 521, 52.5% boys, Mage = 9.72 years) were genotyped and randomly assigned to happy, angry or neutral dynamic facial expressions and vocalizations. Motor and affective emotional reactivity were assessed through children's self-reported negative and positive affect (n = 460) and facial electromyography activity (i.e., fEMG: the zygomaticus or "smile" muscle and the corrugator or "frown" muscle, n = 403). Parents reported on their negative and positive parenting behaviors. Children mimicked and experienced the emotion they were exposed to. However, neither motor reactivity nor affective reactivity to these emotions depended on children's 5-HTTLPR genotype: SS/SL-genotypes did not manifest any stronger response to emotional stimuli than LL-genotypes. This finding remained the same when taking the broader family environment into account, controlling for kinship, age, gender and genetic ancestry, and when including a tri-allelic factor. We found no evidence for an association between the 5-HTTLPR polymorphism and children's emotional reactivity. This finding is important, in discounting one potential underlying endophenotype of G×E between the 5-HTTLPR and affective environmental stressors.

  6. Conversation and Object Manipulation Influence Children's Learning in a Museum.

    PubMed

    Jant, Erin A; Haden, Catherine A; Uttal, David H; Babcock, Elizabeth

    2014-01-01

    The effects of parent-child conversation and object manipulation on children's learning, transfer of knowledge, and memory were examined in two museum exhibits and conversations recorded at home. Seventy-eight children (Mage  = 4.9) and their parents were randomly assigned to receive conversation cards featuring elaborative questions about exhibit objects, the physical objects themselves, both, or neither, before their exhibit visits. Dyads who received the cards engaged in more elaborative talk and joint nonverbal activities with objects in the first exhibit than those who did not. Dyads who received objects engaged in the most parent-child joint talk. Results also illustrate transfer of information across exhibits and from museum to home. Implications for understanding mechanisms of informal learning and transfer are discussed. © 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.

  7. Children's daily well-being: The role of mothers', teachers', and siblings' autonomy support and psychological control.

    PubMed

    van der Kaap-Deeder, Jolene; Vansteenkiste, Maarten; Soenens, Bart; Mabbe, Elien

    2017-02-01

    This study examined the unique relations between multiple sources (i.e., mothers, teachers, and siblings) of perceived daily autonomy support and psychological control and children's basic psychological needs and well-being. During 5 consecutive days, 2 children from 154 families (Mage youngest child = 8.54 years; SD = .89 and Mage oldest child = 10.38 years; SD = .87) provided daily ratings of the study variables. Multilevel analyses showed that each of the sources of perceived autonomy support and psychological control related uniquely to changes in daily well-being and ill-being. These associations were mediated by experienced psychological need satisfaction and frustration, respectively. Overall, the findings testify to the dynamic role of autonomy support and psychological control in children's development. Implications for future research are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  8. MAGEC2, an epithelial-mesenchymal transition inducer, is associated with breast cancer metastasis.

    PubMed

    Yang, Fan; Zhou, Xingchun; Miao, Xia; Zhang, Tao; Hang, Xiaojun; Tie, Ru; Liu, Nan; Tian, Fei; Wang, Fuli; Yuan, Jianlin

    2014-05-01

    MAGEC2 is a member of melanoma antigen (MAGE) family of cancer-testis antigens and associated with tumor relapse and metastasis. Here, we investigated the expression of MAGEC2 in patients with breast cancer and its clinical effects with underlying mechanisms. The expression levels of MAGEC2 were compared between 420 invasive ductal carcinoma (IDC) and 120 ductal carcinoma in situ of the breast. Correlations between MAGEC2 expression and clinico-pathologic factors or survival of patients with IDC were analyzed. In addition, MAGEC2 expression levels in tumor tissues dissected from the primary focus and matched tumor-invaded axillary lymph nodes were analyzed in 8 breast cancer patients. The functional effects of MAGEC2 overexpression were assessed in vitro using scratch assay and transwell chamber assay. MAGEC2 expression was increased in metastatic breast cancer in comparison to the non-metastatic. MAGEC2 expression was significantly associated with ER negative expression (P = 0.037), high tumor grade (P = 0.014) and stage (P = 0.002), high incidence of axillary lymph node metastasis (P = 0.013), and distant metastasis (P = 0.004). Patients with tumor with MAGEC2 positive expression have a worse prognosis and a shorter metastasis free interval. Multivariate analyses showed that MAGEC2 expression was an independent risk factor for patient overall survival and metastasis-free survival. Breast cancer cells that overexpressed MAGEC2 had stronger migratory and invasive potential than control-treated cells. Epithelial markers (E-cadherin and cytokeratin) were down-regulated in MAGEC2-overexpressing cells compared to controls, whereas mesenchymal markers (vimentin and fibronectin) were upregulated. Our results indicate that MAGEC2 has a role in breast cancer metastasis through inducing epithelial-mesenchymal transition. In addition, MAGEC2 is a novel independent poor prognostic factor in patients with IDC. Thus, targeting MAGEC2 may provide a novel therapeutic strategy for breast cancer treatment.

  9. Interactive effect of negative affectivity and anxiety sensitivity in terms of mental health among Latinos in primary care.

    PubMed

    Zvolensky, Michael J; Paulus, Daniel J; Bakhshaie, Jafar; Garza, Monica; Ochoa-Perez, Melissa; Medvedeva, Angela; Bogiaizian, Daniel; Robles, Zuzuky; Manning, Kara; Schmidt, Norman B

    2016-09-30

    From a public health perspective, primary care medical settings represent a strategic location to address mental health disapirty among Latinos. Yet, there is little empirical work that addresses affective vulnerability processes for mental health problems in such settings. To help address this gap in knowledge, the present investigation examined an interactive model of negative affectivity (tendency to experience negative mood states) and anxiety sensitivity (fear of the negative consequences of aversive sensations) among a Latino sample in primary care in terms of a relatively wide range of anxiety/depression indices. Participants included 390 Latino adults (Mage=38.7, SD=11.3; 86.9% female; 95.6% reported Spanish as first language) from a primary care health clinic. Primary dependent measures included depressive, suicidal, social anxiety, and anxious arousal symptoms, number of mood and anxiety disorders, and disability. Consistent with prediction, the interaction between negative affectivity and anxiety sensitivity was significantly related to suicidal, social anxiety, and anxious arousal symptoms, as well as number of mood/anxiety diagnoses and disability among the primary care Latino sample. The form of the interactions indicated a synergistic effect, such that the greatest levels of each outcome were found among those with high negative affectivity and high anxiety sensitivity. There was a trending interaction for depressive symptoms. Overall, these data provide novel empirical evidence suggesting that there is a clinically-relevant interplay between anxiety sensitivity and negative affectivity in regard to the expression of anxiety and depressive symptoms among a Latino primary care sample. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Comparative effects of vildagliptin and sitagliptin determined by continuous glucose monitoring in patients with type 2 diabetes mellitus.

    PubMed

    Koyanagawa, Naohide; Miyoshi, Hideaki; Ono, Kota; Nakamura, Akinobu; Cho, Kyu Yong; Yamamoto, Kohei; Takano, Yoshinari; Dan-Noura, Midori; Atsumi, Tatsuya

    2016-08-31

    The dipeptidyl peptidase-4 inhibitors vildagliptin and sitagliptin are effective in treating patients with type 2 diabetes mellitus. Patients receiving standard doses of sitagliptin plus insulin may require increased doses of sitagliptin or switching to vildagliptin to improve blood glucose control. This study compared the effects of increasing sitagliptin and switching to vildagliptin in type 2 diabetes patients receiving standard doses of sitagliptin plus insulin. This prospective, randomized, parallel-group comparison trial enrolled 33 type 2 diabetes patients receiving 50 mg sitagliptin once daily plus insulin. Seventeen patients were randomized to 50 mg vildagliptin twice daily, and 16 to 100 mg sitagliptin once daily, and evaluated by continuous glucose monitoring at baseline and after 8 weeks. The primary end-point was the change in mean amplitude of glycemic excursions (MAGE). MAGE decreased from baseline in both the vildagliptin (-13.4 ± 35.7 mg/dL) and sitagliptin (-8.4 ± 24.3 mg/dL) groups, but neither within- nor between-group changes were statistically significant. Similarly, the areas under the curve for blood glucose levels ≥180 mg/dL and <70 mg/dL tended to improve in both groups, but these differences were not statistically significant. In contrast, HbA1c was significantly reduced only in the vildagliptin group, from 7.1 ± 0.6% at baseline to 6.8 ± 0.6% at 8 weeks (p=0.006). Increasing sitagliptin dose and switching to vildagliptin had limited effects in improving MAGE in type 2 diabetic patients treated with standard doses of sitagliptin.

  11. Improving in the fasting, but not the postprandial, glucose level is associated with reduction of plasma d-ROMs level in patients with type 2 diabetes.

    PubMed

    Ohara, Makoto; Watanabe, Kentaro; Suzuki, Tatsuya; Sekimizu, Ken-ichi; Motoyama, Masayuki; Ishii, Kazuhito; Sawai, Keisuke; Nakano, Hiroshi; Oba, Kenzo; Mizuno, Kyoichi

    2013-01-01

    This study aimed to evaluate the relationship between improvement of glucose metabolism and plasma levels of diacron-reactive oxygen metabolites (d-ROMs) in patients with type 2 diabetes. As the first daily profile, the plasma levels of glucose and d-ROMs were determined on admission. Then, after treatment to lower plasma glucose levels, the second daily profile of these levels was evaluated. Fasting plasma glucose (FPG), the total area under the curve (AUC) of the daily plasma glucose profile (AUCDP), the AUC of the postprandial plasma glucose levels (AUCPP), the AUC of the daily plasma d-ROMs profile (AUCd-ROMs), the coefficient of variation (CV) of plasma glucose (CVPG), and the mean amplitude of glycemic excursions (MAGE) were calculated. The relationship between the improvement of glucose metabolism and that of oxidative stress in patients with type 2 diabetes was evaluated. The second determinations of FPG, AUCDP, AUCPP, MAGE, and AUCd-ROMs were significantly lower than those of the first determinations, but no significant difference was observed in CVPG. Linear regression analysis demonstrated significant associations between the changes in AUCd-ROMs and the changes in both FPG and AUCDP, whereas no significant association was observed between the change in AUCd-ROMs and the change in AUCPP, CVPG, or MAGE. This study has demonstrated that improvement of the FPG level, but not of the postprandial glucose level, is associated with a reduction of the plasma level of d-ROMs in patients with type 2 diabetes.

  12. [Glycemic variability and oxidative stress in children, with type 1 diabetes attending a summer camp].

    PubMed

    Colomo, N; Tapia, M J; Vallejo, M R; García-Torres, F; Rubio-Martín, E; Caballero, F F; Jiménez, J M; Pelaez, M J; Gómez, A M; Sánchez, I; López-Siguero, J P; Soriguer, F; Ruiz de Adana, M S

    2014-09-01

    To assess glycemic variability, oxidative stress and their relationship in children and adolescents with type 1 diabetes (T1DM) attending a summer camp. Cross-sectional study that included 54 children and adolescents with T1DM aged 7-16, attending a 7 day summer camp. Sociodemographic information, clinical data, and blood glucose values measured using an Accu-Chek Nano® glucose meter were recorded. Glucose variability markers (standard deviation [SD], low blood glucose index [LBGI], high blood glucose index [HBGI], mean amplitude of glycemic excursions [MAGE] and mean of daily differences [MODD]) were calculated. Oxidative stress was assessed by the measurement of 8-iso-prostaglandin F2 alpha (PGF2α) in a 24-hour urine sample collected at the end of the camp in 14 children. The Median SD, MAGE and MODD indexes were in the high range (61, 131 and 58 mg/dl, respectively), LBGI in the moderate range (3.3), and HBGI in the low range (4.5). The mean HbA1c was 7.6% and the median urinary excretion rate of 8-iso-PGF2α was 864.39 pg/mg creatinine. The Spearman correlation coefficients between markers of glycemic variability (SD, HBGI, MAGE, MODD) were significant. Non-significant correlations were found between markers of glycemic variability and urinary 8-iso-PGF2α. High glycemic variability was observed in children and adolescents attending a summer camp. However, no correlations were found between markers of glycemic variability and oxidative stress measured by urinary 8-iso-PGF2α. Further studies are needed to address the relationship between oxidative stress and glycemic variability in children with T1DM. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  13. A Longitudinal Examination of Support, Self-esteem, and Mexican-origin Adolescent Mothers’ Parenting Efficacy

    PubMed Central

    Umaña-Taylor, Adriana J.; Guimond, Amy B.; Updegraff, Kimberly A.; Jahromi, Laudan

    2012-01-01

    Guided by a risk and resilience framework, this study used a prospective longitudinal, multiple-reporter design to examine how social support from a mother figure during pregnancy interacted with Mexican-origin adolescent mothers’ self-esteem to inform their parenting efficacy when their children were 10 months old. Using reports of perceived social support by adolescent mothers (Mage = 16.24, SD =099) and their mother figures (Mage = 40.84, SD = 7.04) in 205 dyads, and controlling for demographic factors (i.e., adolescent age, adolescent nativity, family income, mothers’ educational attainment, adolescent-mother coresidence) and adolescents’ social support from a significant other, findings indicated that social support during pregnancy was positively associated with adolescent mothers’ future parenting efficacy when adolescent mothers had relatively lower self-esteem. Findings were consistent for adolescents’ and mothers’ reports, and emphasize the value of social support from a mother figure among adolescent mothers with lower self-esteem. Implications for interventions are presented. PMID:24244049

  14. Adding to the Education Debt: Depressive Symptoms Mediate the Association between Racial Discrimination and Academic Performance in African Americans

    PubMed Central

    English, Devin; Lambert, Sharon F.; Ialongo, Nicholas S.

    2015-01-01

    Although the United States faces a seemingly intractable divide between white and African American academic performance, there remains a dearth of longitudinal research investigating factors that work to maintain this gap. The present study examined whether racial discrimination predicted the academic performance of African American students through its effect on depressive symptoms. Participants were a community sample of African American adolescents (N = 495) attending urban public schools from grade 7 to grade 9 (Mage = 12.5). Structural equation modeling revealed that experienced racial discrimination predicted increases in depressive symptoms 1 year later, which, in turn, predicted decreases in academic performance the following year. These results suggest that racial discrimination continues to play a critical role in the academic performance of African American students and, as such, contributes to the maintenance of the race-based academic achievement gap in the United States. PMID:27425564

  15. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miller, J.H.; Wilson, W.E.

    The beads on a string model proposed by Ganguly and Magee (A.K. Ganguly and J.L. Magee, J. Chem. Phys. 25, 129 (1956)) was generalized to allow Monte Carlo techniques to be used in calculating the influence of track structure on the yield of free radicals at early times following energy deposition by ionizing radiation in aqueous solutions. The results of the Monte Carlo calculations can be interpreted in terms of an effective linear energy transfer (LET) that is significantly less than the stopping power of the radiation when the track structure has a diffuse radial distribution due to energy transportmore » by delta-rays. By incorporating this effective LET for deuterons and alpha particles into a one radical approximation, the model can account for the effect of track structure on the yield of hydrated electrons measured by Sauer and co-workers (M.C. Sauer, Jr., K.H. Schmidt, E.J. Hart, C.A. Naleway and C.D. Jonah, Radiat. Res. 70, 91 (1977)).« less

  16. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miller, J.H.; Wilson, W.E.

    The beads on a string model proposed by Ganguly and Magee (A.K. Ganguly and J.L. Magee, J. Chem. Phys. 25, 129(1956)) was generalized to allow Monte Carlo techniques to be used in calculating the influence of track structure on the yield of free radicals at early times following energy deposition by ionizing radiation in aqueous solutions. The results of the Monte Carlo calculations can be interpreted in terms of an effective linear energy transfer (LET) that is significantly less than the stopping power of the radiation when the track structure has a diffuse radial distribution due to energy transport bymore » delta-rays. By incorporating this effective LET for deuterons and alpha particles into a one radical approximation, the model can account for the effect of track structure on the yield of hydrated electrons measured by Sauer and co-workers (M.C. Sauer, Jr., K.H. Schmidt, E.J. Hart, C.A. Naleway and C.D. Jonah, Radiat. Res. 70, 91(1977)). 3 figures.« less

  17. Learned social hopelessness: the role of explanatory style in predicting social support during adolescence.

    PubMed

    Ciarrochi, Joseph; Heaven, Patrick C L

    2008-12-01

    Almost no research has examined the impact of explanatory style on social adjustment. We hypothesised that adolescents with a pessimistic style would be less likely to develop and maintain social support networks. Seven hundred and nineteen students (351 males and 366 females; 2 unknown; M(AGE) = 12.28, SD = .49) completed an anonymous survey in Grades 7 through 10. Explanatory style was assessed in Grades 7 and 9, sadness was assessed in Grades 7 through 10, and quantity and quality of social support was assessed in Grades 8, 9, and 10. Structural equation modelling was used to conduct cross-lagged panel analyses of the four waves of data. Pessimistic explanatory style predicted lower levels of social support, and lower social support from the family predicted higher levels of pessimistic explanatory style. Additional analyses suggested that the effects could not be explained by sadness or by assuming that pessimistic adolescents where less liked by their peers. Pessimistic adolescents feel unable to influence their social worlds in positive ways and consequently may not take actions to develop and maintain social support networks.

  18. Self-affirming trait kindness regulates disgust toward one's physical appearance.

    PubMed

    Powell, Philip A; Simpson, Jane; Overton, Paul G

    2015-01-01

    In two studies, self-affirming the behavioral trait of kindness was examined as a method of regulating state disgust toward one's physical appearance. In Study 1, 56 participants (37 women, 19 men, Mage=33.16 years) completed either a questionnaire designed to self-affirm kindness or a control equivalent and rated their disgust, anger, sadness, and happiness toward their appearance and behavior. In Study 2, 116 individuals (83 women, 33 men, Mage=24.90 years) participated in the same experiment over the internet in an ecologically valid context. When controlling for trait self-disgust, the self-affirmed in Study 1 reported significantly less disgust toward their appearance (ηp(2)=.12, p=.011). This effect was replicated in Study 2, but driven by lower state disgust levels in those higher in trait self-disgust (f(2)=.10, p=.001). Affirming valued traits, like kindness, may be a useful tool for regulating disgust toward body image. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Do older adults perceive postural constraints for reach estimation?

    PubMed

    Cordova, Alberto; Gabbard, Carl

    2014-01-01

    BACKGROUND/STUDY CONTEXT: Recent evidence indicates that older persons have difficulty mentally representing intended movements. Furthermore, in an estimation of reach paradigm using motor imagery, a form of mental representation, older persons significantly overestimated their ability compared with young adults. The authors tested the notion that older adults may also have difficulty perceiving the postural constraints associated with reach estimation. The authors compared young (Mage = 22 years) and older (Mage = 67) adults on reach estimation while seated and in a more postural demanding standing and leaning forward position. The expectation was a significant postural effect with the standing condition, as evidenced by reduced overestimation. Whereas there was no difference between groups in the seated condition (both overestimated), older adults underestimated whereas the younger group once again overestimated in the standing condition. From one perspective, these results show that older adults do perceive postural constraints in light of their own physical capabilities. That is, that group perceived greater postural demands with the standing posture and elected to program a more conservative strategy, resulting in underestimation.

  20. Callous-unemotional traits moderate the association between children's early moral understanding and aggression: A short-term longitudinal study.

    PubMed

    Jambon, Marc; Smetana, Judith G

    2018-05-01

    Drawing on the framework of social domain theory, this multi-method, multi-informant longitudinal study examined whether callous-unemotional (CU) tendencies moderated the association between U.S. 4 to 7 year olds' (n = 135; Mage = 5.65, 50% male; 75% White) ability to differentiate hypothetical, prototypical moral and conventional transgressions along theoretical criteria and teacher (n = 49) and parent (n = 128, 91% mothers) ratings of physical aggression. Deficits in domain distinction ability were associated with greater teacher-reported aggression both concurrently and 9 months later, but only for children high in CU traits. No main effects or interactions were found for parent reports. These findings build on a growing body of research demonstrating that children who use aggression in a deliberate and callous manner show deficits in their basic understanding of moral norms. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  1. Considerations of Elder Sibling Closeness in Predicting Younger Sibling Substance Use: Social Learning versus Social Bonding Explanations

    PubMed Central

    Samek, Diana R.; Rueter, Martha A.

    2011-01-01

    Adolescent siblings are often similar in a variety of adjustment outcomes, yet little is known about the processes that explain sibling influences during adolescence. Two alternative explanations were tested, attachment (based in social bonding theory) and anaclitic identification (based in social learning theory). Hypotheses were tested using a sample of 613 adolescent sibling pairs (206 non-adopted, 407 adopted; elder sibling Mage = 16.1, younger sibling Mage = 13.8) across three sibling contexts (gender composition, age difference, and genetic similarity). Attachment explanations were supported such that the greater the perceived sibling emotional and behavioral closeness, the lower the likelihood of substance use; however, there were considerable moderating effects of sibling gender composition. Anaclitic identification explanations were not supported; closeness and elder sibling substance use did not interact to predict younger sibling substance use. Overall, this research adds to a body of work demonstrating important sibling influences on adolescent substance use. PMID:21988080

  2. The Relationship Between Problem-Solving Ability and Self-Harm Amongst People with Mild Intellectual Disabilities.

    PubMed

    Rees, Joanna; Langdon, Peter E

    2016-07-01

    The purpose of this study was to investigate the relationship between depression, hopelessness, problem-solving ability and self-harming behaviours amongst people with mild intellectual disabilities (IDs). Thirty-six people with mild IDs (77.9% women, Mage  = 31.77, SD = 10.73, MIQ  = 62.65, SD = 5.74) who had a history of self-harm were recruited. Participants were asked to complete measures of depression, hopelessness and problem-solving ability. Cutting was most frequently observed, and depression was prevalent amongst the sample. There was a significant positive relationship between depression and hopelessness, while there was no significant relationship between self-harm and depression or hopelessness. Problem-solving ability explained 15% of the variance in self-harm scores. Problem-solving ability appears to be associated with self-harming behaviours in people with mild IDs. © 2015 John Wiley & Sons Ltd.

  3. Effects of an Attachment-Based Intervention on Child Protective Services--Referred Mothers' Event-Related Potentials to Children's Emotions.

    PubMed

    Bernard, Kristin; Simons, Robert; Dozier, Mary

    2015-01-01

    This study examined the neurobiology of maternal sensitivity to children's emotions among mothers involved with Child Protective Services (CPS) and low-risk comparison mothers (M(age) = 31.6 years). CPS-referred mothers participated in the Attachment and Biobehavioral Catch-up (ABC) intervention or a control intervention. Mothers' event-related potentials (ERPs) were measured while they categorized images of children with crying, laughing, and neutral expressions. CPS-referred ABC mothers (n = 19) and low-risk comparison mothers (n = 30) showed a larger enhancement of ERP responses for emotional faces relative to neutral faces than CPS-referred control mothers (n = 21). Additionally, the magnitude of ERP responses to emotional faces was associated with observed maternal sensitivity. Findings add to the understanding of the neurobiology of deficits in parenting and suggest that these deficits are changeable through a parenting intervention. © 2015 The Authors. Child Development © 2015 Society for Research in Child Development, Inc.

  4. Multiplexed in vivo His-tagging of enzyme pathways for in vitro single-pot multienzyme catalysis.

    PubMed

    Wang, Harris H; Huang, Po-Yi; Xu, George; Haas, Wilhelm; Marblestone, Adam; Li, Jun; Gygi, Steven P; Forster, Anthony C; Jewett, Michael C; Church, George M

    2012-02-17

    Protein pathways are dynamic and highly coordinated spatially and temporally, capable of performing a diverse range of complex chemistries and enzymatic reactions with precision and at high efficiency. Biotechnology aims to harvest these natural systems to construct more advanced in vitro reactions, capable of new chemistries and operating at high yield. Here, we present an efficient Multiplex Automated Genome Engineering (MAGE) strategy to simultaneously modify and co-purify large protein complexes and pathways from the model organism Escherichia coli to reconstitute functional synthetic proteomes in vitro. By application of over 110 MAGE cycles, we successfully inserted hexa-histidine sequences into 38 essential genes in vivo that encode for the entire translation machinery. Streamlined co-purification and reconstitution of the translation protein complex enabled protein synthesis in vitro. Our approach can be applied to a growing area of applications in in vitro one-pot multienzyme catalysis (MEC) to manipulate or enhance in vitro pathways such as natural product or carbohydrate biosynthesis.

  5. Genetics Home Reference: PURA syndrome

    MedlinePlus

    ... lead to a reduced amount of functional Purα protein. Although it is not understood how a partial loss of Purα function leads to the ... KJ, Gawne-Cain M; DDD study, Magee AC, Turnpenny PD, Baralle D. Whole exome sequencing in family trios reveals de novo mutations in ...

  6. Empathic Responses to Mother’s Emotions Predict Internalizing Problems in Children of Depressed Mothers

    PubMed Central

    Tully, Erin C.; Donohue, Meghan Rose

    2016-01-01

    Recent theories posit that empathy, typically an adaptive characteristic, may be associated with internalizing problems when children are chronically exposed to mother’s depression. We tested this postulation in a sample of children (N=82, Mage=5 years). Children witnessed their mothers express sadness, anger, and happiness during a simulated phone conversation, and researchers rated children’s negative affective empathy, positive affective empathy, and information-seeking (cognitive empathy) in response to their mother’s emotions. The chronicity of mother's depression during the child’s lifetime moderated associations between children’s empathy and internalizing problems. As predicted, all three empathy measures were related to greater mother-rated internalizing problems in children of chronically (i.e., 2–3 years) depressed mothers. Greater positive empathy was related to lower internalizing problems in children of nondepressed mothers. Positive empathy may contribute to adaptive processes when mothers are not depressed, and positive, negative, and cognitive empathy may contribute to maladaptive processes when mothers are chronically depressed. PMID:27262565

  7. Beauty and the burn: tanning and other appearance-altering attitudes and behaviors.

    PubMed

    Gillen, Meghan M; Markey, Charlotte H

    2017-12-01

    Tanning is often prompted by appearance concerns, yet little is known about associations between tanning and other appearance-altering behaviors. In the current study, we examined potential correlates of indoor and outdoor tanning that, like tanning, may enhance appearance but present health risks. College students (N = 284; Mage = 20.14, SD = 3.39) completed a survey. The main outcome measures were indoor tanning and outdoor sunbathing. Participants also answered questions pertaining to piercings and tattoos, healthy and unhealthy dieting behaviors, cigarette smoking, and interest in cosmetic surgery and enhancements. Results indicate that indoor tanners were more likely to have piercings, tattoos, to engage in healthy dieting behaviors, and to express interest in cosmetic enhancements. Outdoor sunbathers were more interested in cosmetic enhancements than non-outdoor sunbathers, and female outdoor sunbathers reported more unhealthy dieting behaviors than male outdoor sunbathers. These findings provide evidence for college students' engagement in a constellation of appearance-oriented risk behaviors.

  8. Impact of flexible insulin therapy on blood glucose variability, oxidative stress and inflammation in type 1 diabetic patients: the VARIAFIT study.

    PubMed

    Benhamou, P Y; Somers, F; Lablanche, S; Debaty, I; Borel, A L; Nasse, L; Stanke-Labesque, F; Faure, P; Boizel, R; Halimi, S

    2014-09-01

    HbA1c only partially predicts vascular risk in patients with type 1 diabetes (T1D), and a role for blood glucose variability (BGV) is a matter of debate. For this reason, this study investigated the impact of an educational programme of flexible insulin therapy (FIT) on BGV and oxidative stress. Tests were conducted on 30 adult T1D patients in a prospective, single-centre trial at baseline (M0), and at 3 and 6 months (M3 and M6, respectively) of the FIT programme to determine BGV, as reflected by mean amplitude of glycaemic excursions (MAGE), low blood glucose index (LBGI), lability index (LI), average daily risk range (ADRR), glycaemic lability (scored by two diabetologists), urinary leukotriene E4 (LTE4), 11-dehydro-thromboxane B2 (TXB2) and 8-iso-prostaglandin F2α (PGF2). HbA1c (7.7 ± 0.9%), ADRR, MAGE, LBGI and LI did not change from M0 to M3 and M6, although ADRR and LBGI significantly improved at M3 and M6 in patients with the highest baseline indices (≥ 40 and ≥ 5, respectively). TXB2 declined at M6 (832 ± 625 vs. 633 ± 972 pg/mg; P=0.048), whereas LTE4 and PGF2 remained stable. ADRR showed the strongest correlation with glycaemic lability scores at all visits (r≥0.84, P<0.0001). A FIT educational programme improved BGV only in patients with the highest baseline variability, and led to no changes in HbA1c, while ADRR closely correlated with glycaemic lability score. Our data do not support a relationship between BGV and oxidative stress in T1D patients, although the impact of variability on TXB2 deserves further investigation (ClinicalTrials.gov NCT00973492). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. The Sport Motivation Scale for Children: preliminary analysis in physical education classes.

    PubMed

    Zahariadis, Panayotis N; Tsorbatzoudis, Haralambos; Grouios, George

    2005-08-01

    This study was done to test the psychometric properties of the modified version of the Sport Motivation Scale adapted for children in physical education. Participants were elementary school students (N = 452, M(age) = 13.9 +/- 1.04) who responded to the Sport Motivation Scale for Children. The scale assesses three types of motivation at the contextual level, namely, Intrinsic Motivation, Extrinsic Motivation, and Amotivation. Results supported the construct validity (CFI = .95), and internal consistency of the scale (Cronbach alpha > .65). Correlations indicated Sport Motivation Scale for Children simplex pattern exhibiting higher correlations among adjacent subscales than subscales farther apart. The concurrent validity, examined through correlations with scores on the Physical Self-description Questionnaire was satisfactory. Sex differences were examined to assess the discriminant validity. Boys were more intrinsically motivated than girls. Overall, the scale seems a useful one for assessment of motivation in physical education.

  10. Transgenerational aspects of former Swiss child laborers: do second generations suffer from their parents’ adverse early-life experiences?

    PubMed Central

    Küffer, Andreas L.; Thoma, Myriam V.; Maercker, Andreas

    2016-01-01

    Background Recent research suggests that childhood adversity exerts a lasting impact not only on the affected individuals but also on their offspring. Little is known about the role of parental rearing behavior in the transgenerational conveyance of parental childhood adversity and filial psychological health. Objective Hence, it was the aim of the current study to investigate the relationship between parental rearing behavior of former Swiss indentured child laborers (“Verdingkinder”) and psychological health of their adult offspring. Methods We applied a two-generation control-group design with two parental samples (n=16, former “Verdingkinder,” Mage=76.13, SD=6.81 and n=19, parental controls, Mage=72.63, SD=5.96) and their offspring (n=21, former “Verdingkinder” offspring, Mage=52.91, SD=5.90, and n=29 offspring controls, Mage=44.55, SD=7.71). Parental rearing behavior, childhood trauma, and psychological health were assessed with questionnaires. Data were analyzed using Bayesian analyses, where Bayes factors (BF) of 3 or higher were considered as substantial evidence for the tested hypotheses. Results We found that “Verdingkinder” offspring reported more physical abuse (BF10=5.197) and higher total childhood trauma exposure (BF10=2.476). They described both their fathers (BF10=14.246) and mothers (BF10=24.153) as less emotional and their mothers as more punitive (BF10=18.725). An increased sense of reflection, for instance, one's ability to take different perspectives, was found in the offspring controls (BF10=5.245). Furthermore, exploratory analyses revealed that lower perceived familial emotionality was associated with higher psychopathology (all BF10=10.471) and higher pessimism (all BF10=5.396). Discussion Our data provide cross-sectional evidence of a meaningful transgenerational relationship between parental childhood adversity, dysfunctional rearing behavior, and psychological health of offspring. Prospective studies are needed to investigate these findings in a longitudinal setting. Highlights of the article The study showed elevated levels of aversive childhood events in the adult offspring of former indentured childhood laborers.The offspring of former indentured childhood laborers did not exhibit increased general psychopathology (as assessed by the Symptom-Checklist: SCL).However, the recalled childhood rearing behavior was more problematic (higher punishment, less emotional warmth) in the offspring of former indentured childhood laborers as compared to a 2nd generation control group.Second generation group differences for world view variables (optimism, pessimism) were not substantial or in favor of the control participants (reflection facet of sense of coherence-revised). PMID:27784510

  11. Analytical aids in land management planning

    Treesearch

    David R. Betters

    1978-01-01

    Quantitative techniques may be applied to aid in completing various phases of land management planning. Analytical procedures which have been used include a procedure for public involvement, PUBLIC; a matrix information generator, MAGE5; an allocation procedure, linear programming (LP); and an input-output economic analysis (EA). These techniques have proven useful in...

  12. How Accurately Can Parents Judge Their Children’s Boredom in School?

    PubMed Central

    Nett, Ulrike E.; Daschmann, Elena C.; Goetz, Thomas; Stupnisky, Robert H.

    2016-01-01

    The purpose of the present study was to explore what parents know about their Children’s boredom in school; specifically, the frequency, intensity, and antecedents of their Children’s boredom, as well as how they cope with boredom. A questionnaire was administered to 437 grade 9 students (54% female, Mage = 14.82) and their parents (72% mothers, 14% fathers, 12% both parents, Mage = 45.26) measuring variables related to students boredom in mathematics class. Three different measurements were used to evaluate the accuracy of parents’ judgments: (1) the correlation between parents’ and students’ answers, (2) the mean differences between parents’ and students’ answers, and (3) the mean values of absolute differences of parents’ and students’ answers. The results suggest that parents generally have an informed knowledge about their child’s boredom and related facets. This is reflected by a mean correlation of medium size ( = 0.34) and a small mean effect size of the difference between parents’ and students’ judgments over all items ( = 0.20). Parents are also substantially better in judging their Children’s boredom compared to guessing for all variables (mean effect size of = 0.65). They had the most precise judgments for the frequency and intensity of boredom. The antecedents of boredom (e.g., characteristics of instruction) were also well estimated by parents; specifically, parents tend to have a bias in favor for their children evidenced by overestimating antecedents that cannot be influenced by the students and underestimating those that can be influenced by the students. The least concordance was found between parents’ and Children’s perception of boredom coping strategies (e.g., accepting boredom), implying that parents lack information about how their children intentionally cope with boredom. Implications for research on student boredom are discussed as well as practical applications involving parents in boredom prevention. PMID:27445876

  13. "Straight-acting gays": the relationship between masculine consciousness, anti-effeminacy, and negative gay identity.

    PubMed

    Sánchez, Francisco J; Vilain, Eric

    2012-02-01

    Some gay men are preoccupied with traditional notions of masculinity and express negative feelings towards effeminate behavior in gay men. Various scholars have speculated that such attitudes by gay men reflect internalized negative feelings about being gay. Thus, we sought to assess the importance of masculinity among gay men, to compare their ideal versus perceived masculinity-femininity, to ask how gay men assess masculinity, and to test whether masculine consciousness and anti-effeminacy could predict negative feelings about being gay. Results from an online survey of 751 gay men in the United States (MAge=32.64 years, SD=11.94) showed that the majority rated masculinity for themselves and in a same-sex partner as important, and they ideally wished that their behavior was more masculine (Cohen's d=.42) and less feminine (d=.42) than they perceived it to be. Furthermore, one's behavior was more important than how one looks when assessing masculinity. A multiple regression analysis showed that the degree to which they were preoccupied with masculinity and expressed anti-effeminacy accounted for 30% of the variance in negative feelings about being gay. These finding further support the idea that masculinity is an important construct for gay men and that masculine consciousness and anti-effeminacy are related to negative feelings about being gay.

  14. The Female Rescuer in Newbery Books: Who Is She?

    ERIC Educational Resources Information Center

    Roberts, Sherron Killingsworth

    A study used three Newbery books--"The Voyages of Dr. Doolittle (Lofting, 1922), "Charlotte's Web" (White, 1952), and "Maniac Magee" (Spinelli, 1990)--to examine three female characters identified in these books in the role of rescuer, accentuating their commonalities and differences within Jungian and feminist theory in…

  15. Stennis historical marker

    NASA Image and Video Library

    2011-10-25

    Stennis Space Center Director Patrick Scheuermann (second from left) stands at the historical marker erected by the state of Mississippi in honor of the 50th anniversary of the NASA facility. Joining Scheuermann are: (l to r) Ron Magee, Al Watkins, Tish Williams and Ken P'Pool.

  16. Single Nutrients and Immunity

    DTIC Science & Technology

    1982-02-01

    value if various types of encephalitis of increased severity when inoc- antigens are included within their interior ulated with distemper virus in...Magee JL. Piedad-Pascual F. Dietary 162. Newberne PM. Overnutrition on resistance of dogs amino acids and immune response in rats. J Nutr to distemper

  17. Peer Influence on Ethnic-Racial Identity Development: A Multi-Site Investigation.

    PubMed

    Santos, Carlos E; Kornienko, Olga; Rivas-Drake, Deborah

    2017-05-01

    The peer context features prominently in theory, and increasingly in empirical research, about ethnic-racial identity (ERI) development, but no studies have assessed peer influence on ERI using methods designed to properly assess peer influence. We examined peer influence on ERI centrality, private, and public regard using longitudinal social network analysis. Data were drawn from two sites: a predominantly Latina/o Southwestern (SW) school (N = 1034; Mage = 12.10) and a diverse Midwestern (MW) school (N = 513; Mage = 11.99). Findings showed that peers influenced each other's public regard over time at both sites. However, peer influence on centrality was evident in the SW site, whereas peer influence on private regard was evident in the MW site. Importantly, peer influence was evident after controlling for selection effects. Our integration of developmental, contextual, and social network perspectives offers a fruitful approach to explicate how ERI content may shift in early adolescence as a function of peer influence. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

  18. Daily Concordance between Parent and Adolescent Sleep Habits

    PubMed Central

    Fuligni, Andrew J.; Tsai, Kim M.; Krull, Jennifer L.; Gonzales, Nancy A.

    2014-01-01

    Purpose To assess the daily concordance between parent and adolescent daily sleep habits, how that concordance compares to other predictors of sleep, and whether the degree of concordance varies across families. Methods A total of 421 adolescents (Mage = 15.03 years) and their primary caregivers (Mage = 41.93 years) reported their sleep, bed, and wake times on a daily basis for a two-week period. Approximately 80% of the sample repeated the same protocol one year later. Results Multi-level modeling indicated a significant concordance between parent and adolescent sleep, bed, and wake times on a daily basis. Concordance existed independent of other predictors of sleep such as day of the week and adolescent study time. Larger families and those with higher levels of parent-adolescent support exhibited greater concordance. Conclusions Adolescent sleep is connected to the sleep habits of their parents, above and beyond commonly-known structural and experiential factors that can shape teenage sleep. Efforts to improve teenage sleep should pay greater attention to the sleep patterns of parents and potentially other family members. PMID:25620309

  19. Daily concordance between parent and adolescent sleep habits.

    PubMed

    Fuligni, Andrew J; Tsai, Kim M; Krull, Jennifer L; Gonzales, Nancy A

    2015-02-01

    To assess the daily concordance between parent and adolescent daily sleep habits, how that concordance compares to other predictors of sleep, and whether the degree of concordance varies across families. A total of 421 adolescents (Mage = 15.03 years) and their primary caregivers (Mage = 41.93 years) reported their sleep, bed, and wake times on a daily basis for a 2-week period. Approximately 80% of the sample repeated the same protocol 1 year later. Multilevel modeling indicated a significant concordance between parent and adolescent sleep, bed, and wake times on a daily basis. Concordance existed independent of other predictors of sleep such as day of the week and adolescent study time. Larger families and those with higher levels of parent-adolescent support exhibited greater concordance. Adolescent sleep is connected to the sleep habits of their parents, above and beyond commonly known structural and experiential factors that can shape teenage sleep. Efforts to improve teenage sleep should pay greater attention to the sleep patterns of parents and potentially other family members. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  20. Induction of MAGE-A3 and HPV-16 immunity by Trojan vaccines in patients with head and neck carcinoma

    PubMed Central

    Voskens, Caroline J.; Sewell, Duane; Hertzano, Ronna; DeSanto, Jennifer; Rollins, Sandra; Lee, Myounghee; Taylor, Rodney; Wolf, Jeffrey; Suntharalingam, Mohan; Gastman, Brian; Papadimitriou, John C.; Lu, Changwan; Tan, Ming; Morales, Robert; Cullen, Kevin; Celis, Esteban; Mann, Dean; Strome, Scott E.

    2013-01-01

    Background We performed a pilot study using Trojan vaccines in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). These vaccines are composed of HLA-I and HLA-II restricted melanoma antigen E (MAGE)-A3 or human papillomavirus (HPV)-16 derived peptides, joined by furin-cleavable linkers, and linked to a “penetrin” peptide sequence derived from HIV-TAT. Thirty-one patients with SCCHN were screened for the trial and 5 were enrolled. Methods Enrolled patients were treated with 300 lg of Trojan peptide supplemented with Montanide and granulocyte-macrophage colony-stimulating factor (GM-CSF) at 4-week intervals for up to 4 injections. Results Following vaccination, peripheral blood mononuclear cells (PBMCs) from 4 of 5 patients recognized both the full Trojan constructs and constituent HLA-II peptides, whereas responses to HLA-I restricted peptides were less pronounced. Conclusion This treatment regimen seems to have acceptable toxicity and elicits measurable systemic immune responses against HLA-II restricted epitopes in a subset of patients with advanced SCCHN. PMID:22287423

  1. Induction of MAGE-A3 and HPV-16 immunity by Trojan vaccines in patients with head and neck carcinoma.

    PubMed

    Voskens, Caroline J; Sewell, Duane; Hertzano, Ronna; DeSanto, Jennifer; Rollins, Sandra; Lee, Myounghee; Taylor, Rodney; Wolf, Jeffrey; Suntharalingam, Mohan; Gastman, Brian; Papadimitriou, John C; Lu, Changwan; Tan, Ming; Morales, Robert; Cullen, Kevin; Celis, Esteban; Mann, Dean; Strome, Scott E

    2012-12-01

    We performed a pilot study using Trojan vaccines in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). These vaccines are composed of HLA-I and HLA-II restricted melanoma antigen E (MAGE)-A3 or human papillomavirus (HPV)-16 derived peptides, joined by furin-cleavable linkers, and linked to a "penetrin" peptide sequence derived from HIV-TAT. Thirty-one patients with SCCHN were screened for the trial and 5 were enrolled. Enrolled patients were treated with 300 μg of Trojan peptide supplemented with Montanide and granulocyte-macrophage colony-stimulating factor (GM-CSF) at 4-week intervals for up to 4 injections. Following vaccination, peripheral blood mononuclear cells (PBMCs) from 4 of 5 patients recognized both the full Trojan constructs and constituent HLA-II peptides, whereas responses to HLA-I restricted peptides were less pronounced. This treatment regimen seems to have acceptable toxicity and elicits measurable systemic immune responses against HLA-II restricted epitopes in a subset of patients with advanced SCCHN. Copyright © 2012 Wiley Periodicals, Inc.

  2. Reported Exposure and Emotional Reactivity to Daily Stressors: The Roles of Adult-Age and Global Perceived Stress

    PubMed Central

    Stawski, Robert S.; Sliwinski, Martin J.; Almeida, David M.; Smyth, Joshua M.

    2012-01-01

    A central goal of daily stress research is to identify resilience and vulnerability factors associated with exposure and reactivity to daily stressors. The current study examined how age differences and global perceptions of stress relate to exposure and emotional reactivity to daily stressors. Sixty-seven younger (Mage = 20) and 116 older (Mage = 80) adults completed a daily stress diary and measures of positive and negative affect on 6 days over a 14 day period. Participants also completed a measure of global perceived stress. Results revealed that reported exposure to daily stressors is reduced in old age, but that emotional reactivity to daily stressors did not differ between young and older adults. Global perceived stress was associated with greater reported exposure to daily stressors in old adults, and greater stress-related increases in negative affect in younger adults. Furthermore, across days on which daily stressors were reported, intraindividual variability in the number and severity of stressors reported was associated with increased negative affect, but only among younger adults. PMID:18361654

  3. Evaluation of smokers with and without asthma in terms of smoking cessation outcome, nicotine withdrawal symptoms, and craving: Findings from a self-guided quit attempt.

    PubMed

    McLeish, Alison C; Farris, Samantha G; Johnson, Adrienne L; Bernstein, Jonathan A; Zvolensky, Michael J

    2016-12-01

    The aim of the current study was to evaluate smoking cessation outcome, nicotine withdrawal symptoms, and craving between smokers with (n=47; 46.8% male, Mage=40.0years, SD=11.7) and without (n=45; 51.1% male, Mage=37.5years, SD=11.1) asthma during a self-guided quit attempt. After completing a baseline assessment visit, participants attended study sessions on their scheduled quit day as well as follow-up visits (3days, 7days, 14days, and 28days) after their quit day. Smokers with and without asthma did not differ in abstinence rates, smoking lapse, and rate of change in urge to smoke to reduce negative affect. However, smokers with asthma demonstrated a slower rate of decline in nicotine withdrawal symptoms and craving over time. These findings suggest that smokers with asthma may benefit from specialized smoking cessation treatments to address prolonged withdrawal symptoms and craving. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Impact of incretin on early-phase insulin secretion and glucose excursion.

    PubMed

    Shen, Jie; Chen, Zhi; Chen, Chaofeng; Zhu, Xiao; Han, Yajuan

    2013-10-01

    This study investigated the impact of incretin on early-phase insulin secretion and glucose excursion. The normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) groups included 16, 8, and 19 subjects, respectively. Subjects underwent continuous glucose monitoring for 3 days, followed by an oral glucose tolerance test. Plasma glucose, insulin, glucagon, total glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-l (GLP-1) levels were measured at 30-min increments for 2 h after glucose intake. Differences with P < 0.05 were considered statistically significant. The area under the curve (AUC) of total GIP (120-min GIP-AUC) of the T2DM group was significantly lower than those of the NGT and IGT groups. The 120-min GLP-1-AUC of the NGT group was significantly larger than those of the T2DM and IGT groups. The early-phase insulin secretion index (ΔI30/ΔG30) of the T2DM group was significantly lower than those of the NGT and IGT groups. Mean amplitudes of glycemic excursions (MAGEs) went in the order of NGT < IGT < T2DM (P < 0.01, IGT vs. NGT; P < 0.001, T2DM vs. IGT). The 120-min GIP-AUC was negatively correlated with MAGE (r = -0.464), but uncorrelated with ΔI30/ΔG30. The 120-min GLP-1-AUC was positively correlated with ΔI30/ΔG30 (r = 0.580), but negatively correlated with MAGE (r = -0.606). Incretin may ameliorate glucose excursions, and GLP-1 may exert them by promoting early-phase insulin secretion. No correlation was observed between GIP secretion and early-phase insulin secretion.

  5. Distress Tolerance Links Sleep Problems with Stress and Health in Homeless.

    PubMed

    Reitzel, Lorraine R; Short, Nicole A; Schmidt, Norman B; Garey, Lorra; Zvolensky, Michael J; Moisiuc, Alexis; Reddick, Carrie; Kendzor, Darla E; Businelle, Michael S

    2017-11-01

    We examined associations between sleep problems, distress intolerance, and perceived stress and health in a convenience sample of homeless adults. Participants (N = 513, 36% women, Mage = 44.5 ±11.9) self-reported sleep adequacy, sleep duration, unintentional sleep during the daytime, distress tolerance, urban stress, and days of poor mental health and days of poor physical health over the last month. The indirect effects of sleep problems on stress and health through distress tolerance were examined using a non-parametric, bias-corrected bootstrapping procedure. Sleep problems were prevalent (eg, 13.0 ±11.4 days of inadequate sleep and 4.7 ±7.9 days of unintentionally falling asleep during the preceding month). Distress intolerance partially accounted for the associations of inadequate sleep and unintentionally falling asleep, but not sleep duration, with urban stress and more days of poor mental and physical health. Many homeless individuals endure sleep problems. Given the connections between sleep and morbidity and mortality, results further support the need for more attention directed toward facilitating improvements in sleep quality to improve the quality of life of homeless adults, potentially including attention to improving distress tolerance skills.

  6. Warping an atlas derived from serial histology to 5 high-resolution MRIs.

    PubMed

    Tullo, Stephanie; Devenyi, Gabriel A; Patel, Raihaan; Park, Min Tae M; Collins, D Louis; Chakravarty, M Mallar

    2018-06-19

    Previous work from our group demonstrated the use of multiple input atlases to a modified multi-atlas framework (MAGeT-Brain) to improve subject-based segmentation accuracy. Currently, segmentation of the striatum, globus pallidus and thalamus are generated from a single high-resolution and -contrast MRI atlas derived from annotated serial histological sections. Here, we warp this atlas to five high-resolution MRI templates to create five de novo atlases. The overall goal of this work is to use these newly warped atlases as input to MAGeT-Brain in an effort to consolidate and improve the workflow presented in previous manuscripts from our group, allowing for simultaneous multi-structure segmentation. The work presented details the methodology used for the creation of the atlases using a technique previously proposed, where atlas labels are modified to mimic the intensity and contrast profile of MRI to facilitate atlas-to-template nonlinear transformation estimation. Dice's Kappa metric was used to demonstrate high quality registration and segmentation accuracy of the atlases. The final atlases are available at https://github.com/CobraLab/atlases/tree/master/5-atlas-subcortical.

  7. Ethnic Differences in the Developmental Significance of Parentification

    PubMed Central

    Khafi, Tamar Y.; Yates, Tuppett M.; Luthar, Suniya S.

    2014-01-01

    Using an ecological framework, this 2-wave longitudinal study examined the effects of parentification on youth adjustment across the transition to adolescence in a high-risk, low-income sample of African American (58%) and European American (42%) mother-child dyads (T1 Mage = 10.17 years, T2 Mage = 14.89 years; 52.4% female). Children’s provision of family caregiving was moderately stable from early to late adolescence. Emotional and instrumental parentification evidenced distinct long-term effects on adolescents’ psychopathology and the quality of the parent-child relationship. Ethnicity moderated these relations. Emotional and instrumental parentification behaviors were associated with predominantly negative outcomes among European American youth in the form of increased externalizing behavior problems and decreased parent-child relationship quality, whereas emotional parentification was associated with positive outcomes among African American youth in the form of increased parent-child relationship quality, and instrumental parentification was neutral. These findings support a multidimensional view of parentification as a set of culturally-embedded phenomena whose effects can only be understood in consideration of the context in which they occur. PMID:24684188

  8. Prosocial skills may be necessary for better peer functioning in children with symptoms of disruptive behavior disorders

    PubMed Central

    Browne, Dillon T.; Tannock, Rosemary

    2014-01-01

    Children with disruptive behavior disorders experience substantial social challenges; however, the factors that account for (i.e., mediate), or influence (i.e., moderate), peer problems are not well understood. This study tested whether symptoms of Oppositional Defiant Disorder and Conduct Disorder were associated with peer impairment and whether prosocial skills mediated or moderated these associations. Teacher ratings were gathered for 149 children (Mage = 9.09, SD = 1.71, 26% female) referred for behavioral concerns to an urban child psychiatry clinic. Path-analytic linear regressions testing mediation and moderation effects showed that prosocial skills significantly moderated the negative effects of symptoms of Conduct Disorder on peer impairment. Children showed less peer impairment only when they had relatively few conduct symptoms and high prosocial skills. Measurement of prosocial skills, in addition to conduct problems, may best capture factors which contribute to peer problems of children with disruptive behaviors. PMID:25083349

  9. Prosocial skills may be necessary for better peer functioning in children with symptoms of disruptive behavior disorders.

    PubMed

    Andrade, Brendan F; Browne, Dillon T; Tannock, Rosemary

    2014-01-01

    Children with disruptive behavior disorders experience substantial social challenges; however, the factors that account for (i.e., mediate), or influence (i.e., moderate), peer problems are not well understood. This study tested whether symptoms of Oppositional Defiant Disorder and Conduct Disorder were associated with peer impairment and whether prosocial skills mediated or moderated these associations. Teacher ratings were gathered for 149 children (Mage = 9.09, SD = 1.71, 26% female) referred for behavioral concerns to an urban child psychiatry clinic. Path-analytic linear regressions testing mediation and moderation effects showed that prosocial skills significantly moderated the negative effects of symptoms of Conduct Disorder on peer impairment. Children showed less peer impairment only when they had relatively few conduct symptoms and high prosocial skills. Measurement of prosocial skills, in addition to conduct problems, may best capture factors which contribute to peer problems of children with disruptive behaviors.

  10. The antecedents and consequences of racial/ethnic discrimination during adolescence: does the source of discrimination matter?

    PubMed

    Benner, Aprile D; Graham, Sandra

    2013-08-01

    In the current study, we examined the precursors and consequences of discrimination for 876 Latino, African American, and Asian American adolescents (Mage = 16.9 years, SD = 0.43). The race/ethnic characteristics of schools and neighborhoods influenced adolescents' perceptions of the race/ethnic climates of these contexts. In turn, adolescents who viewed climates more negatively were more likely to perceive discriminatory treatment by school personnel, peers, and societal institutions. Discrimination from these 3 sources exerted differential influence on developmental outcomes: Greater discrimination from school personnel was associated with poorer academic performance, greater discrimination from peers was associated with more psychological maladjustment, and greater societal discrimination was associated with heightened racial awareness. Relations were consistent across race/ethnic groups and gender. Implications for intervening to reduce racial discrimination and other social stigmas are discussed. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  11. Constructing the Japanese version of the Maslach Burnout Inventory-Student Survey: Confirmatory factor analysis.

    PubMed

    Tsubakita, Takashi; Shimazaki, Kazuyo

    2016-01-01

    To examine the factorial validity of the Maslach Burnout Inventory-Student Survey, using a sample of 2061 Japanese university students majoring in the medical and natural sciences (67.9% male, 31.8% female; Mage  = 19.6 years, standard deviation = 1.5). The back-translated scale used unreversed items to assess inefficacy. The inventory's descriptive properties and Cronbach's alphas were calculated using SPSS software. The present authors compared fit indices of the null, one factor, and default three factor models via confirmatory factor analysis with maximum-likelihood estimation using AMOS software, version 21.0. Intercorrelations between exhaustion, cynicism, and inefficacy were relatively higher than in prior studies. Cronbach's alphas were 0.76, 0.85, and 0.78, respectively. Although fit indices of the hypothesized three factor model did not meet the respective criteria, the model demonstrated better fit than did the null and one factor models. The present authors added four paths between error variables within items, but the modified model did not show satisfactory fit. Subsequent analysis revealed that a bi-factor model fit the data better than did the hypothesized or modified three factor models. The Japanese version of the Maslach Burnout Inventory-Student Survey needs minor changes to improve the fit of its three factor model, but the scale as a whole can be used to adequately assess overall academic burnout in Japanese university students. Although the scale was back-translated, two items measuring exhaustion whose expressions overlapped should be modified, and all items measuring inefficacy should be reversed in order to statistically clarify the factorial difference between the scale's three factors. © 2015 The Authors. Japan Journal of Nursing Science © 2015 Japan Academy of Nursing Science.

  12. STAT1-Induced HLA class I Upregulation Enhances Immunogenicity and Clinical Response to anti-EGFR mAb Cetuximab Therapy in HNC Patients

    PubMed Central

    Srivastava, Raghvendra M.; Trivedi, Sumita; Concha-Benavente, Fernando; Hyun-bae, Jie; Wang, Lin; Seethala, Raja R.; Branstetter, Barton F.; Ferrone, Soldano; Ferris, Robert L.

    2015-01-01

    The goal of this study was to characterize the molecular mechanisms underlying cetuximab-mediated upregulation of HLA class I antigen-processing machinery components in head and neck cancer (HNC) cells and to determine the clinical significance of these changes in cetuximab-treated HNC patients. Flow cytometry, signaling studies and chromatin immunoprecipitation (ChIP) assays were performed using HNC cells treated with cetuximab alone or with Fcγ receptor (FcγR)-bearing lymphocytes to establish the mechanism of EGFR-dependent regulation of HLA APM expression. A prospective phase II clinical trial of neoadjuvant cetuximab was utilized to correlate HLA class I expression with clinical response in HNC patients. EGFR blockade triggered STAT1 activation and HLA upregulation, in a src homology-containing protein (SHP)-2-dependent fashion, more prominently in HLA-B/C than in HLA-A alleles. EGFR signaling blockade also enhanced IFNγ receptor 1 (IFNAR) expression, augmenting induction of HLA class I and TAP1/2 expression by IFNγ, which was abrogated in STAT1−/− cells. Cetuximab enhanced HNC cell recognition by EGFR853–861-specific CTLs, and notably enhanced surface presentation of a non-EGFR peptide (MAGE-3271–279). HLA class I upregulation was significantly associated with clinical response in cetuximab-treated HNC patients. EGFR induces HLA downregulation through SHP-2/STAT1 suppression. Reversal of HLA class I downregulation was more prominent in clinical responders to cetuximab therapy, supporting an important role for adaptive immunity in cetuximab antitumor activity. Abrogating EGFR-induced immune escape mechanisms and restoring STAT1 signaling to reverse HLA downregulation using cetuximab should be combined with strategies to enhance adaptive cellular immunity. PMID:25972070

  13. Conservatives Anticipate and Experience Stronger Emotional Reactions to Negative Outcomes.

    PubMed

    Joel, Samantha; Burton, Caitlin M; Plaks, Jason E

    2014-02-01

    The present work examined whether conservatives and liberals differ in their anticipation of their own emotional reactions to negative events. In two studies, participants imagined experiencing positive or negative outcomes in domains that do not directly concern politics. In Study 1, 190 American participants recruited online (64 male, Mage  = 32 years) anticipated their emotional responses to romantic relationship outcomes. In Study 2, 97 Canadian undergraduate students (26 male, Mage  = 21 years) reported on their anticipated and experienced emotional responses to academic outcomes. In both studies, more conservative participants predicted they would feel stronger negative emotions following negative outcomes than did more liberal participants. Furthermore, a longitudinal follow-up of Study 2 participants revealed that more conservative participants actually felt worse than more liberal participants after receiving a lower-than-desired exam grade. These effects remained even when controlling for the Big Five traits, prevention focus, and attachment style (Study 1), and optimism (Study 2). We discuss how the relationship between political orientation and anticipated affect likely contributes to differences between conservatives and liberals in styles of decision and policy choices. © 2013 Wiley Periodicals, Inc.

  14. Clarifying the Relation Between Extraversion and Positive Affect.

    PubMed

    Smillie, Luke D; DeYoung, Colin G; Hall, Phillip J

    2015-10-01

    This article clarifies two sources of ambiguity surrounding the relation between extraversion and positive affect. First, positive affect is defined differently across major models of the structure of affect. Second, no previous research has examined potentially diverging associations of lower-order aspects of extraversion (i.e., assertiveness and enthusiasm) with positive affect. Australian (Study 1: N = 437, 78% female, Mage  = 20.41) and American (Study 2: N = 262, 39% female, Mage  = 33.86) participants completed multiple measures of extraversion and positive affect. Correlations were employed to examine relations among these measures. In both studies, extraversion was most clearly associated with positive affect as conceptualized within a major factor model of affect-specifically, as positive activation (Watson & Tellegen, 1985)-rather than the valence-based conceptualization of positive affect provided by a circumplex model of affect (Russell, 1980). This was also the case for the assertiveness and enthusiasm aspects of extraversion. Our findings clarify the nature of the positive affective component of extraversion, which is best described in terms of both positive valence and high activation. © 2014 Wiley Periodicals, Inc.

  15. Relations of age with changes in self-efficacy and physical self-concept in preadolescents participating in a physical activity intervention during afterschool care.

    PubMed

    Annesi, James J

    2007-08-01

    An inference from Piaget's theory of cognitive development suggests that preadolescents of different ages who participate in a physical activity intervention may respond differently on measures of their physical self and self-efficacy, so a field investigation was conducted to assess effects. In a sample of 105 children ages 8 to 12 yr. (42% boys, overall M(age) = 10.1 yr., SD = 0.9), participation in a physical activity intervention during afterschool care, based on social cognitive theory and incorporating instruction in self-management and self-regulatory skills, was associated with significant improvements in measures of exercise-related self-efficacy, perceived physical appearance, and physical self-concept over 12 wk. Analyses suggested, however, no difference in changes on these factors was associated with participants' age or children being in either the concrete operations or formal operations stage of cognitive development. After replication, implications for design of physical activity interventions for preadolescents were suggested.

  16. Sex Differences in Panic-Relevant Responding to a 10% Carbon Dioxide-Enriched Air Biological Challenge

    PubMed Central

    Nillni, Yael I.; Berenz, Erin C.; Rohan, Kelly J.; Zvolensky, Michael J.

    2011-01-01

    The current study examined sex differences in psychological (i.e., self-reported anxiety, panic symptoms, and avoidance) and physiological (i.e., heart rate and skin conductance level) response to, and recovery from, a laboratory biological challenge. Participants were a community-recruited sample of 128 adults (63.3% women; Mage = 23.2 years, SD = 8.9) who underwent a 4-minute 10% CO2-enriched air biological challenge. As predicted, women reported more severe physical panic symptoms and avoidance (i.e., less willingness to participate in another challenge) and demonstrated increased heart rate as compared to men above and beyond the variance accounted for by other theoretically-relevant variables (recent panic attack history, neuroticism, and anxiety sensitivity). Additionally, women demonstrated a faster rate of recovery with respect to heart rate compared to men. These results are in line with literature documenting sex-specific differences in panic psychopathology, and results are discussed in the context of possible mechanisms underlying sex differences in panic vulnerability. PMID:22115836

  17. Adding to the Education Debt: Depressive Symptoms Mediate the Association between Racial Discrimination and Academic Performance in African Americans.

    PubMed

    English, Devin; Lambert, Sharon F; Ialongo, Nicholas S

    2016-08-01

    Although the United States faces a seemingly intractable divide between white and African American academic performance, there remains a dearth of longitudinal research investigating factors that work to maintain this gap. The present study examined whether racial discrimination predicted the academic performance of African American students through its effect on depressive symptoms. Participants were a community sample of African American adolescents (N=495) attending urban public schools from grade 7 to grade 9 (Mage=12.5). Structural equation modeling revealed that experienced racial discrimination predicted increases in depressive symptoms 1year later, which, in turn, predicted decreases in academic performance the following year. These results suggest that racial discrimination continues to play a critical role in the academic performance of African American students and, as such, contributes to the maintenance of the race-based academic achievement gap in the United States. Copyright © 2016 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

  18. A Longitudinal Study of the Associations among Adolescent Conflict Resolution Styles, Depressive Symptoms, and Romantic Relationship Longevity

    ERIC Educational Resources Information Center

    Ha, Thao; Overbeek, Geertjan; Cillessen, Antonius H. N.; Engels, Rutger C. M. E.

    2012-01-01

    This study investigated whether adolescents' conflict resolution styles mediated between depressive symptoms and relationship longevity. Data were used from a sample of 80 couples aged 13-19 years old (Mage = 15.48, SD = 1.16). At Time 1 adolescents reported their depressive symptoms and conflict resolution styles. Additionally, time until…

  19. Exploring Associations of Character Profiles and Out-Of-School Time Activities among Children and Adolescents

    ERIC Educational Resources Information Center

    Shubert, Jennifer; Metzger, Aaron; Wray-Lake, Laura; Syvertsen, Amy K.

    2016-01-01

    Conceptualizing character from a relational developmental systems metatheory, this study utilizes a person- oriented approach to examine profiles of character strengths in children and adolescents. Using Q sort methodology, 90 youth (Mage = 13.0, 51% female) sorted 12 character strengths based on how much each strength represented them. Using Q…

  20. An Evaluation of the Experimental Anthropology Program at Magee Secondary School During the Spring Semester of 1973.

    ERIC Educational Resources Information Center

    Moodie, Allan G.; And Others

    This study was performed to examine the effectiveness of an experimental anthropology program conducted in a secondary school. A semantic differential scale consisting of ten pairs of bipolar adjectives was administered in pre- and post-test sessions to anthropology students to measure their attitudes toward the following concepts: Culture,…

  1. Grade-Level Differences in Future-Oriented Self-Concept During Early Adolescence: Potential Relevance to School Nursing

    PubMed Central

    2016-01-01

    The middle school and early high school years are a time of significant development, including an increasing ability to envision oneself in the future. Little is known about how adolescents’ future-oriented self-concept (i.e., possible selves) differs across grade levels, although this knowledge may aid in establishing rapport with students and building effective health-promotion and risk reduction interventions. Therefore, this study explored grade-level differences in hoped for and feared possible selves in a sample of 6th – 9th grade students (n = 2,498; Mage = 12.72, SD = 1.15; 51.3% female). Findings suggest that adolescents list a variety of possible selves, and the content differs according to grade-level. These findings offer helpful insight for intervention work aimed at improving student outcomes and preventing risk behavior. Understanding what adolescents hope and fear for themselves in the future may be particularly beneficial for school nurses in identifying the unique challenges students experience and tailoring health-promotion efforts. PMID:27222444

  2. Evaluating emotional sensitivity and tolerance factors in the prediction of panic-relevant responding to a biological challenge.

    PubMed

    Kutz, Amanda; Marshall, Erin; Bernstein, Amit; Zvolensky, Michael J

    2010-01-01

    The current study investigated anxiety sensitivity, distress tolerance (Simons & Gaher, 2005), and discomfort intolerance (Schmidt, Richey, Cromer, & Buckner, 2007) in relation to panic-relevant responding (i.e., panic attack symptoms and panic-relevant cognitions) to a 10% carbon dioxide enriched air challenge. Participants were 216 adults (52.6% female; M(age)=22.4, SD=9.0). A series of hierarchical multiple regressions was conducted with covariates of negative affectivity and past year panic attack history in step one of the model, and anxiety sensitivity, discomfort intolerance, and distress tolerance entered simultaneously into step two. Results indicated that anxiety sensitivity, but not distress tolerance or discomfort intolerance, was significantly incrementally predictive of physical panic attack symptoms and cognitive panic attack symptoms. Additionally, anxiety sensitivity was significantly predictive of variance in panic attack status during the challenge. These findings emphasize the important, unique role of anxiety sensitivity in predicting risk for panic psychopathology, even when considered in the context of other theoretically relevant emotion vulnerability variables.

  3. 5-HTTLPR Expression Outside the Skin: An Experimental Test of the Emotional Reactivity Hypothesis in Children

    PubMed Central

    Weeland, Joyce; Slagt, Meike; Brummelman, Eddie; Matthys, Walter; de Castro, Bram Orobio; Overbeek, Geertjan

    2015-01-01

    Background There is increasing evidence that variation in the promoter region of the serotonin transporter gene SLC6A4 (i.e., the 5-HTTLPR polymorphism) moderates the impact of environmental stressors on child psychopathology. Emotional reactivity −the intensity of an individual’s response to other’s emotions− has been put forward as a possible mechanism underlying these gene-by-environment interactions (i.e., G×E). Compared to children homozygous for the L-allele (LL-genotypes), children carrying an S-allele (SS/SL-genotypes), specifically when they have been frequently exposed to negative emotions in the family environment, might be more emotionally reactive and therefore more susceptible to affective environmental stressors. However, the association between 5-HTTLPR and emotional reactivity in children has not yet been empirically tested. Therefore, the goal of this study was to test this association in a large-scale experiment. Methods Children (N = 521, 52.5% boys, Mage = 9.72 years) were genotyped and randomly assigned to happy, angry or neutral dynamic facial expressions and vocalizations. Motor and affective emotional reactivity were assessed through children’s self-reported negative and positive affect (n = 460) and facial electromyography activity (i.e., fEMG: the zygomaticus or “smile” muscle and the corrugator or “frown” muscle, n = 403). Parents reported on their negative and positive parenting behaviors. Results Children mimicked and experienced the emotion they were exposed to. However, neither motor reactivity nor affective reactivity to these emotions depended on children’s 5-HTTLPR genotype: SS/SL-genotypes did not manifest any stronger response to emotional stimuli than LL-genotypes. This finding remained the same when taking the broader family environment into account, controlling for kinship, age, gender and genetic ancestry, and when including a tri-allelic factor. Conclusions We found no evidence for an association between the 5-HTTLPR polymorphism and children’s emotional reactivity. This finding is important, in discounting one potential underlying endophenotype of G×E between the 5-HTTLPR and affective environmental stressors. PMID:26560754

  4. Parenting and later substance use among Mexican-origin youth: Moderation by preference for a common language.

    PubMed

    Schofield, Thomas J; Toro, Rosa I; Parke, Ross D; Cookston, Jeffrey T; Fabricius, William V; Coltrane, Scott

    2017-04-01

    The primary goal of the current study was to test whether parent and adolescent preference for a common language moderates the association between parenting and rank-order change over time in offspring substance use. A sample of Mexican-origin 7th-grade adolescents (Mage = 12.5 years, N = 194, 52% female) was measured longitudinally on use of tobacco, alcohol, and marijuana. Mothers, fathers, and adolescents all reported on consistent discipline and monitoring of adolescents. Both consistent discipline and monitoring predicted relative decreases in substance use into early adulthood but only among parent-offspring dyads who expressed preference for the same language (either English or Spanish). This moderation held after controlling for parent substance use, family structure, having completed schooling in Mexico, years lived in the United States, family income, and cultural values. An unintended consequence of the immigration process may be the loss of parenting effectiveness that is normally present when parents and adolescents prefer to communicate in a common language. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. First evaluation of a population-based screen to detect emotional-behavior disorders in orphaned children in Sub-Saharan Africa

    PubMed Central

    Sharp, Carla; Venta, Amanda; Marais, Lochner; Skinner, Donald; Lenka, Molefi; Serekoane, Joe

    2014-01-01

    Due to the HIV/AIDS pandemic which has left 12 million children orphaned in Sub-Saharan Africa, children are at increased risk for mental health problems. Currently, no validity data exist for any screening measure of emotional-behavior disorders in pre-adolescent children in Sub-Saharan Africa. The aims of the current study were to evaluate the construct validity of the caregiver-, teacher-, and self-report versions of the one-page Strengths and Difficulties Questionnaire (SDQ) in 466 orphans in South Africa between the ages of 7 and 11 (Mage = 9.23 years, SD = 1.33, 51.93% female) and to provide, for the first time, clinical cut-offs for this population. Findings demonstrated support for the caregiver SDQ, but not the teacher and selfreport versions. We provide clinical cut-offs, but caution their use before further research is conducted. There remains a critical need for further psychometric studies of the SDQ in the developing world. PMID:24623068

  6. Contemplative Practices and the Renewal of Legal Education

    ERIC Educational Resources Information Center

    Magee, Rhonda V.

    2013-01-01

    In this chapter, the author uses the phrase "contemplative practices" to encompass an array of personal and pedagogical methods that combine training in awareness and first-person epistemological approaches to knowing and being in the world. These practices include mindfulness meditation (Magee 2011). The gradual inclusion of mindfulness…

  7. 77 FR 3482 - Prospective Grant of Exclusive License: Development of T Cell Receptors and Chimeric Antigen...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-24

    ... contemplating the grant of an exclusive patent license, subject to existing non-exclusive licenses and current non-exclusive license applications under consideration, to practice the inventions embodied in U.S... equivalents thereof entitled ``Anti-MAGE-A3 T cell receptors and related materials and methods of use'' (HHS...

  8. Persuading people with depression to seek help: respect the boomerang.

    PubMed

    Lienemann, Brianna A; Siegel, Jason T; Crano, William D

    2013-01-01

    People with depression are likely to process information with a negative bias when confronted with self-relevant information. Accordingly, we feared exposing depressed people to a public service announcement (PSA) addressing the stigma of depression would possibly boomerang and result in less intention to seek help and in increased self-stigma. College students (N = 271; Mage  = 22.51, SD = 4.71; 63.1% female; 37.3% White, 31.9% Hispanic, 12.9% Asian, 6.8% multiethnic, 3.4% Black, 7.6% other) were randomly assigned to receive a print ad focused on depression or a nonrelevant comparison ad. A paper-and-pencil survey consisting of the Beck Depression Inventory-II, Self-Stigma of Seeking Help scale, help-seeking intentions, and demographics followed. Regression analysis indicated that viewing a depression ad caused people with greater depressive symptoms to experience greater levels of self-stigma than depressed people exposed to a nonrelevant comparison ad. Bootstrap mediation analysis showed that for individuals who viewed a depression PSA, self-stigma mediated the relationship between depressive symptoms and professional help-seeking intentions. While this current study offers no direct evidence in regard to the utility of current and past depression campaigns, results indicate a definite need for caution when developing materials targeting people with depression to seek help.

  9. The Portuguese adaptation of the Gudjonsson Suggestibility Scale (GSS1) in a sample of inmates.

    PubMed

    Pires, Rute; Silva, Danilo R; Ferreira, Ana Sousa

    2014-01-01

    This paper comprises two studies which address the validity of the Portuguese adaptation of the Gudjonsson Suggestibility Scale, GSS1. In study 1, the means and standard deviations for the suggestibility results of a sample of Portuguese inmates (N=40, Mage=37.5 years, SD=8.1) were compared to those of a sample of Icelandic inmates (Gudjonsson, 1997; Gudjonsson & Sigurdsson, 1996). Portuguese inmates' results were in line with the original results. In study 2, the means and standard deviations for the suggestibility results of the sample of Portuguese inmates were compared to those of a general Portuguese population sample (N=57, Mage=36.1 years, SD=12.7). The forensic sample obtained significantly higher scores in suggestibility measures than the general population sample. ANOVA confirmed that the increased suggestibility in the inmates sample was due to the limited memory capacity of this latter group. Given that the results of both studies 1 and 2 are in keeping with the author's original results (Gudjonsson, 1997), this may be regarded as a confirmation of the validity of the Portuguese GSS1. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. The Potential Explanatory Role of Perceived Stress in Associations Between Subjective Social Status and Health-Related Quality of Life Among Homeless Smokers.

    PubMed

    Garey, Lorra; Reitzel, Lorraine R; Kendzor, Darla E; Businelle, Michael S

    2016-01-01

    Homeless individuals smoke at high rates relative to the general population and are at heightened risk of tobacco-related illnesses and poor health-related quality of life (HRQoL). Homeless smokers also report low subjective social status (SSS) or perceived social standing relative to others. SSS may contribute to poor HRQoL, potentially through perceived stress. The current study examined the role of perceived stress in the association of SSS and HRQoL among 227 (70.9% male, Mage = 43.2) homeless smokers. Participants completed self-report measures of SSS, perceived stress, and HRQoL. Perceived stress partially explained the relation between SSS (United States and Community) and HRQoL in covariate-adjusted analyses. Results suggested that perceived stress is a pathway through which SSS contributes to HRQoL among homeless smokers. Findings broaden current understanding of the impact of social disadvantage and perceived stress on HRQoL among homeless smokers. © The Author(s) 2015.

  11. Altering Leadership Thinking and Organizational Behavior Through Web Services

    DTIC Science & Technology

    2010-04-01

    of Government, Harvard University. Galinsky, A. D ., Gruenfeld, D . H., & Magee, J. C . (2003). From power to action. Journal of Personality and...research. Education, 118(3). Keltner , D ., Grunfeld, D ., & Anderson , C . (2003). Power , approach and inhibition. Psychological Review, 110, 265–284...mean and if they are a leading indicator of behavioral change. Power and Behavior Studies have shown the

  12. Pubertal Status and Emotional Reactivity to a Voluntary Hyperventilation Challenge Predicting Panic Symptoms and Somatic Complaints

    ERIC Educational Resources Information Center

    Leen-Feldner, Ellen W.; Reardon, Laura E.; Zvolensky, Michael J.

    2007-01-01

    The main and interactive effects of pubertal status and emotional reactivity to bodily sensations elicited by a voluntary hyperventilation challenge were examined in relation to panic symptoms and self- and parent-reported somatic complaints among 123 (56 females) adolescents between the ages of 12 and 17 years (M[age] = 15.05; SD = 1.50). As…

  13. Scalable Device for Automated Microbial Electroporation in a Digital Microfluidic Platform.

    PubMed

    Madison, Andrew C; Royal, Matthew W; Vigneault, Frederic; Chen, Liji; Griffin, Peter B; Horowitz, Mark; Church, George M; Fair, Richard B

    2017-09-15

    Electrowetting-on-dielectric (EWD) digital microfluidic laboratory-on-a-chip platforms demonstrate excellent performance in automating labor-intensive protocols. When coupled with an on-chip electroporation capability, these systems hold promise for streamlining cumbersome processes such as multiplex automated genome engineering (MAGE). We integrated a single Ti:Au electroporation electrode into an otherwise standard parallel-plate EWD geometry to enable high-efficiency transformation of Escherichia coli with reporter plasmid DNA in a 200 nL droplet. Test devices exhibited robust operation with more than 10 transformation experiments performed per device without cross-contamination or failure. Despite intrinsic electric-field nonuniformity present in the EP/EWD device, the peak on-chip transformation efficiency was measured to be 8.6 ± 1.0 × 10 8 cfu·μg -1 for an average applied electric field strength of 2.25 ± 0.50 kV·mm -1 . Cell survival and transformation fractions at this electroporation pulse strength were found to be 1.5 ± 0.3 and 2.3 ± 0.1%, respectively. Our work expands the EWD toolkit to include on-chip microbial electroporation and opens the possibility of scaling advanced genome engineering methods, like MAGE, into the submicroliter regime.

  14. Relations among Temperament, Self-regulatory Strategies and Gender in Predicting Delay of Gratification

    PubMed Central

    Hong, Fang; Doan, Stacey N.; Lopez, Angelica; Evans, Gary W.

    2017-01-01

    Self-regulation is associated with many positive outcomes, but there is limited information about individual difference regarding children’s spontaneous use of strategies to self-regulate and the relative success of those strategies. In the current study, we examined whether temperament and gender are associated with self-regulation and explored the types of spontaneous strategies children use during Mischel’s delay of gratification protocol. In addition, we investigated whether spontaneous strategy use during the task could moderate the effects of temperament on self-regulation and whether temperament would mediate the effect of gender on self-regulation. Participants were 349 9-year-olds (182 boys, Mage = 9.18, SD = 1.17). Mothers reported on children’s temperament and the Delay of Gratification task was used to assess self-regulation. Both temperament and child’s gender were significantly associated with children’s delay time. Girls were able to delay longer than boys, and children scoring high on activity level were less able to delay. Activity level also mediated the relationship between gender and delay time. Finally, we found an interaction effect between activity level and certain strategies in relation to self-regulatory behavior. PMID:29163300

  15. The DNA Data Bank of Japan launches a new resource, the DDBJ Omics Archive of functional genomics experiments.

    PubMed

    Kodama, Yuichi; Mashima, Jun; Kaminuma, Eli; Gojobori, Takashi; Ogasawara, Osamu; Takagi, Toshihisa; Okubo, Kousaku; Nakamura, Yasukazu

    2012-01-01

    The DNA Data Bank of Japan (DDBJ; http://www.ddbj.nig.ac.jp) maintains and provides archival, retrieval and analytical resources for biological information. The central DDBJ resource consists of public, open-access nucleotide sequence databases including raw sequence reads, assembly information and functional annotation. Database content is exchanged with EBI and NCBI within the framework of the International Nucleotide Sequence Database Collaboration (INSDC). In 2011, DDBJ launched two new resources: the 'DDBJ Omics Archive' (DOR; http://trace.ddbj.nig.ac.jp/dor) and BioProject (http://trace.ddbj.nig.ac.jp/bioproject). DOR is an archival database of functional genomics data generated by microarray and highly parallel new generation sequencers. Data are exchanged between the ArrayExpress at EBI and DOR in the common MAGE-TAB format. BioProject provides an organizational framework to access metadata about research projects and the data from the projects that are deposited into different databases. In this article, we describe major changes and improvements introduced to the DDBJ services, and the launch of two new resources: DOR and BioProject.

  16. Effects of an 8-Week Outdoor Brisk Walking Program on Fatigue in Hi-Tech Industry Employees: A Randomized Control Trial.

    PubMed

    Wu, Li-Ling; Wang, Kuo-Ming; Liao, Po-I; Kao, Yu-Hsiu; Huang, Yi-Ching

    2015-10-01

    Over 73% of hi-tech industry employees in Taiwan lack regular exercise. They are exposed to a highly variable and stressful work environment for extended periods of time, and may subsequently experience depression, detrimental to workers' physiological and mental health. In this cross-sectional survey, the authors explored the effect of an 8-week brisk walking program on the fatigue of employees in the hi-tech industry. The participants, from a hi-tech company in northern Taiwan, were randomly assigned to an experimental group (EG; 41 subjects, Mage = 33.34 ± 6.40) or control group (CG; 45 subjects, Mage = 29.40 ± 3.60). Following the 8-week brisk walking program, the EG showed significantly lower scores for subjective fatigue, working motivation, attention, and overall fatigue. The authors confirmed that the 8-week outdoor brisk walking program significantly improved the level of fatigue among employees of the hi-tech industry. The finding serves as an important reference for health authorities in Taiwan and provides awareness of workplace health promotion in the hi-tech industry. © 2015 The Author(s).

  17. Young Chinese children's beliefs about the implications of subtypes of social withdrawal: A first look at social avoidance.

    PubMed

    Ding, Xuechen; Coplan, Robert J; Sang, Biao; Liu, Junsheng; Pan, Tingting; Cheng, Chen

    2015-06-01

    The goal of this study was to examine young Chinese children's beliefs about the implications of different subtypes of social withdrawal (e.g., shyness, unsociability), including for the first time, social avoidance. Participants were 133 children in kindergarten (n = 58, Mage  = 70.85 months) and grade 1 (n = 75, Mage  = 83.49 months). Children were presented with vignettes describing hypothetical peers displaying shy, unsociable, avoidant, and socially competent behaviours and were then asked a series of questions to assess their beliefs about the implications of these different behaviours. Young children made distinctions between social withdrawal subtypes in terms of underlying motivations and emotions. Children also appeared to hold differential beliefs about the implications of different forms of social withdrawal: Of note, they anticipated that socially avoidant peers would experience the most negative outcomes. These findings provide some of the first evidence to suggest that social avoidance represents a distinct form of social withdrawal among young Chinese children. Results are discussed in terms of the importance of distinguishing between different subtypes of social withdrawal in Chinese culture. © 2015 The British Psychological Society.

  18. Coping with Social Stress: Implications for Psychopathology in Young Adolescent Girls

    ERIC Educational Resources Information Center

    Sontag, Lisa M.; Graber, Julia A.; Brooks-Gunn, Jeanne; Warren, Michelle P.

    2008-01-01

    This study investigated the impact of social stress on symptoms of psychopathology at the entry into adolescence (111 girls, Mage = 11.84, SD = 0.77). We examined whether peer stress and pubertal timing were associated with internalizing distress and aggression, and whether responses to stress and cortisol reactivity mediated or moderated these…

  19. 75 FR 11503 - Approval and Promulgation of Implementation Plans; Texas; Revisions to Chapter 116 Which Relate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-11

    ... direct final rule located in the rules section of this Federal Register. FOR FURTHER INFORMATION CONTACT: If you have questions concerning today's proposal, please contact Ms. Melanie Magee (6PD-R), Air... Application and Permit Renewal Submittal AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule...

  20. Relationships at School and Stage-Environment Fit as Resources for Adolescent Engagement and Achievement

    ERIC Educational Resources Information Center

    Zimmer-Gembeck, Melanie J.; Chipuer, Heather M.; Hanisch, Michelle; Creed, Peter A.; McGregor, Leanne

    2006-01-01

    Guided by Self-Determination and associated theories, we examined whether adolescent (N=324, Mage=15, 52% female) competence (academic engagement and achievement) were supported by relationships at school and school fit. Aspects of relationships and school fit that were measured included adolescents' perceptions of each context as promoting…

  1. Students' Views on Mathematics in Single-Sex and Coed Classrooms in Ghana

    ERIC Educational Resources Information Center

    Bofah, Emmanuel Adu-tutu; Hannula, Markku S.

    2016-01-01

    In this study, we investigated students' views on themselves as learners of mathematics as a function of school-by-sex (N = 2034, MAge = 18.49, SDAge = 1.25; 12th-grade; 58.2% girls). Using latent variable Structural Equation Modeling (SEM), the measurement and structural equivalence as well as the equality of latent means of scores across…

  2. Personality Traits' Effects on Self-Efficacy and Outcome Expectations for High School Major Choice

    ERIC Educational Resources Information Center

    Brown, Dikla; Cinamon, Rachel Gali

    2016-01-01

    The current study focuses on the contribution of the Big Five personality traits to the development of self-efficacy and outcome expectations regarding selection of a high school major among 368 Israeli adolescents (Mage = 16.07, SD = 0.41). Structural equation analyses showed that higher levels of conscientiousness and extraversion and lower…

  3. Correlates of Sense of Control among Older Korean-American Immigrants: Financial Status, Physical Health Constraints, and Environmental Challenges

    ERIC Educational Resources Information Center

    Jang, Yuri; Kim, Giyeon; Chiriboga, David A.

    2006-01-01

    Responding to the need for more research on minority older populations, the present study assessed sense of control among older Korean-American immigrants. The association of sense of control with financial status, physical health constraints, and environmental challenges was examined with a sample of 230 older Korean-Americans (M[age] = 69.8,…

  4. The Interactive Role of Anxiety Sensitivity and Pubertal Status in Predicting Anxious Responding to Bodily Sensations among Adolescents

    ERIC Educational Resources Information Center

    Leen-Feldner, Ellen W.; Reardon, Laura E.; McKee, Laura G.; Feldner, Matthew T.; Babson, Kimberly A.; Zvolensky, Michael J. J.

    2006-01-01

    The present study examined the interaction between pubertal status and anxiety sensitivity (AS) in predicting anxious and fearful responding to a three-minute voluntary hyperventilation challenge among 124 (57 females) adolescents between the ages of 12 and 17 years (Mage = 15.04; SD = 1.49). As predicted, after controlling for baseline anxiety,…

  5. Further evidence of auditory extinction in aphasia.

    PubMed

    Marshall, Rebecca Shisler; Basilakos, Alexandra; Love-Myers, Kim

    2013-02-01

    Preliminary research (Shisler, 2005) suggests that auditory extinction in individuals with aphasia (IWA) may be connected to binding and attention. In this study, the authors expanded on previous findings on auditory extinction to determine the source of extinction deficits in IWA. Seventeen IWA (M(age) = 53.19 years) and 17 neurologically intact controls (M(age) = 55.18 years) participated. Auditory stimuli were spoken letters presented in a free-field listening environment. Stimuli were presented in single-stimulus stimulation (SSS) or double-simultaneous stimulation (DSS) trials across 5 conditions designed to determine whether extinction is related to binding, inefficient attention resource allocation, or overall deficits in attention. All participants completed all experimental conditions. Significant extinction was demonstrated only by IWA when sounds were different, providing further evidence of auditory extinction. However, binding requirements did not appear to influence the IWA's performance. Results indicate that, for IWA, auditory extinction may not be attributed to a binding deficit or inefficient attention resource allocation because of equivalent performance across all 5 conditions. Rather, overall attentional resources may be influential. Future research in aphasia should explore the effect of the stimulus presentation in addition to the continued study of attention treatment.

  6. Motivational dynamics underlying eating regulation in young and adult female dieters: relationships with healthy eating behaviours and disordered eating symptoms.

    PubMed

    Verstuyf, Joke; Vansteenkiste, Maarten; Soetens, Barbara; Soenens, Bart

    2016-06-01

    To investigate whether type of goals and motives underlying females' eating regulation are associated differentially with daily eating behaviours, dependent upon weight and age category. 99 late adolescent female dieters (Mage = 18.94) and 98 adult female dieters (Mage = 45.06), 23.6% of which were overweight, completed a questionnaire and a 7-day diary assessment. Descriptive analysis and path analysis were performed to investigate the research questions. Healthy eating behaviours (HEHS), drive for thinness and binge eating symptoms (EDI). Appearance-focused and controlled eating regulation were positively related to disordered eating symptoms throughout the week. In contrast, autonomous and health-focused eating regulation were associated positively with healthy eating behaviours and were either related negatively or unrelated to disordered eating symptoms. Mean level differences in motivation and eating behaviours emerged according to age and weight status. However, the examined structural model was similar for late adolescent and adult dieters and only few differences emerged between normal-weight and overweight dieters. Dieters' type of motivation helps to explain when eating regulation relates to healthy and disordered eating symptoms.

  7. Calculating the Mean Amplitude of Glycemic Excursions from Continuous Glucose Data Using an Open-Code Programmable Algorithm Based on the Integer Nonlinear Method.

    PubMed

    Yu, Xuefei; Lin, Liangzhuo; Shen, Jie; Chen, Zhi; Jian, Jun; Li, Bin; Xin, Sherman Xuegang

    2018-01-01

    The mean amplitude of glycemic excursions (MAGE) is an essential index for glycemic variability assessment, which is treated as a key reference for blood glucose controlling at clinic. However, the traditional "ruler and pencil" manual method for the calculation of MAGE is time-consuming and prone to error due to the huge data size, making the development of robust computer-aided program an urgent requirement. Although several software products are available instead of manual calculation, poor agreement among them is reported. Therefore, more studies are required in this field. In this paper, we developed a mathematical algorithm based on integer nonlinear programming. Following the proposed mathematical method, an open-code computer program named MAGECAA v1.0 was developed and validated. The results of the statistical analysis indicated that the developed program was robust compared to the manual method. The agreement among the developed program and currently available popular software is satisfied, indicating that the worry about the disagreement among different software products is not necessary. The open-code programmable algorithm is an extra resource for those peers who are interested in the related study on methodology in the future.

  8. REM Theta Activity Enhances Inhibitory Control in Typically Developing Children but not Children with ADHD Symptoms

    PubMed Central

    Cremone, Amanda; Lugo-Candelas, Claudia I.; Harvey, Elizabeth A.; McDermott, Jennifer M.; Spencer, Rebecca M. C.

    2017-01-01

    Sleep disturbances impair cognitive functioning in typically developing populations. Children with attention-deficit/hyperactivity disorder (ADHD), a disorder characterized by impaired inhibitory control and attention, commonly experience sleep disturbances. Whether inhibitory impairments are related to sleep deficits in children with ADHD is unknown. Children with ADHD (n = 18; Mage = 6.70 years) and typically developing controls (n = 15; Mage = 6.73 years) completed a Go/No-Go task to measure inhibitory control and sustained attention before and after polysomnography-monitored overnight sleep. Inhibitory control and sustained attention were improved following overnight sleep in typically developing children. Moreover, morning inhibitory control was positively correlated with rapid eye movement (REM) theta activity in this group. Although REM theta activity was greater in children with ADHD compared to typically developing children, it was functionally insignificant. Neither inhibitory control nor sustained attention were improved following overnight sleep in children with ADHD symptoms, and neither of these behaviors was associated with REM theta activity in this group. Taken together, these results indicate that elevated REM theta activity may be functionally related to ADHD symptomology, possibly reflecting delayed cortical maturation. PMID:28246970

  9. Estimating population salt intake in India using spot urine samples.

    PubMed

    Petersen, Kristina S; Johnson, Claire; Mohan, Sailesh; Rogers, Kris; Shivashankar, Roopa; Thout, Sudhir Raj; Gupta, Priti; He, Feng J; MacGregor, Graham A; Webster, Jacqui; Santos, Joseph Alvin; Krishnan, Anand; Maulik, Pallab K; Reddy, K Srinath; Gupta, Ruby; Prabhakaran, Dorairaj; Neal, Bruce

    2017-11-01

    To compare estimates of mean population salt intake in North and South India derived from spot urine samples versus 24-h urine collections. In a cross-sectional survey, participants were sampled from slum, urban and rural communities in North and in South India. Participants provided 24-h urine collections, and random morning spot urine samples. Salt intake was estimated from the spot urine samples using a series of established estimating equations. Salt intake data from the 24-h urine collections and spot urine equations were weighted to provide estimates of salt intake for Delhi and Haryana, and Andhra Pradesh. A total of 957 individuals provided a complete 24-h urine collection and a spot urine sample. Weighted mean salt intake based on the 24-h urine collection, was 8.59 (95% confidence interval 7.73-9.45) and 9.46 g/day (8.95-9.96) in Delhi and Haryana, and Andhra Pradesh, respectively. Corresponding estimates based on the Tanaka equation [9.04 (8.63-9.45) and 9.79 g/day (9.62-9.96) for Delhi and Haryana, and Andhra Pradesh, respectively], the Mage equation [8.80 (7.67-9.94) and 10.19 g/day (95% CI 9.59-10.79)], the INTERSALT equation [7.99 (7.61-8.37) and 8.64 g/day (8.04-9.23)] and the INTERSALT equation with potassium [8.13 (7.74-8.52) and 8.81 g/day (8.16-9.46)] were all within 1 g/day of the estimate based upon 24-h collections. For the Toft equation, estimates were 1-2 g/day higher [9.94 (9.24-10.64) and 10.69 g/day (9.44-11.93)] and for the Kawasaki equation they were 3-4 g/day higher [12.14 (11.30-12.97) and 13.64 g/day (13.15-14.12)]. In urban and rural areas in North and South India, most spot urine-based equations provided reasonable estimates of mean population salt intake. Equations that did not provide good estimates may have failed because specimen collection was not aligned with the original method.

  10. Positive Parenting and Children’s Prosocial Behavior in Eight Countries

    PubMed Central

    2015-01-01

    Background Research supports the beneficial role of prosocial behaviors on children’s adjustment and successful youth development. Empirical studies point to reciprocal relations between negative parenting and children’s maladjustment, but reciprocal relations between positive parenting and children’s prosocial behavior are understudied. In the present study reciprocal relations between two different dimensions of positive parenting (quality of the mother-child relationship and the use of balanced positive discipline) and children’s prosocial behavior were examined in Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States. Method Mother-child dyads (N = 1105) provided data over 2 years in 2 waves (Mage of child in wave 1 = 9.31 years, SD = .73; 50% female). Results A model of reciprocal relations between parenting dimensions, but not among parenting and children’s prosocial behavior, emerged. In particular, children with higher levels of prosocial behavior at age 9 elicited higher levels of mother-child relationship quality in the following year. Conclusions Findings yielded similar relations across countries, evidencing that being prosocial in late childhood contributes to some degree to the enhancement of a nurturing and involved mother-child relationship in countries that vary widely on sociodemographic profiles and psychological characteristics. Policy and intervention implications of this study are discussed. PMID:26511201

  11. Positive parenting and children's prosocial behavior in eight countries.

    PubMed

    Pastorelli, Concetta; Lansford, Jennifer E; Luengo Kanacri, Bernadette Paula; Malone, Patrick S; Di Giunta, Laura; Bacchini, Dario; Bombi, Anna Silvia; Zelli, Arnaldo; Miranda, Maria Concetta; Bornstein, Marc H; Tapanya, Sombat; Uribe Tirado, Liliana Maria; Alampay, Liane Pena; Al-Hassan, Suha M; Chang, Lei; Deater-Deckard, Kirby; Dodge, Kenneth A; Oburu, Paul; Skinner, Ann T; Sorbring, Emma

    2016-07-01

    Research supports the beneficial role of prosocial behaviors on children's adjustment and successful youth development. Empirical studies point to reciprocal relations between negative parenting and children's maladjustment, but reciprocal relations between positive parenting and children's prosocial behavior are understudied. In this study reciprocal relations between two different dimensions of positive parenting (quality of the mother-child relationship and the use of balanced positive discipline) and children's prosocial behavior were examined in Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States. Mother-child dyads (N = 1105) provided data over 2 years in two waves (Mage of child in wave 1 = 9.31 years, SD = 0.73; 50% female). A model of reciprocal relations between parenting dimensions, but not among parenting and children's prosocial behavior, emerged. In particular, children with higher levels of prosocial behavior at age 9 elicited higher levels of mother-child relationship quality in the following year. Findings yielded similar relations across countries, evidencing that being prosocial in late childhood contributes to some degree to the enhancement of a nurturing and involved mother-child relationship in countries that vary widely on sociodemographic profiles and psychological characteristics. Policy and intervention implications of this study are discussed. © 2015 Association for Child and Adolescent Mental Health.

  12. The Parent Magmas of the Cumulate Eucrites: A Mass Balance Approach

    NASA Technical Reports Server (NTRS)

    Treiman, Allan H.

    1996-01-01

    The cumulate eucrite meteorites are gabbros that are related to the eucrite basalt meteorites. The eucrite basalts are relatively primitive (nearly flat REE patterns with La approx. 8-30 x CI), but the parent magmas of the cumulate eucrites have been inferred as extremely evolved (La to greater than 100 x CI). This inference has been based on mineral/magma partitioning, and on mass balance considering the cumulate eucrites as adcumulates of plagioclase + pigeonite only; both approaches have been criticized as inappropriate. Here, mass balance including magma + equilibrium pigeonite + equilibrium plagiociase is used to test a simple model for the cumulate eucrites: that they formed from known eucritic magma types, that they consisted only of magma + crystals in chemical equilibrium with the magma, and that they were closed to chemical exchange after the accumulation of crystals. This model is tested for major and Rare Earth Elements (REE). The cumulate eucrites Serra de Mage and Moore County are consistent, in both REE and major elements, with formation by this simple model from a eucrite magma with a composition similar to the Nuevo Laredo meteorite: Serra de Mage as 14% magma, 47.5% pigeonite, and 38.5% plagioclase; Moore County as 35% magma, 37.5% pigeonite, and 27.5% plagioclase. These results are insensitive to the choice of mineral/magma partition coefficients. Results for the Moama cumulate eucrite are strongly dependent on choice of partition coefficients; for one reasonable choice, Moama's composition can be modeled as 4% Nuevo Laredo magma, 60% pigeonite, and 36% plagioclase. Selection of parent magma composition relies heavily on major elements; the REE cannot uniquely indicate a parent magma among the eucrite basalts. The major element composition of Y-791195 can be fit adequately as a simple cumulate from any basaltic eucrite composition. However, Y-791195 has LREE abundances and La/Lu too low to be accommodated within the model using any basaltic eucrite composition and any reasonable partition coefficients. Postcumulus loss of incompatible elements seems possible. It is intriguing that Serra de Mage, Moore County, and Moama are consistent with the same parental magma; could they be from the same igneous body on the eucrite parent asteroid (4 Vesta)?

  13. Understanding heterogeneity in social anxiety disorder: dependency and self-criticism moderate fear responses to interpersonal cues.

    PubMed

    Kopala-Sibley, Daniel C; Zuroff, David C; Russell, Jennifer J; Moskowitz, D S

    2014-06-01

    This study examined how the personality traits of self-criticism and dependency moderated the effects of situational interpersonal cues on fear during interpersonal interactions among individuals with social anxiety disorder (SAD). We hypothesized that self-criticism would moderate the fear-inducing effects of situational self-consciousness and that dependency would moderate the fear-inducing effects of situational emotional insecurity. Forty SAD patients (Mage = 29.23) and matched community controls (Mage = 28.93) completed event-contingent record forms after each significant social interaction of over 5 min for a 20-day period. There were 20 female patients and 20 male patients in each group. Event-level self-consciousness was more strongly associated with elevations in fear among socially anxious patients who reported higher levels of self-criticism, while event-level emotional security was more strongly associated with decreases in fear among SAD patients who reported higher levels of dependency. These interactions were not found in the community sample. Findings support the application of personality-vulnerability models to understanding fear during social interactions in patients with SAD. Results also have implications for psychotherapeutic treatments of SAD. © 2013 The British Psychological Society.

  14. Associations Among Individuals’ Perceptions of Future Time, Individual Resources, and Subjective Well-Being in Old Age

    PubMed Central

    Hoppmann, Christiane A.; Infurna, Frank J.; Ram, Nilam; Gerstorf, Denis

    2015-01-01

    Objectives Perceptions of future time are of key interest to aging research because of their implications for subjective well-being. Interestingly, perceptions about future time are only moderately associated with age, pointing to a vast heterogeneity in future time perceptions among older adults. We examine associations between future time perceptions, age, and subjective well-being across two studies, including moderations by individual resources. Method Using data from the Berlin Aging Study (N = 516; Mage = 85 years), we link one operationalization (subjective nearness to death) and age to subjective well-being. Using Health and Retirement Study data (N = 2,596; Mage = 77 years), we examine associations of another future time perception indicator (subjective future life expectancy) and age with subjective well-being. Results Consistent across studies, perceptions of limited time left were associated with poorer subjective well-being (lower life satisfaction and positive affect; more negative affect and depressive symptoms). Importantly, individual resources moderated future time perception–subjective well-being associations with those of better health exhibiting reduced future time perception–subjective well-being associations. Discussion We discuss our findings in the context of the Model of Strength and Vulnerability Integration. PMID:26437862

  15. Panic Attacks and Smoking Cessation among Cancer Patients Receiving Smoking Cessation Treatment

    PubMed Central

    Farris, Samantha G.; Robinson, Jason D.; Zvolensky, Michael J.; Hogan, Julianna; Rabius, Vance; Cinciripini, Paul M.; Karam-Hage, Maher; Blalock, Janice A.

    2018-01-01

    Objective Little is known about factors associated with smoking cessation in cancer patients. This study examined the impact of panic attacks on smoking abstinence likelihood among cancer patients receiving tobacco cessation treatment. Method The relationship of panic attacks to 7-day point-prevalence abstinence at mid-treatment, end of treatment, and 6-month post-end of treatment were examined among cancer patients (N = 2,255 patients; 50.1% female; Mage = 54.9, SD = 11.0) who received counseling and pharmacotherapy for smoking cessation. Panic attack history indexed by two questions from the Patient Health Questionnaire (PHQ). Post-prevalence abstinence was assessed via the Timeline Follow-Back. Results Cancer patients with a history of panic attacks, (n = 493, 21.9%) relative to those without, were less likely to be abstinent at mid-treatment (OR = 0.79, CI95% = 0.64–0.98) and end of treatment (OR = 0.72, CI95% = 0.58–0.89). After adjusting for significant covariates, panic attack history remained predictive of decreased abstinence likelihood at end of treatment (OR = 0.78, CI95% = 0.62–0.99). Conclusions Panic attacks may be related to poorer cessation outcome during smoking treatment among cancer patients, and may be usefully assessed and targeted for intervention. PMID:27235990

  16. Panic attacks and smoking cessation among cancer patients receiving smoking cessation treatment.

    PubMed

    Farris, Samantha G; Robinson, Jason D; Zvolensky, Michael J; Hogan, Julianna; Rabius, Vance; Cinciripini, Paul M; Karam-Hage, Maher; Blalock, Janice A

    2016-10-01

    Little is known about factors associated with smoking cessation in cancer patients. This study examined the impact of panic attacks on smoking abstinence likelihood among cancer patients receiving tobacco cessation treatment. The relationship of panic attacks to 7-day point-prevalence abstinence at mid-treatment, end of treatment, and 6-month post-end of treatment were examined among cancer patients (N=2255 patients; 50.1% female; Mage=54.9, SD=11.0) who received counseling and pharmacotherapy for smoking cessation. Panic attack history indexed by two questions from the Patient Health Questionnaire (PHQ). Point-prevalence abstinence was assessed via the Timeline Follow-Back. Cancer patients with a history of panic attacks, (n=493, 21.9%) relative to those without, were less likely to be abstinent at mid-treatment (OR=0.79, CI95%=0.64-0.98) and end of treatment (OR=0.72, CI95%=0.58-0.89). After adjusting for significant covariates, panic attack history remained predictive of decreased abstinence likelihood at end of treatment (OR =0.78, CI95%=0.62-0.99). Panic attacks may be related to poorer cessation outcome during smoking treatment among cancer patients, and may be usefully assessed and targeted for intervention. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Modulation of T Cell Activation by Malignant Melanoma Initiating Cells

    PubMed Central

    Schatton, Tobias; Schütte, Ute; Frank, Natasha Y.; Zhan, Qian; Hoerning, André; Robles, Susanne C.; Zhou, Jun; Hodi, F. Stephen; Spagnoli, Giulio C.; Murphy, George F.; Frank, Markus H.

    2010-01-01

    Highly immunogenic cancers such as malignant melanoma are capable of inexorable tumor growth despite the presence of antitumor immunity. This raises the possibility that only a restricted minority of tumorigenic malignant cells might possess the phenotypic and functional characteristics to modulate tumor-directed immune activation. Here we provide evidence supporting this hypothesis, by demonstrating that tumorigenic ABCB5+ malignant melanoma-initiating cells (MMICs) possess the capacity to preferentially inhibit interleukin (IL)-2-dependent T cell activation and to support, in a B7.2-dependent manner, regulatory T (Treg) cell induction. Compared to melanoma bulk populations, ABCB5+ MMICs expressed lower levels of the major histocompatibility complex (MHC) class I, showed aberrant positivity for MHC class II, and exhibited lower expression levels of the melanoma-associated antigens (MAAs) MART-1, ML-IAP, NY-ESO-1, and MAGE-A. In addition, tumorigenic ABCB5+ subpopulations preferentially expressed the costimulatory molecules B7.2 and PD-1 in both established melanoma xenografts and clinical tumor specimens in vivo. In immune activation assays, ABCB5+ melanoma cells inhibited mitogen-dependent human peripheral blood mononuclear cell (PBMC) proliferation and IL-2 production more efficiently than ABCB5− populations. Moreover, coculture with ABCB5+ MMICs increased, in a B7.2 signalling-dependent manner, CD4+CD25+FoxP3+ Treg cell abundance and IL-10 production by mitogen-activated PBMCs. Consistent with these findings, ABCB5+ melanoma subsets also preferentially inhibited IL-2 production and induced IL-10 secretion by cocultured patient-derived, syngeneic PBMCs. Our findings identify novel T cell-modulatory functions of ABCB5+ melanoma subpopulations and suggest specific roles for MMICs in the evasion of antitumor immunity and in cancer immunotherapeutic resistance. PMID:20068175

  18. Developmental Course(s) of Lifetime Cigarette Use and Panic Attack Comorbidity

    ERIC Educational Resources Information Center

    Bernstein, Amit; Zvolensky, Michael J.; Schmidt, Norman B.; Sachs-Ericcson, Natalie

    2007-01-01

    The present investigation examined the developmental course(s) of lifetime cigarette use and panic attack comorbidity. Participants included 4,409 adults, ages 15 to 54 years of age (M[Age] = 33.1, SD = 10.7, N (females) = 2,221) from the National Comorbidity Survey (NCS). The primary objective of the present investigation was to better understand…

  19. Historical Perspectives on Elizabeth Seton and Education: School Is My Chief Business

    ERIC Educational Resources Information Center

    McNeil, Betty Ann

    2006-01-01

    Born an Episcopalian in New York, Elizabeth Ann Bayley (1774-1821), married (1794) William Magee Seton (1768-1803). Blessed with three daughters (Anna Maria, Rebecca, and Catherine Charlton, called "Kit") and two sons (William and Richard), the couple briefly enjoyed the comforts of social status and prosperity. They opened their arms to…

  20. Training in Mental Rotation and Spatial Visualization and Its Impact on Orthographic Drawing Performance

    ERIC Educational Resources Information Center

    Samsudin, Khairulanuar; Rafi, Ahmad; Hanif, Abd Samad

    2011-01-01

    This paper reports the findings from an experimental study based on the pretest posttest research design that studied mental rotation (MR) and spatial visualization (SV) training outcomes and their impact on orthographic drawing performance. The sample of the study comprised 98 secondary school students (36 girls, 62 boys, Mage = 15.5 years, age…

  1. NASA Explorer School

    NASA Image and Video Library

    2007-11-08

    The NASA Explorer School-East Oktibbeha County School District team recently celebrated the start of its three-year partnership with NASA during a two-part kickoff event Nov. 7 and 8. Pictured from left are, Oktibbeha County School District Superintendent Dr. Walter Conley; NES Team Administrator James Covington; Stennis Space Center Deputy Director Gene Goldman; Sharon Bonner; NES Team Lead Yolanda Magee; Andrea Temple; Carolyn Rice; and special guest astronaut Roger Crouch.

  2. NASA Explorer School

    NASA Technical Reports Server (NTRS)

    2007-01-01

    The NASA Explorer School-East Oktibbeha County School District team recently celebrated the start of its three-year partnership with NASA during a two-part kickoff event Nov. 7 and 8. Pictured from left are, Oktibbeha County School District Superintendent Dr. Walter Conley; NES Team Administrator James Covington; Stennis Space Center Deputy Director Gene Goldman; Sharon Bonner; NES Team Lead Yolanda Magee; Andrea Temple; Carolyn Rice; and special guest astronaut Roger Crouch.

  3. Classroom Dimensions Predict Early Peer Interaction when Children Are Diverse in Ethnicity, Race, and Home Language

    ERIC Educational Resources Information Center

    Howes, Carollee; Guerra, Alison Wishard; Fuligni, Allison; Zucker, Eleanor; Lee, Linda; Obregon, Nora B.; Spivak, Asha

    2011-01-01

    The purpose of this study was to test a model for predicting preschool-age children's behaviors with peers from dimensions of the classroom and teacher-child relationship quality when the children were from diverse race, ethnic, and home language backgrounds. Eight hundred children, (M=age 63 months, SD=8.1 months), part of the National Evaluation…

  4. Effect of additional administration of acarbose on blood glucose fluctuations and postprandial hyperglycemia in patients with type 2 diabetes mellitus under treatment with alogliptin.

    PubMed

    Kusunoki, Yoshiki; Katsuno, Tomoyuki; Myojin, Makiko; Miyakoshi, Kana; Ikawa, Takashi; Matsuo, Toshihiro; Ochi, Fumihiro; Tokuda, Masaru; Murai, Kazuki; Miuchi, Masayuki; Hamaguchi, Tomoya; Miyagawa, Jun-ichiro; Namba, Mitsuyoshi

    2013-01-01

    Acarbose was administered at 300 mg/day to patients with type 2 diabetes mellitus (T2DM) who had been taking 25 mg/day of alogliptin, and levels of blood glucose were analyzed by continuous glucose monitoring (CGM) for 3 days. The mean blood glucose level with acarbose (136.4 ± 30.7 mg/dL) did not differ significantly from that without acarbose (141.7 ± 28.3 mg/dL). However, in the condition of the combination therapy, there were significant decreases in the standard deviation of the mean blood glucose levels for the 24-hour period (27.6 ± 9.1 vs. 16.2 ± 6.9 mg/dL, p<0.001) and mean amplitude of glycemic excursions (MAGE) (65.8 ± 26.1 vs. 38.8 ± 19.2 mg/dL, p=0.010). In addition, a meal tolerance test was conducted to monitor changes in insulin secretion and active GLP-1 and total GIP values. Ten subjects (5 males, 5 females) of 54.9 ± 6.9 years with BMI 25.9 ± 5.2 kg/m² and HbAlc 9.2 ± 1.2% were enrolled. In the meal tolerance test, active GLP-1 values before and after acarbose administration were 17.0 ± 5.8 and 24.1 ± 9.3 pmol·hr/mL (p=0.054), respectively, showing an increasing tendency, and total GIP(AUC0-180) values were 685.9 ± 209.7 and 404.4 ± 173.7 pmol·hr/mL, respectively, showing a significant decrease (p=0.010). The results indicate that the combined administration of both inhibitors is effective not only in decreasing blood glucose fluctuations and preventing postprandial insulin secretion. The beneficial effects may also protect the endocrine pancreas and inhibit body weight gain.

  5. Comparing Freshman and doctoral engineering students in design: mapping with a descriptive framework

    NASA Astrophysics Data System (ADS)

    Carmona Marques, P.

    2017-11-01

    This paper reports the results of a study of engineering students' approaches to an open-ended design problem. To carry out this, sketches and interviews were collected from 9 freshmen (first year) and 10 doctoral engineering students, when they designed solutions for orange squeezers. Sketches and interviews were analysed and mapped with a descriptive 'ideation framework' (IF) of the design process, to document and compare their design creativity (Carmona Marques, P., A. Silva, E. Henriques, and C. Magee. 2014. "A Descriptive Framework of the Design Process from a Dual Cognitive Engineering Perspective." International Journal of Design Creativity and Innovation 2 (3): 142-164). The results show that the designers worked in a manner largely consistent with the IF for generalisation and specialisation loops. Also, doctoral students produced more alternative solutions during the ideation process. In addition, compared to freshman, doctoral used the generalisation loop of the IF, working at higher levels of abstraction. The iterative nature of design is highlighted during this study - a potential contribution to decrease the gap between both groups in engineering education.

  6. Prediction of intention to continue sport in athlete students: A self-determination theory approach

    PubMed Central

    Keshtidar, Mohammad; Behzadnia, Behzad

    2017-01-01

    Grounded on the self-determination theory (Deci & Ryan, 1985, 2000) and achievement goals theory (Ames, 1992; Nicholls, 1989), this study via structural equation modelling, predicted intention to continue in sport from goal orientations and motivations among athlete students. 268 athlete students (Mage = 21.9), in Iranian universities completed a multi-section questionnaire tapping the targeted variables. Structural equation modelling (SEM) offered an overall support for the proposed model. The results showed that there are positive relationships between intention to continue in sport and both orientations as well as both motivations. A task-involving orientation emerged as a positive predictor of the autonomous motivation, while an ego-involving orientation was a positive predictor controlled motivation as well as autonomous motivation. The results also support positive paths between autonomous motivation and future intention to participate in sport. Autonomous motivation also was a positive mediator in relationship between task orientation and the intentions. As a conclusion, the implications of the task-involving orientation are discussabled in the light of its importance for the quality and potential maintenance of sport involvement among athlete students. PMID:28178308

  7. Prediction of intention to continue sport in athlete students: A self-determination theory approach.

    PubMed

    Keshtidar, Mohammad; Behzadnia, Behzad

    2017-01-01

    Grounded on the self-determination theory (Deci & Ryan, 1985, 2000) and achievement goals theory (Ames, 1992; Nicholls, 1989), this study via structural equation modelling, predicted intention to continue in sport from goal orientations and motivations among athlete students. 268 athlete students (Mage = 21.9), in Iranian universities completed a multi-section questionnaire tapping the targeted variables. Structural equation modelling (SEM) offered an overall support for the proposed model. The results showed that there are positive relationships between intention to continue in sport and both orientations as well as both motivations. A task-involving orientation emerged as a positive predictor of the autonomous motivation, while an ego-involving orientation was a positive predictor controlled motivation as well as autonomous motivation. The results also support positive paths between autonomous motivation and future intention to participate in sport. Autonomous motivation also was a positive mediator in relationship between task orientation and the intentions. As a conclusion, the implications of the task-involving orientation are discussabled in the light of its importance for the quality and potential maintenance of sport involvement among athlete students.

  8. Sex differences in panic-relevant responding to a 10% carbon dioxide-enriched air biological challenge.

    PubMed

    Nillni, Yael I; Berenz, Erin C; Rohan, Kelly J; Zvolensky, Michael J

    2012-01-01

    The current study examined sex differences in psychological (i.e., self-reported anxiety, panic symptoms, and avoidance) and physiological (i.e., heart rate and skin conductance level) response to, and recovery from, a laboratory biological challenge. Participants were a community-recruited sample of 128 adults (63.3% women; M(age)=23.2 years, SD=8.9) who underwent a 4-min 10% CO(2)-enriched air biological challenge. As predicted, women reported more severe physical panic symptoms and avoidance (i.e., less willingness to participate in another challenge) and demonstrated increased heart rate as compared to men above and beyond the variance accounted for by other theoretically relevant variables (recent panic attack history, neuroticism, and anxiety sensitivity). Additionally, women demonstrated a faster rate of recovery with respect to heart rate compared to men. These results are in line with literature documenting sex-specific differences in panic psychopathology, and results are discussed in the context of possible mechanisms underlying sex differences in panic vulnerability. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Rejected by peers-attracted to antisocial media content: rejection-based anger impairs moral judgment among adolescents.

    PubMed

    Plaisier, Xanthe S; Konijn, Elly A

    2013-06-01

    Adolescence is an important developmental stage during which both peers and the media have a strong influence. Both peer rejection and the use of morally adverse media are associated with negative developmental outcomes. This study examines processes by which peer rejection might drive adolescents to select antisocial media content by tying together developmental research on peer rejection and research on media effects. Assumed underlying mechanisms are rejection-based anger and frustration and the adolescent's moral judgment. A between-participants experimental design manipulated peer rejection versus acceptance in adolescents (Mage = 13.88 years; N = 74) and young adults (Mage = 21.37 years; N = 75), applying the Cyberball paradigm. Measures included the State Anger Inventory (STAXI) to assess feelings of rejection and the newly devised Media, Morals, and Youth Questionnaire (MMaYQue) to assess media preferences and moral judgment of media content. Using bootstrapping analyses, a double mediation was established: Higher levels of state anger in peer-rejected adolescents induced more tolerable moral judgments of antisocial media content, subsequently instigating a preference for antisocial media content. In contrast, the young adult sample showed no relations between peer rejection and antisocial media preference. Results are discussed within a downward spiral framework of combined peer and media influences. PsycINFO Database Record (c) 2013 APA, all rights reserved

  10. One-sided and mutually aggressive couples: Differences in attachment, conflict prevalence, and coping.

    PubMed

    Burk, William J; Seiffge-Krenke, Inge

    2015-12-01

    This study investigated concurrent links between adolescent romantic couples' reports of aggression (relational and physical) and relationship functioning (e.g., attachment security, conflict prevalence, coping strategies, jealousy, and affiliative and romantic relationship quality) using a pattern-oriented approach. The sample included 194 romantic partner dyads (Mage=16.99 years for females and Mage=18.41 years for males). A hierarchical cluster analysis identified five distinct subgroups of dyads based on male and female reports of relational and physical aggression, ranging from nonaggressive couples (42%), to those characterized by aggressive females (18%), aggressive males (14%), physically aggressive females (20%), and mutually aggressive females and males (6%). Clusters in which one partner was perceived as either relationally or physically aggressive were characterized by higher rates of conflict, less adaptive coping, and more jealousy (particularly in males). The mutually aggressive couples showed the least adaptive relationship functioning, with high rates of conflict, a deficit in reflection and emotion regulation in conflict situations, and a lack of affiliative relationship qualities. The discussion focuses on the formative character of aggression in these early romantic relations, the aggravating impact of mutual aggression on relationship functioning, and the gender-specific functions of aggression in relationships characterized by unilateral aggression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. On the Determinants and Outcomes of Passion for Playing Pokémon Go

    PubMed Central

    Orosz, Gábor; Zsila, Ágnes; Vallerand, Robert J.; Böthe, Beáta

    2018-01-01

    In 2016, Pokémon Go became the most popular smartphone game. Despite the increasing popularity of this augmented reality game, to date, no studies have investigated passion for playing Pokémon Go. On the theoretical basis of the Dualistic Model of Passion (DMP), our goal was to investigate the associations between Pokémon Go playing motives, passion, and impulsivity. A total of 621 Pokémon Go players participated in the study (54.9% female; Mage = 22.6 years, SDage = 4.4). It was found that impulsivity was more strongly associated with obsessive passion (OP) than with harmonious passion (HP). HP was associated with adaptive motives (i.e., outdoor activity, social, recreation, and nostalgia), while OP was associated with less adaptive motives (i.e., fantasy, escape, boredom, competition, and coping). Therefore, in line with the DMP, HP and OP for playing Pokémon Go can predict an almost perfectly distinguished set of adaptive or maladaptive playing motives, and OP has a noteworthy relationship with impulsivity as a determinant. PMID:29599735

  12. Does Practice Make Perfect? The Relationship Between Self-Reported Treatment Homework Completion and Parental Skill Acquisition and Child Behaviors.

    PubMed

    Stokes, Jocelyn O; Jent, Jason F; Weinstein, Allison; Davis, Eileen M; Brown, Tasha M; Cruz, Laura; Wavering, Hannah

    2016-07-01

    The purpose of the current study was to examine whether the rate and type of parent-reported homework completion is associated with parent-report of child behavior outcomes, number of sessions to master parental skills as measured by therapist observation, and length of treatment in Parent-child Interaction Therapy (PCIT). Sixty-two parent-child dyads (primary caregiver: Mage=36.35years, female 95.20%, 81.60% White, 59.57% Hispanic; child Mage=4.22years; child gender male 64.50%) who completed PCIT were included in the study. A within-subjects hierarchical regression statistical design was used to examine the impact of parent report of homework completion on treatment processes and outcomes. A higher rate of self-reported homework completion was predictive of parental mastery of skill acquisition in fewer sessions and treatment completion in fewer sessions. Parent report of homework completion rate was not related to changes in child disruptive behavior after controlling for child behavior at baseline. Current study findings reinforce the importance of having parents regularly practice PCIT skills outside of session in order to decrease treatment length and facilitate the acquisition of parenting skills, which may reduce family burdens associated with attending a weekly treatment. Copyright © 2016. Published by Elsevier Ltd.

  13. Cross-situational consistency of trait expressions and injunctive norms among Asian Canadian and European Canadian undergraduates.

    PubMed

    Locke, Kenneth D; Sadler, Pamela; McDonald, Kelly

    2018-06-14

    In the current paper, we sought to clarify when and why Asian Americans/Canadians and European Americans/Canadians differ in self-consistency (the consistency of personality traits across situations). European Canadian (n = 220) and second-generation Asian Canadian (n = 166) undergraduates (Mage = 19 years) described the traits they expressed and the traits others wanted them to express (i.e., injunctive norms, or injunctions) in four different social situations (i.e., with parents, with friends, with siblings, and with professors). Self-consistency was greater among European Canadians than Asian Canadians, but only when comparing behavior with parents versus with peers (i.e., friends and siblings). The same pattern was found for injunctive consistency (cross-situational consistency of trait injunctions). Injunctions strongly predicted the behavior of both Asian and European Canadians, but because the injunctions from parents versus peers diverged more for Asian Canadians, so did their behaviors. Controlling for the effect of inconsistent injunctions across situations eliminated the ethnic difference in self-consistency. Finally, Asian Canadians who perceived their immigrant parents as embracing a Canadian identity were as cross-situationally consistent as European Canadians because they tended to behave-and believe their parents approved of their behaving-with parents similarly to how they behaved with peers (e.g., more carefree and outspoken). Contrary to previous theorizing, cultural influences on broad cognitive or motivational dispositions (e.g., dialecticism, collectivism) alone cannot explain the observed pattern of ethnic differences in consistency. To understand when bicultural individuals are less consistent across situations also requires an understanding of the specific situations across which they tend to encounter divergent social norms. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  14. An Evaluation of Anxiety Sensitivity, Emotional Dysregulation, and Negative Affectivity among Daily Cigarette Smokers: Relation to Smoking Motives and Barriers to Quitting

    PubMed Central

    Gonzalez, Adam; Zvolensky, Michael J.; Vujanovic, Anka A.; Leyro, Teresa M.; Marshall, Erin C.

    2008-01-01

    The present investigation evaluated the relations between anxiety sensitivity and motivational bases of cigarette smoking, as well as barriers to quitting smoking, above and beyond concurrent substance use, negative affectivity, and emotional dysregulation among a community sample of 189 daily cigarette smokers (46% women; Mage = 24.97 years, SD = 9.78). Results indicated that anxiety sensitivity was significantly related to coping, addictive, and habitual smoking motives, as well as greater perceived barriers to quitting. These effects were evident above and beyond the variance accounted for by concurrent tobacco, alcohol, and marijuana use and discernable from shared variance with negative affectivity and emotional dysregulation. Emotional dysregulation was significantly related to stimulation, habitual, and sensorimotor smoking motives and greater perceived barriers to quitting, whereas negative affectivity was only significantly related to smoking for relaxation. These findings uniquely add to a growing literature suggesting anxiety sensitivity is an important and unique cognitive factor for better understanding clinically-relevant psychological processes related to cigarette smoking. PMID:18417153

  15. Authoritarian parenting predicts reduced electrocortical response to observed adolescent offspring rewards

    PubMed Central

    Speed, Brittany C.; Nelson, Brady; Bress, Jennifer N.; Hajcak, Greg

    2017-01-01

    Abstract Parenting styles are robust predictors of offspring outcomes, yet little is known about their neural underpinnings. In this study, 44 parent-adolescent dyads (Mage of adolescent = 12.9) completed a laboratory guessing task while EEG was continuously recorded. In the task, each pair member received feedback about their own monetary wins and losses and also observed the monetary wins and losses of the other member of the pair. We examined the association between self-reported parenting style and parents’ electrophysiological responses to watching their adolescent winning and losing money, dubbed the observational Reward Positivity (RewP) and observational feedback negativity (FN), respectively. Self-reported authoritarian parenting predicted reductions in parents’ observational RewP but not FN. This predictive relationship remained after adjusting for sex of both participants, parents’ responsiveness to their own wins, and parental psychopathology. ‘Exploratory analyses found that permissive parenting was associated with a blunting of the adolescents’ response to their parents’ losses’. These findings suggest that parents’ rapid neural responses to their child’s successes may relate to the harsh parenting behaviors associated with authoritarian parenting. PMID:27613780

  16. Nuclear Matrix Proteins in Disparity of Prostate Cancer

    DTIC Science & Technology

    2010-07-01

    Arlington, VA 22202- 4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty... VA Medical Center7, New Orleans, LA, and Vanderbilt University School of Medicine8, Nashville, TN. (** see attached abstract) 3. Manuscript...grant # PC081594). Citation Format: Yang Y, Jia D, Davis R, Moparty K, Thomas R, Moroz K, Agrawal K, Abdel- Mageed A. Heterogeneous nuclear

  17. Secondary School Students' Physical Activity Participation across Physical Education Classes: The Expectancy-Value Theory Approach

    ERIC Educational Resources Information Center

    Gråstén, Arto; Watt, Anthony; Hagger, Martin; Jaakkola, Timo; Liukkonen, Jarmo

    2015-01-01

    The primary purpose of this study was to analyze the link between students' expectancy beliefs, subjective task values, out-of-school activity, and moderate to vigorous physical activity (MVPA) participation across secondary school physical education (PE) classes. The sample comprised 96 students (58 girls, 38 boys; Mage = 15.03, SD = 0.94) from…

  18. Adaptation and Validation of the Basque Version of the Emotional Creativity Inventory in Higher Education.

    PubMed

    Soroa, Goretti; Aritzeta, Aitor; Balluerka, Nekane; Gorostiaga, Arantxa

    2016-06-03

    Emotional creativity is defined as the ability to feel and express emotions in a new, effective and authentic way. There are currently no Basque-language self-report instruments to provide valid and reliable measures of this construct. Thus, this paper describes the process of adapting and validating the Emotional Creativity Inventory (ECI) for the Basque-speaking population. The sample was comprised of 594 higher education students (388 women and 206 men) aged between 18 and 32 years old (Mage = 20.47; SD = 2.48). The Basque version of the ECI was administered along with the TMMS-23, NEO PI-R, and PANAS. The results of exploratory and confirmatory factor analyses on the Basque ECI corroborated the original scale's three-factor structure (preparedness, novelty, and effectiveness/authenticity). Those dimensions showed acceptable indexes of internal consistency (α = .80, .83, and .83) and temporal stability (r = .70, .69, and .74). The study also provided some evidence of external validity (p < .05) based on the relationships found between emotional creativity and emotional intelligence, personality, affect, and sex. The Basque ECI can be regarded as a useful tool to evaluate perceived emotional creativity during the preparation and verification phases of the creative process.

  19. Early-adult correlates of maltreatment in girls with attention-deficit/hyperactivity disorder: Increased risk for internalizing symptoms and suicidality

    PubMed Central

    GUENDELMAN, MAYA D.; OWENS, ELIZABETH B.; GALÁN, CHARDEE; GARD, ARIANNA; HINSHAW, STEPHEN P.

    2016-01-01

    We examined whether maltreatment experienced in childhood and/or adolescence prospectively predicts young adult functioning in a diverse and well-characterized sample of females with childhood-diagnosed attention-deficit/hyperactivity disorder (N = 140). Participants were part of a longitudinal study and carefully evaluated in childhood, adolescence, and young adulthood (Mage = 9.6, 14.3, and 19.7 years, respectively), with high retention rates across time. A thorough review of multisource data reliably established maltreatment status for each participant (Mκ = 0.78). Thirty-two (22.9%) participants experienced at least one maltreatment type (physical abuse, sexual abuse, or neglect). Criterion variables included a broad array of young adult measures of functioning gleaned from multiple-source, multiple-informant instruments. With stringent statistical control of demographic, prenatal, and family status characteristics as well as baseline levels of the criterion variable in question, maltreated participants were significantly more impaired than nonmaltreated participants with respect to self-harm (suicide attempts), internalizing symptomatology (anxiety and depression), eating disorder symptomatology, and well-being (lower overall self-worth). Effect sizes were medium. Comprising the first longitudinal evidence linking maltreatment with key young adult life impairments among a carefully diagnosed and followed sample of females with attention-deficit/hyperactivity disorder, these findings underscore the clinical importance of trauma experiences within this population. PMID:25723055

  20. An Improved Electro-Optical Image Quality Summary Measure.

    DTIC Science & Technology

    1981-10-01

    photo- graphing the display of a vidicon camera system viewing silhouettes of the broadside view of a Soviet KOTLIN class destroyer. Observers were...series ,: hard mages. Transparencies of the broadside KOTLIN silhouette were made with the scale :actor ranqin,, from 13b to 1810 meters per picture...3 warship rather than a merchant ship, and (c) the warsh-,;, is identifiable as beinq )f the nDTLIN class. Obviously, since only KOTLIN images were

  1. Condoning Aggressive Behaviour in Sport: A Cross-Sectional Research in a Few Consecutive Age Categories

    ERIC Educational Resources Information Center

    Fruchart, Eric; Rulence-Pâques, Patricia

    2016-01-01

    The aim of this study was to compare the way in which 216 young handball players ("Mage" = 12.79, SD = 2.20) of different ages (nine- to 10-years-old, 11- to 12-years-old, 13- to 14-years-old, and 15- to 16-years-old) combined and integrated five different information cues (the consequences of the aggression, the current score, the time…

  2. Rumination and Overgeneral Autobiographical Memory in Adolescents: An Integration of Cognitive Vulnerabilities to Depression

    PubMed Central

    Connolly, Samantha L.; Hamilton, Jessica L.; Stange, Jonathan P.; Abramson, Lyn Y.; Alloy, Lauren B.

    2014-01-01

    During adolescence, rates of depression dramatically increase and girls become twice as likely as boys to develop depression. Research suggests that overgeneral autobiographical memory and rumination are vulnerability factors for depressive symptoms in adolescence that may be triggered by stressful life events. The current longitudinal study included 160 early adolescents (Mage = 12.44 years, 60.0 % African American, 40.0 % Caucasian, and 56.2 % female). At baseline, adolescents completed measures of current depressive symptoms, rumination, and specificity of autobiographical memories. Approximately 9 months later, the adolescents completed measures of current depressive symptoms and stressful life events that had occurred between baseline and follow-up. Analyses indicated that girls with more overgeneral autobiographical memories in combination with higher levels of rumination were most vulnerable to experiencing increases in depressive symptoms following stressful life events. Additionally, retrieving more specific autobiographical memories appeared to buffer against the impact of negative life events on depressive symptoms among both boys and girls. Memory specificity may play a protective role in depression risk, suggesting that memory specificity training interventions may prove beneficial for adolescents. PMID:24449170

  3. The third wheel: the impact of Twitter use on relationship infidelity and divorce.

    PubMed

    Clayton, Russell B

    2014-07-01

    The purpose of this study was to examine how social networking site (SNS) use, specifically Twitter use, influences negative interpersonal relationship outcomes. This study specifically examined the mediational effect of Twitter-related conflict on the relationship between active Twitter use and negative relationship outcomes, and how this mechanism may be contingent on the length of the romantic relationship. A total of 581 Twitter users aged 18 to 67 years (Mage=29, SDage=8.9) completed an online survey questionnaire. Moderation-mediation regression analyses using bootstrapping methods indicated that Twitter-related conflict mediated the relationship between active Twitter use and negative relationship outcomes. The length of the romantic relationship, however, did not moderate the indirect effect on the relationship between active Twitter use and negative relationship outcomes. The results from this study suggest that active Twitter use leads to greater amounts of Twitter-related conflict among romantic partners, which in turn leads to infidelity, breakup, and divorce. This indirect effect is not contingent on the length of the romantic relationship. The current study adds to the growing body of literature investigating SNS use and romantic relationship outcomes.

  4. Enhanced Formation of Methylglyoxal-Derived Advanced Glycation End Products in Arabidopsis Under Ammonium Nutrition

    PubMed Central

    Borysiuk, Klaudia; Ostaszewska-Bugajska, Monika; Vaultier, Marie-Noëlle; Hasenfratz-Sauder, Marie-Paule; Szal, Bożena

    2018-01-01

    Nitrate (NO3–) and ammonium (NH4+) are prevalent nitrogen (N) sources for plants. Although NH4+ should be the preferred form of N from the energetic point of view, ammonium nutrition often exhibits adverse effects on plant physiological functions and induces an important growth-limiting stress referred as ammonium syndrome. The effective incorporation of NH4+ into amino acid structures requires high activity of the mitochondrial tricarboxylic acid cycle and the glycolytic pathway. An unavoidable consequence of glycolytic metabolism is the production of methylglyoxal (MG), which is very toxic and inhibits cell growth in all types of organisms. Here, we aimed to investigate MG metabolism in Arabidopsis thaliana plants grown on NH4+ as a sole N source. We found that changes in activities of glycolytic enzymes enhanced MG production and that markedly elevated MG levels superseded the detoxification capability of the glyoxalase pathway. Consequently, the excessive accumulation of MG was directly involved in the induction of dicarbonyl stress by introducing MG-derived advanced glycation end products (MAGEs) to proteins. The severe damage to proteins was not within the repair capacity of proteolytic enzymes. Collectively, our results suggest the impact of MG (mediated by MAGEs formation in proteins) in the contribution to NH4+ toxicity symptoms in Arabidopsis. PMID:29881392

  5. Assessment and Implications of Social Withdrawal Subtypes in Young Chinese Children: The Chinese Version of the Child Social Preference Scale.

    PubMed

    Li, Yan; Zhu, Jing-Jing; Coplan, Robert J; Gao, Zhu-Qing; Xu, Pin; Li, Linhui; Zhang, Huimin

    2016-01-01

    The authors' goals were to evaluate the psychometric properties of the Chinese version of the Child Social Preference Scale (CSPS; R. J. Coplan, K. Prakash, K. O'Neil, & M. Armer, 2004) and examine the links between both shyness and unsociability and indices of socioemotional functioning in young Chinese children. Participants included of two samples recruited from kindergarten classes in two public schools in Shanghai, China. Both samples included children 3-5 years old (Sample 1: n = 350, Mage = 4.72 years, SD = 0.58 years; Sample 2: n = 129, Mage = 4.40 years, SD = 0.58 years). In both samples, mothers rated children's social withdrawal using the newly created Chinese version of the CSPS, and in Sample 2, teachers also provided ratings of socioemotional functioning. Consistent with previous findings from other cultures, results from factor analyses suggested a 2-factor model for the CSPS (shyness and unsociability) among young children in China. In contrast to findings from North America, child shyness and unsociability were associated with socioemotional difficulties in kindergarten. Some gender differences were also noted. Results are discussed in terms of the assessment and implications of social withdrawal in early childhood in China.

  6. When Do Personality and Emotion Predict Destructive Behavior During Relationship Conflict? The Role of Perceived Commitment Asymmetry.

    PubMed

    Lemay, Edward P; Dobush, Sarah

    2015-10-01

    The current research examined whether perceived asymmetries in relationship commitment moderate the associations of personality traits and emotional states with enactment of hostile behavior during relationship conflicts. Participants included both members of 53 heterosexual romantic couples (Mage  = 25.5 years). Participants completed questionnaire measures assessing personality traits, emotional states, relationship commitment, and perceptions of their partner's commitment. Participants then had an observed conflict discussion with their partner, which was rated by a panel of objective observers for hostile behavior. When participants perceived that they were less committed than their partners, their enactment of hostile behavior was predicted by traits and states that are associated with antisocial and pro-social orientations (i.e., agreeableness, trait anger, chronic jealousy, and state negative emotion). In contrast, participants who perceived that they were more committed than their partners tended to refrain from hostile behavior, despite traits or states that may suggest hostile inclinations. These results suggest that perceiving that one is less committed than one's partner promotes behavioral expression of interpersonal dispositions and emotions, whereas perceiving that one is more committed than one's partner motivates inhibition of hostile behavior. © 2014 Wiley Periodicals, Inc.

  7. Translations on Environmental Quality, Number 154.

    DTIC Science & Technology

    1977-11-29

    While some of the padi land is feared to have been permanently da- maged, tests indicate that some other parts could be cultivated again, if the...and Ecotoxicology at the offices of CETESB. According to F. Korte, who spoke on "Routes Followed by Chemical Substances in the Environment...professor began his presentation yesterday by establishing the param- eters for pollutants and then discussed the ecotoxicological effects on the

  8. A team fares well with a fair coach: Predictors of social loafing in interactive female sport teams.

    PubMed

    De Backer, M; Boen, F; De Cuyper, B; Høigaard, R; Vande Broek, G

    2015-12-01

    The present research aimed to develop and test a theoretical model that links players' perceived justice of the coach to a more optimal motivational climate, which in turn increases players' team identification and cohesion, and results in lower levels of social loafing in female sport teams. Belgian elite female basketball, volleyball, and football players (study 1; N = 259; M(age)  = 22.6) and Norwegian world-class female handball players (study 2; N = 110; M(age)  = 22.8) completed questionnaires assessing players' perceived justice (distributive and procedural), motivational climate, team identification, team cohesion (task and social), and social loafing (perceived and self-reported). In both studies, confirmatory and exploratory path analyses indicated that perceived justice was positively related to a mastery climate (P < 0.05) and negatively to a performance climate (P < 0.05). In turn, a mastery climate was linked to increased levels of team identification (P < 0.05) and task cohesion (P < 0.05). Consequently, players' perceived and self-reported social loafing decreased (P < 0.05). The findings of both independent studies demonstrated the impact of coaches' fairness, and consequently, the motivational climate created by the coach on the optimal functioning of female sport teams. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Investigation of a Putative Estrogen-Imprinting Gene, Phosphodiesterase Type IV Variant (Pde4d4), in Determining Prostate Cancer Risk

    DTIC Science & Technology

    2008-04-01

    margins ” of one’s genetic make-up. Keywords DNAmethylation . Histone modification . Chromatin remodeling . Nongenomic heritage . Developmental plasticity...palliative care to personalized preventive medicine which could be based, in part, on the epigenetic marks engraved along the “book- margins ” of one’s...investigations. Other demands for successful utilization of RLGS are he requirements for a fairly elaborate gel electrophoresis set-up and a powerful mage

  10. Measuring Psychobiosocial States in Sport: Initial Validation of a Trait Measure

    PubMed Central

    Bertollo, Maurizio; Ruiz, Montse C.; Bortoli, Laura

    2016-01-01

    We examined the item characteristics, the factor structure, and the concurrent validity of a trait measure of psychobiosocial states. In Study 1, Italian athletes (N = 342, 228 men, 114 women, Mage = 23.93, SD = 6.64) rated the intensity, the frequency, and the perceived impact dimensions of a psychobiosocial states scale, trait version (PBS-ST), which is composed of 20 items (10 functional and 10 dysfunctional) referring to how they usually felt before an important competition. In Study 2, the scale was cross validated in an independent sample (N = 251, 181 men, 70 women, Mage = 24.35, SD = 7.25). The concurrent validity of the PBS-ST scale scores were also examined in comparison with two sport-specific emotion-related measures and a general measure of affect. Exploratory structural equation modeling and confirmatory factor analysis of the data of Study 1 showed that a 2-factor, 15-item solution of the PBS-ST scale (8 functional items and 7 dysfunctional items) reached satisfactory fit indices for the three dimensions (i.e., intensity, frequency, and perceived impact). Results of Study 2 provided evidence of substantial measurement and structural invariance of all dimensions across samples. The low association of the PBS-ST scale with other measures suggests that the scale taps unique constructs. Findings of the two studies offer initial validity evidence for a sport-specific tool to measure psychobiosocial states. PMID:27907111

  11. Pain and emotion as predictive factors of interoception in fibromyalgia

    PubMed Central

    Borg, Céline; Chouchou, Florian; Dayot-Gorlero, Jenny; Zimmerman, Perrine; Maudoux, Delphine; Laurent, Bernard; Michael, George A

    2018-01-01

    Introduction This study investigated interoception in fibromyalgia (FM), a disorder characterized by chronic pain accompanied by mood deregulation. Based on observations on the relationship between somatosensory processing and pain in FM and considering the affective symptoms of this disorder, we tested in FM three dimensions of interoception: interoceptive accuracy (IA), interoceptive awareness (IAW) and interoceptive sensibility (IS). Materials and methods Twenty-one female FM patients (Mage = 50.3) and 21 female matched controls (Mage = 46.3) completed a heartbeat tracking task as an assessment of IA, rated confidence in their responses as a measure of IAW and completed the Multidimensional Assessment of Interoceptive Awareness as a measure of IS. Furthermore, they completed self-report scales that, according to a principal component analysis, targeted anxiety, emotional consciousness and pain-related affect and reactions. Results Multiple regression analyses showed that increased pain-related affect and reactions decrease IA in FM. When the results of each group were examined separately, such effect was found only in FM patients. On its turn, IS was predicted by emotional consciousness and pain-related affect and reactions, but these effects did not differ between FM and controls. Finally, none of the variables we used predicted IAW. Discussion Pain-related affect and reactions in FM patients can reduce their interoceptive ability. Our results help to better understand the integration between bodily signals and emotional processing in chronic pain. PMID:29719416

  12. First-hand sensory experience plays a limited role in children's early understanding of seeing and hearing as sources of knowledge: evidence from typically hearing and deaf children.

    PubMed

    Schmidt, Ellyn; Pyers, Jennie

    2014-11-01

    One early-developing component of theory of mind is an understanding of the link between sensory perception and knowledge formation. We know little about the extent to which children's first-hand sensory experiences drive the development of this understanding, as most tasks capturing this early understanding target vision, with less attention paid to the other senses. In this study, 64 typically hearing children (Mage  = 4.0 years) and 21 orally educated deaf children (Mage  = 5.44 years) were asked to identify which of two informants knew the identity of a toy animal when each had differing perceptual access to the animal. In the 'seeing' condition, one informant saw the animal and the other did not; in the 'hearing' condition, one informant heard the animal and the other did not. For both hearing and deaf children, there was no difference between performance on hearing and seeing trials, but deaf children were delayed in both conditions. Further, within both the hearing and deaf groups, older children outperformed younger children on these tasks, indicating that there is a developmental progression. Taken together, the pattern of results suggests that experiences other than first-hand sensory experiences drive children's developing understanding that sensory perception is associated with knowledge. © 2014 The British Psychological Society.

  13. Confirmatory evidence for a multidimensional model of racial-ethnic socialization for transracially adoptive families.

    PubMed

    Langrehr, Kimberly J; Thomas, Anita Jones; Morgan, Sydney K

    2016-07-01

    The purpose of the current study is to test a recently established model of racial-ethnic socialization (Langrehr, 2014) among 2 samples of White transracially adoptive parents and to assess whether the proposed model functions similarly after accounting for adopted child race. Based on a modified version of the Racial Bias Preparation Scale (Fisher, Wallace, & Fenton, 2000), confirmatory factor analysis was used to test the 3-factor model (i.e., Prejudice Awareness, Racial-Ethnic Pride, and Egalitarianism) among 172 White transracially adoptive parents with Asian children (Mage = 45.72) and 140 White transracially adoptive parents with Black children (Mage = 42.62). In addition, multigroup invariance testing was used to assess whether the proposed model functioned similarly across the 2 groups of parents. Results indicate that the proposed 3-factor model demonstrated partial measurement invariance such that the subconstruct of Egalitarianism functioned similarly across groups, whereas Racial-Ethnic Pride and Prejudice Awareness were deemed noninvariant. Findings are intended to help expand the concept of racial-ethnic socialization for transracially adoptive families and address the degree to which current research on racial-ethnic socialization can be applied to different transracially adoptive families. Results are intended to highlight ways that various social-cultural dimensions of family can culminate into different socialization experiences. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  14. Basic Psychological Need Satisfaction, Emotion Dysregulation, and Non-suicidal Self-Injury Engagement in Young Adults: An Application of Self-Determination Theory.

    PubMed

    Emery, A Ann; Heath, Nancy L; Mills, Devin J

    2016-03-01

    Non-suicidal self-injury (NSSI) is a public health concern that affects young adults at alarming rates. The present study examines the role of satisfaction of self-determination theory's three basic needs for autonomy, competence, and relatedness in young adults' NSSI engagement. University students who reported ever having engaged in NSSI (n = 40, 85 % female; Mage = 20.10, SD = 1.66) reported significantly lower levels of the satisfaction of all three needs, as well as more difficulties with all aspects of emotion regulation (non-acceptance of emotional responses, difficulty engaging in goal directed behavior, impulse control, lack of emotional awareness, limited access to regulation strategies, lack of emotional clarity), compared to students with no history of NSSI (n = 46, 91 % female; Mage = 19.79, SD = 1.37). Results of a logistic regression analysis revealed that need satisfaction added to the prediction of NSSI group membership after controlling for the effects of emotion regulation. Satisfaction of the need for competence and limited access to emotion regulation strategies accounted for significant variance in NSSI in the final model. The findings suggest that self-determination theory may be a useful framework under which to conceptualize NSSI and that the need for competence may be particularly salient for University students.

  15. Sensory Information Processing and Symbolic Computation

    DTIC Science & Technology

    1975-06-01

    filter so that noise is not ft See Appendix B for a discussion of constraints on the Impulse response length imposed by this technique. This approach...from Report) Same IB. SUPPLEMENTARY NOTES 19. KEY WORDS fUont/nu. on «v.r.. ./</. // noe...«y «nd (d.n«/fy by Wo.* numbar) image deblurring ...mage deblurring that extend results report^ in the last semi-annual report (1 July.74 - 31 Dec ^.Technical reports covering this work are planned

  16. Cells, Biomarkers, and Posttraumatic Stress Disorder: Evidence for Peripheral Involvement in a Central Disease

    DTIC Science & Technology

    2012-01-01

    including; Alzheimer’s disease (Mac- cioni et al. 2009), Parkinson’s disease (Hirsch and Hunot 2009), spinal cord injury (Chan 2008), multiple sclerosis ...states such as multiple sclerosis (Kraus et al. 2000), human immunodeficiency virus dementia (Fischer- Smith et al. 2001), and meningitis (Cauwels et al...Immunologic mechanisms of multiple sclerosis . Neuroi- maging Clin. N. Am. 18, 577–588. Gaylord K. M. (2006) The psychosocial effects of combat: the frequently

  17. Delinquent and Aggressive Behavior and Social Desirability Among Roma and Non-Roma Adolescents in Slovakia: A Cross-Sectional Study.

    PubMed

    Kolarcik, Peter; Madarasova Geckova, Andrea; Reijneveld, Sijmen A; van Dijk, Jitse P

    2016-02-01

    Rates of aggression and delinquency are assumed to be higher among Roma and other minorities, but sound evidence of this is lacking. Our aim was to assess delinquent and aggressive behavior among Roma and non-Roma adolescents and the effects on ethnic differences of parental education and social desirability. We conducted a cross-sectional study among Roma from separated and segregated settlements in the eastern part of Slovakia (N = 330; Mage = 14.50; interview) and non-Roma adolescents (N = 722; Mage = 14.86; questionnaire). The effect of ethnicity on antisocial behaviors was analyzed using linear regression (crude) and adjusted for gender, parental education, and social desirability. Adjustment for social desirability diminished the ethnic differences in delinquency (B = 1.08; 95% confidence interval [CI] = [2.12, -0.04]), led to an increase in the differences in hostility (B = 2.43; 95% CI = [0.87, 3.99]), and led to the disappearance of differences in physical aggression (B = 0.45; 95% CI = [1.14, 2.07]). Parental education did not affect the associations in an important way. Our findings indicate that Roma are not that much different from non-Roma, in terms of antisocial behavior, which contradicts the general perception of Roma. Our findings should be confirmed in other settings. © The Author(s) 2014.

  18. Longitudinal effects of sibling relationship quality on adolescent problem behavior: a cross-ethnic comparison.

    PubMed

    Buist, Kirsten L; Paalman, Carmen H; Branje, Susan J T; Deković, Maja; Reitz, Ellen; Verhoeven, Marjolein; Meeus, Wim H J; Koot, Hans M; Hale, William W

    2014-04-01

    The aim of the present study was to examine whether adolescents of Moroccan and Dutch origin differ concerning sibling relationship quality and to examine whether the associations between quality of the sibling relationship and level and change in externalizing and internalizing problem behavior are comparable for Moroccan and Dutch adolescents. Five annual waves of questionnaire data on sibling support and conflict as well as externalizing problems, anxiety and depression were collected from 159 ethnic Moroccan adolescents (Mage = 13.3 years) and from 159 ethnic Dutch adolescents (Mage = 13.0 years). Our findings demonstrated significant mean level differences between the Moroccan and Dutch sample in sibling relationship quality, externalizing problems, and depression, with Moroccan adolescents reporting higher sibling relationship quality and less problem behavior. However, effects of sibling relationship quality on externalizing problems, anxiety, and depression were similar for the Moroccan and Dutch samples. Sibling support was not related to level of externalizing problems, nor to changes in externalizing problems, anxiety, and depression. Additionally, more sibling conflict was related to a higher starting level of and faster decreases in problem behaviors. Our results support the ethnic equivalence model, which holds that the influence of family relationships is similar for different ethnic groups. Moreover, sibling support and conflict affect both the level and the fluctuations in problem behavior over time in specific ethnic groups similarly. Implications for future studies and interventions are subsequently discussed.

  19. Pathways to Self-Esteem in Late Adolescence: The Role of Parent and Peer Attachment, Empathy, and Social Behaviours

    ERIC Educational Resources Information Center

    Laible, Deborah J.; Carlo, Gustavo; Roesch, Scott C.

    2004-01-01

    The goal of this study was to examine both the direct and indirect relations of parent and peer attachment with self-esteem and to examine the potential mediating roles of empathy and social behaviour. 246 college students ("Mage" = 18.6 years, s.d. = 1.61) completed self-report measures of parent and peer attachment, empathy, social behaviour,…

  20. Bullying Predicts Reported Dating Violence and Observed Qualities in Adolescent Dating Relationships.

    PubMed

    Ellis, Wendy E; Wolfe, David A

    2015-10-01

    The relationship between reported bullying, reported dating violence, and dating relationship quality measured through couple observations was examined. Given past research demonstrating similarity between peer and dating contexts, we expected that bullying would predict negative dating experiences. Participants with dating experience (n = 585; 238 males, M(age) = 15.06) completed self-report assessments of bullying and dating violence perpetration and victimization. One month later, 44 opposite-sex dyads (M(age) = 15.19) participated in behavioral observations. In 10-min sessions, couples were asked to rank and discuss areas of relationship conflict while being video-recorded. Qualities of the relationship were later coded by trained observers. Regression analysis revealed that bullying positively predicted dating violence perpetration and victimization. Self-reported bullying also predicted observations of lower relationship support and higher withdrawal. Age and gender interactions further qualified these findings. The bullying of boys, but not girls, was significantly related to dating violence perpetration. Age interactions showed that bullying was positively predictive of dating violence perpetration and victimization for older, but not younger adolescents. Positive affect was also negatively predicted by bullying, but only for girls. These findings add to the growing body of evidence that adolescents carry forward strategies learned in the peer context to their dating relationships. © The Author(s) 2014.

  1. Emotional contrast or compensation? How support reminders influence the pain of acute peer disapproval in preadolescents.

    PubMed

    Thomaes, Sander; Sedikides, Constantine; Reijntjes, Albert; Brummelman, Eddie; Bushman, Brad J

    2015-10-01

    When children experience habitual peer difficulties, adults often remind them that many people care about them. How do such reminders of support impact children's emotional responses to acute experiences of peer disapproval? Intuitively, support reminders would exert compensatory effects attenuating the emotional impact of acute disapproval. Theory suggests, however, that support reminders might also lead to contrast effects magnifying the emotional impact of acute disapproval, especially among socially vulnerable children. These opposing perspectives were pitted against each other. In 2 experiments, children (aged 9-13, M(age) = 11.5) were randomly assigned to reflect on their relationships with either supportive others (support condition) or mere acquaintances (control condition). Children experienced acute peer disapproval immediately after (Experiment 1) or before (Experiment 2) the manipulated support reminder. Among children who experienced higher levels of peer difficulties in their daily life, the support reminder increased externalized emotional reactivity and decreased internalized emotional recovery following disapproval. Thus, consistent with emotional contrast theory, support reminders magnified the disapproval-based emotional responses of socially vulnerable children. (c) 2015 APA, all rights reserved).

  2. Uni-Morbid and Co-Occurring Marijuana and Tobacco Use: Examination of Concurrent Associations with Negative Mood States

    PubMed Central

    Bonn-Miller, Marcel O.; Zvolensky, Michael J.; Johnson, Kirsten A.

    2010-01-01

    The aim of the current investigation was to examine uni-morbid and co-occurring tobacco and marijuana use in relation to the negative emotional symptoms of anxiety and depression. Participants were 250 adult individuals (132 female; mage = 22.43, SD = 9.00), falling into one of four non-overlapping substance use categories: tobacco use only (n = 39), marijuana use only (n = 62), co-occurring tobacco and marijuana use (n = 82), and neither tobacco nor marijuana use (n = 67). Results revealed three key findings. First, tobacco-only using individuals reported significantly greater negative affectivity than any of the other groups. Second, tobacco-only users reported greater anxious arousal symptoms than either the marijuana or non-substance-using groups, but not the combined group. Third, tobacco-only users reported greater levels of depressive symptoms than either marijuana users or non-substance-users. These findings provide novel information about tobacco and marijuana use, and how these variables relate to the experience of general and specific types of negative emotional symptoms. PMID:20390700

  3. A weight-gain-for-gestational-age z score chart for the assessment of maternal weight gain in pregnancy.

    PubMed

    Hutcheon, Jennifer A; Platt, Robert W; Abrams, Barbara; Himes, Katherine P; Simhan, Hyagriv N; Bodnar, Lisa M

    2013-05-01

    To establish the unbiased relation between maternal weight gain in pregnancy and perinatal health, a classification for maternal weight gain is needed that is uncorrelated with gestational age. The goal of this study was to create a weight-gain-for-gestational-age percentile and z score chart to describe the mean, SD, and selected percentiles of maternal weight gain throughout pregnancy in a contemporary cohort of US women. The study population was drawn from normal-weight women with uncomplicated, singleton pregnancies who delivered at the Magee-Womens Hospital in Pittsburgh, PA, 1998-2008. Analyses were based on a randomly selected subset of 648 women for whom serial prenatal weight measurements were available through medical chart record abstraction (6727 weight measurements). The pattern of maternal weight gain throughout gestation was estimated by using a random-effects regression model. The estimates were used to create a chart with the smoothed means, percentiles, and SDs of gestational weight gain for each week of pregnancy. This chart allows researchers to express total weight gain as an age-standardized z score, which can be used in epidemiologic analyses to study the association between pregnancy weight gain and adverse or physiologic pregnancy outcomes independent of gestational age.

  4. The Wave of the Present - Remotely-Piloted Aircraft in Air Force Culture

    DTIC Science & Technology

    2010-06-01

    There is an ever-present danger that doctrine will be allowed to harden into dogma when military men fail to appreciate the implications of a...2 John G. Magee , from well known military aviation poem "High Flight,‖ written on September 3, 1941. 3 David E. Johnson, Fast Tanks and Heavy...change. In 1919, the Army‘s air arm contained a near equal number of lighter-than-air and heavier-than-air craft. 14 The subculture of men created

  5. Tensions Between Science and Intuition Across the Lifespan.

    PubMed

    Shtulman, Andrew; Harrington, Kelsey

    2016-01-01

    The scientific knowledge needed to engage with policy issues like climate change, vaccination, and stem cell research often conflicts with our intuitive theories of the world. How resilient are our intuitive theories in the face of contradictory scientific knowledge? Here, we present evidence that intuitive theories in 10 domains of knowledge-astronomy, evolution, fractions, genetics, germs, matter, mechanics, physiology, thermodynamics, and waves-persist more than four decades beyond the acquisition of a mutually exclusive scientific theory. Participants (104 younger adults, Mage  = 19.6, and 48 older adults, Mage  = 65.1) were asked to verify two types of scientific statements as quickly as possible: those that are consistent with intuition (e.g., "the moon revolves around the Earth") and those that involve the same conceptual relations but are inconsistent with intuition (e.g., "the Earth revolves around the sun"). Older adults were as accurate as younger adults at verifying both types of statements, but the lag in response times between intuition-consistent and intuition-inconsistent statements was significantly larger for older adults than for younger adults. This lag persisted even among professional scientists. Overall, these results suggest that the scientific literacy needed to engage with topics of global importance may be constrained by patterns of reasoning that emerge in childhood but persist long thereafter. Copyright © 2015 Cognitive Science Society, Inc.

  6. Enriching the hierarchical model of achievement motivation: autonomous and controlling reasons underlying achievement goals.

    PubMed

    Michou, Aikaterini; Vansteenkiste, Maarten; Mouratidis, Athanasios; Lens, Willy

    2014-12-01

    The hierarchical model of achievement motivation presumes that achievement goals channel the achievement motives of need for achievement and fear of failure towards motivational outcomes. Yet, less is known whether autonomous and controlling reasons underlying the pursuit of achievement goals can serve as additional pathways between achievement motives and outcomes. We tested whether mastery approach, performance approach, and performance avoidance goals and their underlying autonomous and controlling reasons would jointly explain the relation between achievement motives (i.e., fear of failure and need for achievement) and learning strategies (Study 1). Additionally, we examined whether the autonomous and controlling reasons underlying learners' dominant achievement goal would account for the link between achievement motives and the educational outcomes of learning strategies and cheating (Study 2). Six hundred and six Greek adolescent students (Mage = 15.05, SD = 1.43) and 435 university students (Mage M = 20.51, SD = 2.80) participated in studies 1 and 2, respectively. In both studies, a correlational design was used and the hypotheses were tested via path modelling. Autonomous and controlling reasons underlying the pursuit of achievement goals mediated, respectively, the relation of need for achievement and fear of failure to aspects of learning outcomes. Autonomous and controlling reasons underlying achievement goals could further explain learners' functioning in achievement settings. © 2014 The British Psychological Society.

  7. Associations Among Individuals' Perceptions of Future Time, Individual Resources, and Subjective Well-Being in Old Age.

    PubMed

    Hoppmann, Christiane A; Infurna, Frank J; Ram, Nilam; Gerstorf, Denis

    2017-05-01

    Perceptions of future time are of key interest to aging research because of their implications for subjective well-being. Interestingly, perceptions about future time are only moderately associated with age when looking at the second half of life, pointing to a vast heterogeneity in future time perceptions among older adults. We examine associations between future time perceptions, age, and subjective well-being across two studies, including moderations by individual resources. Using data from the Berlin Aging Study (N = 516; Mage = 85 years), we link one operationalization (subjective nearness to death) and age to subjective well-being. Using Health and Retirement Study data (N = 2,596; Mage = 77 years), we examine associations of another future time perception indicator (subjective future life expectancy) and age with subjective well-being. Consistent across studies, perceptions of limited time left were associated with poorer subjective well-being (lower life satisfaction and positive affect; more negative affect and depressive symptoms). Importantly, individual resources moderated future time perception-subjective well-being associations with those of better health exhibiting reduced future time perception-subjective well-being associations. We discuss our findings in the context of the Model of Strength and Vulnerability Integration. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Perceived Discrimination and Diurnal Cortisol: Examining Relations among Mexican American Adolescents

    PubMed Central

    Zeiders, Katharine H.; Doane, Leah D.; Roosa, Mark W.

    2012-01-01

    Perceived discrimination remains a salient and significant environmental stressor for ethnic and racial minority youth. Although many studies have examined the impact of racial/ethnic discrimination on mental health symptomatology and physical health, little is known of the potential physiological processes underlying such experiences, especially during adolescence. In an attempt to understand how varying perceptions of discrimination relate to functioning of the hypothalamic-pituitary-adrenal axis (HPA axis), the current study examined the relation between Mexican American adolescents’ (N= 100, Mage = 15.3 years old) perceptions of discrimination and aspects of their diurnal cortisol profiles. Three salivary samples (wakeup, +30 waking, bedtime) were collected across three days (total of 9 samples). Utilizing multi-level modeling, results revealed that adolescents’ perceived discrimination related to greater overall cortisol output (area under the curve; AUC) after controlling for other life stressors, depressive symptoms, family income, acculturation level, daily stress levels and daily behaviors. Findings also revealed that perceived discrimination was marginally related to a steeper cortisol awakening response (CAR). Together, these findings suggest that perceived discrimination is a salient and impactful stressor for Mexican American adolescents. Understanding the physiological correlates of discrimination can provide insight into larger health disparities among ethnic and racial minority individuals. PMID:22342577

  9. A monoclonal cytolytic T-lymphocyte response observed in a melanoma patient vaccinated with a tumor-specific antigenic peptide encoded by gene MAGE-3

    PubMed Central

    Coulie, Pierre G.; Karanikas, Vaios; Colau, Didier; Lurquin, Christophe; Landry, Claire; Marchand, Marie; Dorval, Thierry; Brichard, Vincent; Boon, Thierry

    2001-01-01

    Vaccination of melanoma patients with tumor-specific antigens recognized by cytolytic T lymphocytes (CTL) produces significant tumor regressions in a minority of patients. These regressions appear to occur in the absence of massive CTL responses. To detect low-level responses, we resorted to antigenic stimulation of blood lymphocyte cultures in limiting dilution conditions, followed by tetramer analysis, cloning of the tetramer-positive cells, and T-cell receptor (TCR) sequence analysis of the CTL clones that showed strict specificity for the tumor antigen. A monoclonal CTL response against a MAGE-3 antigen was observed in a melanoma patient, who showed partial rejection of a large metastasis after treatment with a vaccine containing only the tumor-specific antigenic peptide. Tetramer analysis after in vitro restimulation indicated that about 1/40,000 postimmunization CD8+ blood lymphocytes were directed against the antigen. The same TCR was present in all of the positive microcultures. TCR evaluation carried out directly on blood lymphocytes by PCR amplification led to a similar frequency estimate after immunization, whereas the TCR was not found among 2.5 × 106 CD8+ lymphocytes collected before immunization. Our results prove unambiguously that vaccines containing only a tumor-specific antigenic peptide can elicit a CTL response. Even though they provide no information about the effector mechanisms responsible for the observed reduction in tumor mass in this patient, they would suggest that low-level CTL responses can initiate tumor rejection. PMID:11517302

  10. Symptoms of fatigue and coping strategies in maritime pilotage.

    PubMed

    Chambers, Timothy P; Main, Luana C

    2015-01-01

    Little is known regarding the symptoms of fatigue that maritime pilots experience during shift work. Moreover, the strategies these individuals use to cope with the onset of fatigue are also unknown. The current study explored the symptoms of fatigue and coping strategies experienced by maritime pilots when on-shift. Fifty maritime pilots were recruited via an advertisement in the national association's quarterly newsletter (Mage = 51.42; SD = 9.81). Participants responded to a modified version of the questionnaire used with aviation pilots that assessed overall fatigue, and the symptoms pilots associated with fatigue on duty. Methods pilots used to cope with fatigue before shift and when on the bridge were also assessed. There were significant effects for pilot vitality on 4 categories of fatigue: cognitive dysfunction; emotional disturbance; mean physical effects; and sleepiness. There were no significant effects for vitality on any of the self-reported coping strategy factors. The findings indicated that maritime pilots experience a variety of physical, behavioural, and cognitive fatigue symptoms when on shift. Some of these symptoms are similar to those reported by aviation pilots. However, unlike aviation pilots, maritime pilots reported utilising self-sufficient coping strategies to deal with the experience of fatigue.

  11. Comparison of Measures of E-cigarette Advertising Exposure and Receptivity

    PubMed Central

    Pokhrel, Pallav; Fagan, Pebbles; Herzog, Thaddeus A.; Schmid, Simone; Kawamoto, Crissy T.; Unger, Jennifer B.

    2018-01-01

    Objectives We tested how various measures of e-cigarette advertising exposure and receptivity are related to each other and compare to each other in their associations with e-cigarette use susceptibility and behavior. Methods Cross-sectional data were collected from young adult college students (N = 470; Mage = 20.9, SD = 2.1; 65% women). Measures of e-cigarette advertising exposure/receptivity compared included a cued recall measure, measures of marketing receptivity, perceived ad exposure, liking of e-cigarette ads, and frequency of convenience store visit, which is considered a measure of point-of-sale ad exposure. Results The cued-recall measure was associated with e-cigarette use experimentation but not current e-cigarette use. Marketing receptivity was associated with current e-cigarette use but not e-cigarette use experimentation. Liking of e-cigarette ads was the only measure associated with e-cigarette use susceptibility. Frequency of convenience store visit was associated with current e-cigarette use but not e-cigarette use experimentation or susceptibility. Conclusion Inclusion of multiple measures of marketing exposure and receptivity is recommended for regulatory research concerning e-cigarette marketing. Marketing receptivity and cued recall measures are strong correlates of current and ever e-cigarette use, respectively. PMID:29516028

  12. Authoritarian parenting predicts reduced electrocortical response to observed adolescent offspring rewards.

    PubMed

    Levinson, Amanda R; Speed, Brittany C; Nelson, Brady; Bress, Jennifer N; Hajcak, Greg

    2017-03-01

    Parenting styles are robust predictors of offspring outcomes, yet little is known about their neural underpinnings. In this study, 44 parent-adolescent dyads (Mage of adolescent = 12.9) completed a laboratory guessing task while EEG was continuously recorded. In the task, each pair member received feedback about their own monetary wins and losses and also observed the monetary wins and losses of the other member of the pair. We examined the association between self-reported parenting style and parents' electrophysiological responses to watching their adolescent winning and losing money, dubbed the observational Reward Positivity (RewP) and observational feedback negativity (FN), respectively. Self-reported authoritarian parenting predicted reductions in parents' observational RewP but not FN. This predictive relationship remained after adjusting for sex of both participants, parents' responsiveness to their own wins, and parental psychopathology. 'Exploratory analyses found that permissive parenting was associated with a blunting of the adolescents' response to their parents' losses'. These findings suggest that parents' rapid neural responses to their child's successes may relate to the harsh parenting behaviors associated with authoritarian parenting. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  13. Effect of combined application insulin and insulin detemir on continous glucose monitor in children with type 1 diabetes mellitus.

    PubMed

    Chen, Xiao-Yun; Dong, Qing; Li, Gui-Mei

    2015-01-01

    Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action, which could strengthen the effects of insulin. This study aims to explore the effects of insulin combined with insulin detemir on the continous glucose in children with type 1 diabetes mellitus. In this study, 150 patients with type 1 diabetes enrolled were included and randomly divided into 3 groups: insulin group (group A), insulin detemir group (group B) and insulin combined with insulin detemir group (group C). Each subject underwent 72 h of continuous glucose monitoring (CGM). MAGE, HbA1c and Noctumal Hypoglycemia levels were examined by using the ELISA kits. The body weight changes were also detected in this study. The results indicated that the information including age, body weight, disease duration and glucose level and HbA1c percentage on the start time point among three groups indicated no statistical differences. Insulin combined with insulin detemir decrease MAGE and HbA1c level in Group C compared to Group A and Group A (P < 0.05). Insulin combined with insulin detemir decreas noctumal hypoglycemia levels and body weight changes (P < 0.05). In conclusion, this study confirmed efficacy of insulin detemir by demonstrating non-inferiority of insulin detemir compared with insulin with respect to HbA1c, with an improved safety profile including significantly fewer hypoglycaemic episodes and less undesirable weight gain in children.

  14. High-Energy Laser for Detection, Inspection, and Non-Destructive Testing

    DTIC Science & Technology

    2011-03-21

    at the gra odes. The -2 at 0.1 Hz -cm-2, and mage thre n array of beam. Th burns on pled to a to measur laser is eq micron lev ent beam ( rget...project or resulting research?  Defense Threat Reduction Agency, “Compact Source of Laser -Driven Monoenergetic Gamma-Rays” --$2,982,685... LASER FOR DETECTION, INSPECTION, AND NON-DESTRUCTIVE TESTING 3) Grant/Contract Number: FA9550-07-1-0521 4) Reporting Period Start: 06/21/2007

  15. AFRRI (Armed Forces Radiobiology Research Institute) Reports, July, August, September 1989.

    DTIC Science & Technology

    1989-11-01

    ippticatnpusit Maged. ineintr -det ic tent rat’ J tier oit l 3 3, Bank ,. W J. Hisiiilig% and citinparati.e tirganilig% A te’. atlas 31-12. 11)𔄁...concentrations of Leu-Leu-OMe (Tbl 1). Mini- he euthanized on day 19 posttransplant due to an accidental, mal CFt ,-(NI growth was observed with 10’ Leu-leu...phospholipid which provides the arachidlonic acid required for syn- veilswtth rgana m baeealsteacvtdga- thesis of prostaglandins and other eicosanoids (1-5

  16. NF-kB2/p52 Activation and Androgen Receptor Signaling in Prostate Cancer

    DTIC Science & Technology

    2010-08-01

    for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202- 4302. Respondents should be aware...Materials and Methods; ref. 38). Statistical analysis. Data are shown as the mean ± SD. Multiple group comparison was performed by one-way ANO- VA followed... Moroz , Byron Crawford, Asim Abdel-Mageed, New Orleans, LA INTRODUCTION AND OBJECTIVES: African American men (AA) have twice the incidence and mortality

  17. Effects of tissue factor, PAR-2 and MMP-9 expression on human breast cancer cell line MCF-7 invasion.

    PubMed

    Lin, Zeng-Mao; Zhao, Jian-Xin; Duan, Xue-Ning; Zhang, Lan-Bo; Ye, Jing-Ming; Xu, Ling; Liu, Yin-Hua

    2014-01-01

    This study aimed to explore the expression of tissue factor (TF), protease activated receptor-2 (PAR-2), and matrix metalloproteinase-9 (MMP-9) in the MCF-7 breast cancer cell line and influence on invasiveness. Stable MCF-7 cells transfected with TF cDNA and with TF ShRNA were established. TF, PAR-2, and MMP-9 protein expression was analyzed using indirect immunofluorescence and invasiveness was evaluated using a cell invasion test. Effects of an exogenous PAR-2 agonist were also examined. TF protein expression significantly differed between the TF cDNA and TF ShRNA groups. MMP-9 protein expression was significantly correlated with TF protein expression, but PAR-2 protein expression was unaffected. The PAR- 2 agonist significantly enhanced MMP-9 expression and slightly increased TF and PAR-2 expression in the TF ShRNA group, but did not significantly affect protein expression in MCF-7 cells transfected with TF cDNA. TF and MMP-9 expression was positively correlated with the invasiveness of tumor cells. TF, PAR-2, and MMP-9 affect invasiveness of MCF-7 cells. TF may increase MMP-9 expression by activating PAR-2.

  18. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Smentkowski, Vincent S., E-mail: smentkow@ge.com

    Changes in the oxidation state of an element can result in significant changes in the ionization efficiency and hence signal intensity during secondary ion mass spectrometry (SIMS) analysis; this is referred to as the SIMS matrix effect [Secondary Ion Mass Spectrometry: A Practical Handbook for Depth Profiling and Bulk Impurity Analysis, edited by R. G. Wilson, F. A. Stevie, and C. W. Magee (Wiley, New York, 1990)]. The SIMS matrix effect complicates quantitative analysis. Quantification of SIMS data requires the determination of relative sensitivity factors (RSFs), which can be used to convert the as measured intensity into concentration units [Secondarymore » Ion Mass Spectrometry: A Practical Handbook for Depth Profiling and Bulk Impurity Analysis, edited by R. G. Wilson, F. A. Stevie, and C. W. Magee (Wiley, New York, 1990)]. In this manuscript, the authors report both: RSFs which were determined for quantification of B in Si and SiO{sub 2} matrices using a dual beam time of flight secondary ion mass spectrometry (ToF-SIMS) instrument and the protocol they are using to provide quantitative ToF-SIMS images and line scan traces. The authors also compare RSF values that were determined using oxygen and Ar ion beams for erosion, discuss the problems that can be encountered when bulk calibration samples are used to determine RSFs, and remind the reader that errors in molecular details of the matrix (density, volume, etc.) that are used to convert from atoms/cm{sup 3} to other concentration units will propagate into errors in the determined concentrations.« less

  19. Promoting theory of mind in older adults: does age play a role?

    PubMed

    Rosi, Alessia; Cavallini, Elena; Bottiroli, Sara; Bianco, Federica; Lecce, Serena

    2016-01-01

    Previous research on age-related changes in Theory of Mind (ToM) showed a decline in older adults, particularly pronounced over 75 years of age. Evidence that ToM may be enhanced in healthy aging people has been demonstrated, but no study has focused on the role of age on the effects of ToM training for elderly people. The present study was designed to examine the efficacy of a ToM training on practiced (ToM Strange Stories) and transfer tasks (ToM Animations) in both young and older adults. The study involved 127 older adults belonging to two age groups: young-old (Mage = 64.41; SD = 2.49; range: 60-69 years) and old-old (Mage = 75.66; SD = 4.38; range: 70-85 years), randomly assigned to either a ToM group or a control group condition. All participants took part in two 2-hour testing sessions and four 2-hour training sessions. Results showed that both young-old and old-old adults in the ToM group condition improved their ability to reason on complex-mental states significantly more than participants in the control group condition. This positive effect of the training was evident on practiced and transfer ToM tasks. Crucially, age did not moderate the effect of the ToM training. These findings demonstrate that young-old and old-old adults equally benefit from the ToM training. Implications for the positive effect of the ToM training in old-old adults are discussed.

  20. Tumour-associated neutrophils and loss of epithelial PTEN can promote corticosteroid-insensitive MMP-9 expression in the chronically inflamed lung microenvironment

    PubMed Central

    Vannitamby, Amanda; Seow, Huei Jiunn; Anderson, Gary; Vlahos, Ross; Thompson, Michelle; Steinfort, Daniel; Irving, Louis B; Bozinovski, Steven

    2017-01-01

    Matrix metalloproteinase-9 (MMP-9) is increased in a number of pathological lung conditions, where the proteinase contributes to deleterious remodelling of the airways. While both lung cancer and COPD are associated with increased MMP-9 expression, the cellular and molecular drivers of MMP-9 remain unresolved. In this study, MMP-9 transcript measured within the tumour region from patients with non-small-cell lung cancer (NSCLC) and coexisting COPD was found to be uniformly increased relative to adjacent tumour-free tissue. MMP-9 gene expression and immunohistochemistry identified tumour-associated neutrophils, but not macrophages, as a predominant source of this proteinase. In addition, PTEN gene expression was significantly reduced in tumour and there was evidence of epithelial MMP-9 expression. To explore whether PTEN can regulate epithelial MMP-9 expression, a small interfering (si)RNA knockdown strategy was used in Beas-2B bronchial epithelial cells. PTEN knockdown by siRNA selectively increased MMP-9 expression in response to lipopolysaccharide in a corticosteroid-insensitive manner. In summary, tumour-associated neutrophils represent an important source of MMP-9 in NSCLC, and loss of epithelial PTEN may further augment steroid-insensitive expression. PMID:28202627

  1. Evaluation of a teacher training program to enhance executive functions in preschool children.

    PubMed

    Walk, Laura M; Evers, Wiebke F; Quante, Sonja; Hille, Katrin

    2018-01-01

    Executive functions (EFs) play a critical role in cognitive and social development. During preschool years, children show not only rapid improvement in their EFs, but also appear sensitive to developmentally appropriate interventions. EMIL is a training program for German preschool teachers that was developed and implemented to improve the EFs of preschoolers. The aim of the present study was to evaluate its effects on the EFs of children between three and six years old. The teacher training (eight sessions, 28.5 hours) was implemented in four preschools. The EFs of children of the intervention group (n = 72, 32 girls, Mage = 48 months) and the control group of four other matched preschools (n = 61, 27 girls, Mage = 48 months) were tested before, during, and after the intervention using different measures assessing working memory, inhibitory control, and cognitive flexibility. The intervention group showed significant gains on three out of seven EF tests (behavioral inhibition, visual-spatial working memory, and combined EFs) compared to the control group. Post hoc analyses for children with low initial EFs scores revealed that participation in the intervention led to significant gains in inhibitory control, visual-spatial working memory, and phonological working memory as well as a marginally significant difference for combined EFs. However, effect sizes were rather small. The results suggest that teacher training can lead to significant improvements in preschooler's EFs. Although preliminary, the results could contribute to the discussion on how teacher training can facilitate the improvement of EFs in preschool children.

  2. Increased expression of ADAM 9 and ADAM 15 mRNA in pancreatic cancer.

    PubMed

    Yamada, Daisuke; Ohuchida, Kenoki; Mizumoto, Kazuhiro; Ohhashi, Seiji; Yu, Jun; Egami, Takuya; Fujita, Hayato; Nagai, Eishi; Tanaka, Masao

    2007-01-01

    A disintegrin and metalloproteases (ADAMs) comprise a multifunctional family of membrane-anchored proteins. ADAM 9 and ADAM 15 are involved in cell migration and invasion. Expression of ADAM 9 and ADAM 15 was reported to be altered in several types of cancer. Quantitative real-time reverse transcription-polymerase chain reaction was performed to measure the expression of ADAM 9 mRNA in bulk pancreatic tissues. Results showed no significant difference in the expression of ADAM 9 mRNA between pancreatic cancer and non-neoplastic pancreas. Primary cultured pancreatic fibroblasts also expressed ADAM 9 mRNA. Therefore, a laser microdissection and pressure catapulting technique was employed to isolate cancer cells from tumor tissues. The expression of ADAM 9 and ADAM 15 mRNA was measured in microdissected samples (cancer cells, n = 11; normal epithelial cells, n = 13 for ADAM 9; cancer cells, n = 9; normal epithelial cells, n = 9 for ADAM 15). Pancreatic cancer cells expressed significantly higher levels of ADAM 9 and ADAM 15 mRNA than did normal pancreatic epithelial cells (p = 0.016 for ADAM 9; p = 0.004 for ADAM 15). ADAM 9 and ADAM 15 are involved in pancreatic cancer. Microdissection-based analysis appears to be indispensable for the accurate analysis of the expression of certain ADAM family members in pancreatic cancer.

  3. Impact of toll-like-receptor-9 (TLR9) deficiency on visceral adipose tissue adipokine expression during chronic DSS-induced colitis in mice.

    PubMed

    Karrasch, T; Schmid, A; Kopp, A; Obermeier, F; Hofmann, C; Schäffler, A

    2015-02-01

    Studies postulate an involvement of adipokines in inflammatory gastrointestinal diseases. Leptin-deficient ob/ob mice as well as TLR9-deficient mice have a more moderate course of chronic DSS-induced colitis (DSS-CC) and adipocytes do express functional TLR9 molecules. Adipokine mRNA expression in visceral adipose tissue of mice before and after the induction of DSS-CC was investigated. Experiments were performed in both TLR9(wt/wt) and TLR9(-/-) mice. In vitro, the effect of TLR9 blocking peptide on leptin and visfatin protein secretion was studied in 3T3-L1 adipocytes. Induction of DSS-CC led to an upregulation of leptin mRNA expression in TLR9(wt/wt) mice, while TLR9(-/-) animals showed a significant reduction of leptin expression even below baseline. While visfatin expression remained unchanged in TLR9(wt/wt) animals, TLR9(-/-) mice exhibited a significant induction during DSS-CC. CTRP-3 expression was reduced after colitis induction only in TLR9(-/-) animals. Of note, IL-6 expression levels remained unchanged, while CXCL1/KC and cyclophilin A expression was reduced in DSS-CC. Inhibition of TLR9 signaling by using TLR9 blocking peptide led to reduced leptin protein secretion into cell culture supernatants in 3T3-L1 adipocytes, while visfatin protein secretion was enhanced. DSS-CC leads to differential adipokine expression profiles in the visceral fat pad in TLR9(wt/wt) vs. TLR9(-/-) mice. In vitro, inhibition of TLR9 signaling induces visfatin secretion while inhibiting leptin secretion in adipocytes. Thus, visceral adipokines are regulated by intact TLR9 signaling pathway and a specific interplay between the leptin- and the TLR9-pathways might be of pathophysiological importance in chronic intestinal inflammation. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Fundamental motor skill, physical activity, and sedentary behavior in socioeconomically disadvantaged kindergarteners.

    PubMed

    Gu, Xiangli

    2016-10-01

    Guided by Stodden et al's conceptual model, the main purpose of the study was to examine the relation between fundamental motor skills (FMS; locomotor and objective control skills), different intensity levels of physical activity (light PA [LPA], moderate-to-vigorous PA [MVPA], and vigorous PA[VPA]), and sedentary behavior (SB) in socioeconomically disadvantaged kindergarteners. A prospective design was used in this study and the data were collected across the 2013-2014 academic school year. Participants were 256 (129 boys; 127 girls; Mage = 5.37, SD = 0.48) kindergarteners recruited from three public schools in the southern United States. Results found that FMS were significantly related to LPA, MVPA, VPA, and SB. Regression analyses indicate that locomotor skills explained significant variance for LPA (6.4%; p < .01), MVPA (7.9%; p < .001), and VPA (5.3%; p < .01) after controlling for weight status. Mediational analysis supports the significant indirect effect of MVPA on the relation between FMS and SB (95% CI: [-0.019, -0.006]). Adequate FMS development during early childhood may result in participating in more varied physical activities, thus leading to lower risk of obesity-related behaviors.

  5. The effect of thiopurine drugs on DNA methylation in relation to TPMT expression.

    PubMed

    Hogarth, L A; Redfern, C P F; Teodoridis, J M; Hall, A G; Anderson, H; Case, M C; Coulthard, S A

    2008-10-15

    The thiopurine drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are well-established agents for the treatment of leukaemia but their main modes of action are controversial. Thiopurine methyltransferase (TPMT) metabolises thiopurine drugs and influences their cytotoxic activity. TPMT, like DNA methyltransferases (DNMTs), transfers methyl groups from S-adenosylmethionine (SAM) and generates S-adenosylhomocysteine (SAH). Since SAM levels are dependent on de novo purine synthesis (DNPS) and the metabolic products of 6-TG and 6-MP differ in their ability to inhibit DNPS, we postulated that 6-TG compared to 6-MP would have differential effects on changes in SAM and SAH levels and global DNA methylation, depending on TPMT status. To test this hypothesis, we used a human embryonic kidney cell line with inducible TPMT. Although changes in SAM and SAH levels occurred with each drug, decrease in global DNA methylation more closely reflected a decrease in DNMT activity. Inhibition was influenced by TPMT for 6-TG, but not 6-MP. The decrease in global methylation and DNMT activity with 6-MP, or with 6-TG when TPMT expression was low, were comparable to 5-aza-2'-deoxycytidine. However, this was not reflected in changes in methylation at the level of an individual marker gene (MAGE1A). The results suggest that a non-TPMT metabolised metabolite of 6-MP and 6-TG and the TPMT-metabolised 6-MP metabolite 6-methylthioguanosine 5'-monophosphate, contribute to a decrease in DNMT levels and global DNA methylation. As demethylating agents have shown promise in leukaemia treatment, inhibition of DNA methylation by the thiopurine drugs may contribute to their cytotoxic affects.

  6. Latino parent acculturation stress: Longitudinal effects on family functioning and youth emotional and behavioral health.

    PubMed

    Lorenzo-Blanco, Elma I; Meca, Alan; Unger, Jennifer B; Romero, Andrea; Gonzales-Backen, Melinda; Piña-Watson, Brandy; Cano, Miguel Ángel; Zamboanga, Byron L; Des Rosiers, Sabrina E; Soto, Daniel W; Villamar, Juan A; Lizzi, Karina M; Pattarroyo, Monica; Schwartz, Seth J

    2016-12-01

    Latino parents can experience acculturation stressors, and according to the Family Stress Model (FSM), parent stress can influence youth mental health and substance use by negatively affecting family functioning. To understand how acculturation stressors come together and unfold over time to influence youth mental health and substance use outcomes, the current study investigated the trajectory of a latent parent acculturation stress factor and its influence on youth mental health and substance use via parent-and youth-reported family functioning. Data came from a 6-wave, school-based survey with 302 recent (<5 years) immigrant Latino parents (74% mothers, Mage = 41.09 years) and their adolescents (47% female, Mage = 14.51 years). Parents' reports of discrimination, negative context of reception, and acculturative stress loaded onto a latent factor of acculturation stress at each of the first 4 time points. Earlier levels of and increases in parent acculturation stress predicted worse youth-reported family functioning. Additionally, earlier levels of parent acculturation stress predicted worse parent-reported family functioning and increases in parent acculturation stress predicted better parent-reported family functioning. While youth-reported positive family functioning predicted higher self-esteem, lower symptoms of depression, and lower aggressive and rule-breaking behavior in youth, parent-reported family positive functioning predicted lower youth alcohol and cigarette use. Findings highlight the need for Latino youth preventive interventions to target parent acculturation stress and family functioning. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  7. Prognostic value of matrix metalloproteinase 9 expression in patients with juvenile nasopharyngeal angiofibroma: tissue microarray analysis.

    PubMed

    Sun, Xicai; Guo, Limin; Wang, Jingjing; Wang, Huan; Liu, Zhuofu; Liu, Juan; Yu, Huapeng; Hu, Li; Li, Han; Wang, Dehui

    2014-08-01

    Although JNA is a benign neoplasm histopathologically, it has a propensity for locally destructive growth and remains a higher postoperative recurrence rate. The aim of this study was to analyze the expression and localization of MMP-9 in JNA using tissue microarray to elucidate its correlation with clinicopathological features and recurrence. The expression of MMP-9 was assessed by immunohistochemistry in a tissue microarray from 70 patients with JNA and 10 control subjects. Correlation between the levels of MMP-9 expression and clinicopathologic variables, as well as tumor recurrence, were analyzed. MMP-9 was detected in perivascular and extravascular less differentiated cells and stromal cells of patients with JNA but not in the matured vascular endothelial cells of these patients. The presence of MMP-9 expression in JNA was correlated with patient's age (p=0.001). Spearman correlation analysis suggested that high expression of MMP-9 in JNA had negative correlation with patient's age (r=-0.412, p<0.001). The recurrence rate in JNA patients with high MMP-9 expression was significantly higher than those with low MMP-9 expression (p=0.002). In multivariate and ROC curve analysis, MMP-9 was a good prognostic factor for tumor recurrence of JNA. Higher MMP-9 expression is a poor prognostic factor for patients with JNA who have been surgically treated. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Sox9 expression in carcinogenesis and its clinical significance in intrahepatic cholangiocarcinoma.

    PubMed

    Matsushima, Hajime; Kuroki, Tamotsu; Kitasato, Amane; Adachi, Tomohiko; Tanaka, Takayuki; Hirabaru, Masataka; Hirayama, Takanori; Kuroshima, Naoki; Hidaka, Masaaki; Soyama, Akihiko; Takatsuki, Mitsuhisa; Kinoshita, Naoe; Sano, Kazunori; Nishida, Noriyuki; Eguchi, Susumu

    2015-12-01

    Intrahepatic cholangiocarcinomas develop through a multi-step carcinogenesis. Precancerous lesions are defined as biliary intraepithelial neoplasia. Sex determining region Y-box9 (Sox9) is required for the normal differentiation of the biliary tract. To evaluate the Sox9 expression in carcinogenesis and its correlation with clinicopathological features in intrahepatic cholangiocarcinoma. Sox9 expression in normal epithelium, biliary intraepithelial neoplasia, and intrahepatic cholangiocarcinoma were investigated immunohistochemically using 43 specimens of intrahepatic cholangiocarcinoma. Sox9 expression in intrahepatic cholangiocarcinoma was compared with the clinicopathological features. The molecular effects of Sox9 were investigated by gene transfection to intrahepatic cholangiocarcinoma cell lines. Sox9 expression was decreased from the normal epithelium to the biliary intraepithelial neoplasia in a stepwise fashion. In 51.2% (22/43) of the patients with intrahepatic cholangiocarcinoma, Sox9 expression was positive, and Sox9 expression was significantly associated with the biliary infiltration (P=0.034) and poor overall survival (P=0.039). Upregulation of Sox9 promoted the cell migration and invasion, and decreased the E-cadherin expression and increased the vimentin and α-SMA expression in cell lines. Decreased Sox9 expression may be related to the early stage of the carcinogenesis of intrahepatic cholangiocarcinoma. Sox9 overexpression in intrahepatic cholangiocarcinoma is related to biliary infiltration and poorer prognosis, and it promotes cell migration and invasion, via the epithelial-to-mesenchymal transition. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  9. [Comparative study of the subjective emotional experience among adolescents showing depressive symptoms associated or not with risk-taking behavior].

    PubMed

    Bréjard, V; Pasquier, A; Bonnet, A; Pedinielli, J-L

    2011-09-01

    Relationships between risk-taking behavior and depressive disorders in young people are considered as a complex psychopathological problem. Previous findings showed strong correlations between substance abuse, risk-taking behavior and depressive symptoms. Nevertheless, questions remain concerning potential common factors of depression and risk-taking behavior. Besides research focusing on personality dimensions, some others highlight the role played by emotions and their pathological aspects. In these studies, pathological emotional processing such as alexithymia or specific deficit in emotional intensity was linked to both risk-taking behavior and depressive disorders. The aim of this study was to investigate potential specific emotional profiles of adolescents engaged in pathological risk-taking or depressive symptomatology, versus adolescents presenting an association of both. Four hundred and eigty-eight adolescents (m(age)=14,93, SD=1,44), with 257 boys (m(age)=15, SD=1,51) and 231 girls (m(age)=14,52, SD=1,23), were spread into four groups: adolescents engaged in high level risk-taking, adolescents showing both high risk-taking and high depressive symptoms, depressed adolescents, and a control group without any pathological aspects. The four groups completed a set of three assessments: Youth Risk Behavior Surveillance Scale (YRBSS), Level of Emotional Awareness Scale (LEAS) and Differential Emotional Scale (DES). Adolescents engaged in risk-taking have the lowest level of emotional awareness and subjective emotional intensity, while adolescents of the second group (depression with risk-taking behavior) have a higher level on both measures. Depressed adolescents present the highest score of emotional awareness within the pathological groups, lower than controls. Paradoxically, their ability to represent themselves others' emotions were higher than the control group, just as the intensity of their subjective emotional experience in case of negative emotions. The results may be explained by a specific developmental hypothesis, in which emotional awareness growth from the early period of life to late childhood, allowing children to gradually experiment more and more complex subjective emotional experiences. However, early exposure to traumatic experiences or inadequate environment may lead to developmental arrests, in which emotional awareness is weak. In this case, a lack of emotional information caused by low emotional awareness may have pathological issues, in terms of depression and risk-taking behavior. Clinical implications of this interpretation are discussed. Copyright © 2010 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  10. Single-cell gene expression analysis reveals diversity among human spermatogonia.

    PubMed

    Neuhaus, N; Yoon, J; Terwort, N; Kliesch, S; Seggewiss, J; Huge, A; Voss, R; Schlatt, S; Grindberg, R V; Schöler, H R

    2017-02-10

    Is the molecular profile of human spermatogonia homogeneous or heterogeneous when analysed at the single-cell level? Heterogeneous expression profiles may be a key characteristic of human spermatogonia, supporting the existence of a heterogeneous stem cell population. Despite the fact that many studies have sought to identify specific markers for human spermatogonia, the molecular fingerprint of these cells remains hitherto unknown. Testicular tissues from patients with spermatogonial arrest (arrest, n = 1) and with qualitatively normal spermatogenesis (normal, n = 7) were selected from a pool of 179 consecutively obtained biopsies. Gene expression analyses of cell populations and single-cells (n = 105) were performed. Two OCT4-positive individual cells were selected for global transcriptional capture using shallow RNA-seq. Finally, expression of four candidate markers was assessed by immunohistochemistry. Histological analysis and blood hormone measurements for LH, FSH and testosterone were performed prior to testicular sample selection. Following enzymatic digestion of testicular tissues, differential plating and subsequent micromanipulation of individual cells was employed to enrich and isolate human spermatogonia, respectively. Endpoint analyses were qPCR analysis of cell populations and individual cells, shallow RNA-seq and immunohistochemical analyses. Unexpectedly, single-cell expression data from the arrest patient (20 cells) showed heterogeneous expression profiles. Also, from patients with normal spermatogenesis, heterogeneous expression patterns of undifferentiated (OCT4, UTF1 and MAGE A4) and differentiated marker genes (BOLL and PRM2) were obtained within each spermatogonia cluster (13 clusters with 85 cells). Shallow RNA-seq analysis of individual human spermatogonia was validated, and a spermatogonia-specific heterogeneous protein expression of selected candidate markers (DDX5, TSPY1, EEF1A1 and NGN3) was demonstrated. The heterogeneity of human spermatogonia at the RNA and protein levels is a snapshot. To further assess the functional meaning of this heterogeneity and the dynamics of stem cell populations, approaches need to be developed to facilitate the repeated analysis of individual cells. Our data suggest that heterogeneous expression profiles may be a key characteristic of human spermatogonia, supporting the model of a heterogeneous stem cell population. Future studies will assess the dynamics of spermatogonial populations in fertile and infertile patients. RNA-seq data is published in the GEO database: GSE91063. This work was supported by the Max Planck Society and the Deutsche Forschungsgemeinschaft DFG-Research Unit FOR 1041 Germ Cell Potential (grant numbers SCHO 340/7-1, SCHL394/11-2). The authors declare that there is no conflict of interest. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  11. The diagnostic utility of separation anxiety disorder symptoms: An item response theory analysis

    PubMed Central

    Cooper-Vince, Christine E.; Emmert-Aronson, Benjamin O.; Pincus, Donna B.; Comer, Jonathan S.

    2013-01-01

    At present, it is not clear whether the current definition of separation anxiety disorder (SAD) is the optimal classification of developmentally inappropriate, severe, and interfering separation anxiety in youth. Much remains to be learned about the relative contributions of individual SAD symptoms for informing diagnosis. Two-parameter logistic Item Response Theory analyses were conducted on the eight core SAD symptoms in an outpatient anxiety sample of treatment-seeking children (N=359, 59.3% female, MAge=11.2) and their parents to determine the diagnostic utility of each of these symptoms. Analyses considered values of item threshold, which characterize the SAD severity level at which each symptom has a 50% chance of being endorsed, and item discrimination, which characterize how well each symptom distinguishes individuals with higher and lower levels of SAD. Distress related to separation and fear of being alone without major attachment figures showed the strongest discrimination properties and the lowest thresholds for being endorsed. In contrast, worry about harm befalling attachment figures showed the poorest discrimination properties, and nightmares about separation showed the highest threshold for being endorsed. Distress related to separation demonstrated crossing differential item functioning associated with age—at lower separation anxiety levels excessive fear at separation was more likely to be endorsed for children ≥9 years, whereas at higher levels this symptom was more likely to be endorsed by children <9 years. Implications are discussed for optimizing the taxonomy of SAD in youth. PMID:23963543

  12. HIF-1α activates hypoxia-induced BCL-9 expression in human colorectal cancer cells

    PubMed Central

    Chen, Tian-Rui; Wei, Hai-feng; Song, Dian-Wen; Liu, Tie-Long; Yang, Xing-Hai; Fu, Chuan-Gang; Hu, Zhi-qian; Zhou, Wang; Yan, Wang-Jun; Xiao, Jian-Ru

    2017-01-01

    B-cell CLL/lymphoma 9 protein (BCL-9), a multi-functional co-factor in Wnt signaling, induced carcinogenesis as well as promoting tumor progression, metastasis and chemo-resistance in colorectal cancer (CRC). However, the mechanisms for increased BCL-9 expression in CRC were not well understood. Here, we report that hypoxia, a hallmark of solid tumors, induced BCL-9 mRNA expression in human CRC cells. Analysis of BCL-9 promoter revealed two functional hypoxia-responsive elements (HRE-B and HRE-C) that can be specifically bound with and be transactivated by hypoxia inducible factors (HIF) -1α but not HIF-2α. Consistently, ectopic expression of HIF-1α but not HIF-2α transcriptionally induced BCL-9 expression levels in cells. Knockdown of endogenous HIF-1α but not HIF-2α by siRNA largely abolished the induction of HIF by hypoxia. Furthermore, there was a strong association of HIF-1α expression with BCL-9 expression in human CRC specimens. In summary, results from this study demonstrated that hypoxia induced BCL-9 expression in human CRC cells mainly through HIF-1α, which could be an important underlying mechanism for increased BCL-9 expression in CRC. PMID:27121066

  13. Between-Person and Within-Person Associations among Processing Speed, Attention Switching and Working Memory in Younger and Older Adults

    PubMed Central

    Stawski, Robert S.; Sliwinski, Martin J.; Hofer, Scott M.

    2013-01-01

    Background/Study Context Theories of cognitive aging predict associations among processes that transpire within individuals, but are often tested by examining between-person relationships. The authors provide an empirical demonstration of how associations among measures of processing speed, attention switching, and working memory are different when considered between persons versus within persons over time. Methods A sample of 108 older adults (Mage: 80.8, range: 66–95) and 68 younger adults (Mage: 20.2, range:18–24) completed measures of processing speed, attention switching, and working memory on six occasions over a 14-day period. Multilevel modeling was used to examine processing speed and attention switching performance as predictors of working memory performance simultaneously across days (within-person) and across individuals (between-person). Results The findings indicates that simple comparison and response speed predicted working memory better than attention switching between persons, whereas attention switching predicted working memory better than simple comparison and response speed within persons over time. Furthermore, the authors did not observe strong evidence of age differences in these associations either within or between persons. Conclusion The findings of the current study suggest that processing speed is important for understanding between-person and age-related differences in working memory, whereas attention switching is more important for understanding within-person variation in working memory. The authors conclude that theories of cognitive aging should be evaluated by analysis of within-person processes, not exclusively age-related individual differences. PMID:23421639

  14. Parent and child distress after war exposure.

    PubMed

    Lai, Betty S; Hadi, Fawzyiah; Llabre, Maria M

    2014-09-01

    The purpose of this study was to examine multiple distress symptoms (i.e., post-traumatic stress [PTS], anxiety, depression) among parents and children exposed to the Gulf Crisis in 1990-1991. Profiles of parent distress were identified, and the relationship between parent distress and specific child distress symptoms was examined. Parents and children were assessed at one time point. Participants included 151 children (Mage = 10.62 years; 51% female) and 140 parents (Mage = 40 years; 81% female). Utilizing latent profile analysis, three parallel profiles of parent distress were identified: low distress, moderate distress, and high distress. Parent distress was a risk factor for child depression, but it was not a risk factor for child PTS or anxiety. Findings support the importance of broadening the scope of research conducted after exposure to traumatic events to include the assessment of anxiety and depression, as well as PTS, among both parents and children. Additional implications for research and clinical work are discussed. Findings support the importance of screening for multiple distress symptoms among both children and parents after war exposure. Based on our findings, clinicians may want to consider including parents in therapy for children reporting psychological distress, especially depression symptoms, after exposure to traumatic events. This study was cross-sectional. Thus, we are not able to infer direction or causality. The generalizability of our study should be interpreted with caution, as findings will need to be replicated across other populations and other cultures. © 2014 The British Psychological Society.

  15. Scanning Tunneling Microscopy, Atomic Force Microscopy, and Related Techniques.

    DTIC Science & Technology

    1992-06-15

    images of the heaoal ekdprotein monolayer pressed powder samples of pismO claim and sea urchin shells found ~ ~ sx inteotrcelwl fDincoccu radioduran...can be in- Semiconductor Substrates. The atomic structure of sem - vastigated using AFM but has not been as extensively re- iconductor-detal interfaces...from SEM mage (D99). Komaica and p-type Si(00) and p-n junctions formed by implantation of ANALYTICAL CHEMISTRY. VOL 84, NO. 12. JILNE 18. 1992 121R

  16. Differential effects of estrogen and estrogen receptor antagonist, ICI 182 780, on the expression of calbindin-D9k in rat pituitary prolactinoma GH₃ cells.

    PubMed

    Wang, Wan; Knosp, Engelbert; Tai, Guixiang; Zhao, Yuanzheng; Liang, Qianlei; Guo, Yongchuan

    2014-01-01

    To detect the effects of 17β-estradiol (E2) on the expression of calbindin-D9k (CaBP-9k) in pituitary GH3 cells, and to determine the antagonistic effect of a selective estrogen receptor (ER) antagonist (ICI 182 780) on CaBP-9k expression. A rat pituitary prolactinoma cell line (GH3 cells) was used in an in vitro model. The localization of CaBP-9k in GH3 cells was observed by immunofluorescence. GH3 cells were cultured with the addition of E2 medium for 24 hours. The levels of CaBP-9k mRNA and protein expression in different groups were analyzed by RT-PCR and Western blot analysis. The ER antagonist, ICI 182 780, was added to GH3 cells before E2 (10(-8) M) at a concentration of 10(-6) M to investigate the regulation of an ER-mediated pathway on CaBP-9k expression. E2 had a stimulatory effect on CaBP-9k expression of GH3 cells in a dose-dependent manner; the level of CaBP-9k expression was higher when treated with a higher concentration of E2. ICI 182 780 suppressed the stimulatory effect of E2 on CaBP-9k expression in GH3 cells. The level of CaBP-9k expression was significantly reduced by co-administration of E2 with ICI 182 780 in GH3 cells. The immunoprecipitation results confirmed that CaBP-9k interacts directly with ERα, and E2 increases the interaction between CaBP-9k and ERα. Estrogen induces CaBP-9k expression via an ERα-mediated pathway and CaBP-9k directly combines with ERα, suggesting that CaBP-9k is involved in the biological effects mediated by an ER pathway in GH3 cells.

  17. Regulation of mouse hepatic CYP2D9 mRNA expression by growth and adrenal hormones.

    PubMed

    Jarukamjorn, Kanokwan; Sakuma, Tsutomu; Jaruchotikamol, Atika; Oguro, Miki; Nemoto, Nobuo

    2006-02-01

    The constitutive expression of CYP2D9 is sexually dimorphic, namely, strong in males, but diminutive in females. Repetition of mimic growth hormone (GH) secretion pattern impressively returned the mRNA expression level to that in intact mice: the GH secretion pattern's regulation of CYP2D9 mRNA expression has been predominantly disrupted by exogenous GH-administration. The extensive decline of CYP2D9 mRNA expression becoming a sexually non-specific P450 in 9-week-old male mice exposed as neonates to monosodium L-glutamate (MSG) suggested that the male GH secretion pattern is a key to the regulation of male-specific CYP2D9 mRNA expression in adult mice. Dexamethasone (Dex) showed possibility to induce CYP2D9 mRNA expression in adult MSG-neonatally treated mice of either sex. However, the antagonism was observed by co-administration of Dex and GH in the males. Dex-administration in adrenalectomized mice significantly elevated CYP2D9 mRNA expression levels. These findings suggest that an adrenal hormone participates in the regulatory mechanism of CYP2D9 mRNA expression in association with GH.

  18. Tetraspanin CD9 modulates human lymphoma cellular proliferation via histone deacetylase activity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Herr, Michael J.; Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163; Department of Molecular Sciences, The University of Tennessee Health Science Center, Memphis, TN 38163

    2014-05-16

    Highlights: • CD9 is differentially expressed in human Burkitt’s lymphoma cells. • We found that CD9 expression promotes these cells proliferation. • CD9 expression also increases HDAC activity. • HDAC inhibition decreased both cell proliferation and importantly CD9 expression. • CD9 may dictate HDAC efficacy and play a role in HDAC regulation. - Abstract: Non-Hodgkin Lymphoma (NHL) is a type of hematological malignancy that affects two percent of the overall population in the United States. Tetraspanin CD9 is a cell surface protein that has been thoroughly demonstrated to be a molecular facilitator of cellular phenotype. CD9 expression varies in twomore » human lymphoma cell lines, Raji and BJAB. In this report, we investigated the functional relationship between CD9 and cell proliferation regulated by histone deacetylase (HDAC) activity in these two cell lines. Introduction of CD9 expression in Raji cells resulted in significantly increased cell proliferation and HDAC activity compared to Mock transfected Raji cells. The increase in CD9–Raji cell proliferation was significantly inhibited by HDAC inhibitor (HDACi) treatment. Pretreatment of BJAB cells with HDAC inhibitors resulted in a significant decrease in endogenous CD9 mRNA and cell surface expression. BJAB cells also displayed decreased cell proliferation after HDACi treatment. These results suggest a significant relationship between CD9 expression and cell proliferation in human lymphoma cells that may be modulated by HDAC activity.« less

  19. Associations of Thalassemia Major and satisfaction with quality of life: The mediating effect of social support

    PubMed Central

    Platania, Silvia; Gruttadauria, Stefania; Citelli, Giulia; Giambrone, Loris; Di Nuovo, Santo

    2017-01-01

    The present research analyzed the elements of thalassemia which affect the patient’s perceived quality of life. Three hundred patients with Thalassemia Major (males = 165, 55%; females = 135, 45%; Mage = 36.13, standard deviation = 8.54) were the sample. Analysis of multiple mediations revealed a direct effect of self-efficacy on the Satisfaction with Life Scale that is mediated only by social support.The findings suggest a need to accentuate help and support to patients with Thalassemia Major. PMID:29379628

  20. JMJD1A, H3K9me1, H3K9me2 and ADM expression as prognostic markers in oral and oropharyngeal squamous cell carcinoma.

    PubMed

    Maia, Lucas de Lima; Peterle, Gabriela Tonini; Dos Santos, Marcelo; Trivilin, Leonardo Oliveira; Mendes, Suzanny Oliveira; de Oliveira, Mayara Mota; Dos Santos, Joaquim Gasparini; Stur, Elaine; Agostini, Lidiane Pignaton; Couto, Cinthia Vidal Monteiro da Silva; Dalbó, Juliana; de Assis, Aricia Leone Evangelista Monteiro; Archanjo, Anderson Barros; Mercante, Ana Maria Da Cunha; Lopez, Rossana Veronica Mendoza; Nunes, Fábio Daumas; de Carvalho, Marcos Brasilino; Tajara, Eloiza Helena; Louro, Iúri Drumond; Álvares-da-Silva, Adriana Madeira

    2018-01-01

    Jumonji Domain-Containing 1A (JMJD1A) protein promotes demethylation of histones, especially at lysin-9 of di-methylated histone H3 (H3K9me2) or mono-methylated (H3K9me1). Increased levels of H3 histone methylation at lysin-9 (H3K9) is related to tumor suppressor gene silencing. JMJD1A gene target Adrenomeduline (ADM) has shown to promote cell growth and tumorigenesis. JMJD1A and ADM expression, as well as H3K9 methylation level have been related with development risk and prognosis of several tumor types. We aimed to evaluate JMJD1A, ADM, H3K9me1 and H3K9me2expression in paraffin-embedded tissue microarrays from 84 oral and oropharyngeal squamous cell carcinoma samples through immunohistochemistry analysis. Our results showed that nuclear JMJD1A expression was related to lymph node metastasis risk. In addition, JMJD1A cytoplasmic expression was an independent risk marker for advanced tumor stages. H3K9me1 cytoplasmic expression was associated with reduced disease-specific death risk. Furthermore, high H3K9me2 nuclear expression was associated with worse specific-disease and disease-free survival. Finally, high ADM cytoplasmic expression was an independent marker of lymph node metastasis risk. JMJD1A, H3K9me1/2 and ADM expression may be predictor markers of progression and prognosis in oral and oropharynx cancer patients, as well as putative therapeutic targets.

  1. JMJD1A, H3K9me1, H3K9me2 and ADM expression as prognostic markers in oral and oropharyngeal squamous cell carcinoma

    PubMed Central

    Peterle, Gabriela Tonini; dos Santos, Marcelo; Trivilin, Leonardo Oliveira; Mendes, Suzanny Oliveira; de Oliveira, Mayara Mota; dos Santos, Joaquim Gasparini; Stur, Elaine; Agostini, Lidiane Pignaton; Couto, Cinthia Vidal Monteiro da Silva; Dalbó, Juliana; de Assis, Aricia Leone Evangelista Monteiro; Archanjo, Anderson Barros; Mercante, Ana Maria Da Cunha; Lopez, Rossana Veronica Mendoza; Nunes, Fábio Daumas; de Carvalho, Marcos Brasilino; Tajara, Eloiza Helena; Louro, Iúri Drumond; Álvares-da-Silva, Adriana Madeira

    2018-01-01

    Aims Jumonji Domain-Containing 1A (JMJD1A) protein promotes demethylation of histones, especially at lysin-9 of di-methylated histone H3 (H3K9me2) or mono-methylated (H3K9me1). Increased levels of H3 histone methylation at lysin-9 (H3K9) is related to tumor suppressor gene silencing. JMJD1A gene target Adrenomeduline (ADM) has shown to promote cell growth and tumorigenesis. JMJD1A and ADM expression, as well as H3K9 methylation level have been related with development risk and prognosis of several tumor types. Methods and results We aimed to evaluate JMJD1A, ADM, H3K9me1 and H3K9me2expression in paraffin-embedded tissue microarrays from 84 oral and oropharyngeal squamous cell carcinoma samples through immunohistochemistry analysis. Our results showed that nuclear JMJD1A expression was related to lymph node metastasis risk. In addition, JMJD1A cytoplasmic expression was an independent risk marker for advanced tumor stages. H3K9me1 cytoplasmic expression was associated with reduced disease-specific death risk. Furthermore, high H3K9me2 nuclear expression was associated with worse specific-disease and disease-free survival. Finally, high ADM cytoplasmic expression was an independent marker of lymph node metastasis risk. Conclusion JMJD1A, H3K9me1/2 and ADM expression may be predictor markers of progression and prognosis in oral and oropharynx cancer patients, as well as putative therapeutic targets. PMID:29590186

  2. Co-expression of HoxA9 and bcr-abl genes in chronic myeloid leukemia.

    PubMed

    Tedeschi, Fabián A; Cardozo, Maria A; Valentini, Rosanna; Zalazar, Fabián E

    2010-05-01

    We have analyzed the co-expression of the bcr-abl and HoxA9 genes in the follow-up of patients with chronic myeloid leukemia (CML). In the present work we measured the HoxA9 and bcr-abl gene expression in sequential samples. In all patients, bcr-abl and HoxA9 were expressed at detectable levels in every sample. When the results were expressed in relation to abl, two different situations were found: (a) patients clinically stable at second sampling, with low relative risk at diagnosis (low Sokal's score), did not show significant differences in both bcr-abl and HoxA9 levels in the sequential samples analyzed, and (b) patients with poor prognosis (showing intermediate or high Sokal's score at diagnosis) had increased expression of bcr-abl as well as HoxA9 genes (p < 0.05). Since HoxA9 gene expression remains at relatively constant levels throughout adult life, our results could reflect actual changes in the expression rate of this gene associated with bcr-abl during the progression of CML.

  3. Tumour-associated neutrophils and loss of epithelial PTEN can promote corticosteroid-insensitive MMP-9 expression in the chronically inflamed lung microenvironment.

    PubMed

    Vannitamby, Amanda; Seow, Huei Jiunn; Anderson, Gary; Vlahos, Ross; Thompson, Michelle; Steinfort, Daniel; Irving, Louis B; Bozinovski, Steven

    2017-12-01

    Matrix metalloproteinase-9 (MMP-9) is increased in a number of pathological lung conditions, where the proteinase contributes to deleterious remodelling of the airways. While both lung cancer and COPD are associated with increased MMP-9 expression, the cellular and molecular drivers of MMP-9 remain unresolved. In this study, MMP-9 transcript measured within the tumour region from patients with non-small-cell lung cancer (NSCLC) and coexisting COPD was found to be uniformly increased relative to adjacent tumour-free tissue. MMP-9 gene expression and immunohistochemistry identified tumour-associated neutrophils, but not macrophages, as a predominant source of this proteinase. In addition, PTEN gene expression was significantly reduced in tumour and there was evidence of epithelial MMP-9 expression. To explore whether PTEN can regulate epithelial MMP-9 expression, a small interfering (si)RNA knockdown strategy was used in Beas-2B bronchial epithelial cells. PTEN knockdown by siRNA selectively increased MMP-9 expression in response to lipopolysaccharide in a corticosteroid-insensitive manner. In summary, tumour-associated neutrophils represent an important source of MMP-9 in NSCLC, and loss of epithelial PTEN may further augment steroid-insensitive expression. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Parental Emotion Socialization and Child Psychological Adjustment among Chinese Urban Families: Mediation through Child Emotion Regulation and Moderation through Dyadic Collaboration

    PubMed Central

    Jin, Zhuyun; Zhang, Xutong; Han, Zhuo Rachel

    2017-01-01

    The theoretical model of emotion regulation and many empirical findings have suggested that children’s emotion regulation may mediate the association between parents’ emotion socialization and children’s psychological adjustment. However, limited research has been conducted on moderators of these relations, despite the argument that the associations between parenting practices and children’s psychological adjustment are probabilistic rather than deterministic. This study examined the mediating role of children’s emotion regulation in linking parents’ emotion socialization and children’s psychological adjustment, and whether dyadic collaboration could moderate the proposed mediation model in a sample of Chinese parents and their children in their middle childhood. Participants were 150 Chinese children (87 boys and 63 girls, Mage = 8.54, SD = 1.67) and their parents (Mage = 39.22, SD = 4.07). Parent–child dyadic collaboration was videotaped and coded from an interaction task. Parents reported on their emotion socialization, children’s emotion regulation and psychopathological symptoms. Results indicated that child emotion regulation mediated the links between parental emotion socialization and child’s psychopathological symptoms. Evidence of moderated mediation was also found: supportive emotion socialization and child emotion regulation were positively correlated only at high and medium levels of dyadic collaboration, with child’s psychopathological symptoms as the dependent variables. Our findings suggested that higher-level parent–child collaboration might further potentiate the protective effect of parental supportive emotion socialization practices against child psychopathological symptoms. PMID:29326629

  5. Spatial expression dynamics of Men-9 delineate the third floral whorl in male and female flowers of dioecious Silene latifolia.

    PubMed

    Robertson, S E; Li, Y; Scutt, C P; Willis, M E; Gilmartin, P M

    1997-07-01

    Sex determination in Silene latifolia is controlled by heteromorphic sex chromosomes. Female flowers have five fused carpels and ten arrested stamen primordia. The male-determining Y chromosome overrides female development to suppress carpel formation and promote stamen development. The isolation and characterization of two S. latifolia. Male enhanced cDNAs, Men-9a and Men-9b, which probably represent different alleles of a novel gene are reported here. Men-9a and Men-9b share 91.8% coding sequence nucleotide identity, yet only 85.4% amino acid identity. The Men-9 cDNAs are related to the previously reported MROS3 cDNA from S. latifolia. However, MROS3 is not present in the S. latifolia population used in these studies and the expression dynamics of Men-9a and Men-9b contrast dramatically with those reported for MROS3. Men-9 cDNAs are expressed primarily in anthers of young male flowers, with highest expression in 1-2 mm buds. Men-9 expression is also observed at a low level in female flowers. In situ hybridization analysis reveals two phases of Men-9 expression. The first phase is during a common stage of early stamen development in male and female flowers prior to stamen arrest in female flowers. The second phase of Men-9 expression is maximal in the epidermis and endothecium of Y chromosome- and Ustilago violacea-induced stamens; expression in male and female flowers extends to the epidermis of the staminal nectaries with strict boundaries at the second and fourth whorls, Men-9 gene expression therefore delineates the boundaries of the third floral whorl in S. latifolia flowers.

  6. Panic Attack History and Smoking Topography

    PubMed Central

    Farris, Samantha G.; Brown, Lily A.; Goodwin, Renee D.; Zvolensky, Michael J.

    2016-01-01

    Background Little is known about panic attacks and puffing topography, a behavioral index of the value of smoking reinforcement. This study examined smoking style during the course of smoking of a single cigarette among adult daily smokers with and without a history of panic attacks. Method Participants (n = 124, Mage = 43.9, SD = 9.7; 44.4% female) were non-treatment seeking daily smokers. Lifetime panic attack history was assessed via diagnostic assessment; 28.2% (n = 35) of the sample had a panic attack history. Participants smoked one cigarette during an ad libitum smoking trial. Puff volume, duration, and inter-puff interval were measured using the Clinical Research Support System (CReSS) pocket device. Results Regression analyses revealed that panic attack status was not associated with significant differences in average puff volume, duration, or inter-puff interval. Multi-level modeling was used to examine puffing trajectories. Puff-level data revealed that there was a significant quadratic time x panic effect for puff volume and duration. Those with a panic attack history demonstrated relatively sustained levels of both puff volume and duration over time, whereas those without a history of panic attacks demonstrated an increase followed by a decrease in volume and duration over time. These effects were not accounted for by the presence of general psychopathology. Discussion Smokers with a panic attack history demonstrate more persistent efforts to self-regulate the delivery of nicotine, and thus may be at risk for continued smoking and dependence. Tailored treatment may be needed to address unique vulnerabilities among this group. PMID:28033542

  7. Comparison of population iodine estimates from 24-hour urine and timed-spot urine samples.

    PubMed

    Perrine, Cria G; Cogswell, Mary E; Swanson, Christine A; Sullivan, Kevin M; Chen, Te-Ching; Carriquiry, Alicia L; Dodd, Kevin W; Caldwell, Kathleen L; Wang, Chia-Yih

    2014-04-01

    Median urine iodine concentration (UIC; μg/L) in spot urine samples is recommended for monitoring population iodine status. Other common measures are iodine:creatinine ratio (I/Cr; μg/g) and estimated 24-hour urine iodine excretion (UIE; I/Cr × predicted 24-hour Cr; μg/day). Despite different units, these measures are often used interchangeably, and it is unclear how they compare with the reference standard 24-hour UIE. Volunteers aged 18-39 years collected all their urine samples for 24 hours (n=400). Voids from morning, afternoon, evening, overnight, and a composite 24-hour sample were analyzed for iodine. We calculated median observed 24-hour UIE and 24-hour UIC, and spot UIC, I/Cr, and two measures of estimated UIE calculated using predicted 24-hour Cr from published estimates by Kesteloot and Joosens (varies by age and sex) and published equations by Mage et al. (varies by age, sex, race, and anthropometric measures). We examined mean differences and relative difference across iodine excretion levels using Bland-Altman plots. Median 24-hour UIE was 173.6 μg/day and 24-hour UIC was 144.8 μg/L. From timed-spot urine samples, estimates were: UIC 147.3-156.2 μg/L; I/Cr 103.6-114.3 μg/g, estimated 24-hour UIE (Kesteloot and Joosens) 145.7-163.3 μg/day; and estimated 24-hour UIE (Mage) 176.5-187.7 μg/day. Iodine measures did not vary consistently by timing of spot urine collection. Compared with observed 24-hour UIE, on average, estimated (Mage) 24-hour UIE was not significantly different, while estimated 24-hour UIE (Kesteloot and Joosens) was significantly different for some ethnicity/sex groups. Compared with 24-hour UIC, on average, spot UIC did not differ. Estimates of UIC, I/Cr, and estimated 24-hour UIE (I/Cr × predicted 24-hour Cr) from spot urine samples should not be used interchangeably. Estimated 24-hour UIE, where predicted 24-hour Cr varies by age, sex, ethnicity, and anthropometric measures and was calculated with prediction equations using data from the sample, was more comparable to observed 24-hour UIE than when predicted 24-hour Cr was from published estimates from a different population. However, currently no cutoffs exist to interpret population estimated 24-hour UIE values.

  8. Multiple magma emplacement and its effect on the superficial deformation: hints from analogue models

    NASA Astrophysics Data System (ADS)

    Montanari, Domenico; Bonini, Marco; Corti, Giacomo; del Ventisette, Chiara

    2017-04-01

    To test the effect exerted by multiple magma emplacement on the deformation pattern, we have run analogue models with synchronous, as well as diachronous magma injection from different, aligned inlets. The distance between injection points, as well as the activation in time of injection points was varied for each model. Our model results show how the position and activation in time of injection points (which reproduce multiple magma batches in nature) strongly influence model evolution. In the case of synchronous injection at different inlets, the intrusions and associated surface deformation were elongated. Forced folds and annular bounding reverse faults were quite elliptical, and with the main axis of the elongated dome trending sub-parallel to the direction of the magma input points. Model results also indicate that the injection from multiple aligned sources could reproduce the same features of systems associated with planar feeder dikes, thereby suggesting that caution should be taken when trying to infer the feeding areas on the basis of the deformation features observed at the surface or in seismic profiles. Diachronous injection from different injection points showed that the deformation observed at surface does not necessarily reflect the location and/or geometry of their feeders. Most notably, these experiments suggest that coeval magma injection from different sources favor the lateral migration of magma rather than the vertical growth, promoting the development of laterally interconnected intrusions. Recently, some authors (Magee et al., 2014, 2016; Schofield et al., 2015) have suggested that, based on seismic reflection data analysis, interconnected sills and inclined sheets can facilitate the transport of magma over great vertical distances and laterally for large distances. Intrusions and volcanoes fed by sill complexes may thus be laterally offset significantly from the melt source. Our model results strongly support these findings, by reproducing in the laboratory a strong lateral magma migration, and suggesting a possible mechanism. The models also confirmed that lateral magma migration could take place with little or no accompanying surface deformation. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement No. 608553 (Project IMAGE). References: Magee et al., 2014. Basin Research, v. 26, p. 85-105, doi: 10 .1111 /bre.12044. Magee et al., 2016. Geosphere, v. 12, p. 809-841, ISSN: 1553-040X. Schofield et al., 2015. Basin Research, v. 29, p. 41-63, doi:10.1111/bre.12164.

  9. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Cheng-hu; Cao, Guo-Fan; Jiang, Qin, E-mail: Jqin710@vip.sina.com

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} induces MMP-9 expression and secretion to promote RPE cell migration. Black-Right-Pointing-Pointer MAPK activation is not critical for TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer Akt and mTORC1 signaling mediate TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-{alpha}. -- Abstract: Tumor necrosis factor-alpha (TNF-{alpha}) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-{alpha} promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-{alpha}-induced in vitro RPE cell migration. Reversely, exogenously-addedmore » active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-{alpha}-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-{alpha} promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.« less

  10. Matrix metalloproteinase-9 expression in folliculostellate cells of rat anterior pituitary gland.

    PubMed

    Ilmiawati, Cimi; Horiguchi, Kotaro; Fujiwara, Ken; Yashiro, Takashi

    2012-03-01

    Folliculostellate (FS) cells of the anterior pituitary gland express a variety of regulatory molecules. Using transgenic rats that express green fluorescent protein specifically in FS cells, we recently demonstrated that FS cells in vitro showed marked changes in motility, proliferation, and that formation of cellular interconnections in the presence of laminin, a component of the extracellular matrix, closely resembled those observed in vivo. These findings suggested that FS cells express matrix metalloproteinase-9 (MMP-9), which assists their function on laminin. In the present study, we investigate MMP-9 expression in rat anterior pituitary gland and examine its role in motility and proliferation of FS cells on laminin. Immunohistochemistry, RT-PCR, immunoblotting, and gelatin zymography were performed to assess MMP-9 expression in the anterior pituitary gland and cultured FS cells. Real-time RT-PCR was used to quantify MMP-9 expression in cultured FS cells under different conditions and treatments. MMP-9 expression was inhibited by pharmacological inhibitor or downregulated by siRNA and time-lapse images were acquired. A 5-bromo-2'-deoxyuridine assay was performed to analyze the proliferation of FS cells. Our results showed that MMP-9 was expressed in FS cells, that this expression was upregulated by laminin, and that laminin induced MMP-9 secretion by FS cells. MMP-9 inhibition and downregulation did not impair FS motility; however, it did impair the capacity of FS cells to form interconnections and it significantly inhibited proliferation of FS cells on laminin. We conclude that MMP-9 is necessary in FS cell interconnection and proliferation in the presence of laminin.

  11. Effects of Vildagliptin Add-on Insulin Therapy on Nocturnal Glycemic Variations in Uncontrolled Type 2 Diabetes.

    PubMed

    Li, Feng-Fei; Shen, Yun; Sun, Rui; Zhang, Dan-Feng; Jin, Xing; Zhai, Xiao-Fang; Chen, Mao-Yuan; Su, Xiao-Fei; Wu, Jin-Dan; Ye, Lei; Ma, Jian-Hua

    2017-10-01

    To investigate whether vildagliptin add-on insulin therapy improves glycemic variations in patients with uncontrolled type 2 diabetes (T2D) compared to patients with placebo therapy. This was a 24-week, single-center, double-blind, placebo-controlled trial. Inadequately controlled T2D patients treated with insulin therapy were recruited between June 2012 and April 2013. The trial included a 2-week screening period and a 24-week randomized period. Subjects were randomly assigned to a vildagliptin add-on insulin therapy group (n = 17) or a matched placebo group (n = 16). Scheduled visits occurred at weeks 4, 8, 12, 16, 20, and 24. Continuous glucose monitoring (CGM) was performed before and at the endpoint of the study. A total of 33 subjects were admitted, with 1 patient withdrawing from the placebo group. After 24 weeks of therapy, HbA1c values were significantly reduced at the endpoint in the vildagliptin add-on group. CGM data showed that patients with vildagliptin add-on therapy had a significantly lower 24-h mean glucose concentration and mean amplitude of glycemic excursion (MAGE). At the endpoint of the study, patients in the vildagliptin add-on group had a significantly lower MAGE and standard deviation compared to the control patients during the nocturnal period (0000-0600). A severe hypoglycemic episode was not observed in either group. Vildagliptin add-on therapy to insulin has the ability to improve glycemic variations, especially during the nocturnal time period, in patients with uncontrolled T2D.

  12. [The correlation of synuclein-γ and matrix metalloproteinase 9 in breast cancer].

    PubMed

    Chen, Jian; Huang, Shuo; Wu, Ke-jin; Wang, Yong-kun; Jia, Yi-jun; Lu, Yun-shu; Weng, Zi-yi

    2013-07-01

    To evaluate the expression of synuclein-γ (SNCG) and metalloproteinase 9 (MMP-9) both in the invasive ductal breast cancer samples and T47D and T47D(SNCG)- cell lines, to investigate the correlation between SNCG and MMP-9. Totally 96 invasive ductal breast cancer samples (female, mean age of (56 ± 8) years) were collected between June 2009 and June 2012. The expressions of SNCG and MMP-9 were investigated by immunohistochemistry. T47D and SNCG knock down T47D(SNCG)- cell lines were established and SNCG and MMP-9 protein expression were investigated by Western blot and gene expression by real-time PCR. Among 96 samples, 26 (27.1%) of them co-expressed SNCG and MMP-9, 30(31.2%) of them expressed neither SNCG nor MMP-9. The expression of SNCG was correlated with the expression of MMP-9 (r = 0.655, P = 0.000).SNCG mRNA level of T47D cell line was 13.5 fold of T47D(SNCG)- cell line and SNCG protein expression was 2.1 fold. While MMP-9 mRNA level of T47D cell line was 7.3 fold of T47D(SNCG)- cell line and MMP-9 protien expression was 1.6 fold.When SNCG was knocked down, the expression of MMP-9 decreased. SNCG and MMP-9 are significantly correlated with each other in breast cancer. SNCG may promote the invasion and metastasis of breast cancer mediated by up-regulating the expression of MMP-9.

  13. Nephrogenic diabetes insipidus.

    PubMed

    Bockenhauer, D; Bichet, Daniel G

    2017-04-01

    In nephrogenic diabetes insipidus (NDI), the kidney is unable to concentrate urine despite elevated concentrations of the antidiuretic hormone arginine-vasopressin. In congenital NDI, polyuria and polydipsia are present from birth and should be immediately recognized to avoid severe episodes of dehydration. Unfortunately, NDI is still often recognized late after a 'diagnostic odyssey' involving false leads and dangerous treatments.Once diagnosed, appropriate treatment can be started. Moreover, laboratory studies have identified promising new compounds, which may help achieve urinary concentration independent of vasopressin. MAGED2 mutations caused X-linked polyhydramnios with prematurity and a severe but transient form of antenatal Bartter's syndrome.We distinguish two types of hereditary NDI: a 'pure' type with loss of water only and a complex type with loss of water and ions. Mutations in the AVPR2 or AQP2 genes, encoding the vasopressin V2 receptor and the water channel Aquaporin2, respectively, lead to a 'pure' NDI with loss of water but normal conservation of ions. Mutations in genes that encode membrane proteins involved in sodium chloride reabsorption in the thick ascending limb of Henle's loop lead to Bartter syndrome, a complex polyuric-polydipsic disorder often presenting with polyhydramnios. A new variant of this was recently identified: seven families were described with transient antenatal Bartter's syndrome, polyhydramnios and MAGED2 mutations.Multiple compounds have been identified experimentally that may stimulate urinary concentration independently of the vasopressin V2 receptor. These compounds may provide new treatments for patients with X-linked NDI. A plea for early consideration of the diagnosis of NDI, confirmation by phenotypic and/or genetic testing and appropriate adjustment of treatment in affected patients.

  14. VizieR Online Data Catalog: CIII] emission in near & far star-forming galaxies (Rigby+, 2015)

    NASA Astrophysics Data System (ADS)

    Rigby, J. R.; Bayliss, M. B.; Gladders, M. D.; Sharon, K.; Wuyts, E.; Dahle, H.; Johnson, T.; Pena-Guerrero, M.

    2016-03-01

    We measure the equivalent widths of Lyα and the C III] doublet in the rest-frame UV spectra of 11 gravitationally lensed galaxies at 1.6

  15. A brief mindfulness intervention reduces unhealthy eating when hungry, but not the portion size effect.

    PubMed

    Marchiori, David; Papies, Esther K

    2014-04-01

    The present research examined the effects of a mindfulness-based intervention to foster healthy eating. Specifically, we tested whether a brief mindfulness manipulation can prevent the portion size effect, and reduce overeating on unhealthy snacks when hungry. 110 undergraduate participants (MAge=20.9±2.3; MBMI=22.3±2.5) were served a small or a large portion of chocolate chip cookies after listening to an audio book or performing a mindfulness exercise (i.e., body scan). Current level of hunger was assessed unobtrusively on a visual analog scale before the eating situation. Calorie intake from chocolate chip cookies. When presented with a large compared to a small portion, participants consumed more cookies (+83kcal). This was not affected by the mindfulness intervention or by hunger. However, while control participants ate more unhealthy food when hungry than when not hungry (+67kcal), participants in the mindfulness condition did not (+1kcal). Findings confirm the prevalence and robustness of the portion size effect and suggest that it may be independent from awareness of internal cues. Prevention strategies may benefit more from targeting awareness of the external environment. However, mindfulness-based interventions may be effective to reduce effects of hunger on unhealthy food consumption. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Toll-like receptor 9 gene expression in the post-thrombotic syndrome, residual thrombosis and recurrent deep venous thrombosis: A case-control study.

    PubMed

    Cheung, Y Whitney; Bouman, Annemieke C; Castoldi, Elisabetta; Wielders, Simone J; Spronk, Henri M H; Ten Cate, Hugo; Ten Cate-Hoek, Arina J; Ten Wolde, Marije

    2016-04-01

    Animal models suggest that toll-like receptor 9 (TLR9) promotes thrombus resolution after acute deep venous thrombosis (DVT). We hypothesized that TLR9 expression is lower in patients with post-thrombotic syndrome (PTS) and investigated the role of TLR9 in residual thrombosis (RT) and recurrence. Patients with a history of DVT with PTS (cases, n=30) and without PTS after minimal 24 months follow-up (controls, n=30) were selected. Healthy individuals (HI, n=29) without DVT were included as reference. TLR9 mRNA expression in leukocytes was determined by qPCR and normalized to the housekeeping succinate dehydrogenase subunit A gene using the ΔCt method. Sub analyses were performed to explore the TLR9 expression in patients with and without RT and multiple DVT episodes. The median TLR9 expression was 0.45 (interquartile range 0.31 to 0.93), 0.39 (0.25 to 0.69) and 0.62 (0.32 to 0.75) in cases, controls and HI respectively (p=0.61). The median TLR9 expression was 0.39 (0.26 to 0.51) in patients with RT compared to 0.55 (0.30 to 0.86, p=0.13) in those without. The median TLR9 expression was significantly lower in patients who had one DVT compared to patients with recurrent DVT, 0.37 (0.23 to 0.63) versus 0.55 (0.43 to 0.96) respectively (p<0.01). No significant difference in TLR9 expression was found between cases, controls and HI. However TLR9 expression seems lower in individuals with DVT and RT, albeit not significant. Interestingly, TLR9 might play a role in recurrent DVT, as the TLR9 expression was significantly higher in patients with recurrent DVT. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. miR-34a Modulates Angiotensin II-Induced Myocardial Hypertrophy by Direct Inhibition of ATG9A Expression and Autophagic Activity

    PubMed Central

    Huang, He; Ye, Jing; Pan, Wei; Zhong, Yun; Cheng, Chuanfang; You, Xiangyu; Liu, Benrong; Xiong, Longgen; Liu, Shiming

    2014-01-01

    Cardiac hypertrophy is characterized by thickening myocardium and decreasing in heart chamber volume in response to mechanical or pathological stress, but the underlying molecular mechanisms remain to be defined. This study investigated altered miRNA expression and autophagic activity in pathogenesis of cardiac hypertrophy. A rat model of myocardial hypertrophy was used and confirmed by heart morphology, induction of cardiomyocyte autophagy, altered expression of autophagy-related ATG9A, LC3 II/I and p62 proteins, and decrease in miR-34a expression. The in vitro data showed that in hypertrophic cardiomyocytes induced by Ang II, miR-34a expression was downregulated, whereas ATG9A expression was up-regulated. Moreover, miR-34a was able to bind to ATG9A 3′-UTR, but not to the mutated 3′-UTR and inhibited ATG9A protein expression and autophagic activity. The latter was evaluated by autophagy-related LC3 II/I and p62 levels, TEM, and flow cytometry in rat cardiomyocytes. In addition, ATG9A expression induced either by treatment of rat cardiomyocytes with Ang II or ATG9A cDNA transfection upregulated autophagic activity and cardiomyocyte hypertrophy in both morphology and expression of hypertrophy-related genes (i.e., ANP and β-MHC), whereas knockdown of ATG9A expression downregulated autophagic activity and cardiomyocyte hypertrophy. However, miR-34a antagonized Ang II-stimulated myocardial hypertrophy, whereas inhibition of miR-34a expression aggravated Ang II-stimulated myocardial hypertrophy (such as cardiomyocyte hypertrophy-related ANP and β-MHC expression and cardiomyocyte morphology). This study indicates that miR-34a plays a role in regulation of Ang II-induced cardiomyocyte hypertrophy by inhibition of ATG9A expression and autophagic activity. PMID:24728149

  18. An experimental test of the effect of acute anxious arousal and anxiety sensitivity on negative reinforcement smoking.

    PubMed

    Farris, Samantha G; Zvolensky, Michael J

    2016-07-01

    Although anxiety sensitivity has been reliably associated with smoking-anxiety comorbidity, there has not been a test of whether this construct moderates the effect of acute anxious arousal on actual smoking behavior. The present study utilized an experimental design to test the moderating role of anxiety sensitivity on laboratory-induced anxious arousal in terms of smoking urges and topography (puff style). Participants were adult daily smokers (n=90; Mage=43.6 SD =9.7); average 15.8 cigarettes per day). A between-subjects design was used; participants were randomly assigned to complete a biological challenge procedure consisting of either a single vital capacity inhalation of 35% carbon dioxide (CO2)-enriched air mixture or compressed room air. Smoking urges and smoking topography (puff behavior) were assessed before and after the challenge. Results revealed a significant interaction between anxiety sensitivity and experimental condition (b=-9.96, p=0.014), such that high anxiety sensitive smokers exposed to 35% CO2-enriched air reported significantly lower levels of smoking urges, relative to low anxiety sensitive smokers; the conditional effect of anxiety sensitivity was not observed for the room air condition. There were no significant interaction effects of experimental manipulation by anxiety sensitivity for any of the smoking topography outcomes. The present results suggest for smokers with higher levels of anxiety sensitivity, the acute experience of anxious arousal is related to decreased subjective smoking urges. These data invite future research to explore the reasons for dampened smoking urges, including cardiorespiratory symptom severity. © The Author(s) 2016.

  19. Arsenic silences hepatic PDK4 expression through activation of histone H3K9 methylatransferase G9a

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Xi; Wu, Jianguo; Choiniere, Jonathan

    It is well established that increased liver cancer incidence is strongly associated with epigenetic silencing of tumor suppressor genes; the latter is contributed by the environmental exposure to arsenic. Pyruvate dehydrogenase kinase 4 (PDK4) is a mitochondrial protein that regulates the TCA cycle. However, the epigenetic mechanisms mediated by arsenic to control PDK4 expression remain elusive. In the present study, we showed that histone methyltransferase G9a- and Suv39H-mediated histone H3 lysine 9 (H3K9) methylations contributed to PDK4 silencing in hepatic cells. The PDK4 expression was induced by G9a inhibitor BRD4770 (BRD) and Suv39H inhibitor Chaetocin (CHA). In contrast, arsenic exposuremore » decreased PDK4 expression by inducing G9a and increasing H3K9 di- and tri-methylations levels (H3K9me2/3). In addition, arsenic exposure antagonizes the effect of BRD by enhancing the enrichment of H3K9me2/3 in the PKD4 promoter. Moreover, knockdown of G9a using siRNA induced PDK4 expression in HCC cells. Furthermore, arsenic decreased hepatic PDK4 expression as well as diminished the induction of PDK4 by BRD in mouse liver and hepatocytes. Overall, the results suggest that arsenic causes aberrant repressive histone modification to silence PDK4 in both HCC cells and in mouse liver. - Graphical abstract: Schematic showing arsenic-mediated epigenetic pathway that inhibits PDK4 expression. (A) BRD induces PDK4 expression by decreasing G9a protein and histone H3K9me2 and H3K9me3 levels as well as diminishing their recruitment to the PDK4 promoter. (B) Arsenic counteracts the effect of BRD by increasing histone H3K9me2 and H3K9me3 levels as well as enhancing their enrichment to the PDK4 promoter. Display Omitted - Highlights: • Histone methyltrasferase G9a inhibitor BRD induces PDK4 expression. • Arsenic decreases PDK4 expression and increases H3K9me2 and me3 levels. • Arsenic enhances H3K9me2/me3 enrichment in the PDK4 promoter. • Arsenic antagonizes the activation of PDK4 by BRD.« less

  20. Motivational Cluster Profiles of Adolescent Athletes: An Examination of Differences in Physical-Self Perception

    PubMed Central

    Çağlar, Emine; Aşçı, F. Hülya

    2010-01-01

    The primary purpose of the present study was to identify motivational profiles of adolescent athletes using cluster analysis in non-Western culture. A second purpose was to examine relationships between physical self-perception differences of adolescent athletes and motivational profiles. One hundred and thirty six male (Mage = 17.46, SD = 1.25 years) and 80 female adolescent athletes (Mage = 17.61, SD = 1.19 years) from a variety of team sports including basketball, soccer, volleyball, and handball volunteered to participate in this study. The Sport Motivation Scale (SMS) and Physical Self-Perception Profile (PSPP) were administered to all participants. Hierarchical cluster analysis revealed a four-cluster solution for this sample: amotivated, low motivated, moderate motivated, and highly motivated. A 4 x 5 (Cluster x PSPP Subscales) MANOVA revealed no significant main effect of motivational clusters on physical self-perception levels (p > 0.05). As a result, findings of the present study showed that motivational types of the adolescent athletes constituted four different motivational clusters. Highly and moderate motivated athletes consistently scored higher than amotivated athletes on the perceived sport competence, physical condition, and physical self-worth subscales of PSPP. This study identified motivational profiles of competitive youth-sport participants. Key points Highly motivated athletes have a tendency to perceive themselves competent in psychomotor domains as compared to the amotivated athletes As the athletes feel more competent in psychomotor domain, they are more intrinsically motivated. The information about motivational profiles of adolescent athletes could be used for developing strategies and interventions designed to improve the strength and quality of sport participants’ motivation. PMID:24149690

  1. Helping motivation and well-being of chronic pain couples: a daily diary study.

    PubMed

    Kindt, Sara; Vansteenkiste, Maarten; Loeys, Tom; Goubert, Liesbet

    2016-07-01

    Receiving support from a romantic partner may yield benefits for individuals with chronic pain (ICPs), but may also carry unintended side effects. The conditions under which partner support provision yields (mal)adaptive effects deserve greater attention. Grounded in Self-determination theory, partners may provide help for autonomous or volitional (eg, enjoyment, full commitment) or rather controlled or pressured (eg, avoiding guilt and criticism) motives. This study examined associations between day-to-day fluctuations in partners' type of helping motivation and several outcomes, among partners and ICPs. Seventy couples, with 1 partner having chronic pain (75.7% female), completed a diary for 14 consecutive days. Daily helping motivation was assessed together with daily affect, relational conflict, and relationship-based need satisfaction. Partners (Mage = 55.14) additionally reported on daily helping exhaustion, whereas ICPs (Mage = 54.71) reported on daily pain intensity, disability, satisfaction with received help, and amount of received help. Providing autonomous help related to improvements in partners' affective (eg, positive affect), relational (eg, conflict), and help-specific (eg, exhaustion) functioning, which were accounted for by improvements in daily relationship-based psychological need satisfaction. Similarly, daily autonomously motivated help yielded a direct (ie, relational conflict; perceived amount of help) or indirect (ie, positive and negative affects; relational conflict; satisfaction with help, disability) contribution in explaining ICP outcomes-through improvements in ICPs' relationship-based psychological need satisfaction. Findings highlight the importance of a motivational and dynamic perspective on help provision within chronic pain couples. Considering reasons why a partner provides help is important to understand when partners and ICPs may benefit from daily support.

  2. High diagnostic yield of clinical exome sequencing in Middle Eastern patients with Mendelian disorders.

    PubMed

    Yavarna, Tarunashree; Al-Dewik, Nader; Al-Mureikhi, Mariam; Ali, Rehab; Al-Mesaifri, Fatma; Mahmoud, Laila; Shahbeck, Noora; Lakhani, Shenela; AlMulla, Mariam; Nawaz, Zafar; Vitazka, Patrik; Alkuraya, Fowzan S; Ben-Omran, Tawfeg

    2015-09-01

    Clinical exome sequencing (CES) has become an increasingly popular diagnostic tool in patients with heterogeneous genetic disorders, especially in those with neurocognitive phenotypes. Utility of CES in consanguineous populations has not yet been determined on a large scale. A clinical cohort of 149 probands from Qatar with suspected Mendelian, mainly neurocognitive phenotypes, underwent CES from July 2012 to June 2014. Intellectual disability and global developmental delay were the most common clinical presentations but our cohort displayed other phenotypes, such as epilepsy, dysmorphism, microcephaly and other structural brain anomalies and autism. A pathogenic or likely pathogenic mutation, including pathogenic CNVs, was identified in 89 probands for a diagnostic yield of 60%. Consanguinity and positive family history predicted a higher diagnostic yield. In 5% (7/149) of cases, CES implicated novel candidate disease genes (MANF, GJA9, GLG1, COL15A1, SLC35F5, MAGE4, NEUROG1). CES uncovered two coexisting genetic disorders in 4% (6/149) and actionable incidental findings in 2% (3/149) of cases. Average time to diagnosis was reduced from 27 to 5 months. CES, which already has the highest diagnostic yield among all available diagnostic tools in the setting of Mendelian disorders, appears to be particularly helpful diagnostically in the highly consanguineous Middle Eastern population.

  3. The development of a theoretically driven generic measure of quality of life for children aged 6-12 years: a preliminary report.

    PubMed

    Eiser, C; Vance, Y H; Seamark, D

    2000-11-01

    To report the development and psychometric properties of a generic computer-delivered measure of quality of life (QoL) suitable for children aged 6-12 years: the Exqol. The theoretical model adopted is based on an assumption that poorer QoL is the result of discrepancies between an individual's actual ('like me') and ideal self ('how I would like to be'). The Exqol consists of 12 pictures, each of which is rated twice; first in terms of 'like me' and second as 'I would like to be'. The Exqol is delivered using a Macintosh Powerbook and takes approximately 20 min to complete. Data are reported for 58 children with asthma (Mage = 8.95 years) and 69 healthy children (Mage = 749 years). In order to determine validity of the Exqol, children with asthma also completed the Childhood Asthma Questionnaire (CAQ) and their mothers completed a measure of child vulnerability and caregiver QoL. Higher discrepancies were found for children with asthma compared with healthy children (P < 0.05). For children with asthma, significant correlations were found between discrepancy scores and two of the four subscales of the CAQ. Children who rated their asthma to be more severe also had higher discrepancy scores (P < 0.05). The Exqol has acceptable internal reliability and validity and distinguishes between children with asthma and healthy children. These data provide preliminary support for the theoretical assumption that QoL reflects perceived discrepancies between an individual's actual and ideal self. Methodological refinements to the Exqol are suggested.

  4. Perception of partner sexual history: Effects on safe-sex intentions.

    PubMed

    Cornelius, Talea; Kershaw, Trace

    2017-07-01

    Sexual intercourse is a dyadic activity, and intentions to engage in safe sex vary across partners. Because pregnant and newly parenting adolescents and young adults are at high risk for sexually transmitted infections (STIs), it is important to understand sexual decision-making in this population. This cross-sectional study examined how participants' own risk behavior and their partners' risk behavior influence perceptions of partner risk, and the impact of risk perceptions on condom use intentions and monogamy intentions in 296 pregnant adolescent and young adult couples (MAgeFemale = 18.71 years; MAgeMale = 21.33 years). Participants' behavior and their partners' behavior both related to increased perceptions of partner risk. Male participants' perceptions were more strongly influenced by female partners' behavior than participants' own behavior. Perceiving a partner as having a history of more risk behaviors trended toward a negative relationship with condom use intentions and monogamy intentions. For females, more previous sex partners related negatively to condom use intentions and positively to monogamy intentions. Having a male partner with more previous sex partners related positively to condom use intentions and monogamy intentions. Perceptions of partner risk did not significantly relate to condom use intentions and monogamy intentions, however, trends suggest that risk perception could reflect similarity bias and ongoing risk engagement. Differences in partner perception by gender suggest that females may communicate more openly about risks. Interventions to reduce STI transmission in couples should work to interrupt trajectories of risky behavior and enhance risk communication. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. Computerization of the standard corsi block-tapping task affects its underlying cognitive concepts: a pilot study.

    PubMed

    Claessen, Michiel H G; van der Ham, Ineke J M; van Zandvoort, Martine J E

    2015-01-01

    The tablet computer initiates an important step toward computerized administration of neuropsychological tests. Because of its lack of standardization, the Corsi Block-Tapping Task could benefit from advantages inherent to computerization. This task, which requires reproduction of a sequence of movements by tapping blocks as demonstrated by an examiner, is widely used as a representative of visuospatial attention and working memory. The aim was to validate a computerized version of the Corsi Task (e-Corsi) by comparing recall accuracy to that on the standard task. Forty university students (Mage = 22.9 years, SD = 2.7 years; 20 female) performed the standard Corsi Task and the e-Corsi on an iPad 3. Results showed higher accuracy in forward reproduction on the standard Corsi compared with the e-Corsi, whereas backward performance was comparable. These divergent performance patterns on the 2 versions (small-to-medium effect sizes) are explained as a result of motor priming and interference effects. This finding implies that computerization has serious consequences for the cognitive concepts that the Corsi Task is assumed to assess. Hence, whereas the e-Corsi was shown to be useful with respect to administration and registration, these findings also stress the need for reconsideration of the underlying theoretical concepts of this task.

  6. Sending Nudes: Sex, Self-Rated Mate Value, and Trait Machiavellianism Predict Sending Unsolicited Explicit Images

    PubMed Central

    March, Evita; Wagstaff, Danielle L.

    2017-01-01

    Modern dating platforms have given rise to new dating and sexual behaviors. In the current study, we examine predictors of sending unsolicited explicit images, a particularly underexplored online sexual behavior. The aim of the current study was to explore the utility of dark personality traits (i.e., narcissism, Machiavellianism, psychopathy, and sadism) and self-rated mate value in predicting attitudes toward and behavior of sending unsolicited explicit images. Two hundred and forty participants (72% female; Mage = 25.96, SD = 9.79) completed an online questionnaire which included a measure of self-rated mate value, a measure of dark personality traits, and questions regarding sending unsolicited explicit images (operationalized as the explicit image scale). Men, compared to women, were found to have higher explicit image scale scores, and both self-rated mate value and trait Machiavellianism were positive predictors of explicit image scale scores. Interestingly, there were no significant interactions between sex and these variables. Further, Machiavellianism mediated all relationships between other dark traits and explicit image scale scores, indicating this behavior is best explained by the personality trait associated with behavioral strategies. In sum, these results provide support for the premise that sending unsolicited explicit images may be a tactic of a short-term mating strategy; however, future research should further explore this claim. PMID:29326632

  7. Profiling Lgals9 splice variant expression at the fetal-maternal interface: implications in normal and pathological human pregnancy.

    PubMed

    Heusschen, Roy; Freitag, Nancy; Tirado-González, Irene; Barrientos, Gabriela; Moschansky, Petra; Muñoz-Fernández, Raquel; Leno-Durán, Ester; Klapp, Burghard F; Thijssen, Victor L J L; Blois, Sandra M

    2013-01-01

    Disruption of fetal-maternal tolerance mechanisms can contribute to pregnancy complications, including spontaneous abortion. Galectin-9 (LGALS9), a tandem repeat lectin associated with immune modulation, is expressed in the endometrium during the mid and late secretory phases and in decidua during human early pregnancy. However, the role of LGALS9 during pregnancy remains poorly understood. We used real-time PCR and immunohistochemical staining to analyze the expression of Lgals9/LGALS9 during mouse gestation as well as in human tissues obtained from normal pregnancy and spontaneous abortions. In mice, three Lgals9 splice variants were detected, the expression of which was differentially regulated during gestation. Furthermore, decidual Lgals9 expression was deregulated in a mouse model of spontaneous abortion, whereas placental levels did not change. We further found that the LGALS9 D5 isoform suppresses interferon gamma production by decidual natural killer cells. In human patients, six Lgals9 splice variants were detected, and a decrease in Lgals9 D5/10 was associated with spontaneous abortion. Altogether, these results show a differential regulation of Lgals9 isoform expression during normal and pathological pregnancies and designate Lgals9 as a potential marker for adverse pregnancy outcomes.

  8. Inflammation Stimulates the Expression of PCSK9

    PubMed Central

    Feingold, Kenneth R.; Moser, Arthur H.; Shigenaga, Judy K.; Patzek, Sophie M.; Grunfeld, Carl

    2008-01-01

    Inflammation induces marked changes in lipid and lipoprotein metabolism. Proprotein convertase subtilisin kexin 9 (PCSK9) plays an important role in regulating LDL receptor degradation. Here we demonstrate that LPS decreases hepatic LDL receptor protein but at the same time hepatic LDL receptor mRNA levels are not decreased. We therefore explored the effect of LPS on PCSK9 expression. LPS results in a marked increase in hepatic PCSK9 mRNA levels (4 hours-2.5 fold increase; 38 hours-12.5 fold increase). The increase in PCSK9 is a sensitive response with 1 ug LPS inducing a ½ maximal response. LPS also increased PCSK9 expression in the kidney. Finally, zymosan and turpentine, other treatments that induce inflammation, also stimulated hepatic expression of PCSK9. Thus, inflammation stimulates PCSK9 expression leading to increased LDL receptor degradation and decreasing LDL receptors thereby increasing serum LDL, which could have beneficial effects on host defense. PMID:18638454

  9. SOX9 regulates ERBB signalling in pancreatic cancer development.

    PubMed

    Grimont, Adrien; Pinho, Andreia V; Cowley, Mark J; Augereau, Cécile; Mawson, Amanda; Giry-Laterrière, Marc; Van den Steen, Géraldine; Waddell, Nicola; Pajic, Marina; Sempoux, Christine; Wu, Jianmin; Grimmond, Sean M; Biankin, Andrew V; Lemaigre, Frédéric P; Rooman, Ilse; Jacquemin, Patrick

    2015-11-01

    The transcription factor SOX9 was recently shown to stimulate ductal gene expression in pancreatic acinar-to-ductal metaplasia and to accelerate development of premalignant lesions preceding pancreatic ductal adenocarcinoma (PDAC). Here, we investigate how SOX9 operates in pancreatic tumourigenesis. We analysed genomic and transcriptomic data from surgically resected PDAC and extended the expression analysis to xenografts from PDAC samples and to PDAC cell lines. SOX9 expression was manipulated in human cell lines and mouse models developing PDAC. We found genetic aberrations in the SOX9 gene in about 15% of patient tumours. Most PDAC samples strongly express SOX9 protein, and SOX9 levels are higher in classical PDAC. This tumour subtype is associated with better patient outcome, and cell lines of this subtype respond to therapy targeting epidermal growth factor receptor (EGFR/ERBB1) signalling, a pathway essential for pancreatic tumourigenesis. In human PDAC, high expression of SOX9 correlates with expression of genes belonging to the ERBB pathway. In particular, ERBB2 expression in PDAC cell lines is stimulated by SOX9. Inactivating Sox9 expression in mice confirmed its role in PDAC initiation; it demonstrated that Sox9 stimulates expression of several members of the ERBB pathway and is required for ERBB signalling activity. By integrating data from patient samples and mouse models, we found that SOX9 regulates the ERBB pathway throughout pancreatic tumourigenesis. Our work opens perspectives for therapy targeting tumourigenic mechanisms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  10. Intimacy, sexual satisfaction, and sexual distress in vulvodynia couples: An observational study.

    PubMed

    Bois, Katy; Bergeron, Sophie; Rosen, Natalie; Mayrand, Marie-Hélène; Brassard, Audrey; Sadikaj, Gentiana

    2016-06-01

    Vulvodynia is a prevalent idiopathic pain condition with deleterious consequences for the sexuality of affected women and their spouses. Intimacy has been identified as a facilitator of adjustment to health difficulties in couples. Two components of intimacy were examined among couples with vulvodynia-empathic response and disclosure-in relation to their sexual satisfaction and sexual distress. Using an observational design, 50 women (Mage = 24.50 years, SD = 4.03) diagnosed with vulvodynia and their spouses (Mage = 26.10 years, SD = 5.70) participated in a filmed discussion focusing on the impact of vulvodynia on their lives. Empathic response and disclosure were assessed by a trained observer and self-reported by participants after engaging in the discussion. The actor-partner interdependence model guided the data analyses. Women's and spouses' higher observed and perceived empathic responses were associated with their own and their partners' greater sexual satisfaction. Women's and spouses' higher perceived disclosures were associated with their own and their partners' greater sexual satisfaction. Women's and spouses' higher observed empathic responses were associated with their own lower sexual distress. Women's higher observed empathic responses were associated with their spouses' lower sexual distress. Women and spouses' perceived greater empathic responses were associated with their own lower sexual distress. Women's and spouses' greater perceived disclosures during the discussion were associated with their own and their partners' lower sexual distress. Promoting empathic response and disclosure through couple interventions may buffer against the sexual distress and sexual dissatisfaction of couples coping with vulvodynia. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  11. How Nurse Gender Influences Patient Priority Assignments in U.S. Emergency Departments

    PubMed Central

    Vigil, Jacob Miguel; Coulombe, Patrick; Alcock, Joe; Stith, Sarah See; Kruger, Eric; Cichowski, Sara

    2016-01-01

    The goals of this study were to compare whether emergency department (ED) patients’ pain intensity (PI) is measured differently by male and female nurses and to determine whether PI, heart rate (HR) and respiratory rate (RR) we’re used to prioritize patient urgency differently by male and female nurses. The associations between patients’ PI|HR|RR and the Emergency Severity Index (ESI) scores they were assigned by attending nurses were analyzed using a national database of electronic medical records of U.S. Veterans Affairs ED patients from 2008 to 2012. A total of 129,991 patients presenting for emergency care (Mage = 59.5, 92% males) and their triage nurses (n = 774, Mage = 47.5, 18% males) were analyzed, resulting in a total of 359,642 patient/provider interactions. Patients’ PI did not differ by nurse’s gender; however a cross-classified mixed-effects model showed that nurse gender influenced how PI and RR measurements informed the ESI levels that male patients received. Higher PI levels were associated with more urgent (higher priority) ESI levels by female nurses, yet less urgent ESI levels by male nurses. In contrast, male patients with high RR received more urgent ESI levels by male nurses, while nurse gender did not influence ESI assignments for female patients. These findings show that ED patients receive disparate treatment based on inherent characteristics of their triage nurses, and more standardized (e.g., automated) protocols that can account for implicit social factors on healthcare practice for reliably assessing and prioritizing ED patients may be currently warranted. PMID:28187101

  12. Adolescents' Sedentary Behaviors in Two European Cities.

    PubMed

    Aibar Solana, Alberto; Bois, Julien E; Zaragoza, Javier; Bru, Noëlle; Paillard, Thierry; Generelo, Eduardo

    2015-01-01

    The aim of this study was to determine and compare the correlates of objective sedentary behavior (SB) and nonschool self-reported SB in adolescents from 2 midsized cities, 1 in France (Tarbes) and 1 in Spain (Huesca). Stability of objective SB and nonschool self-reported SB were also assessed at different time points during 1 academic year. Starting with a total of 829 participants and after applying inclusion criteria, objective SB was assessed for 646 adolescents (Mage = 14.30 ± 0.71 years) with GT3X accelerometers for 7 days at 2 time points. Nonschool self-reported SB was measured for 781 adolescents (Mage = 14.46 ± 0.76 years) at 3 time points by means of a questionnaire. Data were analyzed using multiple regression analysis. Gender and ambient temperature emerged as the main statistically significant correlates in all objective SB models, showing higher objective SB levels in girls and lower objective SB levels when ambient temperature was higher. According to nonschool self-reported SB, a gender effect was found in almost all behaviors. Whereas boys spent more time playing with video games as well as games on their mobile phones, girls spent more time studying and using their computers and mobile phones to communicate with each other. The findings showed a statistically significant city effect on study time (Huesca > Tarbes) and video games and telephone communication time (Tarbes > Huesca). Nonschool self-reported SB patterns were different in Huesca and Tarbes. Intervention programs should be adapted to target the reduction of adolescents' SB according to different contexts.

  13. Early age alcohol use and later alcohol problems in adolescents: individual and peer mediators in a bi-national study.

    PubMed

    Mason, W Alex; Toumbourou, John W; Herrenkohl, Todd I; Hemphill, Sheryl A; Catalano, Richard F; Patton, George C

    2011-12-01

    This paper examines whether there is cross-national similarity in the longitudinal relationship between early age alcohol use and adolescent alcohol problems. Potential mechanisms underlying this relationship also are examined, testing adolescent alcohol use, low self-regulation, and peer deviance as possible mediators. Students (N = 1,945) participating in the International Youth Development Study, a longitudinal panel survey study, responded to questions on alcohol use and influencing factors, and were followed annually over a 3-year period from 2002 to 2004 (98% retention rate). State-representative, community student samples were recruited in grade 7 in Washington State, United States (US, n = 961, 78% of those eligible; Mage = 13.09, SD = .44) and Victoria, Australia (n = 984, 76% of those eligible; Mage = 12.93, SD = .41). Analyses were conducted using multiple-group structural equation modeling. In both states, early age alcohol use (age 13) had a small but statistically significant association with subsequent alcohol problems (age 15). Overall, there was little evidence for mediation of early alcohol effects. Low self-regulation prospectively predicted peer deviance, alcohol use, and alcohol problems in both states. Peer deviance was more positively related to alcohol use and low self-regulation among students in Victoria compared to students in Washington State. The small but persistent association of early age alcohol use with alcohol problems across both samples is consistent with efforts to delay alcohol initiation to help prevent problematic alcohol use. Self-regulation was an important influence, supporting the need to further investigate the developmental contribution of neurobehavioral disinhibition.

  14. A Low Glycaemic Index Diet Incorporating Isomaltulose Is Associated with Lower Glycaemic Response and Variability, and Promotes Fat Oxidation in Asians.

    PubMed

    Henry, Christiani Jeyakumar; Kaur, Bhupinder; Quek, Rina Yu Chin; Camps, Stefan Gerardus

    2017-05-09

    Low glycaemic index (GI) foods minimize large blood glucose fluctuations and have been advocated to enhance fat oxidation and may contribute to weight management. We determined whether the inclusion of isomaltulose compared to sucrose in a low/high GI meal sequence can modulate the glycaemic response and substrate oxidation in an Asian population. Twenty Chinese men (body mass index (BMI): 17-28 kg/m²) followed a 24 h low GI (isomaltulose, Palatinose TM ) or high GI (sucrose) diet in a randomized double-blind, controlled cross-over design. Treatment meals included dinner (day 1), breakfast, lunch, and snack (day 2). Continuous glucose monitoring provided incremental area under the curve (iAUC) and mean amplitude of glycaemic excursion (MAGE) and 10 h indirect calorimetry (whole body calorimeter) (day 2) provided energy expenditure and substrate oxidation. Our results demonstrated that the low GI diet resulted in lower 24 h glucose iAUC (502.5 ± 231.4 vs. 872.6 ± 493.1 mmol/L; p = 0.002) and lower 24 h glycaemic variability (MAGE: 1.67 ± 0.53 vs. 2.68 ± 1.13 mmol/L; p < 0.001). Simultaneously, 10 h respiratory quotient increased more during high GI ( p = 0.014) and fat oxidation was higher after low GI breakfast ( p = 0.026), lunch ( p < 0.001) and snack ( p = 0.013). This indicates that lower GI mixed meals incorporating isomaltulose are able to acutely reduce the glycaemic response and variability and promote fat oxidation.

  15. Validity and reliability of International Physical Activity Questionnaire-Short Form in Chinese youth.

    PubMed

    Wang, Chao; Chen, Peijie; Zhuang, Jie

    2013-12-01

    The psychometric profiles of the widely used International Physical Activity Questionnaire-Short Form (IPAQ-SF) in Chinese youth have not been reported. The purpose of this study was to examine the validity and reliability of the IPAQ-SF using a sample of Chinese youth. One thousand and twenty-one youth (M(age) = 14.26 +/- 1.63 years, 52.8% boys) from 11 cities in China wore accelerometers for 7 consecutive days and completed the IPAQ-SF on the 8th day to recall their physical activity (PA) during accelerometer-wearing days. A subsample of 92 youth (M(age) = 15.90 +/- 1.35 years, 46.7% boys) completed the IPAQ-SF again a week later to recall their PA during accelerometer-wearing days. Differences in PA estimated by the IPAQ-SF and accelerometer were examined by paired-sample t test. Spearman correlation coefficients were used to examine the correlation between the IPAQ-SF and accelerometer. Test-retest reliability of the IPAQ-SF was determined by the intraclass correlation coefficient (ICC). Compared with accelerometer, the IPAQ-SF overestimated sedentary time, moderate PA (MPA), vigorous PA (VPA), and moderate-to-vigorous PA (MVPA). Correlations between PA (total PA, MPA, VPA, and MVPA) and sedentary time measured by 2 instruments ranged from "none" to "low" (p = .08-.31). Test-retest ICC of the IPAQ-SF ranged from "moderate" to "high" (ICC = .43-.83), except for sitting in boys (ICC = .06), sitting for the whole sample (ICC = .32), and VPA in girls (ICC = .35). The IPAQ-SF was not a valid instrument for measuring PA and sedentary behavior in Chinese youth.

  16. A Low Glycaemic Index Diet Incorporating Isomaltulose Is Associated with Lower Glycaemic Response and Variability, and Promotes Fat Oxidation in Asians

    PubMed Central

    Henry, Christiani Jeyakumar; Kaur, Bhupinder; Quek, Rina Yu Chin; Camps, Stefan Gerardus

    2017-01-01

    Low glycaemic index (GI) foods minimize large blood glucose fluctuations and have been advocated to enhance fat oxidation and may contribute to weight management. We determined whether the inclusion of isomaltulose compared to sucrose in a low/high GI meal sequence can modulate the glycaemic response and substrate oxidation in an Asian population. Twenty Chinese men (body mass index (BMI): 17–28 kg/m2) followed a 24 h low GI (isomaltulose, PalatinoseTM) or high GI (sucrose) diet in a randomized double-blind, controlled cross-over design. Treatment meals included dinner (day 1), breakfast, lunch, and snack (day 2). Continuous glucose monitoring provided incremental area under the curve (iAUC) and mean amplitude of glycaemic excursion (MAGE) and 10 h indirect calorimetry (whole body calorimeter) (day 2) provided energy expenditure and substrate oxidation. Our results demonstrated that the low GI diet resulted in lower 24 h glucose iAUC (502.5 ± 231.4 vs. 872.6 ± 493.1 mmol/L; p = 0.002) and lower 24 h glycaemic variability (MAGE: 1.67 ± 0.53 vs. 2.68 ± 1.13 mmol/L; p < 0.001). Simultaneously, 10 h respiratory quotient increased more during high GI (p = 0.014) and fat oxidation was higher after low GI breakfast (p = 0.026), lunch (p < 0.001) and snack (p = 0.013). This indicates that lower GI mixed meals incorporating isomaltulose are able to acutely reduce the glycaemic response and variability and promote fat oxidation. PMID:28486426

  17. Galectin-9 as a prognostic factor with antimetastatic potential in breast cancer.

    PubMed

    Irie, Akemi; Yamauchi, Akira; Kontani, Keiichi; Kihara, Minoru; Liu, Dage; Shirato, Yukako; Seki, Masako; Nishi, Nozomu; Nakamura, Takanori; Yokomise, Hiroyasu; Hirashima, Mitsuomi

    2005-04-15

    Galectin-9, a member of the beta-galactoside-binding galectin family, induces aggregation of certain cell types. We assessed the contribution of galectin-9 to the aggregation of breast cancer cells as well as the relation between galectin-9 expression in tumor tissue and distant metastasis in patients with breast cancer. Subclones of MCF-7 breast cancer cells with high or low levels of galectin-9 expression were established and either cultured on plastic dishes or transplanted into nude mice. The tumors of 84 patients with breast cancer were tested for galectin-9 expression by immunohistochemistry. The patients were followed up for 14 years. MCF-7 subclones with a high level of galectin-9 expression formed tight clusters during proliferation in vitro, whereas a subclone (K10) with the lowest level of galectin-9 expression did not. However, K10 cells stably transfected with a galectin-9 expression vector aggregated in culture and in nude mice. Ectopic expression of galectin-9 also reduced MCF-7 cell adhesion to extracellular matrix proteins. Tumors of 42 of the 84 patients were galectin-9 positive, and those of 19 of the 21 patients with distant metastasis were galectin-9 negative. None of the 13 patients with galectin-9-positive tumors and lymph node metastasis up to level II manifested distant metastasis. The cumulative disease-free survival ratio for galectin-9-positive patients was more favorable than that for the galectin-9-negative group (P < 0.0001). Multivariate analysis revealed that galectin-9 status influenced distant metastasis independently of and to a greater extent than lymph node metastasis. Galectin-9 is a possible prognostic factor with antimetastatic potential in breast cancer.

  18. Sperm associated antigen 9 (SPAG9) a promising therapeutic target of ovarian carcinoma.

    PubMed

    Jagadish, Nirmala; Fatima, Rukhsar; Sharma, Aditi; Devi, Sonika; Suri, Vitusha; Kumar, Vikash; Suri, Anil

    2018-05-01

    SPAG9 is a novel tumor associated antigen, expressed in variety of malignancies. However, its role in ovarian cancer remains unexplored. SPAG9 expression was validated in ovarian cancer cells by real time PCR and Western blot. SPAG9 involvement in cell cycle, DNA damage, apoptosis, paclitaxel sensitivity and epithelial- mesenchymal transition (EMT) was investigated employing RNA interference approach. Combinatorial effect of SPAG9 ablation and paclitaxel treatment was evaluated in in vitro. Quantitative PCR and Western blot analysis revealed SPAG9 expression in A10, SKOV-3 and Caov3 compared to normal ovarian epithelial cells. SPAG9 ablation resulted in reduced cellular proliferation, colony forming ability and enhanced cytotoxicity of chemotherapeutic agent paclitaxel. Effect of ablation of SPAG9 on cell cycle revealed S phase arrest and showed decreased expression of CDK1, CDK2, CDK4, CDK6, cyclin B1, cyclin D1, cyclin E and increased expression of tumor suppressor p21. Ablation of SPAG9 also resulted in increased apoptosis with increased expression of various pro- apoptotic molecules including BAD, BID, PUMA, caspase 3, caspase 7, caspase 8 and cytochrome C. Decreased expression of mesenchymal markers and increased expression of epithelial markers was found in SPAG9 ablated cells. Combinatorial effect of SPAG9 ablation and paclitaxel treatment was evaluated in in vitro assays which showed that ablation of SPAG9 resulted in increased paclitaxel sensitivity and caused enhanced cell death. In vivo ovarian cancer xenograft studies showed that ablation of SPAG9 resulted in significant reduction in tumor growth. Present study revealed therapeutic potential of SPAG9 in ovarian cancer.

  19. The histone methyltransferase G9a: a new therapeutic target in biliary tract cancer.

    PubMed

    Mayr, Christian; Helm, Katharina; Jakab, Martin; Ritter, Markus; Shrestha, Rajeev; Makaju, Ramesh; Wagner, Andrej; Pichler, Martin; Beyreis, Marlena; Staettner, Stefan; Jaeger, Tarkan; Klieser, Eckhard; Kiesslich, Tobias; Neureiter, Daniel

    2018-02-01

    The histone methyltransferase G9a (EHMT2) is a key enzyme for dimethylation of lysine 9 at histone 3 (H3K9me2), a suppressive epigenetic mark. G9a is over-expressed in tumor cells and contributes to cancer aggressiveness. Biliary tract cancer (BTC) is a rare cancer with dismal prognosis due to a lack of effective therapies. Currently, there are no data on the role of G9a in BTC carcinogenesis. We analyzed G9a expression in n=68 BTC patient specimens and correlated the data with clinicopathological and survival data. Moreover, we measured G9a expression in a panel of BTC cell lines and evaluated the cytotoxic effect of G9a inhibition in BTC cells using established small-molecule G9a inhibitors. G9a was considerably expressed in about half of BTC cases and was significantly associated with grading and tumor size. Additionally, we observed significant differences of G9a expression between growth type and tumor localization groups. G9a expression diametrically correlated with Vimentin (positive) and E-Cadherin (negative) expression. Importantly, survival analysis revealed G9a as a significant prognostic factor of poor survival in patients with BTC. In BTC cells, G9a and H3K9me2 were detectable in a cell line-dependent manner on mRNA and/or protein level, respectively. Treatment of BTC cells with established small-molecule G9a inhibitors resulted in reduction of cell viability as well as reduced G9a and H3K9me2 protein levels. The present study strongly suggests that G9a contributes to BTC carcinogenesis and may represent a potential prognostic factor as well as a therapeutic target. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Disintegrin and metalloproteinases (ADAMs) expression in gastroesophageal reflux disease and in esophageal adenocarcinoma.

    PubMed

    Kauttu, T; Mustonen, H; Vainionpää, S; Krogerus, L; Ilonen, I; Räsänen, J; Salo, J; Puolakkainen, P

    2017-01-01

    Clinically useful marker molecules for the progression of gastroesophageal reflux disease and Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) are lacking. Many adenocarcinomas and inflammatory conditions exhibit increased expression of ADAMs, 'a disintegrin and metalloproteinases'. We assessed the expression of five ADAMs (9, 10, 12, 17, 19) in three esophageal cell lines (Het-1A, OE19, OE33) by RT-PCR and Western blotting, and in human samples of normal esophagus, esophagitis, BE, Barrett's dysplasia, and EAC by RT-PCR, and in selected samples by immunohistochemistry. EAC patients showed increased mRNA expression of ADAMs 9, 12, 17 and 19, as compared to controls. At immunohistochemistry, ADAM9 and ADAM10 proteins were increased in EAC. Patient samples also showed increased mRNA expression of ADAM12 in esophagitis, of ADAM9 in BE, and of ADAMs 9, 12 and 19 in Barrett's dysplasia, as compared to controls. Two EAC cell lines showed increased ADAM9 mRNA. ADAM9 expression is increased in EAC. Its predecessors show increased ADAM9 mRNA expression. The importance of the alterations in ADAM expression for the development of EAC, and their use as marker molecules, warrant further studies.

  1. Zinc finger protein 219-like (ZNF219L) and Sox9a regulate synuclein-γ2 (sncgb) expression in the developing notochord of zebrafish.

    PubMed

    Lien, Huang-Wei; Yang, Chung-Hsiang; Cheng, Chia-Hsiung; Liao, Yung-Feng; Han, Yu-San; Huang, Chang-Jen

    2013-12-13

    Zebrafish synuclein-γ2 (sncgb) has been reported to be expressed specifically in the notochord. However, the mechanism by which the sncgb gene promoter is regulated has not been described. In this paper, we demonstrate that Zinc finger protein 219-like (ZNF219L) and sox9a are involved in the regulation of sncgb gene expression. Furthermore, we observed that over-expression of both ZNF219L and Sox9a resulted in increased sncgb expression. In addition, ZNF219L is physically associated with Sox9a, and simultaneous morpholino knockdown of znf219L and sox9a caused a synergistic decrease of sncgb expression in the notochord. Taken together, our results reveal that coordination of ZNF219L with Sox9a is involved in the regulation of notochord-specific expression of sncgb. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Race Disparities and Decreasing Birth Weight: Are All Babies Getting Smaller?

    PubMed Central

    Catov, Janet M.; Lee, MinJae; Roberts, James M.; Xu, Jia; Simhan, Hyagriv N.

    2016-01-01

    The mean infant birth weight in the United States increased for decades, but it might now be decreasing. Given race disparities in fetal growth, we explored race-specific trends in birth weight at Magee-Womens Hospital, Pittsburgh, Pennsylvania, from 1997 to 2011. Among singleton births delivered at 37–41 weeks (n = 70,607), we evaluated the proportions who were small for gestational age and large for gestational age and changes in mean birth weights over time. Results were stratified by maternal race/ethnicity. Since 1997, the number of infants born small for their gestational ages increased (8.7%–9.9%), whereas the number born large for their gestational ages decreased (8.9%–7.7%). After adjustment for gestational week at birth, maternal characteristics, and pregnancy conditions, birth weight decreased by 2.20 g per year (P < 0.0001). Decreases were greater for spontaneous births. Reductions were significantly greater in infants born to African-American women than in those born to white women (−3.78 vs. −1.88 per year; P for interaction = 0.010). Quantile regression models indicated that birth weight decreased across the entire distribution, but reductions among infants born to African-American women were limited to those in the upper quartile after accounting for maternal factors. Limiting the analysis to low-risk women eliminated birth weight reductions. Birth weight has decreased in recent years, and reductions were greater in infants born to African-American women. These trends might be explained by accumulation of risk factors such as hypertension and prepregnancy obesity that disproportionately affect African-American women. Our results raise the possibility of worsening race disparities in fetal growth. PMID:26667251

  3. Interleukin-8 is a prognostic indicator in human hilar cholangiocarcinoma

    PubMed Central

    Sun, Qi; Li, Fanni; Sun, Fengkai; Niu, Jun

    2015-01-01

    Interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9) and neovascularization have been implicated to be associated with biological processes, especially cancer progression. However, few studies have investigated the role of IL-8 in human hilar cholangiocarcinoma. In this study we detected the expression of IL-8 combined with MMP-9 and microvessel density (MVD) in hilar cholangiocarcinoma to evaluate their clinicopathological significance and prognostic value. A total of 62 patients with hilar cholangiocarcinoma who underwent curative surgery were enrolled in this study. The expression of IL-8, MMP-9 and MVD were examined immunohistochemically. The correlation of IL-8 with MMP-9 expression, MVD, clinicopathological features and survival time of patients were then analyzed. Expression of IL-8 was observed in 56.5% tumors, which was related to advanced TNM stage (P = 0.026) and tumor recurrence (P = 0.018). IL-8 had a positive correlation with MMP-9 expression and MVD. Furthermore, patients with high IL-8 expression had a significantly shorter overall survival than those with low IL-8 expression (P = 0.01). Multivariate analysis confirmed IL-8 as an independent prognostic factor (P = 0.005). In conclusion, IL-8 expression significantly correlated with MMP-9 expression and MVD, and IL-8 was a valuable prognostic factor for human hilar cholangiocarcinoma. PMID:26339407

  4. The importance of emotional intelligence and meaning in life in psycho-oncology.

    PubMed

    Teques, Andreia Pereira; Carrera, Glória Bueno; Ribeiro, José Pais; Teques, Pedro; Ramón, Ginés Llorca

    2016-03-01

    Cancer was considered the disease of the 20th century, and the management, treatment, and adaptation of patients to general wellbeing were worldwide concerns. Emotional intelligence has frequently been associated with wellbeing and considered one important factor to optimal human functioning. The purpose of the present study was to test the differences regarding the relationship between emotional intelligence, purpose in life, and satisfaction with life between cancer and healthy people. This model was tested using structural path analysis in two independent samples. First, in a general Portuguese population without chronic disease, 214 participants (nmale  = 41, nfemale  = 173; Mage  = 53). Second, in 202 patients with cancer (nmale  = 40, nfemale  = 162; Mage  = 58.65). A two-step methodology was used to test the research hypothesis. First, a confirmatory factor analysis supported the measurement model. All factors also show reliability, convergent, and discriminate validity. Second, the path coefficients for each model indicate that the proposed relationships differ significantly according to the groups. The perception capacities of emotional intelligence were more related to satisfaction with life and purpose in life in oncologic patients than in the general population without chronic disease, specifically emotional understanding and regulation. Likewise, the relationship between purpose in life and satisfaction with life in oncologic patients was significantly higher than for the general population. The current findings thus suggest that emotional intelligence and purpose in life are potential components to promoting satisfaction in life in healthy people and more so in oncologic patients. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Why and How to Promote Adolescents' Prosocial Behaviors: Direct, Mediated and Moderated Effects of the CEPIDEA School-Based Program.

    PubMed

    Caprara, Gian Vittorio; Luengo Kanacri, Bernadette Paula; Zuffianò, Antonio; Gerbino, Maria; Pastorelli, Concetta

    2015-12-01

    Prosocial behaviors are considered integral to intervention goals that seek to promote successful youth development. This study examines the effect of a school-based intervention program entirely designed to promote prosocial behaviors called Promoting Prosocial and Emotional Skills to Counteract Externalizing Problems in Adolescence (Italian acronym CEPIDEA). The CEPIDEA curriculum was incorporated into routine educational practices and included five major components that reflect the personal determinants of prosocial behavior during adolescence. The present study assessed 151 students (48.7% female; M(age) = 12.4) of the intervention school and 140 students (51.2% female; M(age) = 13.0) of the control school at three points. A multi-group latent curve analysis revealed that the intervention group, compared with the control group, showed an increase in prosocial behavior, interpersonal self-efficacy beliefs, and agreeableness along with a decrease in physical aggression above and beyond the normative developmental trend of the these variables. Participants of the intervention also obtained higher grades than the control group at the end of middle school. Moderation effects for prosocial behavior and agreeableness evidenced that those who benefited most from the intervention were those adolescents with lower normative development of prosocial behavior, low initial level of agreeableness, and high initial level of physical aggression. The results also showed that the increase of prosocial behaviors mediated the decline of verbal aggression in adolescents who had attended the intervention. These findings suggest that interventions aimed at promoting prosocial behaviors while having the potential to support positive outcomes may also counteract or redirect negative trajectories of functioning.

  6. Self-compassion moderates the perfectionism and depression link in both adolescence and adulthood.

    PubMed

    Ferrari, Madeleine; Yap, Keong; Scott, Nicole; Einstein, Danielle A; Ciarrochi, Joseph

    2018-01-01

    Psychological practitioners often seek to directly change the form or frequency of clients' maladaptive perfectionist thoughts, because such thoughts predict future depression. Indirect strategies, such as self-compassion interventions, that seek to change clients' relationships to difficult thoughts, rather than trying to change the thoughts directly could be just as effective. This study aimed to investigate whether self-compassion moderated, or weakened, the relationship between high perfectionism and high depression symptoms in both adolescence and adulthood. The present study utilised anonymous self-report questionnaires to assess maladaptive perfectionism, depression, and self-compassion across two samples covering much of the lifespan. Questionnaires were administered in a high school setting for the adolescent sample (Study 1, Mage = 14.1 years, n = 541), and advertised through university and widely online to attract a convenience sample of adults (Study 2, Mage = 25.22 years, n = 515). Moderation analyses revealed that self-compassion reduced the strength of relationship between maladaptive perfectionism and depression in our adolescent Study 1 (β = -.15, p < .001, R2 = .021.) and our adult study 2 (β = -.14, p < .001, R2 = .020). Cross-sectional self-reported data restricts the application of causal conclusions and also relies on accurate self-awareness and willingness to respond to questionnaire openly. The replication of this finding in two samples and across different age-appropriate measures suggests that self-compassion does moderate the link between perfectionism and depression. Self-compassion interventions may be a useful way to undermine the effects of maladaptive perfectionism, but future experimental or intervention research is needed to fully assess this important possibility.

  7. Gender matters: the relationship between social anxiety and alcohol-related consequences.

    PubMed

    Schry, Amie R; Norberg, Melissa M; Maddox, Brenna B; White, Susan W

    2014-01-01

    Identification of risk factors for alcohol-related consequences is an important public health concern. Both gender and social anxiety have been associated with alcohol-related consequences broadly, but it is unknown whether these variables are differentially related to specific types of alcohol-related consequences for American college students. In the present study, 573 undergraduate students (M(age) = 19.86 years, SD = 1.40; range 18 to 25; 68.9% female) completed an on-line assessment of social anxiety, alcohol use, and four types of alcohol-related consequences (personal, social, physical, and role). Poisson regressions were run to examine social anxiety, gender, and the interaction between social anxiety and gender as predictors of each type of alcohol-related consequences. After controlling for alcohol use, social anxiety was positively associated with all four types of consequences, and females endorsed higher rates of physical, personal, and role consequences. The interaction between social anxiety and gender was statistically significant only for physical consequences, with social anxiety having a stronger effect for males. These findings, which diverge somewhat from those of a prior study with Australian college students, are discussed in the context of a biopsychosocial model of social anxiety and substance use problems. This study highlights the importance of further investigating cultural differences in the relationships among social anxiety, gender, and alcohol-related consequences.

  8. A randomised controlled trial of an online theory-based intervention to improve adult Australians' sun-protective behaviours.

    PubMed

    White, Katherine M; Starfelt, Louise C; Young, Ross McD; Hawkes, Anna L; Cleary, Catherine; Leske, Stuart; Wihardjo, Kylie

    2015-03-01

    To evaluate the effectiveness of a single-session online theory of planned behaviour (TPB)-based intervention to improve sun-protective attitudes and behaviour among Australian adults. Australian adults (N=534; 38.7% males; Mage=39.3 years) from major cities (80.9%), regional (17.6%) and remote areas (1.5%) were recruited and randomly allocated to an intervention (N=265) and information only group (N=267). The online intervention focused on fostering positive attitudes, perceptions of normative support, and control perceptions for sun protection. Participants completed questionnaires assessing standard TPB measures (attitude, subjective norm, perceived behavioural control, intention, behaviour) and extended TPB constructs of group norm (friends, family), personal norm, and image norm, pre-intervention (Time 1) and one week (Time 2) and one month post-intervention (Time 3). Repeated Measures Multivariate Analysis of Variance tested intervention effects across time. Intervention participants reported more positive attitudes towards sun protection and used sun-protective measures more often in the subsequent month than participants receiving information only. The intervention effects on control perceptions and norms were non-significant. A theory-based online intervention fostering more favourable attitudes towards sun safety can increase sun protection attitudes and self-reported behaviour among Australian adults in the short term. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. TLR9 expression is required for the development of cigarette smoke-induced emphysema in mice

    PubMed Central

    Foronjy, Robert F.; Salathe, Matthias A.; Dabo, Abdoulaye J.; Baumlin, Nathalie; Cummins, Neville; Eden, Edward

    2016-01-01

    The expression of Toll-like receptor (TLR)-9, a pathogen recognition receptor that recognizes unmethylated CpG sequences in microbial DNA molecules, is linked to the pathogenesis of several lung diseases. TLR9 expression and signaling was investigated in animal and cell models of chronic obstructive pulmonary disease (COPD). We observed enhanced TLR9 expression in mouse lungs following exposure to cigarette smoke. Tlr9−/− mice were resistant to cigarette smoke-induced loss of lung function as determined by mean linear intercept, total lung capacity, lung compliance, and tissue elastance analysis. Tlr9 expression also regulated smoke-mediated immune cell recruitment to the lung; apoptosis; expression of granulocyte-colony stimulating factor (G-CSF), the CXCL5 protein, and matrix metalloproteinase-2 (MMP-2); and protein tyrosine phosphatase 1B (PTP1B) activity in the lung. PTP1B, a phosphatase with anti-inflammatory abilities, was identified as binding to TLR9. In vivo delivery of a TLR9 agonist enhanced TLR9 binding to PTP1B, which inactivated PTP1B. Ptp1b−/− mice had elevated lung concentrations of G-CSF, CXCL5, and MMP-2, and tissue expression of type-1 interferon following TLR9 agonist administration, compared with wild-type mice. TLR9 responses were further determined in fully differentiated normal human bronchial epithelial (NHBE) cells isolated from nonsmoker, smoker, and COPD donors, and then cultured at air liquid interface. NHBE cells from smokers and patients with COPD expressed more TLR9 and secreted greater levels of G-CSF, IL-6, CXCL5, IL-1β, and MMP-2 upon TLR9 ligand stimulation compared with cells from nonsmoker donors. Although TLR9 combats infection, our results indicate that TLR9 induction can affect lung function by inactivating PTP1B and upregulating expression of proinflammatory cytokines. PMID:27288485

  10. Expression and clinical significance of matrix metalloproteinase-9 in lymphatic invasiveness and metastasis of breast cancer.

    PubMed

    Wu, Qiu-Wan; Yang, Qing-Mo; Huang, Yu-Fan; She, Hong-Qiang; Liang, Jing; Yang, Qiao-Lu; Zhang, Zhi-Ming

    2014-01-01

    Matrix metalloproteinase 9 (MMP-9) is a type-IV collagenase that is highly expressed in breast cancer, but its exact role in tumor progression and metastasis is unclear. MMP-9 mRNA and protein expression was examined by real-time reverse transcriptase PCR and immunohistochemical staining, respectively, in 41 breast cancer specimens with matched peritumoral benign breast epithelial tissue and suspicious metastatic axillary lymph nodes. Lymph vessels were labeled with D2-40 and lymphatic microvessel density (LMVD) was calculated. Correlation of MMP-9 protein expression with clinicopathological parameters and LMVD was also evaluated. MMP-9(+) staining in breast cancer specimens (35/41, 85.4%) was higher than in matched epithelium (21/41, 51.2%; P<0.05) and lymph nodes (13/41, 31.7%; P<0.001). Higher MMP-9 mRNA expression was also detected in tumor specimens compared with matched epithelial tissues and lymph nodes (P<0.05). Elevated MMP-9 expression was correlated with lymph node metastasis and LMVD (P<0.05). MMP-9 was overexpressed in breast cancer specimens compared with peritumoral benign breast epithelium and lymph nodes. Moreover, its expression in the matched epithelium and lymph nodes was positively associated with lymph node metastasis, and its expression in lymph nodes was positively associated with lymphangiogenesis in breast cancer. Thus, MMP-9 is a potential marker for breast cancer progression.

  11. Transient development of ovotestes in XX Sox9 transgenic mice

    PubMed Central

    Gregoire, Elodie P.; Lavery, Rowena; Chassot, Anne-Amandine; Akiyama, Haruhiko; Treier, Mathias; Behringer, Richard R.; Chaboissier, Marie-Christine

    2010-01-01

    The sex of an individual results from the paternal transmission of the SRY gene located on the Y chromosome. In turn, SRY initiates Sox9 expression, a transcription factor required for testicular differentiation. Ectopic activation of SOX9 in XX Wt1:Sox9 transgenic mice, induces female-to-male sex reversal in adult mice. Here we show that complete sex reversal is preceded by a transient phase of ovotestis differentiation with XX Wt1:Sox9 transgenic gonads containing a testicular central region and one or both ovarian poles indicating that Wt1:Sox9 is not as efficient as Sry to induce male development. In XX Wt1:Sox9Tg/+ gonads, transgenic Sox9 is expressed earlier than Sox9 in XY gonads, and is able to induce the expression of EGFP, knocked into the 3′ UTR of Sox9 indicating that SOX9 is involved in the initiation and maintenance of its own expression. However, the delayed onset of expression of endogenous Sox9-EGFP suggests that this activation requires other factors, whose expression depends on SOX9. In the testicular regions of the XX Wt1:Sox9 ovotestes, proliferation of the XX foetal germ cells is hampered and they differentiate as pro-spermatogonia. This indicates that XX germ cells are not competent to respond to proliferative signals released from a testicular environment. In the ovarian regions, despite the continuous mRNA expression of the WT1:Sox9 transgene, the SOX9 protein does not accumulate suggesting that regulation of this gene in ovarian cells involves post-transcriptional mechanisms. Finally, ovarian cells of the XX Wt1:Sox9 ovotestis undergo apoptosis during late embryogenesis leading to complete female-to-male sex reversal of the transgenic mice at birth. PMID:20965161

  12. Geologic Map of the Lavinia Planitia Quadrangle (V-55), Venus

    USGS Publications Warehouse

    Ivanov, Mikhail A.; Head, James W.

    2001-01-01

    Introduction The Lavinia Planitia quadrangle (V-55) is in the southern hemisphere of Venus and extends from 25 to 50 south latitude and from 330 to 360 longitude. It covers the central and northern part of Lavinia Planitia and parts of its margins. Lavinia Planitia consists of a centralized, deformed lowland flooded by volcanic deposits and surrounded by Dione Regio to the west (Keddie and Head, 1995), Alpha Regio tessera (Bindschadler and others, 1992a) and Eve Corona (Stofan and others, 1992) to the northeast, itself an extensive rift zone and coronae belt to the east and south (Baer and others, 1994; Magee and Head, 1995), Mylitta Fluctus to the south (Magee Roberts and others, 1992), and Helen Planitia to the southwest (Senske and others, 1991). In contrast to other areas on Venus, the Lavinia Planitia area is one of several large, relatively equidimensional lowlands (basins) and as such is an important region for the analysis of processes of basin formation and volcanic flooding. Before the Magellan mission, Lavinia Planitia was known on the basis of Pioneer-Venus altimetry to be a lowland area (Pettengill and others, 1980);. Arecibo radar images showed that Lavinia Plaitia was surrounded by several corona-like features and rift-like fractures parallel to the basin margin to the east and south (Senske and others, 1991; Campbell and others, 1990). Arecibo data further revealed that the interior contained complex patterns of deformational features in the form of belts and volcanic plains, and several regions along the margins were seen to be the sources of extensive outpourings of digitate lava flows into the interior (Senske and others, 1991; Campbell and others, 1990). Early Magellan results showed that the ridge belts are composed of complex structures of both extensional and contractional origin (Squyres and others, 1992; Solomon and others, 1992) and that the complex lava flows (fluctus) along the margins (Magee Roberts and others, 1992) emanated from a variety of sources ranging from volcanoes to coronae (Magee and Head, 1995; Keddie and Head, 1995). In addition, global analysis of the distribution of volcanic features revealed that Lavinia Planitia is an area deficient in the distribution of distinctive volcanic sources and corona-like features (Head and others, 1992; Crumpler and others, 1993). Lavinia Planitia gravity and geoid data show that the lowland is characterized by a -30 mGal gravity anomaly and a -10 m geoid anomaly, centered on eastern Lavinia (Bindschadler and others, 1992b; Konopliv and Sjogren, 1994). Indeed, the characteristics and configuration of Lavinia Planitia have been cited as evidence for the region being the site of large-scale mantle down welling (Bindschadler and others, 1992b). Thus, this region is a laboratory for the study of the formation of lowlands, the emplacement of volcanic plains, the formation of associated tectonic features, and their relation to mantle processes. These questions and issues are the basis for our geologic mapping analysis. In our analysis we have focused on the geologic mapping of the Lavinia Planitia quadrangle using traditional methods of geologic unit definition and characterization for the Earth (for example, American Commission on Stratigraphic Nomenclature, 1961) and planets (for example, Wilhelms, 1990) appropriately modified for radar data (Tanaka, 1994). We defined units and mapped key relations using the full resolution Magellan synthetic aperture radar (SAR) data (mosaiced full resolution basic image data records, C1-MIDR's, F-MIDR's, and F-Maps) and transferred these results to the base map compiled at a scale of 1:5 million. In addition to the SAR image data, we incorporated into our analyses digital versions of Magellan altimetry, emissivity, Fresnel reflectivity, and roughness data (root mean square, rms, slope). The background for our unit definition and characterization is described in Tanaka (1994), Basilevsky and Head (1995a, b)

  13. Cell Surface Galectin-9 Expressing Th Cells Regulate Th17 and Foxp3+ Treg Development by Galectin-9 Secretion

    PubMed Central

    Niki, Toshiro; Kadowaki, Takeshi; Ueno, Masaki; Nishi, Nozomu; Yamauchi, Akira; Hattori, Toshio; Masaki, Tsutomu; Hirashima, Mitsuomi

    2012-01-01

    Galectin-9 (Gal-9), a β-galactoside binding mammalian lectin, regulates immune responses by reducing pro-inflammatory IL-17-producing Th cells (Th17) and increasing anti-inflammatory Foxp3+ regulatory T cells (Treg) in vitro and in vivo. These functions of Gal-9 are thought to be exerted by binding to receptor molecules on the cell surface. However, Gal-9 lacks a signal peptide for secretion and is predominantly located in the cytoplasm, which raises questions regarding how and which cells secrete Gal-9 in vivo. Since Gal-9 expression does not necessarily correlate with its secretion, Gal-9-secreting cells in vivo have been elusive. We report here that CD4 T cells expressing Gal-9 on the cell surface (Gal-9+ Th cells) secrete Gal-9 upon T cell receptor (TCR) stimulation, but other CD4 T cells do not, although they express an equivalent amount of intracellular Gal-9. Gal-9+ Th cells expressed interleukin (IL)-10 and transforming growth factor (TGF)-β but did not express Foxp3. In a co-culture experiment, Gal-9+ Th cells regulated Th17/Treg development in a manner similar to that by exogenous Gal-9, during which the regulation by Gal-9+ Th cells was shown to be sensitive to a Gal-9 antagonist but insensitive to IL-10 and TGF-β blockades. Further elucidation of Gal-9+ Th cells in humans indicates a conserved role of these cells through evolution and implies the possible utility of these cells for diagnosis or treatment of immunological diseases. PMID:23144904

  14. Histone acetylation is associated with differential gene expression in the rapid and robust memory CD8+ T-cell response

    PubMed Central

    Fann, Monchou; Godlove, Jason M.; Catalfamo, Marta; Wood, William H.; Chrest, Francis J.; Chun, Nicholas; Granger, Larry; Wersto, Robert; Madara, Karen; Becker, Kevin; Henkart, Pierre A.; Weng, Nan-ping

    2006-01-01

    To understand the molecular basis for the rapid and robust memory T-cell responses, we examined gene expression and chromatin modification by histone H3 lysine 9 (H3K9) acetylation in resting and activated human naive and memory CD8+ T cells. We found that, although overall gene expression patterns were similar, a number of genes are differentially expressed in either memory or naive cells in their resting and activated states. To further elucidate the basis for differential gene expression, we assessed the role of histone H3K9 acetylation in differential gene expression. Strikingly, higher H3K9 acetylation levels were detected in resting memory cells, prior to their activation, for those genes that were differentially expressed following activation, indicating that hyperacetylation of histone H3K9 may play a role in selective and rapid gene expression of memory CD8+ T cells. Consistent with this model, we showed that inducing high levels of H3K9 acetylation resulted in an increased expression in naive cells of those genes that are normally expressed differentially in memory cells. Together, these findings suggest that differential gene expression mediated at least in part by histone H3K9 hyperacetylation may be responsible for the rapid and robust memory CD8+ T-cell response. PMID:16868257

  15. C9orf72 is differentially expressed in the central nervous system and myeloid cells and consistently reduced in C9orf72, MAPT and GRN mutation carriers.

    PubMed

    Rizzu, Patrizia; Blauwendraat, Cornelis; Heetveld, Sasja; Lynes, Emily M; Castillo-Lizardo, Melissa; Dhingra, Ashutosh; Pyz, Elwira; Hobert, Markus; Synofzik, Matthis; Simón-Sánchez, Javier; Francescatto, Margherita; Heutink, Peter

    2016-04-14

    A non-coding hexanucleotide repeat expansion (HRE) in C9orf72 is a common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) acting through a loss of function mechanism due to haploinsufficiency of C9orf72 or a gain of function mediated by aggregates of bidirectionally transcribed HRE-RNAs translated into di-peptide repeat (DPR) proteins. To fully understand regulation of C9orf72 expression we surveyed the C9orf72 locus using Cap Analysis of Gene Expression sequence data (CAGEseq). We observed C9orf72 was generally lowly expressed with the exception of a subset of myeloid cells, particularly CD14+ monocytes that showed up to seven fold higher expression as compared to central nervous system (CNS) and other tissues. The expression profile at the C9orf72 locus showed a complex architecture with differential expression of the transcription start sites (TSSs) for the annotated C9orf72 transcripts between myeloid and CNS tissues suggesting cell and/or tissue specific functions. We further detected novel TSSs in both the sense and antisense strand at the C9orf72 locus and confirmed their existence in brain tissues and CD14+ monocytes. Interestingly, our experiments showed a consistent decrease of C9orf72 coding transcripts not only in brain tissue and monocytes from C9orf72-HRE patients, but also in brains from MAPT and GRN mutation carriers together with an increase in antisense transcripts suggesting these could play a role in regulation of C9orf72. We found that the non-HRE related expression changes cannot be explained by promoter methylation but by the presence of the C9orf72-HRE risk haplotype and unknown functional interactions between C9orf72, MAPT and GRN.

  16. Differential effects of anxiety sensitivity components in the relation between emotional non-acceptance and post-traumatic stress symptoms among trauma-exposed treatment-seeking smokers.

    PubMed

    Bakhshaie, Jafar; Zvolensky, Michael J; Allan, Nicholas; Vujanovic, Anka A; Schmidt, Norman B

    2015-01-01

    Anxiety sensitivity (AS), defined as the extent to which individuals believe anxiety and anxiety-related sensations have harmful consequences, may play an important explanatory role in the relation between emotional non-acceptance and the expression of traumatic stress symptoms among trauma-exposed smokers. This investigation examined whether lower-order dimensions of AS (cognitive, physical, and social concerns) differentially explain the relation between emotional non-acceptance and post-traumatic stress (PTS) symptom clusters (re-experiencing, avoidance, hyperarousal) among trauma-exposed daily smokers (N = 169, 46% female; Mage = 41, SD = 12.3). AS and its lower-order facets of cognitive and social concerns were found to mediate the relations between emotional non-acceptance and avoidance and hyperarousal PTS symptoms. Using a multiple mediation model, the mediational effect of AS cognitive concerns for the relation between emotional non-acceptance and post-traumatic avoidance symptoms was found to be uniquely evident relative to social and physical concerns. All observed AS effects were evident above and beyond the variance accounted for by gender, number of traumatic event exposure types, negative affectivity, number of cigarettes smoked per day, and alcohol use problems. The present findings suggest cognitive-based AS concerns may play a mechanistic role in the relation between emotional non-acceptance and certain PTS symptoms among trauma-exposed daily smokers.

  17. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence

    PubMed Central

    Guyer, Amanda E.; Jarcho, Johanna M.; Pérez-Edgar, Koraly; Degnan, Kathryn A.; Pine, Daniel S.; Fox, Nathan A.; Nelson, Eric E.

    2015-01-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children’s caregiving context. The convergence of a child’s temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (Mage = 17.89 years, N= 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development. PMID:25588884

  18. Trait Self-Control, Identified-Introjected Religiosity and Health-Related-Feelings in Healthy Muslims: A Structural Equation Model Analysis

    PubMed Central

    Briki, Walid; Chaouachi, Anis; Patrick, Thomas; Chamari, Karim

    2015-01-01

    Aim The present study attempted to test McCullough and Willoughby’s hypothesis that self-control mediates the relationships between religiosity and psychosocial outcomes. Specifically, this study examined whether trait self-control (TSC) mediates the relationship of identified-introjected religiosity with positive and negative health-related-feelings (HRF) in healthy Muslims. Methods Two hundred eleven French-speaking participants (116 females, 95 males; Mage = 28.15, SDage = 6.90) answered questionnaires. One hundred ninety participants were retained for the analyses because they reported to be healthy (105 females, 85 males; Mage = 27.72, SDage = 6.80). To examine the relationships between religiosity, TSC and HRF, two competing mediation models were tested using structural equation model analysis: While a starting model used TSC as mediator of the religiosity-HRF relationship, an alternative model used religiosity as mediator of the TSC-HRF relationship. Results The findings revealed that TSC mediated the relationship between identified religiosity and positive HRF, and that identified religiosity mediated the relationship between TSC and positive and negative HRF, thereby validating both models. Moreover, the comparison of both models showed that the starting model explained 13.211% of the variance (goodness of fit = 1.000), whereas the alternative model explained 6.877% of the variance (goodness of fit = 0.987). Conclusion These results show that the starting model is the most effective model to account for the relationships between religiosity, TSC, and HRF. Therefore, this study provides initial insights into how religiosity influences psychological health through TSC. Important practical implications for the religious education are suggested. PMID:25962179

  19. Trait self-control, identified-introjected religiosity and health-related-feelings in healthy muslims: a structural equation model analysis.

    PubMed

    Briki, Walid; Aloui, Asma; Bragazzi, Nicola Luigi; Chaouachi, Anis; Patrick, Thomas; Chamari, Karim

    2015-01-01

    The present study attempted to test McCullough and Willoughby's hypothesis that self-control mediates the relationships between religiosity and psychosocial outcomes. Specifically, this study examined whether trait self-control (TSC) mediates the relationship of identified-introjected religiosity with positive and negative health-related-feelings (HRF) in healthy Muslims. Two hundred eleven French-speaking participants (116 females, 95 males; Mage = 28.15, SDage = 6.90) answered questionnaires. One hundred ninety participants were retained for the analyses because they reported to be healthy (105 females, 85 males; Mage = 27.72, SDage = 6.80). To examine the relationships between religiosity, TSC and HRF, two competing mediation models were tested using structural equation model analysis: While a starting model used TSC as mediator of the religiosity-HRF relationship, an alternative model used religiosity as mediator of the TSC-HRF relationship. The findings revealed that TSC mediated the relationship between identified religiosity and positive HRF, and that identified religiosity mediated the relationship between TSC and positive and negative HRF, thereby validating both models. Moreover, the comparison of both models showed that the starting model explained 13.211% of the variance (goodness of fit = 1.000), whereas the alternative model explained 6.877% of the variance (goodness of fit = 0.987). These results show that the starting model is the most effective model to account for the relationships between religiosity, TSC, and HRF. Therefore, this study provides initial insights into how religiosity influences psychological health through TSC. Important practical implications for the religious education are suggested.

  20. Growth differentiation factor 9 and its spatiotemporal expression and regulation in the zebrafish ovary.

    PubMed

    Liu, Lin; Ge, Wei

    2007-02-01

    Growth differentiation factor 9 (GDF9) is a member of the transforming growth factor beta (TGFB) superfamily. As an oocyte-specific growth factor, GDF9 plays critical roles in controlling folliculogenesis in mammals. In the present study, we cloned a 2.1-kb cDNA of the zebrafish GDF9 homolog (Gdf9, gdf9), which shares approximately 60% homology with that of mammals in the mature region. RT-PCR analysis showed that zebrafish gdf9 expression was present only in the gonads and Northern blot analysis revealed a single transcript of about 2.0 kb in the ovary. Real-time RT-PCR analysis revealed that gdf9 expression was highest in primary growth (PG, stage I) follicles and gradually decreased during follicular development, with the lowest level being found in fully grown (FG) follicles. The expression of gdf9 was maintained through fertilization and early embryonic development until gastrulation, at which point the expression level dramatically decreased. Expression was barely detectable after the late gastrula stage. Within the follicle, gdf9 mRNA was localized exclusively in the oocytes, as demonstrated by RT-PCR of denuded oocytes and freshly isolated follicle layers as well as by in situ hybridization. Interestingly, when amplified for high numbers of cycles, the expression of gdf9 was detected in cultured zebrafish follicular cells that were free of oocytes. The expression of gdf9 was downregulated by hCG in both ovarian fragments and isolated follicles in dose- and time-dependent manners, and this inhibition appeared to be stage-dependent, with the strongest inhibition observed for the FG follicles and no effect seen for the PG follicles. This correlates well with the expression profile of the LH receptor (lhcgr) in zebrafish follicles. In conclusion, as an oocyte-derived growth factor, GDF9 is highly conserved across vertebrates. With its biological advantages, zebrafish provides an alternative model for studying gene function and regulation.

  1. Sox9b Is Required for Epicardium Formation and Plays a Role in TCDD-Induced Heart Malformation in Zebrafish

    PubMed Central

    Hofsteen, Peter; Plavicki, Jessica; Johnson, Shaina D.; Peterson, Richard E.

    2013-01-01

    Activation of the transcription factor aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prevents the formation of the epicardium and leads to severe heart malformations in developing zebrafish (Danio rerio). The downstream genes that cause heart malformation are not known. Because TCDD causes craniofacial malformations in zebrafish by downregulating the sox9b gene, we hypothesized that cardiotoxicity might also result from sox9b downregulation. We found that sox9b is expressed in the developing zebrafish heart ventricle and that TCDD exposure markedly reduces this expression. Furthermore, we found that manipulation of sox9b expression could phenocopy many but not all of the effects of TCDD at the heart. Loss of sox9b prevented the formation of epicardium progenitors comprising the proepicardium on the pericardial wall, and prevented the formation and migration of the epicardial layer around the heart. Zebrafish lacking sox9b showed pericardial edema, an elongated heart, and reduced blood circulation. Fish lacking sox9b failed to form valve cushions and leaflets. Sox9b is one of two mammalian Sox9 homologs, sox9b and sox9a. Knock down of sox9a expression did not cause cardiac malformations, or defects in epicardium development. We conclude that the decrease in sox9b expression in the heart caused by TCDD plays a role in many of the observed signs of cardiotoxicity. We find that while sox9b is expressed in myocardial cells, it is not normally expressed in the affected epicardial cells or progenitors. We therefore speculate that sox9b is involved in signals between the cardiomyocytes and the nascent epicardial cells. PMID:23775563

  2. Normal Levels of Sox9 Expression in the Developing Mouse Testis Depend on the TES/TESCO Enhancer, but This Does Not Act Alone.

    PubMed

    Gonen, Nitzan; Quinn, Alexander; O'Neill, Helen C; Koopman, Peter; Lovell-Badge, Robin

    2017-01-01

    During mouse sex determination, transient expression of the Y-linked gene Sry up-regulates its direct target gene Sox9, via a 3.2 kb testis specific enhancer of Sox9 (TES), which includes a core 1.4 kb element, TESCO. SOX9 activity leads to differentiation of Sertoli cells, rather than granulosa cells from the bipotential supporting cell precursor lineage. Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh. Although human patients heterozygous for null mutations in SOX9, which are assumed to have 50% of normal expression, often show XY female sex reversal, mice deleted for one copy of Sox9 do not. Consistent with this, we did not observe sex reversal in either TESCO-/- or TES-/- XY embryos or adult mice. However, embryos carrying both a conditional Sox9 null allele and the TES deletion developed ovotestes. Quantitative analysis of these revealed levels of 23% expression of Sox9 compared to wild type, and a significant increase in the expression of the granulosa cell marker Foxl2. This indicates that the threshold in mice where sex reversal begins to be seen is about half that of the ~50% levels predicted in humans. Our results demonstrate that TES/TESCO is a crucial enhancer regulating Sox9 expression in the gonad, but point to the existence of additional enhancers that act redundantly.

  3. Normal Levels of Sox9 Expression in the Developing Mouse Testis Depend on the TES/TESCO Enhancer, but This Does Not Act Alone

    PubMed Central

    O’Neill, Helen C.; Koopman, Peter; Lovell-Badge, Robin

    2017-01-01

    During mouse sex determination, transient expression of the Y-linked gene Sry up-regulates its direct target gene Sox9, via a 3.2 kb testis specific enhancer of Sox9 (TES), which includes a core 1.4 kb element, TESCO. SOX9 activity leads to differentiation of Sertoli cells, rather than granulosa cells from the bipotential supporting cell precursor lineage. Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh. Although human patients heterozygous for null mutations in SOX9, which are assumed to have 50% of normal expression, often show XY female sex reversal, mice deleted for one copy of Sox9 do not. Consistent with this, we did not observe sex reversal in either TESCO-/- or TES-/- XY embryos or adult mice. However, embryos carrying both a conditional Sox9 null allele and the TES deletion developed ovotestes. Quantitative analysis of these revealed levels of 23% expression of Sox9 compared to wild type, and a significant increase in the expression of the granulosa cell marker Foxl2. This indicates that the threshold in mice where sex reversal begins to be seen is about half that of the ~50% levels predicted in humans. Our results demonstrate that TES/TESCO is a crucial enhancer regulating Sox9 expression in the gonad, but point to the existence of additional enhancers that act redundantly. PMID:28045957

  4. Transcript expression and genetic variability analysis of caspases in breast carcinomas suggests CASP9 as the most interesting target.

    PubMed

    Brynychova, Veronika; Hlavac, Viktor; Ehrlichova, Marie; Vaclavikova, Radka; Nemcova-Furstova, Vlasta; Pecha, Vaclav; Trnkova, Marketa; Mrhalova, Marcela; Kodet, Roman; Vrana, David; Gatek, Jiri; Bendova, Marie; Vernerova, Zdenka; Kovar, Jan; Soucek, Pavel

    2017-01-01

    Apoptosis plays a critical role in cancer cell survival and tumor development. We provide a hypothesis-generating screen for further research by exploring the expression profile and genetic variability of caspases (2, 3, 7, 8, 9, and 10) in breast carcinoma patients. This study addressed isoform-specific caspase transcript expression and genetic variability in regulatory sequences of caspases 2 and 9. Gene expression profiling was performed by quantitative real-time PCR in tumor and paired non-malignant tissues of two independent groups of patients. Genetic variability was determined by high resolution melting, allelic discrimination, and sequencing analysis in tumor and peripheral blood lymphocyte DNA of the patients. CASP3 A+B and S isoforms were over-expressed in tumors of both patient groups. The CASP9 transcript was down-regulated in tumors of both groups of patients and significantly associated with expression of hormonal receptors and with the presence of rs4645978-rs2020903-rs4646034 haplotype in the CASP9 gene. Patients with a low intratumoral CASP9A/B isoform expression ratio (predicted to shift equilibrium towards anti-apoptotic isoform) subsequently treated with adjuvant chemotherapy had a significantly shorter disease-free survival than those with the high ratio (p=0.04). Inheritance of CC genotype of rs2020903 in CASP9 was associated with progesterone receptor expression in tumors (p=0.003). Genetic variability in CASP9 and expression of its splicing variants present targets for further study.

  5. Pancreatic cancer cells express CD44 variant 9 and multidrug resistance protein 1 during mitosis.

    PubMed

    Kiuchi, Shizuka; Ikeshita, Shunji; Miyatake, Yukiko; Kasahara, Masanori

    2015-02-01

    Pancreatic cancer is one of the most lethal cancers with high metastatic potential and strong chemoresistance. Its intractable natures are attributed to high robustness in tumor cells for their survival. We demonstrate here that pancreatic cancer cells (PCCs) with an epithelial phenotype upregulate cell surface expression of CD44 variant 9 (CD44v9), an important cancer stem cell marker, during the mitotic phases of the cell cycle. Of five human CD44(+) PCC lines examined, three cell lines, PCI-24, PCI-43 and PCI-55, expressed E-cadherin and CD44 variants, suggesting that they have an epithelial phenotype. By contrast, PANC-1 and MIA PaCa-2 cells expressed vimentin and ZEB1, suggesting that they have a mesenchymal phenotype. PCCs with an epithelial phenotype upregulated cell surface expression of CD44v9 in prophase, metaphase, anaphase and telophase and downregulated CD44v9 expression in late-telophase, cytokinesis and interphase. Sorted CD44v9-negative PCI-55 cells resumed CD44v9 expression when they re-entered the mitotic stage. Interestingly, CD44v9(bright) mitotic cells expressed multidrug resistance protein 1 (MDR1) intracellularly. Upregulated expression of CD44v9 and MDR1 might contribute to the intractable nature of PCCs with high proliferative activity. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Fibronectin-mediation cell adhesion is required for induction of 92-kDa type IV collagenase/gelatinase (MMP-9) gene expression during macrophage differentiation : the signaling role of protein kinase C-{beta}.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xie, B.; Laouar, A.; Huberman, E.

    1998-05-08

    Induction of the 92-kDa gelatinase (MMP-9) gene expression is associated with macrophage differentiation. In this study, we explored the regulatory mechanisms underlying this differentiation-associated MMP-9 gene expression in human HL-60 myeloid leukemia cells and human peripheral blood monocytes. Phorbol 12-myristate 13-acetate (PMA) markedly induced MMP-9 gene expression in HL-60 cells; the induction closely paralleled the timing and extent of PMA-induced cell adhesion and spreading, a hallmark of macrophage differentiation. Similarly, treatment with PMA or macrophage-colony stimulating factor stimulated adherence and spreading of blood monocytes with a concurrent 7- or 5-fold increase in MMP-9 production, respectively. In protein kinase C (PKC)-betamore » -deficient HL-60 variant cells (HL-525), PMA failed to induce cell adhesion and MMP-9 gene expression. Transfecting HL-525 cells with a PKC-beta expression plasmid restored PKC-beta levels and PMA inducibility of cell adhesion and spreading as well as MMP-9 gene expression. Induction of cell adhesion and MMP-9 gene expression in HL-60 cells and blood monocytes was strongly inhibited by neutralizing monoclonal antibodies to fibronectin (FN) and its receptor {alpha}5{beta}1 integrin. HL-525 cells, which constitutively display high levels of surface {alpha}5{beta}1 integrin, adhered and spread on immobilized FN with concomitant induction of MMP-9 gene expression. Cytochalasins B and D were each a potent inhibitor of MMP-9 production. Our results suggest that {alpha}5{beta}1 integrin-mediated interaction of immature hematopoietic cells with FN plays a critical role in modulating matrix-degrading activities during macrophage differentiation.« less

  7. Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c.

    PubMed

    Costet, Philippe; Cariou, Bertrand; Lambert, Gilles; Lalanne, Florent; Lardeux, Bernard; Jarnoux, Anne-Laure; Grefhorst, Aldo; Staels, Bart; Krempf, Michel

    2006-03-10

    Familial autosomal dominant hypercholesterolemia is associated with high risk for cardiovascular accidents and is related to mutations in the low density lipoprotein receptor or its ligand apolipoprotein B (apoB). Mutations in a third gene, proprotein convertase subtilisin kexin 9 (PCSK9), were recently associated to this disease. PCSK9 acts as a natural inhibitor of the low density lipoprotein receptor pathway, and both genes are regulated by depletion of cholesterol cell content and statins, via sterol regulatory element-binding protein (SREBP). Here we investigated the regulation of PCSK9 gene expression during nutritional changes. We showed that PCSK9 mRNA quantity is decreased by 73% in mice after 24 h of fasting, leading to a 2-fold decrease in protein level. In contrast PCSK9 expression was restored upon high carbohydrate refeeding. PCSK9 mRNA increased by 4-5-fold in presence of insulin in rodent primary hepatocytes, whereas glucose had no effect. Moreover, insulin up-regulated hepatic PCSK9 expression in vivo during a hyperinsulinemic-euglycemic clamp in mice. Adenoviral mediated overexpression of a dominant or negative form of SREBP-1c confirmed the implication of this transcription factor in insulin-mediated stimulation of PCSK9 expression. Liver X receptor agonist T0901317 also regulated PCSK9 expression via this same pathway (a 2-fold increase in PCSK9 mRNA of primary hepatocytes cultured for 24 h in presence of 1 microm T0901317). As our last investigation, we isolated PCSK9 proximal promoter and verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG. Together, these results show that PCSK9 expression is regulated by nutritional status and insulinemia.

  8. SOX9 expression predicts relapse of stage II colon cancer patients.

    PubMed

    Marcker Espersen, Maiken Lise; Linnemann, Dorte; Christensen, Ib Jarle; Alamili, Mahdi; Troelsen, Jesper T; Høgdall, Estrid

    2016-06-01

    The aim of this study was to investigate if the protein expression of sex-determining region y-box 9 (SOX9) in primary tumors could predict relapse of stage II colon cancer patients. One hundred forty-four patients with stage II primary colon cancer were retrospectively enrolled in the study. SOX9 expression was evaluated by immunohistochemistry, and mismatch repair status was assessed by both immunohistochemistry and promoter hypermethylation assay. High SOX9 expression at the invasive front was significantly associated with lower risk of relapse when including the SOX9 expression as a continuous variable (from low to high expression) in univariate (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.56-0.94; P = .01) and multivariate Cox proportional hazards analyses (HR, 0.75; 95% CI, 0.58-0.96; P = .02), adjusting for mismatch repair deficiency and histopathologic risk factors. Conversely, low SOX9 expression at the invasive front was significantly associated with high risk of relapse, when including SOX9 expression as a dichotomous variable, in univariate (HR, 2.32; 95% CI, 1.14-4.69; P = .02) and multivariate analyses (HR, 2.32; 95% CI, 1.14-4.69; P = .02), adjusting for histopathologic risk factors and mismatch repair deficiency. In conclusion, high levels of SOX9 of primary stage II colon tumors predict low risk of relapse, whereas low levels of SOX9 predict high risk of relapse. SOX9 may have an important value as a biomarker when evaluating risk of relapse for personalized treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Fibroblast growth factor 9 is a novel modulator of negative affect

    PubMed Central

    Aurbach, Elyse L.; Inui, Edny Gula; Turner, Cortney A.; Hagenauer, Megan H.; Prater, Katherine E.; Li, Jun Z.; Absher, Devin; Shah, Najmul; Blandino, Peter; Bunney, William E.; Myers, Richard M.; Barchas, Jack D.; Schatzberg, Alan F.; Watson, Stanley J.; Akil, Huda

    2015-01-01

    Both gene expression profiling in postmortem human brain and studies using animal models have implicated the fibroblast growth factor (FGF) family in affect regulation and suggest a potential role in the pathophysiology of major depressive disorder (MDD). FGF2, the most widely characterized family member, is down-regulated in the depressed brain and plays a protective role in rodent models of affective disorders. By contrast, using three microarray analyses followed by quantitative RT-PCR confirmation, we show that FGF9 expression is up-regulated in the hippocampus of individuals with MDD, and that FGF9 expression is inversely related to the expression of FGF2. Because little is known about FGF9’s function in emotion regulation, we used animal models to shed light on its potential role in affective function. We found that chronic social defeat stress, an animal model recapitulating some aspects of MDD, leads to a significant increase in hippocampal FGF9 expression, paralleling the elevations seen in postmortem human brain tissue. Chronic intracerebroventricular administration of FGF9 increased both anxiety- and depression-like behaviors. In contrast, knocking down FGF9 expression in the dentate gyrus of the hippocampus using a lentiviral vector produced a decrease in FGF9 expression and ameliorated anxiety-like behavior. Collectively, these results suggest that high levels of hippocampal FGF9 play an important role in the development or expression of mood and anxiety disorders. We propose that the relative levels of FGF9 in relation to other members of the FGF family may prove key to understanding vulnerability or resilience in affective disorders. PMID:26351673

  10. Elevated S100A9 expression in tumor stroma functions as an early recurrence marker for early-stage oral cancer patients through increased tumor cell invasion, angiogenesis, macrophage recruitment and interleukin-6 production

    PubMed Central

    Fang, Wei-Yu; Chen, Yi-Wen; Hsiao, Jenn-Ren; Liu, Chiang-Shin; Kuo, Yi-Zih; Wang, Yi-Ching; Chang, Kung-Chao; Tsai, Sen-Tien; Chang, Mei-Zhu; Lin, Siao-Han; Wu, Li-Wha

    2015-01-01

    S100A9 is a calcium-binding protein with two EF-hands and frequently deregulated in several cancer types, however, with no clear role in oral cancer. In this report, the expression of S100A9 in cancer and adjacent tissues from 79 early-stage oral cancer patients was detected by immunohistochemical staining. Although S100A9 protein was present in both tumor and stromal cells, only the early-stage oral cancer patients with high stromal expression had reduced recurrence-free survival. High stromal S100A9 expression was also significantly associated with non-well differentiation and recurrence. In addition to increasing cell migration and invasion, ectopic S100A9 expression in tumor cells promoted xenograft tumorigenesis as well as the dominant expression of myeloid cell markers and pro-inflammatory IL-6. The expression of S100A9 in one stromal component, monocytes, stimulated the aggressiveness of co-cultured oral cancer cells. We also detected the elevation of serum S100A9 levels in early-stage oral cancer patients of a separate cohort of 73 oral cancer patients. The release of S100A9 protein into extracellular milieu enhanced tumor cell invasion, transendothelial monocyte migration and angiogenic activity. S100A9-mediated release of IL-6 requires the crosstalk of tumor cells with monocytes through the activation of NF-κB and STAT-3. Early-stage oral cancer patients with both high S100A9 expression and high CD68+ immune infiltrates in stroma had shortest recurrence-free survival, suggesting the use of both S100A9 and CD68 as poor prognostic markers for oral cancer. Together, both intracellular and extracellular S100A9 exerts a tumor-promoting action through the activation of oral cancer cells and their associated stroma in oral carcinogenesis. PMID:26315114

  11. Elevated S100A9 expression in tumor stroma functions as an early recurrence marker for early-stage oral cancer patients through increased tumor cell invasion, angiogenesis, macrophage recruitment and interleukin-6 production.

    PubMed

    Fang, Wei-Yu; Chen, Yi-Wen; Hsiao, Jenn-Ren; Liu, Chiang-Shin; Kuo, Yi-Zih; Wang, Yi-Ching; Chang, Kung-Chao; Tsai, Sen-Tien; Chang, Mei-Zhu; Lin, Siao-Han; Wu, Li-Wha

    2015-09-29

    S100A9 is a calcium-binding protein with two EF-hands and frequently deregulated in several cancer types, however, with no clear role in oral cancer. In this report, the expression of S100A9 in cancer and adjacent tissues from 79 early-stage oral cancer patients was detected by immunohistochemical staining. Although S100A9 protein was present in both tumor and stromal cells, only the early-stage oral cancer patients with high stromal expression had reduced recurrence-free survival. High stromal S100A9 expression was also significantly associated with non-well differentiation and recurrence. In addition to increasing cell migration and invasion, ectopic S100A9 expression in tumor cells promoted xenograft tumorigenesis as well as the dominant expression of myeloid cell markers and pro-inflammatory IL-6. The expression of S100A9 in one stromal component, monocytes, stimulated the aggressiveness of co-cultured oral cancer cells. We also detected the elevation of serum S100A9 levels in early-stage oral cancer patients of a separate cohort of 73 oral cancer patients. The release of S100A9 protein into extracellular milieu enhanced tumor cell invasion, transendothelial monocyte migration and angiogenic activity. S100A9-mediated release of IL-6 requires the crosstalk of tumor cells with monocytes through the activation of NF-κB and STAT-3. Early-stage oral cancer patients with both high S100A9 expression and high CD68+ immune infiltrates in stroma had shortest recurrence-free survival, suggesting the use of both S100A9 and CD68 as poor prognostic markers for oral cancer. Together, both intracellular and extracellular S100A9 exerts a tumor-promoting action through the activation of oral cancer cells and their associated stroma in oral carcinogenesis.

  12. Elevated expression of matrix metalloproteinase-9 is associated with bladder cancer pathogenesis.

    PubMed

    Wu, Gong-Jin; Bao, Jun-Sheng; Yue, Zhong-Jin; Zeng, Fan-Chang; Cen, Song; Tang, Zheng-Yan; Kang, Xin-Li

    2018-01-01

    This study investigated the association between abnormal matrix metalloproteinase-9 (MMP-9) expression and bladder cancer (BC) development. In a retrospective analysis, this study used tissue samples derived from 92 patients pathologically diagnosed with BC (experimental group), who were hospitalized between September 2012 and June 2014 at the Urinary Surgery of Department of Urology, Lanzhou University Second Hospital. As controls (control group), 63 normal pericancerous bladder mucosal tissues (3 cm distant form edge of BC foci) with confirmed pathology were selected from the same time period. Immunohistochemistry was employed to detect MMP-9 protein expression in the tissues and enzyme-linked immunosorbent assay was performed to measure MMP-9 protein levels in tissue samples of patients and control subjects. Finally, a meta-analysis was conducted to understand the overall impact of MMP-9 on BC pathogenesis. STATA 12.0 software (Stata Corp, College Station, TX, USA) was used for all statistical analyses. The MMP-9 positive expression rate in tissue samples and MMP-9 levels were significantly greater in the experimental group compared to the control group (both P < 0.001). The frequency of MMP-9 positive status showed statistically significant differences between G1 (low-grade) and G3 (high-grade) (P < 0.001), between G2 and G3 (P < 0.05), and between G1/G2 and G3 (P = 0.001). Our meta-analysis findings provided further evidence that MMP-9 positive expression status and MMP-9 levels in the experimental group were significantly higher than the control group (positive expressions: Odds ratio [OR] = 18.59, 95% confidence interval [95% CI] = 11.63-29.71, P < 0.001; expression levels: Standard mean difference = 1.51, 95%CI = 0.63-2.39, P = 0.001). The positive expression status of MMP-9 was notably lower in G1/G2 compared to G3 (OR = 0.24, 95%CI = 0.15-0.36, P < 0.001). Our study demonstrated that both positive expression status in tumor tissue and expression levels of MMP-9 are significantly elevated in BC patients and correlate with disease progression. Thus, MMP-9 can serve as a biomarker to determine the degree of BC malignancy.

  13. Expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder.

    PubMed

    Ai, Xing; Zhang, Xu; Wu, Zhun; Ma, Xin; Ju, Zhenghua; Wang, Baojun; Shi, Taoping

    2007-02-01

    The expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder (TCCB) and its clinical significance were investigated. Immunohistochemistry was used to detect KAI1/CD82 and MRP-1/CD9 protein expression in 52 TCCB specimens. Correlation between the expression of KAI1/CD82 and MRP-1/CD9 to clinicopathologic factors was statistically analyzed. The results showed that the positive rate of KAI1/CD82 and MRP-1/CD9 in TCCB was 50% and 61.5%, respectively. The MRP-1/CD9 and KAI1/CD82 expression was significantly associated with grade of TCCB (P<0.05), but no correlation was found between MRP-1/CD9 or KAI1/CD82 expression and clinical stage of TCCB (P>0.05). The expression level of MRP-1/CD9 and KAI1/CD82 in recurrent TCCB samples was lower than that in non-recurrent samples (P<0.05). Meanwhile, the correlation between the KAI1/CD82 expression and MRP-1/CD9 expression was statistically significant (r=0.316, P<0.05). It was concluded that KAI1/CD82 and MRP-1/CD9 expression may be important prognostic indicators and potentially useful for assessing the biological behavior of TCCB.

  14. Calcium-Binding Proteins S100A8 and S100A9: Investigation of Their Immune Regulatory Effect in Myeloid Cells.

    PubMed

    Yang, Jianxin; Anholts, Jacqueline; Kolbe, Ulrike; Stegehuis-Kamp, Janine A; Claas, Frans H J; Eikmans, Michael

    2018-06-21

    High expression levels of the calcium-binding proteins S100A8 and S100A9 in myeloid cells in kidney transplant rejections are associated with a favorable outcome. Here we investigated the myeloid cell subset expressing these molecules, and their function in inflammatory reactions. Different monocyte subsets were sorted from buffy coats of healthy donors and investigated for S100A8 and S100A9 expression. To characterize S100A9high and S100A9low subsets within the CD14+ classical monocyte subset, intracellular S100A9 staining was combined with flow cytometry (FACS) and qPCR profiling. Furthermore, S100A8 and S100A9 were overexpressed by transfection in primary monocyte-derived macrophages and the THP-1 macrophage cell line to investigate the functional relevance. Expression of S100A8 and S100A9 was primarily found in classical monocytes and to a much lower extent in intermediate and non-classical monocytes. All S100A9+ cells expressed human leukocyte antigen—antigen D related (HLA-DR) on their surface. A small population (<3%) of CD14+ CD11b+ CD33+ HLA-DR− cells, characterized as myeloid derived suppressor cells (MDSCs), also expressed S100A9 to high extent. Overexpression of S100A8 and S00A9 in macrophages led to enhanced extracellular reactive oxygen species (ROS) production, as well as elevated mRNA expression of anti-inflammatory IL-10 . The results suggest that the calcium-binding proteins S100A8 and S100A9 in myeloid cells have an immune regulatory effect.

  15. Dissection of Arabidopsis NCED9 promoter regulatory regions reveals a role for ABA synthesized in embryos in the regulation of GA-dependent seed germination.

    PubMed

    Seo, Mitsunori; Kanno, Yuri; Frey, Anne; North, Helen M; Marion-Poll, Annie

    2016-05-01

    Nine-cis-epoxycarotenoid dioxygenase (NCED) catalyzes the key step of abscisic acid (ABA) biosynthesis. There are five genes encoding NCED in Arabidopsis, which differentially regulate ABA biosynthesis in a spatiotemporal manner in response to endogenous and environmental stimuli. Previous studies have shown that NCED9 is expressed in testa and embryos during seed development. In the present study, we have identified promoter regions required for the expression of NCED9 in testa and embryos, respectively. Electrophoretic mobility shift assays (EMSA) and yeast one-hybrid (Y1H) assays showed that several homeodomain-leucine zipper (HD-Zip) proteins, namely ATHBs, bound to the sequence required for expression of NCED9 in testa, suggesting that they redundantly regulate NCED9 expression. By expressing the NCED9 gene under the control of a deleted NCED9 promoter in an nced9 mutant expression was limited to embryos. Transformants were complemented for the paclobutrazol resistant germination phenotype of the mutant, suggesting that the ABA synthesis mediated by NCED9 in embryos plays an important role in the regulation of gibberellin (GA)-dependent seed germination. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. RANK ligand signaling modulates the matrix metalloproteinase-9 gene expression during osteoclast differentiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sundaram, Kumaran; Nishimura, Riko; Senn, Joseph

    2007-01-01

    Osteoclast differentiation is tightly regulated by receptor activator of NF-{kappa}B ligand (RANKL) signaling. Matrix metalloproteinase-9 (MMP-9), a type IV collagenase is highly expressed in osteoclast cells and plays an important role in degradation of extracellular matrix; however, the molecular mechanisms that regulate MMP-9 gene expression are unknown. In this study, we demonstrate that RANKL signaling induces MMP-9 gene expression in osteoclast precursor cells. We further show that RANKL regulates MMP-9 gene expression through TRAF6 but not TRAF2. Interestingly, blockade of p38 MAPK activity by pharmacological inhibitor, SB203580 increases MMP-9 activity whereas ERK1/2 inhibitor, PD98059 decreases RANKL induced MMP-9 activity inmore » RAW264.7 cells. These data suggest that RANKL differentially regulates MMP-9 expression through p38 and ERK signaling pathways during osteoclast differentiation. Transient expression of MMP-9 gene (+ 1 to - 1174 bp relative to ATG start codon) promoter-luciferase reporter plasmids in RAW264.7 cells and RANKL stimulation showed significant increase (20-fold) of MMP-9 gene promoter activity; however, there is no significant change with respect to + 1 bp to - 446 bp promoter region and empty vector transfected cells. These results indicated that MMP-9 promoter sequence from - 446 bp to - 1174 bp relative to start codon is responsive to RANKL stimulation. Sequence analysis of the mouse MMP-9 gene promoter region further identified the presence of binding motif (- 1123 bp to - 1153 bp) for the nuclear factor of activated T cells 1 (NFATc1) transcription factor. Inhibition of NFATc1 using siRNA and VIVIT peptide inhibitor significantly decreased RANKL stimulation of MMP-9 activity. We further confirm by oligonucleotide pull-down assay that RANKL stimuli enhanced NFATc1 binding to MMP-9 gene promoter element. In addition, over-expression of constitutively active NFAT in RAW264.7 cells markedly increased (5-fold) MMP-9 gene promoter activity in the absence of RANKL. Taken together, our results suggest that RANKL signals through TRAF6 and that NFATc1 is a downstream effector of RANKL signaling to modulate MMP-9 gene expression during osteoclast differentiation.« less

  17. [Knockdown of NEDD9 inhibits the proliferation, invasion and migration of esophageal carcinoma EC109 cells].

    PubMed

    Zhang, Wen; Li, Shaojun; Zhao, Yunlong; Guo, Nannan; Li, Yingjie

    2016-12-01

    Objective To observe the expression of the neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) in esophageal cancer, to investigate the impact of decreased expression of NEDD9 on invasion and migration, and to explicit the function of NEDD9 in EC109 human esophageal cancer cell line. Methods Immunohistochemical staining was used to detect the expression of NEDD9 in human esophageal cancer tissues and paracancerous normal tissues. RNA interfering (RNAi) was used to knockdown NEDD9 in EC109 cells. The interference efficiency was detected by reverse transcription PCR (RT-PCR) and Western blot analysis. Cell proliferation was determined by MTT assay and the invasion and migration abilities of EC109 cells were monitored by Transwell TM assay. The protein levels of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 were tested by Western blotting. Results The positive expression rate of NEDD9 in esophageal carcinoma tissues was significantly higher compared with that in the paracancerous tissues. After NEDD9 expression was successfully downregulated in EC109 cells by siRNA, the proliferation, invasion and migration rates in transfection group were significantly lower than those in control group; meanwhile, the expression of Bcl-2 was reduced and Bax expression was enhanced. Conclusion The protein expression level of NEDD9 is higher in esophageal carcinoma tissues than that in adjacent normal tissues. Knockdown of NEDD9 expression can restrain the proliferation, invasion and migration of EC109 cells.

  18. S100A8/A9 is associated with estrogen receptor loss in breast cancer.

    PubMed

    Bao, Y I; Wang, Antao; Mo, Juanfen

    2016-03-01

    S100A8 and S100A9 are calcium-binding proteins that are secreted primarily by granulocytes and monocytes, and are upregulated during the inflammatory response. S100A8 and S100A9 have been identified to be expressed by epithelial cells involved in malignancy. In the present study, the transcriptional levels of S100A8 and S100A9 were investigated in various subtypes of breast cancer (BC), and the correlation with estrogen receptor 1 (ESR1) and GATA binding protein 3 (GATA3) gene expression was evaluated using microarray datasets. The expression of S100A8 and S100A9 in BC cells was assessed by reverse transcription-polymerase chain reaction (RT-PCR). The regulation of ESR1 and GATA3 by administration of recombinant S100A8/A9 was examined in the BC MCF-7 cell line using quantitative (q)PCR. The association between S100A8 and S100A9 and overall survival (OS) was investigated in GeneChip® data of BC. The expression levels of S100A8 and S100A9 were higher in human epidermal growth factor receptor 2 (Her2)-amplified and basal-like BC. The messenger (m)RNA levels of S100A8 and S100A9 were inversely correlated with ESR1 and GATA3 expression. S100A8/A9 induced a 10-fold decrease in the mRNA levels of ESR1 in MCF-7 cells. Poor OS was associated with high expression levels of S100A9, but not with high expression levels of S100A8 in BC. In conclusion, strong expression and secretion of S100A8/A9 may be associated with the loss of estrogen receptor in BC, and may be involved in the poor prognosis of Her2+/basal-like subtypes of BC.

  19. S100A8/A9 is associated with estrogen receptor loss in breast cancer

    PubMed Central

    BAO, YI; WANG, ANTAO; MO, JUANFEN

    2016-01-01

    S100A8 and S100A9 are calcium-binding proteins that are secreted primarily by granulocytes and monocytes, and are upregulated during the inflammatory response. S100A8 and S100A9 have been identified to be expressed by epithelial cells involved in malignancy. In the present study, the transcriptional levels of S100A8 and S100A9 were investigated in various subtypes of breast cancer (BC), and the correlation with estrogen receptor 1 (ESR1) and GATA binding protein 3 (GATA3) gene expression was evaluated using microarray datasets. The expression of S100A8 and S100A9 in BC cells was assessed by reverse transcription-polymerase chain reaction (RT-PCR). The regulation of ESR1 and GATA3 by administration of recombinant S100A8/A9 was examined in the BC MCF-7 cell line using quantitative (q)PCR. The association between S100A8 and S100A9 and overall survival (OS) was investigated in GeneChip® data of BC. The expression levels of S100A8 and S100A9 were higher in human epidermal growth factor receptor 2 (Her2)-amplified and basal-like BC. The messenger (m)RNA levels of S100A8 and S100A9 were inversely correlated with ESR1 and GATA3 expression. S100A8/A9 induced a 10-fold decrease in the mRNA levels of ESR1 in MCF-7 cells. Poor OS was associated with high expression levels of S100A9, but not with high expression levels of S100A8 in BC. In conclusion, strong expression and secretion of S100A8/A9 may be associated with the loss of estrogen receptor in BC, and may be involved in the poor prognosis of Her2+/basal-like subtypes of BC. PMID:26998104

  20. Triarchic dimensions of psychopathy in young adulthood: Associations with clinical and physiological measures after accounting for adolescent psychopathic traits.

    PubMed

    Kyranides, Melina Nicole; Fanti, Kostas A; Sikki, Maria; Patrick, Christopher J

    2017-04-01

    This study examined associations of psychopathy facets of boldness, meanness, and disinhibition with clinically relevant variables and physiological reactivity to affective stimuli. These associations were examined after accounting for developmental associations with adolescent psychopathic traits, namely callous-unemotional traits, narcissism, and impulsivity. Psychopathic traits were assessed during adolescence using the Antisocial Process Screening Device and the Inventory of Callous Unemotional traits and during young adulthood via the Triarchic Psychopathy Measure. Clinical variables (N = 99, Mage = 15.91, 53% female), as well as affective and physiological responses (heart rate, skin conductance, startle modulation) to violent and erotic videos (N = 88, Mage = 19.92, 50% female) were also assessed during adulthood. After accounting for adolescent psychopathic traits, boldness was associated with high cognitive reappraisal and low anxiety, fear, and hostility, and meanness was related to callous-unemotional traits, hostility, less sympathy to victims, and less use of cognitive reappraisal. Disinhibition, by contrast, was associated with impulsivity, increased anxiety, and hostile and aggressive tendencies, as well as conduct disorder, antisocial personality disorder symptoms, and cognitive suppression. In addition, evidence was found for different physiological measures operating as biological indicators of these distinctive dimensions, with reduced resting heart rate and cardiac reactivity to violent stimuli indicative of boldness, above and beyond adolescent psychopathic traits, and low startle potentiation for violent stimuli indicative of callous-unemotional traits and meanness. These findings provide evidence for the value of a multidomain approach for clarifying neurobiological mechanisms of psychopathic tendencies that can inform prevention and treatment efforts. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  1. Gambling-Related Distortions and Problem Gambling in Adolescents: A Model to Explain Mechanisms and Develop Interventions

    PubMed Central

    Donati, Maria Anna; Chiesi, Francesca; Iozzi, Adriana; Manfredi, Antonella; Fagni, Fabrizio; Primi, Caterina

    2018-01-01

    Although a number of gambling preventive initiatives have been realized with adolescents, many of them have been developed in absence of a clear and explicitly described theoretical model. The present work was aimed to analyze the adequacy of a model to explain gambling behavior referring to gambling-related cognitive distortions (Study 1), and to verify the effectiveness of a preventive intervention developed on the basis of this model (Study 2). Following dual-process theories on cognitive functioning, in Study 1 we tested a model in which mindware gap, i.e., susceptibility to the gambler’s fallacy, and contaminated mindware, i.e., superstitious thinking, were the antecedents of gambling-related cognitive distortions that, in turn, affect gambling frequency and problem gambling. Participants were 306 male adolescents (Mage = 17.2 years). A path analysis indicated that cognitive distortions have a mediating role in the relationship that links probabilistic reasoning fallacy and superstitious thinking with problem gambling. Following these findings, in Study 2 we developed a school-based intervention aimed to reduce gambling-related cognitive distortions acting on the above cited mindware problems. A pre- and post-test design – with a 6 months follow-up – was performed with 34 male adolescents (Mage = 16.8), randomly assigned to two groups (Training and No Training), and their baseline equivalence was verified. A Mixed 2 × 2 ANOVA attested a significant Time X Group interaction, indicating a significant reduction of the cognitive distortions from pre-test to post-test only in the Training group. The follow-up attested to the stability of the training effects and the reduction of gambling frequency over time. These findings suggest that prevention strategies should address mindware problems, which can be considered as predictors of gambling-related cognitive distortions. PMID:29354081

  2. NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes

    PubMed Central

    2012-01-01

    Background Matrix metalloproteinase-9 (MMP-9) plays a crucial role in pathological processes of brain inflammation, injury, and neurodegeneration. Moreover, bradykinin (BK) induces the expression of several inflammatory proteins in brain astrocytes. Recent studies have suggested that increased oxidative stress is implicated in the brain inflammation and injury. However, whether BK induced MMP-9 expression mediated through oxidative stress remains virtually unknown. Herein we investigated the role of redox signals in BK-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells). Results In the study, we first demonstrated that reactive oxygen species (ROS) plays a crucial role in BK-induced MMP-9 expression in cultured brain astrocytes (in vitro) and animal brain tissue (in vivo) models. Next, BK-induced MMP-9 expression is mediated through a Ca2+-mediated PKC-α linking to p47phox/NADPH oxidase 2 (Nox2)/ROS signaling pathway. Nox2-dependent ROS generation led to activation and up-regulation of the downstream transcriptional factor AP-1 (i.e. c-Fos and c-Jun), which bound to MMP-9 promoter region, and thereby turned on transcription of MMP-9 gene. Functionally, BK-induced MMP-9 expression enhanced astrocytic migration. Conclusions These results demonstrated that in RBA-1 cells, activation of AP-1 (c-Fos/c-Jun) by the PKC-α-mediated Nox2/ROS signals is essential for up-regulation of MMP-9 and cell migration enhanced by BK. PMID:23176293

  3. Anhedonia and anxiety sensitivity: prospective relationships to nicotine withdrawal symptoms during smoking cessation.

    PubMed

    Langdon, Kirsten J; Leventhal, Adam M; Stewart, Sherry; Rosenfield, David; Steeves, Dan; Zvolensky, Michael J

    2013-05-01

    The aim of the present investigation was to explore the main and interactive effects of anhedonic depressive symptoms and anxiety sensitivity in terms of the individual components of nicotine withdrawal symptoms experienced on quit day as well as throughout the initial 14 days of cessation. Participants included 65 daily cigarette smokers (38 women; Mage = 46.08 years, SD = 9.12) undergoing psychosocial-pharmacological cessation treatment. Results indicated that, after controlling for the effects of participant sex and nicotine dependence, anhedonic depression symptoms, but not anxiety sensitivity, significantly predicted quit day levels of mood-based nicotine withdrawal symptoms. Conversely, anxiety sensitivity, but not anhedonic depression symptoms, was significantly related to the change in most nicotine withdrawal symptoms over time. Finally, our results revealed a significant interaction between anxiety sensitivity and anhedonic depression symptoms related to the slope of certain withdrawal symptoms over time. Specifically, among participants with higher levels of anxiety sensitivity, greater levels of anhedonic depression symptoms were related to greater increases in withdrawal symptoms over time for two of the nine anxiety-relevant components of nicotine withdrawal (restlessness and frustration). Among high anxiety-sensitivity persons, compared with those low in anxiety sensitivity, anhedonic depression symptoms may be more relevant to the experience of some withdrawal symptoms being more intense and persistent during the early phases of quitting.

  4. Why are people with high self-control happier? The effect of trait self-control on happiness as mediated by regulatory focus

    PubMed Central

    Cheung, Tracy T. L.; Gillebaart, Marleen; Kroese, Floor; De Ridder, Denise

    2014-01-01

    Background: While self-control has often been related to positive outcomes in life such as higher academic achievements and better health, recent insights reveal that people with high trait self-control (TSC) may even experience greater life satisfaction or happiness. Objective: The current study further scrutinizes this potential association between TSC and happiness, and examines how regulatory focus, defined as the way people frame and direct their goal pursuit strategies, plays a role in this relationship. Accordingly, the present study examines the mediating role of regulatory-focus (promotion and prevention focus) on the relationship between TSC and happiness. Method: Data was collected from 545 individuals (65.9% female, Mage = 27.52 years) regarding their TSC, regulatory focus, and happiness. Results: Mediation analyses demonstrate that TSC positively predicts happiness, while this effect was partially mediated by relatively more promotion focus and less prevention focus. Conclusion: Results suggest that people with higher TSC are happier possibly because they are: (1) more promotion-focused on acquiring positive gains thereby facilitating more approach-oriented behaviors, and (2) less prevention-focused on avoiding losses thereby reducing avoidance-oriented behaviors. These findings are relevant for topical scientific debates regarding the underlying mechanisms of self-control regarding initiatory and inhibitory behaviors. PMID:25071683

  5. [Expression of S100A8 and A100A9 in giant cell tumor of bone and its relation with CT and MR imaging findings].

    PubMed

    Liao, Jin-sheng; Ding, Xiao-yi; Xu, Shun-liang

    2015-05-01

    To investigate the mRNA and protein expression levels of S100A8 and S100A9 in giant cell tumor (GCT) of bone, and its relation with radiological findings and biological behavior. Forty three patient with GCT of bone admitted in Ruijin Hospital Shanghai Jiaotong University School of Medicine from January 2009 to June 2012 were enrolled in the study. The expression levels of S100A8 and S100A9 mRNA and protein were detected by using semiquantitative RT-PCR and Western blotting in 43 specimens of GCT and 6 specimens of normal bone marrow. The CT and MRI findings of patients were retrospectively reviewed, its relation with tissue expression of S100A8 and S100A9 was analyzed. Among 43 GCT cases 40 showed positive expression of S100A8 and S100A9 mRNA and protein, and the expression levels were significantly higher than those in normal bone marrow P<0.05). The expression level of S100A8 protein was significantly different in bone GCT with different composition ratio on MRI (P<0.05).The expression level of S100A9 protein was significantly different in GCT with different degree of bone destruction on CT scan (P<0.05). The expression of S100A8 and S100A9 mRNA and protein is up-regulated in GCT of bone. The expression of S100A8 and S100A9 is associated with the real composition ratio and the degree of bone destruction, respectively, indicating that S100A8 and S100A9 may be involved in the biological behavior of bone GCT.

  6. Simply scan--optical methods for elemental carbon measurement in diesel exhaust particulate.

    PubMed

    Forder, James A

    2014-08-01

    This article describes a performance assessment of three optical methods, a Magee Scientific OT21 Transmissometer, a Hach-Lange Microcolor II difference gloss meter, and a combination of an office scanner with Adobe Photoshop software. The optical methods measure filter staining as a proxy for elemental carbon in diesel exhaust particulate (DEP) exposure assessment and the suitability of each as a replacement for the existing Bosch meter optical method. Filters loaded with DEP were produced from air in a non-coal mine and the exhaust gases from a mobile crane. These were measured with each apparatus and then by combustion to obtain a reference elemental carbon value. The results from each apparatus were then plotted against both the Bosch number and reference elemental carbon values. The equations of the best fit lines for these plots were derived, and these gave functions for elemental carbon and Bosch number from the output of each new optical method. For each optical method, the range of DEP loadings which can be measured has been determined, and conversion equations for elemental carbon and Bosch number have been obtained. All three optical methods studied will effectively quantify blackness as a measure of elemental carbon. Of these the Magee Scientific OT21 transmissometer has the best performance. The Microcolor II and scanner/photoshop methods will in addition allow conversion to Bosch number which may be useful if historical Bosch data are available and functions for this are described. The scanner/photoshop method demonstrates a technique to obtain measurements of DEP exposure without the need to purchase specialized instrumentation. © The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  7. Activation of Adiponectin Receptor Regulates Proprotein Convertase Subtilisin/Kexin Type 9 Expression and Inhibits Lesions in ApoE-Deficient Mice.

    PubMed

    Sun, Lei; Yang, Xiaoxiao; Li, Qi; Zeng, Peng; Liu, Ying; Liu, Lipei; Chen, Yuanli; Yu, Miao; Ma, Chuanrui; Li, Xiaoju; Li, Yan; Zhang, Rongxin; Zhu, Yan; Miao, Qing Robert; Han, Jihong; Duan, Yajun

    2017-07-01

    The reduced adiponectin levels are associated with atherosclerosis. Adiponectin exerts its functions by activating adiponectin receptor (AdipoR). Proprotein convertase subtilisin kexin type 9 (PCSK9) degrades LDLR protein (low-density lipoprotein receptor) to increase serum LDL-cholesterol levels. PCSK9 expression can be regulated by PPARγ (peroxisome proliferator-activated receptor γ) or SREBP2 (sterol regulatory element-binding protein 2). The effects of AdipoR agonists on PCSK9 and LDLR expression, serum lipid profiles, and atherosclerosis remain unknown. At cellular levels, AdipoR agonists (ADP355 and AdipoRon) induced PCSK9 transcription/expression that solely depended on activation of PPAR-responsive element in the PCSK9 promoter. AdipoR agonists induced PPARγ expression; thus, the AdipoR agonist-activated PCSK9 expression/production was impaired in PPARγ deficient hepatocytes. Meanwhile, AdipoR agonists transcriptionally activated LDLR expression by activating SRE in the LDLR promoter. Moreover, AMP-activated protein kinase α (AMPKα) was involved in AdipoR agonist-activated PCSK9 expression. In wild-type mice, ADP355 increased PCSK9 and LDLR expression and serum PCSK9 levels, which was associated with activation of PPARγ, AMPKα and SREBP2 and reduction of LDL-cholesterol levels. In contrast, ADP355 reduced PCSK9 expression/secretion in apoE-deficient (apoE -/- ) mice, but it still activated hepatic LDLR, PPARγ, AMPKα, and SREBP2. More importantly, ADP355 inhibited lesions in en face aortas and sinus lesions in aortic root in apoE -/- mice with amelioration of lipid profiles. Our study demonstrates that AdipoR activation by agonists regulated PCSK9 expression differently in wild-type and apoE -/- mice. However, ADP355 activated hepatic LDLR expression and ameliorated lipid metabolism in both types of mice and inhibited atherosclerosis in apoE -/- mice. © 2017 American Heart Association, Inc.

  8. Comparison of CRISPR/Cas9 expression constructs for efficient targeted mutagenesis in rice.

    PubMed

    Mikami, Masafumi; Toki, Seiichi; Endo, Masaki

    2015-08-01

    The CRISPR/Cas9 system is an efficient tool used for genome editing in a variety of organisms. Despite several recent reports of successful targeted mutagenesis using the CRISPR/Cas9 system in plants, in each case the target gene of interest, the Cas9 expression system and guide-RNA (gRNA) used, and the tissues used for transformation and subsequent mutagenesis differed, hence the reported frequencies of targeted mutagenesis cannot be compared directly. Here, we evaluated mutation frequency in rice using different Cas9 and/or gRNA expression cassettes under standardized experimental conditions. We introduced Cas9 and gRNA expression cassettes separately or sequentially into rice calli, and assessed the frequency of mutagenesis at the same endogenous targeted sequences. Mutation frequencies differed significantly depending on the Cas9 expression cassette used. In addition, a gRNA driven by the OsU6 promoter was superior to one driven by the OsU3 promoter. Using an all-in-one expression vector harboring the best combined Cas9/gRNA expression cassette resulted in a much improved frequency of targeted mutagenesis in rice calli, and bi-allelic mutant plants were produced in the T0 generation. The approach presented here could be adapted to optimize the construction of Cas9/gRNA cassettes for genome editing in a variety of plants.

  9. Glucose sensor evaluation of glycemic instability in pediatric type 1 diabetes mellitus.

    PubMed

    Alemzadeh, Ramin; Loppnow, Cindy; Parton, Elaine; Kirby, Midge

    2003-01-01

    Maintaining blood glucose (BG) levels within the target range can be an elusive goal in children with type 1 diabetes mellitus (DM). To identify factor(s) that may contribute to glycemic instability, we analyzed the Continuous Glucose Monitoring System (CGMS) (Medtronic MiniMed, Northridge, CA) profiles of a group of children with type 1 DM and a history of frequent BG fluctuations and hypoglycemia. A total of 30 (17 girls, 13 boys) pediatric patients with a history of frequent BG fluctuations and hypoglycemia (mean age, 10.5 +/- 0.7 years; duration, 5.0 +/- 0.6 years), on three to four injections of insulin daily or insulin pump therapy, were evaluated by the CGMS. The mean BG (MBG), absolute means of daily differences (MODD), mean amplitude of glycemic excursion (MAGE), and number of hypoglycemic events (BG <60 mg/dL) for 48 h were calculated in each patient. There was a significant correlation between MBG and glycosylated hemoglobin (HbA1c) (r(2) = 0.22, p < 0.009). There was also a significant correlation between severity of lipohypertrophy and glycemic control (HbA1c) (r(2) = 0.20, p < 0.01). The MODD values had a positive correlation with the severity of injection site lipohypertrophy (r(2) = 0.37, p < 0.0003). The MAGE values had a positive correlation with bolus:basal insulin ratio (r(2) = 0.22, p < 0.009) and number of hypoglycemic events (r(2) = 0.21, p < 0.008), independent of age, MBG, and glycemic control. The 48-h CGMS profile can help characterize day-to-day and within-day BG variability and identify factors influencing glycemic instability in pediatric type 1 DM.

  10. A soluble form of Siglec-9 provides an antitumor benefit against mammary tumor cells expressing MUC1 in transgenic mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tomioka, Yukiko, E-mail: ytomi@muses.tottori-u.ac.jp; Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553; Morimatsu, Masami, E-mail: mmorimat@vetmed.hokudai.ac.jp

    Highlights: • Tumor-associated antigen MUC1 binds to Siglec-9. • Soluble Siglec-9 reduced proliferation of MUC1-positive tumor in transgenic mice. • Soluble Siglec-9 and MUC1 on tumor cells were colocalized in transgenic mice. • MUC1 expression on tumor cells were reduced in soluble Siglec-9 transgenic mice. - Abstract: Tumor-associated MUC1 binds to Siglec-9, which is expected to mediate tumor cell growth and negative immunomodulation. We hypothesized that a soluble form of Siglec-9 (sSiglec-9) competitively inhibits a binding of MUC1 to its receptor molecules like human Siglec-9, leading to provide antitumor benefit against MUC1-expressing tumor, and generated transgenic mouse lines expressing sSiglec-9more » (sSiglec-9 Tg). When mammary tumor cells expressing MUC1 were intraperitoneally transplanted into sSiglec-9 Tg, tumor proliferation was slower with the lower histological malignancy as compared with non-transgenic mice. The sSiglec-9 was detected in the ascites caused by the tumor in the sSiglec-9 Tg, and sSiglec-9 and MUC1 were often colocalized on surfaces of the tumor cells. PCNA immunohistochemistry also revealed the reduced proliferation of the tumor cells in sSiglec-9 Tg. In sSiglec-9 Tg with remarkable suppression of tumor proliferation, MUC1 expressions were tend to be reduced. In the ascites of sSiglec-9 Tg bearing the tumor, T cells were uniformly infiltrated, whereas aggregations of degenerative T cells were often observed in the non-transgenic mice. These results suggest that sSiglec-9 has an antitumor benefit against MUC1-expressing tumor in the transgenic mice, which may avoid the negative immunomodulation and/or suppress tumor-associated MUC1 downstream signal transduction, and subsequent tumor proliferation.« less

  11. Porcine calbindin-D9k gene: expression in endometrium, myometrium, and placenta in the absence of a functional estrogen response element in intron A.

    PubMed

    Krisinger, J; Jeung, E B; Simmen, R C; Leung, P C

    1995-01-01

    The expression of Calbindin-D9k (CaBP-9k) in the pig uterus and placenta was measured by Northern blot analysis and reverse transcription polymerase chain reaction (PCR), respectively. Progesterone (P4) administration to ovariectomized pigs decreased CaBP-9k mRNA levels. Expression of endometrial CaBP-9k mRNA was high on pregnancy Days 10-12 and below the detection limit on Days 15 and 18. On Day 60, expression could be detected at low levels. In myometrium and placenta, CaBP-9k mRNA expression was not detectable by Northern analysis using total RNA. Reverse-transcribed RNA from both tissues demonstrated the presence of CaBP-9k transcripts by means of PCR. The partial CaBP-9k gene was amplified by PCR and cloned to determine the sequence of intron A. In contrast to the rat CaBP-9k gene, the pig gene does not contain a functional estrogen response element (ERE) within this region. A similar ERE-like sequence located at the identical location was examined by gel retardation analysis and failed to bind the estradiol receptor. A similar disruption of this ERE-like sequence has been described in the human CaBP-9k gene, which is not expressed at any level in placenta, myometrium, or endometrium. It is concluded that the pig CaBP-9k gene is regulated in these reproductive tissues in a manner distinct from that in rat and human tissues. The regulation is probably due to a regulatory region outside of intron A, which in the rat gene contains the key cis element for uterine expression of the CaBP-9k gene.

  12. Thrombin-induced Migration and Matrix Metalloproteinase-9 Expression Are Regulated by MAPK and PI3K Pathways in C6 Glioma Cells

    PubMed Central

    Kim, Jiyoung; Lee, Jae-Won; Kim, Song-In; Choi, Yong-Joon; Lee, Won-Ki; Jeong, Myung-Ja; Cha, Sang-Hoon; Lee, Hee Jae; Chun, Wanjoo

    2011-01-01

    Glioblastoma multiforme is one of the most common and aggressive tumors in central nervous system. It often possesses characteristic necrotic lesions with hemorrhages, which increase the chances of exposure to thrombin. Thrombin has been known as a regulator of MMP-9 expression and cancer cell migration. However, the effects of thrombin on glioma cells have not been clearly understood. In the present study, influences of thrombin on glioma cell migration were examined using Boyden chamber migration assay and thrombin-induced changes in MMP-9 expression were measured using zymography, semi-quantitative RT-PCR, and Western blotting. Furthermore, underlying signaling pathways by which thrombin induces MMP-9 expression were examined. Thrombin-induced migration and MMP-9 expression were significantly potentiated in the presence of wortmannin, a PI3K inhibitor, whereas MAPK inhibitors suppressed thrombin-induced migration and MMP-9 expression in C6 glioma cells. The present data strongly demonstrate that MAPK and PI3K pathways evidently regulate thrombin-induced migration and MMP-9 expression of C6 glioma cells. Therefore, the control of these pathways might be a beneficial therapeutic strategy for treatment of invasive glioblastoma multiforme. PMID:21994479

  13. MiR-9 Promotes Apoptosis Via Suppressing SMC1A Expression in GBM Cell Lines.

    PubMed

    Zu, Yong; Zhu, Zhichuan; Lin, Min; Xu, Dafeng; Liang, Yongjun; Wang, Yueqian; Qiao, Zhengdong; Cao, Ting; Yang, Dan; Gao, Lili; Jin, Pengpeng; Zhang, Peng; Fu, Jianjun; Zheng, Jing

    2017-01-01

    Glioblastomas multiforme (GBM) is the most malignant brain cancer, which presented vast genomic variation with complicated pathologic mechanism. MicroRNA is a delicate post-transcriptional tuner of gene expression in the organisms by targeting and regulating protein coding genes. MiR-9 was reported as a significant biomarker for GBM patient prognosis and a key factor in regulation of GBM cancer stem cells. To explore the effect of miR-9 on GBM cell growth, we over expressed miR-9 in U87 and U251 cells. The cell viability decreased and apoptosis increased after miR-9 overexpression in these cells. To identify the target of miR-9, we scanned miR-9 binding site in the 3'UTRs region of expression SMC1A (structural maintenance of chromosomes 1A) genes and designed a fluorescent reporter assay to measure miR-9 binding to this region. Our results revealed that miR-9 binds to the 3'sUTR region of SMC1A and down-regulated SMC1A expression. Our results indicated that miR-9 was a potential therapeutic target for GBM through triggering apoptosis of cancer cells.

  14. HOXA9 gene expression in the chronic myeloid leukemia progression.

    PubMed

    Tedeschi, Fabian A; Zalazar, Fabian E

    2006-11-01

    In the present work we study the HOXA9 expression in sequential samples of patients with CML using RT-PCR. To obtain a semi-quantitative value, the HOXA9 expression was referred to the ABL gene in the same sample. The relative HOXA9 expression was higher in patients in the accelerated phase of the disease (p<0.005). Interestingly, a patient with poorer prognosis (high Sokal's score), showing the highest HOXA9/ABL ratio, quickly entered a blast crisis and died 5 months later. These first results could be considered as an evidence of an actual biological phenomenon that could provide additional information about the HOXA9 role in the CML progression.

  15. Sperm associated antigen 9 (SPAG9) expression and humoral response in benign and malignant salivary gland tumors

    PubMed Central

    Agarwal, Sumit; Parashar, Deepak; Gupta, Namita; Jagadish, Nirmala; Thakar, Alok; Suri, Vaishali; Kumar, Rajive; Gupta, Anju; Ansari, Abdul S; Lohiya, Nirmal Kumar; Suri, Anil

    2015-01-01

    Salivary gland cancers are highly aggressive epithelial tumor associated with metastatic potential and high mortality. The tumors are biologically diverse and are of various histotypes. Besides, the detection and diagnosis is a major problem of salivary gland cancer for available treatment modalities. In the present study, we have investigated the association of sperm associated antigen 9 (SPAG9) expression with salivary gland tumor (SGT). Clinical specimens of benign (n = 16) and malignant tumors (n = 86) were examined for the SPAG9 expression. In addition, the sera and adjacent non-cancerous tissues (n = 72) from available patients were obtained. Our in situ RNA hybridization and immunohistochemistry (IHC) analysis revealed significant difference (p = 0.0001) in SPAG9 gene and protein expression in benign (63%) and malignant tumor (84%) specimens. Further, significant association was also observed between SPAG9 expression and malignant tumors (P = 0.05). A cut-off value of >10% cells expressing SPAG9 protein designated as positive in IHC, predicted presence of malignant SGT with 83.72% sensitivity, 100% specificity, 100% PPV and 83.72% NPV. Humoral response against SPAG9 protein was generated in 68% of SGT patients. A cut-off value of 0.212 OD for anti-SPAG9 antibodies in ELISA predicted presence of malignant SGT with 69.23% sensitivity, 100% specificity, 100% PPV and 78.94% NPV. Collectively, our data suggests that the majority of SGT show significant difference and association among benign and malignant tumors for SPAG9 gene and protein expression and also exhibit humoral response against SPAG9 protein. Hence, SPAG9 may be developed as a biomarker for detection and diagnosis of salivary gland tumors. PMID:25941602

  16. Mast cells and matrix metalloproteinase 9 expression in actinic cheilitis and lip squamous cell carcinoma.

    PubMed

    Souza Freitas, Valéria; de Andrade Santos, Pedro Paulo; de Almeida Freitas, Roseana; Pereira Pinto, Leão; de Souza, Lélia Batista

    2011-09-01

    The aim of this study was to evaluate mast cell (MC) density and migration and their association with matrix metalloproteinase (MMP) 9 expression in squamous cell carcinoma (SCC) and actinic cheilitis (AC). Tryptase, c-Kit, and MMP-9 expression was evaluated in 20 cases of SCC, 20 cases of AC, and 7 cases of normal lip (control samples) by immunohistochemistry techniques. Tryptase(+) and c-Kit(+) MC densities were significantly higher in SCCs than in ACs and control samples (P < .001). However, no significant difference was found when comparing tryptase(+) and c-Kit(+) MC densities between ACs and control samples (P values .185 and .516, respectively). MMP-9 was strongly expressed in SCCs and moderately expressed in ACs and control samples. A highly significant association was found between tryptase(+) MC density and the expression of MMP-9 (P < .001). The increase in MC density associated with the strong expression of MMP-9 may favor SCC progression. Copyright © 2011 Mosby, Inc. All rights reserved.

  17. Curcumin inhibits oral squamous cell carcinoma SCC-9 cells proliferation by regulating miR-9 expression

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xiao, Can; Department of Stomatology, The First Affiliated Hospital of Soochow University, Suzhou 215006; Wang, Lili

    Highlights: • miR-9 expression level was significantly decreased in OSCC tissues. • Curcumin significantly inhibited SCC-9 cells proliferation. • miR-9 mediates the inhibition of SCC-9 proliferation by curcumin. • Curcumin suppresses Wnt/β-catenin signaling in SCC-9 cells. • miR-9 mediates the suppression of Wnt/β-catenin signaling by curcumin. - Abstract: Curcumin, a phytochemical derived from the rhizome of Curcuma longa, has shown anticancer effects against a variety of tumors. In the present study, we investigated the effects of curcumin on the miR-9 expression in oral squamous cell carcinoma (OSCC) and explored the potential relationships between miR-9 and Wnt/β-catenin pathway in curcumin-mediated OSCCmore » inhibition in vitro. As the results shown, the expression levels of miR-9 were significantly lower in clinical OSCC specimens than those in the adjacent non-tumor tissues. Furthermore, our results indicated that curcumin inhibited OSCC cells (SCC-9 cells) proliferation through up-regulating miR-9 expression, and suppressing Wnt/β-catenin signaling by increasing the expression levels of the GSK-3β, phosphorylated GSK-3β and β-catenin, and decreasing the cyclin D1 level. Additionally, the up-regulation of miR-9 by curcumin in SCC-9 cells was significantly inhibited by delivering anti-miR-9 but not control oligonucleotides. Downregulation of miR-9 by anti-miR-9 not only attenuated the growth-suppressive effects of curcumin on SCC-9 cells, but also re-activated Wnt/β-catenin signaling that was inhibited by curcumin. Therefore, our findings would provide a new insight into the use of curcumin against OSCC in future.« less

  18. Transient development of ovotestes in XX Sox9 transgenic mice.

    PubMed

    Gregoire, Elodie P; Lavery, Rowena; Chassot, Anne-Amandine; Akiyama, Haruhiko; Treier, Mathias; Behringer, Richard R; Chaboissier, Marie-Christine

    2011-01-01

    The sex of an individual results from the paternal transmission of the SRY gene located on the Y chromosome. In turn, SRY initiates Sox9 expression, a transcription factor required for testicular differentiation. Ectopic activation of SOX9 in XX Wt1:Sox9 transgenic mice induces female-to-male sex reversal in adult mice. Here we show that complete sex reversal is preceded by a transient phase of ovotestis differentiation with XX Wt1:Sox9 transgenic gonads containing a testicular central region and one or both ovarian poles indicating that Wt1:Sox9 is not as efficient as Sry to induce male development. In XX Wt1:Sox9(Tg/+) gonads, transgenic Sox9 is expressed earlier than Sox9 in XY gonads and is able to induce the expression of EGFP, knocked into the 3' UTR of Sox9 indicating that SOX9 is involved in the initiation and maintenance of its own expression. However, the delayed onset of expression of endogenous Sox9-EGFP suggests that this activation requires other factors, whose expression depends on SOX9. In the testicular regions of the XX Wt1:Sox9 ovotestes, proliferation of the XX fetal germ cells is hampered and they differentiate as pro-spermatogonia. This indicates that XX germ cells are not competent to respond to proliferative signals released from a testicular environment. In the ovarian regions, despite the continuous mRNA expression of the WT1:Sox9 transgene, the SOX9 protein does not accumulate suggesting that regulation of this gene in ovarian cells involves post-transcriptional mechanisms. Finally, ovarian cells of the XX Wt1:Sox9 ovotestis undergo apoptosis during late embryogenesis leading to complete female-to-male sex reversal of the transgenic mice at birth. Copyright © 2010 Elsevier Inc. All rights reserved.

  19. Induction of the IL-9 gene by HTLV-I Tax stimulates the spontaneous proliferation of primary adult T-cell leukemia cells by a paracrine mechanism

    PubMed Central

    Chen, Jing; Petrus, Mike; Bryant, Bonita R.; Phuc Nguyen, Vinh; Stamer, Mindy; Goldman, Carolyn K.; Bamford, Richard; Morris, John C.; Janik, John E.

    2008-01-01

    The etiologic agent of adult T-cell leukemia (ATL) is human T cell lymphotropic virus type I (HTLV-I). The HTLV-I protein Tax alters gene expression, including those of cytokines and their receptors, which plays an important role in early stages of ATL. Here we demonstrate that expression of interleukin-9 (IL-9) is activated by Tax via an NF-κB motif in its proximal promoter, whereas IL-9 receptor-α (IL-9Rα) expression is not induced by Tax. However, supporting a role for IL-9/IL-9Rα in ATL, a neutralizing monoclonal antibody directed toward IL-9Rα inhibited ex vivo spontaneous proliferation of primary ATL cells from several patients. Fluorescence-activated cell sorter analysis of freshly isolated peripheral blood mononuclear cells from these patients revealed high level expression of IL-9Rα on their CD14-expressing monocytes. Furthermore, purified T cells or monocytes alone from these patients did not proliferate ex vivo, whereas mixtures of these cell types manifested significant proliferation through a contact-dependent manner. Taken together, our data suggest that primary ATL cells, via IL-9, support the action of IL-9Rα/CD14-expressing monocytes, which subsequently support the ex vivo spontaneous proliferation of malignant T cells. In summary, these data support a role for IL-9 and its receptor in ATL by a paracrine mechanism. PMID:18339896

  20. Identification and expression of three new Nicotiana plumbaginifolia genes which encode isoforms of a plasma-membrane H(+)-ATPase, and one of which is induced by mechanical stress.

    PubMed

    Oufattole, M; Arango, M; Boutry, M

    2000-04-01

    To analyze in detail the multigene family encoding the plasma-membrane H(+)-ATPase (pma) in Nicotiana plumbaginifolia Viv., five new pma genes (pma 5-9) were isolated. Three of these (pma 6, 8, 9) were fully characterized and classified into new and independent subfamilies. Their cell-type expression was followed by the beta-glucuronidase (gusA) reporter-gene method. While the pma8-gusA transgene was not expressed in transgenic tobacco, expression of the two other transgenes (pma6- and pma9-gusA) was found to be restricted to particular cell types. In the vegetative tissues, pma6-gusA expression was limited to the head cells of the leaf short trichomes, involved in secretion, and to the cortical parenchyma of the young nodes where the developing leaves and axillary flowering stalks join the stem. In the latter tissues, gene expression was enhanced by mechanical stress, suggesting that H(+)-ATPase might be involved in the strength of the tissues and their resistance to mechanical trauma. The pma9-gusA transgene was mainly expressed in the apical meristem of adventitious roots and axillary buds as well as in the phloem tissues of the stem, in which expression depended on the developmental stage. In flowers, pma9-gusA expression was limited to the mature pollen grains and the young fertilized ovules, while that of pma6-gusA was identified in most of the organs. Reverse transcription-polymerase chain reaction of leaf and stem RNA confirmed the expression of pma 6 and 9, while pma8 was found to be expressed in both organs at a lower level. In conclusion, although pma 6 and 9 had a more restricted expression pattern than the previously characterized pma genes, they were nevertheless expressed in cell types in which H(+)-ATPase had not been previously detected.

  1. Expression of the fructose receptor BmGr9 and its involvement in the promotion of feeding, suggested by its co-expression with neuropeptide F1 in Bombyx mori.

    PubMed

    Mang, Dingze; Shu, Min; Tanaka, Shiho; Nagata, Shinji; Takada, Tomoyuki; Endo, Haruka; Kikuta, Shingo; Tabunoki, Hiroko; Iwabuchi, Kikuo; Sato, Ryoichi

    2016-08-01

    Insect gustatory receptors (Grs) are members of a large family of proteins with seven transmembrane domains that provide insects with the ability to detect chemical signals critical for feeding, mating, and oviposition. To date, 69 Bombyx mori Grs (BmGrs) genes have been identified via genome studies. BmGr9 has been shown to respond specifically to fructose and to function as a ligand-gated ion channel selectively activated by fructose. However, the sites where this Gr are expressed remain unclear. We demonstrated using reverse transcription (RT)-PCR that BmGr9 is widely expressed in the central nervous system (CNS), as well as oral sensory organs. Additionally, immunohistochemistry was performed using anti-BmGr9 antiserum to show that BmGr9 is expressed in cells of the oral sensory organs, including the maxillary galea, maxillary palps, labrum, and labium, as well as in putative neurosecretory cells of the CNS. Furthermore, double immunohistochemical analysis showed that most BmGr9-expressing cells co-localized with putative neuropeptide F1-expressing cells in the brain, suggesting that BmGr9 is involved in the promotion of feeding behaviors. In addition, a portion of BmGr9-expressing cells in the brain co-localized with cells expressing BmGr6, a molecule of the sugar receptor clade, suggesting that sugars other than fructose are involved in the regulation of feeding behaviors in B. mori larvae. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. ER stress triggers MCP-1 expression through SET7/9-induced histone methylation in the kidneys of db/db mice.

    PubMed

    Chen, Jigang; Guo, Yanhong; Zeng, Wei; Huang, Li; Pang, Qi; Nie, Ling; Mu, Jiao; Yuan, Fahuan; Feng, Bing

    2014-04-15

    Epigenetics plays a key role in the pathogenesis of diabetic nephropathy (DN), although the precise regulatory mechanism is still unclear. Here, we examined the role of endoplasmic reticulum (ER) stress in histone H3 lysine 4 (H3K4) methyltransferase SET7/9-induced monocyte chemoattractant protein-1 (MCP-1) expression in the kidneys of db/db mice. Our results indicate that the expression of MCP-1 significantly increased in the kidneys of db/db mice in a time-dependent manner. An increased chromatin mark associated with an active gene (H3K4me1) at MCP-1 promoters accompanied this change in expression. The expression of SET7/9 and the recruitment to these promoters were also elevated. SET7/9 gene silencing with small interfering (si) RNAs significantly attenuated the expression of H3K4me1 and MCP-1. Furthermore, expression of signaling regulator glucose-regulated protein 78 (GRP78), a monitor of ER stress, significantly increased in the kidneys of db/db mice. The expression of spliced X-box binding protein 1 (XBP1s), an ER stress-inducible transcription factor, and recruitment to the SET7/9 promoters were also increased. XBP1s gene silencing with siRNAs significantly attenuated the expression of SET7/9, H3K4me1, and MCP-1. The chaperone betaine not only effectively downregulated the GRP78 and XBP1s expression levels but also markedly decreased the SET7/9, H3K4me1, and MCP-1 levels. Luciferase reporter assay demonstrated that XBP1s participated in ER stress-induced SET7/9 transcription, Taken together, these results reveal that ER stress can trigger the expression of MCP-1, in part through the XBP1s-mediated induction of SET7/9.

  3. Specific overexpression of tumour necrosis factor-α-induced protein (TNFAIP)9 in CD14(+) CD16(-) monocytes in patients with rheumatoid arthritis: comparative analysis with TNFAIP3.

    PubMed

    Takai, C; Matsumoto, I; Inoue, A; Umeda, N; Tanaka, Y; Kurashima, Y; Wada, Y; Narita, I; Sumida, T

    2015-06-01

    The tumour necrosis factor (TNF)-α-induced proteins (TNFAIP)9 and TNFAIP3 play an important pathogenic role in murine arthritis. To clarify their pathophysiological roles in patients with rheumatoid arthritis (RA), we examined their expression and localization in peripheral blood mononuclear cells (PBMC). TNFAIP9 and TNFAIP3 mRNA expression was determined in PBMC of RA patients and healthy subjects (control). Flow cytometry was used to analyse the main TNFAIP9- and TNFAIP3-expressing cell populations. TNFAIP9 and TNFAIP3 mRNA expression levels were examined in vitro on CD14(+) cells stimulated with TNF-α and lipopolysaccharide (LPS). The expression levels of TNFAIP9 and TNFAIP3 mRNA were also measured before and 12 weeks after treatment with tocilizumab and abatacept. TNFAIP9 expression was significantly higher, while TNFAIP3 expression was lower in PBMC of RA (n=36) than the control (n=24) (each P < 0.05). TNFAIP9 was expressed on CD14(+) cells, especially in human leucocyte antigen D-related (HLA-DR)(+) CD14(bright) CD16(-) cells, while TNFAIP3 was expressed mainly on CD3(+) T cells. TNF-α and LPS induced TNFAIP9 and TNFAIP3 in human CD14(+) monocytes in vitro. Treatment with tocilizumab (n=13), but not abatacept (n=11), significantly reduced TNFAIP9 mRNA expression in PBMC, which was associated with reduction in the number of circulating CD14(bright) monocytes. The expression of TNFAIP9 in CD14(+) cells was specifically elevated in patients with RA, regulated by TNF-α and LPS, and suppressed by tocilizumab, while TNFAIP3 in PBMC showed different localization and induction patterns. © 2015 British Society for Immunology.

  4. MYCN and HDAC5 transcriptionally repress CD9 to trigger invasion and metastasis in neuroblastoma

    PubMed Central

    Fabian, Johannes; Opitz, Desirée; Althoff, Kristina; Lodrini, Marco; Hero, Barbara; Volland, Ruth; Beckers, Anneleen; de Preter, Katleen; Decock, Anneleen; Patil, Nitin; Abba, Mohammed; Kopp-Schneider, Annette; Astrahantseff, Kathy; Wünschel, Jasmin; Pfeil, Sebastian; Ercu, Maria; Künkele, Annette; Hu, Jamie; Thole, Theresa; Schweizer, Leonille; Mechtersheimer, Gunhild; Carter, Daniel; Cheung, Belamy B.; Popanda, Odilia; von Deimling, Andreas; Koster, Jan; Versteeg, Rogier; Schwab, Manfred; Marshall, Glenn M.; Speleman, Frank; Erb, Ulrike; Zoeller, Margot; Allgayer, Heike; Simon, Thorsten; Fischer, Matthias; Kulozik, Andreas E.; Eggert, Angelika; Witt, Olaf; Schulte, Johannes H.; Deubzer, Hedwig E.

    2016-01-01

    The systemic and resistant nature of metastatic neuroblastoma renders it largely incurable with current multimodal treatment. Clinical progression stems mainly from the increasing burden of metastatic colonization. Therapeutically inhibiting the migration-invasion-metastasis cascade would be of great benefit, but the mechanisms driving this cycle are as yet poorly understood. In-depth transcriptome analyses and ChIP-qPCR identified the cell surface glycoprotein, CD9, as a major downstream player and direct target of the recently described GRHL1 tumor suppressor. CD9 is known to block or facilitate cancer cell motility and metastasis dependent upon entity. High-level CD9 expression in primary neuroblastomas correlated with patient survival and established markers for favorable disease. Low-level CD9 expression was an independent risk factor for adverse outcome. MYCN and HDAC5 colocalized to the CD9 promoter and repressed transcription. CD9 expression diminished with progressive tumor development in the TH-MYCN transgenic mouse model for neuroblastoma, and CD9 expression in neuroblastic tumors was far below that in ganglia from wildtype mice. Primary neuroblastomas lacking MYCN amplifications displayed differential CD9 promoter methylation in methyl-CpG-binding domain sequencing analyses, and high-level methylation was associated with advanced stage disease, supporting epigenetic regulation. Inducing CD9 expression in a SH-EP cell model inhibited migration and invasion in Boyden chamber assays. Enforced CD9 expression in neuroblastoma cells transplanted onto chicken chorioallantoic membranes strongly reduced metastasis to embryonic bone marrow. Combined treatment of neuroblastoma cells with HDAC/DNA methyltransferase inhibitors synergistically induced CD9 expression despite hypoxic, metabolic or cytotoxic stress. Our results show CD9 is a critical and indirectly druggable suppressor of the invasion-metastasis cycle in neuroblastoma. PMID:27572323

  5. MYCN and HDAC5 transcriptionally repress CD9 to trigger invasion and metastasis in neuroblastoma.

    PubMed

    Fabian, Johannes; Opitz, Desirée; Althoff, Kristina; Lodrini, Marco; Hero, Barbara; Volland, Ruth; Beckers, Anneleen; de Preter, Katleen; Decock, Anneleen; Patil, Nitin; Abba, Mohammed; Kopp-Schneider, Annette; Astrahantseff, Kathy; Wünschel, Jasmin; Pfeil, Sebastian; Ercu, Maria; Künkele, Annette; Hu, Jamie; Thole, Theresa; Schweizer, Leonille; Mechtersheimer, Gunhild; Carter, Daniel; Cheung, Belamy B; Popanda, Odilia; von Deimling, Andreas; Koster, Jan; Versteeg, Rogier; Schwab, Manfred; Marshall, Glenn M; Speleman, Frank; Erb, Ulrike; Zoeller, Margot; Allgayer, Heike; Simon, Thorsten; Fischer, Matthias; Kulozik, Andreas E; Eggert, Angelika; Witt, Olaf; Schulte, Johannes H; Deubzer, Hedwig E

    2016-10-11

    The systemic and resistant nature of metastatic neuroblastoma renders it largely incurable with current multimodal treatment. Clinical progression stems mainly from the increasing burden of metastatic colonization. Therapeutically inhibiting the migration-invasion-metastasis cascade would be of great benefit, but the mechanisms driving this cycle are as yet poorly understood. In-depth transcriptome analyses and ChIP-qPCR identified the cell surface glycoprotein, CD9, as a major downstream player and direct target of the recently described GRHL1 tumor suppressor. CD9 is known to block or facilitate cancer cell motility and metastasis dependent upon entity. High-level CD9 expression in primary neuroblastomas correlated with patient survival and established markers for favorable disease. Low-level CD9 expression was an independent risk factor for adverse outcome. MYCN and HDAC5 colocalized to the CD9 promoter and repressed transcription. CD9 expression diminished with progressive tumor development in the TH-MYCN transgenic mouse model for neuroblastoma, and CD9 expression in neuroblastic tumors was far below that in ganglia from wildtype mice. Primary neuroblastomas lacking MYCN amplifications displayed differential CD9 promoter methylation in methyl-CpG-binding domain sequencing analyses, and high-level methylation was associated with advanced stage disease, supporting epigenetic regulation. Inducing CD9 expression in a SH-EP cell model inhibited migration and invasion in Boyden chamber assays. Enforced CD9 expression in neuroblastoma cells transplanted onto chicken chorioallantoic membranes strongly reduced metastasis to embryonic bone marrow. Combined treatment of neuroblastoma cells with HDAC/DNA methyltransferase inhibitors synergistically induced CD9 expression despite hypoxic, metabolic or cytotoxic stress. Our results show CD9 is a critical and indirectly druggable suppressor of the invasion-metastasis cycle in neuroblastoma.

  6. Transcriptome profiling reveals miR-9-3p as a novel tumor suppressor in gastric cancer.

    PubMed

    Meng, Qingshun; Xiang, Longquan; Fu, Jingwei; Chu, Xianqun; Wang, Chunlin; Yan, Bingzheng

    2017-06-06

    It has been well established that microRNAs (miRNAs) play important roles in biological processes. To comprehensively measure the altered miRNA expression, we presented the miRNA expression profile of gastric cancer using microarray. We identified 33 miRNAs that were significantly differentially regulated in gastric specimens compared to adjacent normal tissues, among which miR-9-3p expression are significantly down-regulated in gastric cancers. Next, a cohort of 100 gastric cancer tissues and matched normal tissues were enrolled. Kaplan-Meier and multivariate Cox survival analyses were applied to evaluate the prognostic value of miR-9-3p expression, and the result showed that patients with lower miR-9-3p expression level have significantly poorer overall survival. The expression level of miR-9-3p has been proved to be an independent prognostic factor for 5-year overall survival. Furthermore, the result indicated that over-expression of miR-9-3p can inhibit gastric cancer cell invasion. Taken together, our results suggested that miR-9-3p plays important role in tumor invasion, and these findings implicated the potential effects of miR-9-3p on prognosis of gastric cancer.

  7. Overexpressed homeobox B9 regulates oncogenic activities by transforming growth factor-β1 in gliomas

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fang, Liping; Xu, Yinghui; Zou, Lijuan, E-mail: zoulijuantg@126.com

    2014-03-28

    Highlights: • HOXB9 is overexpressed in gliomas. • HOXB9 over expression had shorter survival time than down expression in gliomas. • HOXB9 stimulated the proliferation, migration and sphere formation of glioma cells. • Activation of TGF-β1 contributed to HOXB9-induced oncogenic activities. - Abstract: Glioma is the leading cause of deaths related to tumors in the central nervous system. The mechanisms of gliomagenesis remain elusive to date. Homeobox B9 (HOXB9) has a crucial function in the regulation of gene expression and cell survival, but its functions in glioma formation and development have yet to be elucidated. This study showed that HOXB9more » expression in glioma tissues was significantly higher than that in nontumor tissues. Higher HOXB9 expression was also significantly associated with advanced clinical stage in glioma patients. HOXB9 overexpression stimulated the proliferation, migration, and sphere formation of glioma cells, whereas HOXB9 knockdown elicited an opposite effect. HOXB9 overexpression also increased the tumorigenicity of glioma cells in vivo. Moreover, the activation of transforming growth factor-β1 contributed to HOXB9-induced oncogenic activities. HOXB9 could be used as a predictable biomarker to be detected in different pathological and histological subtypes in glioma for diagnosis or prognosis.« less

  8. Immunologic hierarchy, class II MHC promiscuity, and epitope spreading of a melanoma helper peptide vaccine.

    PubMed

    Hu, Yinin; Petroni, Gina R; Olson, Walter C; Czarkowski, Andrea; Smolkin, Mark E; Grosh, William W; Chianese-Bullock, Kimberly A; Slingluff, Craig L

    2014-08-01

    Immunization with a combination melanoma helper peptide (6MHP) vaccine has been shown to induce CD4(+) T cell responses, which are associated with patient survival. In the present study, we define the relative immunogenicity and HLA allele promiscuity of individual helper peptides and identify helper peptide-mediated augmentation of specific CD8(+) T cell responses. Thirty-seven participants with stage IIIB-IV melanoma were vaccinated with 6MHP in incomplete Freund's adjuvant. The 6MHP vaccine is comprised of 6 peptides representing melanocytic differentiation proteins gp100, tyrosinase, Melan-A/MART-1, and cancer testis antigens from the MAGE family. CD4(+) and CD8(+) T cell responses were assessed in peripheral blood and in sentinel immunized nodes (SIN) by thymidine uptake after exposure to helper peptides and by direct interferon-γ ELIspot assay against 14 MHC class I-restricted peptides. Vaccine-induced CD4(+) T cell responses to individual epitopes were detected in the SIN of 63 % (22/35) and in the peripheral blood of 38 % (14/37) of participants for an overall response rate of 65 % (24/37). The most frequently immunogenic peptides were MAGE-A3281-295 (49 %) and tyrosinase386-406 (32 %). Responses were not limited to HLA restrictions originally described. Vaccine-associated CD8(+) T cell responses against class I-restricted peptides were observed in 45 % (5/11) of evaluable participants. The 6MHP vaccine induces both CD4(+) and CD8(+) T cell responses against melanoma antigens. CD4(+) T cell responses were detected beyond reported HLA-DR restrictions. Induction of CD8(+) T cell responses suggests epitope spreading and systemic activity mediated at the tumor site.

  9. Expression of VEGFR and PDGFR-α/-β in 187 canine nasal carcinomas.

    PubMed

    Gramer, I; Killick, D; Scase, T; Chandry, D; Marrington, M; Blackwood, L

    2017-09-01

    Radiotherapy represents the standard of care for intranasal carcinomas. Responses to tyrosine kinase inhibitors (TKIs) have been reported but data on expression of target receptor tyrosine kinases (rTKs) is limited. This study characterizes the expression of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR)-α and PDGFR-β in canine intranasal carcinomas. Histological samples from 187 dogs were retrieved. Immunohistochemistry was performed using commercially available antibodies. Expression of rTKs was classified into weak, moderate or intense and additionally recorded as cytoplasmic, membranous, cytoplasmic-membranous, nuclear or stromal. VEGFR was expressed in 158 dogs with predominantly moderate expression (36.9%) and a cytoplasmic-membranous expression pattern (70.9%). PDGFR-α was detected in 133 with predominantly weak expression (57.9%) and cytoplasmic pattern (87.9%). PDGFR-β was identified in 74 patients with a predominantly moderate expression (17.6%) and cytoplasmic expression pattern (63.5%). Co-expression of rTKs was common. These results confirm expression of VEGFR, PDGFR-α and PDGFR-β in canine intranasal carcinomas and support the utility of TKIs. © 2016 John Wiley & Sons Ltd.

  10. Roles of Soybean Plasma Membrane Intrinsic Protein GmPIP2;9 in Drought Tolerance and Seed Development.

    PubMed

    Lu, Linghong; Dong, Changhe; Liu, Ruifang; Zhou, Bin; Wang, Chuang; Shou, Huixia

    2018-01-01

    Aquaporins play an essential role in water uptake and transport in vascular plants. The soybean genome contains a total of 22 plasma membrane intrinsic protein (PIP) genes. To identify candidate PIPs important for soybean yield and stress tolerance, we studied the transcript levels of all 22 soybean PIPs. We found that a GmPIP2 subfamily member, GmPIP2;9, was predominately expressed in roots and developing seeds. Here, we show that GmPIP2;9 localized to the plasma membrane and had high water channel activity when expressed in Xenopus oocytes. Using transgenic soybean plants expressing a native GmPIP2;9 promoter driving a GUS-reporter gene, it was found high GUS expression in the roots, in particular, in the endoderm, pericycle, and vascular tissues of the roots of transgenic plants. In addition, GmPIP2;9 was also highly expressed in developing pods. GmPIP2;9 expression significantly increased in short term of polyethylene glycol (PEG)-mediated drought stress treatment. GmPIP2;9 overexpression increased tolerance to drought stress in both solution cultures and soil plots. Drought stress in combination with GmPIP2;9 overexpression increased net CO 2 assimilation of photosynthesis, stomata conductance, and transpiration rate, suggesting that GmPIP2;9- overexpressing transgenic plants were less stressed than wild-type (WT) plants. Furthermore, field experiments showed that GmPIP2;9 -overexpressing plants had significantly more pod numbers and larger seed sizes than WT plants. In summary, the study demonstrated that GmPIP2;9 has water transport activity. Its relative high expression levels in roots and developing pods are in agreement with the phenotypes of GmPIP2;9 -overexpressing plants in drought stress tolerance and seed development.

  11. Roles of Soybean Plasma Membrane Intrinsic Protein GmPIP2;9 in Drought Tolerance and Seed Development

    PubMed Central

    Lu, Linghong; Dong, Changhe; Liu, Ruifang; Zhou, Bin; Wang, Chuang; Shou, Huixia

    2018-01-01

    Aquaporins play an essential role in water uptake and transport in vascular plants. The soybean genome contains a total of 22 plasma membrane intrinsic protein (PIP) genes. To identify candidate PIPs important for soybean yield and stress tolerance, we studied the transcript levels of all 22 soybean PIPs. We found that a GmPIP2 subfamily member, GmPIP2;9, was predominately expressed in roots and developing seeds. Here, we show that GmPIP2;9 localized to the plasma membrane and had high water channel activity when expressed in Xenopus oocytes. Using transgenic soybean plants expressing a native GmPIP2;9 promoter driving a GUS-reporter gene, it was found high GUS expression in the roots, in particular, in the endoderm, pericycle, and vascular tissues of the roots of transgenic plants. In addition, GmPIP2;9 was also highly expressed in developing pods. GmPIP2;9 expression significantly increased in short term of polyethylene glycol (PEG)-mediated drought stress treatment. GmPIP2;9 overexpression increased tolerance to drought stress in both solution cultures and soil plots. Drought stress in combination with GmPIP2;9 overexpression increased net CO2 assimilation of photosynthesis, stomata conductance, and transpiration rate, suggesting that GmPIP2;9-overexpressing transgenic plants were less stressed than wild-type (WT) plants. Furthermore, field experiments showed that GmPIP2;9-overexpressing plants had significantly more pod numbers and larger seed sizes than WT plants. In summary, the study demonstrated that GmPIP2;9 has water transport activity. Its relative high expression levels in roots and developing pods are in agreement with the phenotypes of GmPIP2;9-overexpressing plants in drought stress tolerance and seed development. PMID:29755491

  12. SLC9A9 Co-expression modules in autism-associated brain regions.

    PubMed

    Patak, Jameson; Hess, Jonathan L; Zhang-James, Yanli; Glatt, Stephen J; Faraone, Stephen V

    2017-03-01

    SLC9A9 is a sodium hydrogen exchanger present in the recycling endosome and highly expressed in the brain. It is implicated in neuropsychiatric disorders, including autism spectrum disorders (ASDs). Little research concerning its gene expression patterns and biological pathways has been conducted. We sought to investigate its possible biological roles in autism-associated brain regions throughout development. We conducted a weighted gene co-expression network analysis on RNA-seq data downloaded from Brainspan. We compared prenatal and postnatal gene expression networks for three ASD-associated brain regions known to have high SLC9A9 gene expression. We also performed an ASD-associated single nucleotide polymorphism enrichment analysis and a cell signature enrichment analysis. The modules showed differences in gene constituents (membership), gene number, and connectivity throughout time. SLC9A9 was highly associated with immune system functions, metabolism, apoptosis, endocytosis, and signaling cascades. Gene list comparison with co-immunoprecipitation data was significant for multiple modules. We found a disproportionately high autism risk signal among genes constituting the prenatal hippocampal module. The modules were enriched with astrocyte and oligodendrocyte markers. SLC9A9 is potentially involved in the pathophysiology of ASDs. Our investigation confirmed proposed functions for SLC9A9, such as endocytosis and immune regulation, while also revealing potential roles in mTOR signaling and cell survival.. By providing a concise molecular map and interactions, evidence of cell type and implicated brain regions we hope this will guide future research on SLC9A9. Autism Res 2017, 10: 414-429. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

  13. A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination

    PubMed Central

    Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Shi, Yanhong

    2009-01-01

    Summary MicroRNAs are important players in stem cell biology. Among them, microRNA-9 (miR-9) is expressed specifically in neurogenic areas of the brain. Whether miR-9 plays a role in neural stem cell self-renewal and differentiation is unknown. We showed previously that nuclear receptor TLX is an essential regulator of neural stem cell self-renewal. Here we show that miR-9 suppresses TLX expression to negatively regulate neural stem cell proliferation and accelerate neural differentiation. Introducing a TLX expression vector lacking the miR-9 recognition site rescued miR-9-induced proliferation deficiency and inhibited precocious differentiation. In utero electroporation of miR-9 in embryonic brains led to premature differentiation and outward migration of the transfected neural stem cells. Moreover, TLX represses miR-9 pri-miRNA expression. MiR-9, by forming a negative regulatory loop with TLX, establishes a model for controlling the balance between neural stem cell proliferation and differentiation. PMID:19330006

  14. Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region.

    PubMed

    Möbius, Patrick; Preidl, Raimund H M; Weber, Manuel; Amann, Kerstin; Neukam, Friedrich W; Wehrhan, Falk

    2017-11-01

    Surgical treatment of head and neck malignancies frequently includes microvascular free tissue transfer. Preoperative radiotherapy increases postoperative fibrosis-related complications up to transplant loss. Fibrogenesis is associated with re-expression of embryonic preserved tissue developmental mediators: osteopontin (OPN), regulated by sex-determining region Y‑box 9 (Sox9), and homeobox A9 (HoxA9) play important roles in pathologic tissue remodeling and are upregulated in atherosclerotic vascular lesions; dickkopf-1 (DKK1) inhibits pro-fibrotic and atherogenic Wnt signaling. We evaluated the influence of irradiation on expression of these mediators in arteries of the head and neck region. DKK1, HoxA9, OPN, and Sox9 expression was examined immunohistochemically in 24 irradiated and 24 nonirradiated arteries of the lower head and neck region. The ratio of positive cells to total cell number (labeling index) in the investigated vessel walls was assessed semiquantitatively. DKK1 expression was significantly decreased, whereas HoxA9, OPN, and Sox9 expression were significantly increased in irradiated compared to nonirradiated arterial vessels. Preoperative radiotherapy induces re-expression of embryonic preserved mediators in arterial vessels and may thus contribute to enhanced activation of pro-fibrotic downstream signaling leading to media hypertrophy and intima degeneration comparable to fibrotic development steps in atherosclerosis. These histopathological changes may be promoted by HoxA9-, OPN-, and Sox9-related inflammation and vascular remodeling, supported by downregulation of anti-fibrotic DKK1. Future pharmaceutical strategies targeting these vessel alterations, e. g., bisphosphonates, might reduce postoperative complications in free tissue transfer.

  15. Cis Association of Galectin-9 with Tim-3 Differentially Regulates IL-12/IL-23 Expressions in Monocytes via TLR Signaling

    PubMed Central

    Ma, Cheng J.; Li, Guang Y.; Cheng, Yong Q.; Wang, Jia M.; Ying, Ruo S.; Shi, Lei; Wu, Xiao Y.; Niki, Toshiro; Hirashima, Mitsumi; Li, Chuan F.; Moorman, Jonathan P.; Yao, Zhi Q.

    2013-01-01

    Human monocytes/macrophages (M/MФ) of the innate immunity sense and respond to microbial products via specific receptor coupling with stimulatory (such as TLR) and inhibitory (such as Tim-3) receptors. Current models imply that Tim-3 expression on M/MØ can deliver negative signaling to TLR-mediated IL-12 expression through trans association with its ligand Galectin-9 (Gal-9) presented by other cells. However, Gal-9 is also expressed within M/MØ, and the effect of intracellular Gal-9 on Tim-3 activities and inflammatory responses in the same M/MØ remains unknown. In this study, our data suggest that Tim-3 and IL-12/IL-23 gene transcriptions are regulated by enhanced or silenced Gal-9 expression within monocytes through synergizing with TLR signaling. Additionally, TLR activation facilitates Gal-9/Tim-3 cis association within the same M/MØ to differentially regulate IL-12/IL-23 expressions through STAT-3 phosphorylation. These results reveal a ligand (Gal-9) compartment-dependent regulatory effect on receptor (Tim-3) activities and inflammatory responses via TLR pathways—a novel mechanism underlying cellular responses to external or internal cues. PMID:23967307

  16. Self-compassion moderates the perfectionism and depression link in both adolescence and adulthood

    PubMed Central

    Yap, Keong; Scott, Nicole; Einstein, Danielle A.; Ciarrochi, Joseph

    2018-01-01

    Background Psychological practitioners often seek to directly change the form or frequency of clients’ maladaptive perfectionist thoughts, because such thoughts predict future depression. Indirect strategies, such as self-compassion interventions, that seek to change clients’ relationships to difficult thoughts, rather than trying to change the thoughts directly could be just as effective. This study aimed to investigate whether self-compassion moderated, or weakened, the relationship between high perfectionism and high depression symptoms in both adolescence and adulthood. Methods The present study utilised anonymous self-report questionnaires to assess maladaptive perfectionism, depression, and self-compassion across two samples covering much of the lifespan. Questionnaires were administered in a high school setting for the adolescent sample (Study 1, Mage = 14.1 years, n = 541), and advertised through university and widely online to attract a convenience sample of adults (Study 2, Mage = 25.22 years, n = 515). Results Moderation analyses revealed that self-compassion reduced the strength of relationship between maladaptive perfectionism and depression in our adolescent Study 1 (β = -.15, p < .001, R2 = .021.) and our adult study 2 (β = -.14, p < .001, R2 = .020). Limitations Cross-sectional self-reported data restricts the application of causal conclusions and also relies on accurate self-awareness and willingness to respond to questionnaire openly. Conclusions The replication of this finding in two samples and across different age-appropriate measures suggests that self-compassion does moderate the link between perfectionism and depression. Self-compassion interventions may be a useful way to undermine the effects of maladaptive perfectionism, but future experimental or intervention research is needed to fully assess this important possibility. PMID:29466452

  17. Development of a Digital-Based Instrument to Assess Perceived Motor Competence in Children: Face Validity, Test-Retest Reliability, and Internal Consistency

    PubMed Central

    Palmer, Kara K.

    2017-01-01

    Assessing children’s perceptions of their movement abilities (i.e., perceived competence) is traditionally done using picture scales—Pictorial Scale of Perceived Competence and Acceptance for Young Children or Pictorial Scale of Perceived Movement Skill Competence. Pictures fail to capture the temporal components of movement. To address this limitation, we created a digital-based instrument to assess perceived motor competence: the Digital Scale of Perceived Motor Competence. The purpose of this study was to determine the validity, reliability, and internal consistency of the Digital-based Scale of Perceived Motor Skill Competence. The Digital-based Scale of Perceived Motor Skill Competence is based on the twelve fundamental motor skills from the Test of Gross Motor Development-2nd Edition with a similar layout and item structure as the Pictorial Scale of Perceived Movement Skill Competence. Face Validity of the instrument was examined in Phase I (n = 56; Mage = 8.6 ± 0.7 years, 26 girls). Test-retest reliability and internal consistency were assessed in Phase II (n = 54, Mage = 8.7 years ± 0.5 years, 26 girls). Intra-class correlations (ICC) and Cronbach’s alpha were conducted to determine test-retest reliability and internal consistency for all twelve skills along with locomotor and object control subscales. The Digital Scale of Perceived Motor Competence demonstrates excellent test-retest reliability (ICC = 0.83, total; ICC = 0.77, locomotor; ICC = 0.79, object control) and acceptable/good internal consistency (α = 0.62, total; α = 0.57, locomotor; α = 0.49, object control). Findings provide evidence of the reliability of the three level digital-based instrument of perceived motor competence for older children. PMID:29910408

  18. Lack of Evidence for Green Tea Polyphenols as DNA Methylation Inhibitors in Murine Prostate

    PubMed Central

    Morey Kinney, Shannon R.; Zhang, Wa; Pascual, Marien; Greally, John M.; Gillard, Bryan M.; Karasik, Ellen; Foster, Barbara A.; Karpf, Adam R.

    2009-01-01

    Green tea polyphenols (GTPs) have been reported to inhibit DNA methylation in cultured cells. Here we tested whether oral consumption of GTPs affects normal or cancer specific DNA methylation in vivo, using mice. Wildtype (WT) and Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice were administered 0.3% GTPs in drinking water beginning at 4 weeks of age. To monitor DNA methylation, we measured 5-methyl-deoxycytidine (5mdC) levels, methylation of the B1 repetitive element, and methylation of the Mage-a8 gene. Each of these parameters were unchanged in prostate, gut, and liver from WT mice at both 12 and 24 weeks of age, with the single exception of a decrease of 5mdC in the liver at 12 weeks. In GTP-treated TRAMP mice, 5mdC levels and the methylation status of four loci hypermethylated during tumor progression were unaltered in TRAMP prostates at 12 or 24 weeks. Quite surprisingly, GTP treatment did not inhibit tumor progression in TRAMP mice, although known pharmacodynamic markers of GTPs were altered in both WT and TRAMP prostates. We also administered 0.1%, 0.3%, or 0.6% GTPs to TRAMP mice for 12 weeks and measured 5mdC levels and methylation of B1 and Mage-a8 in prostate, gut, and liver tissues. No dose-dependent alterations in DNA methylation status were observed. Genome-wide DNA methylation profiling using the HELP assay also revealed no significant hypomethylating effect of GTP. These data indicate that oral administration of GTPs does not affect normal or cancer-specific DNA methylation in the murine prostate. PMID:19934341

  19. Suppression of HBV replication by the expression of nickase- and nuclease dead-Cas9.

    PubMed

    Kurihara, Takeshi; Fukuhara, Takasuke; Ono, Chikako; Yamamoto, Satomi; Uemura, Kentaro; Okamoto, Toru; Sugiyama, Masaya; Motooka, Daisuke; Nakamura, Shota; Ikawa, Masato; Mizokami, Masashi; Maehara, Yoshihiko; Matsuura, Yoshiharu

    2017-07-21

    Complete removal of hepatitis B virus (HBV) DNA from nuclei is difficult by the current therapies. Recent reports have shown that a novel genome-editing tool using Cas9 with a single-guide RNA (sgRNA) system can cleave the HBV genome in vitro and in vivo. However, induction of a double-strand break (DSB) on the targeted genome by Cas9 risks undesirable off-target cleavage on the host genome. Nickase-Cas9 cleaves a single strand of DNA, and thereby two sgRNAs are required for inducing DSBs. To avoid Cas9-induced off-target mutagenesis, we examined the effects of the expressions of nickase-Cas9 and nuclease dead Cas9 (d-Cas9) with sgRNAs on HBV replication. The expression of nickase-Cas9 with a pair of sgRNAs cleaved the target HBV genome and suppressed the viral-protein expression and HBV replication in vitro. Moreover, nickase-Cas9 with the sgRNA pair cleaved the targeted HBV genome in mouse liver. Interestingly, d-Cas9 expression with the sgRNAs also suppressed HBV replication in vitro without cleaving the HBV genome. These results suggest the possible use of nickase-Cas9 and d-Cas9 with a pair of sgRNAs for eliminating HBV DNA from the livers of chronic hepatitis B patients with low risk of undesirable off-target mutation on the host genome.

  20. Stage-specific control of connective tissue growth factor (CTGF/CCN2) expression in chondrocytes by Sox9 and beta-catenin.

    PubMed

    Huang, Bau-Lin; Brugger, Sean M; Lyons, Karen M

    2010-09-03

    CCN2/connective tissue growth factor is highly expressed in hypertrophic chondrocytes and is required for chondrogenesis. However, the transcriptional mechanisms controlling its expression in cartilage are largely unknown. The activity of the Ccn2 promoter was, therefore, investigated in osteochondro-progenitor cells and hypertrophic chondrocytes to ascertain these mechanisms. Sox9 and T-cell factor (TCF) x lymphoid enhancer factor (LEF) factors contain HMG domains and bind to related consensus sites. TCF x LEF factors are normally repressive but when bound to DNA in a complex with beta-catenin become activators of gene expression. In silico analysis of the Ccn2 proximal promoter identified multiple consensus TCF x LEF elements, one of which was also a consensus binding site for Sox9. Using luciferase reporter constructs, the TCF x LEF x Sox9 site was found to be involved in stage-specific expression of Ccn2. Luciferase, electrophoretic mobility shift assay (EMSA), and ChIP analysis revealed that Sox9 represses Ccn2 expression by binding to the consensus TCF x LEF x Sox9 site. On the other hand, the same assays showed that in hypertrophic chondrocytes, TCF x LEF x beta-catenin complexes occupy the consensus TCF x LEF x Sox9 site and activate Ccn2 expression. Furthermore, transgenic mice in which lacZ expression is driven under the control of the proximal Ccn2 promoter revealed that the proximal Ccn2 promoter responded to Wnt signaling in cartilage. Hence, we propose that differential occupancy of the TCF x LEF x Sox9 site by Sox9 versus beta-catenin restricts high levels of Ccn2 expression to hypertrophic chondrocytes.

  1. Changes in matrix metalloproteinase network in a spontaneous autoimmune uveitis model.

    PubMed

    Hofmaier, Florian; Hauck, Stefanie M; Amann, Barbara; Degroote, Roxane L; Deeg, Cornelia A

    2011-04-08

    Autoimmune uveitis is a sight-threatening disease in which autoreactive T cells cross the blood-retinal barrier. Molecular mechanisms contributing to the loss of eye immune privilege in this autoimmune disease are not well understood. In this study, the authors investigated the changes in the matrix metalloproteinase network in spontaneous uveitis. Matrix metalloproteinase (MMP) MMP2, MMP9, and MMP14 expression and tissue inhibitor of metalloproteinase (TIMP)-2 and lipocalin 2 (LCN2) expression were analyzed using Western blot quantification. Enzyme activities were examined with zymography. Expression patterns of network candidates were revealed with immunohistochemistry, comparing physiological appearance and changes in a spontaneous recurrent uveitis model. TIMP2 protein expression was found to be decreased in both the vitreous and the retina of a spontaneous model for autoimmune uveitis (equine recurrent uveitis [ERU]), and TIMP2 activity was significantly reduced in ERU vitreous. Functionally associated MMPs such as MMP2, MMP14, and MMP9 were found to show altered or shifted expression and activity. Although MMP2 decreased in ERU vitreous, MMP9 expression and activity were found to be increased. These changes were reflected by profound changes within uveitic target tissue, where TIMP2, MMP9, and MMP14 decreased in expression, whereas MMP2 displayed a shifted expression pattern. LCN2, a potential stabilizer of MMP9, was found prominently expressed in equine healthy retina and displayed notable changes in expression patterns accompanied by significant upregulation in autoimmune conditions. Invading cells expressed MMP9 and LCN2. This study implicates a dysregulation or a change in functional protein-protein interactions in this TIMP2-associated protein network, together with altered expression of functionally related MMPs.

  2. In Vitro Studies on the Antimicrobial Peptide Human Beta-Defensin 9 (HBD9): Signalling Pathways and Pathogen-Related Response (An American Ophthalmological Society Thesis)

    PubMed Central

    Dua, Harminder S.; Otri, Ahmad Muneer; Hopkinson, Andrew; Mohammed, Imran

    2014-01-01

    Purpose: Human β-defensins (HBDs) are an important part of the innate immune host defense at the ocular surface. Unlike other defensins, expression of HBD9 at the ocular surface is reduced during microbial infection, but activation of toll-like receptor 2 (TLR2) in corneal epithelial cells has been shown to up-regulate HBD9. Our purpose was to test the hypothesis that TLR2 has a key role in the signalling pathway(s) involved in the overexpression or underexpression of HBD9, and accordingly, different pathogens would induce a different expression pattern of HBD9. Methods: The in vitro RNAi silencing method and response to dexamethasone were used to determine key molecules involved in signalling pathways of HBD9 in immortalized human corneal epithelial cells. The techniques included cell culture with exposure to specific transcription factor inhibitors and bacteria, RNA extraction and cDNA synthesis, quantitative real-time polymerase chain reaction, and immunohistology. Results: This study demonstrates that TLR2 induces HBD9 mRNA and protein expression in a time- and dose-dependent manner. Transforming growth factor-β–activated kinase 1 (TAK1) plays a central role in HBD9 induction by TLR2, and transcription factors c-JUN and activating transcription factor 2 are also involved. Dexamethasone reduces TLR2-mediated up-regulation of HBD9 mRNA and protein levels in mitogen-activated protein kinase phosphatase 1 (MKP1)-dependent and c-JUN-independent manner. HBD9 expression differs with gram-negative and gram-positive bacteria. Conclusions: TLR2-mediated MKPs and nuclear factor-κB signalling pathways are involved in HBD9 expression. TAK-1 is a key molecule. These molecules can be potentially targeted to modulate HBD9 expression. Differential expression of HBD9 with different bacteria could be related to differences in pathogen-associated molecular patterns of these organisms. PMID:25646028

  3. A Twin Factor Mixture Modeling Approach to Childhood Temperament: Differential Heritability

    PubMed Central

    Scott, Brandon G.; Lemery-Chalfant, Kathryn; Clifford, Sierra; Tein, Jenn-Yun; Stoll, Ryan; Goldsmith, H. Hill

    2016-01-01

    Twin factor mixture modeling was used to identify temperament profiles, while simultaneously estimating a latent factor model for each profile with a sample of 787 twin pairs (Mage =7.4 years; SD = .84; 49% female; 88.3% Caucasian), using mother- and father-reported temperament. A 4-profile, 1-factor model fit the data well. Profiles included ‘Regulated, Typical Reactive’, ‘Well-regulated, Positive Reactive’, ‘Regulated, Surgent’, and ‘Dysregulated, Negative Reactive.’ All profiles were heritable, with heritability lower and shared environment also contributing to membership in the ‘Regulated, Typical Reactive’ and ‘Dysregulated, Negative Reactive’ profiles. PMID:27291568

  4. Matrix metalloproteinase 9 and transglutaminase 2 expression at the ocular surface in patients with different forms of dry eye disease.

    PubMed

    Aragona, Pasquale; Aguennouz, M'Hammed; Rania, Laura; Postorino, Elisa; Sommario, Margherita Serena; Roszkowska, Anna Maria; De Pasquale, Maria Grazia; Pisani, Antonina; Puzzolo, Domenico

    2015-01-01

    To evaluate the expression of matrix metalloproteinase 9 (MMP9) and transglutaminase 2 (TG2) in different forms of dry eye. Case control study. Seventy-five female subjects divided into 3 groups: group 1, 15 healthy controls; group 2, 30 subjects with Sjögren syndrome (SS); and group 3, 30 subjects with Meibomian gland dysfunction (MGD). A clinical assessment was carried out and impression cytologic specimens were processed for immunoperoxidase staining for MMP9 and TG2 and real-time polymerase chain reaction analyses were carried out for MMP9, TG2, interleukin-6, interferon-γ, B-cell lymphoma 2, and caspase 3. To study MMP9 and TG2 expression after anti-inflammatory treatment, patients were divided into 2 subgroups, one treated with saline and the other treated with saline plus topical corticosteroid eye drops (0.5% loteprednol etabonate) 4 times daily for 15 days. For statistical analysis, Student t test, Mann-Whitney U test, and Spearman's correlation coefficient were used as appropriate. Conjunctival expression of MMP9 and TG2. MMP9 and TG2 expression were higher in both patient groups than in controls (P < 0.0001). Group 2 patients showed higher expression than group 3 (P < 0.0001). The Spearman's correlation coefficient showed in group 2 a positive correlation between MMP9 and TG2 expression (ρ = 0.437; P = 0.01), but no correlation in group 3 (ρ = 0.143; P = 0.45). Corticosteroid treatment significantly reduced MMP9 and TG2 expression in both groups, ameliorating symptoms and signs. A much higher percentage reduction was observed in SS. The pathogenic mechanisms of the 2 forms of dry eye give an account for the different MMP9 and TG2 expressions in the 2 groups of patients. The higher expression in SS is determined by the direct autoimmune insult to the ocular surface epithelia, whereas in MGD patients, with an epithelial damage due to an unbalanced tear secretion, the molecules expression is significantly lower, although higher than in controls. The corticosteroid treatment induced a reduction of both molecules, although higher in SS than in MGD, because of its direct inhibitory effect on inflammation. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  5. Detection of MMP-9 and TIMP-3 mRNA expression in the villi of patients undergoing early spontaneous abortion: A report of 30 cases.

    PubMed

    Jiang, Guangli; Qi, Yuxia

    2015-05-01

    The aim of the present study was to investigate the correlation of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase inhibitor (TIMP)-3 expression with spontaneous abortion (SA) during early pregnancy. The villus tissues of 30 SA cases and 20 requested abortion cases were collected during surgery and constituted the SA and normal abortion (NA) groups, respectively. The total villous RNA was extracted and the expression levels of MMP -9 and TIMP-3 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR) assay to calculate the MMP-9/TIMP-3 mRNA ratio. The MMP-9 mRNA expression level and MMP-9/TIMP-3 mRNA ratio of the SA group were significantly higher than those of the NA group (P<0.01), while the TIMP-3 mRNA levels of the two groups were similar (P>0.05). The MMP-9 mRNA expression level of the SA group was higher than that of the NA group; thus, the MMP-9/TIMP-3 mRNA ratio was higher. These results suggest that the expression level of MMP-9 mRNA and the MMP-9/TIMP-3 mRNA ratio are associated with SA.

  6. Epigenetic regulation of matrix metalloproteinase expression in ameloblastoma

    PubMed Central

    2012-01-01

    Background An ameloblastoma is a benign odontogenic neoplasm with aggressive behaviour and high recurrence rates. The increased expression of matrix metalloproteinases (MMPs) has been reported in ameloblastomas. In the present study, we hypothesised that epigenetic alterations may regulate MMP expression in ameloblastomas. Methods We investigated the methylation status of the genes MMP-2 and MMP-9 in addition to mRNA transcription and protein expression in ameloblastomas. Methylation analysis was performed by both methylation-specific polymerase chain reaction (MSP-PCR) and restriction enzyme digestion to evaluate the methylation profile of MMP-2 and MMP-9 in 12 ameloblastoma samples and 12 healthy gingiva fragments, which were included as controls. Furthermore, we investigated the transcription levels of the genes by quantitative reverse-transcription PCR (qRT-PCR). Zymography was performed to verify protein expression in ameloblastomas. Results The ameloblastomas showed a high frequency of unmethylated MMP-2 and MMP-9, whereas the healthy gingival samples presented a sharp prevalence of methylated MMPs. Higher expression levels of MMP-9 were found in ameloblastomas compared to healthy gingiva. However, no significant differences in the MMP-2 mRNA expression between groups was found. All ameloblastomas showed positive expression of MMP-2 and MMP-9 proteins. Conclusions Our findings suggest that expression of MMP-9 is increased in ameloblastomas and is possibly modulated by unmethylation of the gene. PMID:22866959

  7. H3K9ac and HDAC2 Activity Are Involved in the Expression of Monocarboxylate Transporter 1 in Oligodendrocyte

    PubMed Central

    Lai, Qingwei; Du, Wantong; Wu, Jian; Wang, Xiao; Li, Xinyu; Qu, Xuebin; Wu, Xiuxiang; Dong, Fuxing; Yao, Ruiqin; Fan, Hongbin

    2017-01-01

    Recently, it is reported that monocarboxylate transporter 1 (MCT1) plays crucial role in oligodendrocyte differentiation and myelination. We found that MCT1 is strongly expressed in oligodendrocyte but weakly expressed in oligodendrocyte precursors (OPCs), and the underlying mechanisms remain elusive. Histone deacetylases (HDACs) activity is required for induction of oligodendrocyte differentiation and maturation. We asked whether HDACs are involved in the regulation of MCT1 expression. This work revealed that the acetylation level of histone H3K9 (H3K9ac) was much higher in mct1 gene (Slc16a1) promoter in OPCs than that in oligodendrocyte. H3K9ac regulates MCT1 expression was confirmed by HDAC acetyltransferase inhibitors trichostatin A and curcumin. Of note, there was a negative correlation between H3K9ac and MCT1 expression in oligodendrocyte. Further, we found that the levels of HDAC1, 2, and 3 protein in oligodendrocyte were obviously higher than those in OPCs. However, specific knockdown of HDAC2 but not HDAC1 and HDAC3 significantly decreased the expression of MCT1 in oligodendrocyte. Conversely, overexpression of HDAC2 remarkably enhanced the expression of MCT1. The results imply that HDAC2 is involved in H3K9ac modification which regulates the expression of MCT1 during the development of oligodendrocyte. PMID:29184483

  8. Aspiring to have the looks of a celebrity: young girls' engagement in appearance management behaviors.

    PubMed

    Trekels, Jolien; Eggermont, Steven

    2017-07-01

    Research suggests that sexualizing media messages are present in teen media and negatively affect young girls' body image. Yet, it is unknown whether exposure to teen television programs is associated with girls' engagement in appearance management behaviors. Two-wave longitudinal data among 785 girls (Mage = 11.65 years) were collected. Results show that teen television exposure was longitudinally related to appearance management, while the reverse relation was not supported. Approximately half of the girls indicated to manage their appearance to some extent, and 13- to 14-year-old girls were more likely to invest in their appearance than younger girls. Thirty percent of those who did not manage their appearance at the start of the study indicated to have initiated appearance management 6 months later. Frequent viewers were four times, three times, and twice as more likely to style their hair, wear heels, and apply make-up compared to non-viewers. The current study showed that teen media exposure plays a role in young girls' appearance management. The findings point to a need to teach young girls about stereotypical messages in media content directed towards them. Prevention efforts should focus on girls who frequently watch teen media. What is Known: • Sexualizing media messages are present in teen media. • Gender identity development is one of the key tasks during adolescence. What is New: • Tween television exposure predicts 9- to 14-year-old girls' engagement in appearance management over time. • Engagement in appearance management behaviors did not predict 9- to 14-year-old girls' exposure to tween television programs.

  9. Age differences in workplace intervention effects on employees’ nighttime and daytime sleep

    PubMed Central

    Lee, Soomi; Almeida, David M.; Berkman, Lisa; Olson, Ryan; Moen, Phyllis; Buxton, Orfeu M.

    2017-01-01

    Objectives To examine the effects of a workplace flexibility/support intervention on employees’ sleep quantity and quality during nights and days and whether the effects differ by employee age. Design Cluster-randomized controlled trial. Setting Information technology industry workplaces. Participants US employees (Mage = 46.9 years) at an information technology firm who provided actigraphy at baseline and a 12-month follow-up (N = 396; n = 195 intervention, n = 201 control). Intervention The Work, Family, and Health Study intervention aimed to increase workplace flexibility and support. The intervention consisted of facilitated discussions to help employees increase control over when and where they work as well as manager-specific training sessions to increase manager support for employees’ work-family issues. Measurements Nighttime sleep duration, wake after sleep onset (WASO), and nap duration were measured with wrist actigraphy. Day-to-day variability in these variables (min2) was also estimated. Results Intervention employees increased nighttime sleep duration at 12 months, by 9 minutes per day, relative to control employees. There were interaction effects between the intervention and age on daytime nap duration and day-to-day variability in WASO. Older employees (56–70 years) in the intervention condition decreased nap duration at 12 months relative to older employees in the control condition. Older employees in the intervention condition also exhibited a greater decrease in day-to-day variability of WASO at 12 months compared with their baseline. Conclusions The workplace flexibility/support intervention was effective in enhancing employees’ sleep health by increasing nighttime sleep duration. Furthermore, the intervention was particularly effective for older employees in decreasing their daytime nap duration and day-to-day variability in WASO. PMID:28105463

  10. Expression of MMP-9 decreases metastatic potential of Chondrosarcoma: an immunohistochemical study.

    PubMed

    Malcherczyk, Dominik; Heyse, Thomas J; El-Zayat, Bilal F; Kunzke, Vanessa; Moll, Roland; Fuchs-Winkelmann, Susanne; Paletta, Jürgen R J

    2018-01-09

    Chondrosarcoma is the second most common primary malignant bone tumor. Because of their heterogeneity, with differences in invasive and metastatic behavior, it is important to identify biological markers that will allow for a more accurate estimation of prognosis in patients with these tumors. Matrix metalloproteinases (MMP) play a crucial role in tumor progression, invasion and metastasis. The mechanism of tumor progression dependent of MMPs is complex and influences malignant transformation, angiogenesis and tumor growth at the primary and metastatic sites. The purpose of this study was to investigate immunohistochemicaly the influence of MMP-1, MMP-3, MMP-9 and MMP-13 expression on prognostic parameter in chondrosarcoma. We investigated tissue samples of 28 patients with chondrosarcoma. Immunohistochemical staining to evaluate the expression of MMP-1, MMP-3, MMP-9 and MMP-13 was performed. Subsequently, the expression level was correlated with metastatic potential, histological grading and overall survival in patients with this neoplasm. In consideration of semi quantitative scoring 64% of chondrosarcoma were scored as positive for MMP-1, 46% for MMP-3, 61% for MMP-9. The specimens had shown no expression of MMP-13. High expression of MMP-9 was associated with better histological differentiation, decreased metastatic potential and favourable overall survival. No correlation was found for expression of MMP-1, MMP-3 or MMP-13. MMP-1, MMP-3 and MMP-9 are expressed in chondrosarcoma. Our findings suggest that the expression of MMP-9 is associated with clinical outcome parameters in chondrosarcoma.

  11. Multiplex Conditional Mutagenesis Using Transgenic Expression of Cas9 and sgRNAs

    PubMed Central

    Yin, Linlin; Maddison, Lisette A.; Li, Mingyu; Kara, Nergis; LaFave, Matthew C.; Varshney, Gaurav K.; Burgess, Shawn M.; Patton, James G.; Chen, Wenbiao

    2015-01-01

    Determining the mechanism of gene function is greatly enhanced using conditional mutagenesis. However, generating engineered conditional alleles is inefficient and has only been widely used in mice. Importantly, multiplex conditional mutagenesis requires extensive breeding. Here we demonstrate a system for one-generation multiplex conditional mutagenesis in zebrafish (Danio rerio) using transgenic expression of both cas9 and multiple single guide RNAs (sgRNAs). We describe five distinct zebrafish U6 promoters for sgRNA expression and demonstrate efficient multiplex biallelic inactivation of tyrosinase and insulin receptor a and b, resulting in defects in pigmentation and glucose homeostasis. Furthermore, we demonstrate temporal and tissue-specific mutagenesis using transgenic expression of Cas9. Heat-shock-inducible expression of cas9 allows temporal control of tyr mutagenesis. Liver-specific expression of cas9 disrupts insulin receptor a and b, causing fasting hypoglycemia and postprandial hyperglycemia. We also show that delivery of sgRNAs targeting ascl1a into the eye leads to impaired damage-induced photoreceptor regeneration. Our findings suggest that CRISPR/Cas9-based conditional mutagenesis in zebrafish is not only feasible but rapid and straightforward. PMID:25855067

  12. Inhibition of EMMPRIN and MMP-9 Expression by Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor in PMA-Induced Macrophages.

    PubMed

    Wang, Qi-Ming; Wang, Hao; Li, Ya-Fei; Xie, Zhi-Yong; Ma, Yao; Yan, Jian-Jun; Gao, Yi Fan Wei; Wang, Ze-Mu; Wang, Lian-Sheng

    2016-01-01

    It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer) and MMPs (matrix metalloproteinases) by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG) has a variety of pharmacological properties and exerts cardiovascular protective effects. Recently, the 67-kD laminin receptor (67LR) has been identified as a cell surface receptor of EGCG. The aim of the present study was to evaluate the effects of EGCG on the expression of EMMPRIN and MMP-9 in PMA-induced macrophages, and the potential mechanisms underlying its effects. Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Protein expression and MMP-9 activity were assayed by Western blot and Gelatin zymography, respectively. Real-time PCR was used to examine EMMPRIN and MMP-9 mRNA expression. We showed that EGCG (10-50µmol/L) significantly inhibited the expression of EMMPRIN and MMP-9 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) in PMA-induced macrophages. Downregulation of EMMPRIN by gene silencing hindered PMA-induced MMP-9 secretion and expression, indicating an important role of EMMPRIN in the inhibition of MMP-9 by EGCG. Moreover, 67LR was involved in EGCG-mediated suppression of EMMPRIN and MMP-9 expression. Anti-67LR antibody treatment led to abrogation of the inhibitory action of EGCG on the expression of EMMPRIN and MMP-9 and activation of ERK1/2, p38, and JNK. Our results indicate that EGCG restrains EMMPRIN and MMP-9 expression via 67LR in PMA-induced macrophages, which also suggests that EGCG may be a possible therapeutic agent for stabilizing atherosclerotic plaque. © 2016 The Author(s) Published by S. Karger AG, Basel.

  13. A decrease in hepatic microRNA-9 expression impairs gluconeogenesis by targeting FOXO1 in obese mice.

    PubMed

    Yan, Caifeng; Chen, Jinfeng; Li, Min; Xuan, Wenying; Su, Dongming; You, Hui; Huang, Yujie; Chen, Nuoqi; Liang, Xiubin

    2016-07-01

    MicroRNA-9 (miR-9) is involved in the regulation of pancreatic beta cell function. However, its role in gluconeogenesis is still unclear. Our objective was to investigate the role of miR-9 in hepatic glucose production (HGP). MiR-9 expression was measured in livers of high-fat diet (HFD) mice and ob/ob mice. The methylation status of the miR-9-3 promoter regions in hepatocytes was determined by the methylation-specific PCR procedure. The binding activity of DNA methyltransferase (DNMT)1, DNMT3a and DNMT3b on the miR-9-3 promoter was detected by chromatin immunoprecipitation (ChIP) and quantitative real-time PCR assays. HGP was evaluated in vitro and in vivo. Glucose tolerance, insulin tolerance and pyruvate tolerance tests were also performed. Reduced miR-9 expression and hypermethylation of the miR-9-3 promoter were observed in the livers of obese mice. Further study showed that the binding of DNMT1, but not of DNMT3a and DNMT3b, to the miR-9-3 promoter was increased in hepatocytes from ob/ob mice. Knockdown of DNMT1 alleviated the decrease in hepatic miR-9 expression in vivo and in vitro. Overexpression of hepatic miR-9 improved insulin sensitivity in obese mice and inhibited HGP. In addition, deletion of hepatic miR-9 led to an increase in random and fasting blood glucose levels in lean mice. Importantly, silenced forkhead box O1 (FOXO1) expression reversed the gluconeogenesis and glucose production in hepatocytes induced by miR-9 deletion. Our observations suggest that the decrease in miR-9 expression contributes to an inappropriately activated gluconeogenesis in obese mice.

  14. Tim-3-expressing macrophages are functionally suppressed and expanded in oral squamous cell carcinoma due to virus-induced Gal-9 expression.

    PubMed

    Dong, Jianfeng; Cheng, Lijun; Zhao, Minchao; Pan, Xiangfeng; Feng, Zhiqiang; Wang, Dawei

    2017-05-01

    Oropharyngeal head and neck squamous cell carcinoma is a common malignant tumor in the oral cavity. High-risk human papillomavirus 16 infection is a major cause of oropharyngeal head and neck squamous cell carcinoma development. Strong antitumor immune responses, especially CD8 + T cell responses, are thought to be essential to effective cancer treatment and are associated with better prognosis in oropharyngeal head and neck squamous cell carcinoma. In this study, we examined the role of the Tim-3/Gal-9 pathway in oropharyngeal head and neck squamous cell carcinoma patients. We found that Gal-9 expression by CD4 + T cells was increased in human papillomavirus-positive oropharyngeal head and neck squamous cell carcinoma patients, but not in human papillomavirus-negative oropharyngeal head and neck squamous cell carcinoma patients. Increased Gal-9 secretion by CD4 + T cells presented multiple immunosuppressive effects. Coculturing monocytes with high Gal-9-expressing CD4 + T cells resulted in the expansion of Tim-3 + monocytes, which suppressed interferon gamma production by activated CD8 + T cells. Subsequently, total monocytes incubated with exogenous Gal-9, or high Gal-9-expressing CD4 + T cells, suppressed the expression of interferon gamma by CD8 + T cells. Exogenous Gal-9 and high Gal-9-expressing CD4 + T cells also suppressed the secretion of both interleukin 10 and interleukin 12 by monocytes. These effects are Tim-3/Gal-9-dependent because blocking Tim-3 and/or Gal-9 could enhance the support of CD8 + T cell interferon gamma production and the interleukin 10 and interleukin 12 secretion by monocytes. Together, these data suggest that the high Tim-3 expression in monocytes could be utilized by tumor-promoting Gal-9 expression on CD4 + T cells. Immunotherapy in human papillomavirus-positive oropharyngeal head and neck squamous cell carcinoma patients therefore faces an additional challenge posed by Tim-3 and Gal-9 and likely requires the blockade of these molecules.

  15. GSK's antigen-specific cancer immunotherapy programme: pilot results leading to Phase III clinical development.

    PubMed

    Brichard, Vincent G; Lejeune, Diane

    2007-09-27

    From the first evidence that the immune system could recognize tumors, different types of tumor antigens have been identified and deeply characterized. Several different approaches aimed at targeting these antigens have already been the subject of clinical studies. In this field, the GSK Biologicals' approach relying on recombinant proteins combined with an immunological Adjuvant System in a specific clinical setting, has entertained hopes of developing a new class of well tolerated anti-cancer therapy. This methodology led to promising advances with MAGE-A3 immunotherapy in NSCLC and has the potential to be applied to all tumor types.

  16. Expression of matrix metalloproteinase-9 and bombesin/gastrin-releasing peptide in human prostate cancers and their lymph node metastases.

    PubMed

    Ishimaru, Hisashi; Kageyama, Yukio; Hayashi, Tetsuo; Nemoto, Tetsuo; Eishi, Yoshinobu; Kihara, Kazunori

    2002-01-01

    Neuroendocrine differentiation and subsequent excretion of neuropeptides have been demonstrated to be associated with progression of human prostate cancer. Among neuropeptides found to exist in the prostate, bombesin/gastrin-releasing peptide has been shown to upregulate matrix metalloproteinase-9 (MMP-9) in human prostate cancer cell lines. Expression levels of bombesin, MMP-9, and neuron-specific enolase were examined by immunohistochemistry in 41 cases of clinically organ-confined prostate cancers including 9 with microscopic lymph node metastases. Twenty-seven (64%) of the 41 radical prostatectomy specimens were positive for both MMP-9 and bombesin. Expression of these molecules was observed in almost the same population of the cancer cells. The remaining 14 cases were negative for both MMP-9 and bombesin. High-grade tumors (Gleason sum > or = 7) were more likely to express MMP-9 and bombesin (21/24:88%) than low-grade tumors (Gleason sum > or = 6) (7/17:41%). In eight of the nine cases with pathological lymph node metastases, expression of MMP-9 and bombesin was also noted in metastatic sites. Neuron-specific enolase was positive in 16 cases (39%) and not always associated with the expression of bombesin. Expression of bombesin and expression of MMP-9 are common in human prostate cancers and may be related to an aggressive phenotype.

  17. CDKN2B expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Svensson, Per-Arne; Wahlstrand, Björn; Olsson, Maja

    2014-04-18

    Highlights: • The tumor suppressor gene CDKN2B is highly expressed in human adipose tissue. • Risk alleles at the 9p21 locus modify CDKN2B expression in a BMI-dependent fashion. • There is an inverse relationship between expression of CDKN2B and adipogenic genes. • CDKN2B expression influences to postprandial triacylglycerol clearance. • CDKN2B expression in adipose tissue is linked to markers of hepatic steatosis. - Abstract: Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biologicalmore » mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis.« less

  18. A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination.

    PubMed

    Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Shi, Yanhong

    2009-04-01

    MicroRNAs have been implicated as having important roles in stem cell biology. MicroRNA-9 (miR-9) is expressed specifically in neurogenic areas of the brain and may be involved in neural stem cell self-renewal and differentiation. We showed previously that the nuclear receptor TLX is an essential regulator of neural stem cell self-renewal. Here we show that miR-9 suppresses TLX expression to negatively regulate neural stem cell proliferation and accelerate neural differentiation. Introducing a TLX expression vector that is not prone to miR-9 regulation rescued miR-9-induced proliferation deficiency and inhibited precocious differentiation. In utero electroporation of miR-9 in embryonic brains led to premature differentiation and outward migration of the transfected neural stem cells. Moreover, TLX represses expression of the miR-9 pri-miRNA. By forming a negative regulatory loop with TLX, miR-9 provides a model for controlling the balance between neural stem cell proliferation and differentiation.

  19. Nitric Oxide Promotes Airway Epithelial Wound Repair through Enhanced Activation of MMP-9

    PubMed Central

    Bove, Peter F.; Wesley, Umadevi V.; Greul, Anne-Katrin; Hristova, Milena; Dostmann, Wolfgang R.; van der Vliet, Albert

    2007-01-01

    The airway epithelium provides a protective barrier against inhaled environmental toxins and microorganisms, and epithelial injury initiates a number of processes to restore its barrier integrity, including activation of matrix metalloproteinases such as MMP-9 (92-kD gelatinase B). Airway epithelial cells continuously produce nitric oxide (NO), which has been linked to cell migration and MMP-9 regulation in several cell types, but the importance of epithelial NO in mediating airway epithelial repair or MMP-9 activation is unknown. Using primary or immortalized human bronchial epithelial cells, we demonstrate that low concentrations of NO promote epithelial cell migration and wound repair in an in vitro wound assay, which was associated with increased localized expression and activation of MMP-9. In addition, in HBE1 cells that were stably transfected with inducible NOS (NOS2), to mimic constitutive epithelial NOS2 expression in vivo, NOS inhibition decreased epithelial wound repair and MMP-9 expression. The stimulatory effects of NO on epithelial wound repair and MMP-9 expression were dependent on cGMP-mediated pathways and were inhibited by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase. Inhibition of cGMP-dependent protein kinase (PKG) attenuated NO-mediated epithelial wound closure, but did not affect MMP-9 expression. However, pharmacologic MMP inhibition and siRNA knockdown of MMP-9 expression demonstrated the contribution of MMP-9 to NO-mediated wound closure. Overall, our results demonstrate that NOS2-derived NO contributes to airway epithelial repair by both PKG-dependent and -independent mechanisms, and involves NO-dependent expression and activation of MMP-9. PMID:16980554

  20. Upregulated SOX9 expression indicates worse prognosis in solid tumors: a systematic review and meta-analysis

    PubMed Central

    Ruan, Haihua; Hu, Shuangyan; Zhang, Hongyu; Du, Gang; Li, Xiaoting; Li, Xiaobo; Li, Xichuan

    2017-01-01

    It was recently reported that increased SOX9 expression drives tumor growth and promotes cancer invasion during human tumorigenicity and metastasis. However, the prognostic value of SOX9 for the survival of patients with solid tumors remains controversial. The present meta-analysis was thus performed to highlight the link between dysregulated SOX9 expression and prognosis in cancer patients. A systematic literature search was conducted using the electronic databases PubMed, Web of Science and Embase to identify eligible studies. A random-effects meta-analytical model was employed to correlate SOX9 expression with overall survival (OS), disease-free survival (DFS) and clinicopathological features. In total, 17 studies with 3307 patients were eligible for the final analysis. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) suggested that high SOX9 expression has an unfavourable impact on OS (HR = 1.66, 95% CI 1.36–2.02, P < 0.001) and DFS (HR = 3.54, 95% CI 2.29–5.47, P = 0.008) in multivariate analysis. Additionally, the pooled odds ratios (ORs) indicated that SOX9 over-expression is associated with large tumor size, lymph node metastasis, distant metastasis and a higher clinical stage. Overall, these results indicated that SOX9 over-expression in patients with solid tumors might be related to poor prognosis and could serve as a potential predictive marker of poor clinicopathological prognosis factor. PMID:29348895

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