A Protective Mechanism of Visible Red Light in Normal Human Dermal Fibroblasts: Enhancement of GADD45A-Mediated DNA Repair Activity.

PubMed

Kim, Yeo Jin; Kim, Hyoung-June; Kim, Hye Lim; Kim, Hyo Jeong; Kim, Hyun Soo; Lee, Tae Ryong; Shin, Dong Wook; Seo, Young Rok

2017-02-01

The phototherapeutic effects of visible red light on skin have been extensively investigated, but the underlying biological mechanisms remain poorly understood. We aimed to elucidate the protective mechanism of visible red light in terms of DNA repair of UV-induced oxidative damage in normal human dermal fibroblasts. The protective effect of visible red light on UV-induced DNA damage was identified by several assays in both two-dimensional and three-dimensional cell culture systems. With regard to the protective mechanism of visible red light, our data showed alterations in base excision repair mediated by growth arrest and DNA damage inducible, alpha (GADD45A). We also observed an enhancement of the physical activity of GADD45A and apurinic/apyrimidinic endonuclease 1 (APE1) by visible red light. Moreover, UV-induced DNA damages were diminished by visible red light in an APE1-dependent manner. On the basis of the decrease in GADD45A-APE1 interaction in the activating transcription factor-2 (ATF2)-knockdown system, we suggest a role for ATF2 modulation in GADD45A-mediated DNA repair upon visible red light exposure. Thus, the enhancement of GADD45A-mediated base excision repair modulated by ATF2 might be a potential protective mechanism of visible red light. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Gadd45a deletion aggravates hematopoietic stem cell dysfunction in ATM-deficient mice.

PubMed

Chen, Yulin; Yang, Runan; Guo, Peng; Ju, Zhenyu

2014-01-01

Ataxia telangiectasia mutated (ATM) kinase plays an essential role in the maintenance of genomic stability. ATM-deficient (ATM(-/-)) mice exhibit hematopoietic stem cell (HSC) dysfunction and a high incidence of lymphoma. Gadd45a controls cell cycle arrest, apoptosis and DNA repair, and is involved in the ATM-p53 mediated DNA damage response. However, the role of Gadd45a in regulating the functionality of ATM(-/-) HSCs is unknown. Here we report that Gadd45a deletion did not rescue the defects of T-cells and B-cells development in ATM(-/-) mice. Instead, ATM and Gadd45a double knockout (ATM(-/-) Gadd45a(-/-)) HSCs exhibited an aggravated defect in long-term self-renewal capacity compared to ATM(-/-) HSCs in HSC transplantation experiments. Further experiments revealed that the aggravated defect of ATM(-/-) Gadd45a(-/-) HSCs was due to a reduction of cell proliferation, associated with an accumulation of DNA damage and subsequent activation of DNA damage response including an up-regulation of p53-p21 signaling pathway. Additionally, ATM(-/-) Gadd45a(-/-) mice showed an increased incidence of hematopoietic malignancies, as well as an increased rate of metastasis than ATM(-/-) mice. In conclusion, Gadd45a deletion aggravated the DNA damage accumulation, which subsequently resulted in a further impaired self-renewal capacity and an increased malignant transformation in ATM(-/-) HSCs.

Inducement of mitosis delay by cucurbitacin E, a novel tetracyclic triterpene from climbing stem of Cucumis melo L., through GADD45γ in human brain malignant glioma (GBM) 8401 cells.

PubMed

Hsu, Y-C; Chen, M-J; Huang, T-Y

2014-02-27

Cucurbitacin E (CuE) is a natural compound previously shown to have anti-feedant, antioxidant and antitumor activities as well as a potent chemo-preventive action against cancer. The present study investigates its anti-proliferative property using MTT assay; CuE demonstrated cytotoxic activity against malignant glioma GBM 8401 cells and induced cell cycle G2/M arrest in these cells. CuE-treated cells accumulated in metaphase (CuE 2.5-10 μM) as determined using MPM-2 by flow cytometry. We attempted to characterize the molecular pathways responsible for cytotoxic effects of CuE in GBM 8401 cells. We studied the genome-wide gene expression profile on microarrays and molecular networks by using pathway analysis tools of bioinformatics. The CuE reduced the expression of 558 genes and elevated the levels of 1354 genes, suggesting an existence of the common pathways involved in induction of G2/M arrest. We identified the RB (GADD45β and GADD45γ) and the p53 (GADD45α) signaling pathways as the common pathways, serving as key molecules that regulate cell cycle. Results indicate that CuE produced G2/M arrest as well as the upregulation of GADD45 γ and binding with CDC2. Both effects increased proportionally with the dose of CuE, suggesting that the CuE-induced mitosis delay is regulated by GADD45γ overexpression. Our findings suggest that, in addition to the known effects on cancer prevention, CuE may have antitumor activity in glioma therapy.

Cell death caused by the synergistic effects of zinc and dopamine is mediated by a stress sensor gene Gadd45b - implication in the pathogenesis of Parkinson's disease.

PubMed

Yang, Tien-Chun; Wu, Pei-Chun; Chung, I-Fang; Jiang, Jhih-Hang; Fann, Ming-Ji; Kao, Lung-Sen

2016-10-01

The pathogenesis of Parkinson's disease (PD) is not completely understood, Zinc (Zn(2+) ) and dopamine (DA) have been shown to involve in the degeneration of dopaminergic cells. By microarray analysis, we identified Gadd45b as a candidate molecule that mediates Zn(2+) and DA-induced cell death; the mRNA and protein levels of Gadd45b are increased by Zn(2+) treatment and raised to an even higher level by Zn(2+) plus DA treatment. Zn(2+) plus DA treatment-induced PC12 cell death was enhanced when there was over-expression of Gadd45b and was decreased by knock down of Gadd45b. MAPK p38 and JNK signaling was able to cross-talk with Gadd45b during Zn(2+) and DA treatment. The synergistic effects of Zn(2+) and DA on PC12 cell death can be accounted for by an activation of the Gadd45b-induced cell death pathway and an inhibition of p38/JNK survival pathway. Furthermore, the in vivo results show that the levels of Gadd45b protein expression and phosphorylation of p38 were increased in the substantia nigra by the infusion of Zn(2+) /DA in the mouse brain and the level of Gadd45b mRNA is significantly higher in the substantia nigra of male PD patients than normal controls. The novel role of Gadd45b and its interactions with JNK and p38 will help our understanding of the pathogenesis of PD and help the development of future treatments for PD. Zinc and dopamine are implicated in the degeneration of dopaminergic neurons. We previously demonstrated that zinc and dopamine induced synergistic effects on PC12 cell death. Results from this study show that these synergistic effects can be accounted for by activation of the Gadd45b-induced cell death pathway and inhibition of the p38/JNK survival pathway. We provide in vitro and in vivo evidence to support a novel role for Gadd45b in the pathogenesis of Parkinson's disease. © 2016 International Society for Neurochemistry.

Gadd45a opens up the promoter regions of miR-295 facilitating pluripotency induction

PubMed Central

Li, Linpeng; Chen, Keshi; Wu, Yi; Long, Qi; Zhao, Danyun; Ma, Bochao; Pei, Duanqing; Liu, Xingguo

2017-01-01

MicroRNAs (miRNAs) play crucial roles in the establishment of pluripotent state by controlling pluripotent network. However, the molecular mechanisms controlling miRNAs during somatic cell reprogramming remain obscure. In this study, we show Gadd45a (growth arrest and DNA-damage-inducible protein 45a) enhances reprogramming by activating miR-295. Furthermore, we show that Gadd45a binds the promoter regions of miR-295. Nuclease accessibility assay indicates that Gadd45a opens the promoter regions of miR-295. Levels of H3K9Ac and H3K27Ac on the promoter regions of miR-295 were also increased. In conclusion, our results indicate that Gadd45a relaxes the promoter regions of miR-295 and promotes the expression of miR-295 during reprogramming, implying a concise mechanism of Gadd45a and miR-290 cluster cooperation in cell-fate determination. PMID:29022923

Gadd45a, the gene induced by the mood stabilizer valproic acid, regulates neurite outgrowth through JNK and the substrate paxillin in N1E-115 neuroblastoma cells.

PubMed

Yamauchi, Junji; Miyamoto, Yuki; Murabe, Mayu; Fujiwara, Yoko; Sanbe, Atsushi; Fujita, Yuko; Murase, Shoko; Tanoue, Akito

2007-05-15

Valproic acid (VPA), a mood stabilizer and anticonvulsant, has a variety of neurotrophic functions; however, less is known about how VPA regulates neurite outgrowth. Here, using N1E-115 neuroblastoma cells as the model, we show that VPA upregulates Gadd45a to trigger activation of the downstream JNK cascade controlling neurite outgrowth. VPA induces the phosphorylation of c-Jun N-terminal kinase (JNK) and the substrate paxillin, while VPA induction of neurite outgrowth is inhibited by JNK inhibitors (SP600125 and the small JNK-binding peptide) or a paxillin construct harboring a Ser 178-to-Ala mutation at the JNK phosphorylation. Transfection of Gadd45a, acting through the effector MEKK4, leads to the phosphorylation of the JNK cascade. Conversely, knockdown of Gadd45a with siRNA reduces the effect of VPA. Taken together, these results suggest that upregulation of Gadd45a explains one of the mechanisms whereby VPA induces the neurotrophic effect, providing a new role of Gadd45a in neurite outgrowth.

Gadd45b prevents autophagy and apoptosis against rat cerebral neuron oxygen-glucose deprivation/reperfusion injury.

PubMed

He, Guoqian; Xu, Wenming; Tong, Linyan; Li, Shuaishuai; Su, Shiceng; Tan, Xiaodan; Li, Changqing

2016-04-01

Autophagic (type II) cell death has been suggested to play pathogenetic roles in cerebral ischemia. Growth arrest and DNA damage response 45b (Gadd45b) has been shown to protect against rat brain ischemia injury through inhibiting apoptosis. However, the relationship between Gadd45b and autophagy in cerebral ischemia/reperfusion (I/R) injury remains uncertain. The aim of this study is to investigate the effect of Gadd45b on autophagy. We adopt the oxygen-glucose deprivation and reperfusion (OGD/R) model of rat primary cortex neurons, and lentivirus interference used to silence Gadd45b expression. Cell viability and injury assay were performed using CCK-8 and LDH kit. Autophagy activation was monitored by expression of ATG5, LC3, Beclin-1, ATG7 and ATG3. Neuron apoptosis was monitored by expression of Bcl-2, Bax, cleaved caspase3, p53 and TUNEL assay. Neuron neurites were assayed by double immunofluorescent labeling with Tuj1 and LC3B. Here, we demonstrated that the expression of Gadd45b was strongly up-regulated at 24 h after 3 h OGD treatment. ShRNA-Gadd45b increased the expression of autophagy related proteins, aggravated OGD/R-induced neuron cell apoptosis and neurites injury. ShRNA-Gadd45b co-treatment with autophagy inhibitor 3-methyladenine (3-MA) or Wortmannin partly inhibited the ratio of LC3II/LC3I, and slightly ameliorated neuron cell apoptosis under OGD/R. Furthermore, shRNA-Gadd45b inhibited the p-p38 level involved in autophagy, but increased the p-JNK level involved in apoptosis. ShRNA-Gadd45b co-treatment with p38 inhibitor obviously induced autophagy. ShRNA-Gadd45b co-treatment with JNK inhibitor alleviated neuron cell apoptosis. In conclusion, our data suggested that Gadd45b inhibited autophagy and apoptosis under OGD/R. Gadd45b may be a common regulatory protein to control autophagy and apoptosis.

Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4.

PubMed

Bullard, Steven A; Seo, Seongjin; Schilling, Birgit; Dyle, Michael C; Dierdorff, Jason M; Ebert, Scott M; DeLau, Austin D; Gibson, Bradford W; Adams, Christopher M

2016-08-19

Skeletal muscle atrophy is a serious and highly prevalent condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves an increase in skeletal muscle Gadd45a expression, which is necessary and sufficient for skeletal muscle fiber atrophy. However, the direct mechanism by which Gadd45a promotes skeletal muscle atrophy was unknown. To address this question, we biochemically isolated skeletal muscle proteins that associate with Gadd45a as it induces atrophy in mouse skeletal muscle fibers in vivo We found that Gadd45a interacts with multiple proteins in skeletal muscle fibers, including, most prominently, MEKK4, a mitogen-activated protein kinase kinase kinase that was not previously known to play a role in skeletal muscle atrophy. Furthermore, we found that, by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is both sufficient to induce skeletal muscle fiber atrophy and required for Gadd45a-mediated skeletal muscle fiber atrophy. Together, these results identify a direct biochemical mechanism by which Gadd45a induces skeletal muscle atrophy and provide new insight into the way that skeletal muscle atrophy occurs at the molecular level. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Nuclear Calcium Signaling Controls Expression of a Large Gene Pool: Identification of a Gene Program for Acquired Neuroprotection Induced by Synaptic Activity

PubMed Central

Zhang, Sheng-Jia; Zou, Ming; Lu, Li; Lau, David; Ditzel, Désirée A. W.; Delucinge-Vivier, Celine; Aso, Yoshinori; Descombes, Patrick; Bading, Hilmar

2009-01-01

Synaptic activity can boost neuroprotection through a mechanism that requires synapse-to-nucleus communication and calcium signals in the cell nucleus. Here we show that in hippocampal neurons nuclear calcium is one of the most potent signals in neuronal gene expression. The induction or repression of 185 neuronal activity-regulated genes is dependent upon nuclear calcium signaling. The nuclear calcium-regulated gene pool contains a genomic program that mediates synaptic activity-induced, acquired neuroprotection. The core set of neuroprotective genes consists of 9 principal components, termed Activity-regulated Inhibitor of Death (AID) genes, and includes Atf3, Btg2, GADD45β, GADD45γ, Inhibin β-A, Interferon activated gene 202B, Npas4, Nr4a1, and Serpinb2, which strongly promote survival of cultured hippocampal neurons. Several AID genes provide neuroprotection through a common process that renders mitochondria more resistant to cellular stress and toxic insults. Stereotaxic delivery of AID gene-expressing recombinant adeno-associated viruses to the hippocampus confers protection in vivo against seizure-induced brain damage. Thus, treatments that enhance nuclear calcium signaling or supplement AID genes represent novel therapies to combat neurodegenerative conditions and neuronal cell loss caused by synaptic dysfunction, which may be accompanied by a deregulation of calcium signal initiation and/or propagation to the cell nucleus. PMID:19680447

Rosemary (Rosmarinus officinalis) extract modulates CHOP/GADD153 to promote androgen receptor degradation and decreases xenograft tumor growth.

PubMed

Petiwala, Sakina M; Berhe, Saba; Li, Gongbo; Puthenveetil, Angela G; Rahman, Ozair; Nonn, Larisa; Johnson, Jeremy J

2014-01-01

The Mediterranean diet has long been attributed to preventing or delaying the onset of cardiovascular disease, diabetes and various solid organ cancers. In this particular study, a rosemary extract standardized to carnosic acid was evaluated for its potential in disrupting the endoplasmic reticulum machinery to decrease the viability of prostate cancer cells and promote degradation of the androgen receptor. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells procured from two different patients undergoing radical prostatectomy were treated with standardized rosemary extract and evaluated by flow cytometry, MTT, BrdU, Western blot and fluorescent microscopy. A significant modulation of endoplasmic reticulum stress proteins was observed in cancer cells while normal prostate epithelial cells did not undergo endoplasmic reticulum stress. This biphasic response suggests that standardized rosemary extract may preferentially target cancer cells as opposed to "normal" cells. Furthermore, we observed standardized rosemary extract to decrease androgen receptor expression that appears to be regulated by the expression of CHOP/GADD153. Using a xenograft tumor model we observed standardized rosemary extract when given orally to significantly suppress tumor growth by 46% compared to mice not receiving standardized rosemary extract. In the last several years regulatory governing bodies (e.g. European Union) have approved standardized rosemary extracts as food preservatives. These results are especially significant as it is becoming more likely that individuals will be receiving standardized rosemary extracts that are a part of a natural preservative system in various food preparations. Taken a step further, it is possible that the potential benefits that are often associated with a "Mediterranean Diet" in the future may begin to extend beyond the Mediterranean diet as more of the population is consuming standardized rosemary extracts.

MiR-148a increases glioma cell migration and invasion by downregulating GADD45A in human gliomas with IDH1 R132H mutations.

PubMed

Cui, Daming; Sajan, Pandey; Shi, Jinlong; Shen, Yiwen; Wang, Ke; Deng, Xianyu; Zhou, Lin; Hu, Pingping; Gao, Liang

2017-04-11

High-grade gliomas are severe tumors with poor prognosis. An R132H mutation in the isocitrate dehydrogenase (IDH1) gene prolongs the life of glioma patients. In this study, we investigated which genes are differentially regulated in IDH1 wild type (IDH1WT) or IDH1 R132H mutation (IDH1R132H) glioblastoma cells. Growth arrest and DNA-damage-inducible protein (GADD45A) was downregulated and microRNA 148a (miR-148a) was upregulated in in IDH1R132H human glioblastomas tissues. The relationship between GADD45A and miR-148a is unknown. In vitro experiments showed that GADD45A negatively regulates IDH1R132H glioma cell proliferation, migration, and invasion, and neurosphere formation in IDH1R132H glioblastoma stem cells (GSC). In addition, a human orthotopic xenograft mouse model showed that GADD45A reduced tumorigenesis in vivo. Our findings demonstrated that miR-148a promotes glioma cell invasion and tumorigenesis by downregulating GADD45A. Our findings provide novel insights into how GADD45A is downregulated by miR-148a in IDH1R132H glioma and may help to identify therapeutic targets for the effective treatment of high-grade glioma.

Curcumin inhibits endoplasmic reticulum stress induced by cerebral ischemia-reperfusion injury in rats

PubMed Central

Zhu, Haiying; Fan, Yanxia; Sun, Hongyu; Chen, Liyan; Man, Xiao

2017-01-01

The aim of the present study was to observe the dynamic changes of the growth arrest and DNA damage-inducible 153 (GADD153) gene and caspase-12 in the brain tissue of rats with cerebral ischemia-reperfusion injury (CIRI) and the impact of curcumin pretreatment. A total of 60 rats were randomly divided into the normal group (N), the sham operation group (S), the dimethyl sulfoxide control group (D) and the curcumin treatment group (C). For group D and C, 12 (T1), 24 (T2) and 72 h (T3) of reperfusion were performed after 2 h ischemia. The expression levels of GADD153 and caspase-12 in the brain tissue were detected and compared among the groups by immunohistochemistry, immunofluorescence double staining and western blotting. The expression levels of GADD153 and caspase-12 were increased at T1compared with groups N and S, and the expression of caspase-12 peaked at T2 in group D, while GADD153 was increased until T3 in group D. Compared with group D, the expression levels of GADD153 and caspase-12 in group C at T2 and T3 were significantly decreased (P<0.05). Endoplasmic reticulum stress is involved in the pathological process of CIRI. Curcumin may decrease the expression levels of the above two factors, thus exhibiting protective effects against CIRI in rats. PMID:29067098

Involvement of Dopamine Receptors in Binge Methamphetamine-Induced Activation of Endoplasmic Reticulum and Mitochondrial Stress Pathways

PubMed Central

Beauvais, Genevieve; Atwell, Kenisha; Jayanthi, Subramaniam; Ladenheim, Bruce; Cadet, Jean Lud

2011-01-01

Single large doses of methamphetamine (METH) cause endoplasmic reticulum (ER) stress and mitochondrial dysfunctions in rodent striata. The dopamine D1 receptor appears to be involved in these METH-mediated stresses. The purpose of this study was to investigate if dopamine D1 and D2 receptors are involved in ER and mitochondrial stresses caused by single-day METH binges in the rat striatum. Male Sprague-Dawley rats received 4 injections of 10 mg/kg of METH alone or in combination with a putative D1 or D2 receptor antagonist, SCH23390 or raclopride, respectively, given 30 min prior to each METH injection. Rats were euthanized at various timepoints afterwards. Striatal tissues were used in quantitative RT-PCR and western blot analyses. We found that binge METH injections caused increased expression of the pro-survival genes, BiP/GRP-78 and P58IPK, in a SCH23390-sensitive manner. METH also caused up-regulation of ER-stress genes, Atf2, Atf3, Atf4, CHOP/Gadd153 and Gadd34. The expression of heat shock proteins (HSPs) was increased after METH injections. SCH23390 completely blocked induction in all analyzed ER stress-related proteins that included ATF3, ATF4, CHOP/Gadd153, HSPs and caspase-12. The dopamine D2-like antagonist, raclopride, exerted small to moderate inhibitory influence on some METH-induced changes in ER stress proteins. Importantly, METH caused decreases in the mitochondrial anti-apoptotic protein, Bcl-2, but increases in the pro-apoptotic proteins, Bax, Bad and cytochrome c, in a SCH23390-sensitive fashion. In contrast, raclopride provided only small inhibition of METH-induced changes in mitochondrial proteins. These findings indicate that METH-induced activation of striatal ER and mitochondrial stress pathways might be more related to activation of SCH23390-sensitive receptors. PMID:22174933

Flavagline analog FL3 induces cell cycle arrest in urothelial carcinoma cell of the bladder by inhibiting the Akt/PHB interaction to activate the GADD45α pathway.

PubMed

Yuan, Gangjun; Chen, Xin; Liu, Zhuowei; Wei, Wensu; Shu, Qinghai; Abou-Hamdan, Hussein; Jiang, Lijuan; Li, Xiangdong; Chen, Rixin; Désaubry, Laurent; Zhou, Fangjian; Xie, Dan

2018-02-07

Prohibitin 1 (PHB) is a potential target for the treatment of urothelial carcinoma of the bladder (UCB). FL3 is a newly synthesized agent that inhibits cancer cell proliferation by targeting the PHB protein; however, the effect of FL3 in UCB cells remains unexplored. FL3 was identified to be a potent inhibitor of UCB cell viability using CCK-8 (cell counting kit-8) assay. Then a series of in vitro and in vivo experiments were conducted to further demonstrate the inhibitory effect of FL3 on UCB cell proliferation and to determine the underlying mechanisms. FL3 inhibited UCB cell proliferation and growth both in vitro and in vivo. By targeting the PHB protein, FL3 inhibited the interaction of Akt and PHB as well as Akt-mediated PHB phosphorylation, which consequently decreases the localization of PHB in the mitochondria. In addition, FL3 treatment resulted in cell cycle arrest in the G2/M phase, and this inhibitory effect of FL3 could be mimicked by knockdown of PHB. Through the microarray analysis of mRNA expression after FL3 treatment and knockdown of PHB, we found that the mRNA expression of the growth arrest and DNA damage-inducible alpha (GADD45α) gene were significantly upregulated. When knocked down the expression of GADD45α, the inhibitory effect of FL3 on cell cycle was rescued, suggesting that FL3-induced cell cycle inhibition is GADD45α dependent. Our data provide that FL3 inhibits the interaction of Akt and PHB, which in turn activates the GADD45α-dependent cell cycle inhibition in the G2/M phase.

MiR-148a increases glioma cell migration and invasion by downregulating GADD45A in human gliomas with IDH1 R132H mutations

PubMed Central

Shi, Jinlong; Shen, Yiwen; Wang, Ke; Deng, Xianyu; Zhou, Lin; Hu, Pingping; Gao, Liang

2017-01-01

High-grade gliomas are severe tumors with poor prognosis. An R132H mutation in the isocitrate dehydrogenase (IDH1) gene prolongs the life of glioma patients. In this study, we investigated which genes are differentially regulated in IDH1 wild type (IDH1WT) or IDH1 R132H mutation (IDH1R132H) glioblastoma cells. Growth arrest and DNA-damage-inducible protein (GADD45A) was downregulated and microRNA 148a (miR-148a) was upregulated in in IDH1R132H human glioblastomas tissues. The relationship between GADD45A and miR-148a is unknown. In vitro experiments showed that GADD45A negatively regulates IDH1R132H glioma cell proliferation, migration, and invasion, and neurosphere formation in IDH1R132H glioblastoma stem cells (GSC). In addition, a human orthotopic xenograft mouse model showed that GADD45A reduced tumorigenesis in vivo. Our findings demonstrated that miR-148a promotes glioma cell invasion and tumorigenesis by downregulating GADD45A. Our findings provide novel insights into how GADD45A is downregulated by miR-148a in IDH1R132H glioma and may help to identify therapeutic targets for the effective treatment of high-grade glioma. PMID:28445981

Co-regulation of intragenic microRNA miR-153 and its host gene Ia-2 β: identification of miR-153 target genes with functions related to IA-2β in pancreas and brain.

PubMed

Mandemakers, W; Abuhatzira, L; Xu, H; Caromile, L A; Hébert, S S; Snellinx, A; Morais, V A; Matta, S; Cai, T; Notkins, A L; De Strooper, B

2013-07-01

We analysed the genomic organisation of miR-153, a microRNA embedded in genes that encode two of the major type 1 diabetes autoantigens, islet-associated protein (IA)-2 and IA-2β. We also identified miR-153 target genes that correlated with IA-2β localisation and function. A bioinformatics approach was used to identify miR-153's genomic organisation. To analyse the co-regulation of miR-153 and IA-2β, quantitative PCR analysis of miR-153 and Ia-2β (also known as Ptprn2) was performed after a glucose stimulation assay in MIN6B cells and isolated murine pancreatic islets, and also in wild-type Ia-2 (also known as Ptprn), Ia-2β single knockout and Ia-2/Ia-2β double knockout mouse brain and pancreatic islets. Bioinformatics identification of miR-153 target genes and validation via luciferase reporter assays, western blotting and quantitative PCR were also carried out. Two copies of miR-153, miR-153-1 and miR-153-2, are localised in intron 19 of Ia-2 and Ia-2β, respectively. In rodents, only miR-153-2 is conserved. We demonstrated that expression of miR-153-2 and Ia-2β in rodents is partially co-regulated as demonstrated by a strong reduction of miR-153 expression levels in Ia-2β knockout and Ia-2/Ia-2β double knockout mice. miR-153 levels were unaffected in Ia-2 knockout mice. In addition, glucose stimulation, which increases Ia-2 and Ia-2β expression, also significantly increased expression of miR-153. Several predicted targets of miR-153 were reduced after glucose stimulation in vitro, correlating with the increase in miR-153 levels. This study suggests the involvement of miR-153, IA-2β and miR-153 target genes in a regulatory network, which is potentially relevant to insulin and neurotransmitter release.

Fasting-induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health.

PubMed

Fuhrmeister, Jessica; Zota, Annika; Sijmonsma, Tjeerd P; Seibert, Oksana; Cıngır, Şahika; Schmidt, Kathrin; Vallon, Nicola; de Guia, Roldan M; Niopek, Katharina; Berriel Diaz, Mauricio; Maida, Adriano; Blüher, Matthias; Okun, Jürgen G; Herzig, Stephan; Rose, Adam J

2016-06-01

Recent studies have demonstrated that repeated short-term nutrient withdrawal (i.e. fasting) has pleiotropic actions to promote organismal health and longevity. Despite this, the molecular physiological mechanisms by which fasting is protective against metabolic disease are largely unknown. Here, we show that, metabolic control, particularly systemic and liver lipid metabolism, is aberrantly regulated in the fasted state in mouse models of metabolic dysfunction. Liver transcript assays between lean/healthy and obese/diabetic mice in fasted and fed states uncovered "growth arrest and DNA damage-inducible" GADD45β as a dysregulated gene transcript during fasting in several models of metabolic dysfunction including ageing, obesity/pre-diabetes and type 2 diabetes, in both mice and humans. Using whole-body knockout mice as well as liver/hepatocyte-specific gain- and loss-of-function strategies, we revealed a role for liver GADD45β in the coordination of liver fatty acid uptake, through cytoplasmic retention of FABP1, ultimately impacting obesity-driven hyperglycaemia. In summary, fasting stress-induced GADD45β represents a liver-specific molecular event promoting adaptive metabolic function. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

"Gadd45b" Knockout Mice Exhibit Selective Deficits in Hippocampus-Dependent Long-Term Memory

ERIC Educational Resources Information Center

Leach, Prescott T.; Poplawski, Shane G.; Kenney, Justin W.; Hoffman, Barbara; Liebermann, Dan A.; Abel, Ted; Gould, Thomas J.

2012-01-01

Growth arrest and DNA damage-inducible [beta] ("Gadd45b") has been shown to be involved in DNA demethylation and may be important for cognitive processes. "Gadd45b" is abnormally expressed in subjects with autism and psychosis, two disorders associated with cognitive deficits. Furthermore, several high-throughput screens have identified "Gadd45b"…

GADD45α sensitizes cervical cancer cells to radiotherapy via increasing cytoplasmic APE1 level.

PubMed

Li, Qing; Wei, Xi; Zhou, Zhi-Wei; Wang, Shu-Nan; Jin, Hua; Chen, Kui-Jun; Luo, Jia; Westover, Kenneth D; Wang, Jian-Min; Wang, Dong; Xu, Cheng-Xiong; Shan, Jin-Lu

2018-05-09

Radioresistance remains a major clinical challenge in cervical cancer therapy. However, the mechanism for the development of radioresistance in cervical cancer is unclear. Herein, we determined that growth arrest and DNA-damage-inducible protein 45α (GADD45α) is decreased in radioresistant cervical cancer compared to radiosensitive cancer both in vitro and in vivo. In addition, silencing GADD45α prevents cervical cancer cells from undergoing radiation-induced DNA damage, cell cycle arrest, and apoptosis. More importantly, our data show that the overexpression of GADD45α significantly enhances the radiosensitivity of radioresistant cervical cancer cells. These data show that GADD45α decreases the cytoplasmic distribution of APE1, thereby enhancing the radiosensitivity of cervical cancer cells. Furthermore, we show that GADD45α inhibits the production of nitric oxide (NO), a nuclear APE1 export stimulator, by suppressing both endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) in cervical cancer cells. In conclusion, our findings suggest that decreased GADD45α expression significantly contributes to the development of radioresistance and that ectopic expression of GADD45α sensitizes cervical cancer cells to radiotherapy. GADD45α inhibits the NO-regulated cytoplasmic localization of APE1 through inhibiting eNOS and iNOS, thereby enhancing the radiosensitivity of cervical cancer cells.

(−)-Xanthatin Selectively Induces GADD45γ and Stimulates Caspase-Independent Cell Death in Human Breast Cancer MDA-MB-231 Cells

PubMed Central

Takeda, Shuso; Matsuo, Kazumasa; Yaji, Kentaro; Okajima-Miyazaki, Shunsuke; Harada, Mari; Miyoshi, Hiroko; Okamoto, Yoshiko; Amamoto, Toshiaki; Shindo, Mitsuru; Omiecinski, Curtis J.; Aramaki, Hironori

2014-01-01

exo-Methylene lactone group-containing compounds, such as (−)-xanthatin, are present in a large variety of biologically active natural products, including extracts of Xanthium strumarium (Cocklebur). These substances are reported to possess diverse functional activities, exhibiting anti-inflammatory, antimalarial, and anticancer potential. In this study, we synthesized six structurally related xanthanolides containing exo-methylene lactone moieties, including (−)-xanthatin and (+)-8-epi-xanthatin, and examined the effects of these chemically defined substances on the highly aggressive and farnesyltransferase inhibitor (FTI)-resistant MDA-MB-231 cancer cell line. The results obtained demonstrate that (−)-xanthatin was a highly effective inhibitor of MDA-MB-231 cell growth, inducing caspase-independent cell death, and that these effects were independent of FTase inhibition. Further, our results show that among the GADD45 isoforms, GADD45γ was selectively induced by (−)-xanthatin and that GADD45γ-primed JNK and p38 signaling pathways are, at least in part, involved in mediating the growth inhibition and potential anticancer activities of this agent. Given that GADD45γ is becoming increasingly recognized for its tumor suppressor function, the results presented here suggest the novel possibility that (−)-xanthatin may have therapeutic value as a selective inducer of GADD45γ in human cancer cells, in particular in FTI-resistant aggressive breast cancers. PMID:21568272

Hes-1 SUMOylation by protein inhibitor of activated STAT1 enhances the suppressing effect of Hes-1 on GADD45α expression to increase cell survival

PubMed Central

2014-01-01

Background Hairy and Enhancer of split 1 (Hes-1) is a transcriptional repressor that plays an important role in neuronal differentiation and development, but post-translational modifications of Hes-1 are much less known. In the present study, we aimed to investigate whether Hes-1 could be SUMO-modified and identify the candidate SUMO acceptors on Hes-1. We also wished to examine the role of the SUMO E3 ligase protein inhibitor of activated STAT1 (PIAS1) in SUMOylation of Hes-1 and the molecular mechanism of Hes-1 SUMOylation. Further, we aimed to identify the molecular target of Hes-1 and examine how Hes-1 SUMOylation affects its molecular target to affect cell survival. Results In this study, by using HEK293T cells, we have found that Hes-1 could be SUMO-modified and Hes-1 SUMOylation was greatly enhanced by the SUMO E3 ligase PIAS1 at Lys8, Lys27 and Lys39. Furthermore, Hes-1 SUMOylation stabilized the Hes-1 protein and increased the transcriptional suppressing activity of Hes-1 on growth arrest and DNA damage-inducible protein alpha (GADD45α) expression. Overexpression of GADD45α increased, whereas knockdown of GADD45αα expression decreased cell apoptosis. In addition, H2O2 treatment increased the association between PIAS1 and Hes-1 and enhanced the SUMOylation of Hes-1 for endogenous protection. Overexpression of Hes-1 decreased H2O2-induced cell death, but this effect was blocked by transfection of the Hes-1 triple sumo-mutant (Hes-1 3KR). Overexpression of PIAS1 further facilitated the anti-apoptotic effect of Hes-1. Moreover, Hes-1 SUMOylation was independent of Hes-1 phosphorylation and vice versa. Conclusions The present results revealed, for the first time, that Hes-1 could be SUMO-modified by PIAS1 and GADD45α is a novel target of Hes-1. Further, Hes-1 SUMOylation mediates cell survival through enhanced suppression of GADD45α expression. These results revealed a novel role of Hes-1 in addition to its involvement in Notch signaling. They also

Inhibition of microRNA-1 attenuates hypoxia/re-oxygenation-induced apoptosis of cardiomyocytes by directly targeting Bcl-2 but not GADD45Beta

PubMed Central

Zhai, Changlin; Tang, Guanmin; Peng, Lei; Hu, Huilin; Qian, Gang; Wang, Shijun; Yao, Jiankang; Zhang, Xiaoping; Fang, Ying; Yang, Shuang; Zhang, Xiumei

2015-01-01

MicroRNAs are small non-coding RNAs that are able to regulate gene expression and play important roles in some biological and pathological processes, including the myocardial ischemia/reperfusion (I/R) injury. Recent findings demonstrated that miR-1 exacerbated I/R-induced injury. This study was to investigate theanti-apoptotic property of miR-1 inhibition and the potential regulatory mechanism. Results showed miR-1 expression reduced in the heart of rats undergoing myocardial I/R and the cardiomyocytes receiving hypoxia/reoxygenation (H/R) injury, but the serum miR-1 expression increased. The targets of miR-1 were predicted by cDNA microarray, and Bcl-2 and GADD45β were selected as candidate targets. Western blot assay and qPCR showed Bcl-2 and GADD45β protein and mRNA expressions increased after I/R injury and H/R injury. Bcl-2 was a direct target of miR-1 as shown in previous studies. Luciferase assay and Western blot assay revealed GADD45β was a direct target of miR-1, and miR-1 suppressed GADD45β expression via binding to its 3’UTR. Furthermore, miR-1 inhibition increased Bcl-2 expression and reduced IA/AAR (infarct area/area at risk) ratio and cell apoptosis in rats undergoing myocardial I/R as well as in cardiomyocytes receiving H/R injury. Importantly, Bcl-2 knockdown restored these consequences following miR-1 inhibition. However, GADD45β knockdown reduced IA/AAR ratio and cell apoptosis in vivo and in vitro, but failed torestore above consequences after miR-1 inhibition. In conclusion miR-1 inhibition protects against H/R-induced apoptosis of myocytes by directly targeting Bcl-2 but not GADD45β. PMID:26692938

43 CFR 15.3 - Dredging, filling, excavating and building activities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Dredging, filling, excavating and building activities. 15.3 Section 15.3 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.3 Dredging, filling, excavating and building activities. No dredging, excavating, or...

43 CFR 15.3 - Dredging, filling, excavating and building activities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Dredging, filling, excavating and building activities. 15.3 Section 15.3 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.3 Dredging, filling, excavating and building activities. No dredging, excavating, or...

43 CFR 15.3 - Dredging, filling, excavating and building activities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Dredging, filling, excavating and building activities. 15.3 Section 15.3 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.3 Dredging, filling, excavating and building activities. No dredging, excavating, or...

43 CFR 15.3 - Dredging, filling, excavating and building activities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Dredging, filling, excavating and building activities. 15.3 Section 15.3 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.3 Dredging, filling, excavating and building activities. No dredging, excavating, or...

43 CFR 15.3 - Dredging, filling, excavating and building activities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Dredging, filling, excavating and building activities. 15.3 Section 15.3 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.3 Dredging, filling, excavating and building activities. No dredging, excavating, or...

Simultaneous silencing of ACSL4 and induction of GADD45B in hepatocellular carcinoma cells amplifies the synergistic therapeutic effect of aspirin and sorafenib

PubMed Central

Xia, Hongping; Lee, Kee Wah; Chen, Jianxiang; Kong, Shik Nie; Sekar, Karthik; Deivasigamani, Amudha; Seshachalam, Veerabrahma Pratap; Goh, Brian Kim Poh; Ooi, London Lucien; Hui, Kam M

2017-01-01

Sorafenib is currently the only US Food and Drug Administration (FDA)-approved molecular inhibitor for the systemic therapy of advanced hepatocellular carcinoma (HCC). Aspirin has been studied extensively as an anti-inflammation, cancer preventive and therapeutic agent. However, the potential synergistic therapeutic effects of sorafenib and aspirin on advanced HCC treatment have not been well studied. Drug combination studies and their synergy quantification were performed using the combination index method of Chou-Talalay. The synergistic therapeutic effects of sorafenib and aspirin were evaluated using an orthotopic mouse model of HCC and comprehensive gene profiling analyses were conducted to identify key factors mediating the synergistic therapeutic effects of sorafenib and aspirin. Sorafenib was determined to act synergistically on HCC cells with aspirin in vitro. Using Hep3B and HuH7 HCC cells, it was demonstrated that sorafenib and aspirin acted synergistically to induce apoptosis. Mechanistic studies demonstrated that combining sorafenib and aspirin yielded significant synergistically anti-tumor effects by simultaneously silencing ACSL4 and the induction of GADD45B expression in HCC cells both in vitro and in the orthotopic HCC xenograft mouse model. Importantly, clinical evidence has independently corroborated that survival of HCC patients expressing ACSL4highGADD45Blow was significantly poorer compared to patients with ACSL4lowGADD45Bhigh, thus demonstrating the potential clinical value of combining aspirin and sorafenib for HCC patients expressing ACSL4highGADD45Blow. In conclusion, sorafenib and aspirin provide synergistic therapeutic effects on HCC cells that are achieved through simultaneous silencing of ACSL4 and induction of GADD45B expression. Targeting HCC with ACSL4highGADD45Blow expression with aspirin and sorafenib could provide potential synergistic therapeutic benefits. PMID:28900541

The C-type lectin homologue gene (EP153R) of African swine fever virus inhibits apoptosis both in virus infection and in heterologous expression.

PubMed

Hurtado, Carolina; Granja, Aitor G; Bustos, María J; Nogal, María L; González de Buitrago, Gonzalo; de Yébenes, Virginia G; Salas, María L; Revilla, Yolanda; Carrascosa, Angel L

2004-08-15

The open reading frame EP153R of African swine fever virus (ASFV) encodes a nonessential protein that has been involved in the hemadsorption process induced in virus-infected cells. By the use of a virus deletion mutant lacking the EP153R gene, we have detected, in several virus-sensitive cells, increased levels of caspase-3 and cell death as compared with those obtained after infection with the parental BA71V strain. Both transient and stable expression of the EP153R gene in Vero or COS cells resulted in a partial protection of the transfected lines from the apoptosis induced in response to virus infection or external stimuli. The presence of gene EP153R resulted in a reduction of the transactivating activity of the cellular protein p53 in Vero cell cultures in which apoptosis was induced by virus infection or staurosporine treatment. This is to our knowledge the first description of a viral C-type lectin with anti-apoptotic properties.

N-terminally truncated GADD34 proteins are convenient translation enhancers in a human cell-derived in vitro protein synthesis system.

PubMed

Mikami, Satoshi; Kobayashi, Tominari; Machida, Kodai; Masutani, Mamiko; Yokoyama, Shigeyuki; Imataka, Hiroaki

2010-07-01

Human cell-derived in vitro protein synthesis systems are useful for the production of recombinant proteins. Productivity can be increased by supplementation with GADD34, a protein that is difficult to express in and purify from E. coli. Deletion of the N-terminal 120 or 240 amino acids of GADD34 improves recovery of this protein from E. coli without compromising its ability to boost protein synthesis in an in vitro protein synthesis system. The use of N-terminally truncated GADD34 proteins in place of full-length GADD34 should improve the utility of human cell-based cell-free protein synthesis systems.

A Novel Post-translational Modification of Nucleolin, SUMOylation at Lys-294, Mediates Arsenite-induced Cell Death by Regulating gadd45α mRNA Stability*

PubMed Central

Zhang, Dongyun; Liang, Yuguang; Xie, Qipeng; Gao, Guangxun; Wei, Jinlong; Huang, Haishan; Li, Jingxia; Gao, Jimin; Huang, Chuanshu

2015-01-01

Nucleolin is a ubiquitously expressed protein and participates in many important biological processes, such as cell cycle regulation and ribosomal biogenesis. The activity of nucleolin is regulated by intracellular localization and post-translational modifications, including phosphorylation, methylation, and ADP-ribosylation. Small ubiquitin-like modifier (SUMO) is a category of recently verified forms of post-translational modifications and exerts various effects on the target proteins. In the studies reported here, we discovered SUMOylational modification of human nucleolin protein at Lys-294, which facilitated the mRNA binding property of nucleolin by maintaining its nuclear localization. In response to arsenic exposure, nucleolin-SUMO was induced and promoted its binding with gadd45α mRNA, which increased gadd45α mRNA stability and protein expression, subsequently causing GADD45α-mediated cell death. On the other hand, ectopic expression of Mn-SOD attenuated the arsenite-generated superoxide radical level, abrogated nucleolin-SUMO, and in turn inhibited arsenite-induced apoptosis by reducing GADD45α expression. Collectively, our results for the first time demonstrate that nucleolin-SUMO at K294R plays a critical role in its nucleus sequestration and gadd45α mRNA binding activity. This novel biological function of nucleolin is distinct from its conventional role as a proto-oncogene. Therefore, our findings here not only reveal a new modification of nucleolin protein and its novel functional paradigm in mRNA metabolism but also expand our understanding of the dichotomous roles of nucleolin in terms of cancer development, which are dependent on multiple intracellular conditions and consequently the appropriate regulations of its modifications, including SUMOylation. PMID:25561743

Cytotoxicity and expression of c-fos, HSP70, and GADD45/153 proteins in human liver carcinoma (HepG2) cells exposed to dinitrotoluenes.

PubMed

Glass, Konsuela Y; Newsome, Cecilia R; Tchounwou, Paul B

2005-08-01

range of 0-200 microg/mL for 2,6-DNT. The 45-kDa growth arrest and damage protein was significantly expressed at the dose range of 200 - 250 microg/mL for 2,6-DNT and at the dose range of 200 - 400 microg/mL for 2,4-DNT. Expression of 153-kDa growth arrest and DNA damage protein was significant at the 100, 200, and 250 microg/mL doses for 2,6-DNT and at the 200 microg/mL dose for 2,4-DNT. Overall, these results indicate the potential of DNTs to induce cytotoxic, proteotoxic (HSP70), and genotoxic (GADD45/153) effects, as well as oxidative stress and pro-inflammatory reactions (c-fos).

Expression of NF-kappaB dependent genes in human cells in response to heavy ion beams

NASA Astrophysics Data System (ADS)

Hellweg, Christine; Baumstark-Khan, Christa; Ruland, Rebecca; Schmitz, Claudia; Lau, Patrick; Testard, Isabelle; Reitz, Guenther

Space radiation is a primary concern for manned spaceflight and is a potentially limiting factor for long term orbital and interplanetary missions. Understanding of the cellular and molecular processes underlying cell death and transformation related events by space radiation may allow better risk estimation and development of appropriate countermeasures. The pathway leading to activation of the transcription factor nuclear factor κB (NF-κB) and increased transcription of its target gene might modulate cellular radiation response. Previous studies suggest a linear energy transfer (LET) dependency of transcription factor nuclear factor κB (NF-κB) activation: high LET radiation activates NF-κB more efficiently than low LET radiation. In this work, the relative expressions of several NF-κB regulated genes (Gadd45β, NFKBIA encoding the NF-κB inhibitor IκBα, and the anti-apoptotic genes XIAP, bcl-2, and bcl-xL) were examined by quantitative real-time Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR). Human embryonic cells with neuronal differentiation potential (HEK/293) were exposed to accelerated heavy ions or to X-rays (200 kV) or incubated in presence of the strong NF-κB activator tumor necrosis factor α (TNF-α). Target gene expression data were normalized to the expression index of several unregulated reference genes (B2M, GAPDH, PBGD, HPRT). NFKBIA expression is enhanced for 24 h after TNF-α treatment, while Gadd45β expression was only temporarily up-regulated. High doses of X-rays (8 and 16 Gy) and of 13 C ions (75 MeV/n, LET 33 keV/µm, 4.7 Gy) up-regulate NFKBIA and Gadd45β expression temporarily. 13 C ion with higher LET (35 MeV/n, 73 keV/µm) enhance NFKBIA expression already after 1 Gy, and a passing up-regulation of Bcl-2, bcl-xL and XIAP expression was observed 2 h after 0.5 Gy. 20 Ne (95 MeV/A, 80 keV/µm) and 36 Ar ions (95 MeV/A, 271 keV/µm) were the strongest inducers of Gadd45β, NFKBIA, and XIAP with doses from 0.5 to 3.8 Gy

The D153del Mutation in GNB3 Gene Causes Tissue Specific Signalling Patterns and an Abnormal Renal Morphology in Rge Chickens

PubMed Central

Tummala, Hemanth; Fleming, Stewart; Hocking, Paul M.; Wehner, Daniel; Naseem, Zahid; Ali, Manir; Inglehearn, Christopher F.; Zhelev, Nikolai; Lester, Douglas H.

2011-01-01

Background The GNB3 gene is expressed in cone but not rod photoreceptors of vertebrates, where it acts as the β transducin subunit in the colour visual transduction process. A naturally occurring mutation ‘D153del’ in the GNB3 gene causes the recessively inherited blinding phenotype retinopathy globe enlarged (rge) disease in chickens. GNB3 is however also expressed in most other vertebrate tissues suggesting that the D153del mutation may exert pathological effects that outlie from eye. Principal Findings Recombinant studies in COS-7 cells that were transfected with normal and mutant recombinant GNB3 constructs and subjected to cycloheximide chase showed that the mutant GNB3d protein had a much shorter half life compared to normal GNB3. GNB3 codes for the Gβ3 protein subunit that, together with different Gγ and Gα subunits, activates and regulates phosphorylation cascades in different tissues. As expected, the relative levels of cGMP and cAMP secondary messengers and their activated kinases such as MAPK, AKT and GRK2 were also found to be altered significantly in a tissue specific manner in rge chickens. Histochemical analysis on kidney tissue sections, from rge homozygous affected chickens, showed the chickens had enlargement of the glomerular capsule, causing glomerulomegaly and tubulointerstitial inflammation whereas other tissues (brain, heart, liver, pancreas) were unaffected. Significance These findings confirm that the D153del mutation in GNB3 gene targets GNB3 protein to early degradation. Lack of GNB3 signalling causes reduced phosphorylation activity of ERK2 and AKT leading to severe pathological phenotypes such as blindness and renal abnormalities in rge chickens. PMID:21887213

Activation of the EIF2α/ATF4 and ATF6 Pathways in DU-145 Cells by Boric Acid at the Concentration Reported in Men at the US Mean Boron Intake.

PubMed

Kobylewski, Sarah E; Henderson, Kimberly A; Yamada, Kristin E; Eckhert, Curtis D

2017-04-01

Fruits, nuts, legumes, and vegetables are rich sources of boron (B), an essential plant nutrient with chemopreventive properties. Blood boric acid (BA) levels reflect recent B intake, and men at the US mean intake have a reported non-fasting level of 10 μM. Treatment of DU-145 prostate cancer cells with physiological concentrations of BA inhibits cell proliferation without causing apoptosis and activates eukaryotic initiation factor 2 (eIF2α). EIF2α induces cell differentiation and protects cells by redirecting gene expression to manage endoplasmic reticulum stress. Our objective was to determine the temporal expression of endoplasmic reticulum (ER) stress-activated genes in DU-145 prostate cells treated with 10 μM BA. Immunoblots showed post-treatment increases in eIF2α protein at 30 min and ATF4 and ATF6 proteins at 1 h and 30 min, respectively. The increase in ATF4 was accompanied by an increase in the expression of its downstream genes growth arrest and DNA damage-induced protein 34 (GADD34) and homocysteine-induced ER protein (Herp), but a decrease in GADD153/CCAAT/enhancer-binding protein homologous protein (CHOP), a pro-apoptotic gene. The increase in ATF6 was accompanied by an increase in expression of its downstream genes GRP78/BiP, calreticulin, Grp94, and EDEM. BA did not activate IRE1 or induce cleavage of XBP1 mRNA, a target of IRE1. Low boron status has been associated with increased cancer risk, low bone mineralization, and retinal degeneration. ATF4 and BiP/GRP78 function in osteogenesis and bone remodeling, calreticulin is required for tumor suppressor p53 function and mineralization of teeth, and BiP/GRP78 and EDEM prevent the aggregation of misfolded opsins which leads to retinal degeneration. The identification of BA-activated genes that regulate its phenotypic effects provides a molecular underpinning for boron nutrition and biology.

Phenotype comparison confirms ZMYND11 as a critical gene for 10p15.3 microdeletion syndrome.

PubMed

Tumiene, Birute; Čiuladaitė, Ž; Preikšaitienė, E; Mameniškienė, R; Utkus, A; Kučinskas, V

2017-11-01

Proper epigenetic regulation processes are crucial in the normal development of the human brain. An ever-increasing group of neurodevelopmental disorders due to derangements of epigenetic regulation involve both microdeletion and monogenic syndromes. Some of these syndromes have overlapping clinical phenotypes due to haploinsufficiency-sensitive genes involved in microdeletions. It was shown recently that the ZMYND11 gene has important functions in epigenetic regulation as an unconventional transcription co-repressor of highly expressed genes, possibly acting in the repression of cryptic transcription from gene bodies. The aim of our study was to compare the clinical phenotypes of patients with 10p15.3 deletions with the phenotypes of patients with loss-of-function ZMYND11 mutations. The results of our study further confirm that the ZMYND11 gene is the critical gene for the clinical phenotype of 10p15.3 microdeletion involving the terminal ~4 Mb of chromosome 10p. In addition, accumulating clinical data allow for further characterisation of this syndrome, including neurodevelopmental disorder, characteristic dysmorphic features and some other more frequent symptoms, such as behavioural disturbances, hypotonia, seizures, low birth weight, short stature in those older than 10 years of age, genitourinary malformations and recurrent infections.

The Modulation of Fibrosis in Scleroderma by 3-Deoxyglucosone

DTIC Science & Technology

2010-06-01

stained and analyzed for expression of GADD153 in the nucleus by immunofluorescence analysis using Cy3- conjugated secondary antibody . Mean...with the anti-Nox4 polyclonal antibody and Cy2-conjugated secondary antibody . Images were taken at 40 X magnification on an epi-fluorescence...GADD153 in the nucleus by immunofluorescence using a Cy3-conjugated secondary antibody . Representative images were taken at 40 X magnification on an

Dichlorodiphenyltrichloroethane technical mixture regulates cell cycle and apoptosis genes through the activation of CAR and ERα in mouse livers

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

Kazantseva, Yuliya A.; Yarushkin, Andrei A.; Pustylnyak, Vladimir O., E-mail: pustylnyak@ngs.ru

Dichlorodiphenyltrichloroethane (DDT) is a widely used organochlorine pesticide and a xenoestrogen that promotes rodent hepatomegaly and tumours. A recent study has shown significant correlation between DDT serum concentration and liver cancer incidence in humans, but the underlying mechanisms remain elusive. We hypothesised that a mixture of DDT isomers could exert effects on the liver through pathways instead of classical ERs. The acute effects of a DDT mixture containing the two major isomers p,p′-DDT (85%) and o,p′-DDT (15%) on CAR and ERα receptors and their cell cycle and apoptosis target genes were studied in mouse livers. ChIP results demonstrated increased CARmore » and ERα recruitment to their specific target gene binding sites in response to the DDT mixture. The results of real-time RT-PCR were consistent with the ChIP data and demonstrated that the DDT was able to activate both CAR and ERα in mouse livers, leading to target gene transcriptional increases including Cyp2b10, Gadd45β, cMyc, Mdm2, Ccnd1, cFos and E2f1. Western blot analysis demonstrated increases in cell cycle progression proteins cMyc, Cyclin D1, CDK4 and E2f1 and anti-apoptosis proteins Mdm2 and Gadd45β. In addition, DDT exposure led to Rb phosphorylation. Increases in cell cycle progression and anti-apoptosis proteins were accompanied by a decrease in p53 content and its transcriptional activity. However, the DDT was unable to stimulate the β-catenin signalling pathway, which can play an important role in hepatocyte proliferation. Thus, our results indicate that DDT treatment may result in cell cycle progression and apoptosis inhibition through CAR- and ERα-mediated gene activation in mouse livers. These findings suggest that the proliferative and anti-apoptotic conditions induced by CAR and ERα activation may be important contributors to the early stages of hepatocarcinogenesis as produced by DDT in rodent livers. - Highlights: • DDT activated both CAR and ERα and their

The YPR153W gene is essential for the pressure tolerance of tryptophan permease Tat2 in the yeast Saccharomyces cerevisiae

NASA Astrophysics Data System (ADS)

Kurosaka, Goyu; Abe, Fumiyoshi

2018-01-01

In the yeast Saccharomyces cerevisiae, hydrostatic pressure at 25 MPa is known to be nonlethal but significantly impairs the uptake of tryptophan by the permease Tat2, thereby inhibiting the growth of strains that require tryptophan from the medium. Here, we found that the lack of the YPR153W gene, so far poorly characterized for its role in yeast, caused a serious adverse effect on the growth at 10-25 MPa in the strain that required tryptophan. Deletion for YPR153W resulted in an increased rate of pressure-induced degradation of Tat2, suggesting that Tat2 is destabilized in the YPR153W deletion mutant at 25 MPa. Overexpression of the TAT2 gene enabled the deletion mutant to grow at 25 MPa. These results suggest that Ypr153w is essential for the stability and proper transport function of Tat2 under pressure at 10-25 MPa.

miR-153 regulates apoptosis and autophagy of cardiomyocytes by targeting Mcl-1.

PubMed

Zou, Yuhai; Liu, Wenting; Zhang, Jinxia; Xiang, Dingcheng

2016-07-01

MicroRNAs (miRs) are a class of important regulators, which are involved in the regulation of apoptosis. Oxidative stress‑induced apoptosis is the predominant factor accounting for cardiac ischemia‑reperfusion injury. miR‑153 has been previously shown to have an antitumor effect in cancer. However, whether miR‑153 is involved in oxidative stress‑induced apoptosis in the heart remains to be elucidated. To this end, the present study used reverse transcription‑quantitative polymerase chain reaction to detect miR-153 levels upon oxidative stress, and evaluated apoptosis, autophagy and expression of critical genes by western blotting. A luciferase assay was also used to confirm the potential target gene. In the present study, it was found that the expression of miR‑153 was significantly increased upon H2O2 stimulation, and the inhibition of endogenous miR‑153 decreased apoptosis. To further identify the mechanism underlying the pro‑apoptotic effect of miR‑153, the present study analyzed the 3'untranslated region of myeloid cell leukemia‑1 (Mcl‑1), and found that Mcl‑1 was potentially targeted by miR‑153. The forced expression of miR‑153 inhibited the expression of Mcl‑1 and luciferase activity, which was reversed by its antisense inhibitor. Furthermore, it was shown that the inhibition of miR‑153 induced autophagy during oxidative stress, and that its effects of autophagy induction and apoptosis inhibition were efficiently abrogated by Mcl‑1 small interfering RNA. In conclusion, the results of the present study elucidated a novel mechanism by which miR‑153 regulates the survival of cardimyocytes during oxidative stress through the modulation of apoptosis and autophagy. These effects may be mediated directly by targeting Mcl‑1. These finding revealed the potential clinical value of miR‑153 in the treatment of cardiovascular disease.

Neutron Activated Samarium-153 Microparticles for Transarterial Radioembolization of Liver Tumour with Post-Procedure Imaging Capabilities

PubMed Central

Hashikin, Nurul Ab. Aziz; Yeong, Chai-Hong; Abdullah, Basri Johan Jeet; Ng, Kwan-Hoong; Chung, Lip-Yong; Dahalan, Rehir; Perkins, Alan Christopher

2015-01-01

Introduction Samarium-153 (153Sm) styrene divinylbenzene microparticles were developed as a surrogate for Yttrium-90 (90Y) microspheres in liver radioembolization therapy. Unlike the pure beta emitter 90Y, 153Sm possess both therapeutic beta and diagnostic gamma radiations, making it possible for post-procedure imaging following therapy. Methods The microparticles were prepared using commercially available cation exchange resin, Amberlite IR-120 H+ (620–830 μm), which were reduced to 20–40 μm via ball mill grinding and sieve separation. The microparticles were labelled with 152Sm via ion exchange process with 152SmCl3, prior to neutron activation to produce radioactive 153Sm through 152Sm(n,γ)153Sm reaction. Therapeutic activity of 3 GBq was referred based on the recommended activity used in 90Y-microspheres therapy. The samples were irradiated in 1.494 x 1012 n.cm-2.s-1 neutron flux for 6 h to achieve the nominal activity of 3.1 GBq.g-1. Physicochemical characterisation of the microparticles, gamma spectrometry, and in vitro radiolabelling studies were carried out to study the performance and stability of the microparticles. Results Fourier Transform Infrared (FTIR) spectroscopy of the Amberlite IR-120 resins showed unaffected functional groups, following size reduction of the beads. However, as shown by the electron microscope, the microparticles were irregular in shape. The radioactivity achieved after 6 h neutron activation was 3.104 ± 0.029 GBq. The specific activity per microparticle was 53.855 ± 0.503 Bq. Gamma spectrometry and elemental analysis showed no radioactive impurities in the samples. Radiolabelling efficiencies of 153Sm-Amberlite in distilled water and blood plasma over 48 h were excellent and higher than 95%. Conclusion The laboratory work revealed that the 153Sm-Amberlite microparticles demonstrated superior characteristics for potential use in hepatic radioembolization. PMID:26382059

Nutrients Can Enhance the Abundance and Expression of Alkane Hydroxylase CYP153 Gene in the Rhizosphere of Ryegrass Planted in Hydrocarbon-Polluted Soil

PubMed Central

Arslan, Muhammad; Afzal, Muhammad; Amin, Imran; Iqbal, Samina; Khan, Qaiser M.

2014-01-01

Plant-bacteria partnership is a promising strategy for the remediation of soil and water polluted with hydrocarbons. However, the limitation of major nutrients (N, P and K) in soil affects the survival and metabolic activity of plant associated bacteria. The objective of this study was to explore the effects of nutrients on survival and metabolic activity of an alkane degrading rhizo-bacterium. Annual ryegrass (Lolium multiflorum) was grown in diesel-contaminated soil and inoculated with an alkane degrading bacterium, Pantoea sp. strain BTRH79, in greenhouse experiments. Two levels of nutrients were applied and plant growth, hydrocarbon removal, and gene abundance and expression were determined after 100 days of sowing of ryegrass. Results obtained from these experiments showed that the bacterial inoculation improved plant growth and hydrocarbon degradation and these were further enhanced by nutrients application. Maximum plant biomass production and hydrocarbon mineralization was observed by the combined use of inoculum and higher level of nutrients. The presence of nutrients in soil enhanced the colonization and metabolic activity of the inoculated bacterium in the rhizosphere. The abundance and expression of CYP153 gene in the rhizosphere of ryegrass was found to be directly associated with the level of applied nutrients. Enhanced hydrocarbon degradation was associated with the population of the inoculum bacterium, the abundance and expression of CYP153 gene in the rhizosphere of ryegrass. It is thus concluded that the combination between vegetation, inoculation with pollutant-degrading bacteria and nutrients amendment was an efficient approach to reduce hydrocarbon contamination. PMID:25360680

Effect of neoadjuvant chemotherapy and its correlation with HPV status, EGFR, Her-2-neu, and GADD45 expression in oral squamous cell carcinoma.

PubMed

Pandey, Manoj; Kannepali, Krishna Kiran; Dixit, Ruhi; Kumar, Mohan

2018-01-31

Head and neck cancers are the commonest cancer in Southeast Asia. Despite being a surface cancer, it is associated with significant morbidity as despite early detection by the patients they often report for treatment late and hence are associated with poor prognosis. The role of neoadjuvant chemotherapy in head and neck cancer is still under evaluation; there is a large subgroup of population that does not respond to chemotherapy, and hence, most studies have failed to show any survival benefit. This study evaluated the role of neoadjuvant therapy with docetaxel and carboplatin in patients with oral cancer and correlated the response to human papilloma virus, EGFR1, EGFR2, and GADD45 expression. A total of 24 locally advanced, non-metastatic oral cancer patients were included in the study. Tumor biopsies were taken prior to the start of neoadjuvant therapy for expression of EGFR, Her-2-Neu, and GADD45 by immunohistochemistry and for HPV by PCR. The response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria after three cycles of chemotherapy. Statistical analysis was performed using correlation and Kaplan-Meier analysis; the difference in survival was calculated with log rank test. A total of 21 male and 3 female with a mean age of 53.12 years were enrolled. Sixty-five percent of these received three cycles of chemotherapy. Five patients were positive for HPV 16 and none for HPV 18. Twenty-two of 24 patients showed GADD45 expression, 3 showed expression of Her-2-Neu while all 24 showed expression for EGFR1 protein. Two-year overall survival was 81%; GADD45 expressions were found to significantly affect the overall and disease-free survival, while any of the other protein expression studied and HPV status was not significant. The result of the present study shows significant downgrading of the oral cancers with neoadjuvant chemotherapy suggesting its utility in borderline operable cases. However, the response of chemotherapy does not

The Ia-2β intronic miRNA, miR-153, is a negative regulator of insulin and dopamine secretion through its effect on the Cacna1c gene in mice.

PubMed

Xu, Huanyu; Abuhatzira, Liron; Carmona, Gilberto N; Vadrevu, Suryakiran; Satin, Leslie S; Notkins, Abner L

2015-10-01

miR-153 is an intronic miRNA embedded in the genes that encode IA-2 (also known as PTPRN) and IA-2β (also known as PTPRN2). Islet antigen (IA)-2 and IA-2β are major autoantigens in type 1 diabetes and are important transmembrane proteins in dense core and synaptic vesicles. miR-153 and its host genes are co-regulated in pancreas and brain. The present experiments were initiated to decipher the regulatory network between miR-153 and its host gene Ia-2β (also known as Ptprn2). Insulin secretion was determined by ELISA. Identification of miRNA targets was assessed using luciferase assays and by quantitative real-time PCR and western blots in vitro and in vivo. Target protector was also employed to evaluate miRNA target function. Functional studies revealed that miR-153 mimic suppresses both glucose- and potassium-induced insulin secretion (GSIS and PSIS, respectively), whereas miR-153 inhibitor enhances both GSIS and PSIS. A similar effect on dopamine secretion also was observed. Using miRNA target prediction software, we found that miR-153 is predicted to target the 3'UTR region of the calcium channel gene, Cacna1c. Further studies confirmed that Cacna1c mRNA and protein are downregulated by miR-153 mimics and upregulated by miR-153 inhibitors in insulin-secreting freshly isolated mouse islets, in the insulin-secreting mouse cell line MIN6 and in the dopamine-secreting cell line PC12. miR-153 is a negative regulator of both insulin and dopamine secretion through its effect on Cacna1c expression, which suggests that IA-2β and miR-153 have opposite functional effects on the secretory pathway.

DNA damage-inducible genes as biomarkers for exposures to environmental agents

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

Johnson, N.F.; Carpenter, T.R.; Jaramillo, R.J.

1997-06-01

A biodosimetric approach to determine alpha-particle dose to the respiratory tract epithelium from known exposures to radon has been developed in the rat. Cytotoxicity assays have been used to obtain dose-conversion factors for cumulative exposures typical of those encountered by underground uranium miners. However, this approach is not sensitive enough to derive close-conversion factors for indoor radon exposures. The expression of DNA damage-inducible genes is being investigated as a biomarker of exposure to radon progeny. Exposure of cultures of A549 cells to alpha particles resulted in an increase in the protein levels of the DNA damage-inducible genes, p53, Cip 1,more » and Gadd45. These protein changes were associated with a transient arrest of cells passing through the cell cycle. This arrest was typified by an increase in the number of cells in the G{sub 1} and G{sub 2} phases and a decrease in the number of cells in the S phase. The effect of inhaled alpha particles (radon progeny) in rats was examined in the epithelial cells of the lateral wall of the anterior nasal cavity. Exposures to radon progeny resulted in a significant increase in the number of cells in the G{sub 1} phase and a decrease in the number of cells in the S phase. These cell-cycle changes were concomitant with an increase in the number of cells containing DNA strand breaks. In addition to ionizing radiation, A549 cells were exposed to 4-nitroquinoline-1-oxide, methyl methanesulphonate, crocidolite asbestos, and glass microfiber. These studies showed that physical and chemical agents induce different expression patterns of p53, Cip 1, and Gadd153 proteins and they could be used to discriminate between toxic and nontoxic materials such as asbestos and glass microfiber. The measurement of gene expression in A549 cells may provide a means to identify a broad spectrum of physical and chemical toxicants encountered in the environment. 9 figs., 42 refs.« less

C3 exoenzyme impairs cell proliferation and apoptosis by altering the activity of transcription factors.

PubMed

von Elsner, Leonie; Hagemann, Sandra; Just, Ingo; Rohrbeck, Astrid

2016-09-01

C3 exoenzyme from C. botulinum is an ADP-ribosyltransferase that inactivates selectively RhoA, B, and C by coupling an ADP-ribose moiety. Rho-GTPases are involved in various cellular processes, such as regulation of actin cytoskeleton, cell proliferation, and apoptosis. Previous studies of our group with the murine hippocampal cell line HT22 revealed a C3-mediated inhibition of cell proliferation after 48 h and a prevention of serum-starved cells from apoptosis. For both effects, alterations of various signaling pathways are already known, including also changes on the transcriptional level. Investigations on the transcriptional activity in HT22 cells treated with C3 for 48 h identified five out of 48 transcription factors namely Sp1, ATF2, E2F-1, CBF, and Stat6 with a significantly regulated activity. For validation of identified transcription factors, studies on the protein level of certain target genes were performed. Western blot analyses exhibited an enhanced abundance of Sp1 target genes p21 and COX-2 as well as an increase in phosphorylation of c-Jun. In contrast, the level of p53 and apoptosis-inducing GADD153, a target gene of ATF2, was decreased. Our results reveal that C3 regulates the transcriptional activity of Sp1 and ATF2 resulting downstream in an altered protein abundance of various target genes. As the affected proteins are involved in the regulation of cell proliferation and apoptosis, thus the C3-mediated anti-proliferative and anti-apoptotic effects are consequences of the Rho-dependent alterations of the activity of certain transcriptional factors.

40 CFR 93.153 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-07-01

... control activities and adopting approach, departure, and enroute procedures for aircraft operations above... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Applicability. 93.153 Section 93.153 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) DETERMINING...

Food additives: Sodium benzoate, potassium sorbate, azorubine, and tartrazine modify the expression of NFκB, GADD45α, and MAPK8 genes.

PubMed

Raposa, B; Pónusz, R; Gerencsér, G; Budán, F; Gyöngyi, Z; Tibold, A; Hegyi, D; Kiss, I; Koller, Á; Varjas, T

2016-09-01

It has been reported that some of the food additives may cause sensitization, inflammation of tissues, and potentially risk factors in the development of several chronic diseases. Thus, we hypothesized that expressions of common inflammatory molecules - known to be involved in the development of various inflammatory conditions and cancers - are affected by these food additives. We investigated the effects of commonly used food preservatives and artificial food colorants based on the expressions of NFκB, GADD45α, and MAPK8 (JNK1) from the tissues of liver. RNA was isolated based on Trizol protocol and the activation levels were compared between the treated and the control groups. Tartrazine alone could elicit effects on the expressions of NFκB (p = 0.013) and MAPK8 (p = 0.022). Azorubine also resulted in apoptosis according to MAPK8 expression (p = 0.009). Preservatives were anti-apoptotic in high dose. Sodium benzoate (from low to high doses) dose-dependently silenced MAPK8 expression (p = 0.004 to p = 0.002). Addition of the two preservatives together elicited significantly greater expression of MAPK8 at half-fold dose (p = 0.002) and at fivefold dose (p = 0.008). This study suggests that some of the food preservatives and colorants can contribute to the activation of inflammatory pathways.

Comparison of the in vitro effects of TCDD, PCB 126 and PCB 153 on thyroid-restricted gene expression and thyroid hormone secretion by the chicken thyroid gland.

PubMed

Katarzyńska, Dorota; Hrabia, Anna; Kowalik, Kinga; Sechman, Andrzej

2015-03-01

The aim of this study was to compare the in vitro effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pentachlorobiphenyl (PCB 126; a coplanar PCB congener) and 2,2'4,4',5,5'-hexachlorobiphenyl (PCB153; non-coplanar PCB) on mRNA expression of thyroid-restricted genes, i.e. sodium iodide symporter (NIS), thyroid peroxidase (TPO) and thyroglobulin (TG), and thyroid hormone secretion from the thyroid gland of the laying chicken. Relative expression levels of NIS, TG and TPO genes and thyroxine (T4) and triiodothyronine (T3) secretion from the thyroidal explants were quantified by the real-time qPCR and RIA methods, respectively. In comparison with the control group, TCDD and PCB 126 significantly increased mRNA expression of TPO and TG genes. TCDD did not affect NIS mRNA levels, but PCB 126 decreased its expression. No effect of PCB 153 on the expression of these genes was observed. TCDD and PCB 126 significantly decreased T4 and T3 secretion. There was no significant effect of PCB 153 on these hormone secretions. In conclusion, the results obtained show that in comparison with non-coplanar PCB 153, TCDD and coplanar PCB 126 can directly affect thyroid hormone synthesis and secretion, and in consequence, they may disrupt the endocrine function of the thyroid gland of the laying chicken. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of an Antimutagenic 1,4-Dihydropyridine AV-153 on Expression of Nitric Oxide Synthases and DNA Repair-related Enzymes and Genes in Kidneys of Rats with a Streptozotocin Model of Diabetes Mellitus.

PubMed

Ošiņa, Kristīne; Rostoka, Evita; Isajevs, Sergejs; Sokolovska, Jelizaveta; Sjakste, Tatjana; Sjakste, Nikolajs

2016-11-01

Development of complications of diabetes mellitus (DM), including diabetic nephropathy, is a complex multi-stage process, dependent on many factors including the modification of nitric oxide (NO) production and an impaired DNA repair. The goal of this work was to study in vivo effects of 1,4-dihydropyridine AV-153, known as antimutagen and DNA binder, on the expression of several genes and proteins involved in NO metabolism and DNA repair in the kidneys of rats with a streptozotocin (STZ)-induced model of DM. Transcription intensity was monitored by means of real-time RT-PCR and the expression of proteins by immunohistochemistry. Development of DM significantly induced PARP1 protein expression, while AV-153 (0.5 mg/kg) administration decreased it. AV-153 increased the expression of Parp1 gene in the kidneys of both intact and diabetic animals. Expression of H2afx mRNA and γH2AX histone protein, a marker of DNA breakage, was not changed in diabetic animals, but AV-153 up-regulated the expression of the gene without any impact on the protein expression. Development of DM was followed by a significant increase in iNOS enzyme expression, while AV-153 down-regulated the enzyme expression up to normal levels. iNos gene expression was also found to be increased in diabetic animals, but unlike the protein, the expression of mRNA was found to be enhanced by AV-153 administration. Expression of both eNOS protein and eNos gene in the kidneys was down-regulated, and the administration of AV-153 normalized the expression level. The effects of the compound in the kidneys of diabetic animals appear to be beneficial, as a trend for the normalization of expression of NO synthases is observed. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Coactivation of the PI3K/Akt and ERK signaling pathways in PCB153-induced NF-κB activation and caspase inhibition

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

Liu, Changjiang; Key Lab of Birth Defects and Reproductive Health of National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing 400020; Yang, Jixin

2014-06-15

Polychlorinated biphenyls (PCBs) are a group of persistent and widely distributed environmental pollutants that have various deleterious effects, e.g., neurotoxicity, endocrine disruption and reproductive abnormalities. In order to verify the hypothesis that the PI3K/Akt and MAPK pathways play important roles in hepatotoxicity induced by PCBs, Sprague–Dawley (SD) rats were dosed with PCB153 intraperitoneally at 0, 4, 16 and 32 mg/kg for five consecutive days; BRL cells (rat liver cell line) were treated with PCB153 (0, 1, 5, and 10 μM) for 24 h. Results indicated that the PI3K/Akt and ERK pathways were activated in vivo and in vitro after exposuremore » to PCB153, and protein levels of phospho-Akt and phospho-ERK were significantly increased. Nuclear factor-κB (NF-κB) activation and caspase-3, -8 and -9 inhibition caused by PCB153 were also observed. Inhibiting the ERK pathway significantly attenuated PCB153-induced NF-κB activation, whereas inhibiting the PI3K/Akt pathway hardly influenced phospho-NF-κB level. However, inhibiting the PI3K/Akt pathway significantly elevated caspase-3, -8 and -9 activities, while the ERK pathway only synergistically regulated caspase-9. Proliferating cell nuclear antigen (PCNA), a reliable indicator of cell proliferation, was also induced. Moreover, PCB153 led to hepatocellular hypertrophy and elevated liver weight. Taken together, PCB153 leads to aberrant proliferation and apoptosis of hepatocytes through NF-κB activation and caspase inhibition, and coactivated PI3K/Akt and ERK pathways play critical roles in PCB153-induced hepatotoxicity. - Highlights: • PCB153 led to hepatotoxicity through NF-κB activation and caspase inhibition. • The PI3K/Akt and ERK pathways were coactivated in vivo and in vitro by PCB153. • The ERK pathway regulated levels of phospho-NF-κB and caspase-9. • The PI3K/Akt pathway regulated levels of caspase-3, -8 and -9.« less

Partial construction of apoptotic pathway in PBMC obtained from active SLE patients and the significance of plasma TNF-alpha on this pathway.

PubMed

Pitidhammabhorn, Dhanesh; Kantachuvesiri, Surasak; Totemchokchyakarn, Kitti; Kitiyanant, Yindee; Ubol, Sukathida

2006-09-01

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder that affects various organs and systems. Increased apoptosis, together with defects in the uptake of apoptotic bodies, are thought to have a pathogenic role in SLE. By detection of chromatin condensation, 30% of apoptosis was detected in peripheral blood mononuclear cells (PBMC) from Thai patients with active SLE. Therefore, understanding of the molecular processes in PBMC apoptosis may allow us to gain insight into pathophysiology of SLE. Thus, genes involved in the apoptosis of PBMC from these patients were investigated ex vivo by cDNA array analysis. Seventeen apoptosis-related genes were stimulated in active SLE, more than twofold higher than in inactive SLE. These genes are classified into six groups, namely death receptors, death ligands, caspases, bcl-family, and neutral proteases and genes involved in endoplasmic reticulum stress-mediated apoptosis, such as caspase-4 and GADD153. Among those stimulated genes, tumor necrosis factor (TNF) and the TNF-receptor family were drastically up-regulated 60- and 19-fold higher than in healthy controls, respectively. Moreover, the degree of apoptosis correlated with the level of TNF-alpha in plasma, suggesting that the TNF family plays a role in the induction of apoptosis in SLE. To verify this hypothesis, PBMC from healthy individuals were treated with plasma from active SLE patients in the presence or absence of etanercept, a TNF inhibitor. In the presence of etanercept, active SLE plasma reduced the level of apoptosis to 26.43%. In conclusion, massive apoptotic death of PBMC occurred during the active stage of SLE. The molecular pathway of SLE-PBMC apoptosis was mediated at least via TNF/TNFR signaling pathway, which was confirmed by functional test of TNF-alpha in SLE patients' plasma.

Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary adenoma

PubMed Central

Zhou, Yunli; Zhang, Xun; Klibanski, Anne

2013-01-01

Human pituitary adenomas are the most common intracranial neoplasms. Approximately 5% of them are familial adenomas. Patients with familial tumors carry germline mutations in predisposition genes, including AIP, MEN1 and PRKAR1A. These mutations are extremely rare in sporadic pituitary adenomas, which therefore are caused by different mechanisms. Multiple tumor suppressive genes linked to sporadic tumors have been identified. Their inactivation is caused by epigenetic mechanisms, mainly promoter hypermethylation, and can be placed into two groups based on their functional interaction with tumor suppressors RB or p53. The RB group includes CDKN2A, CDKN2B, CDKN2C, RB1, BMP4, CDH1, CDH13, GADD45B and GADD45G; AIP and MEN1 genes also belong to this group. The p53 group includes MEG3, MGMT, PLAGL1, RASSF1, RASSF3 and SOCS1. We propose that the tumor suppression function of these genes is mainly mediated by the RB and p53 pathways. We also discuss possible tumor suppression mechanisms for individual genes. PMID:24035864

Evaluation of the GADD45α-GFP GreenScreen HC assay for rapid and reliable in vitro early genotoxicity screening.

PubMed

Luzy, Anne-Pascale; Orsini, Nicolas; Linget, Jean-Michel; Bouvier, Guy

2013-11-01

Twenty-two of Galderma's proprietary compounds were tested in the GADD45α-GFP 'GreenScreen HC' assay (GS), the SOS-ChromoTest and the Mini-Ames to evaluate GSs performance for early genotoxicity screening purposes. Forty more characterized compounds were also tested, including antibiotics: metronidazole, clindamycin, tetracycline, lymecycline and neomycin; and catecholamines: resorcinol mequinol, hydroquinone, one aneugen carbendazim, one corticoid dexamethasone, one peroxisome proliferator-activated receptor rosiglitazone, one pesticide carbaryl and two further proprietary molecules with in vitro genotoxicity data. With proprietary molecules, this study concluded that the GS renders the SOS-ChromoTest obsolete for in vitro screening. The GS confirmed all results of the Mini-Ames test (100% concordance). Compared with the micronucleus test, the GS showed a concordance of 82%. With known compounds, the GS ranked the potency of positive results for catecholamines in accordance with other genotoxicity tests and showed very reproducible results. It confirmed positive results for carbendazim, for tetracycline antibiotics and for carbaryl. The GS produced negative results for metronidazole, a nitroreduction-specific bacterial mutagen, for dexamethasone (a non-genotoxic apoptosis inducer), for rosiglitazone (a GADD45γ promoter inducer) and for clindamycin and neomycin (inhibitors of macromolecular synthesis in bacteria). As such, the GS appears to be a reproducible, robust, specific and sensitive test for genotoxicity screening. Copyright © 2012 John Wiley & Sons, Ltd.

7 CFR 15.3 - Discrimination prohibited.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 1 2012-01-01 2012-01-01 false Discrimination prohibited. 15.3 Section 15.3... Discrimination prohibited. (a) General. No person in the United States shall, on the ground of race, color, or... discrimination under any program or activity of the applicant or recipient to which these regulations apply...

7 CFR 15.3 - Discrimination prohibited.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 1 2014-01-01 2014-01-01 false Discrimination prohibited. 15.3 Section 15.3... Discrimination prohibited. (a) General. No person in the United States shall, on the ground of race, color, or... discrimination under any program or activity of the applicant or recipient to which these regulations apply...

7 CFR 15.3 - Discrimination prohibited.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 1 2013-01-01 2013-01-01 false Discrimination prohibited. 15.3 Section 15.3... Discrimination prohibited. (a) General. No person in the United States shall, on the ground of race, color, or... discrimination under any program or activity of the applicant or recipient to which these regulations apply...

Role of Growth Arrest and DNA Damage–inducible α in Akt Phosphorylation and Ubiquitination after Mechanical Stress-induced Vascular Injury

PubMed Central

Mitra, Sumegha; Sammani, Saad; Wang, Ting; Boone, David L.; Meyer, Nuala J.; Dudek, Steven M.; Moreno-Vinasco, Liliana; Garcia, Joe G. N.

2011-01-01

Rationale: The stress-induced growth arrest and DNA damage–inducible α (GADD45a) gene is up-regulated by mechanical stress with GADD45a knockout (GADD45a−/−) mice demonstrating both increased susceptibility to ventilator-induced lung injury (VILI) and reduced levels of the cell survival and vascular permeability signaling effector (Akt). However, the functional role of GADD45a in the pathogenesis of VILI is unknown. Objectives: We sought to define the role of GADD45a in the regulation of Akt activation induced by mechanical stress. Methods: VILI-challenged GADD45a−/− mice were administered a constitutively active Akt1 vector and injury was assessed by bronchoalveolar lavage cell counts and protein levels. Human pulmonary artery endothelial cells (EC) were exposed to 18% cyclic stretch (CS) under conditions of GADD45a silencing and used for immunoprecipitation, Western blotting or immunofluoresence. EC were also transfected with mutant ubiquitin vectors to characterize site-specific Akt ubiquitination. DNA methylation was measured using methyl-specific polymerase chain reaction assay. Measurements and Main Results: Studies exploring the linkage of GADD45a with mechanical stress and Akt regulation revealed VILI-challenged GADD45a−/− mice to have significantly reduced lung injury on overexpression of Akt1 transgene. Increased mechanical stress with 18% CS in EC induced Akt phosphorylation via E3 ligase tumor necrosis factor receptor–associated factor 6 (TRAF6)–mediated Akt K63 ubiquitination resulting in Akt trafficking and activation at the membrane. GADD45a is essential to this process because GADD45a-silenced endothelial cells and GADD45a−/− mice exhibited increased Akt K48 ubiquitination leading to proteasomal degradation. These events involve loss of ubiquitin carboxyl terminal hydrolase 1 (UCHL1), a deubiquitinating enzyme that normally removes K48 polyubiquitin chains bound to Akt thus promoting Akt K63 ubiquitination. Loss of GADD45a

Sesamin induces ER stress-mediated apoptosis and activates autophagy in cervical cancer cells.

PubMed

Dou, Haowen; Yang, Shasha; Hu, Yulai; Xu, Dongyuan; Liu, Lan; Li, Xiangdan

2018-05-01

Sesamin, a major lignan of sesame oil, has demonstrated anticancer properties. However, its anticancer effects on cervical cancer have not been studied. Here, we investigated the effects of sesamin on cervical cancer (HeLa) cell line and explored the underlying mechanisms. HeLa cells were cultured with sesamin. CCK-8 and scratch wound test were applied to detect the proliferation and migration ability, while flow cytometry and TUNEL staining were applied to detect apoptosis. The expression of Bax and Bcl-2 was assessed by Western blotting. Further observe the ultrastructure using transmission electron microscopy (TEM) and detect the expression of caspase-12, GRP78, GADD153, IRE1α, p-IRE1α, JNK, p-JNK, LC3I/II and beclin-1. In addition, HeLa cells were treated with 3-MA (an autophagy inhibitor) and/or sesamin. Then detect the expression of LC3I/II and cell viability. CCK-8 and scratch wound test revealed that sesamin inhibits HeLa cells proliferation and migration, while flow cytometry and TUNEL staining indicated that sesamin induces apoptosis in these cells. In sesamin group, the expression of Bax, caspase-12, GRP78, GADD153, p-IRE1α, p-JNK, LC3I/II and beclin-1 was up-regulated while Bcl-2 was down-regulated compared to control group. Further research revealed that sesamin also induces Hela cells autophagy and inhibition of autophagy increases cell viability of sesamin-treated HeLa cells. Sesamin inhibits proliferation/migration of HeLa cells and induces ER stress-mediated apoptosis through IRE1α/JNK pathway, and that it activates autophagy and autophagic death in these cells, further validate the anticancer effect of sesamin. Copyright © 2018 Elsevier Inc. All rights reserved.

PCB153 reduces telomerase activity and telomere length in immortalized human skin keratinocytes (HaCaT) but not in human foreskin keratinocytes (NFK)

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

Senthilkumar, P.K.; Robertson, L.W.; Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA

Polychlorinated biphenyls (PCBs), ubiquitous environmental pollutants, are characterized by long term-persistence in the environment, bioaccumulation, and biomagnification in the food chain. Exposure to PCBs may cause various diseases, affecting many cellular processes. Deregulation of the telomerase and the telomere complex leads to several biological disorders. We investigated the hypothesis that PCB153 modulates telomerase activity, telomeres and reactive oxygen species resulting in the deregulation of cell growth. Exponentially growing immortal human skin keratinocytes (HaCaT) and normal human foreskin keratinocytes (NFK) were incubated with PCB153 for 48 and 24 days, respectively, and telomerase activity, telomere length, superoxide level, cell growth, and cellmore » cycle distribution were determined. In HaCaT cells exposure to PCB153 significantly reduced telomerase activity, telomere length, cell growth and increased intracellular superoxide levels from day 6 to day 48, suggesting that superoxide may be one of the factors regulating telomerase activity, telomere length and cell growth compared to untreated control cells. Results with NFK cells showed no shortening of telomere length but reduced cell growth and increased superoxide levels in PCB153-treated cells compared to untreated controls. As expected, basal levels of telomerase activity were almost undetectable, which made a quantitative comparison of treated and control groups impossible. The significant down regulation of telomerase activity and reduction of telomere length by PCB153 in HaCaT cells suggest that any cell type with significant telomerase activity, like stem cells, may be at risk of premature telomere shortening with potential adverse health effects for the affected organism. -- Highlights: ► Human immortal (HaCaT) and primary (NFK) keratinocytes were exposed to PCB153. ► PCB153 significantly reduced telomerase activity and telomere length in HaCaT. ► No effect on telomere length

Garlic extract diallyl sulfide (DAS) activates nuclear receptor CAR to induce the Sult1e1 gene in mouse liver.

PubMed

Sueyoshi, Tatsuya; Green, William D; Vinal, Kellie; Woodrum, Tyler S; Moore, Rick; Negishi, Masahiko

2011-01-01

Constituent chemicals in garlic extract are known to induce phase I and phase II enzymes in rodent livers. Here we have utilized Car(+/+) and Car(-/-) mice to demonstrate that the nuclear xenobiotic receptor CAR regulated the induction of the estrogen sulfotransferase Sult1e1 gene by diallyl sulfide (DAS) treatment in mouse liver. DAS treatment caused CAR accumulation in the nucleus, resulting in a remarkable increase of SULT1E1 mRNA (3,200 fold) and protein in the livers of Car(+/+) females but not of Car(-/-) female mice. DAS also induced other CAR-regulated genes such as Cyp2b10, Cyp3a11 and Gadd45β. Compared with the rapid increase of these mRNA levels, which began as early as 6 hours after DAS treatment, the levels of SULT1E1 mRNA began increasing after 24 hours. This slow response to DAS suggested that CAR required an additional factor to activate the Sult1e1 gene or that this activation was indirect. Despite the remarkable induction of SULT1E1, there was no decrease in the serum levels of endogenous E2 or increase of estrone sulfate while the clearance of exogenously administrated E2 was accelerated in DAS treated mice.

Elucidation of a novel phenformin derivative on glucose-deprived stress responses in HT-29 cells.

PubMed

Oh-Hashi, Kentaro; Irie, Nao; Sakai, Takayuki; Okuda, Kensuke; Nagasawa, Hideko; Hirata, Yoko; Kiuchi, Kazutoshi

2016-08-01

Recently, we developed a variety of phenformin derivatives as selective antitumor agents. Based on previous findings, this study evaluated a promising compound, 2-(2-chlorophenyl)ethylbiguanide (2-Cl-Phen), on the basis of stress responses in the human colon cancer cell line HT-29 under a serum- and glucose-deprived condition. 2-Cl-Phen triggered morphological changes such as shrinkage and plasma membrane disintegration, as well as a decrease in mitochondrial activity and an increase in LDH leakage. To understand intracellular issues relating to 2-Cl-Phen, this study focused on the expression levels of ER stress-inducible genes and several oncogenic genes. Serum and glucose deprivation significantly induced a variety of ER stress-inducible genes, but a 12-h treatment of 2-Cl-Phen down-regulated expression of several ER stress-related genes, with the exception of GADD153. Interestingly, the expression levels of ATF6α, GRP78, MANF, and CRELD2 mRNA were almost completely decreased by 2-Cl-Phen. This study also observed that a 24-h treatment of 2-Cl-Phen attenuated the expression levels of GRP78, GADD153, and c-Myc protein. The decrease in c-Myc protein occurred before the fluctuation of GRP78 protein, while the expression of c-Myc mRNA showed little change with cotreatment of serum and glucose deprivation with 2-Cl-Phen. To further understand the 2-Cl-Phen-induced down-regulation of ATF6-related genes, this study investigated the stability of ATF6α and GRP78 proteins using NanoLuc-tagged constructs. The expression levels of NanoLuc-tagged ATF6α and GRP78 were significantly down-regulated by 2-Cl-Phen in the presence or absence of the translation inhibitor cycloheximide. Taken together, our novel phenformin derivative 2-Cl-Phen has the unique characteristic of diminishing tumor adaptive responses, especially the expression of ATF6-related genes, as well as that of c-Myc protein, in a transcriptional and posttranscriptional manner under a serum- and glucose

Cellular responses to oxidative stress: the [Ah] gene battery as a paradigm.

PubMed Central

Nebert, D W; Petersen, D D; Fornace, A J

1990-01-01

A major source of oxidative stress in animals is plant stress metabolites, also termed phytoalexins. The aromatic hydrocarbon-responsive [Ah] gene battery is considered here as a model system in which we can study metabolically coordinated enzymes that respond to phytoalexin-induced oxidative stress. In the mouse, the [Ah] battery comprises at least six genes: two Phase I genes, CYP1A1 and CYP1A2; and four Phase II genes, Nmo-1, Aldh-1, Ugt-1, and Gt-1. All six genes appear to be regulated positively by inducers such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other ligands of the Ah receptor. In the absence of foreign inducer, the control of Nmo-1 gene expression is independent of the control of CYP1A1 and CYP1A2 gene expression. The radiation deletion homozygote c14CoS/c14CoS mouse is lacking about 1.1 centiMorgans of chromosome 7. Although having no detectable CYP1A1 or CYP1A2 activation, the untreated c14CoS/c14CoS mouse exhibits markedly elevated transcripts of the Nmo-1 gene and three growth arrest- and DNA damage-inducible (gadd) genes. These data suggest that the missing region on chromosome 7 in the c14CoS/c14CoS mouse contains a gene(s), which we propose to call Nmo-1n, encoding a trans-acting factor(s) that is a negative effector of the Nmo-1 and gadd genes. The three other [Ah] battery Phase II genes behave similarly to Nmo-1 in the c14CoS/c14CoS mouse. This coordinated response to oxidative stress and DNA damage, by way of the release of a mammalian battery of genes from negative control, bears an interesting resemblance to the SOS response in bacteria. PMID:2272308

6 CFR 15.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... major life activities. (4) Is regarded as having an impairment means: (i) Has a physical or mental... DISABILITY IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF HOMELAND SECURITY § 15.3 Definitions. For... of, programs or activities conducted by the Department. For example, auxiliary aids useful for...

Non-coplanar polychlorinated biphenyls (PCBs) are direct agonists for the human pregnane-X receptor and constitutive androstane receptor, and activate target gene expression in a tissue-specific manner

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

Al-Salman, Fadheela; Plant, Nick, E-mail: N.Plant@Surrey.ac.uk

The polychlorinated biphenyl group possesses high environmental persistence, leading to bioaccumulation and a number of adverse effects in mammals. Whilst coplanar PCBs elicit their toxic effects through agonism of the aryl hydrocarbon receptor; however, non-coplanar PCBs are not ligands for AhR, but may be ligands for members of the nuclear receptor family of proteins. To better understand the biological actions of non-coplanar PCBs, we have undertaken a systematic analysis of their ability to activate PXR and CAR-mediated effects. Cells were exposed to a range of non-coplanar PCBs (99, 138, 153, 180 and 194), or the coplanar PCB77: Direct activation ofmore » PXR and CAR was measured using a mammalian receptor activation assay in human liver cells, with rifampicin and CITCO used as positive controls ligands for PXR and CAR, respectively; activation of target gene expression was examined using reporter gene plasmids for CYP3A4 and MDR1 transfected into liver, intestine and lung cell lines. Several of the non-coplanar PCBs directly activated PXR and CAR, whilst the coplanar PCB77 did not. Non-coplanar PCBs were also able to activate PXR/CAR target gene expression in a substitution- and tissue-specific manner. Non-coplanar PCBs act as direct activators for the nuclear receptors PXR and CAR, and are able to elicit transcriptional activation of target genes in a substitution- and tissue-dependent manner. Chronic activation of PXR/CAR is linked to adverse effects and must be included in any risk assessment of PCBs. -- Highlights: ► Several Non-coplanar PCBs are able to directly activate both PXR and CAR in vitro. ► PCB153 is the most potent direct activator of PXR and CAR nuclear receptors. ► Non-coplanar PCB activation of CYP3A4/MDR1 reporter genes is structure-dependent. ► Non-coplanar PCB activate CYP3A4/MDR1 reporter genes in a tissue-dependent. ► PCB153 is the most potent activator of PXR/CAR target gene in all tissues.« less

DDE and PCB 153 independently induce aryl hydrocarbon receptor (AhR) expression in peripheral blood mononuclear cells.

PubMed

Gaspar-Ramírez, Octavio; Pérez-Vázquez, Francisco J; Salgado-Bustamante, Mariana; González-Amaro, Roberto; Hernandez-Castro, Berenice; Pérez-Maldonado, Ivan N

2015-01-01

Recent studies have demonstrated that compounds inducing pro-inflammatory cytokines enhance AhR expression. The aim of this study was 2-fold: (1) to determine if two pro-inflammatory compounds, dichlorodiphenyldichloroethylene (DDE) and 2,2',4,4',5,5'-hexa-chlorobiphenyl (PCB 153), independently affect AhR gene expression in peripheral blood mononuclear cells (PBMC); and (2) if affected, to determine whether the mechanism involved was due to AhR activation or to a pro-inflammatory effect of the chemicals. PBMC isolated from healthy individuals were incubated in the presence of DDE (10 µg/ml) and PCB 153 (20 ng/ml) over time and AhR and CYP1A1 expression was assessed with a real-time PCR technique. The results indicated there was over-expression of the AhR mRNA in PBMC when the cells were treated with DDE and PCB 153. No changes in expression levels of CYP1A1 mRNA were found. Importantly, when the cells were exposed to DDE and PCB 153 in the presence of an antagonist of tumor necrosis factor (TNF)-α, the over-expression of AhR was abolished; as expected, the expression of CYP1A1 was unaffected. In conclusion, these studies demonstrated for the first time an increment of AhR expression "in vitro" in PBMC treated with two pro-inflammatory environmental pollutants, DDE and PCB153. Moreover, the over-expression of AhR was dependent of TNFα induced by DDE and PCB 153 and was independent of AhR activation.

Minimal traumatic brain injury causes persistent changes in DNA methylation at BDNF gene promoters in rat amygdala: A possible role in anxiety-like behaviors.

PubMed

Sagarkar, Sneha; Bhamburkar, Tanmayi; Shelkar, Gajanan; Choudhary, Amit; Kokare, Dadasaheb M; Sakharkar, Amul J

2017-10-01

Minimal traumatic brain injury (MTBI) often transforms into chronic neuropsychiatric conditions including anxiety, the underlying mechanisms of which are largely unknown. In the present study, we employed the closed-head injury paradigm to induce MTBI in rats and examined whether DNA methylation can explain long-term changes in the expression of the brain-derived neurotrophic factor (BDNF) in the amygdala as well as trauma-induced anxiety-like behaviors. The MTBI caused anxiety-like behaviors and altered the expression of DNA methyltransferase (DNMT) isoforms (DNMT1, DNMT3a, and DNMT3b) and factors involved in DNA demethylation such as the growth arrest and DNA damage 45 (GADD45a and GADD45b). After 30days of MTBI, the over-expression of DNMT3a and DNMT3b corresponded to heightened DNMT activity, whereas the mRNA levels of GADD45a and GADD45b were declined. The methylated cytosine levels at the BDNF promoters (Ip, IVp and IXp) were increased in the amygdala of the trauma-induced animals; these coincided negatively with the mRNA levels of exon IV and IXa, but not of exon I. Interestingly, treatment with 5-azacytidine, a pan DNMT inhibitor, normalized the MTBI-induced DNMT activity and DNA hypermethylation at exon IVp and IXp. Furthermore, 5-azacytidine also corrected the deficits in the expression of exons IV and IXa and reduced the anxiety-like behaviors. These results suggest that the DNMT-mediated DNA methylation at the BDNF IVp and IXp might be involved in the regulation of BDNF gene expression in the amygdala. Further, it could also be related to MTBI-induced anxiety-like behaviors via the regulation of synaptic plasticity. Copyright © 2017 Elsevier Inc. All rights reserved.

Garlic Extract Diallyl Sulfide (DAS) Activates Nuclear Receptor CAR to Induce the Sult1e1 Gene in Mouse Liver

PubMed Central

Sueyoshi, Tatsuya; Green, William D.; Vinal, Kellie; Woodrum, Tyler S.; Moore, Rick; Negishi, Masahiko

2011-01-01

Constituent chemicals in garlic extract are known to induce phase I and phase II enzymes in rodent livers. Here we have utilized Car +/+ and Car −/− mice to demonstrate that the nuclear xenobiotic receptor CAR regulated the induction of the estrogen sulfotransferase Sult1e1 gene by diallyl sulfide (DAS) treatment in mouse liver. DAS treatment caused CAR accumulation in the nucleus, resulting in a remarkable increase of SULT1E1 mRNA (3,200 fold) and protein in the livers of Car +/+ females but not of Car −/− female mice. DAS also induced other CAR-regulated genes such as Cyp2b10, Cyp3a11 and Gadd45β. Compared with the rapid increase of these mRNA levels, which began as early as 6 hourrs after DAS treatment, the levels of SULT1E1 mRNA began increasing after 24 hours. This slow response to DAS suggested that CAR required an additional factor to activate the Sult1e1 gene or that this activation was indirect. Despite the remarkable induction of SULT1E1, there was no decrease in the serum levels of endogenous E2 or increase of estrone sulfate while the clearance of exogenously administrated E2 was accelerated in DAS treated mice. PMID:21698271

Activation of ERK and JNK signaling pathways by mycotoxin citrinin in human cells

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

Chang, C.-H.; Yu, F.-Y.; Wang, L.-T.

2009-06-15

Mycotoxin citrinin (CTN) is commonly found in foods and feeds that are contaminated/inoculated with Penicillium, Aspergillus and Monascus species. The exposure of human embryonic kidney (HEK293) and HeLa cells to CTN resulted in a dose-dependent increase in the phosphorylation of two major mitogen-activated protein kinases (MAPKs), ERK1/2 and JNK. In HEK293 cultures, the administering of CTN increased both the mRNA and protein levels of egr-1, c-fos and c-jun genes; additionally, the ERK1/2 pathway contributed to the upregulation of Egr-1 and c-Fos protein expression. CTN treatment also induced the transcription activity of Egr-1 and AP-1 proteins, as evidenced by luciferase reportermore » assays. Bioinformatic analyses indicated two genes Gadd45{beta} and MMP3 have Egr-1 and AP-1 response elements in their promoters, respectively. Furthermore, co-exposure of HEK293 cells to CTN and MAPK pathway inhibitors demonstrated that CTN increased the levels of Gadd45{beta} mRNA through ERK1/2 signaling pathway and up-regulated the MMP3 transcripts majorly via JNK pathway. Finally, CTN-triggered caspase 3 activity was significantly reduced in the presence of MAPK inhibitors. Our results suggest that CTN positively regulates ERK1/2 and JNK pathways as well as their downstream effectors in human cells; activated MAPK pathways are also involved in CTN-induced apoptosis.« less

Study of interaction of antimutagenic 1,4-dihydropyridine AV-153-Na with DNA-damaging molecules and its impact on DNA repair activity.

PubMed

Leonova, Elina; Rostoka, Evita; Sauvaigo, Sylvie; Baumane, Larisa; Selga, Turs; Sjakste, Nikolajs

2018-01-01

1,4-dihydropyridines (1,4-DHP) possesses important biochemical and pharmacological properties, including antioxidant and antimutagenic activities. It was shown that the antimutagenic 1,4-dihydropyridine AV-153-Na interacts with DNA. The aim of the current study was to test the capability of the compound to scavenge peroxynitrite and hydroxyl radical, to test intracellular distribution of the compound, and to assess the ability of the compound to modify the activity of DNA repair enzymes and to protect the DNA in living cells against peroxynitrite-induced damage. Peroxynitrite decomposition was assayed by UV spectroscopy, hydroxyl radical scavenging-by EPR spectroscopy. DNA breakage was determined by the "comet method", activity of DNA repair enzymes-using Glyco-SPOT and ExSy-SPOT assays. Intracellular distribution of the compound was studied by laser confocal scanning fluorescence microscopy. Fluorescence spectroscopy titration and circular dichroism spectroscopy were used to study interactions of the compound with human serum albumin. Some ability to scavenge hydroxyl radical by AV-153-Na was detected by the EPR method, but it turned out to be incapable of reacting chemically with peroxynitrite. However, AV-153-Na effectively decreased DNA damage produced by peroxynitrite in cultured HeLa cells. The Glyco-SPOT test essentially revealed an inhibition by AV-153-Na of the enzymes involved thymine glycol repair. Results with ExSy-SPOT chip indicate that AV-153-Na significantly stimulates excision/synthesis repair of 8-oxoguanine (8-oxoG), abasic sites (AP sites) and alkylated bases. Laser confocal scanning fluorescence microscopy demonstrated that within the cells AV-153-Na was found mostly in the cytoplasm; however, a stain in nucleolus was also detected. Binding to cytoplasmic structures might occur due to high affinity of the compound to proteins revealed by spectroscopical methods. Activation of DNA repair enzymes after binding to DNA appears to be the basis for

Impact of α-targeted radiation therapy on gene expression in a pre-clinical model for disseminated peritoneal disease when combined with paclitaxel.

PubMed

Yong, Kwon Joong; Milenic, Diane E; Baidoo, Kwamena E; Brechbiel, Martin W

2014-01-01

To better understand the molecular basis of the enhanced cell killing effected by the combined modality of paclitaxel and ²¹²Pb-trastuzumab (Pac/²¹²Pb-trastuzumab), gene expression in LS-174T i.p. xenografts was investigated 24 h after treatment. Employing a real time quantitative PCR array (qRT-PCR array), 84 DNA damage response genes were quantified. Differentially expressed genes following therapy with Pac/²¹²Pb-trastuzumab included those involved in apoptosis (BRCA1, CIDEA, GADD45α, GADD45γ, GML, IP6K3, PCBP4, PPP1R15A, RAD21, and p73), cell cycle (BRCA1, CHK1, CHK2, GADD45α, GML, GTSE1, NBN, PCBP4, PPP1R15A, RAD9A, and SESN1), and damaged DNA repair (ATRX, BTG2, EXO1, FEN1, IGHMBP2, OGG1, MSH2, MUTYH, NBN, PRKDC, RAD21, and p73). This report demonstrates that the increased stressful growth arrest conditions induced by the Pac/²¹²Pb-trastuzumab treatment suppresses cell proliferation through the regulation of genes which are involved in apoptosis and damaged DNA repair including single and double strand DNA breaks. Furthermore, the study demonstrates that ²¹²Pb-trastuzumab potentiation of cell killing efficacy results from the perturbation of genes related to the mitotic spindle checkpoint and BASC (BRCA1-associated genome surveillance complex), suggesting cross-talk between DNA damage repair and the spindle damage response.

4-Phenylbutyrate Inhibits Tunicamycin-Induced Acute Kidney Injury via CHOP/GADD153 Repression

PubMed Central

Carlisle, Rachel E.; Brimble, Elise; Werner, Kaitlyn E.; Cruz, Gaile L.; Ask, Kjetil; Ingram, Alistair J.; Dickhout, Jeffrey G.

2014-01-01

Different forms of acute kidney injury (AKI) have been associated with endoplasmic reticulum (ER) stress; these include AKI caused by acetaminophen, antibiotics, cisplatin, and radiocontrast. Tunicamycin (TM) is a nucleoside antibiotic known to induce ER stress and is a commonly used inducer of AKI. 4-phenylbutyrate (4-PBA) is an FDA approved substance used in children who suffer from urea cycle disorders. 4-PBA acts as an ER stress inhibitor by aiding in protein folding at the molecular level and preventing misfolded protein aggregation. The main objective of this study was to determine if 4-PBA could protect from AKI induced by ER stress, as typified by the TM-model, and what mechanism(s) of 4-PBA's action were responsible for protection. C57BL/6 mice were treated with saline, TM or TM plus 4-PBA. 4-PBA partially protected the anatomic segment most susceptible to damage, the outer medullary stripe, from TM-induced AKI. In vitro work showed that 4-PBA protected human proximal tubular cells from apoptosis and TM-induced CHOP expression, an ER stress inducible proapoptotic gene. Further, immunofluorescent staining in the animal model found similar protection by 4-PBA from CHOP nuclear translocation in the tubular epithelium of the medulla. This was accompanied by a reduction in apoptosis and GRP78 expression. CHOP−/− mice were protected from TM-induced AKI. The protective effects of 4-PBA extended to the ultrastructural integrity of proximal tubule cells in the outer medulla. When taken together, these results indicate that 4-PBA acts as an ER stress inhibitor, to partially protect the kidney from TM-induced AKI through the repression of ER stress-induced CHOP expression. PMID:24416259

Identification of Epithelial-Mesenchymal Transition-related Target Genes Induced by the Mutation of Smad3 Linker Phosphorylation.

PubMed

Park, Sujin; Yang, Kyung-Min; Park, Yuna; Hong, Eunji; Hong, Chang Pyo; Park, Jinah; Pang, Kyoungwha; Lee, Jihee; Park, Bora; Lee, Siyoung; An, Haein; Kwak, Mi-Kyung; Kim, Junil; Kang, Jin Muk; Kim, Pyunggang; Xiao, Yang; Nie, Guangjun; Ooshima, Akira; Kim, Seong-Jin

2018-03-01

Smad3 linker phosphorylation plays essential roles in tumor progression and metastasis. We have previously reported that the mutation of Smad3 linker phosphorylation sites (Smad3-Erk/Pro-directed kinase site mutant constructs [EPSM]) markedly reduced the tumor progression while increasing the lung metastasis in breast cancer. We performed high-throughput RNA-Sequencing of the human prostate cancer cell lines infected with adenoviral Smad3-EPSM to identify the genes regulated by Smad3-EPSM. In this study, we identified genes which are differentially regulated in the presence of Smad3-EPSM. We first confirmed that Smad3-EPSM strongly enhanced a capability of cell motility and invasiveness as well as the expression of epithelial-mesenchymal transition marker genes, CDH2 , SNAI1 , and ZEB1 in response to TGF-β1 in human pancreatic and prostate cancer cell lines. We identified GADD45B , CTGF , and JUNB genes in the expression profiles associated with cell motility and invasiveness induced by the Smad3-EPSM. These results suggested that inhibition of Smad3 linker phosphorylation may enhance cell motility and invasiveness by inducing expression of GADD45B , CTGF , and JUNB genes in various cancers.

Activation of endoplasmic reticulum stress response by enhanced polyamine catabolism is important in the mediation of cisplatin-induced acute kidney injury

PubMed Central

Barone, Sharon; Destefano-Shields, Christina; Brooks, Marybeth; Murray-Stewart, Tracy; Dunworth, Matthew; Li, Weimin; Doherty, Joanne R.; Hall, Mark A.; Smith, Roger D.; Cleveland, John L.; Casero, Robert A.; Soleimani, Manoocher

2017-01-01

Cisplatin-induced nephrotoxicity limits its use in many cancer patients. The expression of enzymes involved in polyamine catabolism, spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMOX) increase in the kidneys of mice treated with cisplatin. We hypothesized that enhanced polyamine catabolism contributes to tissue damage in cisplatin acute kidney injury (AKI). Using gene knockout and chemical inhibitors, the role of polyamine catabolism in cisplatin AKI was examined. Deficiency of SSAT, SMOX or neutralization of the toxic products of polyamine degradation, H2O2 and aminopropanal, significantly diminished the severity of cisplatin AKI. In vitro studies demonstrated that the induction of SSAT and elevated polyamine catabolism in cells increases the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and enhances the expression of binding immunoglobulin protein BiP/GRP78) and CCAAT-enhancer-binding protein homologous protein (CHOP/GADD153). The increased expression of these endoplasmic reticulum stress response (ERSR) markers was accompanied by the activation of caspase-3. These results suggest that enhanced polyamine degradation in cisplatin AKI may lead to tubular damage through the induction of ERSR and the consequent onset of apoptosis. In support of the above, we show that the ablation of the SSAT or SMOX gene, as well as the neutralization of polyamine catabolism products modulate the onset of ERSR (e.g. lower BiP and CHOP) and apoptosis (e.g. reduced activated caspase-3). These studies indicate that enhanced polyamine catabolism and its toxic products are important mediators of ERSR and critical to the pathogenesis of cisplatin AKI. PMID:28886181

Activation of endoplasmic reticulum stress response by enhanced polyamine catabolism is important in the mediation of cisplatin-induced acute kidney injury.

PubMed

Zahedi, Kamyar; Barone, Sharon; Destefano-Shields, Christina; Brooks, Marybeth; Murray-Stewart, Tracy; Dunworth, Matthew; Li, Weimin; Doherty, Joanne R; Hall, Mark A; Smith, Roger D; Cleveland, John L; Casero, Robert A; Soleimani, Manoocher

2017-01-01

Cisplatin-induced nephrotoxicity limits its use in many cancer patients. The expression of enzymes involved in polyamine catabolism, spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMOX) increase in the kidneys of mice treated with cisplatin. We hypothesized that enhanced polyamine catabolism contributes to tissue damage in cisplatin acute kidney injury (AKI). Using gene knockout and chemical inhibitors, the role of polyamine catabolism in cisplatin AKI was examined. Deficiency of SSAT, SMOX or neutralization of the toxic products of polyamine degradation, H2O2 and aminopropanal, significantly diminished the severity of cisplatin AKI. In vitro studies demonstrated that the induction of SSAT and elevated polyamine catabolism in cells increases the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and enhances the expression of binding immunoglobulin protein BiP/GRP78) and CCAAT-enhancer-binding protein homologous protein (CHOP/GADD153). The increased expression of these endoplasmic reticulum stress response (ERSR) markers was accompanied by the activation of caspase-3. These results suggest that enhanced polyamine degradation in cisplatin AKI may lead to tubular damage through the induction of ERSR and the consequent onset of apoptosis. In support of the above, we show that the ablation of the SSAT or SMOX gene, as well as the neutralization of polyamine catabolism products modulate the onset of ERSR (e.g. lower BiP and CHOP) and apoptosis (e.g. reduced activated caspase-3). These studies indicate that enhanced polyamine catabolism and its toxic products are important mediators of ERSR and critical to the pathogenesis of cisplatin AKI.

Intestinal exposure to PCB 153 induces inflammation via the ATM/NEMO pathway.

PubMed

Phillips, Matthew C; Dheer, Rishu; Santaolalla, Rebeca; Davies, Julie M; Burgueño, Juan; Lang, Jessica K; Toborek, Michal; Abreu, Maria T

2018-01-15

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that adversely affect human health. PCBs bio-accumulate in organisms important for human consumption. PCBs accumulation in the body leads to activation of the transcription factor NF-κB, a major driver of inflammation. Despite dietary exposure being one of the main routes of exposure to PCBs, the gut has been widely ignored when studying the effects of PCBs. We investigated the effects of PCB 153 on the intestine and addressed whether PCB 153 affected intestinal permeability or inflammation and the mechanism by which this occurred. Mice were orally exposed to PCB 153 and gut permeability was assessed. Intestinal epithelial cells (IECs) were collected and evaluated for evidence of genotoxicity and inflammation. A human IEC line (SW480) was used to examine the direct effects of PCB 153 on epithelial function. NF-кB activation was measured using a reporter assay, DNA damage was assessed, and cytokine expression was ascertained with real-time PCR. Mice orally exposed to PCB 153 had an increase in intestinal permeability and inflammatory cytokine expression in their IECs; inhibition of NF-кB ameliorated both these effects. This inflammation was associated with genotoxic damage and NF-кB activation. Exposure of SW480 cells to PCB 153 led to similar effects as seen in vivo. We found that activation of the ATM/NEMO pathway by genotoxic stress was upstream of NF-kB activation. These results demonstrate that oral exposure to PCB 153 is genotoxic to IECs and induces downstream inflammation and barrier dysfunction in the intestinal epithelium. Copyright © 2017 Elsevier Inc. All rights reserved.

Promoter methylation, mRNA expression of goat tumor‑associated genes and mRNA expression of DNA methyltransferase in enzootic nasal tumors.

PubMed

Quan, Zifang; Ye, Ni; Hao, Zhongxiang; Wen, Caifang; Liao, Hong; Zhang, Manli; Luo, Lu; Cao, Sanjie; Wen, Xintian; Wu, Rui; Yan, Qigui

2015-10-01

The aim of the present study was to investigate the promoter methylation status and mRNA expression of goat tumor‑associated genes, in addition to the mRNA expression of DNA methyltransferase genes in enzootic nasal tumors (ENT). Methylation‑specific polymerase chain reaction and SYBR Green reverse transcription‑quantitative polymerase chain reaction were used to detect the methylation status and the mRNA expression levels of DNA methyltransferases (DNMTs), O6‑methylguanine‑DNA methyltransferase (MGMT), the tumor suppressor genes P73, P53, GADD45G, CHFR and THBS1, the transcription factor CEBPA, the proto‑oncogenes KRAS, NRAS and C‑myc and EGFR in 24 nasal tumor tissue samples and 20 normal nasal epithelia tissue samples. The associations between promoter methylation and DNMT, and promoter methylation and mRNA expression of the genes were analyzed. The results indicated that the expression levels of DNMT1 increased by 56% compared with those in normal nasal epithelial tissues, while MGMT, DNMT3a and DNMT3b had similar expression levels in the two tissue types. The expression levels of P53 decreased by 36.8% and those of THBS1 by 43%, while C‑myc increased by 2.9‑fold and CEBPA by 2‑fold compared with that in normal nasal epithelial tissues. GADD45G, P73, CHFR and NRAS were observed to have similar expression levels in the two tissue types. However, no expression was observed for EGFR and KRAS. CHFR, GADD45G and THBS1 were identified to be methylated in tumor suppressor genes. The methylation expression rate of the CHFR gene was ~60% in the two tissue types and for THBS1 it was 100% in the nasal tumor tissues as opposed to 20% in the normal nasal epithelial tissues. The exhaustive methylation expression rate of GADD45G was 62.5% and the partial methylation expression rate was 37.5% in nasal tumor tissue, while no methylation was observed in normal nasal epithelial tissues. C‑myc was the only gene identified to be methylated amongst proto�

Adenosine monophosphate activated protein kinase (AMPK), a mediator of estradiol-induced apoptosis in long-term estrogen deprived breast cancer cells.

PubMed

Chen, Haiyan; Wang, Ji-Ping; Santen, Richard J; Yue, Wei

2015-06-01

Estrogens stimulate growth of hormone-dependent breast cancer but paradoxically induce tumor regress under certain circumstances. We have shown that long-term estrogen deprivation (LTED) enhances the sensitivity of hormone dependent breast cancer cells to estradiol (E2) so that physiological concentrations of estradiol induce apoptosis in these cells. E2-induced apoptosis involve both intrinsic and extrinsic pathways but precise mechanisms remain unclear. We found that exposure of LTED MCF-7 cells to E2 activated AMP activated protein kinase (AMPK). In contrast, E2 inhibited AMPK activation in wild type MCF-7 cells where E2 prevents apoptosis. As a result of AMPK activation, the transcriptional activity of FoxO3, a downstream factor of AMPK, was up-regulated in E2 treatment of LTED. Increased activity of FoxO3 was demonstrated by up-regulation of three FoxO3 target genes, Bim, Fas ligand (FasL), and Gadd45α. Among them, Bim and FasL mediate intrinsic and extrinsic apoptosis respectively and Gadd45α causes cell cycle arrest at the G2/M phase. To further confirm the role of AMPK in apoptosis, we used AMPK activator AICAR in wild type MCF-7 cells and examined apoptosis, proliferation and expression of Bim, FasL, and Gadd45α. The effects of AICAR on these parameters recapitulated those observed in E2-treated LTED cells. Activation of AMPK by AICAR also increased expression of Bax in MCF-7 cells and its localization to mitochondria, which is a required process for apoptosis. These results reveal that AMPK is an important factor mediating E2-induced apoptosis in LTED cells, which is implicative of therapeutic potential for relapsing breast cancer after hormone therapy.

6 CFR 15.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... specific learning disabilities. The term physical or mental impairment includes, but is not limited to... DISABILITY IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF HOMELAND SECURITY § 15.3 Definitions. For... disabilities shall also identify (where possible) the alleged victims of discrimination. (c) Facility means all...

Characteristics of nobiletin-mediated alteration of gene expression in cultured cell lines

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

Nemoto, Kiyomitsu, E-mail: nemoto@u-shizuoka-ken.ac.jp; Ikeda, Ayaka; Yoshida, Chiaki

Highlights: ► Nobiletin-mediated alterations of gene expression were examined with DNA microarrays. ► Three organ-derived cell lines were treated with 100 μM nobiletin for 24 h. ► In all cell lines, 3 endoplasmic reticulum stress-responsive genes were up-regulated. ► Some cell cycle-regulating and oxidative stress-promoting genes were down-regulated. ► These alterations may contribute to nobiletin-mediated biological effects. -- Abstract: Nobiletin, a polymethoxylated flavonoid that is highly contained in the peels of citrus fruits, exerts a wide variety of beneficial effects, including anti-proliferative effects in cancer cells, repressive effects in hyperlipidemia and hyperglycemia, and ameliorative effects in dementia at in vitromore » and in vivo levels. In the present study, to further understand the mechanisms of these actions of nobiletin, the nobiletin-mediated alterations of gene expression in three organ-derived cell lines – 3Y1 rat fibroblasts, HuH-7 human hepatocarcinoma cells, and SK-N-SH human neuroblastoma cells – were first examined with DNA microarrays. In all three cell lines, treatments with nobiletin (100 μM) for 24 h resulted in more than 200% increases in the expression levels of five genes, including the endoplasmic reticulum stress-responsive genes Ddit3, Trib3, and Asns, and in less than 50% decreases in the expression levels of seven genes, including the cell cycle-regulating genes Ccna2, Ccne2, and E2f8 and the oxidative stress-promoting gene Txnip. It was also confirmed that in each nobiletin-treated cell line, the levels of the DDIT3 (DNA-damage-inducible transcript 3, also known as CHOP and GADD153) and ASNS (asparagine synthetase) proteins were increased, while the level of the TXNIP (thioredoxin-interacting protein, also known as VDUP1 and TBP-2) protein was decreased. All these findings suggest that nobiletin exerts a wide variety of biological effects, at least partly, through induction of endoplasmic reticulum

AAV delivery of GRP78/BiP promotes adaptation of human RPE cell to ER stress.

PubMed

Ghaderi, Shima; Ahmadian, Shahin; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Samiei, Shahram; Kheitan, Samira; Pirmardan, Ehsan R

2018-02-01

Adeno associated virus (AAV)-mediated gene delivery of GRP78 (78 kDa glucose-regulated protein) attenuates the condition of endoplasmic reticulum (ER) stress and prevents apoptotic loss of photoreceptors in Retinitis pigmentosa (RP) rats. In the current study we overexpressed Grp78 with the help of AAV-2 in primary human retinal pigmented epithelium (hRPE) cell cultures and examined its effect on cell response to ER stress. The purpose of this work was studying potential stimulating effect of GRP78 on adaptation/pro-survival of hRPE cells under ER stress, as an in vitro model for RPE degeneration. To investigate the effect of Grp78 overexpression on unfolded protein response (UPR) markers under ER stress, hRPE primary cultures were transduced by recombinant virus rAAV/Grp78, and treated with ER stressor drug, tunicamycin. Expression changes of four UPR markers including GRP78, PERK, ATF6α, and GADD153/CHOP, were assessed by real-time PCR and western blotting. We found that GRP78 has a great contribution in modulation of UPR markers to favor adaptive response in ER-stressed hRPE cells. In fact, GRP78 overexpression affected adaptation and apoptotic phases of early UPR, through enhancement of two master regulators/ER stress sensors (PERK and ATF6α) and down-regulation of a key pro-apoptotic cascade activator (GADD153/CHOP). Together these findings demonstrate the promoting effect of GRP78 on adaptation/pro-survival of hRPE cells under ER stress. This protein with anti-apoptotic actions in the early UPR and important role in cell fate regulation, can be recruited as a useful candidate for future investigations of RPE degenerative diseases. © 2017 Wiley Periodicals, Inc.

Identification of Epithelial-Mesenchymal Transition-related Target Genes Induced by the Mutation of Smad3 Linker Phosphorylation

PubMed Central

Park, Sujin; Yang, Kyung-Min; Park, Yuna; Hong, Eunji; Hong, Chang Pyo; Park, Jinah; Pang, Kyoungwha; Lee, Jihee; Park, Bora; Lee, Siyoung; An, Haein; Kwak, Mi-Kyung; Kim, Junil; Kang, Jin Muk; Kim, Pyunggang; Xiao, Yang; Nie, Guangjun; Ooshima, Akira

2018-01-01

Background Smad3 linker phosphorylation plays essential roles in tumor progression and metastasis. We have previously reported that the mutation of Smad3 linker phosphorylation sites (Smad3-Erk/Pro-directed kinase site mutant constructs [EPSM]) markedly reduced the tumor progression while increasing the lung metastasis in breast cancer. Methods We performed high-throughput RNA-Sequencing of the human prostate cancer cell lines infected with adenoviral Smad3-EPSM to identify the genes regulated by Smad3-EPSM. Results In this study, we identified genes which are differentially regulated in the presence of Smad3-EPSM. We first confirmed that Smad3-EPSM strongly enhanced a capability of cell motility and invasiveness as well as the expression of epithelial-mesenchymal transition marker genes, CDH2, SNAI1, and ZEB1 in response to TGF-β1 in human pancreatic and prostate cancer cell lines. We identified GADD45B, CTGF, and JUNB genes in the expression profiles associated with cell motility and invasiveness induced by the Smad3-EPSM. Conclusions These results suggested that inhibition of Smad3 linker phosphorylation may enhance cell motility and invasiveness by inducing expression of GADD45B, CTGF, and JUNB genes in various cancers. PMID:29629343

Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication

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

Di Nunzio, Francesca, E-mail: francesca.di-nunzio@pasteur.fr; Fricke, Thomas; Miccio, Annarita

The early steps of HIV-1 replication involve the entry of HIV-1 into the nucleus, which is characterized by viral interactions with nuclear pore components. HIV-1 developed an evolutionary strategy to usurp the nuclear pore machinery and chromatin in order to integrate and efficiently express viral genes. In the current work, we studied the role of nucleoporins 153 and 98 (Nup153 and Nup98) in infection of human Jurkat lymphocytes by HIV-1. We showed that Nup153-depleted cells exhibited a defect in nuclear import, while depletion of Nup 98 caused a slight defect in HIV integration. To explore the biochemical viral determinants formore » the requirement of Nup153 and Nup98 during HIV-1 infection, we tested the ability of these nucleoporins to interact with HIV-1 cores. Our findings showed that both nucleoporins bind HIV-1 cores suggesting that this interaction is important for HIV-1 nuclear import and/or integration. Distribution analysis of integration sites in Nup153-depleted cells revealed a reduced tendency of HIV-1 to integrate in intragenic sites, which in part could account for the large infectivity defect observed in Nup153-depleted cells. Our work strongly supports a role for Nup153 in HIV-1 nuclear import and integration. - Highlights: ► We studied the role of Nup98 and Nup153 in HIV-1 infection. ► Nup98 binds the HIV-1 core and is involved in HIV-1 integration. ► Nup153 binds the HIV-1 core and is involved in HIV-1 nuclear import. ► Depletion of Nup153 decreased the integration of HIV-1 in transcriptionally active sites.« less

40 CFR 161.153 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Definitions. 161.153 Section 161.153 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR REGISTRATION OF ANTIMICROBIAL PESTICIDES Product Chemistry Data Requirements § 161.153 Definitions...

40 CFR 161.153 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Definitions. 161.153 Section 161.153 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR REGISTRATION OF ANTIMICROBIAL PESTICIDES Product Chemistry Data Requirements § 161.153 Definitions...

Evidence that endoplasmic reticulum (ER) stress and caspase-4 activation occur in human neutrophils

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

Binet, Francois; Chiasson, Sonia; Girard, Denis, E-mail: denis.girard@iaf.inrs.ca

2010-01-01

Apoptosis can result from activation of three major pathways: the extrinsic, the intrinsic, and the most recently identified endoplasmic reticulum (ER) stress-mediated pathway. While the two former pathways are known to be operational in human polymorphonuclear neutrophils (PMNs), the existence of the ER stress-mediated pathway, generally involving caspase-4, has never been reported in these cells. Recently, we have documented that arsenic trioxide (ATO) induced apoptosis in human PMNs by a mechanism that needs to be further investigated. In this study, using immunofluorescence and electron microscopy, we present evidence of ER alterations in PMNs activated by the ER stress inducer arsenicmore » trioxide (ATO). Several key players of the unfolded protein response, including GRP78, GADD153, ATF6, XBP1 and eIF2{alpha} are expressed and activated in PMNs treated with ATO or other ER stress inducers. Although caspase-4 is expressed and activated in neutrophils, treatment with a caspase-4 inhibitor did not attenuate the pro-apoptotic effect of ATO at a concentration that reverses caspase-4 processing and activation. Our results demonstrate for the first time that the ER stress-mediated apoptotic pathway operates in human neutrophils.« less

10 CFR 15.3 - Communications.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Communications. 15.3 Section 15.3 Energy NUCLEAR REGULATORY COMMISSION DEBT COLLECTION PROCEDURES Application and Coverage § 15.3 Communications. Unless otherwise specified, communications concerning the regulations in this part may be addressed to the...

46 CFR 153.1060 - Benzene.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Benzene. 153.1060 Section 153.1060 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures § 153.1060 Benzene...

46 CFR 153.1060 - Benzene.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Benzene. 153.1060 Section 153.1060 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures § 153.1060 Benzene...

46 CFR 153.1060 - Benzene.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Benzene. 153.1060 Section 153.1060 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures § 153.1060 Benzene...

46 CFR 153.1060 - Benzene.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Benzene. 153.1060 Section 153.1060 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures § 153.1060 Benzene...

46 CFR 153.1060 - Benzene.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Benzene. 153.1060 Section 153.1060 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures § 153.1060 Benzene...

33 CFR 153.107 - [Reserved

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false [Reserved] 153.107 Section 153.107 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION CONTROL OF POLLUTION BY OIL AND HAZARDOUS SUBSTANCES, DISCHARGE REMOVAL General § 153.107 [Reserved] ...

33 CFR 153.107 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false [Reserved] 153.107 Section 153.107 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION CONTROL OF POLLUTION BY OIL AND HAZARDOUS SUBSTANCES, DISCHARGE REMOVAL General § 153.107 [Reserved] ...

33 CFR 153.107 - [Reserved

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false [Reserved] 153.107 Section 153.107 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION CONTROL OF POLLUTION BY OIL AND HAZARDOUS SUBSTANCES, DISCHARGE REMOVAL General § 153.107 [Reserved] ...

33 CFR 153.107 - [Reserved

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false [Reserved] 153.107 Section 153.107 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION CONTROL OF POLLUTION BY OIL AND HAZARDOUS SUBSTANCES, DISCHARGE REMOVAL General § 153.107 [Reserved] ...

33 CFR 153.107 - [Reserved

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false [Reserved] 153.107 Section 153.107 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION CONTROL OF POLLUTION BY OIL AND HAZARDOUS SUBSTANCES, DISCHARGE REMOVAL General § 153.107 [Reserved] ...

33 CFR 153.401 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Purpose. 153.401 Section 153.401 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION CONTROL OF POLLUTION BY OIL AND HAZARDOUS SUBSTANCES, DISCHARGE REMOVAL Administration of the Pollution Fund § 153.401...

33 CFR 153.401 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Purpose. 153.401 Section 153.401 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION CONTROL OF POLLUTION BY OIL AND HAZARDOUS SUBSTANCES, DISCHARGE REMOVAL Administration of the Pollution Fund § 153.401...

33 CFR 153.401 - Purpose.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Purpose. 153.401 Section 153.401 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION CONTROL OF POLLUTION BY OIL AND HAZARDOUS SUBSTANCES, DISCHARGE REMOVAL Administration of the Pollution Fund § 153.401...

33 CFR 153.401 - Purpose.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Purpose. 153.401 Section 153.401 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION CONTROL OF POLLUTION BY OIL AND HAZARDOUS SUBSTANCES, DISCHARGE REMOVAL Administration of the Pollution Fund § 153.401...

33 CFR 153.401 - Purpose.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Purpose. 153.401 Section 153.401 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION CONTROL OF POLLUTION BY OIL AND HAZARDOUS SUBSTANCES, DISCHARGE REMOVAL Administration of the Pollution Fund § 153.401...

14 CFR 93.153 - Communications.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Communications. 93.153 Section 93.153... § 93.153 Communications. (a) When the Ketchikan Flight Service Station is in operation, no person may... International Airport, unless that person has established two-way radio communications with the Ketchikan Flight...

45 CFR 153.20 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Definitions. 153.20 Section 153.20 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT General Provisions § 153.20...

45 CFR 153.20 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Definitions. 153.20 Section 153.20 Public Welfare Department of Health and Human Services REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT General Provisions § 153.20...

45 CFR 153.20 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Definitions. 153.20 Section 153.20 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT General Provisions § 153.20...

14 CFR 93.153 - Communications.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Communications. 93.153 Section 93.153... § 93.153 Communications. (a) When the Ketchikan Flight Service Station is in operation, no person may... International Airport, unless that person has established two-way radio communications with the Ketchikan Flight...

14 CFR 93.153 - Communications.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Communications. 93.153 Section 93.153... § 93.153 Communications. (a) When the Ketchikan Flight Service Station is in operation, no person may... International Airport, unless that person has established two-way radio communications with the Ketchikan Flight...

Regioselective alkane hydroxylation with a mutant CYP153A6 enzyme

DOEpatents

Koch, Daniel J.; Arnold, Frances H.

2013-01-29

Cytochrome P450 CYP153A6 from Myobacterium sp. strain HXN1500 was engineered using in-vivo directed evolution to hydroxylate small-chain alkanes regioselectively. Mutant CYP153A6-BMO1 selectively hydroxylates butane and pentane at the terminal carbon to form 1-butanol and 1-pentanol, respectively, at rates greater than wild-type CYP153A6 enzymes. This biocatalyst is highly active for small-chain alkane substrates and the regioselectivity is retained in whole-cell biotransformations.

25 CFR 153.6 - Appeals.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Appeals. 153.6 Section 153.6 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER DETERMINATION OF COMPETENCY: CROW INDIANS § 153.6 Appeals. An appeal to the Secretary of the Interior may be made within 30 days from the date of notice to...

Ferulic acid (FA) abrogates γ-radiation induced oxidative stress and DNA damage by up-regulating nuclear translocation of Nrf2 and activation of NHEJ pathway.

PubMed

Das, Ujjal; Manna, Krishnendu; Khan, Amitava; Sinha, Mahuya; Biswas, Sushobhan; Sengupta, Aaveri; Chakraborty, Anindita; Dey, Sanjit

2017-01-01

The present study was aimed to evaluate the radioprotective effect of ferulic acid (FA), a naturally occurring plant flavonoid in terms of DNA damage and damage related alterations of repair pathways by gamma radiation. FA was administered at a dose of 50 mg/kg body weight for five consecutive days prior to exposing the swiss albino mice to a single dose of 10 Gy gamma radiation. Ionising radiation induces oxidative damage manifested by decreased expression of Cu, Zn-SOD (SOD stands for super oxide dismutase), Mn-SOD and catalase. Gamma radiation promulgated reactive oxygen species (ROS) mediated DNA damage and modified repair pathways. ROS enhanced nuclear translocation of p53, activated ATM (ataxia telangiectasia-mutated protein), increased expression of GADD45a (growth arrest and DNA-damage-inducible protein) gene and inactivated Non homologous end joining (NHEJ) repair pathway. The comet formation in irradiated mice peripheral blood mononuclear cells (PBMC) reiterated the DNA damage in IR exposed groups. FA pretreatment significantly prevented the comet formation and regulated the nuclear translocation of p53, inhibited ATM activation and expression of GADD45a gene. FA promoted the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and activated NHEJ repair pathway to overcome ROS mediated oxidative stress and DNA damage. Therefore, the current study stated that FA can challenge the oxidative stress by (i) inducing nuclear translocation of Nrf2, (ii) scavenging ROS, and (iii) activating NHEJ DNA repair process.

Anti-prostate cancer activity of a beta-carboline alkaloid enriched extract from Rauwolfia vomitoria.

PubMed

Bemis, D L; Capodice, J L; Gorroochurn, P; Katz, A E; Buttyan, R

2006-11-01

The tropical shrub, Rauwolfia vomitoria, is a medicinal plant used traditionally to treat a variety of ailments. A bioactive beta-carboline alkaloid, alstonine, present in this extract was previously shown to have anti-cancer activity against cancer cell lines. This study considers the potential anti-prostate cancer activity of this extract in vitro and in vivo. Rauwolfia vomitoria extract standardized for beta-carboline alkaloids was tested for ability to influence the growth and survival of the human LNCaP prostate cancer cell line. A WST-1 assay was used to measure cell growth, and cell cycle analyses were conducted with flow cytometry. Western blot detection of PARP cleavage and accumulation of cells containing sub-genomic DNA indicated induction of apoptosis. Pathway specific microarray analyses were utilized to identify the effect of Rauwolfia extract on the expression of 225 genes. Mice xenografted with LNCaP cells were treated with the extract or placebo control, and tumor growth was measured for 5 weeks. The effects of the extract on xenografted tumor cell proliferation and apoptosis were measured by in situ BrdU incorporation and TUNEL staining. Rauwolfia extract decreased in vitro cell growth in a dose-dependent manner (p<0.001) and induced the accumulation of G1 phase cells. PARP cleavage demonstrated that apoptosis was induced only at the highest concentration tested (500 microg/ml) which was confirmed by detection of cells containing sub-genomic DNA. The expression of genes associated with DNA damage signaling pathway was up-regulated by Rauwolfia treatment, including that of GADD153 and MDG. The expression of a few cell cycle genes (p21, cyclin D1 and E2F1) was also modulated. These alterations were confirmed by RT-PCR. Tumor volumes were decreased by 60%, 70% and 58% in the groups fed the 75, 37.5 or 7.5 mg/kg Rauwolfia, respectively (Kruskal-Wallis test, p<0.001). The Rauwolfia vomitoria extract significantly suppressed the growth and cell cycle

A New Ochratoxin A Biodegradation Strategy Using Cupriavidus basilensis Őr16 Strain

PubMed Central

Krifaton, Csilla; Szoboszlay, Sándor; Kukolya, József; Szőke, Zsuzsanna; Kőszegi, Balázs; Albert, Mihály; Barna, Teréz; Mézes, Miklós; Kovács, Krisztina J.; Kriszt, Balázs

2014-01-01

Ochratoxin-A (OTA) is a mycotoxin with possibly carcinogenic and nephrotoxic effects in humans and animals. OTA is often found as a contaminant in agricultural commodities. The aim of the present work was to evaluate OTA-degrading and detoxifying potential of Cupriavidus basilensis ŐR16 strain. In vivo administration of OTA in CD1 male mice (1 or 10 mg/kg body weight for 72 hours or 0.5 mg/kg body weight for 21 days) resulted in significant elevation of OTA levels in the blood, histopathological alterations- and transcriptional changes in OTA-dependent genes (annexinA2, clusterin, sulphotransferase and gadd45 and gadd153) in the renal cortex. These OTA-induced changes were not seen in animals that have been treated with culture supernatants in which OTA was incubated with Cupriavidus basilensis ŐR16 strain for 5 days. HPLC and ELISA methods identified ochratoxin α as the major metabolite of OTA in Cupriavidus basilensis ŐR16 cultures, which is not toxic in vivo. This study has demonstrated that Cupriavidus basilensis ŐR16 efficiently degrade OTA without producing toxic adventitious metabolites. PMID:25302950

Subtelomeric Deletion of Chromosome 10p15.3: Clinical Findings and Molecular Cytogenetic Characterization

PubMed Central

DeScipio, Cheryl; Conlin, Laura; Rosenfeld, Jill; Tepperberg, James; Pasion, Romela; Patel, Ankita; McDonald, Marie T; Aradhya, Swaroop; Ho, Darlene; Goldstein, Jennifer; McGuire, Marianne; Mulchandani, Surabhi; Medne, Livija; Rupps, Rosemarie; Serrano, Alvaro H.; Thorland, Erik C; Tsai, Anne C-H; Hilhorst-Hofstee, Yvonne; Ruivenkamp, Claudia AL; Van Esch, Hilde; Addor, Marie-Claude; Martinet, Danielle; Mason, Thornton B.A.; Clark, Dinah; Spinner, Nancy B; Krantz, Ian D

2012-01-01

We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion have been reported to date; however, only limited clinical information is available for these probands and the deleted region has not been molecularly mapped. Comprehensive clinical history was obtained for 12 of the 19 individuals described in this study. Common features among these 12 individuals include: cognitive/behavioral/developmental differences (11/11), speech delay/language disorder (10/10), motor delay (10/10), craniofacial dysmorphism (9/12), hypotonia (7/11,), brain anomalies (4/6) and seizures (3/7). Parental studies were performed for nine of the 19 individuals; the 10p15.3 deletion was de novo in seven of the probands, not maternally inherited in one proband and inherited from an apparently affected mother in one proband. Molecular mapping of the 19 individuals reported in this study has identified two genes, ZMYND11 (OMIM# 608668) and DIP2C (OMIM# 611380) (UCSC Genome Browser), mapping within 10p15.3 which are most commonly deleted. Although no single gene has been identified which is deleted in all 19 individuals studied, the deleted region in all but one individual includes ZMYND11 and the deleted region in all but one other individual includes DIP2C. There is not a clearly identifiable phenotypic difference between these two individuals and the size of the deleted region does not generally predict clinical features. Little is currently known about these genes complicating a direct genotype/phenotype correlation at this time. These data however, suggest that ZMYND11 and/or DIP2C haploinsufficiency contributes to the clinical features associated with 10p15 deletions in probands described in this study. PMID:22847950

Subtelomeric deletion of chromosome 10p15.3: clinical findings and molecular cytogenetic characterization.

PubMed

DeScipio, Cheryl; Conlin, Laura; Rosenfeld, Jill; Tepperberg, James; Pasion, Romela; Patel, Ankita; McDonald, Marie T; Aradhya, Swaroop; Ho, Darlene; Goldstein, Jennifer; McGuire, Marianne; Mulchandani, Surabhi; Medne, Livija; Rupps, Rosemarie; Serrano, Alvaro H; Thorland, Erik C; Tsai, Anne C-H; Hilhorst-Hofstee, Yvonne; Ruivenkamp, Claudia A L; Van Esch, Hilde; Addor, Marie-Claude; Martinet, Danielle; Mason, Thornton B A; Clark, Dinah; Spinner, Nancy B; Krantz, Ian D

2012-09-01

We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion have been reported to date; however, only limited clinical information is available for these probands and the deleted region has not been molecularly mapped. Comprehensive clinical history was obtained for 12 of the 19 individuals described in this study. Common features among these 12 individuals include: cognitive/behavioral/developmental differences (11/11), speech delay/language disorder (10/10), motor delay (10/10), craniofacial dysmorphism (9/12), hypotonia (7/11), brain anomalies (4/6) and seizures (3/7). Parental studies were performed for nine of the 19 individuals; the 10p15.3 deletion was de novo in seven of the probands, not maternally inherited in one proband and inherited from an apparently affected mother in one proband. Molecular mapping of the 19 individuals reported in this study has identified two genes, ZMYND11 (OMIM 608668) and DIP2C (OMIM 611380; UCSC Genome Browser), mapping within 10p15.3 which are most commonly deleted. Although no single gene has been identified which is deleted in all 19 individuals studied, the deleted region in all but one individual includes ZMYND11 and the deleted region in all but one other individual includes DIP2C. There is not a clearly identifiable phenotypic difference between these two individuals and the size of the deleted region does not generally predict clinical features. Little is currently known about these genes complicating a direct genotype/phenotype correlation at this time. These data however, suggest that ZMYND11 and/or DIP2C haploinsufficiency contributes to the clinical features associated with 10p15 deletions in probands described in this study. Copyright © 2012 Wiley Periodicals, Inc.

42 CFR 413.153 - Interest expense.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 2 2012-10-01 2012-10-01 false Interest expense. 413.153 Section 413.153 Public... PRINCIPLES OF REASONABLE COST REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Capital-Related Costs § 413.153 Interest...

42 CFR 413.153 - Interest expense.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false Interest expense. 413.153 Section 413.153 Public... PRINCIPLES OF REASONABLE COST REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Capital-Related Costs § 413.153 Interest...

42 CFR 413.153 - Interest expense.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 2 2014-10-01 2014-10-01 false Interest expense. 413.153 Section 413.153 Public... PRINCIPLES OF REASONABLE COST REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Capital-Related Costs § 413.153 Interest...

42 CFR 413.153 - Interest expense.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Interest expense. 413.153 Section 413.153 Public... PRINCIPLES OF REASONABLE COST REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Capital-Related Costs § 413.153 Interest...

42 CFR 413.153 - Interest expense.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 2 2013-10-01 2013-10-01 false Interest expense. 413.153 Section 413.153 Public... PRINCIPLES OF REASONABLE COST REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Capital-Related Costs § 413.153 Interest...

46 CFR 153.806 - Loading information.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Loading information. 153.806 Section 153.806 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING... Inspection § 153.806 Loading information. Each tankship must have a manual containing information that...

46 CFR 153.806 - Loading information.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Loading information. 153.806 Section 153.806 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING... Inspection § 153.806 Loading information. Each tankship must have a manual containing information that...

46 CFR 153.466 - Electrical equipment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Electrical equipment. 153.466 Section 153.466 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING... Requirements for Flammable Or Combustible Cargoes § 153.466 Electrical equipment. A tankship carrying a...

46 CFR 153.466 - Electrical equipment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Electrical equipment. 153.466 Section 153.466 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING... Requirements for Flammable Or Combustible Cargoes § 153.466 Electrical equipment. A tankship carrying a...

46 CFR 153.466 - Electrical equipment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Electrical equipment. 153.466 Section 153.466 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING... Requirements for Flammable Or Combustible Cargoes § 153.466 Electrical equipment. A tankship carrying a...

46 CFR 153.466 - Electrical equipment.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Electrical equipment. 153.466 Section 153.466 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING... Requirements for Flammable Or Combustible Cargoes § 153.466 Electrical equipment. A tankship carrying a...

46 CFR 153.466 - Electrical equipment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Electrical equipment. 153.466 Section 153.466 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING... Requirements for Flammable Or Combustible Cargoes § 153.466 Electrical equipment. A tankship carrying a...

33 CFR 153.109 - CERCLA delegations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false CERCLA delegations. 153.109 Section 153.109 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION CONTROL OF POLLUTION BY OIL AND HAZARDOUS SUBSTANCES, DISCHARGE REMOVAL General § 153.109 CERCLA...

33 CFR 153.109 - CERCLA delegations.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false CERCLA delegations. 153.109 Section 153.109 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION CONTROL OF POLLUTION BY OIL AND HAZARDOUS SUBSTANCES, DISCHARGE REMOVAL General § 153.109 CERCLA...

33 CFR 153.109 - CERCLA delegations.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false CERCLA delegations. 153.109 Section 153.109 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION CONTROL OF POLLUTION BY OIL AND HAZARDOUS SUBSTANCES, DISCHARGE REMOVAL General § 153.109 CERCLA...

33 CFR 153.109 - CERCLA delegations.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false CERCLA delegations. 153.109 Section 153.109 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION CONTROL OF POLLUTION BY OIL AND HAZARDOUS SUBSTANCES, DISCHARGE REMOVAL General § 153.109 CERCLA...

33 CFR 153.109 - CERCLA delegations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false CERCLA delegations. 153.109 Section 153.109 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION CONTROL OF POLLUTION BY OIL AND HAZARDOUS SUBSTANCES, DISCHARGE REMOVAL General § 153.109 CERCLA...

7 CFR 1789.153 - Borrower funding.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 12 2014-01-01 2013-01-01 true Borrower funding. 1789.153 Section 1789.153... Consultant Services Funded by Borrowers-General § 1789.153 Borrower funding. Borrowers shall use their general funds for the purposes of funding consultant services hereunder. Borrowers may not use the...

7 CFR 1789.153 - Borrower funding.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 12 2012-01-01 2012-01-01 false Borrower funding. 1789.153 Section 1789.153... Consultant Services Funded by Borrowers-General § 1789.153 Borrower funding. Borrowers shall use their general funds for the purposes of funding consultant services hereunder. Borrowers may not use the...

7 CFR 1789.153 - Borrower funding.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 12 2011-01-01 2011-01-01 false Borrower funding. 1789.153 Section 1789.153... Consultant Services Funded by Borrowers-General § 1789.153 Borrower funding. Borrowers shall use their general funds for the purposes of funding consultant services hereunder. Borrowers may not use the...

7 CFR 1789.153 - Borrower funding.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Borrower funding. 1789.153 Section 1789.153... Consultant Services Funded by Borrowers-General § 1789.153 Borrower funding. Borrowers shall use their general funds for the purposes of funding consultant services hereunder. Borrowers may not use the...

7 CFR 1789.153 - Borrower funding.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 12 2013-01-01 2013-01-01 false Borrower funding. 1789.153 Section 1789.153... Consultant Services Funded by Borrowers-General § 1789.153 Borrower funding. Borrowers shall use their general funds for the purposes of funding consultant services hereunder. Borrowers may not use the...

46 CFR 153.1046 - Sulfuric acid.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Sulfuric acid. 153.1046 Section 153.1046 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures § 153...

46 CFR 153.1046 - Sulfuric acid.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Sulfuric acid. 153.1046 Section 153.1046 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures § 153...

46 CFR 153.1046 - Sulfuric acid.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Sulfuric acid. 153.1046 Section 153.1046 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures § 153...

Redistribution of cell cycle by arsenic trioxide is associated with demethylation and expression changes of cell cycle related genes in acute promyelocytic leukemia cell line (NB4).

PubMed

Hassani, Saeed; Khaleghian, Ali; Ahmadian, Shahin; Alizadeh, Shaban; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Ghaffari, Seyed H

2018-01-01

PML-RARα perturbs the normal epigenetic setting, which is essential to oncogenic transformation in acute promyelocytic leukemia (APL). Transcription induction and recruitment of DNA methyltransferases (DNMTs) by PML-RARα and subsequent hypermethylation are components of this perturbation. Arsenic trioxide (ATO), an important drug in APL therapy, concurrent with degradation of PML-RARα induces cell cycle change and apoptosis. How ATO causes cell cycle alteration has remained largely unexplained. Here, we investigated DNA methylation patterns of cell cycle regulatory genes promoters, the effects of ATO on the methylated genes and cell cycle distribution in an APL cell line, NB4. Analysis of promoter methylation status of 22 cell cycle related genes in NB4 revealed that CCND1, CCNE1, CCNF, CDKN1A, GADD45α, and RBL1 genes were methylated 60.7, 84.6, 58.6, 8.7, 33.4, and 73.7%, respectively, that after treatment with 2 μM ATO for 48 h, turn into 0.6, 13.8, 0.1, 6.6, 10.7, and 54.5% methylated. ATO significantly reduced the expression of DNMT1, 3A, and 3B. ATO induced the expression of CCND1, CCNE1, and GADD45α genes, suppressed the expression of CCNF and CDKN1A genes, which were consistent with decreased number of cells in G1 and S phases and increased number of cells in G2/M phase. In conclusion, demethylation and alteration in the expression level of the cell cycle related genes may be possible mechanisms in ATO-induced cell cycle arrest in APL cells. It may suggest that ATO by demethylation of CCND1 and CCNE1 and their transcriptional activation accelerates G1 and S transition into the G2/M cell cycle arrest.

10 CFR 63.153 - Physical requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Physical requirements. 63.153 Section 63.153 Energy... REPOSITORY AT YUCCA MOUNTAIN, NEVADA Training and Certification of Personnel § 63.153 Physical requirements. The physical condition and the general health of personnel certified for operations that are important...

46 CFR 153.236 - Prohibited materials.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Prohibited materials. 153.236 Section 153.236 Shipping... BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Containment Systems § 153.236 Prohibited materials. When one of the following paragraphs of this section is...

46 CFR 153.238 - Required materials.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Required materials. 153.238 Section 153.238 Shipping... BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Containment Systems § 153.238 Required materials. When one of the following paragraphs of this section is...

46 CFR 153.238 - Required materials.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Required materials. 153.238 Section 153.238 Shipping... BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Containment Systems § 153.238 Required materials. When one of the following paragraphs of this section is...

46 CFR 153.236 - Prohibited materials.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Prohibited materials. 153.236 Section 153.236 Shipping... BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Containment Systems § 153.236 Prohibited materials. When one of the following paragraphs of this section is...

46 CFR 153.238 - Required materials.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Required materials. 153.238 Section 153.238 Shipping... BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Containment Systems § 153.238 Required materials. When one of the following paragraphs of this section is...

46 CFR 153.236 - Prohibited materials.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Prohibited materials. 153.236 Section 153.236 Shipping... BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Containment Systems § 153.236 Prohibited materials. When one of the following paragraphs of this section is...

10 CFR 63.153 - Physical requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Physical requirements. 63.153 Section 63.153 Energy... REPOSITORY AT YUCCA MOUNTAIN, NEVADA Training and Certification of Personnel § 63.153 Physical requirements. The physical condition and the general health of personnel certified for operations that are important...

10 CFR 63.153 - Physical requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Physical requirements. 63.153 Section 63.153 Energy... REPOSITORY AT YUCCA MOUNTAIN, NEVADA Training and Certification of Personnel § 63.153 Physical requirements. The physical condition and the general health of personnel certified for operations that are important...

10 CFR 63.153 - Physical requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Physical requirements. 63.153 Section 63.153 Energy... REPOSITORY AT YUCCA MOUNTAIN, NEVADA Training and Certification of Personnel § 63.153 Physical requirements. The physical condition and the general health of personnel certified for operations that are important...

10 CFR 63.153 - Physical requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Physical requirements. 63.153 Section 63.153 Energy... REPOSITORY AT YUCCA MOUNTAIN, NEVADA Training and Certification of Personnel § 63.153 Physical requirements. The physical condition and the general health of personnel certified for operations that are important...

1 CFR 15.3 - Staff assistance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 1 General Provisions 1 2011-01-01 2011-01-01 false Staff assistance. 15.3 Section 15.3 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER PREPARATION, TRANSMITTAL, AND PROCESSING OF DOCUMENTS SERVICES TO FEDERAL AGENCIES General § 15.3 Staff assistance. The staff of the Office of the...

1 CFR 15.3 - Staff assistance.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 1 General Provisions 1 2013-01-01 2012-01-01 true Staff assistance. 15.3 Section 15.3 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER PREPARATION, TRANSMITTAL, AND PROCESSING OF DOCUMENTS SERVICES TO FEDERAL AGENCIES General § 15.3 Staff assistance. The staff of the Office of the...

1 CFR 15.3 - Staff assistance.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 1 General Provisions 1 2012-01-01 2012-01-01 false Staff assistance. 15.3 Section 15.3 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER PREPARATION, TRANSMITTAL, AND PROCESSING OF DOCUMENTS SERVICES TO FEDERAL AGENCIES General § 15.3 Staff assistance. The staff of the Office of the...

1 CFR 15.3 - Staff assistance.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 1 General Provisions 1 2014-01-01 2012-01-01 true Staff assistance. 15.3 Section 15.3 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER PREPARATION, TRANSMITTAL, AND PROCESSING OF DOCUMENTS SERVICES TO FEDERAL AGENCIES General § 15.3 Staff assistance. The staff of the Office of the...

1 CFR 15.3 - Staff assistance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 1 General Provisions 1 2010-01-01 2010-01-01 false Staff assistance. 15.3 Section 15.3 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER PREPARATION, TRANSMITTAL, AND PROCESSING OF DOCUMENTS SERVICES TO FEDERAL AGENCIES General § 15.3 Staff assistance. The staff of the Office of the...

46 CFR 153.923 - Inerting systems.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Inerting systems. 153.923 Section 153.923 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK... Requirements § 153.923 Inerting systems. The master shall ensure that the inert gas systems for any cargo that...

46 CFR 153.923 - Inerting systems.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Inerting systems. 153.923 Section 153.923 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK... Requirements § 153.923 Inerting systems. The master shall ensure that the inert gas systems for any cargo that...

46 CFR 153.923 - Inerting systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Inerting systems. 153.923 Section 153.923 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK... Requirements § 153.923 Inerting systems. The master shall ensure that the inert gas systems for any cargo that...

45 CFR 153.420 - Data collection.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Data collection. 153.420 Section 153.420 Public... Issuer and Group Health Plan Standards Related to the Reinsurance Program § 153.420 Data collection. (a) Data requirement. To be eligible for reinsurance payments, an issuer of a reinsurance-eligible plan...

45 CFR 153.710 - Data requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Data requirements. 153.710 Section 153.710 Public... RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT Distributed Data Collection for HHS-Operated Programs § 153.710 Data requirements. (a) Enrollment, claims, and encounter data...

45 CFR 153.420 - Data collection.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Data collection. 153.420 Section 153.420 Public... Issuer and Group Health Plan Standards Related to the Reinsurance Program § 153.420 Data collection. (a) Data requirement. To be eligible for reinsurance payments, an issuer of a reinsurance-eligible plan...

45 CFR 153.710 - Data requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Data requirements. 153.710 Section 153.710 Public... RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT Distributed Data Collection for HHS-Operated Programs § 153.710 Data requirements. (a) Enrollment, claims, and encounter data...

46 CFR 153.1045 - Inorganic acids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Inorganic acids. 153.1045 Section 153.1045 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING... § 153.1045 Inorganic acids. When Table 1 refers to this section, the person in charge of cargo transfer...

46 CFR 153.1045 - Inorganic acids.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Inorganic acids. 153.1045 Section 153.1045 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING... § 153.1045 Inorganic acids. When Table 1 refers to this section, the person in charge of cargo transfer...

46 CFR 153.923 - Inerting systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Inerting systems. 153.923 Section 153.923 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK... Requirements § 153.923 Inerting systems. The master shall ensure that the inert gas systems for any cargo that...

46 CFR 153.907 - Cargo information.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo information. 153.907 Section 153.907 Shipping... Information § 153.907 Cargo information. (a) The master shall ensure that the following information for each... process for the vessel. (b) The master shall make sure that the following information for cargoes other...

25 CFR 153.3 - Application form.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Application form. 153.3 Section 153.3 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER DETERMINATION OF COMPETENCY: CROW INDIANS § 153.3 Application form. The application form shall include, among other things: (a) The name of the...

46 CFR 153.1040 - Carbon disulfide.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Carbon disulfide. 153.1040 Section 153.1040 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures § 153.1040 Carbon disulfide. (a) No person may...

46 CFR 153.907 - Cargo information.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo information. 153.907 Section 153.907 Shipping... Information § 153.907 Cargo information. (a) The master shall ensure that the following information for each... process for the vessel. (b) The master shall make sure that the following information for cargoes other...

46 CFR 153.266 - Tank linings.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Tank linings. 153.266 Section 153.266 Shipping COAST... LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Tanks § 153.266 Tank linings. A tank lining must be: (a) At least as elastic as the tank material; and (b) Applied or...

46 CFR 153.266 - Tank linings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Tank linings. 153.266 Section 153.266 Shipping COAST... LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Tanks § 153.266 Tank linings. A tank lining must be: (a) At least as elastic as the tank material; and (b) Applied or...

46 CFR 153.266 - Tank linings.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Tank linings. 153.266 Section 153.266 Shipping COAST... LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Tanks § 153.266 Tank linings. A tank lining must be: (a) At least as elastic as the tank material; and (b) Applied or...

46 CFR 153.266 - Tank linings.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Tank linings. 153.266 Section 153.266 Shipping COAST... LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Tanks § 153.266 Tank linings. A tank lining must be: (a) At least as elastic as the tank material; and (b) Applied or...

46 CFR 153.266 - Tank linings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Tank linings. 153.266 Section 153.266 Shipping COAST... LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Tanks § 153.266 Tank linings. A tank lining must be: (a) At least as elastic as the tank material; and (b) Applied or...

46 CFR 153.432 - Cooling systems.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Cooling systems. 153.432 Section 153.432 Shipping COAST... Control Systems § 153.432 Cooling systems. (a) Each cargo cooling system must have an equivalent standby... cooling system. (b) Each tankship that has a cargo tank with a required cooling system must have a manual...

46 CFR 153.432 - Cooling systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Cooling systems. 153.432 Section 153.432 Shipping COAST... Control Systems § 153.432 Cooling systems. (a) Each cargo cooling system must have an equivalent standby... cooling system. (b) Each tankship that has a cargo tank with a required cooling system must have a manual...

46 CFR 153.432 - Cooling systems.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Cooling systems. 153.432 Section 153.432 Shipping COAST... Control Systems § 153.432 Cooling systems. (a) Each cargo cooling system must have an equivalent standby... cooling system. (b) Each tankship that has a cargo tank with a required cooling system must have a manual...

46 CFR 153.432 - Cooling systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Cooling systems. 153.432 Section 153.432 Shipping COAST... Control Systems § 153.432 Cooling systems. (a) Each cargo cooling system must have an equivalent standby... cooling system. (b) Each tankship that has a cargo tank with a required cooling system must have a manual...

7 CFR 58.153 - Dry storage.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 3 2014-01-01 2014-01-01 false Dry storage. 58.153 Section 58.153 Agriculture... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Storage of Finished Product § 58.153 Dry storage. The product should be stored at least 18 inches from the wall in aisles, rows, or...

7 CFR 58.153 - Dry storage.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Dry storage. 58.153 Section 58.153 Agriculture... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Storage of Finished Product § 58.153 Dry storage. The product should be stored at least 18 inches from the wall in aisles, rows, or...

7 CFR 58.153 - Dry storage.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 3 2013-01-01 2013-01-01 false Dry storage. 58.153 Section 58.153 Agriculture... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Storage of Finished Product § 58.153 Dry storage. The product should be stored at least 18 inches from the wall in aisles, rows, or...

7 CFR 58.153 - Dry storage.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 3 2011-01-01 2011-01-01 false Dry storage. 58.153 Section 58.153 Agriculture... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Storage of Finished Product § 58.153 Dry storage. The product should be stored at least 18 inches from the wall in aisles, rows, or...

7 CFR 58.153 - Dry storage.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 3 2012-01-01 2012-01-01 false Dry storage. 58.153 Section 58.153 Agriculture... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Storage of Finished Product § 58.153 Dry storage. The product should be stored at least 18 inches from the wall in aisles, rows, or...

Neuroprotective Effects of the Glutamate Transporter Activator (R)-(−)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153) following Traumatic Brain Injury in the Adult Rat

PubMed Central

Fox, Douglas P.; Zoubroulis, Argie; Valente Mortensen, Ole; Raghupathi, Ramesh

2016-01-01

Abstract Traumatic brain injury (TBI) in humans and in animals leads to an acute and sustained increase in tissue glutamate concentrations within the brain, triggering glutamate-mediated excitotoxicity. Excitatory amino acid transporters (EAATs) are responsible for maintaining extracellular central nervous system glutamate concentrations below neurotoxic levels. Our results demonstrate that as early as 5 min and up to 2 h following brain trauma in brain-injured rats, the activity (Vmax) of EAAT2 in the cortex and the hippocampus was significantly decreased, compared with sham-injured animals. The affinity for glutamate (KM) and the expression of glutamate transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST) were not altered by the injury. Administration of (R)-(−)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), a GLT-1 activator, beginning immediately after injury and continuing for 24 h, significantly decreased neurodegeneration, loss of microtubule-associated protein 2 and NeuN (+) immunoreactivities, and attenuated calpain activation in both the cortex and the hippocampus at 24 h after the injury; the reduction in neurodegeneration remained evident up to 14 days post-injury. In synaptosomal uptake assays, MS-153 up-regulated GLT-1 activity in the naïve rat brain but did not reverse the reduced activity of GLT-1 in traumatically-injured brains. This study demonstrates that administration of MS-153 in the acute post-traumatic period provides acute and long-term neuroprotection for TBI and suggests that the neuroprotective effects of MS-153 are related to mechanisms other than GLT-1 activation, such as the inhibition of voltage-gated calcium channels. PMID:26200170

A targeted gene expression platform allows for rapid analysis of chemical-induced antioxidant mRNA expression in zebrafish larvae.

PubMed

Mills, Margaret G; Gallagher, Evan P

2017-01-01

Chemical-induced oxidative stress and the biochemical pathways that protect against oxidative damage are of particular interest in the field of toxicology. To rapidly identify oxidative stress-responsive gene expression changes in zebrafish, we developed a targeted panel of antioxidant genes using the Affymetrix QuantiGene Plex (QGP) platform. The genes contained in our panel include eight putative Nrf2 (Nfe2l2a)-dependent antioxidant genes (hmox1a, gstp1, gclc, nqo1, prdx1, gpx1a, sod1, sod2), a stress response gene (hsp70), an inducible DNA damage repair gene (gadd45bb), and three reference genes (actb1, gapdh, hprt1). We tested this platform on larval zebrafish exposed to tert-butyl hydroperoxide (tBHP) and cadmium (Cd), two model oxidative stressors with different modes of action, and compared our results with those obtained using the more common quantitative PCR (qPCR) method. Both methods showed that exposure to tBHP and Cd induced expression of prdx1, gstp1, and hmox1a (2- to 12-fold increase via QGP), indicative of an activated Nrf2 response in larval zebrafish. Both compounds also elicited a general stress response as reflected by elevation of hsp70 and gadd45bb, with Cd being the more potent inducer. Transient changes were observed in sod2 and gpx1a expression, whereas nqo1, an Nrf2-responsive gene in mammalian cells, was minimally affected by either tBHP or Cd chemical exposures. Developmental expression analysis of the target genes by QGP revealed marked upregulation of sod2 between 0-96hpf, and to a lesser extent, of sod1 and gstp1. Once optimized, QGP analysis of these experiments was accomplished more rapidly, using far less tissue, and at lower total costs than qPCR analysis. In summary, the QGP platform as applied to higher-throughput zebrafish studies provides a reasonable cost-effective alternative to qPCR or more comprehensive transcriptomics approaches to rapidly assess the potential for chemicals to elicit oxidative stress as a mechanism of

An inversion inv(4)(p12-p15.3) in autistic siblings implicates the 4p GABA receptor gene cluster.

PubMed

Vincent, J B; Horike, S I; Choufani, S; Paterson, A D; Roberts, W; Szatmari, P; Weksberg, R; Fernandez, B; Scherer, S W

2006-05-01

We describe the case of two brothers diagnosed with autism who both carry a paracentic inversion of the short arm of chromosome 4 (46,XY, inv(4)(p12-p15.3)). We have determined that this inversion is inherited from an apparently unaffected mother and unaffected maternal grandfather. Methods/ Using fluorescence in situ hybridisation analysis and Southern blot hybridisation we identified the breakpoints. The proximal breakpoint (4p12) maps to a region containing a cluster of gamma-aminobutyric acid A (GABA(A)) receptor genes, and directly interrupts the GABRG1 gene, the distal-most gene of the cluster. We also identified an insertion/deletion polymorphism for a approximately 2 kb LINE1 (L1) element that occurs within intron 7 of GABRG1. Our genotype analysis amongst autism families indicated that the L1 deletion allele did not show increased transmission to affected individuals. No linkage disequilibrium was evident between the L1 and single nucleotide polymorphisms in adjacent GABA(A) receptor genes on 4p, where a recent study has identified significant association with autism. Despite this, the identification of an inversion breakpoint disrupting GABRG1 provides solid support for the genetic involvement of the short arm of chromosome 4 in the genetic aetiology of autism, and for the hypothesis of disrupted GABA neurotransmission in autism.

Fisetin Protects PC12 Cells from Tunicamycin-Mediated Cell Death via Reactive Oxygen Species Scavenging and Modulation of Nrf2-Driven Gene Expression, SIRT1 and MAPK Signaling in PC12 Cells.

PubMed

Yen, Jui-Hung; Wu, Pei-Shan; Chen, Shu-Fen; Wu, Ming-Jiuan

2017-04-17

Fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonol and exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However, high concentration of fisetin is reported to produce reactive oxygen species (ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer cells. The aim of this study is to investigate the cytoprotective effects of low concentration of fisetin against tunicamycin (Tm)-mediated cytotoxicity in neuronal-like catecholaminergic PC12 cells. Cell viability was assayed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and apoptotic and autophagic markers were analyzed by Western blot. Gene expression of unfolded protein response (UPR) and Phase II enzymes was further investigated using RT-Q-PCR or Western blotting. Intracellular ROS level was measured using 2',7'-dichlorodihydrofluorescein diacetate (H₂DCFDA) by a fluorometer. The effects of fisetin on mitogen activated protein kinases (MAPKs) and SIRT1 (Sirtuin 1) signaling pathways were examined using Western blotting and specific inhibitors. Fisetin (<20 µM) restored cell viability and repressed apoptosis, autophagy and ROS production in Tm-treated cells. Fisetin attenuated Tm-mediated expression of ER stress genes, such as glucose-regulated proteins 78 (GRP78), C/EBP homologous protein (CHOP also known as GADD153) and Tribbles homolog 3 (TRB3), but induced the expression of nuclear E2 related factor (Nrf)2-targeted heme oxygenase (HO)-1, glutamate cysteine ligase (GCL) and cystine/glutamate transporter (xCT/SLC7A11), in both the presence and absence of Tm. Moreover, fisetin enhanced phosphorylation of ERK (extracellular signal-regulated kinase), JNK (c-JUN NH₂-terminal protein kinase), and p38 MAPK. Addition of JNK and p38 MAPK inhibitor significantly antagonized its cytoprotective activity and modulatory effects on UPR. Fisetin also restored Tm-inhibited SIRT1 expression and addition of sirtinol (SIRT1 activation inhibitor

Silica nanoparticles mediated neuronal cell death in corpus striatum of rat brain: implication of mitochondrial, endoplasmic reticulum and oxidative stress

NASA Astrophysics Data System (ADS)

Parveen, Arshiya; Rizvi, Syed Husain Mustafa; Mahdi, Farzana; Tripathi, Sandeep; Ahmad, Iqbal; Shukla, Rajendra K.; Khanna, Vinay K.; Singh, Ranjana; Patel, Devendra K.; Mahdi, Abbas Ali

2014-11-01

Extensive uses of silica nanoparticles (SiNPs) in biomedical and industrial fields have increased the risk of exposure, resulting concerns about their safety. We focussed on some of the safety aspects by studying neurobehavioural impairment, oxidative stress (OS), neurochemical and ultrastructural changes in corpus striatum (CS) of male Wistar rats exposed to 80-nm SiNPs. Moreover, its role in inducing mitochondrial and endoplasmic reticulum (ER) stress-mediated neuronal apoptosis was also investigated. The results demonstrated impairment in neurobehavioural indices, and a significant increase in lipid peroxide levels (LPO), hydrogen peroxide (H2O2), superoxide (O2 -) and protein carbonyl content, whereas there was a significant decrease in the activities of the enzymes, manganese superoxide dismutase (Mn SOD), glutathione peroxidase (GPx), catalase (CAT) and reduced glutathione (GSH) content, suggesting impaired antioxidant defence system. Protein (cytochrome c, Bcl-2, Bax, p53, caspase-3, caspase 12 and CHOP/Gadd153) and mRNA (Bcl-2, Bax, p53 and CHOP/Gadd153, cytochrome c) expression studies of mitochondrial and ER stress-related apoptotic factors suggested that both the cell organelles were involved in OS-mediated apoptosis in treated rat brain CS. Moreover, electron microscopic studies clearly showed mitochondrial and ER dysfunction. In conclusion, the result of the study suggested that subchronic SiNPs' exposure has the potential to alter the behavioural activity and also to bring about changes in biochemical, neurochemical and ultrastructural profiles in CS region of rat brain. Furthermore, we also report SiNPs-induced apoptosis in CS, through mitochondrial and ER stress-mediated signalling.

46 CFR Appendix II to Part 153 - Metric Units Used in Part 153

Code of Federal Regulations, 2013 CFR

2013-10-01

.../cm2. ......do kPa 1×10 3 N/m 2. Temperature Degree Celsius °C 5/9 (°F-32). Viscosity milli-Pascal... 46 Shipping 5 2013-10-01 2013-10-01 false Metric Units Used in Part 153 II Appendix II to Part 153... common metric Force Newton N 0.225 lbs. Length Meter m 39.37 in. Centimeter cm .3937 in. Pressure Pascal...

46 CFR Appendix II to Part 153 - Metric Units Used in Part 153

Code of Federal Regulations, 2012 CFR

2012-10-01

.../cm2. ......do kPa 1×10 3 N/m 2. Temperature Degree Celsius °C 5/9 (°F-32). Viscosity milli-Pascal... 46 Shipping 5 2012-10-01 2012-10-01 false Metric Units Used in Part 153 II Appendix II to Part 153... common metric Force Newton N 0.225 lbs. Length Meter m 39.37 in. Centimeter cm .3937 in. Pressure Pascal...

46 CFR Appendix II to Part 153 - Metric Units Used in Part 153

Code of Federal Regulations, 2014 CFR

2014-10-01

.../cm2. ......do kPa 1×10 3 N/m 2. Temperature Degree Celsius °C 5/9 (°F-32). Viscosity milli-Pascal... 46 Shipping 5 2014-10-01 2014-10-01 false Metric Units Used in Part 153 II Appendix II to Part 153... common metric Force Newton N 0.225 lbs. Length Meter m 39.37 in. Centimeter cm .3937 in. Pressure Pascal...

Regulation of macroautophagy in ovarian cancer cells in vitro and in vivo by controlling Glucose regulatory protein 78 and AMPK

PubMed Central

Kandala, Prabodh K.; Srivastava, Sanjay K.

2012-01-01

In this study we show that diindolylmethane (DIM) induces autophagy in ovarian cancer cells by regulating endoplasmic reticulum (ER) stress and AMPK. Treatment of SKOV-3, OVCAR-3 and TOV-21G ovarian cancer cells with varying concentrations of DIM for 24 hours resulted in a concentration dependent induction of autophagy as measured by flowcytometry. Electron microscopy confirmed the presence of autophagosomes in DIM treated cells. Western blot analysis showed that DIM treatment increased the expression of LC3B, a hall mark of autophagy as well as p62 and Atg 12 proteins that are accumulated during autophagy. Autophagy inhibitors bafilomycin or chloroquine inhibited DIM induced autophagy. Furthermore, DIM treatment significantly increased the expression of ER stress regulators such as Grp78, IRE1 and GADD153. Cycloheximide or ER stress inhibitor mithramycin not only blocked ER stress proteins that were activated by DIM but also autophagy. Silencing Grp78 or GADD 153 significantly blocked the expression of LC3B and p62 indicating that autophagy in our model is mediated by ER stress. Knocking out LC3B inhibited DIM induced autophagy. DIM treatment increased the cytosolic calcium levels which lead to the activation of AMPK in our model. Chelating cytosolic calcium with BAPT-AM abrogated not only the phosphorylation of AMPK but also prevented DIM induced autophagy. Inhibiting AMPK by a chemical inhibitor or siRNA blocked the induction of LC3B or p62, indicating that DIM mediated autophagy requires activation of AMPK. Oral administration of DIM significantly suppressed SKOV-3 tumor xenografts in nude mice. Activation of ER stress and autophagy were observed in the tumors of DIM treated mice. Taken together, these results suggest that induction of autophagy by DIM in ovarian cancer cells was associated with ER stress and AMPK activation. PMID:22564965

28 CFR 115.152-115.153 - [Reserved

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false [Reserved] 115.152-115.153 Section 115.152-115.153 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Lockups Reporting §§ 115.152-115.153 [Reserved] ...

46 CFR 153.1502 - Fixed ballast relocation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Fixed ballast relocation. 153.1502 Section 153.1502 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Maintenance § 153...

46 CFR 153.1502 - Fixed ballast relocation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Fixed ballast relocation. 153.1502 Section 153.1502 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Maintenance § 153...

46 CFR 153.1502 - Fixed ballast relocation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Fixed ballast relocation. 153.1502 Section 153.1502 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Maintenance § 153...

46 CFR 153.1502 - Fixed ballast relocation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Fixed ballast relocation. 153.1502 Section 153.1502 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Maintenance § 153...

46 CFR 153.1502 - Fixed ballast relocation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Fixed ballast relocation. 153.1502 Section 153.1502 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Maintenance § 153...

49 CFR 37.153 - FTA waiver determination.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false FTA waiver determination. 37.153 Section 37.153 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Paratransit as a Complement to Fixed Route Service § 37.153 FTA waiver determination. (a...

33 CFR 117.153 - Corte Madera Creek.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Corte Madera Creek. 117.153 Section 117.153 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements California § 117.153 Corte Madera Creek. The draw of...

33 CFR 117.153 - Corte Madera Creek.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Corte Madera Creek. 117.153 Section 117.153 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements California § 117.153 Corte Madera Creek. The draw of...

46 CFR 153.30 - Special area endorsement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Special area endorsement. 153.30 Section 153.30 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.30 Special area...

46 CFR 153.4 - Incorporation by reference.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Incorporation by reference. 153.4 Section 153.4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.4 Incorporation by...

46 CFR 153.30 - Special area endorsement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Special area endorsement. 153.30 Section 153.30 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.30 Special area...

46 CFR 153.30 - Special area endorsement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Special area endorsement. 153.30 Section 153.30 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.30 Special area...

46 CFR 153.4 - Incorporation by reference.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Incorporation by reference. 153.4 Section 153.4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.4 Incorporation by...

46 CFR 153.4 - Incorporation by reference.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Incorporation by reference. 153.4 Section 153.4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.4 Incorporation by...

46 CFR 153.30 - Special area endorsement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Special area endorsement. 153.30 Section 153.30 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.30 Special area...

46 CFR 153.4 - Incorporation by reference.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Incorporation by reference. 153.4 Section 153.4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.4 Incorporation by...

46 CFR 153.4 - Incorporation by reference.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Incorporation by reference. 153.4 Section 153.4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.4 Incorporation by...

45 CFR 153.600 - [Reserved

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false [Reserved] 153.600 Section 153.600 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT Health Insurance Issuer...

45 CFR 153.600 - [Reserved

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false [Reserved] 153.600 Section 153.600 Public Welfare Department of Health and Human Services REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT Health Insurance Issuer...

45 CFR 153.600 - [Reserved

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false [Reserved] 153.600 Section 153.600 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT Health Insurance Issuer...

The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways.

PubMed

Youns, Mаhmoud; Abdel Halim Hegazy, Wael

2017-01-01

Digestive cancers are major causes of mortality and morbidity worldwide. Fisetin, a naturally occurring flavonoid, has been previously shown anti-proliferative, anti-cancer, neuroprotective, and antioxidant activities. In our study, the anti-tumor activities in addition to regulatory effects of fisetin on some cancer cell lines were investigated. Data presented here showed that fisetin induces growth inhibition, and apoptosis in hepatic (HepG-2), colorectal (Caco-2) and pancreatic (Suit-2) cancer cell lines. Gene expression results showed that 1307 genes were significantly regulated in their expression in hepatic and pancreatic cell lines. 350 genes were commonly up-regulated and 353 genes were commonly down-regulated. Additionally, 604 genes were oppositely expressed in both tumor cells. CDK5 signaling, NRF2-mediated oxidative stress response, glucocorticoid signaling, and ERK/MAPK signaling were among most prominent signaling pathways modulating the growth inhibitory effects of fisetin on hepatic and pancreatic cancer cells. The present analysis showed, for the first time, that the anti-tumor effect of fisetin was mediated mainly through modulation of multiple signaling pathways and via activation of CDKN1A, SEMA3E, GADD45B and GADD45A and down-regulation of TOP2A, KIF20A, CCNB2 and CCNB1 genes.

The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways

PubMed Central

Youns, Mаhmoud; Abdel Halim Hegazy, Wael

2017-01-01

Digestive cancers are major causes of mortality and morbidity worldwide. Fisetin, a naturally occurring flavonoid, has been previously shown anti-proliferative, anti-cancer, neuroprotective, and antioxidant activities. In our study, the anti-tumor activities in addition to regulatory effects of fisetin on some cancer cell lines were investigated. Data presented here showed that fisetin induces growth inhibition, and apoptosis in hepatic (HepG-2), colorectal (Caco-2) and pancreatic (Suit-2) cancer cell lines. Gene expression results showed that 1307 genes were significantly regulated in their expression in hepatic and pancreatic cell lines. 350 genes were commonly up-regulated and 353 genes were commonly down-regulated. Additionally, 604 genes were oppositely expressed in both tumor cells. CDK5 signaling, NRF2-mediated oxidative stress response, glucocorticoid signaling, and ERK/MAPK signaling were among most prominent signaling pathways modulating the growth inhibitory effects of fisetin on hepatic and pancreatic cancer cells. The present analysis showed, for the first time, that the anti-tumor effect of fisetin was mediated mainly through modulation of multiple signaling pathways and via activation of CDKN1A, SEMA3E, GADD45B and GADD45A and down-regulation of TOP2A, KIF20A, CCNB2 and CCNB1 genes. PMID:28052097

Gene Therapy Using Therapeutic and Diagnostic Recombinant Oncolytic Vaccinia Virus GLV-1h153 for Management of Colorectal Peritoneal Carcinomatosis

PubMed Central

Eveno, Clarisse; Mojica, Kelly; Ady, Justin W.; Thorek, Daniel L.J.; Longo, Valerie; Belin, Laurence J.; Gholami, Sepideh; Johnsen, Clark; Zanzonico, Pat; Chen, Nanhai; Yu, Tony; Szalay, Aladar A.; Fong, Yuman

2015-01-01

Background Peritoneal carcinomatosis (PC) is a terminal progression of colorectal cancer (CRC). Poor response to cytoreductive surgery and chemotherapy, coupled with the inability to reliably track disease progression using established diagnostic methods make this a deadly disease. This paper examines the effectiveness of the oncolytic vaccinia virus GLV-1h153 as a therapeutic and diagnostic vehicle. We believe that viral expression of the human sodium iodide transporter (hNIS) can provide both real-time monitoring of viral therapy and effective treatment of colorectal peritoneal carcinomatosis (CRPC). Methods Infectivity and cytotoxic effect of GLV-1h153 on CRC cell lines was assayed in-vitro. Viral replication was examined by standard viral plaque assays. Orthotopic CRPC xenografts were generated in athymic nude mice, and subsequently administered GLV-1h153 intraperitoneally. Reduction of tumor burden was assessed by mass. Orthotopic tumors were visualized by SPECT/CT after Iodine (131I) administration and by fluorescence optical imaging. Results GLV-1h153 infected and killed CRC cells in a time and concentration dependent manner. Viral replication demonstrated greater than a 2.35 log increase in titer over 4 days. Intraperitoneal treatment of orthotopic CRPC xenografts resulted in a significant reduction of tumor burden. Infection of orthotopic xenografts was both therapeutic and facilitated monitoring by 131I-SPECT/CT via expression of hNIS in infected tissue. Conclusions GLV-1h153 effectively kills CRC in-vitro and dramatically reduces tumor burden in-vivo. We demonstrate that GLV-1h153 can be used as an agent to provide accurate delineation of tumor burden in-vivo. These findings indicate that GLV-1h153 has significant potential for use as theragnostic agent in the treatment of CRPC. PMID:25616946

46 CFR 153.234 - Fore and aft location.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Containment Systems § 153.234 Fore and aft location. Except as allowed in § 153.7, each ship must meet the... 46 Shipping 5 2014-10-01 2014-10-01 false Fore and aft location. 153.234 Section 153.234 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING...

46 CFR 153.933 - Chemical protective clothing.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Chemical protective clothing. 153.933 Section 153.933... § 153.933 Chemical protective clothing. When table 1 refers to this section, the following apply: (a) The master shall ensure that the following chemical protective clothing constructed of materials...

46 CFR 153.933 - Chemical protective clothing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Chemical protective clothing. 153.933 Section 153.933... § 153.933 Chemical protective clothing. When table 1 refers to this section, the following apply: (a) The master shall ensure that the following chemical protective clothing constructed of materials...

46 CFR 153.936 - Illness, alcohol, drugs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Illness, alcohol, drugs. 153.936 Section 153.936 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... § 153.936 Illness, alcohol, drugs. The master shall ensure that no person participates in cargo related...

25 CFR 153.4 - Factors determining competency.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Factors determining competency. 153.4 Section 153.4 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER DETERMINATION OF COMPETENCY: CROW INDIANS § 153.4 Factors determining competency. Among the matters to be considered by the...

46 CFR 153.440 - Cargo temperature sensors.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo temperature sensors. 153.440 Section 153.440... CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Temperature Control Systems § 153.440 Cargo temperature sensors. (a) Except as prescribed in paragraph (c) of...

46 CFR 153.440 - Cargo temperature sensors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo temperature sensors. 153.440 Section 153.440... CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Temperature Control Systems § 153.440 Cargo temperature sensors. (a) Except as prescribed in paragraph (c) of...

46 CFR 153.933 - Chemical protective clothing.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Chemical protective clothing. 153.933 Section 153.933... § 153.933 Chemical protective clothing. When table 1 refers to this section, the following apply: (a) The master shall ensure that the following chemical protective clothing constructed of materials...

46 CFR 153.933 - Chemical protective clothing.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Chemical protective clothing. 153.933 Section 153.933... § 153.933 Chemical protective clothing. When table 1 refers to this section, the following apply: (a) The master shall ensure that the following chemical protective clothing constructed of materials...

46 CFR 153.933 - Chemical protective clothing.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Chemical protective clothing. 153.933 Section 153.933... § 153.933 Chemical protective clothing. When table 1 refers to this section, the following apply: (a) The master shall ensure that the following chemical protective clothing constructed of materials...

45 CFR 153.700 - Distributed data environment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Distributed data environment. 153.700 Section 153... Distributed Data Collection for HHS-Operated Programs § 153.700 Distributed data environment. (a) Dedicated distributed data environments. For each benefit year in which HHS operates the risk adjustment or reinsurance...

45 CFR 153.700 - Distributed data environment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Distributed data environment. 153.700 Section 153... Distributed Data Collection for HHS-Operated Programs § 153.700 Distributed data environment. (a) Dedicated distributed data environments. For each benefit year in which HHS operates the risk adjustment or reinsurance...

45 CFR 153.200 - [Reserved

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false [Reserved] 153.200 Section 153.200 Public Welfare Department of Health and Human Services REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT State Standards Related to the...

45 CFR 153.300 - [Reserved

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false [Reserved] 153.300 Section 153.300 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT State Standards Related to the...

45 CFR 153.200 - [Reserved

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false [Reserved] 153.200 Section 153.200 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT State Standards Related to the...

45 CFR 153.200 - [Reserved

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false [Reserved] 153.200 Section 153.200 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT State Standards Related to the...

45 CFR 153.300 - [Reserved

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false [Reserved] 153.300 Section 153.300 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT State Standards Related to the...

45 CFR 153.300 - [Reserved

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false [Reserved] 153.300 Section 153.300 Public Welfare Department of Health and Human Services REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT State Standards Related to the...

46 CFR 153.215 - Safety equipment lockers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Safety equipment lockers. 153.215 Section 153.215... Vessel Requirements § 153.215 Safety equipment lockers. Each self-propelled ship must have the following: (a) Each tankship must have at least two safety equipment lockers. (b) One safety equipment locker...

46 CFR 153.215 - Safety equipment lockers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Safety equipment lockers. 153.215 Section 153.215... Vessel Requirements § 153.215 Safety equipment lockers. Each self-propelled ship must have the following: (a) Each tankship must have at least two safety equipment lockers. (b) One safety equipment locker...

46 CFR 153.215 - Safety equipment lockers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Safety equipment lockers. 153.215 Section 153.215... Vessel Requirements § 153.215 Safety equipment lockers. Each self-propelled ship must have the following: (a) Each tankship must have at least two safety equipment lockers. (b) One safety equipment locker...

46 CFR 153.215 - Safety equipment lockers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Safety equipment lockers. 153.215 Section 153.215... Vessel Requirements § 153.215 Safety equipment lockers. Each self-propelled ship must have the following: (a) Each tankship must have at least two safety equipment lockers. (b) One safety equipment locker...

46 CFR 153.215 - Safety equipment lockers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Safety equipment lockers. 153.215 Section 153.215... Vessel Requirements § 153.215 Safety equipment lockers. Each self-propelled ship must have the following: (a) Each tankship must have at least two safety equipment lockers. (b) One safety equipment locker...

46 CFR 153.3 - Right of appeal.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Right of appeal. 153.3 Section 153.3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.3 Right of appeal. Any person...

25 CFR 153.2 - Application and examination.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Application and examination. 153.2 Section 153.2 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER DETERMINATION OF COMPETENCY: CROW INDIANS § 153.2 Application and examination. The Commissioner of Indian Affairs or his duly authorized...

46 CFR 153.368 - Pressure-vacuum valves.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Pressure-vacuum valves. 153.368 Section 153.368 Shipping... BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Venting Systems § 153.368 Pressure-vacuum valves. (a) The pressure side of a required pressure-vacuum relief valve...

46 CFR 153.368 - Pressure-vacuum valves.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Pressure-vacuum valves. 153.368 Section 153.368 Shipping... BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Venting Systems § 153.368 Pressure-vacuum valves. (a) The pressure side of a required pressure-vacuum relief valve...

46 CFR 153.368 - Pressure-vacuum valves.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Pressure-vacuum valves. 153.368 Section 153.368 Shipping... BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Venting Systems § 153.368 Pressure-vacuum valves. (a) The pressure side of a required pressure-vacuum relief valve...

46 CFR 153.368 - Pressure-vacuum valves.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Pressure-vacuum valves. 153.368 Section 153.368 Shipping... BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Venting Systems § 153.368 Pressure-vacuum valves. (a) The pressure side of a required pressure-vacuum relief valve...

46 CFR 153.368 - Pressure-vacuum valves.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Pressure-vacuum valves. 153.368 Section 153.368 Shipping... BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Venting Systems § 153.368 Pressure-vacuum valves. (a) The pressure side of a required pressure-vacuum relief valve...

46 CFR 153.3 - Right of appeal.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Right of appeal. 153.3 Section 153.3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.3 Right of appeal. Any person...

46 CFR 153.3 - Right of appeal.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Right of appeal. 153.3 Section 153.3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.3 Right of appeal. Any person...

46 CFR 153.3 - Right of appeal.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Right of appeal. 153.3 Section 153.3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.3 Right of appeal. Any person...

46 CFR 153.3 - Right of appeal.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Right of appeal. 153.3 Section 153.3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.3 Right of appeal. Any person...

46 CFR 153.408 - Tank overflow control.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Tank overflow control. 153.408 Section 153.408 Shipping... Systems § 153.408 Tank overflow control. (a) When table 1 references this section, a cargo containment... the tank (automatic shutdown system). (b) The high level alarm and the cargo overflow alarm or...

46 CFR 153.1065 - Sodium chlorate solutions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Sodium chlorate solutions. 153.1065 Section 153.1065... Procedures § 153.1065 Sodium chlorate solutions. (a) No person may load sodium chlorate solutions into a... before loading. (b) The person in charge of cargo transfer shall make sure that spills of sodium chlorate...

46 CFR 153.1065 - Sodium chlorate solutions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Sodium chlorate solutions. 153.1065 Section 153.1065... Procedures § 153.1065 Sodium chlorate solutions. (a) No person may load sodium chlorate solutions into a... before loading. (b) The person in charge of cargo transfer shall make sure that spills of sodium chlorate...

46 CFR 153.1065 - Sodium chlorate solutions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Sodium chlorate solutions. 153.1065 Section 153.1065... Procedures § 153.1065 Sodium chlorate solutions. (a) No person may load sodium chlorate solutions into a... before loading. (b) The person in charge of cargo transfer shall make sure that spills of sodium chlorate...

Epidemiological survey of idiopathic scoliosis and sequence alignment analysis of multiple candidate genes.

PubMed

Yang, Tao; Jia, Quanzhang; Guo, Hong; Xu, Jianzhong; Bai, Yun; Yang, Kai; Luo, Fei; Zhang, Zehua; Hou, Tianyong

2012-06-01

To investigate the effects of genetic factors on idiopathic scoliosis (IS) and genetic modes through genetic epidemiological survey on IS in Chongqing City, China, and to determine whether SH3GL1, GADD45B, and FGF22 in the chromosome 19p13.3 are the pathogenic genes of IS through genetic sequence analysis. 214 nuclear families were investigated to analyse the age incidence, familial aggregation, and heritability. SH3GL1, GADD45B, and FGF22 were chosen as candidate genes for mutation screening in 56 IS patients of 214 families. The sequence alignment analysis was performed to determine mutations and predict the protein structure. The average age of onset of 10.8 years suggests that IS is a early onset disease. Incidences of IS in first-, second-, third-degree relatives and the overall incidence in families (5.68%) were also significantly higher than that of the general population (1.04%). The U test indicated a significant difference, suggesting that IS has a familial aggregation. The heritability of first-degree relatives (77.68 ±10.39%), second-degree relatives (69.89 ±3.14%), and third-degree relatives (62.14 ±11.92%) illustrated that genetic factors play an important role in IS pathogenesis. The incidence of first-degree relatives (10.01%), second-degree relatives (2.55%) and third-degree relatives (1.76%) illustrated that IS is not in simple accord with monogenic Mendel's law but manifests as traits of multifactorial hereditary diseases. Sequence alignment of exons of SH3GL1, GADD45B, and FGF22 showed 17 base mutations, of which 16 mutations do not induce open reading frame (ORF) shift or amino acid changes whereas one mutation (C→T)occurred in SH3GL1 results in formation of the termination codon, which induces variation of protein reading frame. Prediction analysis of protein sequence showed that the SH3GL1 mutant encoded a truncated protein, thus affecting the protein structure. IS is a multifactorial genetic disease and SH3GL1 may be one of the

46 CFR 153.251 - Independent cargo tanks.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Independent cargo tanks. 153.251 Section 153.251... CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Tanks § 153.251 Independent cargo tanks. All independent cargo tank must meet § 38.05-10 (a)(1), (b), (d), and...

46 CFR 153.251 - Independent cargo tanks.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Independent cargo tanks. 153.251 Section 153.251... CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Tanks § 153.251 Independent cargo tanks. All independent cargo tank must meet § 38.05-10 (a)(1), (b), (d), and...

46 CFR 153.465 - Flammable vapor detector.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Flammable vapor detector. 153.465 Section 153.465... Requirements for Flammable Or Combustible Cargoes § 153.465 Flammable vapor detector. (a) A tankship that carries a flammable cargo must have two vapor detectors that meet § 35.30-15(b) of this chapter. (b) At...

46 CFR 153.465 - Flammable vapor detector.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Flammable vapor detector. 153.465 Section 153.465... Requirements for Flammable Or Combustible Cargoes § 153.465 Flammable vapor detector. (a) A tankship that carries a flammable cargo must have two vapor detectors that meet § 35.30-15(b) of this chapter. (b) At...

46 CFR 153.465 - Flammable vapor detector.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Flammable vapor detector. 153.465 Section 153.465... Requirements for Flammable Or Combustible Cargoes § 153.465 Flammable vapor detector. (a) A tankship that carries a flammable cargo must have two vapor detectors that meet § 35.30-15(b) of this chapter. (b) At...

46 CFR 153.465 - Flammable vapor detector.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Flammable vapor detector. 153.465 Section 153.465... Requirements for Flammable Or Combustible Cargoes § 153.465 Flammable vapor detector. (a) A tankship that carries a flammable cargo must have two vapor detectors that meet § 35.30-15(b) of this chapter. (b) At...

46 CFR 153.465 - Flammable vapor detector.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Flammable vapor detector. 153.465 Section 153.465... Requirements for Flammable Or Combustible Cargoes § 153.465 Flammable vapor detector. (a) A tankship that carries a flammable cargo must have two vapor detectors that meet § 35.30-15(b) of this chapter. (b) At...

46 CFR 153.936 - Illness, alcohol, drugs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Illness, alcohol, drugs. 153.936 Section 153.936... § 153.936 Illness, alcohol, drugs. The master shall ensure that no person participates in cargo related operations who appears to be intoxicated by alcohol or drugs or to be so ill as to be unfit for the...

46 CFR 153.936 - Illness, alcohol, drugs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Illness, alcohol, drugs. 153.936 Section 153.936... § 153.936 Illness, alcohol, drugs. The master shall ensure that no person participates in cargo related operations who appears to be intoxicated by alcohol or drugs or to be so ill as to be unfit for the...

46 CFR 153.936 - Illness, alcohol, drugs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Illness, alcohol, drugs. 153.936 Section 153.936... § 153.936 Illness, alcohol, drugs. The master shall ensure that no person participates in cargo related operations who appears to be intoxicated by alcohol or drugs or to be so ill as to be unfit for the...

46 CFR 153.936 - Illness, alcohol, drugs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Illness, alcohol, drugs. 153.936 Section 153.936... § 153.936 Illness, alcohol, drugs. The master shall ensure that no person participates in cargo related operations who appears to be intoxicated by alcohol or drugs or to be so ill as to be unfit for the...

46 CFR 153.526 - Toxic vapor detectors.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Toxic vapor detectors. 153.526 Section 153.526 Shipping... Requirements § 153.526 Toxic vapor detectors. (a) When Table 1 refers to this section, a tankship must have two toxic vapor detectors, at least one of which must be portable, each able to measure vapor concentrations...

46 CFR 153.526 - Toxic vapor detectors.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Toxic vapor detectors. 153.526 Section 153.526 Shipping... Requirements § 153.526 Toxic vapor detectors. (a) When Table 1 refers to this section, a tankship must have two toxic vapor detectors, at least one of which must be portable, each able to measure vapor concentrations...

46 CFR 153.526 - Toxic vapor detectors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Toxic vapor detectors. 153.526 Section 153.526 Shipping... Requirements § 153.526 Toxic vapor detectors. (a) When Table 1 refers to this section, a tankship must have two toxic vapor detectors, at least one of which must be portable, each able to measure vapor concentrations...

46 CFR 153.526 - Toxic vapor detectors.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Toxic vapor detectors. 153.526 Section 153.526 Shipping... Requirements § 153.526 Toxic vapor detectors. (a) When Table 1 refers to this section, a tankship must have two toxic vapor detectors, at least one of which must be portable, each able to measure vapor concentrations...

46 CFR 153.526 - Toxic vapor detectors.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Toxic vapor detectors. 153.526 Section 153.526 Shipping... Requirements § 153.526 Toxic vapor detectors. (a) When Table 1 refers to this section, a tankship must have two toxic vapor detectors, at least one of which must be portable, each able to measure vapor concentrations...

46 CFR 153.409 - High level alarms.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false High level alarms. 153.409 Section 153.409 Shipping... Systems § 153.409 High level alarms. When Table 1 refers to this section or requires a cargo to have a closed gauging system, the cargo's containment system must have a high level alarm: (a) That gives an...

46 CFR 153.330 - Access.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Pumprooms § 153.330 Access. (a) The access door to a cargo pump-room must open on the weatheredeck. (b) The access way to a cargo pump-room and its valving must allow passage of a man wearing the breathing apparatus required by § 153...

The functionally conserved nucleoporins Nup124p from fission yeast and the human Nup153 mediate nuclear import and activity of the Tf1 retrotransposon and HIV-1 Vpr.

PubMed

Varadarajan, Padmapriya; Mahalingam, Sundarasamy; Liu, Peiyun; Ng, Sarah Boon Hsi; Gandotra, Sheetal; Dorairajoo, Desmond Suresh Kumar; Balasundaram, David

2005-04-01

We report that the fission yeast nucleoporin Nup124p is required for the nuclear import of both, retrotransposon Tf1-Gag as well as the retroviral HIV-1 Vpr. Failure to import Tf1-Gag into the nucleus in a nup124 null mutant resulted in complete loss of Tf1 transposition. Similarly, nuclear import of HIV-1 Vpr was impaired in nup124 null mutant strains and cells became resistant to Vpr's cell-killing activity. On the basis of protein domain similarity, the human nucleoporin Nup153 was identified as a putative homolog of Nup124p. We demonstrate that in vitro-translated Nup124p and Nup153 coimmunoprecipitate Tf1-Gag or HIV-1 Vpr. Though full-length Nup153 was unable to complement the Tf1 transposition defect in a nup124 null mutant, we provide evidence that both nucleoporins share a unique N-terminal domain, Nup124p(AA264-454) and Nup153(AA448-634) that is absolutely essential for Tf1 transposition. Epigenetic overexpression of this domain in a wild-type (nup124(+)) background blocked Tf1 activity implying that sequences from Nup124p and the human Nup153 challenged the same pathway affecting Tf1 transposition. Our results establish a unique relationship between two analogous nucleoporins Nup124p and Nup153 wherein the function of a common domain in retrotransposition is conserved.

Alpha fetoprotein mediates HBx induced carcinogenesis in the hepatocyte cytoplasm.

PubMed

Zhang, Chao; Chen, Xiangmei; Liu, Hui; Li, Hui; Jiang, Wei; Hou, Wenting; McNutt, Michael A; Lu, Fengmin; Li, Gang

2015-10-15

Although tumor-associated fetal protein AFP has demonstrated utility as a clinical tumor marker, the significance of intracellular AFP is still unclear. The aim of this study was to explore the role of cytoplasmic AFP during HBx induced carcinogenesis, which had not previously been recognized; 614 HCC patients were analyzed for correlation of HBV infection with AFP level, and much higher AFP levels were found in HBsAg positive patients. Tumor tissue specimens from 20 HCC patients were used for analysis of AFP and GADD45α. Analysis of HCC specimens showed that upregulation of cytoplasmic AFP is associated with down-regulation of GADD45α in neoplastic tissue. Transfected HBx promotes transcription of AFP by acting on the elements in the AFP gene regulatory region. HBx itself did not directly impact transcription of GADD45α. However, the obstruction of RAR signaling by HBx induced elevation of AFP, which led to down-regulation of GADD45α. Cytoplasmic AFP was able to interact with RAR, disrupting its entrance into the nucleus and binding to the elements in the regulatory region of the GADD45α gene. Knockdown of AFP in siRNA-transfected AFP positive cell lines was synchronously associated with an incremental increase of RAR binding to DNA, as well as upregulation of GADD45α and it was contrary in AFP gene-transfected AFP negative cell lines. These results indicate cytoplasmic AFP is not only a histochemical tumor biomarker for human hepatoma but is also an intracellular signal molecule and potential participant in HBx induced hepatocarcinogenesis. © 2015 UICC.

7 CFR 457.153 - Peach crop insurance provisions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Peach crop insurance provisions. 457.153 Section 457.153 Agriculture Regulations of the Department of Agriculture (Continued) FEDERAL CROP INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.153 Peach crop insurance...

47 CFR 25.153 - Repetitious applications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Repetitious applications. 25.153 Section 25.153 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS... of 12 months from the effective date of the Commission's action. The Commission may, for good cause...

47 CFR 25.153 - Repetitious applications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Repetitious applications. 25.153 Section 25.153 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS... of 12 months from the effective date of the Commission's action. The Commission may, for good cause...

46 CFR 153.983 - Termination procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Termination procedures. 153.983 Section 153.983 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Cargo Transfer Procedures...

46 CFR 153.1045 - Inorganic acids.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Inorganic acids. 153.1045 Section 153.1045 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures...

46 CFR 153.1045 - Inorganic acids.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Inorganic acids. 153.1045 Section 153.1045 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures...

46 CFR 153.1045 - Inorganic acids.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Inorganic acids. 153.1045 Section 153.1045 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures...

46 CFR 153.983 - Termination procedures.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Termination procedures. 153.983 Section 153.983 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Cargo Transfer Procedures...

46 CFR 153.983 - Termination procedures.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Termination procedures. 153.983 Section 153.983 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Cargo Transfer Procedures...

46 CFR 153.983 - Termination procedures.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Termination procedures. 153.983 Section 153.983 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Cargo Transfer Procedures...

46 CFR 153.983 - Termination procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Termination procedures. 153.983 Section 153.983 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Cargo Transfer Procedures...

The Functionally Conserved Nucleoporins Nup124p from Fission Yeast and the Human Nup153 Mediate Nuclear Import and Activity of the Tf1 Retrotransposon and HIV-1 VprV⃞

PubMed Central

Varadarajan, Padmapriya; Mahalingam, Sundarasamy; Liu, Peiyun; Ng, Sarah Boon Hsi; Gandotra, Sheetal; Dorairajoo, Desmond Suresh Kumar; Balasundaram, David

2005-01-01

We report that the fission yeast nucleoporin Nup124p is required for the nuclear import of both, retrotransposon Tf1-Gag as well as the retroviral HIV-1 Vpr. Failure to import Tf1-Gag into the nucleus in a nup124 null mutant resulted in complete loss of Tf1 transposition. Similarly, nuclear import of HIV-1 Vpr was impaired in nup124 null mutant strains and cells became resistant to Vpr's cell-killing activity. On the basis of protein domain similarity, the human nucleoporin Nup153 was identified as a putative homolog of Nup124p. We demonstrate that in vitro–translated Nup124p and Nup153 coimmunoprecipitate Tf1-Gag or HIV-1 Vpr. Though full-length Nup153 was unable to complement the Tf1 transposition defect in a nup124 null mutant, we provide evidence that both nucleoporins share a unique N-terminal domain, Nup124pAA264–454 and Nup153AA448–634 that is absolutely essential for Tf1 transposition. Epigenetic overexpression of this domain in a wild-type (nup124+) background blocked Tf1 activity implying that sequences from Nup124p and the human Nup153 challenged the same pathway affecting Tf1 transposition. Our results establish a unique relationship between two analogous nucleoporins Nup124p and Nup153 wherein the function of a common domain in retrotransposition is conserved. PMID:15659641

10 CFR 52.153 - Relationship to other subparts.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Relationship to other subparts. 52.153 Section 52.153 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Manufacturing Licenses § 52.153 Relationship to other subparts. (a) A nuclear power reactor...

10 CFR 52.153 - Relationship to other subparts.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Relationship to other subparts. 52.153 Section 52.153 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Manufacturing Licenses § 52.153 Relationship to other subparts. (a) A nuclear power reactor...

46 CFR 153.1500 - Venting system rupture disks.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Venting system rupture disks. 153.1500 Section 153.1500 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Maintenance § 153...

46 CFR 153.1500 - Venting system rupture disks.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Venting system rupture disks. 153.1500 Section 153.1500 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Maintenance § 153...

46 CFR 153.1500 - Venting system rupture disks.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Venting system rupture disks. 153.1500 Section 153.1500 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Maintenance § 153...

46 CFR 153.1500 - Venting system rupture disks.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Venting system rupture disks. 153.1500 Section 153.1500 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Maintenance § 153...

46 CFR 153.1500 - Venting system rupture disks.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Venting system rupture disks. 153.1500 Section 153.1500 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Maintenance § 153...

42 CFR 431.153 - Evidentiary hearing.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 4 2013-10-01 2013-10-01 false Evidentiary hearing. 431.153 Section 431.153 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS STATE ORGANIZATION AND GENERAL ADMINISTRATION Appeals Process for NFs and ICFs...

42 CFR 431.153 - Evidentiary hearing.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 4 2011-10-01 2011-10-01 false Evidentiary hearing. 431.153 Section 431.153 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS STATE ORGANIZATION AND GENERAL ADMINISTRATION Appeals Process for NFs and ICFs...

42 CFR 431.153 - Evidentiary hearing.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 4 2012-10-01 2012-10-01 false Evidentiary hearing. 431.153 Section 431.153 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS STATE ORGANIZATION AND GENERAL ADMINISTRATION Appeals Process for NFs and ICFs...

42 CFR 431.153 - Evidentiary hearing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Evidentiary hearing. 431.153 Section 431.153 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS STATE ORGANIZATION AND GENERAL ADMINISTRATION Appeals Process for NFs and ICFs...

42 CFR 431.153 - Evidentiary hearing.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 4 2014-10-01 2014-10-01 false Evidentiary hearing. 431.153 Section 431.153 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS STATE ORGANIZATION AND GENERAL ADMINISTRATION Appeals Process for NFs and ICFs...

40 CFR 205.153 - Engine displacement.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Engine displacement. 205.153 Section... TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Motorcycles § 205.153 Engine displacement. (a) Engine displacement must be calculated using nominal engine values and rounded to the nearest whole cubic centimeter...

40 CFR 205.153 - Engine displacement.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Engine displacement. 205.153 Section... TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Motorcycles § 205.153 Engine displacement. (a) Engine displacement must be calculated using nominal engine values and rounded to the nearest whole cubic centimeter...

40 CFR 205.153 - Engine displacement.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Engine displacement. 205.153 Section... TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Motorcycles § 205.153 Engine displacement. (a) Engine displacement must be calculated using nominal engine values and rounded to the nearest whole cubic centimeter...

40 CFR 205.153 - Engine displacement.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Engine displacement. 205.153 Section... TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Motorcycles § 205.153 Engine displacement. (a) Engine displacement must be calculated using nominal engine values and rounded to the nearest whole cubic centimeter...

40 CFR 205.153 - Engine displacement.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Engine displacement. 205.153 Section... TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Motorcycles § 205.153 Engine displacement. (a) Engine displacement must be calculated using nominal engine values and rounded to the nearest whole cubic centimeter...

Inhibition of endoplasmic reticulum stress by intermedin1-53 attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE KO Mice.

PubMed

Ni, Xian-Qiang; Lu, Wei-Wei; Zhang, Jin-Sheng; Zhu, Qing; Ren, Jin-Ling; Yu, Yan-Rong; Liu, Xiu-Ying; Wang, Xiu-Jie; Han, Mei; Jing, Qing; Du, Jie; Tang, Chao-Shu; Qi, Yong-Fen

2018-06-26

Endoplasmic reticulum stress (ERS) is involved in the development of abdominal aortic aneurysm (AAA). Since bioactive peptide intermedin (IMD)1-53 protects against AAA formation, here we investigated whether IMD1-53 attenuates AAA by inhibiting ERS. AAA model was induced by angiotensin II (AngII) in ApoE KO mouse background. AngII-treated mouse aortas showed increased ERS gene transcription of caspase12, eukaryotic translation initiation factor 2a (eIf2a) and activating transcription factor 4(ATF4).The protein level of ERS marker glucose regulated protein 94(GRP94), ATF4 and C/EBP homologous protein 10(CHOP) was also up-regulated by AngII. Increased ERS levels were accompanied by severe VSMC apoptosis in human AAA aorta. In vivo administration of IMD1-53 greatly reduced AngII-induced AAA and abrogated the activation of ERS. To determine whether IMD inhibited AAA by ameliorating ERS, we used 2 non-selective ERS inhibitors phenyl butyrate (4-PBA) and taurine (TAU). Similar to IMD, PBA, and TAU significantly reduced the incidence of AAA and AAA-related pathological disorders. In vitro, AngII infusion up-regulated CHOP, caspase12 expression and led to VSMC apoptosis. IMD siRNA aggravated the CHOP, caspase12-mediated VSMC apoptosis, which was abolished by ATF4 silencing. IMD infusion promoted the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in aortas in ApoE KO mice, and the AMPK inhibitor compound C abolished the protective effect of IMD on VSMC ERS and apoptosis induced by AngII. In conclusion, IMD may protect against AAA formation by inhibiting ERS via activating AMPK phosphorylation.

46 CFR 153.977 - Supervision of cargo transfer.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Supervision of cargo transfer. 153.977 Section 153.977 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.977 Supervision of cargo transfer. The person in charge of cargo transfer shall: (a...

46 CFR 153.977 - Supervision of cargo transfer.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Supervision of cargo transfer. 153.977 Section 153.977 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.977 Supervision of cargo transfer. The person in charge of cargo transfer shall: (a...

46 CFR 153.977 - Supervision of cargo transfer.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Supervision of cargo transfer. 153.977 Section 153.977 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.977 Supervision of cargo transfer. The person in charge of cargo transfer shall: (a...

46 CFR 153.977 - Supervision of cargo transfer.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Supervision of cargo transfer. 153.977 Section 153.977 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.977 Supervision of cargo transfer. The person in charge of cargo transfer shall: (a...

46 CFR 153.977 - Supervision of cargo transfer.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Supervision of cargo transfer. 153.977 Section 153.977 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.977 Supervision of cargo transfer. The person in charge of cargo transfer shall: (a...

Chemopreventive agents alters global gene expression pattern: predicting their mode of action and targets.

PubMed

Narayanan, Bhagavathi A

2006-12-01

Chemoprevention has the potential to be a major component of colon, breast, prostate and lung cancer control. Epidemiological, experimental, and clinical studies provide evidence that antioxidants, anti-inflammatory agents, n-3 polyunsaturated fatty acids and several other phytochemicals possess unique modes of action against cancer growth. However, the mode of action of several of these agents at the gene transcription level is not completely understood. Completion of the human genome sequence and the advent of DNA microarrays using cDNAs enhanced the detection and identification of hundreds of differentially expressed genes in response to anticancer drugs or chemopreventive agents. In this review, we are presenting an extensive analysis of the key findings from studies using potential chemopreventive agents on global gene expression patterns, which lead to the identification of cancer drug targets. The summary of the study reports discussed in this review explains the extent of gene alterations mediated by more than 20 compounds including antioxidants, fatty acids, NSAIDs, phytochemicals, retinoids, selenium, vitamins, aromatase inhibitor, lovastatin, oltipraz, salvicine, and zinc. The findings from these studies further reveal the utility of DNA microarray in characterizing and quantifying the differentially expressed genes that are possibly reprogrammed by the above agents against colon, breast, prostate, lung, liver, pancreatic and other cancer types. Phenolic antioxidant resveratrol found in berries and grapes inhibits the formation of prostate tumors by acting on the regulatory genes such as p53 while activating a cascade of genes involved in cell cycle and apoptosis including p300, Apaf-1, cdk inhibitor p21, p57 (KIP2), p53 induced Pig 7, Pig 8, Pig 10, cyclin D, DNA fragmentation factor 45. The group of genes significantly altered by selenium includes cyclin D1, cdk5, cdk4, cdk2, cdc25A and GADD 153. Vitamine D shows impact on p21(Waf1/Cip1) p27 cyclin B

Inhibition of the promotion of hepatocarcinogenesis by 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) by the deletion of the p50 subunit of NF-{kappa}B in mice

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

Glauert, Howard P.; Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40506; Tharappel, Job C.

Polychlorinated biphenyls (PCBs) are persistent and ubiquitous environmental chemicals that bioaccumulate and have hepatic tumor promoting activity in rodents. The present study examined the effect of deleting the p50 subunit of NF-{kappa}B on the hepatic tumor promoting activity of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) in mice. Both wild-type and p50-/- male mice were injected i.p. with diethylnitrosamine (DEN, 90 mg/kg) and then subsequently injected biweekly with 20 i.p. injections of PCB-153 (300 {mu}mol/kg/injection). p50 deletion decreased the tumor incidence in both PCB- and vehicle-treated mice, whereas PCB-153 slightly (P = 0.09) increased the tumor incidence in wild-type and p50-/- mice. PCB-153 increased themore » total tumor volume in both wild-type and p50-/- mice, but the total tumor volume was not affected by p50 deletion in either PCB- or vehicle-treated mice. The volume of tumors that were positive for glutamine synthetase (GS), which is indicative of mutations in the beta-catenin gene, was increased in both wild-type and p50-/- mice administered PCB-153 compared to vehicle controls, and inhibited in p50-/- mice compared to wild-type mice (in both PCB- and vehicle-treated mice). The volume of tumors that were negative for GS was increased in p50-/- mice compared to wild-type mice but was not affected by PCB-153. PCB-153 increased cell proliferation in normal hepatocytes in wild-type but not p50-/- mice; this increase was inhibited in p50-/- mice. In hepatic tumors, the rate of cell proliferation was much higher than in normal hepatocytes, but was not affected by PCB treatment or p50 deletion. The rate of apoptosis, as measured by the TUNEL assay, was not affected by PCB-153 or p50 deletion in normal hepatocytes. In hepatic tumors, the rate of apoptosis was lower than in normal hepatocytes; PCB-153 slightly (P = 0.10) increased apoptosis in p50-/- but not wild-type mice; p50 deletion had no effect. Taken together, these data indicate that

50 CFR 217.153 - Permissible methods of taking.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Permissible methods of taking. 217.153 Section 217.153 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC... Natural Gas Deepwater Port in the Gulf of Mexico § 217.153 Permissible methods of taking. (a) Under LOAs...

46 CFR 153.1025 - Motor fuel antiknock compounds.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Motor fuel antiknock compounds. 153.1025 Section 153... Cargo Procedures § 153.1025 Motor fuel antiknock compounds. (a) No person may load or carry any other cargo in a containment system approved for motor fuel antiknock compounds containing lead alkyls except...

46 CFR 153.1025 - Motor fuel antiknock compounds.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Motor fuel antiknock compounds. 153.1025 Section 153... Cargo Procedures § 153.1025 Motor fuel antiknock compounds. (a) No person may load or carry any other cargo in a containment system approved for motor fuel antiknock compounds containing lead alkyls except...

46 CFR 153.953 - Signals during cargo transfer.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Signals during cargo transfer. 153.953 Section 153.953 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.953 Signals during cargo transfer. The master shall ensure that: (a) The tankship displays a...

46 CFR 153.953 - Signals during cargo transfer.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Signals during cargo transfer. 153.953 Section 153.953 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.953 Signals during cargo transfer. The master shall ensure that: (a) The tankship displays a...

46 CFR 153.1025 - Motor fuel antiknock compounds.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Motor fuel antiknock compounds. 153.1025 Section 153... Cargo Procedures § 153.1025 Motor fuel antiknock compounds. (a) No person may load or carry any other cargo in a containment system approved for motor fuel antiknock compounds containing lead alkyls except...

25 CFR 153.5 - Children of competent Indians.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false Children of competent Indians. 153.5 Section 153.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER DETERMINATION OF COMPETENCY: CROW INDIANS § 153.5 Children of competent Indians. Children of competent Indians who have attained or...

25 CFR 153.5 - Children of competent Indians.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false Children of competent Indians. 153.5 Section 153.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER DETERMINATION OF COMPETENCY: CROW INDIANS § 153.5 Children of competent Indians. Children of competent Indians who have attained or...

25 CFR 153.5 - Children of competent Indians.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false Children of competent Indians. 153.5 Section 153.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER DETERMINATION OF COMPETENCY: CROW INDIANS § 153.5 Children of competent Indians. Children of competent Indians who have attained or...

25 CFR 153.5 - Children of competent Indians.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Children of competent Indians. 153.5 Section 153.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER DETERMINATION OF COMPETENCY: CROW INDIANS § 153.5 Children of competent Indians. Children of competent Indians who have attained or...

46 CFR 153.953 - Signals during cargo transfer.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Signals during cargo transfer. 153.953 Section 153.953 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.953 Signals during cargo transfer. The master shall ensure that: (a) The tankship displays a...

46 CFR 153.953 - Signals during cargo transfer.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Signals during cargo transfer. 153.953 Section 153.953 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.953 Signals during cargo transfer. The master shall ensure that: (a) The tankship displays a...

46 CFR 153.1046 - Sulfuric acid.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Sulfuric acid. 153.1046 Section 153.1046 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK....1046 Sulfuric acid. No person may liquefy frozen or congealed sulfuric acid other than by external tank...

46 CFR 153.1046 - Sulfuric acid.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Sulfuric acid. 153.1046 Section 153.1046 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK....1046 Sulfuric acid. No person may liquefy frozen or congealed sulfuric acid other than by external tank...

46 CFR 153.281 - Piping to independent tanks.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Piping to independent tanks. 153.281 Section 153.281... Systems and Cargo Handling Equipment § 153.281 Piping to independent tanks. Piping for an independent cargo tank must penetrate the tank only through that part of the tank or dome extending above the...

46 CFR 153.281 - Piping to independent tanks.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Piping to independent tanks. 153.281 Section 153.281... Systems and Cargo Handling Equipment § 153.281 Piping to independent tanks. Piping for an independent cargo tank must penetrate the tank only through that part of the tank or dome extending above the...

46 CFR 153.430 - Heat transfer systems; general.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Heat transfer systems; general. 153.430 Section 153.430... Temperature Control Systems § 153.430 Heat transfer systems; general. Each cargo cooling system required by... separated from all other cooling and heating systems; and (c) Allow manual regulation of the system's heat...

46 CFR 153.430 - Heat transfer systems; general.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Heat transfer systems; general. 153.430 Section 153.430... Temperature Control Systems § 153.430 Heat transfer systems; general. Each cargo cooling system required by... separated from all other cooling and heating systems; and (c) Allow manual regulation of the system's heat...

46 CFR 153.430 - Heat transfer systems; general.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Heat transfer systems; general. 153.430 Section 153.430... Temperature Control Systems § 153.430 Heat transfer systems; general. Each cargo cooling system required by... separated from all other cooling and heating systems; and (c) Allow manual regulation of the system's heat...

46 CFR 153.430 - Heat transfer systems; general.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Heat transfer systems; general. 153.430 Section 153.430... Temperature Control Systems § 153.430 Heat transfer systems; general. Each cargo cooling system required by... separated from all other cooling and heating systems; and (c) Allow manual regulation of the system's heat...

46 CFR 153.430 - Heat transfer systems; general.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Heat transfer systems; general. 153.430 Section 153.430... Temperature Control Systems § 153.430 Heat transfer systems; general. Each cargo cooling system required by... separated from all other cooling and heating systems; and (c) Allow manual regulation of the system's heat...

46 CFR 153.216 - Shower and eyewash fountains.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Shower and eyewash fountains. 153.216 Section 153.216... Vessel Requirements § 153.216 Shower and eyewash fountains. (a) Each non-self-propelled ship must have a fixed or portable shower and eyewash fountain that operates during cargo transfer and meets paragraph (c...

46 CFR 153.216 - Shower and eyewash fountains.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Shower and eyewash fountains. 153.216 Section 153.216... Vessel Requirements § 153.216 Shower and eyewash fountains. (a) Each non-self-propelled ship must have a fixed or portable shower and eyewash fountain that operates during cargo transfer and meets paragraph (c...

25 CFR 153.5 - Children of competent Indians.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 1 2012-04-01 2011-04-01 true Children of competent Indians. 153.5 Section 153.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER DETERMINATION OF COMPETENCY: CROW INDIANS § 153.5 Children of competent Indians. Children of competent Indians who have attained or upon...

46 CFR 153.966 - Discharge by liquid displacement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Discharge by liquid displacement. 153.966 Section 153... Transfer Procedures § 153.966 Discharge by liquid displacement. The person in charge of cargo transfer may not authorize cargo discharge by liquid displacement unless the liquid supply line to the tank has: (a...

46 CFR 153.966 - Discharge by liquid displacement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Discharge by liquid displacement. 153.966 Section 153... Transfer Procedures § 153.966 Discharge by liquid displacement. The person in charge of cargo transfer may not authorize cargo discharge by liquid displacement unless the liquid supply line to the tank has: (a...

46 CFR 153.966 - Discharge by liquid displacement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Discharge by liquid displacement. 153.966 Section 153... Transfer Procedures § 153.966 Discharge by liquid displacement. The person in charge of cargo transfer may not authorize cargo discharge by liquid displacement unless the liquid supply line to the tank has: (a...

46 CFR 153.966 - Discharge by liquid displacement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Discharge by liquid displacement. 153.966 Section 153... Transfer Procedures § 153.966 Discharge by liquid displacement. The person in charge of cargo transfer may not authorize cargo discharge by liquid displacement unless the liquid supply line to the tank has: (a...

46 CFR 153.966 - Discharge by liquid displacement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Discharge by liquid displacement. 153.966 Section 153... Transfer Procedures § 153.966 Discharge by liquid displacement. The person in charge of cargo transfer may not authorize cargo discharge by liquid displacement unless the liquid supply line to the tank has: (a...

18 CFR 153.13 - Emergency reconstruction.

Code of Federal Regulations, 2010 CFR

2010-04-01

... loss of gas supply or capacity are applicable to facilities subject to section 3 of the Natural Gas Act... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Emergency reconstruction. 153.13 Section 153.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY...

50 CFR 20.153 - Regulations committee.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Regulations committee. 20.153 Section 20... Regulations § 20.153 Regulations committee. (a) Notice of meetings. Notice of each meeting of the Regulations... meeting of the Regulations Committee for which notice is published pursuant to paragraph (a) of this...

50 CFR 20.153 - Regulations committee.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Regulations committee. 20.153 Section 20... Regulations § 20.153 Regulations committee. (a) Notice of meetings. Notice of each meeting of the Regulations... meeting of the Regulations Committee for which notice is published pursuant to paragraph (a) of this...

24 CFR 850.153 - Rent control.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false Rent control. 850.153 Section 850... PROGRAM) HOUSING DEVELOPMENT GRANTS Project Management § 850.153 Rent control. A project constructed or substantially rehabilitated with a housing development grant is not subject to State or local rent control...

24 CFR 850.153 - Rent control.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false Rent control. 850.153 Section 850... PROGRAM) HOUSING DEVELOPMENT GRANTS Project Management § 850.153 Rent control. A project constructed or substantially rehabilitated with a housing development grant is not subject to State or local rent control...

24 CFR 850.153 - Rent control.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Rent control. 850.153 Section 850... PROGRAM) HOUSING DEVELOPMENT GRANTS Project Management § 850.153 Rent control. A project constructed or substantially rehabilitated with a housing development grant is not subject to State or local rent control...

46 CFR 45.153 - Through-hull piping: General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Through-hull piping: General. 45.153 Section 45.153... Conditions of Assignment § 45.153 Through-hull piping: General. (a) All through-hull pipes required by this subpart must be made of steel or material equivalent to the hull in strength and fatigue resistance. (b...

49 CFR 38.153 - Doors, steps and thresholds.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Doors, steps and thresholds. 38.153 Section 38.153... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Over-the-Road Buses and Systems § 38.153 Doors, steps and thresholds. (a) Floor surfaces on aisles, step treads and areas where wheelchair and mobility aid users are to be...

46 CFR 153.239 - Use of cast iron.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Use of cast iron. 153.239 Section 153.239 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK... Systems § 153.239 Use of cast iron. (a) Cast iron used in a cargo containment system must meet the...

46 CFR 69.153 - Application of other laws.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Application of other laws. 69.153 Section 69.153... MEASUREMENT OF VESSELS Dual Measurement System § 69.153 Application of other laws. (a) If a vessel is assigned... inspection, manning, and load line laws and regulations to the vessel. (b) Tonnage marks are not to be...

46 CFR 69.153 - Application of other laws.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Application of other laws. 69.153 Section 69.153... MEASUREMENT OF VESSELS Dual Measurement System § 69.153 Application of other laws. (a) If a vessel is assigned... inspection, manning, and load line laws and regulations to the vessel. (b) Tonnage marks are not to be...

42 CFR 417.153 - Offer of HMO alternative.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Offer of HMO alternative. 417.153 Section 417.153... § 417.153 Offer of HMO alternative. (a) Basic rule. An employing entity that is subject to this subpart and that elects to include one or more qualified HMOs must offer the HMO alternative in accordance...

37 CFR 41.153 - Records of the Office.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Records of the Office. 41.153 Section 41.153 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE PRACTICE BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES Contested Cases § 41.153 Records of the Office. Certification is not...

Effects of PCB 126 and PCB 153 on secretion of steroid hormones and mRNA expression of steroidogenic genes (STAR, HSD3B, CYP19A1) and estrogen receptors (ERα, ERβ) in prehierarchical chicken ovarian follicles.

PubMed

Sechman, Andrzej; Batoryna, Marta; Antos, Piotr A; Hrabia, Anna

2016-12-15

The objective of this study was to assess the in vitro effects of dioxin-like PCB 126 and non-dioxin-like PCB 153 on basal and ovine LH (oLH)-stimulated testosterone (T) and estradiol (E2) secretion and expression of steroidogenic genes (STAR, HSD3B and CYP19A1) and estrogen receptors α (ERα) and β (ERβ) in white (WF) and yellowish (YF) prehierarchical follicles of the hen ovary. Steroid concentrations in a medium and gene expression in follicles following 6h of exposition were determined by RIA and real-time qPCR, respectively. Both PCBs increased basal and oLH-stimulated T secretion by the WF follicles. PCB 126 reduced basal E2 secretion by the WF follicles. PCB 153 elevated but PCB 126 reduced oLH-stimulated E2 secretion by the prehierarchical follicles. PCB 126 increased basal STAR and HSD3B and reduced CYP19A1 mRNA expression in these follicles. PCB 153 increased basal expression of STAR and HSD3B in YF follicles, but diminished HSD3B mRNA levels in the WF. The studied PCBs had an opposite effect on basal and oLH-stimulated CYP19A1 mRNA expression in prehierarchical follicles. Both PCBs modulated basal and inhibited oLH-stimulated ERα and ERβ gene expression in the prehierarchical follicles. In conclusion, data of the current study demonstrate the congener-specific effects of PCBs on sex steroid secretion by prehierarchical follicles of the chicken ovary, which are at least partly related to STAR, HSD3B and CYP19A1 gene expression. It is suggested that PCBs, by influencing follicular steroidogenesis and expression of estrogen receptors, may impair development and selection of yellowish follicles to the preovulatory hierarchy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways–Novel Insight into the Origins of Enamel Pathologies

PubMed Central

Yin, Kaifeng; Lin, Wenting; Guo, Jing; Sugiyama, Toshihiro; Snead, Malcolm L.; Hacia, Joseph G.; Paine, Michael L.

2017-01-01

Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3′-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI. PMID:28287144

MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways-Novel Insight into the Origins of Enamel Pathologies.

PubMed

Yin, Kaifeng; Lin, Wenting; Guo, Jing; Sugiyama, Toshihiro; Snead, Malcolm L; Hacia, Joseph G; Paine, Michael L

2017-03-13

Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3'-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI.

The development of GADD45α luciferase reporter assays in human cells for assessing the genotoxicity of environmental pollutants.

PubMed

Xin, Lili; Wang, Jianshu; Wu, Yanhu; Guo, Sifan

2015-02-01

In order to assess the potential carcinogenic and genotoxic responses induced by environmental pollutants, genotoxicity test systems based on a GADD45α promoter-driven luciferase reporter in human A549 and HepG2 cells were established. Four different types of environmental toxicants including DNA alkylating agents, precarcinogenic agents, DNA cross-linking agents and non-carcinogenic agents, and three environmental samples collected from a coke oven plant were used to evaluate the test systems. After treated with the tested agents and environmental samples for 12 h, the cell viabilities and luciferase activities of the luciferase reporter cells were determined, respectively. Methyl methanesulfonate, benzo[a]pyrene, formaldehyde and the extractable organic matter (EOM) from coke oven emissions in ambient air generally produced significant induction of relative luciferase activity in a similar dose-dependent manner in A549- and HepG2-luciferase cells. No significant increases in relative luciferase activity were observed in pyrene-treated A549- or HepG2-luciferase cells. Significant increase in relative luciferase activity was already evident after 2.5 µM benzo[a]pyrene, 5 µM formaldehyde, 0.006 µg/L bottom-EOM, 0.10 µg/L side-EOM or 0.06 µg/L top-EOM, where no cytotoxic damage was observed. Compared with the A549-luciferase cells, the tested pollutants produced higher induction of relative luciferase activity in HepG2-luciferase cells. Therefore, the new genotoxicity test systems can detect different types of genotoxic agents and low concentrations of environmental samples. The luciferase reporter cells, especially the HepG2-luciferase cells, could provide a valuable tool for rapid screening of the genotoxic damage of environmental pollutants and their complex mixtures.

The APP intracellular domain (AICD) potentiates ER stress-induced apoptosis.

PubMed

Kögel, Donat; Concannon, Caoimhín G; Müller, Thorsten; König, Hildegard; Bonner, Caroline; Poeschel, Simone; Chang, Steffi; Egensperger, Rupert; Prehn, Jochen H M

2012-09-01

Here we employed human SHEP neuroblastoma cells either stably or inducibly expressing the amyloid precursor protein (APP) intracellular domain (AICD) to investigate its ability to modulate stress-induced cell death. Analysis of effector caspase activation revealed that AICD overexpression was specifically associated with an increased sensitivity to apoptosis induced by the 2 endoplasmic reticulum (ER) stressors thapsigargin and tunicamycin, but not by staurosporine (STS). Basal and ER stress-induced expression of Bip/Grp78 and C/EBP-homologous protein/GADD153 were not altered by AICD implying that AICD potentiated cell death downstream or independent of the conserved unfolded protein response (UPR). Interestingly, quantitative polymerase chain reaction analysis and reporter gene assays revealed that AICD significantly downregulated messenger RNA levels of the Alzheimer's disease susceptibility gene ApoJ/clusterin, indicating transcriptional repression. Knockdown of ApoJ/clusterin mimicked the effect of AICD on ER stress-induced apoptosis, but had no discernible effect on staurosporine-induced cell death. Our data suggest that altered levels of AICD may abolish the prosurvival function of ApoJ/clusterin and increase the susceptibility of neurons to ER stress-mediated cell death, a pathway that may contribute to the pathogenesis of Alzheimer's disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Identification of genes involved in cold-shock response in rainbow trout (Oncorhynchus mykiss).

PubMed

Borchel, Andreas; Verleih, Marieke; Rebl, Alexander; Goldammer, Tom

2017-09-01

A rapid decline in temperature poses a major challenge for poikilothermic fish, as their entire metabolism depends on ambient temperature. The gene expression of rainbow trout Oncorhynchus mykiss having undergone such a cold shock (0◦C) was compared to a control (5◦C) in a microarray and quantitative real-time PCR based study. The tissues of gill, kidney and liver were examined. The most differently expressed genes were found in liver, many of them contributing to the network 'cellular compromise, cellular growth and proliferation'.However, the number of genes found to be regulated at 0◦Cwas surprisingly low. Instead of classical genes involved in temperature shock, the three genes encoding fibroblast growth factor 1 (fgf1), growth arrest and DNA-damageinducible, alpha (gadd45a) and sclerostin domain-containing protein 1 (sostdc1) were upregulated in the liver upon cold shock in two different rainbow trout strains, suggesting that these genes may be considered as general biomarkers for cold shock in rainbow trout.

14 CFR 153.5 - Aviation safety inspector airport access.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Aviation safety inspector airport access. 153.5 Section 153.5 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS AIRPORT OPERATIONS Aviation Safety Inspector Access § 153.5 Aviation safety...

14 CFR 153.5 - Aviation safety inspector airport access.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Aviation safety inspector airport access. 153.5 Section 153.5 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS AIRPORT OPERATIONS Aviation Safety Inspector Access § 153.5 Aviation safety...

14 CFR 153.5 - Aviation safety inspector airport access.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Aviation safety inspector airport access. 153.5 Section 153.5 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS AIRPORT OPERATIONS Aviation Safety Inspector Access § 153.5 Aviation safety...

14 CFR 153.5 - Aviation safety inspector airport access.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Aviation safety inspector airport access. 153.5 Section 153.5 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS AIRPORT OPERATIONS Aviation Safety Inspector Access § 153.5 Aviation safety...

Swift/XRT detection of an outburst from SXP 15.3

NASA Astrophysics Data System (ADS)

Ducci, L.; Romano, P.; Kennea, J. A.; Malacaria, C.; Covino, S.; Santangelo, A.; Evans, P. A.; Coe, M. J.; Townsend, L. J.

2017-12-01

During an observation of the Small Magellanic Cloud (SMC) carried out from December 2nd 2017, 11:12:03 UT to 19:30:52 UT (total exposure time of 7 ks), Swift/XRT detected renewed activity from the Be X-ray binary SXP 15.3.

46 CFR 153.350 - Location of B/3 vent discharges.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Location of B/3 vent discharges. 153.350 Section 153.350 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Venting Systems § 153.350 Location of B/3 vent discharges. Except as prescribed in § 153.353, a B/3...

Evaluation of serum CA27.29, CA15-3 and CEA in patients with breast cancer.

PubMed

Hou, M F; Chen, Y L; Tseng, T F; Lin, C M; Chen, M S; Huang, C J; Huang, Y S; Hsieh, J S; Huang, T J; Jong, S B; Huang, Y F

1999-09-01

The Truquant BR radioimmunoassay (RIA) using monoclonal antibody BR 27.29 to recognize a peptide sequence on the MUC-1 gene product for quantification of the CA 27.29 antigen in serum was used in this report to evaluate in 145 patients with breast cancer and compared the other conventional serum markers such as CA15-3 and CEA. The upper limit of normal (25 u/ml) was determined from CA27.29 values 12.4 +/- 4.1 u/ml (mean +/- 3 S.D.) for 112 female subjects apparently free of disease. The CA15-3 levels above 25 u/ml and CEA levels above 5 ng/ml were considered positive values. Thirty-seven cases of 145 patients studied had elevated CA 27.29 levels (sensitivity: 25.5%), 35 of 145 had positive CA15-3 levels (sensitivity 24.1%) and 27 of 145 patients had positive CEA levels (sensitivity: 18.6%) (p < 0.05). One hundred and ten cases of the breast cancer patients (75.8%) did not have metastatic disease. In this group CA 27.29 sensitivity was 6.4%, while CA15-3 sensitivity was 5.5% and CEA sensitivity was 4.5% (p > 0.05). Mean values were 10.2 +/- 9.2 u/ml for CA 27.29, 14.1 +/- 5.6 u/ml for CA 15-3 and 1.7 +/- 1.5 ng/ml for CEA. Thirty-five patients (24.2%) had metastatic disease. In this group CA 27.29 sensitivity was 85.7%, CA15-3 sensitivity was 82.8% and CEA sensitivity was 62.8% (p < 0.05). Mean values for CA27.29 was 152.6 +/- 131.6 u/ml, CA15-3 was 123.1 +/- 107.6 u/ml and 21.8 +/- 36.9 ng/ml of CEA. With regard to the correlation of three tumor markers with clinical stages, patients had significantly higher levels of CA27.29 than CEA, but they were similar to CA 15-3 in metastatic breast cancer. These results suggest CA27.29 to be more sensitive and specific than CEA, but that it is similar to CA15-3 for metastatic breast cancer detection and monitoring.

Estimated human absorbed dose of a new (153)Sm bone seeking agent based on biodistribution data in mice: Comparison with (153)Sm-EDTMP.

PubMed

Yousefnia, Hassan; Zolghadri, Samaneh

2015-11-01

The main goal in radiotherapy is to deliver the absorbed dose within the target organs in highest possible amount, while the absorbed dose of the other organs, especially the critical organs, should be kept as low as possible. In this work, the absorbed dose to human organs for a new (153)Sm bone-seeking agent was investigated. (153)Sm-(4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid ((153)Sm-BPAMD) complex was successfully prepared. The biodistribution of the complex was investigated in male Syrian mice up to 48 h post injection. The human absorbed dose of the complex was estimated based on the biodistribution data of the mice by radiation absorbed dose assessment resource (RADAR) method. The target to non-target absorbed dose ratios for (153)Sm-BPAMD were compared with these ratios for (153)Sm-EDTMP. The highest absorbed dose for (153)Sm-BPAMD was observed in bone surface with 5.828 mGy/MBq. The dose ratios of the bone surface to the red marrow and to the total body for (153)Sm-BPAMD were 5.3 and 20.0, respectively, while these ratios for (153)Sm-EDTMP were 4.4 and 18.3, respectively. This means, for a given dose to the bone surface as the target organ, the red marrow (as the main critical organ) and the total body would receive lesser absorbed dose in the case of (153)Sm-BPAMD. Generally, the human absorbed dose estimation of (153)Sm-BPAMD indicated that all other tissues approximately received insignificant absorbed dose in comparison with bone surface and therefore can be regarded as a new potential agent for bone pain palliation therapy. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

46 CFR 153.351 - Location of 4m vent discharges.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Location of 4m vent discharges. 153.351 Section 153.351 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Venting Systems § 153.351 Location of 4m vent discharges. Except as prescribed in § 153.353, a 4m venting...

Fisetin Protects PC12 Cells from Tunicamycin-Mediated Cell Death via Reactive Oxygen Species Scavenging and Modulation of Nrf2-Driven Gene Expression, SIRT1 and MAPK Signaling in PC12 Cells

PubMed Central

Yen, Jui-Hung; Wu, Pei-Shan; Chen, Shu-Fen; Wu, Ming-Jiuan

2017-01-01

Background: Fisetin (3,7,3′,4′-tetrahydroxyflavone) is a dietary flavonol and exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However, high concentration of fisetin is reported to produce reactive oxygen species (ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer cells. The aim of this study is to investigate the cytoprotective effects of low concentration of fisetin against tunicamycin (Tm)-mediated cytotoxicity in neuronal-like catecholaminergic PC12 cells. Methods: Cell viability was assayed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and apoptotic and autophagic markers were analyzed by Western blot. Gene expression of unfolded protein response (UPR) and Phase II enzymes was further investigated using RT-Q-PCR or Western blotting. Intracellular ROS level was measured using 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) by a fluorometer. The effects of fisetin on mitogen activated protein kinases (MAPKs) and SIRT1 (Sirtuin 1) signaling pathways were examined using Western blotting and specific inhibitors. Results: Fisetin (<20 µM) restored cell viability and repressed apoptosis, autophagy and ROS production in Tm-treated cells. Fisetin attenuated Tm-mediated expression of ER stress genes, such as glucose-regulated proteins 78 (GRP78), C/EBP homologous protein (CHOP also known as GADD153) and Tribbles homolog 3 (TRB3), but induced the expression of nuclear E2 related factor (Nrf)2-targeted heme oxygenase (HO)-1, glutamate cysteine ligase (GCL) and cystine/glutamate transporter (xCT/SLC7A11), in both the presence and absence of Tm. Moreover, fisetin enhanced phosphorylation of ERK (extracellular signal-regulated kinase), JNK (c-JUN NH2-terminal protein kinase), and p38 MAPK. Addition of JNK and p38 MAPK inhibitor significantly antagonized its cytoprotective activity and modulatory effects on UPR. Fisetin also restored Tm-inhibited SIRT1 expression and addition of

18 CFR 153.16 - Contents of application.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... 153.16 Section 153.16 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER NATURAL GAS ACT APPLICATIONS FOR AUTHORIZATION TO CONSTRUCT, OPERATE... proposing to amend the article(s) of an existing Presidential Permit (other than facilities aspects) must...

18 CFR 153.16 - Contents of application.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... 153.16 Section 153.16 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER NATURAL GAS ACT APPLICATIONS FOR AUTHORIZATION TO CONSTRUCT, OPERATE... proposing to amend the article(s) of an existing Presidential Permit (other than facilities aspects) must...

46 CFR 153.970 - Cargo transfer piping.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo transfer piping. 153.970 Section 153.970 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Cargo Transfer Procedures...

46 CFR 153.970 - Cargo transfer piping.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo transfer piping. 153.970 Section 153.970 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Cargo Transfer Procedures...

46 CFR 153.1020 - Unusually toxic cargoes.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Unusually toxic cargoes. 153.1020 Section 153.1020 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo...

46 CFR 153.1020 - Unusually toxic cargoes.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Unusually toxic cargoes. 153.1020 Section 153.1020 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo...

46 CFR 153.968 - Cargo transfer conference.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo transfer conference. 153.968 Section 153.968 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Cargo Transfer...

46 CFR 153.1065 - Sodium chlorate solutions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Sodium chlorate solutions. 153.1065 Section 153.1065 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo...

46 CFR 153.1020 - Unusually toxic cargoes.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Unusually toxic cargoes. 153.1020 Section 153.1020 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo...

46 CFR 153.968 - Cargo transfer conference.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo transfer conference. 153.968 Section 153.968 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Cargo Transfer...

46 CFR 153.970 - Cargo transfer piping.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo transfer piping. 153.970 Section 153.970 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Cargo Transfer Procedures...

46 CFR 153.1020 - Unusually toxic cargoes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Unusually toxic cargoes. 153.1020 Section 153.1020 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo...

46 CFR 153.1065 - Sodium chlorate solutions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Sodium chlorate solutions. 153.1065 Section 153.1065 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo...

46 CFR 153.968 - Cargo transfer conference.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo transfer conference. 153.968 Section 153.968 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Cargo Transfer...

46 CFR 153.1020 - Unusually toxic cargoes.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Unusually toxic cargoes. 153.1020 Section 153.1020 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo...

46 CFR 153.968 - Cargo transfer conference.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo transfer conference. 153.968 Section 153.968 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Cargo Transfer...

46 CFR 153.970 - Cargo transfer piping.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo transfer piping. 153.970 Section 153.970 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Cargo Transfer Procedures...

46 CFR 153.970 - Cargo transfer piping.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo transfer piping. 153.970 Section 153.970 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Cargo Transfer Procedures...

Expression of genes associated with stress conditions by Listeria monocytogenes in interaction with nisin producer Lactococcus lactis.

PubMed

Miranda, Rodrigo Otávio; Campos-Galvão, Maria Emilene Martino; Nero, Luís Augusto

2018-03-01

The use of nisin producers in foods is considered a mitigation strategy to control foodborne pathogens growth, such as Listeria monocytogenes, due to the production of this bacteriocin in situ. However, when the bacteriocin does not reach an adequate concentration, the target bacteria can develop a cross-response to different stress conditions in food, such as acid, thermal and osmotic. This study aimed to evaluate the interaction of a nisin-producing strain of Lactococcus lactis DY-13 and L. monocytogenes in BHI and skim milk, and its influence on general (sigB), acid (gadD2), thermal (groEL) and osmotic (gbu) stress-related genes of the pathogen. L. monocytogenes populations decreased approximately 2log in BHI and 1log in milk after 24h in co-culture with the nisin producer L. lactis, coherent with the increasing expression of nisK. Expression of stress-related genes by L. monocytogenes presented lower oscillation in BHI than in milk, indicating its better ability to survive in milk, despite the higher nisin production. Stress-related genes presented a varied expression by L. monocytogenes in the tested conditions: sigB expression remained stable or reduced over time; gadD2 presented high expression in milk; groEL presented low expression in BHI when compared to milk, trending to decrease overtime; gbu expression in milk after 24h was lower than in BHI. The presented study demonstrated the growth of a nisin producer L. lactis can affect the expression of stress-related genes by L. monocytogenes, and understating these mechanisms is crucial to enhance the conservation methods employed in foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hydrogen Peroxide responsive miR153 targets Nrf2/ARE cytoprotection in paraquat induced dopaminergic neurotoxicitya

PubMed Central

Narasimhan, Madhusudhanan; Riar, Amanjot Kaur; Rathinam, Mary Latha; Vedpathak, Dhanashree; Henderson, George; Mahimainathan, Lenin

2014-01-01

Epidemiological and animal studies suggest that environmental toxins including paraquat (PQ) increase the risk of developing Parkinson's disease (PD) by damaging nigrostriatal dopaminergic neurons. We previously showed that overexpression of a group of microRNAs (miRs) affects the antioxidant promoting factor, Nrf2 and related glutathione-redox homeostasis in SH-SY5Y dopaminergic neurons. Although, dysregulation of redox balance by PQ is well documented, the role for miRs and their impact have not been elucidated. In the current study we investigated whether PQ impairs Nrf2 and its related cytoprotective machinery by misexpression of specific fine tune miRs in SH-SY5Y neurons. Real time PCR analysis revealed that PQ significantly (p<0.05) increased the expression of brain enriched miR153 with an associated decrease in Nrf2 and its function as revealed by decrease in 4× ARE activity and expression of GCLC and NQO1. Also, PQ and H2O2-induced decrease in Nrf2 3′ UTR activity was restored on miR153 site mutation suggesting a 3′ UTR interacting role. Overexpression of either anti-miR153 or Nrf2 cDNA devoid of 3′ UTR prevented PQ and H2O2-induced loss in Nrf2 activity confirming that PQ could cause miR153 to bind to and target Nrf2 3′ UTR thereby weakening the cellular antioxidant defense. Adenovirus mediated overexpression of cytoplasmic catalase (Ad cCAT) confirmed that PQ induced miR153 is hydrogen peroxide (H2O2) dependent. In addition, Ad cCAT significantly (p<0.05) negated the PQ induced dysregulation of Nrf2 and function along with minimizing ROS, caspase 3/7 activation and neuronal death. Altogether, these results suggest a critical role for oxidant mediated miR153-Nrf2/ARE pathway interaction in paraquat neurotoxicity. This novel finding facilitates the understanding of molecular mechanisms and to develop appropriate management alternatives to counteract PQ-induced neuronal pathogenesis. PMID:24866057

46 CFR 153.333 - Cargo pump discharge pressure gauge.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo pump discharge pressure gauge. 153.333 Section 153... SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Pumprooms § 153.333 Cargo pump discharge pressure gauge. Each cargo pump within a pump-room must...

46 CFR 153.285 - Valving for cargo pump manifolds.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Valving for cargo pump manifolds. 153.285 Section 153... SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Piping Systems and Cargo Handling Equipment § 153.285 Valving for cargo pump manifolds. (a) When cargo...

46 CFR 153.333 - Cargo pump discharge pressure gauge.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo pump discharge pressure gauge. 153.333 Section 153... SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Pumprooms § 153.333 Cargo pump discharge pressure gauge. Each cargo pump within a pump-room must...

46 CFR 153.333 - Cargo pump discharge pressure gauge.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo pump discharge pressure gauge. 153.333 Section 153... SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Pumprooms § 153.333 Cargo pump discharge pressure gauge. Each cargo pump within a pump-room must...

46 CFR 153.333 - Cargo pump discharge pressure gauge.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo pump discharge pressure gauge. 153.333 Section 153... SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Pumprooms § 153.333 Cargo pump discharge pressure gauge. Each cargo pump within a pump-room must...

46 CFR 153.333 - Cargo pump discharge pressure gauge.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo pump discharge pressure gauge. 153.333 Section 153... SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Pumprooms § 153.333 Cargo pump discharge pressure gauge. Each cargo pump within a pump-room must...

29 CFR 780.153 - Delivery “to storage.”

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 3 2012-07-01 2012-07-01 false Delivery âto storage.â 780.153 Section 780.153 Labor... of Agriculture Specified Delivery Operations § 780.153 Delivery “to storage.” The term “delivery to storage” includes taking agricultural or horticultural commodities, dairy products, livestock, bees or...

29 CFR 780.153 - Delivery “to storage.”

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 3 2011-07-01 2011-07-01 false Delivery âto storage.â 780.153 Section 780.153 Labor... of Agriculture Specified Delivery Operations § 780.153 Delivery “to storage.” The term “delivery to storage” includes taking agricultural or horticultural commodities, dairy products, livestock, bees or...

29 CFR 780.153 - Delivery “to storage.”

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 3 2013-07-01 2013-07-01 false Delivery âto storage.â 780.153 Section 780.153 Labor... of Agriculture Specified Delivery Operations § 780.153 Delivery “to storage.” The term “delivery to storage” includes taking agricultural or horticultural commodities, dairy products, livestock, bees or...

29 CFR 780.153 - Delivery “to storage.”

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 3 2014-07-01 2014-07-01 false Delivery âto storage.â 780.153 Section 780.153 Labor... of Agriculture Specified Delivery Operations § 780.153 Delivery “to storage.” The term “delivery to storage” includes taking agricultural or horticultural commodities, dairy products, livestock, bees or...

45 CFR 153.310 - Risk adjustment administration.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Risk adjustment administration. 153.310 Section 153.310 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE...

45 CFR 153.400 - Reinsurance contribution funds.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Reinsurance contribution funds. 153.400 Section 153.400 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE...

45 CFR 153.310 - Risk adjustment administration.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Risk adjustment administration. 153.310 Section 153.310 Public Welfare Department of Health and Human Services REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE...

45 CFR 153.310 - Risk adjustment administration.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Risk adjustment administration. 153.310 Section 153.310 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE...

46 CFR 153.520 - Special requirements for carbon disulfide.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Special requirements for carbon disulfide. 153.520 Section 153.520 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Special Requirements § 153.520 Special...

46 CFR 153.520 - Special requirements for carbon disulfide.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Special requirements for carbon disulfide. 153.520 Section 153.520 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Special Requirements § 153.520 Special...

46 CFR 153.520 - Special requirements for carbon disulfide.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Special requirements for carbon disulfide. 153.520 Section 153.520 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Special Requirements § 153.520 Special...

14 CFR 23.153 - Control during landings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Control during landings. 23.153 Section 23.153 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... safely complete a landing without exceeding the one-hand control force limits specified in § 23.143(c...

14 CFR 23.153 - Control during landings.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Control during landings. 23.153 Section 23.153 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... safely complete a landing without exceeding the one-hand control force limits specified in § 23.143(c...

14 CFR 23.153 - Control during landings.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Control during landings. 23.153 Section 23.153 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... safely complete a landing without exceeding the one-hand control force limits specified in § 23.143(c...

14 CFR 23.153 - Control during landings.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Control during landings. 23.153 Section 23.153 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... safely complete a landing without exceeding the one-hand control force limits specified in § 23.143(c...

14 CFR 23.153 - Control during landings.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Control during landings. 23.153 Section 23.153 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... safely complete a landing without exceeding the one-hand control force limits specified in § 23.143(c...

34 CFR 300.153 - Filing a complaint.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 2 2011-07-01 2010-07-01 true Filing a complaint. 300.153 Section 300.153 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION OF CHILDREN WITH...

18 CFR 153.21 - Conformity with requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Energy Projects may reject the application within 10 days of filing as provided by § 385.2001(b) of this... requirements. 153.21 Section 153.21 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER NATURAL GAS ACT APPLICATIONS FOR AUTHORIZATION TO...

18 CFR 153.21 - Conformity with requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Energy Projects may reject the application within 10 days of filing as provided by § 385.2001(b) of this... requirements. 153.21 Section 153.21 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER NATURAL GAS ACT APPLICATIONS FOR AUTHORIZATION TO...

18 CFR 153.21 - Conformity with requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Energy Projects may reject the application within 10 days of filing as provided by § 385.2001(b) of this... requirements. 153.21 Section 153.21 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER NATURAL GAS ACT APPLICATIONS FOR AUTHORIZATION TO...

40 CFR 153.155 - Seed treatment products.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Seed treatment products. 153.155... REGISTRATION POLICIES AND INTERPRETATIONS Coloration and Discoloration of Pesticides § 153.155 Seed treatment products. (a) Pesticide products intended for use in treating seeds must contain an EPA-approved dye to...

40 CFR 153.155 - Seed treatment products.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Seed treatment products. 153.155... REGISTRATION POLICIES AND INTERPRETATIONS Coloration and Discoloration of Pesticides § 153.155 Seed treatment products. (a) Pesticide products intended for use in treating seeds must contain an EPA-approved dye to...

46 CFR 153.968 - Cargo transfer conference.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo transfer conference. 153.968 Section 153.968 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... the facility. (b) The person in charge of cargo transfer shall discuss the important aspects of the...

46 CFR 153.334 - Bilge pumping systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

... pumping system must have: (1) Complete remote operating controls outside the cargo pumproom; and (2) An... 46 Shipping 5 2010-10-01 2010-10-01 false Bilge pumping systems. 153.334 Section 153.334 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING...

14 CFR 121.153 - Aircraft requirements: General.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Aircraft requirements: General. 121.153... REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Aircraft Requirements § 121.153 Aircraft requirements... aircraft unless that aircraft— (1) Is registered as a civil aircraft of the United States and carries an...

14 CFR 121.153 - Aircraft requirements: General.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Aircraft requirements: General. 121.153... REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Aircraft Requirements § 121.153 Aircraft requirements... aircraft unless that aircraft— (1) Is registered as a civil aircraft of the United States and carries an...

14 CFR 121.153 - Aircraft requirements: General.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Aircraft requirements: General. 121.153... REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Aircraft Requirements § 121.153 Aircraft requirements... aircraft unless that aircraft— (1) Is registered as a civil aircraft of the United States and carries an...

14 CFR 121.153 - Aircraft requirements: General.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Aircraft requirements: General. 121.153... REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Aircraft Requirements § 121.153 Aircraft requirements... aircraft unless that aircraft— (1) Is registered as a civil aircraft of the United States and carries an...

Double blind glucocorticoid controlled trial of samarium-153 particulate hydroxyapatite radiation synovectomy for chronic knee synovitis.

PubMed

O'Duffy, E K; Clunie, G P; Lui, D; Edwards, J C; Ell, P J

1999-09-01

Samarium-153 particulate hydroxyapatite (Sm-153 PHYP) is a relatively new radiation synovectomy agent developed for the treatment of chronic synovitis. Although it has been shown that the levels of unwanted extra-articular radiation are lower after intra-articular injection of Sm-153 PHYP than yttrium-90 colloid, its clinical efficacy has not been rigorously studied. To establish whether Sm-153 PHYP radiation synovectomy results in a clinically useful benefit sustained at one year. In a randomised double blind study, patients received either intra-articular 40 mg triamcinolone hexacetonide alone or 40 mg triamcinolone hexacetonide combined with Sm-153 PHYP in an outpatient clinic. Sixty patients (28 male, 32 female), median age 51 (18-75) with chronic knee synovitis were studied. Diagnoses included: rheumatoid arthritis (n=29); psoriatic arthritis (n=9); ankylosing spondylitis (n=3); reactive arthritis (n=2); undifferentiated seronegative oligoarthritis (n=13) and miscellaneous inflammatory conditions (n=4). More patients who received Sm-153 PHYP/triamcinolone hexacetonide sustained clinical benefit a year after treatment compared with patients who received corticosteroid alone (12 of 31 (39%) v 6 of 29 (21%), a difference of 18% more patients (95% CI -5% to 41%)) though the difference was not significant (chi(2)=2.31, 0.2>p>0.1, n=60). Despite the variation in injected activity (median 563 MBq, range 218-840 MBq), there was no obvious relation between low levels of injected activity (<555 MBq) and relapse within 12 months of treatment (chi(2) =2.61, 0.2>p>0.1, n=31). There was no clear beneficial clinical effect of combined Sm-153 PHYP/triamcinolone hexacetonide injection over triamcinolone hexacetonide alone a year after treatment for chronic knee synovitis.

Double blind glucocorticoid controlled trial of samarium-153 particulate hydroxyapatite radiation synovectomy for chronic knee synovitis

PubMed Central

O'Duffy, E; Clunie, G; Lui, D; Edwards, J; Ell, P

1999-01-01

BACKGROUND—Samarium-153 particulate hydroxyapatite (Sm-153 PHYP) is a relatively new radiation synovectomy agent developed for the treatment of chronic synovitis. Although it has been shown that the levels of unwanted extra-articular radiation are lower after intra-articular injection of Sm-153 PHYP than yttrium-90 colloid, its clinical efficacy has not been rigorously studied.
OBJECTIVES—To establish whether Sm-153 PHYP radiation synovectomy results in a clinically useful benefit sustained at one year.
METHODS—In a randomised double blind study, patients received either intra-articular 40 mg triamcinolone hexacetonide alone or 40 mg triamcinolone hexacetonide combined with Sm-153 PHYP in an outpatient clinic.
RESULTS—Sixty patients (28 male, 32 female), median age 51 (18-75) with chronic knee synovitis were studied. Diagnoses included: rheumatoid arthritis (n=29); psoriatic arthritis (n=9); ankylosing spondylitis (n=3); reactive arthritis (n=2); undifferentiated seronegative oligoarthritis (n=13) and miscellaneous inflammatory conditions (n=4). More patients who received Sm-153 PHYP/triamcinolone hexacetonide sustained clinical benefit a year after treatment compared with patients who received corticosteroid alone (12 of 31 (39%) v 6 of 29 (21%), a difference of 18% more patients (95% CI −5% to 41%)) though the difference was not significant (χ2=2.31, 0.2>p>0.1, n=60). Despite the variation in injected activity (median 563 MBq, range 218-840 MBq), there was no obvious relation between low levels of injected activity (<555 MBq) and relapse within 12 months of treatment (χ2 =2.61, 0.2>p>0.1, n=31).
CONCLUSIONS—There was no clear beneficial clinical effect of combined Sm-153 PHYP/triamcinolone hexacetonide injection over triamcinolone hexacetonide alone a year after treatment for chronic knee synovitis.

 PMID:10460188

46 CFR 153.955 - Warning signs during cargo transfer.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Warning signs during cargo transfer. 153.955 Section 153... Transfer Procedures § 153.955 Warning signs during cargo transfer. (a) When transferring cargo while fast to a dock or at anchor in port, the master shall ensure that the tankship displays a warning sign at...

46 CFR 153.955 - Warning signs during cargo transfer.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Warning signs during cargo transfer. 153.955 Section 153... Transfer Procedures § 153.955 Warning signs during cargo transfer. (a) When transferring cargo while fast to a dock or at anchor in port, the master shall ensure that the tankship displays a warning sign at...

46 CFR 153.955 - Warning signs during cargo transfer.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Warning signs during cargo transfer. 153.955 Section 153... Transfer Procedures § 153.955 Warning signs during cargo transfer. (a) When transferring cargo while fast to a dock or at anchor in port, the master shall ensure that the tankship displays a warning sign at...

46 CFR 153.955 - Warning signs during cargo transfer.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Warning signs during cargo transfer. 153.955 Section 153... Transfer Procedures § 153.955 Warning signs during cargo transfer. (a) When transferring cargo while fast to a dock or at anchor in port, the master shall ensure that the tankship displays a warning sign at...

46 CFR 153.955 - Warning signs during cargo transfer.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Warning signs during cargo transfer. 153.955 Section 153... Transfer Procedures § 153.955 Warning signs during cargo transfer. (a) When transferring cargo while fast to a dock or at anchor in port, the master shall ensure that the tankship displays a warning sign at...

46 CFR 153.935a - Storage of cargo samples.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Storage of cargo samples. 153.935a Section 153.935a Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... § 153.935a Storage of cargo samples. (a) The master shall make sure that any cargo samples are stored in...

27 CFR 6.153 - Criteria for determining retailer independence.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Criteria for determining retailer independence. 6.153 Section 6.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Exclusion § 6.153 Criteria for determining retailer independence. The criteria...

An electrochemical approach for removal of radionuclidic contaminants of Eu from 153Sm for effective use in metastatic bone pain palliation.

PubMed

Chakravarty, Rubel; Chakraborty, Sudipta; Khan, Mohammed Sahiralam; Ram, Ramu; Sarma, Haladhar Dev; Dash, Ashutosh

2018-03-01

Thermal neutron activation of 152 Sm [ 152 Sm(n,γ) 153 Sm] using natural or isotopically enriched (by 152 Sm) samarium target is the established route for production of 153 Sm used for preparation of 153 Sm-EDTMP for pain palliation in cancer patients with disseminated bone metastases. However, some long-lived radionuclidic contaminants of Eu, such as, 154 Eu (t ½ =8.6y) are also produced during the target activation process. This leads to detectable amount of Eu radionuclidic contaminants in patients' skeleton even years after administration with therapeutic doses of 153 Sm-EDTMP. Further, the presence of such contaminants in 153 Sm raises concerns related to radioactive waste management. The aim of the present study was to develop and demonstrate a viable method for large-scale purification of 153 Sm from radionuclidic contaminants of Eu. A radiochemical separation procedure adopting electroamalgamation approach has been critically evaluated. The influence of different experimental parameters for the quantitative removal radionuclidic contaminants of Eu from 153 Sm was investigated and optimized. The effectiveness of the method was demonstrated by purification of ~37 GBq of 153 Sm in several batches. As a proof of concept, 153 Sm-EDTMP was administered in normal Wistar rats and ex vivo γ-spectrometry of bone samples were carried out. After carrying out the electrolysis under the optimized conditions, the radionuclidic contaminants of Eu could not be detected in purified 153 Sm solution by γ-spectrometry. The overall yield of 153 Sm obtained after the purification process was >85%. The reliability of this approach was amply demonstrated in several batches, wherein the performance remained consistent. Ex vivo γ-spectrometry of bone samples of Wistar rats administered with 153 Sm-EDTMP (prepared using electrochemically purified 153 Sm) did not show photo peaks corresponding to radionuclidic contaminants of Eu. A viable electrochemical strategy for the large

25 CFR 153.1 - Purpose of regulations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Purpose of regulations. 153.1 Section 153.1 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER DETERMINATION OF COMPETENCY: CROW... the competency of Crow Indians under Public Law 303, 81st Congress, approved September 8, 1949. ...

Inhibition of microRNA-153 protects neurons against ischemia/reperfusion injury in an oxygen-glucose deprivation and reoxygenation cellular model by regulating Nrf2/HO-1 signaling.

PubMed

Ji, Qiong; Gao, Jianbo; Zheng, Yan; Liu, Xueli; Zhou, Qiangqiang; Shi, Canxia; Yao, Meng; Chen, Xia

2017-07-01

MicroRNAs are emerging as critical regulators in cerebral ischemia/reperfusion injury; however, their exact roles remain poorly understood. miR-153 is reported to be a neuron-related miRNA involved in neuroprotection. In this study, we aimed to investigate the precise role of miR-153 in regulating neuron survival during cerebral ischemia/reperfusion injury using an oxygen-glucose deprivation and reoxygenation (OGD/R) cellular model. We found that miR-153 was significantly upregulated in neurons subjected to OGD/R treatment. Inhibition of miR-153 significantly attenuated OGD/R-induced injury and oxidative stress in neurons. Nuclear factor erythroid 2-related factor 2 (Nrf2) was identified as a target gene of miR-153. Inhibition of miR-153 significantly promoted the expression of Nrf2 and heme oxygenase-1 (HO-1). However, silencing of Nrf2 significantly blocked the protective effects of miR-153 inhibition. Our study indicates that the inhibition of miR-153 protects neurons against OGD/R-induced injury by regulating Nrf2/HO-1 signaling and suggests a potential therapeutic target for cerebral ischemia/reperfusion injury. © 2017 Wiley Periodicals, Inc.

38 CFR 17.153 - Training in the use of appliances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... appliances. 17.153 Section 17.153 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Prosthetic, Sensory, and Rehabilitative Aids § 17.153 Training in the use of appliances. Beneficiaries supplied prosthetic and similar appliances will be additionally entitled to fitting and training...

Global gene expression and Ingenuity biological functions analysis on PCBs 153 and 138 induced human PBMC in vitro reveals differential mode(s) of action in developing toxicities.

PubMed

Ghosh, Somiranjan; Zang, Shizhu; Mitra, Partha S; Ghimbovschi, Svetlana; Hoffman, Eric P; Dutta, Sisir K

2011-07-01

Several reports have indicated that low level of polychlorinated biphenyl (PCB) exposure can adversely affect a multitude of physiological disorders and diseases in in vitro, in vivo, and as reported in epidemiological studies. This investigation is focused on the possible contribution of two most prevalent PCB congeners in vitro in developing toxicities. We used PCBs 138 and 153 at the human equivalence level as model agents to test their specificity in developing toxicities. We chose a global approach using oligonucleotide microarray technology to investigate modulated gene expression for biological effects, upon exposure of PCBs, followed by Ingenuity Pathway Analysis (IPA), to understand the underlying consequence in developing disease and disorders. We performed in vitro studies with human peripheral blood mononuclear cells (PBMC), where PBMC cells were exposed to respective PCBs for 48 h. Overall, our observation on gene expression indicated that PCB produces a unique signature affecting different pathways, specific for each congener. While analyzing these data through IPA, the prominent and interesting disease and disorders were neurological disease, cancer, cardiovascular disease, respiratory disease, as well as endocrine system disorders, genetic disorders, and reproductive system disease. They showed strong resemblances with in vitro, in vivo, and in the epidemiological studies. A distinct difference was observed in renal and urological diseases, organisimal injury and abnormalities, dental disease, ophthalmic disease, and psychological disorders, which are only revealed by PCB 138 exposure, but not in PCB 153. The present study emphasizes the challenges of global gene expression in vitro and was correlated with the results of exposed human population. The microarray results give a molecular mechanistic insight and functional effects, following PCB exposure. The extent of changes in genes related to several possible mode(s) of action highlights the

Genotoxicity and induction of DNA damage responsive genes by food-borne heterocyclic aromatic amines in human hepatoma HepG2 cells.

PubMed

Pezdirc, Marko; Žegura, Bojana; Filipič, Metka

2013-09-01

Heterocyclic aromatic amines (HAAs) are potential human carcinogens formed in well-done meats and fish. The most abundant are 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-Amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx) and 2-Amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ). HAAs exert genotoxic activity after metabolic transformation by CYP1A enzymes, that is well characterized, however the genomic and intervening responses are not well explored. We have examined cellular and genomic responses of human hepatoma HepG2 cells after 24h exposure to HAAs. Comet assay revealed increase in formation of DNA strand breaks by PhIP, MeIQx and IQ but not 4,8-DiMeIQx, whereas increased formation of micronuclei was not observed. The four HAAs up-regulated expression of genes encoding metabolic enzymes CYP1A1, CYP1A2 and UGT1A1 and expression of TP53 and its downstream regulated genes CDKN1A, GADD45α and BAX. Consistent with the up-regulation of CDKN1A and GADD45α the cell-cycle analysis showed arrest in S-phase by PhIP and IQ, and in G1-phase by 4,8-DiMeIQx and MeIQx. The results indicate that upon exposure to HAAs the cells respond with the cell-cycle arrest, which enables cells to repair the damage or eliminate them by apoptosis. However, elevated expression of BCL2 and down-regulation of BAX may indicate that HAAs could suppress apoptosis meaning higher probability of damaged cells to survive and mutate. Copyright © 2013 Elsevier Ltd. All rights reserved.

46 CFR 153.284 - Characteristics of required quick closing valves.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Characteristics of required quick closing valves. 153.284 Section 153.284 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK... and Equipment Piping Systems and Cargo Handling Equipment § 153.284 Characteristics of required quick...

46 CFR 153.284 - Characteristics of required quick closing valves.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Characteristics of required quick closing valves. 153.284 Section 153.284 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK... and Equipment Piping Systems and Cargo Handling Equipment § 153.284 Characteristics of required quick...

45 CFR 153.510 - Risk corridors establishment and payment methodology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... methodology. 153.510 Section 153.510 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT Health Insurance Issuer Standards Related to the Risk Corridors Program § 153...

45 CFR 153.510 - Risk corridors establishment and payment methodology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... methodology. 153.510 Section 153.510 Public Welfare Department of Health and Human Services REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT Health Insurance Issuer Standards Related to the Risk Corridors Program § 153...

7 CFR 701.153 - Debris removal and water for livestock.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 7 2011-01-01 2011-01-01 false Debris removal and water for livestock. 701.153 Section 701.153 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY... Conservation Program § 701.153 Debris removal and water for livestock. Subject to the other eligibility...

7 CFR 767.153 - Sale of real estate inventory property.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 7 2012-01-01 2012-01-01 false Sale of real estate inventory property. 767.153 Section 767.153 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY....153 Sale of real estate inventory property. (a) Pricing. (1) The Agency will advertise property for...

7 CFR 767.153 - Sale of real estate inventory property.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 7 2013-01-01 2013-01-01 false Sale of real estate inventory property. 767.153 Section 767.153 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY....153 Sale of real estate inventory property. (a) Pricing. (1) The Agency will advertise property for...

7 CFR 767.153 - Sale of real estate inventory property.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 7 2014-01-01 2014-01-01 false Sale of real estate inventory property. 767.153 Section 767.153 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY....153 Sale of real estate inventory property. (a) Pricing. (1) The Agency will advertise property for...

7 CFR 767.153 - Sale of real estate inventory property.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 7 2011-01-01 2011-01-01 false Sale of real estate inventory property. 767.153 Section 767.153 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY....153 Sale of real estate inventory property. (a) Pricing. (1) The Agency will advertise property for...

7 CFR 767.153 - Sale of real estate inventory property.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Sale of real estate inventory property. 767.153 Section 767.153 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY....153 Sale of real estate inventory property. (a) Pricing. (1) The Agency will advertise property for...

46 CFR 153.16 - Requirements for foreign flag vessel permits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Requirements for foreign flag vessel permits. 153.16 Section 153.16 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.16...

46 CFR 153.16 - Requirements for foreign flag vessel permits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Requirements for foreign flag vessel permits. 153.16 Section 153.16 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.16...

46 CFR 153.16 - Requirements for foreign flag vessel permits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Requirements for foreign flag vessel permits. 153.16 Section 153.16 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.16...

46 CFR 153.16 - Requirements for foreign flag vessel permits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Requirements for foreign flag vessel permits. 153.16 Section 153.16 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.16...

46 CFR 153.16 - Requirements for foreign flag vessel permits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Requirements for foreign flag vessel permits. 153.16 Section 153.16 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS General § 153.16...

10 CFR 455.153 - Review by the Deputy Assistant Secretary.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 3 2010-01-01 2010-01-01 false Review by the Deputy Assistant Secretary. 455.153 Section 455.153 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION GRANT PROGRAMS FOR SCHOOLS AND HOSPITALS AND BUILDINGS OWNED BY UNITS OF LOCAL GOVERNMENT AND PUBLIC CARE INSTITUTIONS Administrative Review § 455.153...

45 CFR 153.530 - Risk corridors data requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 153.530 Public Welfare Department of Health and Human Services REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT Health Insurance Issuer Standards Related to the Risk Corridors Program § 153.530 Risk corridors...

45 CFR 153.530 - Risk corridors data requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 153.530 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT Health Insurance Issuer Standards Related to the Risk Corridors Program § 153.530 Risk corridors...

45 CFR 153.530 - Risk corridors data requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 153.530 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS STANDARDS RELATED TO REINSURANCE, RISK CORRIDORS, AND RISK ADJUSTMENT UNDER THE AFFORDABLE CARE ACT Health Insurance Issuer Standards Related to the Risk Corridors Program § 153.530 Risk corridors...

46 CFR 153.1004 - Inhibited and stabilized cargoes.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Inhibited and stabilized cargoes. 153.1004 Section 153.1004 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special...

46 CFR 153.964 - Discharge by gas pressurization.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Discharge by gas pressurization. 153.964 Section 153.964 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Cargo Transfer...

46 CFR 153.972 - Connecting a cargo hose.

Code of Federal Regulations, 2013 CFR