Parental involvement of Asian American immigrant mothers: Investigating social capital, English proficiency, length of U.S. residency, and social class

The major purpose of the present study was to examine how the parent social and cultural contexts are related to Asian American immigrant mothers' educational involvement. This study investigated four parents' socio-cultural background variables: a) parent's social capital, b) parent's self-perceived English proficiency, c) parent's length of residence in the United States, and d) parent's social class status. In addition, the current study sought to determine the underlying dimensions of Asian American immigrant mothers' parental involvement in order to examine how parent social and cultural background factors influence each of the dimensions differently. The subjects for the current study were 597 nationally representative Asian American immigrant mothers who completed the parent questionnaire of the base-year Educational Longitudinal Study of 2002 (ELS: 2002). Five dimensions of parental involvement were identified in the current study sample of Asian American immigrant mothers. These include parent's engagement in social activities with her child, parent's positive school contact, parent's monitoring, parent's school contact for problems, and parent's participation at school functions. A series of multiple regression and logistic regression analyses were conducted to assess the relationships between parent's social and cultural backgrounds and each of five dimensions of the Asian American parental involvement. The results showed that Asian American immigrant mothers' social capital, English proficiency, and social class were significantly related to parent's engagement in social activities with her child. Further, mother's social capital, English proficiency, and social class status were significantly positively related to parent's monitoring. Of the various parent's social and cultural background variables, only parent's social capital significantly predicted Asian American immigrant mothers' positive school contact and participation at school functions. No relationship was found between parent social and cultural background variables and Asian American immigrant mothers' school contact for problems

Method to Minimize the Errors of AI: Quantifying and Exploiting Uncertainty of Deep Learning in Brain Tumor Segmentation

Despite the unprecedented success of deep learning in various fields, it has been recognized that clinical diagnosis requires extra caution when applying recent deep learning techniques because false prediction can result in severe consequences. In this study, we proposed a reliable deep learning framework that could minimize incorrect segmentation by quantifying and exploiting uncertainty measures. The proposed framework demonstrated the effectiveness of a public dataset: Multimodal Brain Tumor Segmentation Challenge 2018. By using this framework, segmentation performances, particularly for small lesions, were improved. Since the segmentation of small lesions is difficult but also clinically significant, this framework could be effectively applied to the medical imaging field

Differential roles of Sirt1 in HIF-1 alpha and HIF-2 alpha mediated hypoxic responses

Hypoxia-inducible factors 1 alpha and 2 alpha (H1F-1 alpha and HIF-2 alpha) determine cancer cell fate under hypoxia. Despite the similarities of their structures, HIF-1 alpha and HIF-2 alpha have distinct roles in cancer growth under hypoxia, that is, HIF-1 alpha induces growth arrest whereas HIF-2 alpha promotes cell growth. Recently, sirtuin 1 (Sirt1) was reported to fine-tune cellular responses to hypoxia by deacetylating HIF-1 alpha and HIF-2 alpha. Yet, the roles of Sirt1 in HIF-1 alpha and HIF-2 alpha functions have been controversial. We here investigated the precise roles of Sirt1 in HIF-1 alpha and HIF-2 alpha regulations. Immunological analyses revealed that HIF-lot K674 and HIF-2 alpha K741 are acetylated by PCAF and CBP, respectively, but are deacetylated commonly by Sirt1. In the Gal4 reporter systems, Sirt1 was found to repress HIF-la activity constantly in ten cancer cell-lines but to regulate HIF-2 alpha activity cell type-dependently. Moreover, Sirt1 determined cell growth under hypoxia depending on HIF-1 alpha and HIF-2 alpha. Under hypoxia, Sirt1 promoted cell proliferation of HepG2, in which Sirt1 differentially regulates HIF-1 alpha and HIF-2 alpha. In contrast, such an effect of Sirt1 was not shown in HCT116, in which Sirt1 inactivates both HIF-1 alpha and HIF-2 alpha because conflicting actions of HIF-1 alpha and HIF-2 alpha on cell growth may be offset. Our results provide a better understanding of the roles of Sirt1 in HIF-mediated hypoxic responses and also a basic concept for developing anticancer strategy targeting Sirt1. (C) 2014 Elsevier Inc. All rights reserved

FIH Is an Oxygen Sensor in Ovarian Cancer for G9a/GLP-Driven Epigenetic Regulation of Metastasis-Related Genes

The prolyl hydroxylase domain-containing proteins (PHD-13) and the asparaginyl hydroxlyase factor inhibiting HIF (FIH) are oxygen sensors for hypoxia-inducible factor-driven transcription of hypoxia-induced genes, but whether these sensors affect oxygen-dependent epigenetic regulation more broadly is not known. Here, we show that FIH exerts an additional role as an oxygen sensor in epigenetic control by the histone lysine methyltransferases G9a and GLP. FIH hydroxylated and inhibited G9a and GLP under normoxia. When the FIH reaction was limited under hypoxia, G9a and GLP were activated and repressed metastasis suppressor genes, thereby triggering cancer cell migration and peritoneal dissemination of ovarian cancer xenografts. In clinical specimens of ovarian cancer, expression of FIH and G9a were reciprocally associated with patient outcomes. We also identified mutations of FIH target motifs in G9a and GLP, which exhibited excessive H3K9 methylation and facilitated cell invasion. This study provides insight into a new function of FIH as an upstream regulator of oxygen-dependent chromatin remodeling. It also implies that the FIH-G9a/GLP pathway could be a potential target for inhibiting hypoxia-induced cancer metastasis. Significance: These findings deepen understanding of oxygen-dependent gene regulation and cancer metastasis in response to hypoxia. (C) 2017 AACR

Sirtuin 1 attenuates nasal polypogenesis by suppressing epithelial-to-mesenchymal transition

Background: Nasal polyps (NPs) imply a refractory clinical course in patients with chronic rhinosinusitis (CRS). Previously, we showed that hypoxia-inducible factor (HIF) 1 could mediate nasal polypogenesis through epithelial-to-mesenchymal transition (EMT). Sirtuin 1 (SIRT1), a histone deacetylase, reportedly suppresses the transcriptional activity of HIF-1. Thus we hypothesized that SIRT1 attenuates nasal polyposis by inhibiting HIF-1-induced EMT. Objective: We sought to determine the role of SIRT1 in patients with nasal polyposis. Methods: The effects of SIRT1 on nasal polypogenesis were investigated in previously developed murine models. Immunohistochemistry, immunoblotting, and immunoprecipitation were done to evaluate SIRT1, EMT, and hypoxicmarkers in human nasal epithelial cells or sinonasal tissues from the mice and the patients with CRS with or without NPs. Results: SIRT1 transgenic mice had significantly fewer mucosal lesions with epithelial disruption and fewer NPs than wild-type (WT) mice. In addition, resveratrol (a SIRT1 activator) treatment suppressed nasal polypogenesis in WT mice; however, sirtinol (a SIRT1 inhibitor) administration increased the polyp burden in SIRT1 transgenic mice. In sinonasal specimens from patients with CRS, SIRT1 was downregulated in the mucosa from patients with polyps compared with levels seen in patients without polyps. SIRT1 overexpression or activation reversed hypoxia-induced EMT in human nasal epithelial cells. The intranasal transfection of a small hairpin SIRT1 lentiviral vector induced more nasal polypoid lesions in SIRT1 transgenic mice. Finally, mucosal extracts from patients with CRS without NPs increased SIRT1 expression in nasal epithelial cells, whereas those from patients with CRS with NPs did not. Conclusion: SIRT1 suppressed NP formation, possibly because of inhibition of HIF-1-induced EMT. Thus nasal epithelium SIRT1 might be a therapeutic target for NPs

Human Fetal Brain-Derived Neural Stem/Progenitor Cells Grafted into the Adult Epileptic Brain Restrain Seizures in Rat Models of Temporal Lobe Epilepsy

<div><p>Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. <i>In vitro</i>, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K⁺ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III⁺ neurons (∼34%), APC-CC1⁺ oligodendrocytes (∼28%), and GFAP⁺ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal brain-derived NSPCs possess some therapeutic effect for TLE treatments although further studies to both increase the yield of NSPC grafts-derived functionally integrated GABAergic neurons and improve cognitive deficits are still needed.</p></div

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hNSCs express diverse trophic factors. (A) In vitro proliferating and differentiated hNSCs expressed BDNF, NTF3, NTF4, NGF, VEGF, FGF2, and GDNF. (B) Western blotting analysis showed that hNSCs secreted higher levels of BDNF, NTF3, NTF4, NGF, and VEGF into the culture medium than human foreskin fibroblasts secrete. (TIFF 127 kb

Differentiation of human NSPCs following transplantation into the hippocampus of kindled rats.

<p>(A–F) BrdU⁺ grafted cells (green) were co-stained with TUJ1 (red, arrowheads in B, C, E, F) in the CA3 region of the hippocampus (A–C) and fimbria (D–F) in rats. (G–J) hNP⁺ grafted cells (red, arrowheads in G, I, J) were co-localized with TUJ1 (green, arrowheads in H–J) in the hilus of the hippocampus. (J) Orthogonal view from confocal <i>z</i>-series showed that hNP (red) in nuclei and TUJ1 (green) in cytoplasm were expressed in the same cell. (K, M) Under the dual-filter microscope, BrdU⁺ grafted cells co-expressed APC-CC1 in the fimbria (arrows in K), and hNuc⁺ grafted cells co-expressed GFAP in the CA3 region (an arrow in M). Scale bar; 200 µm (A), 20 µm (D), 10 µm (G, J), 20 µm (K).</p

HPLC analysis for GABA in human NSPCs.

<p>(A) huNSPCs contain GABA under both proliferation (Prol) and differentiation (Diff) conditions in culture. Note that the total intracellular GABA content of NSPCs was significantly higher under Diff conditions than under Prol conditions. (B, C) NSPCs under Diff conditions were incubated in basal (4 mM KCl) or high K⁺ (53 mM KCl) medium, and intracellular GABA content (B) and GABA release into the medium (C) were quantified. * Significantly different from that under Prol conditions at <i>P</i><0.05; † significantly different from that in the basal medium at <i>P</i><0.05; error bars indicate ±SEM.</p

Effect of human NSPC grafting on hippocampal-kindled seizures in rats.

<p>The mean values of afterdischarge duration (ADD) in electroencephalograms (A), behavioral seizure duration (B), and seizure stage (C) between vehicle-injected and NSPC-transplanted groups were compared before (pre-Tx) and after NSPC grafting (post-Tx). Error bars indicate ±SEM. huNSPC grafting significantly reduced all three seizure parameters—ADD, behavioral seizure duration, and seizure stage—although this seizure-suppressing effect was not permanent. * Significantly different from the vehicle-injected group at <i>P</i><0.05; ** significantly different from the vehicle-injected group at <i>P</i><0.01.</p