1,103 research outputs found

    Cross-Cultural Validation of the Inventory of School Motivation (ISM) in the Asian Setting: Hong Kong and the Philippines

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    Students’ achievement goals in school have received increasing research attention because they have been shown to be important in predicting important outcomes. As such, there has been a growing interest in measuring and comparing them across different cultural groups. However, these comparisons cannot be made until validity evidence has been attained to support the use of an instrument in the new cultural setting. In this study, we investigated the cross-cultural applicability of the Inventory of School Motivation (ISM, McInerney et al. American Educational Research Journal 34:207-236, 1997) in the Hong Kong Chinese and Philippine contexts using both within-network and between-network approaches to construct validation. The ISM measures four types of achievement goals: mastery, performance, social, and extrinsic goals. 1,406 high school students from Hong Kong (n = 697) and the Philippines (n = 709) participated. Results of the within-network test showed that the ISM had good internal consistency reliability and the confirmatory factor analysis provided support for the hypothesized four-factor model. Multigroup confirmatory factor analyses supported invariance of factor loadings across the two samples. The between-network test also indicated that these achievement goals correlated systematically with different aspects of students’ self-concepts. These findings support the applicability of the ISM among Hong Kong Chinese and Filipino students

    Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model

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    <p>Abstract</p> <p>Background</p> <p>Angiogenesis is the formation of neovasculature from a pre-existing vascular network. Progression of solid tumors including lung cancer is angiogenesis-dependent. We previously introduced a bioinformatics-based methodology to identify endogenous anti-angiogenic peptide sequences, and validated these predictions <it>in vitro </it>in human umbilical vein endothelial cell (HUVEC) proliferation and migration assays.</p> <p>Methods</p> <p>One family of peptides with high activity is derived from the α-fibrils of type IV collagen. Based on the results from the <it>in vitro </it>screening, we have evaluated the ability of a 20 amino acid peptide derived from the α5 fibril of type IV collagen, pentastatin-1, to suppress vessel growth in an angioreactor-based directed <it>in vivo </it>angiogenesis assay (DIVAA). In addition, pentastatin-1 suppressed tumor growth with intraperitoneal peptide administration in a small cell lung cancer (SCLC) xenograft model in nude mice using the NCI-H82 human cancer cell line.</p> <p>Results</p> <p>Pentastatin-1 decreased the invasion of vessels into angioreactors <it>in vivo </it>in a dose dependent manner. The peptide also decreased the rate of tumor growth and microvascular density <it>in vivo </it>in a small cell lung cancer xenograft model.</p> <p>Conclusions</p> <p>The peptide treatment significantly decreased the invasion of microvessels in angioreactors and the rate of tumor growth in the xenograft model, indicating potential treatment for angiogenesis-dependent disease, and for translational development as a therapeutic agent for lung cancer.</p

    Active Nuclear Receptors Exhibit Highly Correlated AF-2 Domain Motions

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    Nuclear receptor ligand binding domains (LBDs) convert ligand binding events into changes in gene expression by recruiting transcriptional coregulators to a conserved activation function-2 (AF-2) surface. While most nuclear receptor LBDs form homo- or heterodimers, the human nuclear receptor pregnane X receptor (PXR) forms a unique and essential homodimer and is proposed to assemble into a functional heterotetramer with the retinoid X receptor (RXR). How the homodimer interface, which is located 30 Å from the AF-2, would affect function at this critical surface has remained unclear. By using 20- to 30-ns molecular dynamics simulations on PXR in various oligomerization states, we observed a remarkably high degree of correlated motion in the PXR–RXR heterotetramer, most notably in the four helices that create the AF-2 domain. The function of such correlation may be to create “active-capable” receptor complexes that are ready to bind to transcriptional coactivators. Indeed, we found in additional simulations that active-capable receptor complexes involving other orphan or steroid nuclear receptors also exhibit highly correlated AF-2 domain motions. We further propose a mechanism for the transmission of long-range motions through the nuclear receptor LBD to the AF-2 surface. Taken together, our findings indicate that long-range motions within the LBD scaffold are critical to nuclear receptor function by promoting a mobile AF-2 state ready to bind coactivators

    Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

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    The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

    Reproducibility of Heart Rate Variability Indices in Children with Cystic Fibrosis

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    Fundamental to the potential utilisation of heart rate variability (HRV) indices as a prognostic tool is the reproducibility of these measures. The purpose of the present study was therefore to investigate the reproducibility of 24-hour derived HRV indices in a clinical paediatric population. Eighteen children (10 boys; 12.4 ± 2.8 years) with mild to moderate Cystic Fibrosis (CF; FVC: 83 ± 12% predicted; FEV1: 80 ± 9% predicted) and eighteen age- and sex-matched controls (10 boys; 12.5 ± 2.7 years) wore a combined ECG and accelerometer for two consecutive days. Standard time and frequency domain indices of HRV were subsequently derived. Reproducibility was assessed by Bland-Altman plots, 95% limits of agreement and intra-class correlation coefficients (ICC). In both groups, there was no systematic difference between days, with the variables demonstrating a symmetrical, homoscedastic distribution around the zero line. The time domain parameters demonstrated a good to excellent reproducibility irrespective of the population considered (ICC: 0.56 to 0.86). In contrast, whilst the frequency domain parameters similarly showed excellent reproducibility in the healthy children (ICC: 0.70 to 0.96), the majority of the frequency domain parameters illustrated a poor to moderate reproducibility in those with CF (ICC: 0.22 to 0.43). The exceptions to this trend were the normalised LF and HF components which were associated with a good to excellent reproducibility. These findings thereby support the utilisation of time and relative frequency domain HRV indices as a prognostic tool in children with CF. Furthermore, the present results highlight the excellent reproducibility of HRV in healthy children, indicating that this may be a useful tool to assess intervention effectiveness in this population

    A Measurement of Rb using a Double Tagging Method

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    The fraction of Z to bbbar events in hadronic Z decays has been measured by the OPAL experiment using the data collected at LEP between 1992 and 1995. The Z to bbbar decays were tagged using displaced secondary vertices, and high momentum electrons and muons. Systematic uncertainties were reduced by measuring the b-tagging efficiency using a double tagging technique. Efficiency correlations between opposite hemispheres of an event are small, and are well understood through comparisons between real and simulated data samples. A value of Rb = 0.2178 +- 0.0011 +- 0.0013 was obtained, where the first error is statistical and the second systematic. The uncertainty on Rc, the fraction of Z to ccbar events in hadronic Z decays, is not included in the errors. The dependence on Rc is Delta(Rb)/Rb = -0.056*Delta(Rc)/Rc where Delta(Rc) is the deviation of Rc from the value 0.172 predicted by the Standard Model. The result for Rb agrees with the value of 0.2155 +- 0.0003 predicted by the Standard Model.Comment: 42 pages, LaTeX, 14 eps figures included, submitted to European Physical Journal

    Hedgehog-interacting protein is highly expressed in endothelial cells but down-regulated during angiogenesis and in several human tumors

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    BACKGROUND: The Hedgehog (Hh) signaling pathway regulates a variety of developmental processes, including vasculogenesis, and can also induce the expression of pro-angiogenic factors in fibroblasts postnatally. Misregulation of the Hh pathway has been implicated in a variety of different types of cancer, including pancreatic and small-cell lung cancer. Recently a putative antagonist of the pathway, Hedgehog-interacting protein (HIP), was identified as a Hh binding protein that is also a target of Hh signaling. We sought to clarify possible roles for HIP in angiogenesis and cancer. METHODS: Inhibition of Hh signaling by HIP was assayed by measuring the induction of Ptc-1 mRNA in TM3 cells treated with conditioned medium containing Sonic hedgehog (Shh). Angiogenesis was assayed in vitro by EC tube formation on Matrigel. Expression of HIP mRNA was assayed in cells and tissues by Q-RT-PCR and Western blot. HIP expression in human tumors or mouse xenograft tumors compared to normal tissues was assayed by Q-RT-PCR or hybridization of RNA probes to a cancer profiling array. RESULTS: We show that Hedgehog-interacting protein (HIP) is abundantly expressed in vascular endothelial cells (EC) but at low or undetectable levels in other cell types. Expression of HIP in mouse epithelial cells attenuated their response to Shh, demonstrating that HIP can antagonize Hh signaling when expressed in the responding cell, and supporting the hypothesis that HIP blocks Hh signaling in EC. HIP expression was significantly reduced in tissues undergoing angiogenesis, including PC3 human prostate cancer and A549 human lung cancer xenograft tumors, as well as in EC undergoing tube formation on Matrigel. HIP expression was also decreased in several human tumors of the liver, lung, stomach, colon and rectum when compared to the corresponding normal tissue. CONCLUSION: These results suggest that reduced expression of HIP, a naturally occurring Hh pathway antagonist, in tumor neo-vasculature may contribute to increased Hh signaling within the tumor and possibly promote angiogenesis
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