Novel mutation in forkhead box G1 (FOXG1) gene in an Indian patient with Rett syndrome.

PubMed

Das, Dhanjit Kumar; Jadhav, Vaishali; Ghattargi, Vikas C; Udani, Vrajesh

2014-03-15

Rett syndrome (RTT) is a severe neurodevelopmental disorder characterized by the progressive loss of intellectual functioning, fine and gross motor skills and communicative abilities, deceleration of head growth, and the development of stereotypic hand movements, occurring after a period of normal development. The classic form of RTT involves mutation in MECP2 while the involvement of CDKL5 and FOXG1 genes has been identified in atypical RTT phenotype. FOXG1 gene encodes for a fork-head box protein G1, a transcription factor acting primarily as transcriptional repressor through DNA binding in the embryonic telencephalon as well as a number of other neurodevelopmental processes. In this report we have described the molecular analysis of FOXG1 gene in Indian patients with Rett syndrome. FOXG1 gene mutation analysis was done in a cohort of 34 MECP2/CDKL5 mutation negative RTT patients. We have identified a novel mutation (p. D263VfsX190) in FOXG1 gene in a patient with congenital variant of Rett syndrome. This mutation resulted into a frameshift, thereby causing an alteration in the reading frames of the entire coding sequence downstream of the mutation. The start position of the frameshift (Asp263) and amino acid towards the carboxyl terminal end of the protein was found to be well conserved across species using multiple sequence alignment. Since the mutation is located at forkhead binding domain, the resultant mutation disrupts the secondary structure of the protein making it non-functional. This is the first report from India showing mutation in FOXG1 gene in Rett syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

Insulin Is Required to Maintain Albumin Expression by Inhibiting Forkhead Box O1 Protein*

PubMed Central

Chen, Qing; Lu, Mingjian; Monks, Bobby R.; Birnbaum, Morris J.

2016-01-01

Diabetes is accompanied by dysregulation of glucose, lipid, and protein metabolism. In recent years, much effort has been spent on understanding how insulin regulates glucose and lipid metabolism, whereas the effect of insulin on protein metabolism has received less attention. In diabetes, hepatic production of serum albumin decreases, and it has been long established that insulin positively controls albumin gene expression. In this study, we used a genetic approach in mice to identify the mechanism by which insulin regulates albumin gene transcription. Albumin expression was decreased significantly in livers with insulin signaling disrupted by ablation of the insulin receptor or Akt. Concomitant deletion of Forkhead Box O1 (Foxo1) in these livers rescued the decreased albumin secretion. Furthermore, activation of Foxo1 in the liver is sufficient to suppress albumin expression. These results suggest that Foxo1 acts as a repressor of albumin expression. PMID:26668316

Coordination of NF-kappaB and NFAT antagonism by the forkhead transcription factor Foxd1.

PubMed

Lin, Ling; Peng, Stanford L

2006-04-15

Forkhead transcription factors play critical roles in the maintenance of immune homeostasis. In this study, we demonstrate that this regulation most likely involves intricate interactions between the forkhead family members and inflammatory transcription factors: the forkhead member Foxd1 coordinates the regulation of the activity of two key inflammatory transcription factors, NF-AT and NF-kappaB, with Foxd1 deficiency resulting in multiorgan, systemic inflammation, exaggerated Th cell-derived cytokine production, and T cell proliferation in autologous MLRs. Foxd1-deficient T cells possess increased activity of both NF-AT and NF-kappaB: the former correlates with the ability of Foxd1 to regulate casein kinase 1, an NF-AT inhibitory kinase; the latter with the ability of Foxd1 to regulate Foxj1, which regulates the NF-kappaB inhibitory subunit IkappaB beta. Thus, Foxd1 modulates inflammatory reactions and prevents autoimmunity by directly regulating anti-inflammatory regulators of the NF-AT pathway, and by coordinating the suppression of the NF-kappaB pathway via Foxj1. These findings indicate the presence of a general network of forkhead proteins that enforce T cell quiescence.

High expression of forkhead box protein C2 is associated with aggressive phenotypes and poor prognosis in clinical hepatocellular carcinoma.

PubMed

Shimoda, Yuki; Ubukata, Yasunari; Handa, Tadashi; Yokobori, Takehiko; Watanabe, Takayoshi; Gantumur, Dolgormaa; Hagiwara, Kei; Yamanaka, Takahiro; Tsukagoshi, Mariko; Igarashi, Takamichi; Watanabe, Akira; Kubo, Norio; Araki, Kenichiro; Harimoto, Norifumi; Katayama, Ayaka; Hikino, Toshiaki; Sano, Takaaki; Ogata, Kyoichi; Kuwano, Hiroyuki; Shirabe, Ken; Oyama, Tetsunari

2018-05-25

Hepatocellular carcinoma (HCC) is one of the major causes of tumor death; thus, the identification of markers related to its diagnosis and prognosis is critical. Previous studies have revealed that epithelial-to-mesenchymal transition (EMT) is involved in tumor invasion and metastasis, and the forkhead box protein C2 (FOXC2) has been shown to promote tumor cell proliferation, invasion, and EMT. In the present study, we examined the clinicopathological significance of FOXC2 and EMT-related markers in clinical HCC specimens and identified factors related to the diagnosis and prognosis of HCC. The expression of FOXC2 and EMT-related markers was evaluated by immunohistochemistry in 84 cases of hepatocellular carcinoma. A high expression of FOXC2 was observed in 26 of 84 cases, and expression was significantly correlated with background liver cirrhosis, poor tumor differentiation, high serum AFP, and elevated cell proliferation markers. In addition, this high expression was related to the induction of the Cadherin switch and vimentin expression and was an independent predictor for poor prognosis. The high expression of FOXC2 in HCC is correlated with tumor malignancy and poor prognosis, suggesting that FOXC2 may be an important prognostic factor for HCC.

Forkhead Transcription Factor Fd3F Cooperates with Rfx to Regulate a Gene Expression Program for Mechanosensory Cilia Specialization

PubMed Central

Newton, Fay G.; zur Lage, Petra I.; Karak, Somdatta; Moore, Daniel J.; Göpfert, Martin C.; Jarman, Andrew P.

2012-01-01

Summary Cilia have evolved hugely diverse structures and functions to participate in a wide variety of developmental and physiological processes. Ciliary specialization requires differences in gene expression, but few transcription factors are known to regulate this, and their molecular function is unclear. Here, we show that the Drosophila Forkhead box (Fox) gene, fd3F, is required for specialization of the mechanosensory cilium of chordotonal (Ch) neurons. fd3F regulates genes for Ch-specific axonemal dyneins and TRPV ion channels, which are required for sensory transduction, and retrograde transport genes, which are required to differentiate their distinct motile and sensory ciliary zones. fd3F is reminiscent of vertebrate Foxj1, a motile cilia regulator, but fd3F regulates motility genes as part of a broader sensory regulation program. Fd3F cooperates with the pan-ciliary transcription factor, Rfx, to regulate its targets directly. This illuminates pathways involved in ciliary specialization and the molecular mechanism of transcription factors that regulate them. PMID:22698283

Forkhead-box series expression network is associated with outcome of clear-cell renal cell carcinoma.

PubMed

Jia, Zhongwei; Wan, Fangning; Zhu, Yao; Shi, Guohai; Zhang, Hailiang; Dai, Bo; Ye, Dingwei

2018-06-01

Previous studies have demonstrated that several members of the Forkhead-box (FOX) family of genes are associated with tumor progression and metastasis. The objective of the current study was to screen candidate FOX family genes identified from analysis of molecular networks in clear cell renal cell carcinoma (ccRCC). The expression of FOX family genes as well as FOX family-associated genes was examined, and Kaplan-Meier survival analysis was performed in The Cancer Genome Atlas (TCGA) cohort (n=525). Patient characteristics, including sex, age, tumor diameter, laterality, tumor-node-metastasis, tumor grade, stage, white blood cell count, platelet count, the levels of hemoglobin, overall survival (OS) and disease-free survival (DFS), were collected for univariate and multivariate Cox proportional hazards ratio analyses. A total of seven candidate FOX family genes were selected from the TCGA database subsequent to univariate and multivariate Cox proportional hazards ratio analyses. FOXA1, FOXA2, FOXD1, FOXD4L2, FOXK2 and FOXL1 were associated with poor OS time, while FOXA1, FOXA2, FOXD1 and FOXK2 were associated with poor DFS time (P<0.05). FOXN2 was associated with favorable outcomes for overall and disease-free survival (P<0.05). In the gene cluster network analysis, the expression of FOX family-associated genes, including nuclear receptor coactivator ( NCOA ) 1 , NADH-ubiquinone oxidoreductase flavoprotein 3 ( NDUFV3 ), phosphatidylserine decarboxylase ( PISD ) and pyruvate kinase liver and red blood cell ( PKLR ), were independent prognostic factors for OS in patients with ccRCC. Results of the present study revealed that the expression of FOX family genes, including FOXA1, FOXA2, FOXD1, FOXD4L2, FOXK2 and FOXL1 , and FOX family-associated genes, including NCOA1, NDUFV3, PISD and PKLR , are independent prognostic factors for patients with ccRCC.

Skin expression of mammalian target of rapamycin and forkhead box transcription factor O1, and serum insulin-like growth factor-1 in patients with acne vulgaris and their relationship with diet.

PubMed

Agamia, N F; Abdallah, D M; Sorour, O; Mourad, B; Younan, D N

2016-06-01

Acne vulgaris is a multifactorial disorder of the pilosebaceous units. Several studies have reported that insulin-like growth factor (IGF)-1, forkhead box transcription factor (Fox)O1 and mammalian target of rapamycin (mTOR) interactions may be the key to understanding the links between genetic and environmental factors in acne vulgaris. To evaluate the immunohistochemical detection of mTOR and FoxO1 in the skin, and the serum level of IGF-1 in patients with acne vulgaris. This study was carried out on 60 participants, including 40 patients with acne and 20 controls. A diet questionnaire was administered to the patients and controls. Serum levels of IGF-1 were measured using enzyme-linked immunosorbent assay, and skin biopsies were taken from lesions on the backs of the patients and controls. FoxO1 and mTOR expression was detected using immunohistochemistry. A significantly higher serum IGF-1 level was found in the patients with acne than in the controls. The cytoplasmic expression of FoxO1 was found to be significantly greater in the acne group, whereas in the control subjects this expression was likely to be nuclear. Both the cytoplasmic expression and the nuclear expression of mTOR were significantly more intense in the patients with acne than in the controls. Excess consumption of a high-glycaemic-load diet was significantly associated with higher serum levels of IGF-1 and cytoplasmic expression of FoxO1 and mTOR. These results suggest that FoxO1, mTOR, serum IGF-1 and a high-glycaemic-load diet may play a role in acne pathogenesis. © 2016 British Association of Dermatologists.

Human monocyte-derived suppressor cells control graft-versus-host disease by inducing regulatory forkhead box protein 3-positive CD8+ T lymphocytes.

PubMed

Janikashvili, Nona; Trad, Malika; Gautheron, Alexandrine; Samson, Maxime; Lamarthée, Baptiste; Bonnefoy, Francis; Lemaire-Ewing, Stéphanie; Ciudad, Marion; Rekhviashvili, Khatuna; Seaphanh, Famky; Gaugler, Béatrice; Perruche, Sylvain; Bateman, Andrew; Martin, Laurent; Audia, Sylvain; Saas, Philippe; Larmonier, Nicolas; Bonnotte, Bernard

2015-06-01

Adoptive transfer of immunosuppressive cells has emerged as a promising strategy for the treatment of immune-mediated disorders. However, only a limited number of such cells can be isolated from in vivo specimens. Therefore efficient ex vivo differentiation and expansion procedures are critically needed to produce a clinically relevant amount of these suppressive cells. We sought to develop a novel, clinically relevant, and feasible approach to generate ex vivo a subpopulation of human suppressor cells of monocytic origin, referred to as human monocyte-derived suppressive cells (HuMoSCs), which can be used as an efficient therapeutic tool to treat inflammatory disorders. HuMoSCs were generated from human monocytes cultured for 7 days with GM-CSF and IL-6. The immune-regulatory properties of HuMoSCs were investigated in vitro and in vivo. The therapeutic efficacy of HuMoSCs was evaluated by using a graft-versus-host disease (GvHD) model of humanized mice (NOD/SCID/IL-2Rγc(-/-) [NSG] mice). CD33+ HuMoSCs are highly potent at inhibiting the proliferation and activation of autologous and allogeneic effector T lymphocytes in vitro and in vivo. The suppressive activity of these cells depends on signal transducer and activator of transcription 3 activation. Of therapeutic relevance, HuMoSCs induce long-lasting memory forkhead box protein 3-positive CD8+ regulatory T lymphocytes and significantly reduce GvHD induced with human PBMCs in NSG mice. Ex vivo-generated HuMoSCs inhibit effector T lymphocytes, promote the expansion of immunosuppressive forkhead box protein 3-positive CD8+ regulatory T cells, and can be used as an efficient therapeutic tool to prevent GvHD. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Immunoexpression of interleukin 17, transforming growth factor β1, and forkhead box P3 in periapical granulomas, radicular cysts, and residual radicular cysts.

PubMed

Andrade, Ana Luiza Dias Leite de; Nonaka, Cassiano Francisco Weege; Gordón-Núñez, Manuel Antonio; Freitas, Roseana de Almeida; Galvão, Hébel Cavalcanti

2013-08-01

Different cell types and cytokines have been identified as contributors to the formation of periapical lesions. In this perspective, this study aimed to evaluate the immunoexpression of interleukin (IL)-17, transforming growth factor (TGF)-β1, and the forkhead box P3 (FoxP3) in periapical lesions, correlating them with the type of lesion, the intensity of the inflammatory infiltrate, and the thickness of the cystic epithelial lining. Twenty periapical granulomas (PGs), 20 radicular cysts (RCs), and 20 residual radicular cysts (RRCs) were submitted to immunohistochemical analysis using anti-IL-17, anti-TGF-β1, and anti-FoxP3 antibodies. In comparison with PGs and RCs, RRCs exhibited a lower immunoexpression of IL-17 and TGF-β1 (P = .021 and P < .001, respectively). The number of FoxP3+ cells increased in this order: RRCs, RCs, and PGs (P < .001). In comparison with lesions with inflammatory infiltrates grades I and II, lesions with inflammatory infiltrate grade III exhibited a higher number of FoxP3+ cells (P = .002). Similarly, in comparison with lesions with inflammatory infiltrates grades II and III, lesions with inflammatory infiltrate grade I showed a tendency for a lower expression of IL-17 and TGF-β1 (P = .085 and P = .051, respectively). For all groups, there was a positive correlation between the immunoexpressions of IL-17 and TGF-β1 (P < .05). Positive correlations between the number of FoxP3+ cells and the immunoexpressions of IL-17 and TGF-β1 (P < .05) were found only in PGs. Th17 and Treg cells seem to interact at the site of injury, suggesting the involvement of proinflammatory and immunoregulatory cytokines in the pathogenesis of periapical lesions. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Cell-penetrable mouse forkhead box protein 3 alleviates experimental arthritis in mice by up-regulating regulatory T cells.

PubMed

Liu, Xia; Ji, Baoju; Sun, Mengyi; Wu, Weijiang; Huang, Lili; Sun, Aihua; Zong, Yangyong; Xia, Sheng; Shi, Liyun; Qian, Hui; Xu, Wenrong; Shao, Qixiang

2015-07-01

Regulatory T cells (T(regs)) have potential applications in clinical disease therapy, such as autoimmune diseases and transplant rejection. However, their numbers are limited. Forkhead box protein 3 (FoxP3) is a key transcription factor that controls T(reg) development and function. Here, we generated a cell-permeable fusion protein, protein transduction domain (PTD)-conjugated mouse FoxP3 protein (PTD-mFoxP3), and evaluated whether PTD-mFoxp3 can alleviate rheumatoid arthritis (RA) in the collagen-induced arthritis (CIA) mouse model. As expected, PTD-mFoxP3 was transduced into cells effectively, and inhibited T cell activation and attenuated the cell proliferation. It decreased interleukin (IL) 2 and interferon (IFN)-γ expression, and increased IL-10 expression in activated CD4(+)CD25(-) T cells. PTD-mFoxP3-transduced CD4(+)CD25(-) T cells attenuated proliferation of activated CD4(+)CD25(-) T cells. In addition, PTD-mFoxP3 blocked the Th17 differentiation programme in vitro and down-regulated IL-17 production from T cells by modulating induction and levels of retinoid-related orphan receptor gamma t (RORγt). Intra-articular delivery of PTD-mFoxP3 delayed disease incidence remarkably and alleviated autoimmune symptoms of CIA mice. Moreover, protective effects of PTD-mFoxP3 were associated with regulating the balance of T helper type 17 (Th17) and T(regs). These results suggest that PTD-mFoxP3 may be a candidate for RA therapy. © 2015 British Society for Immunology.

X-chromosome Forkhead Box P3 polymorphisms associate with atopy in girls in three Dutch birth cohorts.

PubMed

Bottema, R W B; Kerkhof, M; Reijmerink, N E; Koppelman, G H; Thijs, C; Stelma, F F; Smit, H A; Brunekreef, B; van Schayck, C P; Postma, D S

2010-07-01

The Forkhead Box P3 (FOXP3) gene, located on the X-chromosome, encodes a transcription factor that directs T cells toward a regulatory phenotype. Regulatory T cells may suppress development of atopy. We evaluated whether single-nucleotide polymorphisms (SNPs) of FOXP3 are associated with atopy development in childhood. Seven SNPs in FOXP3 were genotyped in 3062 children (51% boys) participating in the Allergenic study, which consists of three Dutch birth cohorts (PIAMA, PREVASC and KOALA). Association of FOXP3 SNPs with total serum IgE and sensitisation (presence of specific serum IgE to egg, milk, and indoor, i.e. house-dust mite, cat, and/or dog allergens) was investigated at ages 1, 2, 4, and 8. Analysis of variance and logistic regression were performed, stratified for gender. Our most consistent finding was observed for sensitisation to egg and indoor allergens. In girls, five FOXP3 SNPs (rs5906761, rs2294021, rs2294019, rs6609857 and rs3761548) were significantly associated with sensitisation to egg at ages 1 and 2 and with sensitisation to indoor allergens at age 2 (P < 0.05), but not at 4 and 8, a finding that was observed across the three cohorts. Rs5906761 and rs2294021 were associated with remission of sensitisation to food allergens in boys, as tested in the PIAMA cohort. This is the first study showing across three cohorts that X-chromosomal FOXP3 genotypes may contribute to development of sensitisation against egg and indoor allergens in girls in early childhood. In addition, an association with remission of sensitisation to food allergens existed in boys only.

Advanced glycosylation end product promotes forkhead box O1 and inhibits Wnt pathway to suppress capacities of epidermal stem cells.

PubMed

Zhu, Jie; Wang, Peng; Yu, Zhimin; Lai, Wei; Cao, Yi; Huang, Pinbo; Xu, Qiaodong; Yu, Menglei; Xu, Junyao; Huang, Zitong; Zeng, Bing

2016-01-01

Diabetes mellitus is frequently accompanied by chronic complications like delayed wound healing, which is consider to be attributed to the accumulation of advanced glycosylation end product (AGE). However, the impacts of AGE on epidermal stem cells (ESCs) are largely unknown. This study aims to address the influence and mechanism of AGE on ESCs. ESCs isolated from rats were cultured in AGE-modified bovine serum albumin and transfected with small interfering RNA to knock down AGE-specific receptor (AGER). Expression of stem cell markers integrin β1 (ITGB1) and keratin 19 (KRT19), cell viability, apoptosis and reactive oxygen species (ROS) were examined. Wnt pathway-related factors Wnt family member 1 (WNT1), WNT3A, β-catenin, v-myc avian myelocytomatosis viral oncogene homolog (MYC), cyclin D1 (CCND1) and matrix metallopeptidase 7 (MMP7) were quantified. The interaction between forkhead box O1 (FOXO1) and β-catenin was assessed by co-immunoprecipitation. Results indicated that AGE down-regulated ITGB1 and KRT19 expression, suppressed ESC viability and promoted apoptosis, and ROS level ( P < 0.01), implying decreased capacities of ESCs. AGE also promoted AGER and FOXO1, while AGER knockdown had the opposite effects. Moreover, AGER knockdown elevated the level of WNT1, WNT3A, MYC, CCND1 and MMP7 that were suppressed by AGE ( P < 0.01). Immunoprecipitation analysis showed that FOXO1 could compete with lymphoid enhancer binding factor 1 to interact with β-catenin, which might help to elucidate the mechanism of AGE repressing ESCs. This study helps to understand the mechanism of accumulated AGE in affecting ESC capacities, and provides potential therapeutic targets to meliorate diabetic wound healing.

Forkhead transcription factor foxe1 regulates chondrogenesis in zebrafish.

PubMed

Nakada, Chisako; Iida, Atsumi; Tabata, Yoko; Watanabe, Sumiko

2009-12-15

Forkhead transcription factor (Fox) e1 is a causative gene for Bamforth-Lazarus syndrome, which is characterized by hypothyroidism and cleft palate. Applying degenerate polymerase chain reaction using primers specific for the conserved forkhead domain, we identified zebrafish foxe1 (foxe1). Foxe1 is expressed in the thyroid, pharynx, and pharyngeal skeleton during development; strongly expressed in the gill and weakly expressed in the brain, eye, and heart in adult zebrafish. A loss of function of foxe1 by morpholino antisense oligo (MO) exhibited abnormal craniofacial development, shortening of Meckel's cartilage and the ceratohyals, and suppressed chondrycytic proliferation. However, at 27 hr post fertilization, the foxe1 MO-injected embryos showed normal dlx2, hoxa2, and hoxb2 expression, suggesting that the initial steps of pharyngeal skeletal development, including neural crest migration and specification of the pharyngeal arch occurred normally. In contrast, at 2 dpf, a severe reduction in the expression of sox9a, colIIaI, and runx2b, which play roles in chondrocytic proliferation and differentiation, was observed. Interestingly, fgfr2 was strongly upregulated in the branchial arches of the foxe1 MO-injected embryos. Unlike Foxe1-null mice, normal thyroid development in terms of morphology and thyroid-specific marker expression was observed in foxe1 MO-injected zebrafish embryos. Taken together, our results indicate that Foxe1 plays an important role in chondrogenesis during development of the pharyngeal skeleton in zebrafish, probably through regulation of fgfr2 expression. Furthermore, the roles reported for FOXE1 in mammalian thyroid development may have been acquired during evolution. (c) 2009 Wiley-Liss, Inc.

Molecular Mechanism of Betaine on Hepatic Lipid Metabolism: Inhibition of Forkhead Box O1 (FoxO1) Binding to Peroxisome Proliferator-Activated Receptor Gamma (PPARγ).

PubMed

Kim, Dae Hyun; Lee, Bonggi; Kim, Min Jo; Park, Min Hi; An, Hye Jin; Lee, Eun Kyeong; Chung, Ki Wung; Park, June Whoun; Yu, Byung Pal; Choi, Jae Sue; Chung, Hae Young

2016-09-14

Betaine is a major water-soluble component of Lycium chinensis. Although there are reports about the protective effects of betaine on hepatic steatosis, the underlying mechanisms are unclear. We used db/db mice and HepG2 cells to examine the mechanism underlying betaine-mediated protection against hepatic steatosis. Here, we showed increased hepatic lipid accumulation in db/db mice, which is associated with increased activation of lipogenic transcription factors including forkhead box O1 (FoxO1) and peroxisome proliferator-activated receptor gamma (PPARγ), whereas betaine administration by oral gavage reversed these characteristics. We investigated whether betaine ameliorates hepatic steatosis by inhibiting FoxO1/PPARγ signaling in HepG2 cells. Although adenovirus-mediated FoxO1 overexpression notably increased mRNA expression levels of PPARγ and its target genes including FAS and ACC, betaine treatment reversed them. Furthermore, betaine inhibited FoxO1 binding to the PPARγ promoter and PPARγ transcriptional activity in HepG2 cells, which was previously shown to induce hepatic steatosis. We concluded that betaine ameliorates hepatic steatosis, at least in part, by inhibiting the FoxO1 binding to PPARγ and their downstream lipogenic signaling cascade.

The forkhead transcription factor FoxY regulates Nanos

PubMed Central

Song, Jia L.; Wessel, Gary M.

2012-01-01

FoxY is a member of the forkhead transcription factor family that appeared enriched in the presumptive germ line of sea urchins (Ransick et al., 2002, Dev Biol 246:132). Here we test the hypothesis that FoxY is involved in germ line determination in this animal. We found two splice forms of FoxY that share the same DNA-binding domain but vary in the carboxy-terminal trans-activation/repression domain. Both forms of the FoxY protein are present in the ovary and in the early embryo, and their mRNAs accumulate to their highest levels in the small micromeres and adjacent non-skeletogenic mesoderm. Knockdown of FoxY resulted in a dramatic decrease in the Nanos mRNA and protein levels as well as a loss of coelomic pouches in the 2-week-old larvae. Our results indicate that FoxY positively regulates Nanos at the transcriptional level and is essential for reproductive potential in this organism. PMID:22777754

The forkhead transcription factor FoxY regulates Nanos.

PubMed

Song, Jia L; Wessel, Gary M

2012-10-01

FoxY is a member of the forkhead transcription factor family that appeared enriched in the presumptive germ line of sea urchins (Ransick et al. Dev Biol 2002;246:132). Here, we test the hypothesis that FoxY is involved in germ line determination in this animal. We found two splice forms of FoxY that share the same DNA-binding domain, but vary in the carboxy-terminal trans-activation/repression domain. Both forms of the FoxY protein are present in the egg and in the early embryo, and their mRNAs accumulate to their highest levels in the small micromeres and adjacent non-skeletogenic mesoderm. Knockdown of FoxY resulted in a dramatic decrease in Nanos mRNA and protein levels as well as a loss of coelomic pouches in 2-week-old larvae. Our results indicate that FoxY positively regulates Nanos at the transcriptional level and is essential for reproductive potential in this organism. Copyright © 2012 Wiley Periodicals, Inc.

Association between forkhead-box P2 gene polymorphism and clinical symptoms in chronic schizophrenia in a Chinese population.

PubMed

Rao, Wenwang; Du, Xiangdong; Zhang, Yingyang; Yu, Qiong; Hui, Li; Yu, Yaqin; Kou, Changgui; Yin, Guangzhong; Zhu, Xiaomin; Man, Lijuan; Soares, Jair C; Zhang, Xiang Yang

2017-07-01

The forkhead-box P2 (FOXP2) gene polymorphism has been reported to be involved in the susceptibility to schizophrenia; however, few studies have investigated the association between FOXP2 gene polymorphism and clinical symptoms in schizophrenia. This study investigated whether the FOXP2 gene was associated with the development and symptoms of schizophrenia in relatively genetically homogeneous Chinese population. The FOXP2 rs10447760 polymorphism was genotyped in 1069 schizophrenia inpatients and 410 healthy controls using a case-control design. The patients' psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). We found no significant differences in the genotype and allele distributions between the patient and control groups. Interestingly, we found significant differences in PANSS total, positive symptom, and general psychopathology scores between genotypic subgroups in patients, with the higher score in patients with CC genotype than those with CT genotype (all p < 0.05). After adjusting demographic and clinical variables, the difference still remained significant for the PANSS positive symptom score and general psychopathology (both p < 0.05). Our findings suggest that the FOXP2 rs10447760 polymorphism may not contribute to the development of schizophrenia, but may contribute to the clinical symptoms of schizophrenia among Han Chinese.

An association study of sequence variants in the forkhead box P2 (FOXP2) gene and adulthood attention-deficit/hyperactivity disorder in two European samples.

PubMed

Ribasés, Marta; Sánchez-Mora, Cristina; Ramos-Quiroga, Josep Antoni; Bosch, Rosa; Gómez, Núria; Nogueira, Mariana; Corrales, Montse; Palomar, Gloria; Jacob, Christian P; Gross-Lesch, Silke; Kreiker, Susanne; Reif, Andreas; Lesch, Klaus Peter; Cormand, Bru; Casas, Miquel; Bayés, Mónica

2012-08-01

Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder manifesting as symptoms of inattention, hyperactivity, and/or impulsivity. Learning disabilities co-occur with ADHD in 20-30% of cases and this high co-occurrence raises the possibility of a common etiological background. Forkhead box P2 (FOXP2) encodes a transcription factor involved in speech and language impairment and in the control of the corticobasal ganglia circuits known to be relevant in ADHD, suggesting a possible role of FOXP2 in ADHD. Our aim was to carry out an association study between FOXP2 and adulthood ADHD. We carried out a case-control association study in 643 adult ADHD patients and 619 controls from Germany and in 361 adult ADHD patients and 442 controls from Spain with 12 tagging single nucleotide polymorphisms covering the FOXP2 gene. The single-marker and multiple-marker analyses showed an association between FOXP2 and combined ADHD in the German cohort [rs12533005: P=0.0033; odds ratio=1.30 (1.09-1.56); rs12533005/rs1229761: P=4.1e-04; odds ratio=1.38 (1.15-1.66)]. These positive results, however, were not confirmed in the Spanish sample. Although these preliminary findings provide a tentative evidence for the contribution of FOXP2 to ADHD and suggest common genetic factors for this psychiatric disorder and learning disabilities, they should be interpreted with caution. Further studies in larger samples are needed to clarify the role of this transcription factor in ADHD.

Forkhead Box O1 Regulates Macrophage Polarization Following Staphylococcus aureus Infection: Experimental Murine Data and Review of the Literature.

PubMed

Wang, Yu-Chen; Ma, Hong-Di; Yin, Xue-Ying; Wang, Yin-Hu; Liu, Qing-Zhi; Yang, Jing-Bo; Shi, Qing-Hua; Sun, Baolin; Gershwin, M Eric; Lian, Zhe-Xiong

2016-12-01

The functions of macrophages that lead to effective host responses are critical for protection against Staphylococcus aureus. Deep tissue-invading S. aureus initially countered by macrophages trigger macrophage accumulation and induce inflammatory responses through surface receptors, especially toll-like receptor 2 (TLR2). Here, we found that macrophages formed sporadic aggregates in the liver during infection. Within those aggregates, macrophages co-localized with T cells and were indispensable for their infiltration. In addition, we have focused on the mechanisms underlying the polarization of macrophages in Forkhead box transcription factor O1 (FoxO1) conditional knockout Lys Cre/+ FoxO1 fl/fl mice following S. aureus infection and report herein that macrophage M1-M2 polarization via TLR2 is intrinsically regulated by FoxO1. Indeed, for effective FoxO1 activity, stimulation of TLR2 is essential. However, following S. aureus challenge, there was a decrease in macrophage FoxO1, with increased phosphorylation of FoxO1 because of TLR2-mediated activation of PI3K/Akt and c-Raf/MEK/ERK pathway. Following infection in Lys Cre/+ FoxO1 fl/fl mice, mice became more susceptible to S. aureus with reduced macrophage aggregation in the liver and attenuated Th1 and Th17 responses. FoxO1 abrogation reduced M1 pro-inflammatory responses triggered by S. aureus and enhanced M2 polarization in macrophages. In contrast, overexpression of FoxO1 in macrophages increased pro-inflammatory mediators and functional surface molecule expression. In conclusion, macrophage FoxO1 is critical to promote M1 polarization and maintain a competent T cell immune response against S. aureus infection in the liver. FoxO1 regulates macrophage M1-M2 polarization downstream of TLR2 dynamically through phosphorylation.

Effect of cell density and HLA-DR incompatibility on T-cell proliferation and forkhead box P3 expression in human mixed lymphocyte reaction.

PubMed

Song, E Y; Han, S; Yang, B; Morris, G P; Bui, J D

2015-04-01

The proliferation rates of human T cells in vitro are affected by some factors such as initial T-cell number, dose of stimulating cells, and duration of culture. The transcription factor forkhead box P3 (FoxP3) has been used to identify regulatory T cells in humans and is thought to correlate with tolerance to allogeneic organ transplant. Thus, it is important to optimize conditions to expand FoxP3 cell proliferation to improve engraftment of allogeneic organ transplants. We studied proliferative responses and FoxP3 expression in divided T cells with the use of flow cytometric analysis of Ki-67 in culture of different concentrations of responding cells (6 × 10(6), 4 × 10(6), 2 × 10(6), 1 × 10(6), and 0.5 × 10(6)cells/mL), different types of stimulating cells (lymphocytes and low density cells), and different numbers of HLA mismatches. The proportion of CD3(+) cells, CD4(+)CD25(+) cells, and CD4(+)CD25(+)FoxP3(+) cells among mononuclear cells were highest at initial cell concentration of 2 × 10(6) responder cells/mL with lymphocytes as stimulators at day-5 mixed lymphocyte reaction (MLR). They were highest at a concentration of 4 × 10(6) responder cells/mL with low density cells as stimulators. The recovery (%), proportion of CD3(+) cells, CD4(+)CD25(+) cells, and CD4(+)CD25(+)FoxP3(+) cells with 2 HLA-DR incompatibility were significantly higher than those of 1 HLA-DR incompatibility at day-5 MLR. Initial cell concentration and HLA-DR incompatibility can affect the generation of FoxP3+ T cells in human MLR. These factors could be considered for efficient generation of Tregs for clinical trials in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

A Key Evolutionary Mutation Enhances DNA Binding of the FOXP2 Forkhead Domain.

PubMed

Morris, Gavin; Fanucchi, Sylvia

2016-04-05

Forkhead box (FOX) transcription factors share a conserved forkhead DNA binding domain (FHD) and are key role players in the development of many eukaryotic species. Their involvement in various congenital disorders and cancers makes them clinically relevant targets for novel therapeutic strategies. Among them, the FOXP subfamily of multidomain transcriptional repressors is unique in its ability to form DNA binding homo and heterodimers. The truncated FOXP2 FHD, in the absence of the leucine zipper, exists in equilibrium between monomeric and domain-swapped dimeric states in vitro. As a consequence, determining the DNA binding properties of the FOXP2 FHD becomes inherently difficult. In this work, two FOXP2 FHD hinge loop mutants have been generated to successfully prevent both the formation (A539P) and the dissociation (F541C) of the homodimers. This allows for the separation of the two species for downstream DNA binding studies. Comparison of DNA binding of the different species using electrophoretic mobility shift assay, fluorescence anisotropy and isothermal titration calorimetry indicates that the wild-type FOXP2 FHD binds DNA as a monomer. However, comparison of the DNA-binding energetics of the monomer and wild-type FHD, reveals that there is a difference in the mechanism of binding between the two species. We conclude that the naturally occurring reverse mutation (P539A) seen in the FOXP subfamily increases DNA binding affinity and may increase the potential for nonspecific binding compared to other FOX family members.

Minireview: roles of the forkhead transcription factor FOXL2 in granulosa cell biology and pathology.

PubMed

Pisarska, Margareta D; Barlow, Gillian; Kuo, Fang-Ting

2011-04-01

The forkhead transcription factor (FOXL2) is an essential transcription factor in the ovary. It is important in ovarian development and a key factor in female sex determination. In addition, FOXL2 plays a significant role in the postnatal ovary and follicle maintenance. The diverse transcriptional activities of FOXL2 are likely attributable to posttranslational modifications and binding to other key proteins involved in granulosa cell function. Mutations of FOXL2 lead to disorders of ovarian function ranging from premature follicle depletion and ovarian failure to unregulated granulosa cell proliferation leading to tumor formation. Thus, FOXL2 is a key regulator of granulosa cell function and a master transcription factor in these cells.

Minireview: Roles of the Forkhead Transcription Factor FOXL2 in Granulosa Cell Biology and Pathology

PubMed Central

Barlow, Gillian; Kuo, Fang-Ting

2011-01-01

The forkhead transcription factor (FOXL2) is an essential transcription factor in the ovary. It is important in ovarian development and a key factor in female sex determination. In addition, FOXL2 plays a significant role in the postnatal ovary and follicle maintenance. The diverse transcriptional activities of FOXL2 are likely attributable to posttranslational modifications and binding to other key proteins involved in granulosa cell function. Mutations of FOXL2 lead to disorders of ovarian function ranging from premature follicle depletion and ovarian failure to unregulated granulosa cell proliferation leading to tumor formation. Thus, FOXL2 is a key regulator of granulosa cell function and a master transcription factor in these cells. PMID:21248146

Temporal expression and mitochondrial localization of a Foxp2 isoform lacking the forkhead domain in developing Purkinje cells.

PubMed

Tanabe, Yuko; Fujiwara, Yuji; Matsuzaki, Ayumi; Fujita, Eriko; Kasahara, Tadashi; Yuasa, Shigeki; Momoi, Takashi

2012-07-01

FOXP2, a forkhead box-containing transcription factor, forms homo- or hetero-dimers with FOXP family members and localizes to the nucleus, while FOXP2(R553H), which contains a mutation related to speech/language disorders, features reduced DNA binding activity and both cytoplasmic and nuclear localization. In addition to being a loss-of-function mutation, it is possible that FOXP2(R553H) also may act as a gain-of-function mutation to inhibit the functions of FOXP2 isoforms including FOXP2Ex10+ lacking forkhead domain. Foxp2(R552H) knock-in mouse pups exhibit impaired ultrasonic vocalization and poor dendritic development in Purkinje cells. However, expressions of Foxp2 isoforms in the developing Purkinje are unclear. The appearance of 'apical cytoplasmic swelling' (mitochondria-rich regions that are the source of budding processes) correlates with dendritic development of Purkinje cells. In the present study, we focused on Foxp2 isoforms localizing to the apical cytoplasmic swelling and identified two isoforms lacking forkhead domain: Foxp2Ex12+ and Foxp2Ex15. They partly localized to the membrane fraction that includes mitochondria. Foxp2Ex12+ mainly localized to the apical cytoplasmic swelling in early developing Purkinje cells at the stellate stage (P2-P4). Mitochondrial localization of Foxp2Ex12+ in Purkinje cells was confirmed by immune-electron microscopic analysis. Foxp2Ex12+ may play a role in dendritic development in Purkinje cells. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

A forkhead Transcription Factor Is Wound-Induced at the Planarian Midline and Required for Anterior Pole Regeneration

PubMed Central

Scimone, M. Lucila; Lapan, Sylvain W.; Reddien, Peter W.

2014-01-01

Planarian regeneration requires positional information to specify the identity of tissues to be replaced as well as pluripotent neoblasts capable of differentiating into new cell types. We found that wounding elicits rapid expression of a gene encoding a Forkhead-family transcription factor, FoxD. Wound-induced FoxD expression is specific to the ventral midline, is regulated by Hedgehog signaling, and is neoblast-independent. FoxD is subsequently expressed within a medial subpopulation of neoblasts at wounds involving head regeneration. Ultimately, FoxD is co-expressed with multiple anterior markers at the anterior pole. Inhibition of FoxD with RNA interference (RNAi) results in the failure to specify neoblasts expressing anterior markers (notum and prep) and in anterior pole formation defects. FoxD(RNAi) animals fail to regenerate a new midline and to properly pattern the anterior blastema, consistent with a role for the anterior pole in organizing pattern of the regenerating head. Our results suggest that wound signaling activates a forkhead transcription factor at the midline and, if the head is absent, FoxD promotes specification of neoblasts at the prior midline for anterior pole regeneration. PMID:24415944

Update: the role of FoxP3 in allergic disease.

PubMed

Paik, Young; Dahl, Matthew; Fang, Deyu; Calhoun, Karen

2008-06-01

T-regulatory cells play a key role in allergic and asthmatic inflammatory airway diseases. This review discusses the importance of a critical gene associated with T-regulatory cells. Forkhead box P3 is a forkhead-winged helix transcription factor gene involved in immune function in allergy and asthma. Recently, many functions of forkhead box P3 and its influence on the immune system have been elucidated. T-regulatory cells that are CD4+CD25+ and express forkhead box P3, influence the development and expression of atopy and allergic response. The exact mechanisms are not yet delineated, but multiple recent studies provide greater understanding of the mechanism of forkhead box P3 and its influence on these T-regulatory cells. Greater understanding of the molecular and immunological mechanisms underlying the T-regulatory cells and forkhead box P3 will permit the development of targeted treatment modalities to influence disease processes such as allergic rhinitis and bronchial asthma.

Dissociation of lipotoxicity and glucotoxicity in a mouse model of obesity associated diabetes: role of forkhead box O1 (FOXO1) in glucose-induced beta cell failure.

PubMed

Kluth, O; Mirhashemi, F; Scherneck, S; Kaiser, D; Kluge, R; Neschen, S; Joost, H-G; Schürmann, A

2011-03-01

Carbohydrate-free diet prevents hyperglycaemia and beta cell destruction in the New Zealand Obese (NZO) mouse model. Here we have used a sequential dietary regimen to dissociate the effects of obesity and hyperglycaemia on beta cell function and integrity, and to study glucose-induced alterations of key transcription factors over 16 days. Mice were rendered obese by feeding a carbohydrate-free diet for 18 weeks. Thereafter, a carbohydrate-containing diet was given. Plasma glucose, plasma insulin and total pancreatic insulin were determined, and forkhead box O1 protein (FOXO1) phosphorylation and the transcription factors pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 protein (NKX6.1) and v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (avian) (MAFA) were monitored by immunohistochemistry for 16 days. Dietary carbohydrates produced a rapid and continuous increase in plasma glucose in NZO mice between day 2 and 16 after the dietary challenge. Hyperglycaemia caused a dramatic dephosphorylation of FOXO1 at day 2, followed by a progressive depletion of insulin stores. The loss of beta cells was triggered by apoptosis (detectable at day 8), associated with reduction of crucial transcription factors (PDX1, NKX6.1 and MAFA). Incubation of isolated islets from carbohydrate-restricted NZO mice or MIN6 cells with palmitate and glucose for 48 h resulted in a dephosphorylation of FOXO1 and thymoma viral proto-oncogene 1 (AKT) without changing the protein levels of both proteins. The dietary regimen dissociates the effects of obesity (lipotoxicity) from those of hyperglycaemia (glucotoxicity) in NZO mice. Obese NZO mice are unable to compensate for the carbohydrate challenge by increasing insulin secretion or synthesising adequate amounts of insulin. In response to the hyperglycaemia, FOXO1 is dephosphorylated, leading to reduced levels of beta cell-specific transcription factors and to apoptosis of the cells.

Natura-alpha targets forkhead box m1 and inhibits androgen-dependent and -independent prostate cancer growth and invasion.

PubMed

Li, Yirong; Ligr, Martin; McCarron, James P; Daniels, Garrett; Zhang, David; Zhao, Xin; Ye, Fei; Wang, Jinhua; Liu, Xiaomei; Osman, Iman; Mencher, Simon K; Lepor, Hebert; Wang, Long G; Ferrari, Anna; Lee, Peng

2011-07-01

The development of new effective therapeutic agents with minimal side effects for prostate cancer (PC) treatment is much needed. Indirubin, an active molecule identified in the traditional Chinese herbal medicine-Qing Dai (Indigo naturalis), has been used to treat leukemia for decades. However, the anticancer properties of Natura-alpha, an indirubin derivative, are not well studied in solid tumors, particularly in PC. The growth kinetics and invasion ability of on human PC cell lines with or without Natura-alpha treatment were measured by cell proliferation and invasion assays. The antitumor effects of Natura-alpha were examined in nude mice tumor xenograft models, and in a patient with advanced hormone-refractory metastatic PC. Signal network proteins targeted by Natura-alpha were analyzed by using proteomic pathway array analysis (PPAA) on xenografts. Natura-alpha inhibited the growth of both androgen-dependent (LNCaP) and androgen-independent (LNCaP-AI, PC-3, and DU145) PC cells with IC(50) between 4 to 10 mmol/L, and also inhibited invasion of androgen-independent PC cells. Its antitumor effects were further evident in in vivo tumor reduction in androgen-dependent and androgen-independent nude mice tumor xenograft models and reduced tumor volume in the patient with hormone refractory metastatic PC. PPAA revealed that antiproliferative and antiinvasive activities of Natura-alpha on PC might primarily be through its downregulation of Forkhead box M1 (FOXM1) protein. Forced overexpression of FOXM1 largely reversed the inhibition of growth and invasion by Natura-alpha. Natura-alpha could serve as a novel and effective therapeutic agent for treatment of both hormone-sensitive and hormone-refractory PC with minimal side effects.

Fox (forkhead) genes are involved in the dorso-ventral patterning of the Xenopus mesoderm.

PubMed

El-Hodiri, H; Bhatia-Dey, N; Kenyon, K; Ault, K; Dirksen, M; Jamrich, M

2001-01-01

Fox (forkhead/winged helix) genes encode a family of transcription factors that are involved in embryonic pattern formation, regulation of tissue specific gene expression and tumorigenesis. Several of them are transcribed during Xenopus embryogenesis and are important for the patterning of ectoderm, mesoderm and endoderm. We have isolated three forkhead genes that are activated during gastrulation and play an important role in the dorso-ventral patterning of the mesoderm. XFKH1 (FoxA4b), the first vertebrate forkhead gene to be implicated in embryonic pattern formation, is expressed in the Spemann-Mangold organizer region and later in the embryonic notochord. XFKH7, the Xenopus orthologue of the murine Mfh1(Foxc2), is expressed in the presomitic mesoderm, but not in the notochord or lateral plate mesoderm. Finally, XFD-13'(FoxF1b)1 is expressed in the lateral plate mesoderm, but not in the notochord or presomitic mesoderm. Expression pattern and functional experiments indicate that these three forkhead genes are involved in the dorso-ventral patterning of the mesoderm.

Forkhead box-P3+ regulatory T cells and toll-like receptor 2 co-expression in oral squamous cell carcinoma.

PubMed

Hussaini, H M; Parachuru, V P B; Seymour, G J; Rich, A M

2017-04-01

The function of forkhead box-P3 (FoxP3) regulatory T cells (Treg) and toll-like receptor (TLR)2 protein in the oral cancer microenvironment is not fully understood, but evidence from other malignancies suggests it is likely they are involved with tumour development and progression. The aim of this study was to investigate the distribution of FoxP3 + cells, TLR2 + cells and double-labelled FoxP3 + TLR2 + immune cells in oral squamous cell carcinoma (OSCC), using immunohistochemistry (IHC) and immunofluorescence (IF). 25 archival cases of OSCC were immunostained with anti-FoxP3 and anti-TLR2 antibodies. Inflamed hyperplastic oral mucosal tissues were used as controls. The proportion of single-labelled, double-labelled and negative cells was determined. A higher frequency of double-labelled FoxP3 + TLR2 + Tregs was observed within the immune cells of OSCC compared to inflamed controls using IHC (p<0.05). Cell-to-cell contact between single-stained TLR2 + cells and FoxP3 + cells was noted. Double IF studies validated demonstration of co-expression of FoxP3 + /TLR2 + immune cells in OSCC. The presence of FoxP3 + TLR2 + cells within the OSCC microenvironment may represent a dendritic cell-dependent pathway capable of inhibiting Treg suppressive activity, potentially enhancing the anti-tumour response. Modulation of TLR2-Treg interactions should be further explored to determine if they have a role in the therapeutic management of OSCC. Copyright © 2017 Elsevier GmbH. All rights reserved.

No significant impact of Foxf1 siRNA treatment in acute and chronic CCl4 liver injury.

PubMed

Abshagen, Kerstin; Rotberg, Tobias; Genz, Berit; Vollmar, Brigitte

2017-08-01

Chronic liver injury of any etiology is the main trigger of fibrogenic responses and thought to be mediated by hepatic stellate cells. Herein, activating transcription factors like forkhead box f1 are described to stimulate pro-fibrogenic genes in hepatic stellate cells. By using a liver-specific siRNA delivery system (DBTC), we evaluated whether forkhead box f1 siRNA treatment exhibit beneficial effects in murine models of acute and chronic CCl 4 -induced liver injury. Systemic administration of DBTC-forkhead box f1 siRNA in mice was only sufficient to silence forkhead box f1 in acute CCl 4 model, but was not able to attenuate liver injury as measured by liver enzymes and necrotic liver cell area. Therapeutic treatment of mice with DBTC-forkhead box f1 siRNA upon chronic CCl 4 exposition failed to inhibit forkhead box f1 expression and hence lacked to diminish hepatic stellate cells activation or fibrosis development. As a conclusion, DBTC-forkhead box f1 siRNA reduced forkhead box f1 expression in a model of acute but not chronic toxic liver injury and showed no positive effects in either of these mice models. Impact statement As liver fibrosis is a worldwide health problem, antifibrotic therapeutic strategies are urgently needed. Therefore, further developments of new technologies including validation in different experimental models of liver disease are essential. Since activation of hepatic stellate cells is a key event upon liver injury, the activating transcription factor forkhead box f1 (Foxf1) represents a potential target gene. Previously, we evaluated Foxf1 silencing by a liver-specific siRNA delivery system (DBTC), exerting beneficial effects in cholestasis. The present study was designed to confirm the therapeutic potential of Foxf1 siRNA in models of acute and chronic CCl 4 -induced liver injury. DBTC-Foxf1 siRNA was only sufficient to silence Foxf1 in acute CCl 4 model and did not ameliorate liver injury or fibrogenesis. This underlines the

Natura-Alpha Targets Forkhead Box M1 and Inhibits Androgen-Dependent and -Independent Prostate Cancer Growth and Invasion

PubMed Central

Li, Yirong; Ligr, Martin; McCarron, James P; Daniels, Garrett; Zhang, David; Zhao, Xin; Ye, Fei; Wang, Jinhua; Liu, Xiaomei; Osman, Iman; Mencher, Simon K; Lepor, Hebert; Wang, Long G; Lee, Peng

2011-01-01

Purpose The development of new effective therapeutic agents with minimal side effects for prostate cancer treatment is much needed. Indirubin, an active molecule identified in the traditional Chinese herbal medicine – Qing Dai (Indigo Naturalis), has been used to treat leukemia for decades. However, the anti-cancer properties of Natura-alpha, an indirubin derivative, are not well studied in solid tumors, particularly in prostate cancer. Experimental Design Human prostate cancer cell lines were treated with or without Natura-alpha followed by cell growth and invasion assays measured. The anti-tumor effects of Natura-alpha were examined in nude mice tumor xenograft models, as well as in a patient with advanced hormone refractory metastatic prostate cancer. Signal network proteins targeted by Natura-alpha were analyzed using Proteomic Pathway Array Analysis (PPAA) on xenografts. Results Natura-alpha inhibited the growth of both androgen-dependent (LNCaP), and androgen-independent (LNCaP-AI, PC-3, and DU145) prostate cancer cells with IC50 between 4 to 10 Μm, also inhibits invasion of androgen-independent prostate cancer cells. Its anti-tumor effects were further evident in vivo tumor reduction in androgen-dependent and -independent nude mice tumor xenograft models as well as reduced tumor volume in the patient with hormone refractory metastatic prostate cancer. PPAA revealed that anti-proliferative and anti-invasive activities of Natura-alpha on prostate cancer might primarily be through its down-regulation of Forkhead box M1 (FOXM1) protein. Forced over-expression of FOXM1 largely reversed the inhibition by Natura-alpha. Conclusion Natura-alpha could serve as a novel and effective therapeutic agent for treatment of both hormone sensitive and hormone refractory prostate cancer with minimal side effects. PMID:21606178

The anti-Müllerian hormone (AMH) induces forkhead box L2 (FOXL2) expression in primary culture of human granulosa cells in vitro.

PubMed

Sacchi, Sandro; Marinaro, Federica; Xella, Susanna; Marsella, Tiziana; Tagliasacchi, Daniela; La Marca, Antonio

2017-09-01

Anti-Müllerian hormone (AMH) and forkhead box L2 (FOXL2) are two pivotal genes expressed in human granulosa cells (hGCs) where both genes share similar inhibitory functions on activation and follicular growth in order to preserve the ovarian follicle reserve. Furthermore, AMH and FOXL2 contribute to inhibit steroidogenesis, decreasing or preventing the activation of gonadotrophin-dependent aromatase CYP19A1 cytochrome P450 family 19 subfamily A member 1 (CYP19A1). The purpose of this study is to evaluate the role of AMH in regulating the expression of FOXL2. Primary cultures of hGCs were treated with increasing concentrations of recombinant human AMH (rhAMH; range 10-100 ng/ml) for 3 h. Negative controls were performed using corresponding amounts of AMH vehicle. Total RNA or proteins were purified and quantified by spectrophotometry. FOXL2 and CYP19A1 gene expression, normalized by reference gene ribosomal protein S7 (RpS7), was evaluated by RT-qPCR. Each reaction was repeated in triplicate. Statistical analysis was performed. Extracted proteins were analyzed by immunoblot using anti-FOXL2 and anti-β-actin as primary antibodies. rhAMH treatments tested did not modulate the basal expression of aromatase CYP19A1 gene. rhAMH (50 ng/ml) was able to increase FOXL2 gene expression and its intracellular content. This study demonstrated the existence of an AMH-FOXL2 relationship in hGCs. AMH is capable of increasing both gene and protein expression of FOXL2. Because FOXL2 induces AMH transcription, these ovarian factors could be finely regulated by a positive feedback loop mechanism to preserve the ovarian follicle reserve.

The Human T-Cell Leukemia Virus Type 1 Oncoprotein Tax Controls Forkhead Box O4 Activity through Degradation by the Proteasome▿

PubMed Central

Oteiza, Alexandra; Mechti, Nadir

2011-01-01

Activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway by the viral Tax oncoprotein plays a pivotal role in clonal expansion of human T-cell leukemia virus type 1 (HTLV-1)-infected cells. As the Forkhead box O (FoxO) tumor suppressors act as downstream effectors of PI3K/Akt, they represent good candidate targets whose dysregulation by Tax might be involved in HTLV-1-mediated activation and transformation of infected cells. In this report, we provide evidence showing that Tax induces a dose-dependent degradation of FoxO4 by the ubiquitin-proteasome pathway. Consistent with that, we demonstrate that Tax expression increases the interaction between FoxO4 and Mdm2 E3 ligase, leading to a strong FoxO4 polyubiquitination. These processes require the phosphorylation of FoxO4 by Akt, since a mutant of FoxO4 with mutations on its three Akt phosphorylation sites appears to be resistant to Tax-mediated degradation and ubiquitination. In addition, we show that Tax expression is associated with degradation and phosphorylation of endogenous FoxO4 in Jurkat T cells. Finally, we demonstrate that Tax represses FoxO4 transcriptional activity. Our study demonstrates that Tax can control FoxO4 protein stability and transcriptional activity and provides new insight into the subversion of cell signaling pathways during HTLV-1 infection. PMID:21525355

The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome.

PubMed

Crisponi, L; Deiana, M; Loi, A; Chiappe, F; Uda, M; Amati, P; Bisceglia, L; Zelante, L; Nagaraja, R; Porcu, S; Ristaldi, M S; Marzella, R; Rocchi, M; Nicolino, M; Lienhardt-Roussie, A; Nivelon, A; Verloes, A; Schlessinger, D; Gasparini, P; Bonneau, D; Cao, A; Pilia, G

2001-02-01

In type I blepharophimosis/ptosis/epicanthus inversus syndrome (BPES), eyelid abnormalities are associated with ovarian failure. Type II BPES shows only the eyelid defects, but both types map to chromosome 3q23. We have positionally cloned a novel, putative winged helix/forkhead transcription factor gene, FOXL2, that is mutated to produce truncated proteins in type I families and larger proteins in type II. Consistent with an involvement in those tissues, FOXL2 is selectively expressed in the mesenchyme of developing mouse eyelids and in adult ovarian follicles; in adult humans, it appears predominantly in the ovary. FOXL2 represents a candidate gene for the polled/intersex syndrome XX sex-reversal goat.

Downregulation of Forkhead box F1 gene expression in the pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia.

PubMed

Zimmer, J; Takahashi, T; Hofmann, A D; Puri, Prem

2016-12-01

High mortality and morbidity in infants born with congenital diaphragmatic hernia (CDH) are attributed to pulmonary hypoplasia and pulmonary hypertension (PH). Forkhead box (Fox) transcription factors are known to be crucial for cell proliferation and homeostasis. FoxF1 is essential for lung morphogenesis, vascular development, and endothelial proliferation. Mutations in FoxF1 and also the Fox family member FoxC2 have been identified in neonates with PH. In human and experimental models of arterial PH, the Fox protein FoxO1 was found to be downregulated. We hypothesized that Fox expression is altered in the lungs of the nitrofen-induced CDH rat model and investigated the expression of FoxF1, FoxC2, and FoxO1. Following ethical approval (Rec 913b), time-pregnant Sprague-Dawley rats received nitrofen or vehicle on gestational day (D9). Fetuses were sacrificed on D21, inspected for CDH and divided into CDH (n = 11) and control group (n = 11). Gene expression of FoxF1, FoxC2, and FoxO1 was evaluated with qRT-PCR. Detected alterations of mRNA levels were subsequently assessed on the protein level by performing western blot analysis and laser scanning confocal microscopy. The relative mRNA level of FoxF1 was significantly downregulated in CDH lungs compared to controls (FoxF1 CDH 1.047 ± 0.108, FoxF1 Ctrl 1.419 ± 0.01, p = 0.014). Relative mRNA levels of FoxC2 and FoxO1 were not found to be altered between the experimental groups (FoxC2 CDH 30.74 ± 8.925, FoxC2 Ctrl 27.408 ± 7.487, p = 0.776; FoxO1 CDH 0.011 ± 0.002, FoxO1 Ctrl 0.011 ± 0.001, p = 0.809). On the protein level, western blotting demonstrated a reduced pulmonary protein expression of FoxF1 in CDH lungs. Confocal microscopy showed a markedly diminished expression of FoxF1 in the pulmonary vasculature of CDH lungs compared to controls. Our study demonstrates a strikingly reduced expression of FoxF1 in the pulmonary vasculature of nitrofen-induced CDH. Altered FoxF1 gene expression

PcFKH1, a novel regulatory factor from the forkhead family, controls the biosynthesis of penicillin in Penicillium chrysogenum.

PubMed

Domínguez-Santos, Rebeca; García-Estrada, Carlos; Kosalková, Katarina; Prieto, Carlos; Santamarta, Irene; Martín, Juan-Francisco

2015-08-01

Penicillin biosynthesis in Penicillium chrysogenum (re-identified as Penicillium rubens) is a good example of a biological process subjected to complex global regulatory networks and serves as a model to study fungal secondary metabolism. The winged-helix family of transcription factors recently described, which includes the forkhead type of proteins, is a key type of regulatory proteins involved in this process. In yeasts and humans, forkhead transcription factors are involved in different processes (cell cycle regulation, cell death control, pre-mRNA processing and morphogenesis); one member of this family of proteins has been identified in the P. chrysogenum genome (Pc18g00430). In this work, we have characterized this novel transcription factor (named PcFKH1) by generating knock-down mutants and overexpression strains. Results clearly indicate that PcFKH1 positively controls antibiotic biosynthesis through the specific interaction with the promoter region of the penDE gene, thus regulating penDE mRNA levels. PcFKH1 also binds to the pcbC promoter, but with low affinity. In addition, it also controls other ancillary genes of the penicillin biosynthetic process, such as phlA (encoding phenylacetyl CoA ligase) and ppt (encoding phosphopantetheinyl transferase). PcFKH1 also plays a role in conidiation and spore pigmentation, but it does not seem to be involved in hyphal morphology or cell division in the improved laboratory reference strain Wisconsin 54-1255. A genome-wide analysis of processes putatively coregulated by PcFKH1 and PcRFX1 (another winged-helix transcription factor) in P. chrysogenum provided evidence of the global effect of these transcription factors in P. chrysogenum metabolism. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Forkhead Transcription Factors: Formulating a FOXO Target for Cognitive Loss.

PubMed

Maiese, Kenneth

2017-01-01

With almost 47 million individuals worldwide suffering from some aspect of dementia, it is clear that cognitive loss impacts a significant proportion of the global population. Unfortunately, definitive treatments to resolve or prevent the onset of cognitive loss are limited. In most cases such care is currently non-existent prompting the need for novel treatment strategies. Mammalian forkhead transcription factors of the O class (FoxO) are one such avenue of investigation that offer an exciting potential to bring new treatments forward for disorders that involve cognitive loss. Here we examine the background, structure, expression, and function of FoxO transcription factors and their role in cognitive loss, programmed cell death in the nervous system with apoptosis and autophagy, and areas to target FoxOs for dementia and specific disorders such as Alzheimer's disease. FoxO proteins work in concert with a number of other cell survival pathways that involve growth factors, such as erythropoietin and neurotrophins, silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), Wnt1 inducible signaling pathway protein 1 (WISP1), Wnt signaling, and cancer-related pathways. FoxO transcription factors oversee proinflammatory pathways, affect nervous system amyloid (Aβ) production and toxicity, lead to mitochondrial dysfunction, foster neuronal apoptotic cell death, and accelerate the progression of degenerative disease. However, under some scenarios such as those involving autophagy, FoxOs also can offer protection in the nervous system and reduce toxic intracellular protein accumulations and potentially limit Aβ toxicity. Given the ability of FoxOs to not only promote apoptotic cell death in the nervous system, but also through the induction of autophagy offer protection against degenerative disease that can lead to dementia, a fine balance in the activity of FoxOs may be required to target cognitive loss in individuals. Future work should

Induction of Chromosome Instability by Activation of Yes-Associated Protein and Forkhead Box M1 in Liver Cancer.

PubMed

Weiler, Sofia M E; Pinna, Federico; Wolf, Thomas; Lutz, Teresa; Geldiyev, Aman; Sticht, Carsten; Knaub, Maria; Thomann, Stefan; Bissinger, Michaela; Wan, Shan; Rössler, Stephanie; Becker, Diana; Gretz, Norbert; Lang, Hauke; Bergmann, Frank; Ustiyan, Vladimir; Kalin, Tatiana V; Singer, Stephan; Lee, Ju-Seog; Marquardt, Jens U; Schirmacher, Peter; Kalinichenko, Vladimir V; Breuhahn, Kai

2017-06-01

Many different types of cancer cells have chromosome instability. The hippo pathway leads to phosphorylation of the transcriptional activator yes-associated protein 1 (YAP1, YAP), which regulates proliferation and has been associated with the development of liver cancer. We investigated the effects of hippo signaling via YAP on chromosome stability and hepatocarcinogenesis in humans and mice. We analyzed transcriptome data from 242 patients with hepatocellular carcinoma (HCC) to search for gene signatures associated with chromosomal instability (CIN); we investigated associations with overall survival time and cancer recurrence using Kaplan-Meier curves. We analyzed changes in expression of these signature genes, at mRNA and protein levels, after small interfering RNA-mediated silencing of YAP in Sk-Hep1, SNU182, HepG2, or pancreatic cancer cells, as well as incubation with thiostrepton (an inhibitor of forkhead box M1 [FOXM1]) or verteporfin (inhibitor of the interaction between YAP and TEA domain transcription factor 4 [TEAD4]). We performed co-immunoprecipitation and chromatin immunoprecipitation experiments. We collected liver tissues from mice that express a constitutively active form of YAP (YAP S127A ) and analyzed gene expression signatures and histomorphologic parameters associated with chromosomal instability. Mice were given injections of thiostrepton and livers were collected and analyzed by immunoblotting, immunohistochemistry, histology, and real-time polymerase chain reaction. We performed immunohistochemical analyses on tissue microarrays of 105 HCCs and 7 nontumor liver tissues. Gene expression patterns associated with chromosome instability, called CIN25 and CIN70, were detected in HCCs from patients with shorter survival time or early cancer recurrence. TEAD4 and YAP were required for CIN25 and CIN70 signature expression via induction and binding of FOXM1. Disrupting the interaction between YAP and TEAD4 with verteporfin, or inhibiting FOXM1

Minimal phenotype of mice homozygous for a null mutation in the forkhead/winged helix gene, Mf2.

PubMed

Kume, T; Deng, K; Hogan, B L

2000-02-01

Mf2 (mesoderm/mesenchyme forkhead 2) encodes a forkhead/winged helix transcription factor expressed in numerous tissues of the mouse embryo, including paraxial mesoderm, somites, branchial arches, vibrissae, developing central nervous system, and developing kidney. We have generated mice homozygous for a null mutation in the Mf2 gene (Mf2(lacZ)) to examine its role during embryonic development. The lacZ allele also allows monitoring of Mf2 gene expression. Homozygous null mutants are viable and fertile and have no major developmental defects. Some mutants show renal abnormalities, including kidney hypoplasia and hydroureter, but the penetrance of this phenotype is only 40% or lower, depending on the genetic background. These data suggest that Mf2 can play a unique role in kidney development, but there is functional redundancy in this organ and other tissues with other forkhead/winged helix genes.

Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3).

PubMed

Syed, Aleena; Garcia, Marco A; Lyu, Shu-Chen; Bucayu, Robert; Kohli, Arunima; Ishida, Satoru; Berglund, Jelena P; Tsai, Mindy; Maecker, Holden; O'Riordan, Gerri; Galli, Stephen J; Nadeau, Kari C

2014-02-01

The mechanisms contributing to clinical immune tolerance remain incompletely understood. This study provides evidence for specific immune mechanisms that are associated with a model of operationally defined clinical tolerance. Our overall objective was to study laboratory changes associated with clinical immune tolerance in antigen-induced T cells, basophils, and antibodies in subjects undergoing oral immunotherapy (OIT) for peanut allergy. In a phase 1 single-site study, we studied participants (n = 23) undergoing peanut OIT and compared them with age-matched allergic control subjects (n = 20) undergoing standard of care (abstaining from peanut) for 24 months. Participants were operationally defined as clinically immune tolerant (IT) if they had no detectable allergic reactions to a peanut oral food challenge after 3 months of therapy withdrawal (IT, n = 7), whereas those who had an allergic reaction were categorized as nontolerant (NT; n = 13). Antibody and basophil activation measurements did not statistically differentiate between NT versus IT participants. However, T-cell function and demethylation of forkhead box protein 3 (FOXP3) CpG sites in antigen-induced regulatory T cells were significantly different between IT versus NT participants. When IT participants were withdrawn from peanut therapy for an additional 3 months (total of 6 months), only 3 participants remained classified as IT participants, and 4 participants regained sensitivity along with increased methylation of FOXP3 CpG sites in antigen-induced regulatory T cells. In summary, modifications at the DNA level of antigen-induced T-cell subsets might be predictive of a state of operationally defined clinical immune tolerance during peanut OIT. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Two Forkhead transcription factors regulate the division of cardiac progenitor cells by a Polo-dependent pathway

PubMed Central

Ahmad, Shaad M.; Tansey, Terese R.; Busser, Brian W.; Nolte, Michael T.; Jeffries, Neal; Gisselbrecht, Stephen S.; Rusan, Nasser M.; Michelson, Alan M.

2012-01-01

SUMMARY The development of a complex organ requires the specification of appropriate numbers of each of its constituent cell types, as well as their proper differentiation and correct positioning relative to each other. During Drosophila cardiogenesis, all three of these processes are controlled by jumeau (jumu) and Checkpoint suppressor homologue (CHES-1-like), two genes encoding forkhead transcription factors that we discovered utilizing an integrated genetic, genomic and computational strategy for identifying genes expressed in the developing Drosophila heart. Both jumu and CHES-1-like are required during asymmetric cell division for the derivation of two distinct cardiac cell types from their mutual precursor, and in symmetric cell divisions that produce yet a third type of heart cell. jumu and CHES-1-like control the division of cardiac progenitors by regulating the activity of Polo, a kinase involved in multiple steps of mitosis. This pathway demonstrates how transcription factors integrate diverse developmental processes during organogenesis. PMID:22814603

Minimal Phenotype of Mice Homozygous for a Null Mutation in the Forkhead/Winged Helix Gene, Mf2

PubMed Central

Kume, Tsutomu; Deng, Keyu; Hogan, Brigid L. M.

2000-01-01

Mf2 (mesoderm/mesenchyme forkhead 2) encodes a forkhead/winged helix transcription factor expressed in numerous tissues of the mouse embryo, including paraxial mesoderm, somites, branchial arches, vibrissae, developing central nervous system, and developing kidney. We have generated mice homozygous for a null mutation in the Mf2 gene (Mf2lacZ) to examine its role during embryonic development. The lacZ allele also allows monitoring of Mf2 gene expression. Homozygous null mutants are viable and fertile and have no major developmental defects. Some mutants show renal abnormalities, including kidney hypoplasia and hydroureter, but the penetrance of this phenotype is only 40% or lower, depending on the genetic background. These data suggest that Mf2 can play a unique role in kidney development, but there is functional redundancy in this organ and other tissues with other forkhead/winged helix genes. PMID:10648626

Forkhead Box O1 Is Present in Quiescent Pituitary Cells during Development and Is Increased in the Absence of p27Kip1

PubMed Central

Majumdar, Sreeparna; Farris, Corrie L.; Kabat, Brock E.; Jung, Deborah O.; Ellsworth, Buffy S.

2012-01-01

Congenital pituitary hormone deficiencies have been reported in approximately one in 4,000 live births, however studies reporting mutations in some widely studied transcription factors account for only a fraction of congenital hormone deficiencies in humans. Anterior pituitary hormones are required for development and function of several glands including gonads, adrenals, and thyroid. In order to identify additional factors that contribute to human congenital hormone deficiencies, we are investigating the forkhead transcription factor, FOXO1, which has been implicated in development of several organs including ovary, testis, and brain. We find that FOXO1 is present in the nuclei of non-dividing pituitary cells during embryonic development, consistent with a role in limiting proliferation and/or promoting differentiation. FOXO1 is present in a subset of differentiated cells at e18.5 and in adult with highest level of expression in somatotrope cells. We detected FOXO1 in p27Kip1-positive cells at e14.5. In the absence of p27Kip1 the number of pituitary cells containing FOXO1 is significantly increased at e14.5 suggesting that a feedback loop regulates the interplay between FOXO1 and p27Kip1. PMID:23251696

Luteolin and fisetin suppress oxidative stress by modulating sirtuins and forkhead box O3a expression under in vitro diabetic conditions.

PubMed

Kim, Arang; Lee, Wooje; Yun, Jung-Mi

2017-10-01

Chronic hyperglycemia induces oxidative stress via accumulation of reactive oxygen species (ROS) and contributes to diabetic complications. Hyperglycemia induces mitochondrial superoxide anion production through the increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to determine whether fisetin and luteolin treatments suppress the oxidative stress by modulating the expression of sirtuins (SIRTs) and forkhead box O3a (FOXO3a) under hyperglycemic conditions in human monocytes. Human monocytic cells (THP-1) were cultured under osmotic control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin and luteolin for 48 h. To determine the effect of fisetin and luteolin treatments on high glucose-induced oxidative stress, western blotting and intracellular staining were performed. Hyperglycemic conditions increased the ROS production, as compared to normoglycemic condition. However, fisetin and luteolin treatments inhibited ROS production under hyperglycemia. To obtain further insight into ROS production in hyperglycemic conditions, evaluation of p47phox expression revealed that fisetin and luteolin treatments inhibited p47phox expression under hyperglycemic conditions. Conversely, the expression levels of SIRT1, SIRT3, SIRT6, and FOXO3a were decreased under high glucose conditions compared to normal glucose conditions, but exposure to fisetin and luteolin induced the expression of SIRT1, SIRT3, SIRT6, and FOXO3a. The above findings suggest that fisetin and luteolin inhibited high glucose-induced ROS production in monocytes through the activation of SIRTs and FOXO3a. The results of our study supports current researches that state fisetin and luteolin as potential agents for the development of novel strategies for diabetes.

Luteolin and fisetin suppress oxidative stress by modulating sirtuins and forkhead box O3a expression under in vitro diabetic conditions

PubMed Central

Kim, Arang; Lee, Wooje

2017-01-01

BACKGROUND/OBJECTIVE Chronic hyperglycemia induces oxidative stress via accumulation of reactive oxygen species (ROS) and contributes to diabetic complications. Hyperglycemia induces mitochondrial superoxide anion production through the increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to determine whether fisetin and luteolin treatments suppress the oxidative stress by modulating the expression of sirtuins (SIRTs) and forkhead box O3a (FOXO3a) under hyperglycemic conditions in human monocytes. MATERIALS/METHODS Human monocytic cells (THP-1) were cultured under osmotic control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin and luteolin for 48 h. To determine the effect of fisetin and luteolin treatments on high glucose-induced oxidative stress, western blotting and intracellular staining were performed. RESULTS Hyperglycemic conditions increased the ROS production, as compared to normoglycemic condition. However, fisetin and luteolin treatments inhibited ROS production under hyperglycemia. To obtain further insight into ROS production in hyperglycemic conditions, evaluation of p47phox expression revealed that fisetin and luteolin treatments inhibited p47phox expression under hyperglycemic conditions. Conversely, the expression levels of SIRT1, SIRT3, SIRT6, and FOXO3a were decreased under high glucose conditions compared to normal glucose conditions, but exposure to fisetin and luteolin induced the expression of SIRT1, SIRT3, SIRT6, and FOXO3a. The above findings suggest that fisetin and luteolin inhibited high glucose-induced ROS production in monocytes through the activation of SIRTs and FOXO3a. CONCLUSIONS The results of our study supports current researches that state fisetin and luteolin as potential agents for the development of novel strategies for diabetes. PMID:28989580

Suppression of forkhead box Q1 by microRNA-506 represses the proliferation and epithelial-mesenchymal transition of cervical cancer cells.

PubMed

Zhang, Mingting; Xu, Qingli; Yan, Shufen; Li, Zhigang; Yan, Wei; Jia, Xiaojing

2016-05-01

MicroRNAs (miRNAs) play a pivotal role in cancer progression and development, representing novel therapeutic tools for cancer therapy. Forkhead box Q1 (FOXQ1) functions as an oncogene in various cancer types. However, the functional significance of FOXQ1 in cervical cancer remains unknown. In this study, we investigated the biological function of FOXQ1 in cervical cancer and tested whether or not FOXQ1 can be targeted and regulated by specific miRNAs. We found that FOXQ1 was highly expressed in cervical cancer cell lines. Knockdown of FOXQ1 by small interfering RNA (siRNA) significantly suppressed the proliferation and epithelial-mesenchymal transition (EMT) of cervical cancer cells. FOXQ1 was predicted as a target gene of microRNA-506 (miR-506), and this prediction was validated by dual-luciferase reporter assay. Quantitative real-time PCR and western blot analyses demonstrated that mRNA and protein expression was negatively regulated by miR-506. The expression of miR-506 was downregulated in cervical cancer tissues, and miR-506 expression was inversely correlated with FOXQ1 expression in cervical cancer. The overexpression of miR-506 dramatically suppressed the proliferation and EMT of cervical cancer cells that mimicked the suppression of FOXO1 siRNA. Furthermore, the restoration of FOXQ1 expression significantly reversed the inhibitory effect of miR-506. Overall, our study demonstrated that miR-506 inhibited the proliferation and EMT of cervical cancer cells by targeting FOXQ1 and provided evidence that the miR-506/FOXQ1 axis plays an important role in the pathogenesis of cervical cancer, representing potential molecular targets for the development of anticancer agents for cervical cancer treatment.

Diabetic complications within the context of aging: Nicotinamide adenine dinucleotide redox, insulin C-peptide, sirtuin 1-liver kinase B1-adenosine monophosphate-activated protein kinase positive feedback and forkhead box O3.

PubMed

Ido, Yasuo

2016-07-01

Recent research in nutritional control of aging suggests that cytosolic increases in the reduced form of nicotinamide adenine dinucleotide and decreasing nicotinamide adenine dinucleotide metabolism plays a central role in controlling the longevity gene products sirtuin 1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK) and forkhead box O3 (FOXO3). High nutrition conditions, such as the diabetic milieu, increase the ratio of reduced to oxidized forms of cytosolic nicotinamide adenine dinucleotide through cascades including the polyol pathway. This redox change is associated with insulin resistance and the development of diabetic complications, and might be counteracted by insulin C-peptide. My research and others' suggest that the SIRT1-liver kinase B1-AMPK cascade creates positive feedback through nicotinamide adenine dinucleotide synthesis to help cells cope with metabolic stress. SIRT1 and AMPK can upregulate liver kinase B1 and FOXO3, key factors that help residential stem cells cope with oxidative stress. FOXO3 directly changes epigenetics around transcription start sites, maintaining the health of stem cells. 'Diabetic memory' is likely a result of epigenetic changes caused by high nutritional conditions, which disturb the quiescent state of residential stem cells and impair tissue repair. This could be prevented by restoring SIRT1-AMPK positive feedback through activating FOXO3. © 2016 The Author. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Fox transcription factors: from development to disease.

PubMed

Golson, Maria L; Kaestner, Klaus H

2016-12-15

Forkhead box (Fox) transcription factors are evolutionarily conserved in organisms ranging from yeast to humans. They regulate diverse biological processes both during development and throughout adult life. Mutations in many Fox genes are associated with human disease and, as such, various animal models have been generated to study the function of these transcription factors in mechanistic detail. In many cases, the absence of even a single Fox transcription factor is lethal. In this Primer, we provide an overview of the Fox family, highlighting several key Fox transcription factor families that are important for mammalian development. © 2016. Published by The Company of Biologists Ltd.

FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons

PubMed Central

Gilley, Jonathan; Coffer, Paul J.; Ham, Jonathan

2003-01-01

Developing sympathetic neurons die by apoptosis when deprived of NGF. BIM, a BH3-only member of the BCL-2 family, is induced after NGF withdrawal in these cells and contributes to NGF withdrawal–induced death. Here, we have investigated the involvement of the Forkhead box, class O (FOXO) subfamily of Forkhead transcription factors in the regulation of BIM expression by NGF. We find that overexpression of FOXO transcription factors induces BIM expression and promotes death of sympathetic neurons in a BIM-dependent manner. In addition, we find that FKHRL1 (FOXO3a) directly activates the bim promoter via two conserved FOXO binding sites and that mutation of these sites abolishes bim promoter activation after NGF withdrawal. Finally, we show that FOXO activity contributes to the NGF deprivation–induced death of sympathetic neurons. PMID:12913110

The Forkhead Transcription Factor Hcm1 Promotes Mitochondrial Biogenesis and Stress Resistance in Yeast*

PubMed Central

Rodriguez-Colman, Maria José; Reverter-Branchat, Gemma; Sorolla, M. Alba; Tamarit, Jordi; Ros, Joaquim; Cabiscol, Elisa

2010-01-01

In Saccharomyces cerevisiae, the forkhead transcription factor Hcm1 is involved in chromosome segregation, spindle pole dynamics, and budding. We found that Hcm1 interacts with the histone deacetylase Sir2 and shifts from cytoplasm to the nucleus in the G1/S phase or in response to oxidative stress stimuli. The nuclear localization of Hcm1 depends on the activity of Sir2 as revealed by activators and inhibitors of the sirtuins and the Δsir2 mutant. Hcm1-overexpressing cells display more mitochondria that can be attributed to increased amounts of Abf2, a protein involved in mitochondrial biogenesis. These cells also show higher rates of oxygen consumption and improved resistance to oxidative stress that would be explained by increased catalase and Sod2 activities and molecular chaperones such as Hsp26, Hsp30, and members of Hsp70 family. Microarray analyses also reveal increased expression of genes involved in mitochondrial energy pathways and those allowing the transition from the exponential to the stationary phase. Taken together, these results describe a new and relevant role of Hcm1 for mitochondrial functions, suggesting that this transcription factor would participate in the adaptation of cells from fermentative to respiratory metabolism. PMID:20847055

Nuclear factor ETF specifically stimulates transcription from promoters without a TATA box.

PubMed

Kageyama, R; Merlino, G T; Pastan, I

1989-09-15

Transcription factor ETF stimulates the expression of the epidermal growth factor receptor (EGFR) gene which does not have a TATA box in the promoter region. Here, we show that ETF recognizes various GC-rich sequences including stretches of deoxycytidine or deoxyguanosine residues and GC boxes with similar affinities. ETF also binds to TATA boxes but with a lower affinity. ETF stimulated in vitro transcription from several promoters without TATA boxes but had little or no effect on TATA box-containing promoters even though they had strong ETF-binding sites. These inactive ETF-binding sites became functional when placed upstream of the EGFR promoter whose own ETF-binding sites were removed. Furthermore, when a TATA box was introduced into the EGFR promoter, the responsiveness to ETF was abolished. These results indicate that ETF is a specific transcription factor for promoters which do not contain TATA elements.

Mutation spectrum of fork-head transcriptional factor gene (FOXL2) in Indian Blepharophimosis Ptosis Epicanthus Inversus Syndrome (BPES) patients.

PubMed

Kaur, Inderjeet; Hussain, Avid; Naik, Milind N; Murthy, Ramesh; Honavar, Santosh G

2011-06-01

The fork-head transcription factor gene (FOXL2) gene has been implicated in Blepharophimosis Ptosis Epicanthus Inversus Syndrome (BPES) type I and type II. The authors aimed to evaluate the involvement of FOXL2 in familial and sporadic cases of BPES in an Indian cohort. The present cohort comprised clinically well-characterised BPES cases that included six affected families, two sporadic cases and 60 unaffected normal controls. The 5' untranslated and coding region of FOXL2 was screened by resequencing and confirmed by restriction digestion. Further, genotype-phenotype correlations were done to understand the implications of the observed mutation. Six mutations were observed in eight cases (87.5%). These included a novel deletion (c.860delC), three previously reported duplications (c.663-692dup 30, c.672-701dup30 and c.843-859dup17), a frame shift (c.804dupC) and a homozygous missense mutation (p.E69K). The p.E69k mutation was seen in both heterozygous and homozygous form in a large four-generational family, and disease severity was found to be directly linked to the allelic dosage. Two SNPs (c.501C→T, c.536C→G) were also noted. An unusual coexistence of polycystic ovarian disease (PCOD) with BPES was also seen in one of the families. Mutations in the region downstream of the fork-head domain were predominantly responsible for BPES among Indian patients.

PTEN regulates p300-dependent hypoxia-inducible factor 1 transcriptional activity through Forkhead transcription factor 3a (FOXO3a)

PubMed Central

Emerling, Brooke M.; Weinberg, Frank; Liu, Juinn-Lin; Mak, Tak W.; Chandel, Navdeep S.

2008-01-01

The tumor suppressor PTEN is mutated or deleted in many tumors, causing the activation of the PI3K pathway. Here, we show that the loss of PTEN increases the transcriptional activity of hypoxia-inducible factor 1 (HIF-1) through the inactivation of Forkhead transcription factors (FOXO) in PTEN-null cells. Reintroduction of PTEN into the nucleus, overexpression of a nonphosphorylatable FOXO3a, which accumulates in the nucleus, or inhibition of nuclear export of FOXO3a by leptomycin B represses HIF-1 transcriptional activity in PTEN-null cells. HIF-1 transcriptional activity increases in PTEN-positive cells depleted of FOXO3a with siRNA. PTEN and FOXO3a regulate the transactivation domain of HIF-1α. Chromatin immunoprecipitation indicates that FOXO3a complexes with HIF-1α and p300 on the Glut-1 promoter, a HIF-1 target gene. Overexpression of p300 reverses FOXO3a-mediated repression of HIF-1 transcriptional activity. Coimmunoprecipitation and GAL4-HIF-1α transactivation assays reveal that FOXO3a interferes with p300-dependent HIF-1 transcriptional activity. Thus, FOXO3a negatively regulates HIF-1 transcriptional activity. PMID:18268343

Effect of pH on the Structure and DNA Binding of the FOXP2 Forkhead Domain.

PubMed

Blane, Ashleigh; Fanucchi, Sylvia

2015-06-30

Forkhead box P2 (FOXP2) is a transcription factor expressed in cardiovascular, intestinal, and neural tissues during embryonic development and is implicated in language development. FOXP2 like other FOX proteins contains a DNA binding domain known as the forkhead domain (FHD). The FHD interacts with DNA by inserting helix 3 into the major groove. One of these DNA-protein interactions is a direct hydrogen bond that is formed with His554. FOXP2 is localized in the nuclear compartment that has a pH of 7.5. Histidine contains an imidazole side chain in which the amino group typically has a pKa of ~6.5. It seems possible that pH fluctuations around 6.5 may result in changes in the protonation state of His554 and thus the ability of the FOXP2 FHD to bind DNA. To investigate the effect of pH on the FHD, both the structure and the binding affinity were studied in the pH range of 5-9. This was done in the presence and absence of DNA. The structure was assessed using size exclusion chromatography, far-UV circular dichroism, and intrinsic and extrinsic fluorescence. The results indicated that while pH did not affect the secondary structure in the presence or absence of DNA, the tertiary structure was pH sensitive and the protein was less compact at low pH. Furthermore, the presence of DNA caused the protein to become more compact at low pH and also had the potential to increase the dimerization propensity. Fluorescence anisotropy was used to investigate the effect of pH on the FOXP2 FHD DNA binding affinity. It was found that pH had a direct effect on binding affinity. This was attributed to the altered hydrogen bonding patterns upon protonation or deprotonation of His554. These results could implicate pH as a means of regulating transcription by the FOXP2 FHD, which may also have repercussions for the behavior of this protein in cancer cells.

Effects of oral Lactobacillus administration on antioxidant activities and CD4+CD25+forkhead box P3 (FoxP3)+ T cells in NZB/W F1 mice.

PubMed

Tzang, Bor-Show; Liu, Chung-Hsien; Hsu, Kuo-Ching; Chen, Yi-Hsing; Huang, Chih-Yang; Hsu, Tsai-Ching

2017-09-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterised by a dysregulation of the immune system, which causes inflammation responses, excessive oxidative stress and a reduction in the number of cluster of differentiation (CD)4+CD25+forkhead box P3 (FoxP3)+ T cells. Supplementation with certain Lactobacillus strains has been suggested to be beneficial in the comprehensive treatment of SLE. However, little is known about the effect and mechanism of certain Lactobacillus strains on SLE. To investigate the effects of Lactobacillus on SLE, NZB/W F1 mice were orally gavaged with Lactobacillus paracasei GMNL-32 (GMNL-32), Lactobacillus reuteri GMNL-89 (GMNL-89) and L. reuteri GMNL-263 (GMNL-263). Supplementation with GMNL-32, GMNL-89 and GMNL-263 significantly increased antioxidant activity, reduced IL-6 and TNF-α levels and significantly decreased the toll-like receptors/myeloid differentiation primary response gene 88 signalling in NZB/W F1 mice. Notably, supplementation with GMNL-263, but not GMNL-32 and GMNL-89, in NZB/W F1 mice significantly increased the differentiation of CD4+CD25+FoxP3+ T cells. These findings reveal beneficial effects of GMNL-32, GMNL-89 and GMNL-263 on NZB/W F1 mice and suggest that these specific Lactobacillus strains can be used as part of a comprehensive treatment of SLE patients.

The Forkhead Transcription Factor, Foxd1, Is Necessary for Pituitary Luteinizing Hormone Expression in Mice

PubMed Central

Gumbel, Jason H.; Patterson, Elizabeth M.; Owusu, Sarah A.; Kabat, Brock E.; Jung, Deborah O.; Simmons, Jasmine; Hopkins, Torin; Ellsworth, Buffy S.

2012-01-01

The pituitary gland regulates numerous physiological functions including growth, reproduction, temperature and metabolic homeostasis, lactation, and response to stress. Pituitary organogenesis is dependent on signaling factors that are produced in and around the developing pituitary. The studies described in this report reveal that the forkhead transcription factor, Foxd1, is not expressed in the developing mouse pituitary gland, but rather in the mesenchyme surrounding the pituitary gland, which is an essential source of signaling factors that regulate pituitary organogenesis. Loss of Foxd1 causes a morphological defect in which the anterior lobe of the pituitary gland protrudes through the cartilage plate that is developing ventral to the pituitary at embryonic days (e)14.5, e16.5, and e18.5. The number of proliferating pituitary cells is increased at e14.5 and e16.5. Loss of Foxd1 also results in significantly decreased levels of Lhb expression at e18.5. This decrease in Lhb expression does not appear to be due to a change in the number of gonadotrope cells in the pituitary gland. Previous studies have shown that loss of the LIM homeodomain factor, Lhx3, which is activated by the FGF signaling pathway, results in loss of LH production. Although there is a difference in Lhb expression in Foxd1 null mice, the expression pattern of LHX3 is not altered in Foxd1 null mice. These studies suggest that Foxd1 is indirectly required for normal Lhb expression and cartilage formation. PMID:23284914

GSK3 Protein Positively Regulates Type I Insulin-like Growth Factor Receptor through Forkhead Transcription Factors FOXO1/3/4

PubMed Central

Huo, Xiaodong; Liu, Shu; Shao, Ting; Hua, Hui; Kong, Qingbin; Wang, Jiao; Luo, Ting; Jiang, Yangfu

2014-01-01

Glycogen synthase kinase-3 (GSK3) has either tumor-suppressive roles or pro-tumor roles in different types of human tumors. A number of GSK3 targets in diverse signaling pathways have been uncovered, such as tuberous sclerosis complex subunit 2 and β-catenin. The O subfamily of forkhead/winged helix transcription factors (FOXO) is known as tumor suppressors that induce apoptosis. In this study, we find that FOXO binds to type I insulin-like growth factor receptor (IGF-IR) promoter and stimulates its transcription. GSK3 positively regulates the transactivation activity of FOXO and stimulates IGF-IR expression. Although kinase-dead GSK3β cannot up-regulate IGF-IR, the constitutively active GSK3β induces IGF-IR expression in a FOXO-dependent manner. Serum starvation or Akt inhibition leads to an increase in IGF-IR expression, which could be blunted by GSK3 inhibition. GSK3β knockdown or GSK3 inhibitor suppresses IGF-I-induced IGF-IR, Akt, and ERK1/2 phosphorylation. Moreover, knockdown of GSK3β or FOXO1/3/4 leads to a decrease in cellular proliferation and abrogates IGF-I-induced hepatoma cell proliferation. These results suggest that GSK3 and FOXO may positively regulate IGF-I signaling and hepatoma cell proliferation. PMID:25053419

Associations between Forkhead Box O1 (FoxO1) Expression and Indicators of Hepatic Glucose Production in Transition Dairy Cows Supplemented with Dietary Nicotinic Acid.

PubMed

Kinoshita, Asako; Locher, Lena; Tienken, Reka; Meyer, Ulrich; Dänicke, Sven; Rehage, Jürgen; Huber, Korinna

2016-01-01

Forkhead box protein O1 (FoxO1) is a transcription factor which promotes hepatic glucose production (HGP) by up-regulating the transcription of gluconeogenic enzymes in monogastric species. The activity of FoxO1 is inhibited by insulin-induced phosphorylation. The aims of the present study were to find associations between FoxO1 expression and variables associated with HGP as affected by feeding regimen in dairy cows during the transition period. Twenty one healthy German Holstein cows were allocated to four groups (LC-CON, HC-CON, LC-NA with 5 cows/group and HC-NA with 6 cows/group, respectively). Cows received 0 (LC-CON and HC-CON) or 24 (LC-NA and HC-NA) g/d nicotinic acid with high (HC) or low (LC) concentrate proportion from -42 days (-41.8 + 4.8; mean + standard deviation) relative to expected calving date (d-42) to d24. Liver biopsy was taken at d-42, 1, 21, and 100. The total protein expression of FoxO1 (tFoxO1) and the extent of phosphorylation of FoxO1 at serine 256 (pFoxO1) were analysed semiquantitatively by Western Blotting. The expression of hepatic mRNA of FoxO1 and seven genes associated with HGP was measured by real-time RT-PCR. Mixed model and Pearson's correlation were used for statistical evaluation with the level of significance at P<0.05. No dietary effect was observed either on feed intake, energy balance, or on the concentration of blood metabolites. Neither time nor diet affected the expression of FoxO1 total protein and mRNA. A NA × concentrate interaction was found in pFoxO1. However, no corresponding dietary effect was found in the mRNA expression of investigated genes. Different patterns of correlations between FoxO1-related variables and investigated indicators for HGP were found at d21 and 100. The results indicated that the regulation of HGP did not take place on the levels of mRNA and protein expression and the phosphorylation of FoxO1 in dairy cows in early lactation.

Associations between Forkhead Box O1 (FoxO1) Expression and Indicators of Hepatic Glucose Production in Transition Dairy Cows Supplemented with Dietary Nicotinic Acid

PubMed Central

Kinoshita, Asako; Locher, Lena; Tienken, Reka; Meyer, Ulrich; Dänicke, Sven; Rehage, Jürgen; Huber, Korinna

2016-01-01

Forkhead box protein O1 (FoxO1) is a transcription factor which promotes hepatic glucose production (HGP) by up-regulating the transcription of gluconeogenic enzymes in monogastric species. The activity of FoxO1 is inhibited by insulin-induced phosphorylation. The aims of the present study were to find associations between FoxO1 expression and variables associated with HGP as affected by feeding regimen in dairy cows during the transition period. Twenty one healthy German Holstein cows were allocated to four groups (LC-CON, HC-CON, LC-NA with 5 cows/group and HC-NA with 6 cows/group, respectively). Cows received 0 (LC-CON and HC-CON) or 24 (LC-NA and HC-NA) g/d nicotinic acid with high (HC) or low (LC) concentrate proportion from -42 days (-41.8 + 4.8; mean + standard deviation) relative to expected calving date (d-42) to d24. Liver biopsy was taken at d-42, 1, 21, and 100. The total protein expression of FoxO1 (tFoxO1) and the extent of phosphorylation of FoxO1 at serine 256 (pFoxO1) were analysed semiquantitatively by Western Blotting. The expression of hepatic mRNA of FoxO1 and seven genes associated with HGP was measured by real-time RT-PCR. Mixed model and Pearson’s correlation were used for statistical evaluation with the level of significance at P<0.05. No dietary effect was observed either on feed intake, energy balance, or on the concentration of blood metabolites. Neither time nor diet affected the expression of FoxO1 total protein and mRNA. A NA × concentrate interaction was found in pFoxO1. However, no corresponding dietary effect was found in the mRNA expression of investigated genes. Different patterns of correlations between FoxO1-related variables and investigated indicators for HGP were found at d21 and 100. The results indicated that the regulation of HGP did not take place on the levels of mRNA and protein expression and the phosphorylation of FoxO1 in dairy cows in early lactation. PMID:26800252

Temporal and Spatial Acoustical Factors for Listeners in the Boxes of Historical Opera Theatres

NASA Astrophysics Data System (ADS)

Sakai, H.; Ando, Y.; Prodi, N.; Pompoli, R.

2002-11-01

Acoustical measurements were conducted in a horseshoe-shaped opera house to clarify the acoustical quality of a sound field for listeners inside the boxes of an historical opera house. In order to investigate the effects of multiple reflections between the walls inside a box and scattering by the heads of people, the location of the receiver and the number of persons in the box were varied. In each configuration, four orthogonal factors and supplementary factors were derived as temporal and spatial factors by analysis of binaural impulse responses. Each factor is compared to that at a typical location in the stalls of the same theatre. An omni-directional sound source was located on the stage to emulate a singer or in the orchestra pit to reproduce the location of the musicians. Thus, in this paper, temporal and spatial factors in relation to subjective evaluation are characterized against changes in the listening conditions inside a box, and procedures for improvement and design methods for boxes are proposed. The main conclusions reached are as follows. As strong reflections from the lateral walls of a hall are screened by the front or side walls of a box for a receiver in a seat deeper in the box, the maximum listening level ( LL) in the boxes was observed at the front of the box, and the maximum range of LL values for each box was found to be 5 dB. Concerning the initial time delay gap ( Δt1), a more uniform listening environment was obtained in boxes further back in the theatre than in one closer to the stage. The subsequent reverberation time ( Tsub) lengthens for boxes closer to the stage due to the stage house with its huge volume, and a peak is observed at 1 kHz. For the box at the back, Tsub monotonically decreases with frequency in the same way as in the stalls, and moreover, its values approach those in the stalls. As the contribution of multiple reflections relatively increases for a receiver deeper in the box, the IACC in such positions decreases in

Stem cell-dependent formation of a functional anterior regeneration pole in planarians requires Zic and Forkhead transcription factors.

PubMed

Vogg, Matthias C; Owlarn, Suthira; Pérez Rico, Yuvia A; Xie, Jianlei; Suzuki, Yoko; Gentile, Luca; Wu, Wei; Bartscherer, Kerstin

2014-06-15

Planarians can regenerate their head within days. This process depends on the direction of adult stem cells to wound sites and the orchestration of their progenitors to commit to appropriate lineages and to arrange into patterned tissues. We identified a zinc finger transcription factor, Smed-ZicA, as a downstream target of Smed-FoxD, a Forkhead transcription factor required for head regeneration. Smed-zicA and Smed-FoxD are co-expressed with the Wnt inhibitor notum and the Activin inhibitor follistatin in a cluster of cells at the anterior-most tip of the regenerating head - the anterior regeneration pole - and in surrounding stem cell progeny. Depletion of Smed-zicA and Smed-FoxD by RNAi abolishes notum and follistatin expression at the pole and inhibits head formation downstream of initial polarity decisions. We suggest a model in which ZicA and FoxD transcription factors synergize to control the formation of Notum- and Follistatin-producing anterior pole cells. Pole formation might constitute an early step in regeneration, resulting in a signaling center that orchestrates cellular events in the growing tissue. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Curcumin induces apoptosis in pancreatic cancer cells through the induction of forkhead box O1 and inhibition of the PI3K/Akt pathway.

PubMed

Zhao, Zhiming; Li, Chenggang; Xi, Hao; Gao, Yuanxing; Xu, Dabin

2015-10-01

Previous population investigations have suggested that the application of curcumin may be associated with decreased incidence and improved prognosis in certain types of cancer. Forkhead box O1 (FOXO1) has been implicated in the regulation of several biological processes, including stress resistance, metabolism, DNA repair, cell cycle and apoptosis. The aims of the present study were to investigate the effects and molecular mechanisms of curcumin on the induction of anti‑proliferation, cell cycle arrest and apoptosis, by FOXO1, in pancreatic cancer cells. The MTT assay and ELISA‑Brdu assay were used to assess cell proliferation. Reverse transcription‑quantitative polymerase chain reaction and western blot analyses were used to detect the expression of PCNA, Ki‑67, B‑cell lymphoma‑2 (Bcl‑2), B‑cell‑associated X protein (Bax), cyclin D1, p21, p27 and FOXO1. Cell apoptosis was detected using a Cell Death ELISA detection kit. A Caspase‑3/9 Fluorescent Assay kit was used to detect caspase activity. The findings revealed that curcumin significantly decreased cell proliferation, which was associated with increased expression of the p21/CIP1 and p27/KIP1 cyclin‑dependent kinase inhibitors, and inhibited expression of cyclin D1. In addition, curcumin induced apoptosis by decreasing the Bcl‑2/Bax protein ratio and increasing caspase‑9/3 activation in the pancreatic cancer cells. Using siRNA against FOXO1, and Akt inhibitor and activator, the present study confirmed that curcumin induced the expression of FOXO1 by inhibition of phosphoinositide 3‑kinase/Akt signaling, leading to cell cycle arrest and apoptosis. In conclusion, these findings offer support for a mechanism that may underlie the anti‑neoplastic effects of curcumin and justify further investigation to examine the potential roles for activators of FOXO1 in the prevention and treatment of pancreatic cancer.

Forkhead box O3 plays a role in skeletal muscle atrophy through expression of E3 ubiquitin ligases MuRF-1 and atrogin-1 in Cushing's syndrome.

PubMed

Kang, Seol-Hee; Lee, Hae-Ahm; Kim, Mina; Lee, Eunjo; Sohn, Uy Dong; Kim, Inkyeom

2017-06-01

Cushing's syndrome is caused by overproduction of the adrenocorticotropic hormone (ACTH), which stimulates the adrenal grand to make cortisol. Skeletal muscle wasting occurs in pathophysiological response to Cushing's syndrome. The forkhead box (FOX) protein family has been implicated as a key regulator of muscle loss under conditions such as diabetes and sepsis. However, the mechanistic role of the FOXO family in ACTH-induced muscle atrophy is not understood. We hypothesized that FOXO3a plays a role in muscle atrophy through expression of the E3 ubiquitin ligases, muscle RING finger protein-1 (MuRF-1), and atrogin-1 in Cushing's syndrome. For establishment of a Cushing's syndrome animal model, Sprague-Dawley rats were implanted with osmotic minipumps containing ACTH (40 ng·kg -1 ·day -1 ). ACTH infusion significantly reduced muscle weight. In ACTH-infused rats, MuRF-1, atrogin-1, and FOXO3a were upregulated and the FOXO3a promoter was targeted by the glucocorticoid receptor (GR). Transcriptional activity and expression of FOXO3a were significantly decreased by the GR antagonist RU486. Treatment with RU486 reduced MuRF-1 and atrogin-1 expression in accordance with reduced enrichment of FOXO3a and Pol II on the promoters. Knockdown of FOXO3a prevented dexamethasone-induced MuRF-1 and atrogin-1 expression. These results indicate that FOXO3a plays a role in muscle atrophy through expression of MuRF-1 and atrogin-1 in Cushing's syndrome. Copyright © 2017 the American Physiological Society.

Regulation of glucose metabolism via hepatic forkhead transcription factor 1 (FoxO1) by Morinda citrifolia (noni) in high-fat diet-induced obese mice.

PubMed

Nerurkar, Pratibha V; Nishioka, Adrienne; Eck, Philip O; Johns, Lisa M; Volper, Esther; Nerurkar, Vivek R

2012-07-01

Renewed interest in alternative medicine among diabetic individuals prompted us to investigate anti-diabetic effects of Morinda citrifolia (noni) in high-fat diet (HFD)-fed mice. Type 2 diabetes is associated with increased glucose production due to the inability of insulin to suppress hepatic gluconeogenesis and promote glycolysis. Insulin inhibits gluconeogenesis by modulating transcription factors such as forkhead box O (FoxO1). Based on microarray analysis data, we tested the hypothesis that fermented noni fruit juice (fNJ) improves glucose metabolism via FoxO1 phosphorylation. C57BL/6 male mice were fed a HFD and fNJ for 12 weeks. Body weights and food intake were monitored daily. FoxO1 expression was analysed by real-time PCR and Western blotting. Specificity of fNJ-associated FoxO1 regulation of gluconeogenesis was confirmed by small interfering RNA (siRNA) studies using human hepatoma cells, HepG2. Supplementation with fNJ inhibited weight gain and improved glucose and insulin tolerance and fasting glucose in HFD-fed mice. Hypoglycaemic properties of fNJ were associated with the inhibition of hepatic FoxO1 mRNA expression, with a concomitant increase in FoxO1 phosphorylation and nuclear expulsion of the proteins. Gluconeogenic genes, phosphoenolpyruvate C kinase (PEPCK) and glucose-6-phosphatase (G6P), were significantly inhibited in mice fed a HFD+fNJ. HepG2 cells demonstrated more than 80 % inhibition of PEPCK and G6P mRNA expression in cells treated with FoxO1 siRNA and fNJ. These data suggest that fNJ improves glucose metabolism via FoxO1 regulation in HFD-fed mice.

Regulation of glucose metabolism via hepatic forkhead transcription factor 1 (FoxO1) by Morinda citrifolia (noni) in high-fat diet-induced obese mice

PubMed Central

Nerurkar, Pratibha V.; Nishioka, Adrienne; Eck, Philip O.; Nerurkar, Vivek R.

2016-01-01

Renewed interest in alternative medicine among diabetic individuals prompted us to investigate anti-diabetic effects of Morinda citrifolia (noni) in high-fat diet (HFD)-fed mice. Type 2 diabetes is associated with increased glucose production due to the inability of insulin to suppress hepatic gluconeogenesis and promote glycolysis. Insulin inhibits gluconeogenesis by modulating transcription factors such as forkhead box O (FoxO1). Based on microarray analysis data, we tested the hypothesis that fermented noni fruit juice (fNJ) improves glucose metabolism via FoxO1 phosphorylation. C57BL/6 male mice were fed a HFD and fNJ for 12 weeks. Body weights and food intake were monitored daily. FoxO1 expression was analysed by real-time PCR and Western blotting. Specificity of fNJ-associated FoxO1 regulation of gluconeogenesis was confirmed by small interfering RNA (siRNA) studies using human hepatoma cells, HepG2. Supplementation with fNJ inhibited weight gain and improved glucose and insulin tolerance and fasting glucose in HFD-fed mice. Hypoglycaemic properties of fNJ were associated with the inhibition of hepatic FoxO1 mRNA expression, with a concomitant increase in FoxO1 phosphorylation and nuclear expulsion of the proteins. Gluconeogenic genes, phosphoenolpyruvate C kinase (PEPCK) and glucose-6-phosphatase (G6P), were significantly inhibited in mice fed a HFD + fNJ. HepG2 cells demonstrated more than 80% inhibition of PEPCK and G6P mRNA expression in cells treated with FoxO1 siRNA and fNJ. These data suggest that fNJ improves glucose metabolism via FoxO1 regulation in HFD-fed mice. PMID:22011624

Altered balance between self-reactive T helper (Th)17 cells and Th10 cells and between full-length forkhead box protein 3 (FoxP3) and FoxP3 splice variants in Hashimoto's thyroiditis.

PubMed

Kristensen, B; Hegedüs, L; Madsen, H O; Smith, T J; Nielsen, C H

2015-04-01

T helper type 17 (Th17) cells play a pathogenic role in autoimmune disease, while interleukin (IL)-10-producing Th10 cells serve a protective role. The balance between the two subsets is regulated by the local cytokine milieu and by the relative expression of intact forkhead box protein 3 (FoxP3) compared to FoxP3Δ2, missing exon 2. Th17 and Th10 cell differentiation has usually been studied using polyclonal stimuli, and little is known about the ability of physiologically relevant self-antigens to induce Th17 or Th10 cell differentiation in autoimmune thyroid disease. We subjected mononuclear cells from healthy donors and patients with Hashimoto's thyroiditis (HT) or Graves' disease (GD) to polyclonal stimulation, or stimulation with human thyroglobulin (TG), human thyroid peroxidase (TPO), or Esherichia coli lipopolysaccharide (LPS). TPO and LPS induced increased differentiation of naive CD4(+) CD45RA(+) CD45R0(-) T cells from HT patients into Th17 cells. Th10 cell proportions were decreased in HT after polyclonal stimulation, but were comparable to those of healthy donors after antigen-specific stimulation. Taken together, our data show that an increased Th17 : Th10 ratio was found in HT patients after stimulation with thyroid-specific self-antigens. We also observed an elevated baseline production of IL-6 and transforming growth factor (TGF)-β1 and of mRNA encoding FoxP3Δ2 rather than intact FoxP3. This may contribute to the skewing towards Th17 cell responses in HT. © 2014 British Society for Immunology.

Identification and analysis of evolutionary selection pressures acting at the molecular level in five forkhead subfamilies.

PubMed

Fetterman, Christina D; Rannala, Bruce; Walter, Michael A

2008-09-24

Members of the forkhead gene family act as transcription regulators in biological processes including development and metabolism. The evolution of forkhead genes has not been widely examined and selection pressures at the molecular level influencing subfamily evolution and differentiation have not been explored. Here, in silico methods were used to examine selection pressures acting on the coding sequence of five multi-species FOX protein subfamily clusters; FoxA, FoxD, FoxI, FoxO and FoxP. Application of site models, which estimate overall selection pressures on individual codons throughout the phylogeny, showed that the amino acid changes observed were either neutral or under negative selection. Branch-site models, which allow estimated selection pressures along specified lineages to vary as compared to the remaining phylogeny, identified positive selection along branches leading to the FoxA3 and Protostomia clades in the FoxA cluster and the branch leading to the FoxO3 clade in the FoxO cluster. Residues that may differentiate paralogs were identified in the FoxA and FoxO clusters and residues that differentiate orthologs were identified in the FoxA cluster. Neutral amino acid changes were identified in the forkhead domain of the FoxA, FoxD and FoxP clusters while positive selection was identified in the forkhead domain of the Protostomia lineage of the FoxA cluster. A series of residues under strong negative selection adjacent to the N- and C-termini of the forkhead domain were identified in all clusters analyzed suggesting a new method for refinement of domain boundaries. Extrapolation of domains among cluster members in conjunction with selection pressure information allowed prediction of residue function in the FoxA, FoxO and FoxP clusters and exclusion of known domain function in residues of the FoxA and FoxI clusters. Consideration of selection pressures observed in conjunction with known functional information allowed prediction of residue function and

Prolactin Signaling through the Short Form of Its Receptor Represses Forkhead Transcription Factor FOXO3 and Its Target Gene Galt Causing a Severe Ovarian Defect

PubMed Central

Halperin, Julia; Devi, Sangeeta Y.; Elizur, Shai; Stocco, Carlos; Shehu, Aurora; Rebourcet, Diane; Unterman, Terry G.; Leslie, Nancy D.; Le, Jamie; Binart, Nadine; Gibori, Geula

2008-01-01

Prolactin (PRL) is a hormone with over 300 biological activities. Although the signaling pathway downstream of the long form of its receptor (RL) has been well characterized, little is known about PRL actions upon activation of the short form (RS). Here, we show that mice expressing only RS exhibit an ovarian phenotype of accelerated follicular recruitment followed by massive follicular death leading to premature ovarian failure. Consequently, RS-expressing ovaries of young adults are depleted of functional follicles and formed mostly by interstitium. We also show that activation of RS represses the expression of the transcription factor Forkhead box O3 (FOXO3) and that of the enzyme galactose-1-phosphate uridyltransferase (Galt), two proteins known to be essential for normal follicular development. Our finding that FOXO3 regulates the expression of Galt and enhances its transcriptional activity indicates that it is the repression of FOXO3 by PRL acting through RS that prevents Galt expression in the ovary and causes follicular death. Coexpression of RL with RS prevents PRL inhibition of Galt, and the ovarian defect is no longer seen in RS transgenic mice that coexpress RL, suggesting that RL prevents RS-induced ovarian impairment. In summary, we show that PRL signals through RS and causes, in the absence of RL, a severe ovarian pathology by repressing the expression of FOXO3 and that of its target gene Galt. We also provide evidence of a link between the premature ovarian failure seen in mice expressing RS and in mice with FOXO3 gene deletion as well as in human with Galt mutation. PMID:17975019

FOXO Transcriptional Factors and Long-Term Living

PubMed Central

Rashid, Rehana; Muneer, Saiqa; Hasan, Syed Muhammad Farid

2017-01-01

Several pathologies such as neurodegeneration and cancer are associated with aging, which is affected by many genetic and environmental factors. Healthy aging conceives human longevity, possibly due to carrying the defensive genes. For instance, FOXO (forkhead box O) genes determine human longevity. FOXO transcription factors are involved in the regulation of longevity phenomenon via insulin and insulin-like growth factor signaling. Only one FOXO gene (FOXO DAF-16) exists in invertebrates, while four FOXO genes, that is, FOXO1, FOXO3, FOXO4, and FOXO6 are found in mammals. These four transcription factors are involved in the multiple cellular pathways, which regulate growth, stress resistance, metabolism, cellular differentiation, and apoptosis in mammals. However, the accurate mode of longevity by FOXO factors is unclear until now. This article describes briefly the existing knowledge that is related to the role of FOXO factors in human longevity. PMID:28894507

A Network of HMG-box Transcription Factors Regulates Sexual Cycle in the Fungus Podospora anserina

PubMed Central

Ait Benkhali, Jinane; Coppin, Evelyne; Brun, Sylvain; Peraza-Reyes, Leonardo; Martin, Tom; Dixelius, Christina; Lazar, Noureddine; van Tilbeurgh, Herman; Debuchy, Robert

2013-01-01

High-mobility group (HMG) B proteins are eukaryotic DNA-binding proteins characterized by the HMG-box functional motif. These transcription factors play a pivotal role in global genomic functions and in the control of genes involved in specific developmental or metabolic pathways. The filamentous ascomycete Podospora anserina contains 12 HMG-box genes. Of these, four have been previously characterized; three are mating-type genes that control fertilization and development of the fruit-body, whereas the last one encodes a factor involved in mitochondrial DNA stability. Systematic deletion analysis of the eight remaining uncharacterized HMG-box genes indicated that none were essential for viability, but that seven were involved in the sexual cycle. Two HMG-box genes display striking features. PaHMG5, an ortholog of SpSte11 from Schizosaccharomyces pombe, is a pivotal activator of mating-type genes in P. anserina, whereas PaHMG9 is a repressor of several phenomena specific to the stationary phase, most notably hyphal anastomoses. Transcriptional analyses of HMG-box genes in HMG-box deletion strains indicated that PaHMG5 is at the hub of a network of several HMG-box factors that regulate mating-type genes and mating-type target genes. Genetic analyses revealed that this network also controls fertility genes that are not regulated by mating-type transcription factors. This study points to the critical role of HMG-box members in sexual reproduction in fungi, as 11 out of 12 members were involved in the sexual cycle in P. anserina. PaHMG5 and SpSte11 are conserved transcriptional regulators of mating-type genes, although P. anserina and S. pombe diverged 550 million years ago. Two HMG-box genes, SOX9 and its upstream regulator SRY, also play an important role in sex determination in mammals. The P. anserina and S. pombe mating-type genes and their upstream regulatory factor form a module of HMG-box genes analogous to the SRY/SOX9 module, revealing a commonality of sex

Combining glass box and black box evaluations in the identification of heart disease risk factors and their temporal relations from clinical records.

PubMed

Grouin, Cyril; Moriceau, Véronique; Zweigenbaum, Pierre

2015-12-01

The determination of risk factors and their temporal relations in natural language patient records is a complex task which has been addressed in the i2b2/UTHealth 2014 shared task. In this context, in most systems it was broadly decomposed into two sub-tasks implemented by two components: entity detection, and temporal relation determination. Task-level ("black box") evaluation is relevant for the final clinical application, whereas component-level evaluation ("glass box") is important for system development and progress monitoring. Unfortunately, because of the interaction between entity representation and temporal relation representation, glass box and black box evaluation cannot be managed straightforwardly at the same time in the setting of the i2b2/UTHealth 2014 task, making it difficult to assess reliably the relative performance and contribution of the individual components to the overall task. To identify obstacles and propose methods to cope with this difficulty, and illustrate them through experiments on the i2b2/UTHealth 2014 dataset. We outline several solutions to this problem and examine their requirements in terms of adequacy for component-level and task-level evaluation and of changes to the task framework. We select the solution which requires the least modifications to the i2b2 evaluation framework and illustrate it with our system. This system identifies risk factor mentions with a CRF system complemented by hand-designed patterns, identifies and normalizes temporal expressions through a tailored version of the Heideltime tool, and determines temporal relations of each risk factor with a One Rule classifier. Giving a fixed value to the temporal attribute in risk factor identification proved to be the simplest way to evaluate the risk factor detection component independently. This evaluation method enabled us to identify the risk factor detection component as most contributing to the false negatives and false positives of the global system. This

Injury rates and risk factors in competitive professional boxing.

PubMed

Zazryn, Tsharni R; McCrory, Paul R; Cameron, Peter A

2009-01-01

To determine injury rates and risk factors for injury in a cohort of professional boxers. Retrospective cohort design reporting on data collected for a fight statistics database maintained by the Professional Boxing and Combat Sports Board of Victoria, Australia. Data were extracted for the years January 1997 through June 2005. Victoria, Australia. 545 professional boxers (age, 18 to 43 years) who participated in a total of 907 fights over the study period. Independent variables under investigation included age, gender, weight, bout exposure, and location of the bout (within or outside of the State of Victoria). Physician-reported acute boxing injuries occurring during bouts of any region or nature. 214 injuries were sustained over the 8.5 years, corresponding to an injury rate of 23.6 per 100 professional fights. The majority of these injuries were lacerations to the head and face. An increasing age and an increasing number of fights were both significant predictors of injury. Injury reduction strategies for professional boxing might include restrictions of eligibility to fight based on age and boxing bout exposure. Future research using prospective cohort designs and standardized injury definitions are needed to confirm these results. Greater mechanistic detail and more complete data entry are necessary to ensure that optimal injury prevention strategies can be developed and implemented. Upon confirmation of the results of this study, the Professional Boxing and Combat Sports Board of Victoria may consider different criteria upon which to sanction a fight.

Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation

USDA-ARS?s Scientific Manuscript database

Sirtuin deacetylases and FOXO (Forkhead box, class O) transcription factors have important roles in many biological pathways, including cancer development. SIRT1 and SIRT2 deacetylate FOXO factors to regulate FOXO function. Because acetylation and ubiquitination both modify the '-amino group of lysi...

SEPALLATA3: the 'glue' for MADS box transcription factor complex formation

PubMed Central

Immink, Richard GH; Tonaco, Isabella AN; de Folter, Stefan; Shchennikova, Anna; van Dijk, Aalt DJ; Busscher-Lange, Jacqueline; Borst, Jan W; Angenent, Gerco C

2009-01-01

Background Plant MADS box proteins play important roles in a plethora of developmental processes. In order to regulate specific sets of target genes, MADS box proteins dimerize and are thought to assemble into multimeric complexes. In this study a large-scale yeast three-hybrid screen is utilized to provide insight into the higher-order complex formation capacity of the Arabidopsis MADS box family. SEPALLATA3 (SEP3) has been shown to mediate complex formation and, therefore, special attention is paid to this factor in this study. Results In total, 106 multimeric complexes were identified; in more than half of these at least one SEP protein was present. Besides the known complexes involved in determining floral organ identity, various complexes consisting of combinations of proteins known to play a role in floral organ identity specification, and flowering time determination were discovered. The capacity to form this latter type of complex suggests that homeotic factors play essential roles in down-regulation of the MADS box genes involved in floral timing in the flower via negative auto-regulatory loops. Furthermore, various novel complexes were identified that may be important for the direct regulation of the floral transition process. A subsequent detailed analysis of the APETALA3, PISTILLATA, and SEP3 proteins in living plant cells suggests the formation of a multimeric complex in vivo. Conclusions Overall, these results provide strong indications that higher-order complex formation is a general and essential molecular mechanism for plant MADS box protein functioning and attribute a pivotal role to the SEP3 'glue' protein in mediating multimerization. PMID:19243611

The forkhead transcription factor Foxf1 is required for differentiation of extra-embryonic and lateral plate mesoderm.

PubMed

Mahlapuu, M; Ormestad, M; Enerbäck, S; Carlsson, P

2001-01-01

The murine Foxf1 gene encodes a forkhead transcription factor expressed in extra-embryonic and lateral plate mesoderm and later in splanchnic mesenchyme surrounding the gut and its derivatives. We have disrupted Foxf1 and show that mutant embryos die at midgestation due to defects in mesodermal differentiation and cell adhesion. The embryos do not turn and become deformed by the constraints of a small, inflexible amnion. Extra-embryonic structures exhibit a number of differentiation defects: no vasculogenesis occurs in yolk sac or allantois; chorioallantoic fusion fails; the amnion does not expand with the growth of the embryo, but misexpresses vascular and hematopoietic markers. Separation of the bulk of yolk sac mesoderm from the endodermal layer and adherence between mesoderm of yolk sac and amnion, indicate altered cell adhesion properties and enhanced intramesodermal cohesion. A possible cause of this is misexpression of the cell-adhesion protein VCAM1 in Foxf1-deficient extra-embryonic mesoderm, which leads to co-expression of VCAM with its receptor, alpha(4)-integrin. The expression level of Bmp4 is decreased in the posterior part of the embryo proper. Consistent with this, mesodermal proliferation in the primitive streak is reduced and somite formation is retarded. Expression of Foxf1 and the homeobox gene Irx3 defines the splanchnic and somatic mesodermal layers, respectively. In Foxf1-deficient embryos incomplete separation of splanchnic and somatic mesoderm is accompanied by misexpression of Irx3 in the splanchnopleure, which implicates Foxf1 as a repressor of Irx3 and as a factor involved in coelom formation.

Dynamic Regulation of FoxA1 by Steroid Receptors | Center for Cancer Research

Cancer.gov

The estrogen receptor (ER) is a key regulator in breast cancer initiation and progression. A widely discussed model proposes that forkhead box protein A1 (FoxA1) acts as a pioneer factor in cancer by binding and penetrating closed chromatin to allow access by transcription factors (TFs), including ER.

The ins and outs of FoxO shuttling: mechanisms of FoxO translocation and transcriptional regulation.

PubMed Central

Van Der Heide, Lars P; Hoekman, Marco F M; Smidt, Marten P

2004-01-01

FoxO (forkhead box O; forkhead members of the O class) are transcription factors that function under the control of insulin/insulin-like signalling. FoxO factors have been associated with a multitude of biological processes, including cell-cycle, cell death, DNA repair, metabolism and protection from oxidative stress. Central to the regulation of FoxO factors is a shuttling system, which confines FoxO factors to either the nucleus or the cytosol. Shuttling of FoxO requires protein phosphorylation within several domains, and association with 14-3-3 proteins and the nuclear transport machinery. Description of the FoxO-shuttling mechanism contributes to the understanding of FoxO function in relation to signalling and gene regulation. PMID:15005655

The Tomato Transcription Factor Pti4 Regulates Defense-Related Gene Expression via GCC Box and Non-GCC Box cis ElementsW⃞

PubMed Central

Chakravarthy, Suma; Tuori, Robert P.; D'Ascenzo, Mark D.; Fobert, Pierre R.; Després, Charles; Martin, Gregory B.

2003-01-01

The tomato transcription factor Pti4, an ethylene-responsive factor (ERF), interacts physically with the disease resistance protein Pto and binds the GCC box cis element that is present in the promoters of many pathogenesis-related (PR) genes. We reported previously that Arabidopsis plants expressing Pti4 constitutively express several GCC box–containing PR genes and show reduced disease symptoms compared with wild-type plants after inoculation with Pseudomonas syringae pv tomato or Erysiphe orontii. To gain insight into how genome-wide gene expression is affected by Pti4, we used serial analysis of gene expression (SAGE) to compare transcripts in wild-type and Pti4-expressing Arabidopsis plants. SAGE provided quantitative measurements of >20,000 transcripts and identified the 50 most highly expressed genes in Arabidopsis vegetative tissues. Comparison of the profiles from wild-type and Pti4-expressing Arabidopsis plants revealed 78 differentially abundant transcripts encoding defense-related proteins, protein kinases, ribosomal proteins, transporters, and two transcription factors (TFs). Many of the genes identified were expressed differentially in wild-type Arabidopsis during infection by Pseudomonas syringae pv tomato, supporting a role for them in defense-related processes. Unexpectedly, the promoters of most Pti4-regulated genes did not have a GCC box. Chromatin immunoprecipitation experiments confirmed that Pti4 binds in vivo to promoters lacking this cis element. Potential binding sites for ERF, MYB, and GBF TFs were present in statistically significantly increased numbers in promoters regulated by Pti4. Thus, Pti4 appears to regulate gene expression directly by binding the GCC box and possibly a non-GCC box element and indirectly by either activating the expression of TF genes or interacting physically with other TFs. PMID:14630974

Dynamic Magnification Factor in a Box-Shape Steel Girder

NASA Astrophysics Data System (ADS)

Rahbar-Ranji, A.

2014-01-01

The dynamic effect of moving loads on structures is treated as a dynamic magnification factor when resonant is not imminent. Studies have shown that the calculated magnification factors from field measurements could be higher than the values specified in design codes. It is the main aim of present paper to investigate the applicability and accuracy of a rule-based expression for calculation of dynamic magnification factor for lifting appliances used in marine industry. A steel box shape girder of a crane is considered and transient dynamic analysis using computer code ANSYS is implemented. Dynamic magnification factor is calculated for different loading conditions and compared with rule-based equation. The effects of lifting speeds, acceleration, damping ratio and position of cargo are examined. It is found that rule-based expression underestimate dynamic magnification factor.

Bet v 1-specific T-cell receptor/forkhead box protein 3 transgenic T cells suppress Bet v 1-specific T-cell effector function in an activation-dependent manner.

PubMed

Schmetterer, Klaus G; Haiderer, Daniela; Leb-Reichl, Victoria M; Neunkirchner, Alina; Jahn-Schmid, Beatrice; Küng, Hans J; Schuch, Karina; Steinberger, Peter; Bohle, Barbara; Pickl, Winfried F

2011-01-01

Regulatory T (Treg) cells establish and maintain tolerance to self-antigens and many foreign antigens, such as allergens, by suppressing effector T-cell proliferation and function. We have previously shown that human T-cell receptor (TCR) αβ-chains specific for allergen-derived epitopes confer allergen specificity on peripheral blood T cells of individuals with and without allergy. To study the feasibility of generating allergen-specific human Treg cells by retroviral transduction of a transcription unit encoding forkhead box protein 3 (FOXP3) and allergen-specific TCR αβ-chains. cDNAs encoding the α and β-chains of a Bet v 1(142-153)-specific TCR (TCR alpha variable region 6/TCR beta variable region 20) and human FOXP3 were linked via picornaviral 2A sequences and expressed as single translational unit from an internal ribosomal entry site-green fluorescence protein-containing retroviral vector. Retrovirally transduced peripheral blood T cells were tested for expression of transgenes, Treg phenotype, and regulatory capacity toward allergen-specific effector T cells. Transduced T cells displayed a Treg phenotype with clear-cut upregulation of CD25, CD39, and cytotoxic T-lymphocyte antigen 4. The transduced cells were hyporesponsive in cytokine production and secretion and, like naturally occurring Treg cells, did not proliferate after antigen-specific or antigen-mimetic stimulation. However, proliferation was inducible upon exposure to exogenous IL-2. In coculture experiments, TRAV6(+)TRBV20(+)FOXP3(+) transgenic T cells, unlike FOXP3(+) single transgenic T cells or naturally occurring Treg cells, highly significantly suppressed T cell cytokine production and proliferation of corresponding allergen-specific effector T cells in an allergen-specific, dose-dependent manner. We demonstrate a transgenic approach to engineer human allergen-specific Treg cells that exert their regulatory function in an activation-dependent manner. Customized Treg cells might become

Alpha-lipoic acid improves high-fat diet-induced hepatic steatosis by modulating the transcription factors SREBP-1, FoxO1 and Nrf2 via the SIRT1/LKB1/AMPK pathway.

PubMed

Yang, Yi; Li, Wang; Liu, Yang; Sun, Yuning; Li, Yan; Yao, Qing; Li, Jianning; Zhang, Qian; Gao, Yujing; Gao, Ling; Zhao, Jiajun

2014-11-01

Understanding the mechanism by which alpha-lipoic acid supplementation has a protective effect upon nonalcoholic fatty liver disease in vivo and in vitro may lead to targets for preventing hepatic steatosis. Male C57BL/6J mice were fed a normal diet, high-fat diet or high-fat diet supplemented with alpha-lipoic acid for 24 weeks. HepG2 cells were incubated with normal medium, palmitate or alpha-lipoic acid. The lipid-lowering effects were measured. The protein expression and distribution were analyzed by Western blot, immunoprecipitation and immunofluorescence, respectively. We found that alpha-lipoic acid enhanced sirtuin 1 deacetylase activity through liver kinase B1 and stimulated AMP-activated protein kinase. By activating the sirtuin 1/liver kinase B1/AMP-activated protein kinase pathway, the translocation of sterol regulatory element-binding protein-1 into the nucleus and forkhead box O1 into the cytoplasm was prevented. Alpha-lipoic acid increased adipose triacylglycerol lipase expression and decreased fatty acid synthase abundance. In in vivo and in vitro studies, alpha-lipoic acid also increased nuclear NF-E2-related factor 2 levels and downstream target amounts via the sirtuin 1 pathway. Alpha-lipoic acid eventually reduced intrahepatic and serum triglyceride content. The protective effects of alpha-lipoic acid on hepatic steatosis appear to be associated with the transcription factors sterol regulatory element-binding protein-1, forkhead box O1 and NF-E2-related factor 2. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Attenuation correction factors for cylindrical, disc and box geometry

NASA Astrophysics Data System (ADS)

Agarwal, Chhavi; Poi, Sanhita; Mhatre, Amol; Goswami, A.; Gathibandhe, M.

2009-08-01

In the present study, attenuation correction factors have been experimentally determined for samples having cylindrical, disc and box geometry and compared with the attenuation correction factors calculated by Hybrid Monte Carlo (HMC) method [ C. Agarwal, S. Poi, A. Goswami, M. Gathibandhe, R.A. Agrawal, Nucl. Instr. and. Meth. A 597 (2008) 198] and with the near-field and far-field formulations available in literature. It has been observed that the near-field formulae, although said to be applicable at close sample-detector geometry, does not work at very close sample-detector configuration. The advantage of the HMC method is that it is found to be valid for all sample-detector geometries.

Cyanidin 3-glucoside attenuates obesity-associated insulin resistance and hepatic steatosis in high-fat diet-fed and db/db mice via the transcription factor FoxO1.

PubMed

Guo, Honghui; Xia, Min; Zou, Tangbin; Ling, Wenhua; Zhong, Ruimin; Zhang, Weiguo

2012-04-01

Obesity is a major risk factor for the development of type 2 diabetes, and both conditions are now recognized to possess significant inflammatory components underlying their pathophysiologies. Here, we hypothesized that cyanidin 3-glucoside (C3G), a typical anthocyanin reported to possess potent anti-inflammatory properties, would ameliorate obesity-associated inflammation and metabolic disorders, such as insulin resistance and hepatic steatosis in mouse models of diabesity. Male C57BL/6J obese mice fed a high-fat diet for 12 weeks and genetically diabetic db/db mice at an age of 6 weeks received dietary C3G supplementation (0.2%) for 5 weeks. We found that dietary C3G lowered fasting glucose levels and markedly improved the insulin sensitivity in both high-fat diet fed and db/db mice as compared with unsupplemented controls. White adipose tissue messenger RNA levels and serum concentrations of inflammatory cytokines (tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1) were reduced by C3G, as did macrophage infiltration in adipose tissue. Concomitantly, hepatic triglyceride content and steatosis were alleviated by C3G. Moreover, C3G treatment decreased c-Jun N-terminal kinase activation and promoted phosphorylation and nuclear exclusion of forkhead box O1 after refeeding. These findings clearly indicate that C3G has significant potency in antidiabetic effects by modulating the c-Jun N-terminal kinase/forkhead box O1 signaling pathway and the related inflammatory adipocytokines. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Triptolide Upregulates Myocardial Forkhead Helix Transcription Factor p3 Expression and Attenuates Cardiac Hypertrophy

PubMed Central

Ding, Yuan-Yuan; Li, Jing-Mei; Guo, Feng-Jie; Liu, Ya; Tong, Yang-Fei; Pan, Xi-Chun; Lu, Xiao-Lan; Ye, Wen; Chen, Xiao-Hong; Zhang, Hai-Gang

2016-01-01

The forkhead/winged helix transcription factor (Fox) p3 can regulate the expression of various genes, and it has been reported that the transfer of Foxp3-positive T cells could ameliorate cardiac hypertrophy and fibrosis. Triptolide (TP) can elevate the expression of Foxp3, but its effects on cardiac hypertrophy remain unclear. In the present study, neonatal rat ventricular myocytes (NRVM) were isolated and stimulated with angiotensin II (1 μmol/L) to induce hypertrophic response. The expression of Foxp3 in NRVM was observed by using immunofluorescence assay. Fifty mice were randomly divided into five groups and received vehicle (control), isoproterenol (Iso, 5 mg/kg, s.c.), one of three doses of TP (10, 30, or 90 μg/kg, i.p.) for 14 days, respectively. The pathological morphology changes were observed after Hematoxylin and eosin, lectin and Masson’s trichrome staining. The levels of serum brain natriuretic peptide (BNP) and troponin I were determined by enzyme-linked immunosorbent assay and chemiluminescence, respectively. The mRNA and protein expressions of α- myosin heavy chain (MHC), β-MHC and Foxp3 were determined using real-time PCR and immunohistochemistry, respectively. It was shown that TP (1, 3, 10 μg/L) treatment significantly decreased cell size, mRNA and protein expression of β-MHC, and upregulated Foxp3 expression in NRVM. TP also decreased heart weight index, left ventricular weight index and, improved myocardial injury and fibrosis; and decreased the cross-scetional area of the myocardium, serum cardiac troponin and BNP. Additionally, TP markedly reduced the mRNA and protein expression of myocardial β-MHC and elevated the mRNA and protein expression of α-MHC and Foxp3 in a dose-dependent manner. In conclusion, TP can effectively ameliorate myocardial damage and inhibit cardiac hypertrophy, which is at least partly related to the elevation of Foxp3 expression in cardiomyocytes. PMID:27965581

Forkhead Box Transcription Factors of the FOXA Class Are Required for Basal Transcription of Angiotensin-Converting Enzyme 2

PubMed Central

Pedersen, Kim Brint; Chodavarapu, Harshita

2017-01-01

Angiotensin-converting enzyme 2 (ACE2) has protective effects on a wide range of morbidities associated with elevated angiotensin-II signaling. Most tissues, including pancreatic islets, express ACE2 mainly from the proximal promoter region. We previously found that hepatocyte nuclear factors 1α and 1β stimulate ACE2 expression from three highly conserved hepatocyte nuclear factor 1 binding motifs in the proximal promoter region. We hypothesized that other highly conserved motifs would also affect ACE2 expression. By systematic mutation of conserved elements, we identified five regions affecting ACE2 expression, of which two regions bound transcriptional activators. One of these is a functional FOXA binding motif. We further identified the main protein binding the FOXA motif in 832/13 insulinoma cells as well as in mouse pancreatic islets as FOXA2. PMID:29082356

Decreased akt activity is associated with activation of forkhead transcription factor after transient forebrain ischemia in gerbil hippocampus.

PubMed

Kawano, Takayuki; Morioka, Motohiro; Yano, Shigetoshi; Hamada, Jun-Ichiro; Ushio, Yukitaka; Miyamoto, Eishichi; Fukunaga, Kohji

2002-08-01

The authors recently reported that sodium orthovanadate rescues cells from delayed neuronal death in gerbil hippocampus after transient forebrain ischemia through phosphatidylinositol 3-kinase-protein kinase B (Akt) pathway (Kawano et al., 2001). In the current study, they demonstrated that the activation of FKHR, a Forkhead transcription factor and a substrate for Akt, preceded delayed neuronal death in CA1 regions after transient forebrain ischemia. Adult Mongolian gerbils were subjected to 5-minute forebrain ischemia. Immunoblotting analysis with anti-phospho-FKHR antibody showed that phosphorylation of FKHR at serine-256 in the CA1 region decreased immediately after and 0.5 and 1 hour after reperfusion. The dephosphorylation of FKHR was correlated with the decreased Akt activity. Intracerebroventricular injection of orthovanadate 30 minutes before ischemia inhibited dephosphorylation of FKHR after reperfusion, and blocked delayed neuronal death in the CA1 region. Gel mobility shift analysis using nuclear extracts from the CA1 region prepared immediately after reperfusion revealed increases in DNA binding activity for the FKHR-responsive element on the Fas ligand promoter. The orthovanadate injection administered before ischemia inhibited its binding activity. Two days after reperfusion, expression of Fas ligand increased in the CA1 region and the orthovanadate injection inhibited this increased expression. These results suggest that the inactivation of Akt results in the activation of FKHR and, in turn, relates to the expression of Fas ligand in the CA1 region after transient forebrain ischemia.

Multiple interactions amongst floral homeotic MADS box proteins.

PubMed Central

Davies, B; Egea-Cortines, M; de Andrade Silva, E; Saedler, H; Sommer, H

1996-01-01

Most known floral homeotic genes belong to the MADS box family and their products act in combination to specify floral organ identity by an unknown mechanism. We have used a yeast two-hybrid system to investigate the network of interactions between the Antirrhinum organ identity gene products. Selective heterodimerization is observed between MADS box factors. Exclusive interactions are detected between two factors, DEFICIENS (DEF) and GLOBOSA (GLO), previously known to heterodimerize and control development of petals and stamens. In contrast, a third factor, PLENA (PLE), which is required for reproductive organ development, can interact with the products of MADS box genes expressed at early, intermediate and late stages. We also demonstrate that heterodimerization of DEF and GLO requires the K box, a domain not found in non-plant MADS box factors, indicating that the plant MADS box factors may have different criteria for interaction. The association of PLENA and the temporally intermediate MADS box factors suggests that part of their function in mediating between the meristem and organ identity genes is accomplished through direct interaction. These data reveal an unexpectedly complex network of interactions between the factors controlling flower development and have implications for the determination of organ identity. Images PMID:8861961

The plant G box promoter sequence activates transcription in Saccharomyces cerevisiae and is bound in vitro by a yeast activity similar to GBF, the plant G box binding factor.

PubMed Central

Donald, R G; Schindler, U; Batschauer, A; Cashmore, A R

1990-01-01

G box and I box sequences of the Arabidopsis thaliana ribulose-bisphosphate-1,5-carboxylase small subunit (RBCS) promoter are required for expression mediated by the Arabidopsis rbcS-1A promoter in transgenic tobacco plants and are bound in vitro by factors from plant nuclear extracts termed GBF and GA-1, respectively. We show here that a -390 to -60 rbcS-1A promoter fragment containing the G box and two I boxes activates transcription from a truncated iso-1-cytochrome c (CYC1) gene promoter in Saccharomyces cerevisiae. Mutagenesis of either the rbcS-1A G box or both I box sequences eliminated the expression mediated by this fragment. When polymerized, I box oligonucleotides were also capable of enhancing expression from the truncated CYC1 promoter. Single-copy G box sequences from the Arabidopsis rbcS-1A, Arabidopsis Adh and tomato rbcS-3A promoters were more potent activators and were used in mobility shift assays to identify a DNA binding activity in yeast functionally similar to GBF. In methylation interference experiments, the binding specificity of the yeast protein was indistinguishable from that obtained with plant nuclear extracts. Images Fig. 3. Fig. 4. Fig. 5. Fig. 6. PMID:2161333

Expression of the ctenophore Brain Factor 1 forkhead gene ortholog (ctenoBF-1) mRNA is restricted to the presumptive mouth and feeding apparatus: implications for axial organization in the Metazoa

NASA Technical Reports Server (NTRS)

Yamada, Atsuko; Martindale, Mark Q.

2002-01-01

Ctenophores are thoroughly modern animals whose ancestors are derived from a separate evolutionary branch than that of other eumetazoans. Their major longitudinal body axis is the oral-aboral axis. An apical sense organ, called the apical organ, is located at the aboral pole and contains a highly innervated statocyst and photodetecting cells. The apical organ integrates sensory information and controls the locomotory apparatus of ctenophores, the eight longitudinal rows of ctene/comb plates. In an effort to understand the developmental and evolutionary organization of axial properties of ctenophores we have isolated a forkhead gene from the Brain Factor 1 (BF-1) family. This gene, ctenoBF-1, is the first full-length nuclear gene reported from ctenophores. This makes ctenophores the most basal metazoan (to date) known to express definitive forkhead class transcription factors. Orthologs of BF-1 in vertebrates, Drosophila, and Caenorhabditis elegans are expressed in anterior neural structures. Surprisingly, in situ hybridizations with ctenoBF-1 antisense riboprobes show that this gene is not expressed in the apical organ of ctenophores. CtenoBF-1 is expressed prior to first cleavage. Transcripts become localized to the aboral pole by the 8-cell stage and are inherited by ectodermal micromeres generated from this region at the 16- and 32-cell stages. Expression in subsets of these cells persists and is seen around the edge of the blastopore (presumptive mouth) and in distinct ectodermal regions along the tentacular poles. Following gastrulation, stomodeal expression begins to fade and intense staining becomes restricted to two distinct domains in each tentacular feeding apparatus. We suggest that the apical organ is not homologous to the brain of bilaterians but that the oral pole of ctenophores corresponds to the anterior pole of bilaterian animals.

The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21WAF1/CIP1 in 143B Osteosarcoma Cell Growth Arrest.

PubMed

Gascoyne, Duncan M; Spearman, Hayley; Lyne, Linden; Puliyadi, Rathi; Perez-Alcantara, Marta; Coulton, Les; Fisher, Simon E; Croucher, Peter I; Banham, Alison H

2015-01-01

Mutations of the forkhead transcription factor FOXP2 gene have been implicated in inherited speech-and-language disorders, and specific Foxp2 expression patterns in neuronal populations and neuronal phenotypes arising from Foxp2 disruption have been described. However, molecular functions of FOXP2 are not completely understood. Here we report a requirement for FOXP2 in growth arrest of the osteosarcoma cell line 143B. We observed endogenous expression of this transcription factor both transiently in normally developing murine osteoblasts and constitutively in human SAOS-2 osteosarcoma cells blocked in early osteoblast development. Critically, we demonstrate that in 143B osteosarcoma cells with minimal endogenous expression, FOXP2 induced by growth arrest is required for up-regulation of p21WAF1/CIP1. Upon growth factor withdrawal, FOXP2 induction occurs rapidly and precedes p21WAF1/CIP1 activation. Additionally, FOXP2 expression could be induced by MAPK pathway inhibition in growth-arrested 143B cells, but not in traditional cell line models of osteoblast differentiation (MG-63, C2C12, MC3T3-E1). Our data are consistent with a model in which transient upregulation of Foxp2 in pre-osteoblast mesenchymal cells regulates a p21-dependent growth arrest checkpoint, which may have implications for normal mesenchymal and osteosarcoma biology.

The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21WAF1/CIP1 in 143B Osteosarcoma Cell Growth Arrest

PubMed Central

Gascoyne, Duncan M.; Spearman, Hayley; Lyne, Linden; Puliyadi, Rathi; Perez-Alcantara, Marta; Coulton, Les; Fisher, Simon E.; Croucher, Peter I.; Banham, Alison H.

2015-01-01

Mutations of the forkhead transcription factor FOXP2 gene have been implicated in inherited speech-and-language disorders, and specific Foxp2 expression patterns in neuronal populations and neuronal phenotypes arising from Foxp2 disruption have been described. However, molecular functions of FOXP2 are not completely understood. Here we report a requirement for FOXP2 in growth arrest of the osteosarcoma cell line 143B. We observed endogenous expression of this transcription factor both transiently in normally developing murine osteoblasts and constitutively in human SAOS-2 osteosarcoma cells blocked in early osteoblast development. Critically, we demonstrate that in 143B osteosarcoma cells with minimal endogenous expression, FOXP2 induced by growth arrest is required for up-regulation of p21WAF1/CIP1. Upon growth factor withdrawal, FOXP2 induction occurs rapidly and precedes p21WAF1/CIP1 activation. Additionally, FOXP2 expression could be induced by MAPK pathway inhibition in growth-arrested 143B cells, but not in traditional cell line models of osteoblast differentiation (MG-63, C2C12, MC3T3-E1). Our data are consistent with a model in which transient upregulation of Foxp2 in pre-osteoblast mesenchymal cells regulates a p21-dependent growth arrest checkpoint, which may have implications for normal mesenchymal and osteosarcoma biology. PMID:26034982

Phylogenetic relationships of the Fox (Forkhead) gene family in the Bilateria

NASA Technical Reports Server (NTRS)

Mazet, Francoise; Yu, Jr Kai; Liberles, David A.; Holland, Linda Z.; Shimeld, Sebastian M.

2003-01-01

The Forkhead or Fox gene family encodes putative transcription factors. There are at least four Fox genes in yeast, 16 in Drosophila melanogaster (Dm) and 42 in humans. Recently, vertebrate Fox genes have been classified into 17 groups named FoxA to FoxQ. Here, we extend this analysis to invertebrates, using available sequences from D. melanogaster, Anopheles gambiae (Ag), Caenorhabditis elegans (Ce), the sea squirt Ciona intestinalis (Ci) and amphioxus Branchiostoma floridae (Bf), from which we also cloned several Fox genes. Phylogenetic analyses lend support to the previous overall subclassification of vertebrate genes, but suggest that four subclasses (FoxJ, L, N and Q) could be further subdivided to reflect their relationships to invertebrate genes. We were unable to identify orthologs of Fox subclasses E, H, I, J, M and Q1 in D. melanogaster, A. gambiae or C. elegans, suggesting either considerable loss in ecdysozoans or the evolution of these subclasses in the deuterostome lineage. Our analyses suggest that the common ancestor of protostomes and deuterostomes had a minimum complement of 14 Fox genes.

Mutation in the γ2-subunit of AMP-activated protein kinase stimulates cardiomyocyte proliferation and hypertrophy independent of glycogen storage.

PubMed

Kim, Maengjo; Hunter, Roger W; Garcia-Menendez, Lorena; Gong, Guohua; Yang, Yu-Ying; Kolwicz, Stephen C; Xu, Jason; Sakamoto, Kei; Wang, Wang; Tian, Rong

2014-03-14

AMP-activated protein kinase is a master regulator of cell metabolism and an attractive drug target for cancer and metabolic and cardiovascular diseases. Point mutations in the regulatory γ2-subunit of AMP-activated protein kinase (encoded by Prkag2 gene) caused a unique form of human cardiomyopathy characterized by cardiac hypertrophy, ventricular preexcitation, and glycogen storage. Understanding the disease mechanisms of Prkag2 cardiomyopathy is not only beneficial for the patients but also critical to the use of AMP-activated protein kinase as a drug target. We sought to identify the pro-growth-signaling pathway(s) triggered by Prkag2 mutation and to distinguish it from the secondary response to glycogen storage. In a mouse model of N488I mutation of the Prkag2 gene (R2M), we rescued the glycogen storage phenotype by genetic inhibition of glucose-6-phosphate-stimulated glycogen synthase activity. Ablation of glycogen storage eliminated the ventricular preexcitation but did not affect the excessive cardiac growth in R2M mice. The progrowth effect in R2M hearts was mediated via increased insulin sensitivity and hyperactivity of Akt, resulting in activation of mammalian target of rapamycin and inactivation of forkhead box O transcription factor-signaling pathways. Consequently, cardiac myocyte proliferation during the postnatal period was enhanced in R2M hearts followed by hypertrophic growth in adult hearts. Inhibition of mammalian target of rapamycin activity by rapamycin or restoration of forkhead box O transcription factor activity by overexpressing forkhead box O transcription factor 1 rescued the abnormal cardiac growth. Our study reveals a novel mechanism for Prkag2 cardiomyopathy, independent of glycogen storage. The role of γ2-AMP-activated protein kinase in cell growth also has broad implications in cardiac development, growth, and regeneration.

The Effects of Biomechanical Factors to Teach Different Hook Punch Techniques in Boxing and Education Strategies

ERIC Educational Resources Information Center

Bingul, Bergun Meric; Bulgun, Cigdem; Tore, Ozlem; Bal, Erdal; Aydin, Mensure

2018-01-01

The aim of this study was to investigate the effects of biomechanic factors to teach different hook punches in boxing. Eight light middleweight boxing athletes (mean age ± SD 19.00 ± 2.00 yrs, mean height ± SD 173.88 ± 3.89 cm, mean weight ± SD 64.25 ± 4.66 kg) participated in this study. Athletes performed a trial using three different hook punch…

Transforming growth factor β-mediated suppression of antitumor T cells requires FoxP1 transcription factor expression.

PubMed

Stephen, Tom L; Rutkowski, Melanie R; Allegrezza, Michael J; Perales-Puchalt, Alfredo; Tesone, Amelia J; Svoronos, Nikolaos; Nguyen, Jenny M; Sarmin, Fahmida; Borowsky, Mark E; Tchou, Julia; Conejo-Garcia, Jose R

2014-09-18

Tumor-reactive T cells become unresponsive in advanced tumors. Here we have characterized a common mechanism of T cell unresponsiveness in cancer driven by the upregulation of the transcription factor Forkhead box protein P1 (Foxp1), which prevents CD8⁺ T cells from proliferating and upregulating Granzyme-B and interferon-γ in response to tumor antigens. Accordingly, Foxp1-deficient lymphocytes induced rejection of incurable tumors and promoted protection against tumor rechallenge. Mechanistically, Foxp1 interacted with the transcription factors Smad2 and Smad3 in preactivated CD8⁺ T cells in response to microenvironmental transforming growth factor-β (TGF-β), and was essential for its suppressive activity. Therefore, Smad2 and Smad3-mediated c-Myc repression requires Foxp1 expression in T cells. Furthermore, Foxp1 directly mediated TGF-β-induced c-Jun transcriptional repression, which abrogated T cell activity. Our results unveil a fundamental mechanism of T cell unresponsiveness different from anergy or exhaustion, driven by TGF-β signaling on tumor-associated lymphocytes undergoing Foxp1-dependent transcriptional regulation. Copyright © 2014 Elsevier Inc. All rights reserved.

Development-related expression patterns of protein-coding and miRNA genes involved in porcine muscle growth.

PubMed

Wang, F J; Jin, L; Guo, Y Q; Liu, R; He, M N; Li, M Z; Li, X W

2014-11-27

Muscle growth and development is associated with remarkable changes in protein-coding and microRNA (miRNA) gene expression. To determine the expression patterns of genes and miRNAs related to muscle growth and development, we measured the expression levels of 25 protein-coding and 16 miRNA genes in skeletal and cardiac muscles throughout 5 developmental stages by quantitative reverse transcription-polymerase chain reaction. The Short Time-Series Expression Miner (STEM) software clustering results showed that growth-related genes were downregulated at all developmental stages in both the psoas major and longissimus dorsi muscles, indicating their involvement in early developmental stages. Furthermore, genes related to muscle atrophy, such as forkhead box 1 and muscle ring finger, showed unregulated expression with increasing age, suggesting a decrease in protein synthesis during the later stages of skeletal muscle development. We found that development of the cardiac muscle was a complex process in which growth-related genes were highly expressed during embryonic development, but they did not show uniform postnatal expression patterns. Moreover, the expression level of miR-499, which enhances the expression of the β-myosin heavy chain, was significantly different in the psoas major and longissimus dorsi muscles, suggesting the involvement of miR-499 in the determination of skeletal muscle fiber types. We also performed correlation analyses of messenger RNA and miRNA expression. We found negative relationships between miR-486 and forkhead box 1, and miR-133a and serum response factor at all developmental stages, suggesting that forkhead box 1 and serum response factor are potential targets of miR-486 and miR-133a, respectively.

Box-Cox transformation for QTL mapping.

PubMed

Yang, Runqing; Yi, Nengjun; Xu, Shizhong

2006-01-01

The maximum likelihood method of QTL mapping assumes that the phenotypic values of a quantitative trait follow a normal distribution. If the assumption is violated, some forms of transformation should be taken to make the assumption approximately true. The Box-Cox transformation is a general transformation method which can be applied to many different types of data. The flexibility of the Box-Cox transformation is due to a variable, called transformation factor, appearing in the Box-Cox formula. We developed a maximum likelihood method that treats the transformation factor as an unknown parameter, which is estimated from the data simultaneously along with the QTL parameters. The method makes an objective choice of data transformation and thus can be applied to QTL analysis for many different types of data. Simulation studies show that (1) Box-Cox transformation can substantially increase the power of QTL detection; (2) Box-Cox transformation can replace some specialized transformation methods that are commonly used in QTL mapping; and (3) applying the Box-Cox transformation to data already normally distributed does not harm the result.

Control of Floral Meristem Determinacy in Petunia by MADS-Box Transcription Factors1[W

PubMed Central

Ferrario, Silvia; Shchennikova, Anna V.; Franken, John; Immink, Richard G.H.; Angenent, Gerco C.

2006-01-01

The shoot apical meristem (SAM), a small group of undifferentiated dividing cells, is responsible for the continuous growth of plants. Several genes have been identified that control the development and maintenance of the SAM. Among these, WUSCHEL (WUS) from Arabidopsis (Arabidopsis thaliana) is thought to be required for maintenance of a stem cell pool in the SAM. The MADS-box gene AGAMOUS, in combination with an unknown factor, has been proposed as a possible negative regulator of WUS, leading to the termination of meristematic activity within the floral meristem. Transgenic petunia (Petunia hybrida) plants were produced in which the E-type and D-type MADS-box genes FLORAL BINDING PROTEIN2 (FBP2) and FBP11, respectively, are simultaneously overexpressed. These plants show an early arrest in development at the cotyledon stage. Molecular analysis of these transgenic plants revealed a possible combined action of FBP2 and FBP11 in repressing the petunia WUS homolog, TERMINATOR. Furthermore, the ectopic up-regulation of the C-type and D-type homeotic genes FBP6 and FBP7, respectively, suggests that they may also participate in a complex, which causes the determinacy in transgenic plants. These data support the model that a transcription factor complex consisting of C-, D-, and E-type MADS-box proteins controls the stem cell population in the floral meristem. PMID:16428599

HbMADS4, a MADS-box Transcription Factor from Hevea brasiliensis, Negatively Regulates HbSRPP.

PubMed

Li, Hui-Liang; Wei, Li-Ran; Guo, Dong; Wang, Ying; Zhu, Jia-Hong; Chen, Xiong-Ting; Peng, Shi-Qing

2016-01-01

In plants MADS-box transcription factors (TFs) play important roles in growth and development. However, no plant MADS-box gene has been identified to have a function related to secondary metabolites regulation. Here, a MADS-box TF gene, designated as HbMADS4 , was isolated from Hevea brasiliensis by the yeast one-hybrid experiment to screen the latex cDNA library using the promoter of the gene encoding H. brasiliensis small rubber particle protein (HbSRPP) as bait. HbMADS4 was 984-bp containing 633-bp open reading frame encoding a deduced protein of 230 amino acid residues with a typical conserved MADS-box motif at the N terminus. HbMADS4 was preferentially expressed in the latex, but little expression was detected in the leaves, flowers, and roots. Its expression was inducible by methyl jasmonate and ethylene. Furthermore, transient over-expression and over-expression of HbMADS4 in transgenic tobacco plants significantly suppressed the activity of the HbSRP promoter. Altogether, it is proposed that HbMADS4 is a negative regulator of HbSRPP which participates in the biosynthesis of natural rubber.

Bearded-Ear Encodes a MADS-box Transcription Factor Critical for Maize Floral Development

USDA-ARS?s Scientific Manuscript database

We cloned bde by positional cloning and found that it encodes zag3, a MADS-box transcription factor in the conserved AGL6 clade. Mutants in the maize homolog of AGAMOUS, zag1, have a subset of bde floral defects. bde; zag1 double mutants have a severe ear phenotype, not observed in either single m...

Live-cell monitoring of periodic gene expression in synchronous human cells identifies Forkhead genes involved in cell cycle control

PubMed Central

Grant, Gavin D.; Gamsby, Joshua; Martyanov, Viktor; Brooks, Lionel; George, Lacy K.; Mahoney, J. Matthew; Loros, Jennifer J.; Dunlap, Jay C.; Whitfield, Michael L.

2012-01-01

We developed a system to monitor periodic luciferase activity from cell cycle–regulated promoters in synchronous cells. Reporters were driven by a minimal human E2F1 promoter with peak expression in G1/S or a basal promoter with six Forkhead DNA-binding sites with peak expression at G2/M. After cell cycle synchronization, luciferase activity was measured in live cells at 10-min intervals across three to four synchronous cell cycles, allowing unprecedented resolution of cell cycle–regulated gene expression. We used this assay to screen Forkhead transcription factors for control of periodic gene expression. We confirmed a role for FOXM1 and identified two novel cell cycle regulators, FOXJ3 and FOXK1. Knockdown of FOXJ3 and FOXK1 eliminated cell cycle–dependent oscillations and resulted in decreased cell proliferation rates. Analysis of genes regulated by FOXJ3 and FOXK1 showed that FOXJ3 may regulate a network of zinc finger proteins and that FOXK1 binds to the promoter and regulates DHFR, TYMS, GSDMD, and the E2F binding partner TFDP1. Chromatin immunoprecipitation followed by high-throughput sequencing analysis identified 4329 genomic loci bound by FOXK1, 83% of which contained a FOXK1-binding motif. We verified that a subset of these loci are activated by wild-type FOXK1 but not by a FOXK1 (H355A) DNA-binding mutant. PMID:22740631

daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans.

PubMed

Lin, K; Dorman, J B; Rodan, A; Kenyon, C

1997-11-14

The wild-type Caenorhabditis elegans nematode ages rapidly, undergoing development, senescence, and death in less than 3 weeks. In contrast, mutants with reduced activity of the gene daf-2, a homolog of the insulin and insulin-like growth factor receptors, age more slowly than normal and live more than twice as long. These mutants are active and fully fertile and have normal metabolic rates. The life-span extension caused by daf-2 mutations requires the activity of the gene daf-16. daf-16 appears to play a unique role in life-span regulation and encodes a member of the hepatocyte nuclear factor 3 (HNF-3)/forkhead family of transcriptional regulators. In humans, insulin down-regulates the expression of certain genes by antagonizing the activity of HNF-3, raising the possibility that aspects of this regulatory system have been conserved.

Load Distribution Factors for Composite Multicell Box Girder Bridges

NASA Astrophysics Data System (ADS)

Tiwari, Sanjay; Bhargava, Pradeep

2017-12-01

Cellular steel section composite with a concrete deck is one of the most suitable superstructures in resisting torsional and warping effects induced by highway loading. This type of structure has inherently created new design problems for engineers in estimating its load distribution when subjected to moving vehicles. Indian Codes of Practice does not provide any specific guidelines for the design of straight composite concrete deck-steel multi-cell bridges. To meet the practical requirements arising during the design process, a simple design method is needed for straight composite multi-cell bridges in the form of load distribution factors for moment and shear. This work presents load distribution characteristics of straight composite multi-cell box girder bridges under IRC trains of loads.

Mouse Mesenchyme forkhead 2 (Mf2): expression, DNA binding and induction by sonic hedgehog during somitogenesis.

PubMed

Wu, S C; Grindley, J; Winnier, G E; Hargett, L; Hogan, B L

1998-01-01

Cloning and sequencing of mouse Mf2 (mesoderm/mesenchyme forkhead 2) cDNAs revealed an open reading frame encoding a putative protein of 492 amino acids which, after in vitro translation, binds to a DNA consensus sequence. Mf2 is expressed at high levels in the ventral region of newly formed somites, in sclerotomal derivatives, in lateral plate and cephalic mesoderm and in the first and second branchial arches. Other regions of mesodermal expression include the developing tongue, meninges, nose, whiskers, kidney, genital tubercule and limb joints. In the nervous system Mf2 is transcribed in restricted regions of the mid- and forebrain. In several tissues, including the early somite, Mf2 is expressed in cell populations adjacent to regions expressing sonic hedgehog (Shh) and in explant cultures of presomitic mesoderm Mf2 is induced by Shh secreted by COS cells. These results suggest that Mf2, like other murine forkhead genes, has multiple roles in embryogenesis, possibly mediating the response of cells to signaling molecules such as SHH.

Antiproliferative and pro-apoptotic effects of three fungal exocellular β-glucans in MCF-7 breast cancer cells is mediated by oxidative stress, AMP-activated protein kinase (AMPK) and the Forkhead transcription factor, FOXO3a.

PubMed

Queiroz, Eveline A I F; Fortes, Zuleica B; da Cunha, Mário A A; Barbosa, Aneli M; Khaper, Neelam; Dekker, Robert F H

2015-10-01

Fungal β-d-glucans of the (1→3)-type are known to exhibit direct antitumor effects, and can also indirectly decrease tumor proliferation through immunomodulatory responses. The underlying molecular mechanisms involved in decreasing tumor formation, however, are not well understood. In this study, we examined the antiproliferative role and mechanism of action of three different fungal exocellular β-glucans in MCF-7 breast cancer cells. The β-glucans were obtained from Botryosphaeria rhodina MAMB-05 [two botryosphaerans; (1→3)(1→6)-β-d-glucan; one produced on glucose, the other on fructose] and Lasiodiplodia theobromae MMPI [lasiodiplodan; (1→6)-β-d-glucan, produced on glucose]. Using the cell proliferation-MTT assay, we showed that the β-glucans exhibited a time- and concentration-dependent antiproliferative activity (IC50, 100μg/ml). Markers of cell cycle, apoptosis, necrosis and oxidative stress were analyzed using flow cytometry, RT-PCR and Western blotting. Exposure to β-glucans increased apoptosis, necrosis, oxidative stress, mRNA expression of p53, p27 and Bax; the activity of AMP-activated protein-kinase, Forkhead transcription factor FOXO3a, Bax and caspase-3; and decreased the activity of p70S6K in MCF-7 cells. In the presence of hydrogen peroxide, the fungal β-glucans increased oxidative stress, which was associated with reduced cell viability. We showed that these β-glucans exhibited an antiproliferative effect that was associated with apoptosis, necrosis and oxidative stress. This study demonstrated for the first time that the apoptosis induced by β-glucans was mediated by AMP-activated protein-kinase and Forkhead transcription factor, FOXO3a. Our findings provide novel mechanistic insights into their antiproliferative roles, and compelling evidence that these β-glucans possess a broad range of biomodulatory properties that may prove useful in cancer treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Boxing: traumatology and prevention].

PubMed

Cabanis, Emmanuel-Alain; Iba-Zizen, Marie-Thérèse; Perez, Georges; Senegas, Xavier; Furgoni, Julien; Pineau, Jean-Claude; Louquet, Jean-Louis; Henrion, Roger

2010-10-01

In 1986, a surgeon who, as an amateur boxer himself was concerned with boxers' health, approached a pioneering Parisian neuroimaging unit. Thus began a study in close cooperation with the French Boxing Federation, spanning 25 years. In a first series of 52 volunteer boxers (13 amateurs and 39 professionals), during which MRI gradually replaced computed tomography, ten risk factors were identified, which notably included boxing style: only one of 40 "stylists" with a good boxing technique had cortical atrophy (4.5 %), compared to 15 % of "sloggers". Changes to the French Boxing Federation rules placed the accent on medical prevention. The second series, of 247 boxers (81 amateurs and 266 professionals), showed a clear improvement, as lesions were suspected in 14 individuals, of which only 4 (1.35 %) were probably due to boxing. The third and fourth series were part of a protocol called "Brain-Boxing-Ageing", which included 76 boxers (11 having suffered KOs) and 120 MRI scans, with reproducible CT and MRI acquisitions (9 sequences with 1.5 T then 3 T, and CT). MRI anomalies secondary to boxing were found in 11 % of amateurs and 38 % of professionals (atrophy, high vascular T2 signal areas, 2 cases of post-KO subdural bleeding). CT revealed sinus damage in 13 % of the amateurs and 19 % of the professionals. The risk of acute and chronic facial and brain damage was underline, along with detailed precautionary measures (organization of bouts, role of the referee and ringside doctor, and application of French Boxing Federation rules).

Magical Boxes

ERIC Educational Resources Information Center

Costello, Judith

2005-01-01

Students get excited when they realize that they can transform a flat sheet of paper into a box. By using different sizes of paper, they can make different sizes of boxes and put a box inside a box, inside a box. These magical boxes within boxes can contain unwanted emotions or special treasures. The project described in this article incorporates…

Msx1 and Msx2 are functional interacting partners of T-box factors in the regulation of Connexin43.

PubMed

Boogerd, Kees-Jan; Wong, L Y Elaine; Christoffels, Vincent M; Klarenbeek, Meinke; Ruijter, Jan M; Moorman, Antoon F M; Barnett, Phil

2008-06-01

T-box factors Tbx2 and Tbx3 play key roles in the development of the cardiac conduction system, atrioventricular canal, and outflow tract of the heart. They regulate the gap-junction-encoding gene Connexin43 (Cx43) and other genes critical for heart development and function. Discovering protein partners of Tbx2 and Tbx3 will shed light on the mechanisms by which these factors regulate these gene programs. Employing an yeast 2-hybrid screen and subsequent in vitro pull-down experiments we demonstrate that muscle segment homeobox genes Msx1 and Msx2 are able to bind the cardiac T-box proteins Tbx2, Tbx3, and Tbx5. This interaction, as that of the related Nkx2.5 protein, is supported by the T-box and homeodomain alone. Overlapping spatiotemporal expression patterns of Msx1 and Msx2 together with the T-box genes during cardiac development in mouse and chicken underscore the biological significance of this interaction. We demonstrate that Msx proteins together with Tbx2 and Tbx3 suppress Cx43 promoter activity and down regulate Cx43 gene activity in a rat heart-derived cell line. Using chromatin immunoprecipitation analysis we demonstrate that Msx1 can bind the Cx43 promoter at a conserved binding site located in close proximity to a previously defined T-box binding site, and that the activity of Msx proteins on this promoter appears dependent in the presence of Tbx3. Msx1 and Msx2 can function in concert with the T-box proteins to suppress Cx43 and other working myocardial genes.

The forkhead-like transcription factor (Fhl1p) maintains yeast replicative lifespan by regulating ribonucleotide reductase 1 (RNR1) gene transcription

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

Tai, Akiko; Kamei, Yuka; Mukai, Yukio

In eukaryotes, numerous genetic factors contribute to the lifespan including metabolic enzymes, signal transducers, and transcription factors. As previously reported, the forkhead-like transcription factor (FHL1) gene was required for yeast replicative lifespan and cell proliferation. To determine how Fhl1p regulates the lifespan, we performed a DNA microarray analysis of a heterozygous diploid strain deleted for FHL1. We discovered numerous Fhl1p-target genes, which were then screened for lifespan-regulating activity. We identified the ribonucleotide reductase (RNR) 1 gene (RNR1) as a regulator of replicative lifespan. RNR1 encodes a large subunit of the RNR complex, which consists of two large (Rnr1p/Rnr3p) and twomore » small (Rnr2p/Rnr4p) subunits. Heterozygous deletion of FHL1 reduced transcription of RNR1 and RNR3, but not RNR2 and RNR4. Chromatin immunoprecipitation showed that Fhl1p binds to the promoter regions of RNR1 and RNR3. Cells harboring an RNR1 deletion or an rnr1-C428A mutation, which abolishes RNR catalytic activity, exhibited a short lifespan. In contrast, cells with a deletion of the other RNR genes had a normal lifespan. Overexpression of RNR1, but not RNR3, restored the lifespan of the heterozygous FHL1 mutant to the wild-type (WT) level. The Δfhl1/FHL1 mutant conferred a decrease in dNTP levels and an increase in hydroxyurea (HU) sensitivity. These findings reveal that Fhl1p regulates RNR1 gene transcription to maintain dNTP levels, thus modulating longevity by protection against replication stress. - Highlights: • Fhl1p regulates replicative lifespan and transcription of RNR large subunit genes. • Rnr1p uniquely acts as a lifespan regulator independent of the RNR complex. • dNTP levels modulate longevity by protection against replication stress.« less

Infectious disease and boxing.

PubMed

King, Osric S

2009-10-01

There are no unique boxing diseases but certain factors contributing to the spread of illnesses apply strongly to the boxer, coach, and the training facility. This article examines the nature of the sport of boxing and its surrounding environment, and the likelihood of spread of infection through airborne, contact, or blood-borne routes of transmission. Evidence from other sports such as running, wrestling, and martial arts is included to help elucidate the pathophysiologic elements that could be identified in boxers.

The Forkhead transcription factor Hcm1 regulates chromosome segregation genes and fills the S-phase gap in the transcriptional circuitry of the cell cycle.

PubMed

Pramila, Tata; Wu, Wei; Miles, Shawna; Noble, William Stafford; Breeden, Linda L

2006-08-15

Transcription patterns shift dramatically as cells transit from one phase of the cell cycle to another. To better define this transcriptional circuitry, we collected new microarray data across the cell cycle of budding yeast. The combined analysis of these data with three other cell cycle data sets identifies hundreds of new highly periodic transcripts and provides a weighted average peak time for each transcript. Using these data and phylogenetic comparisons of promoter sequences, we have identified a late S-phase-specific promoter element. This element is the binding site for the forkhead protein Hcm1, which is required for its cell cycle-specific activity. Among the cell cycle-regulated genes that contain conserved Hcm1-binding sites, there is a significant enrichment of genes involved in chromosome segregation, spindle dynamics, and budding. This may explain why Hcm1 mutants show 10-fold elevated rates of chromosome loss and require the spindle checkpoint for viability. Hcm1 also induces the M-phase-specific transcription factors FKH1, FKH2, and NDD1, and two cell cycle-specific transcriptional repressors, WHI5 and YHP1. As such, Hcm1 fills a significant gap in our understanding of the transcriptional circuitry that underlies the cell cycle.

Circadian regulation of intestinal lipid absorption by apolipoprotein AIV involves forkhead transcription factors A2 and O1 and microsomal triglyceride transfer protein.

PubMed

Pan, Xiaoyue; Munshi, Mohamed Khalid; Iqbal, Jahangir; Queiroz, Joyce; Sirwi, Alaa Ahmed; Shah, Shrenik; Younus, Abdullah; Hussain, M Mahmood

2013-07-12

We have shown previously that Clock, microsomal triglyceride transfer protein (MTP), and nocturnin are involved in the circadian regulation of intestinal lipid absorption. Here, we clarified the role of apolipoprotein AIV (apoAIV) in the diurnal regulation of plasma lipids and intestinal lipid absorption in mice. Plasma triglyceride in apoAIV(-/-) mice showed diurnal variations similar to apoAIV(+/+) mice; however, the increases in plasma triglyceride at night were significantly lower in these mice. ApoAIV(-/-) mice absorbed fewer lipids at night and showed blunted response to daytime feeding. To explain reasons for these lower responses, we measured MTP expression; intestinal MTP was low at night, and its induction after food entrainment was less in apoAIV(-/-) mice. Conversely, apoAIV overexpression increased MTP mRNA in hepatoma cells, indicating transcriptional regulation. Mechanistic studies revealed that sequences between -204/-775 bp in the MTP promoter respond to apoAIV and that apoAIV enhances expression of FoxA2 and FoxO1 transcription factors and their binding to the identified cis elements in the MTP promoter at night. Knockdown of FoxA2 and FoxO1 abolished apoAIV-mediated MTP induction. Similarly, knockdown of apoAIV in differentiated Caco-2 cells reduced MTP, FoxA2, and FoxO1 mRNA levels, cellular MTP activity, and media apoB. Moreover, FoxA2 and FoxO1 expression showed diurnal variations, and their expression was significantly lower in apoAIV(-/-) mice. These data indicate that apoAIV modulates diurnal changes in lipid absorption by regulating forkhead transcription factors and MTP and that inhibition of apoAIV expression might reduce plasma lipids.

Upregulation of MiR-212 Inhibits Migration and Tumorigenicity and Inactivates Wnt/β-Catenin Signaling in Human Hepatocellular Carcinoma.

PubMed

Jia, Pengbo; Wei, Guangbing; Zhou, Cancan; Gao, Qi; Wu, Yunhua; Sun, Xuejun; Li, Xuqi

2018-01-01

MicroRNAs are involved in hepatocellular carcinoma metastasis, a principal cause of hepatocellular carcinoma-related death in patients worldwide. MiR-212 is a microRNA that has been identified in several types of cancers and is postulated to influence cell signaling and subsequent malignant pathogenesis. Despite emerging reports suggesting that miR-212 plays a significant role in the onset, progression, and migration of these types of malignant tumors, its involvement in the development of hepatocellular carcinoma has not been fully elucidated. Quantitative reverse transcription polymerase chain reaction, wound healing, transwell migration and invasion assays, Western blotting, and xenograft tumor growth models were performed to test the expression levels and functions of miR-212 in hepatocellular carcinoma. Luciferase reporter assay, quantitative reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry were used to identify and verify the target of miR-212. In this study, we identify significant repression of miR-212 in hepatocellular carcinoma and demonstrate that overexpression of miR-212 inhibits the migration of hepatocellular carcinoma cells in vitro and in vivo. Furthermore, we identify forkhead box M1, whose expression is inversely related to that of miR-212, as a direct target of miR-212. Additionally, reexpression of forkhead box M1 rescues the miR-212-mediated inhibition of cell migration. We observed that inhibition of miR-212 activates forkhead box M1 but inhibits the Wnt/β-catenin pathway by suppressing Wnt, LEF-1, c-Myc, and nuclear β-catenin. Finally, in vivo studies confirmed the inhibitory effect of miR-212 on hepatocellular carcinoma growth. Our present findings indicate that miR-212 is a potential prognostic biomarker of hepatocellular carcinoma and that the miR-212/forkhead box M1 regulatory axis may represent a new therapeutic objective for hepatocellular carcinoma treatment.

FOXP2 promotes the nuclear translocation of POT1, but FOXP2(R553H), mutation related to speech-language disorder, partially prevents it.

PubMed

Tanabe, Yuko; Fujita, Eriko; Momoi, Takashi

2011-07-08

FOXP2 is a forkhead box-containing transcription factor with several recognizable sequence motifs. However, little is known about the FOXP2-associated proteins except for C-terminal binding protein (CtBP). In the present study, we attempted to isolate the FOXP2-associated protein with a yeast two-hybrid system using the C-terminal region, including the forkhead domain, as a bait probe, and identified protection of telomeres 1 (POT1) as a FOXP2-associated protein. Immunoprecipitation assay confirmed the association with FOXP2 and POT1. POT1 alone localized in the cytoplasm but co-localized with FOXP2 and the forkhead domain of FOXP2 in nuclei. However, both FOXP2 with mutated nuclear localization signals and (R553H) mutated forkhead, which is associated with speech-language disorder, prevented the nuclear translocation of POT1. These results suggest that FOXP2 is a binding partner for the nuclear translocation of POT1. As loss of POT1 function induces the cell arrest, the impaired nuclear translocation of POT1 in the developing neuronal cells may be associated with the pathogenesis of speech-language disorder with FOXP2(R553H) mutation. Copyright © 2011 Elsevier Inc. All rights reserved.

An Arabidopsis F-box protein acts as a transcriptional co-factor to regulate floral development.

PubMed

Chae, Eunyoung; Tan, Queenie K-G; Hill, Theresa A; Irish, Vivian F

2008-04-01

Plants flower in response to both environmental and endogenous signals. The Arabidopsis LEAFY (LFY) transcription factor is crucial in integrating these signals, and acts in part by activating the expression of multiple floral homeotic genes. LFY-dependent activation of the homeotic APETALA3 (AP3) gene requires the activity of UNUSUAL FLORAL ORGANS (UFO), an F-box component of an SCF ubiquitin ligase, yet how this regulation is effected has remained unclear. Here, we show that UFO physically interacts with LFY both in vitro and in vivo, and this interaction is necessary to recruit UFO to the AP3 promoter. Furthermore, a transcriptional repressor domain fused to UFO reduces endogenous LFY activity in plants, supporting the idea that UFO acts as part of a transcriptional complex at the AP3 promoter. Moreover, chemical or genetic disruption of proteasome activity compromises LFY-dependent AP3 activation, indicating that protein degradation is required to promote LFY activity. These results define an unexpected role for an F-box protein in functioning as a DNA-associated transcriptional co-factor in regulating floral homeotic gene expression. These results suggest a novel mechanism for promoting flower development via protein degradation and concomitant activation of the LFY transcription factor. This mechanism may be widely conserved, as homologs of UFO and LFY have been identified in a wide array of plant species.

The forkhead domain gene unc-130 generates chemosensory neuron diversity in C. elegans

PubMed Central

Sarafi-Reinach, Trina R.; Sengupta, Piali

2000-01-01

Caenorhabditis elegans responds to its complex chemical environment using a small number of chemosensory neurons. Each of these neurons exhibits a unique sensory response repertoire. The developmental mechanisms that generate this diversity of function are largely unknown. Many C. elegans chemosensory neurons, including the AWA and ASG neurons, arise as lineal sisters of an asymmetric division. Here we describe the gene unc-130, which plays a role in the generation of the AWA and ASG neurons. In unc-130 mutants, the ASG neurons adopt the fate of the AWA neurons. unc-130 encodes a member of the forkhead domain family of transcription factors, and is expressed in the precursors to AWA and ASG neurons. Misexpression of unc-130 in the AWA neurons is partly sufficient to repress the AWA fate, but not to promote ASG fate. unc-130 also plays a role in the development of additional chemosensory neurons. Our experiments show that the ASG neurons share a developmental default state in common with three types of olfactory neurons. We propose that distinct cell fates and hence diversity of function in the chemosensory neurons of C. elegans are generated in a hierarchical manner, utilizing both lineage-dependent and independent mechanisms. PMID:11018015

Evaluation of Pre-marketing Factors to Predict Post-marketing Boxed Warnings and Safety Withdrawals.

PubMed

Schick, Andreas; Miller, Kathleen L; Lanthier, Michael; Dal Pan, Gerald; Nardinelli, Clark

2017-06-01

An important goal in drug regulation is understanding serious safety issues with new drugs as soon as possible. Achieving this goal requires us to understand whether information provided during the Food and Drug Administration (FDA) drug review can predict serious safety issues that are usually identified after the product is approved. However, research on this topic remains understudied. In this paper, we examine whether any pre-marketing drug characteristics are associated with serious post-marketing safety actions. We study this question using an internal FDA database containing every new small molecule drug submitted to the FDA's Center for Drug Evaluation and Research (CDER) on or after November 21, 1997, and approved and commercially launched before December 31, 2009. Serious post-marketing safety actions include whether these drugs ever experienced either a post-marketing boxed warning or a withdrawal from the market due to safety concerns. A random effects logistic regression model was used to test whether any pre-marketing characteristics were associated with either post-marketing safety action. A total of 219 new molecular entities were analyzed. Among these drugs, 11 experienced a safety withdrawal and 30 received boxed warnings by July 31, 2016. Contrary to prevailing hypotheses, we find that neither clinical trial sample sizes nor review time windows are associated with the addition of a post-marketing boxed warning or safety withdrawal. However, we do find that new drugs approved with either a boxed warning or priority review are more likely to experience post-marketing boxed warnings. Furthermore, drugs approved with boxed warnings tend to receive post-marketing boxed warnings resulting from new safety information that are unrelated to the original warning. Drugs approved with a boxed warning are 3.88 times more likely to receive a post-marketing boxed warning, while drugs approved with a priority review are 3.51 times more likely to receive a post

The Box Turtle: Room with a View on Species Decline.

ERIC Educational Resources Information Center

Belzer, Bill; Steisslinger, Mary Beth

1999-01-01

Surveys salient aspects of eastern box-turtle natural history. Explores the societal and ecological factors that have contributed to the decline of the box-turtle population. Contains 18 references. (WRM)

Identification of the Transformational Properties and Transcriptional Targets of the Oncogenic SRY Transcription Factor SOX4

DTIC Science & Technology

2010-01-01

using linker -mediated PCR as described previously (25). Amplified DNA was labeled and hybridized in triplicate by NimbleGen Systems, Inc., to their human...leading edge analysis (37) of these gene sets identified TGFb–induced SMAD3 direct target genes (Supplementary Table S5) as enriched in SOX4 target...3.06E11 PAX5 Paired box 2.07E10 WHN Forkhead 2.94E10 SMAD3 SMAD 1.82E09 SMAD4 SMAD 3.33E09 MYC MYC 6.25E09 NFKAPPAB NF-nB 2.95E08 LEF1/TCF1 LEF

Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor X (RFX) transcription factors through X-box promoter motifs

PubMed Central

Tammimies, Kristiina; Bieder, Andrea; Lauter, Gilbert; Sugiaman-Trapman, Debora; Torchet, Rachel; Hokkanen, Marie-Estelle; Burghoorn, Jan; Castrén, Eero; Kere, Juha; Tapia-Páez, Isabel; Swoboda, Peter

2016-01-01

DYX1C1, DCDC2, and KIAA0319 are three of the most replicated dyslexia candidate genes (DCGs). Recently, these DCGs were implicated in functions at the cilium. Here, we investigate the regulation of these DCGs by Regulatory Factor X transcription factors (RFX TFs), a gene family known for transcriptionally regulating ciliary genes. We identify conserved X-box motifs in the promoter regions of DYX1C1, DCDC2, and KIAA0319 and demonstrate their functionality, as well as the ability to recruit RFX TFs using reporter gene and electrophoretic mobility shift assays. Furthermore, we uncover a complex regulation pattern between RFX1, RFX2, and RFX3 and their significant effect on modifying the endogenous expression of DYX1C1 and DCDC2 in a human retinal pigmented epithelial cell line immortalized with hTERT (hTERT-RPE1). In addition, induction of ciliogenesis increases the expression of RFX TFs and DCGs. At the protein level, we show that endogenous DYX1C1 localizes to the base of the cilium, whereas DCDC2 localizes along the entire axoneme of the cilium, thereby validating earlier localization studies using overexpression models. Our results corroborate the emerging role of DCGs in ciliary function and characterize functional noncoding elements, X-box promoter motifs, in DCG promoter regions, which thus can be targeted for mutation screening in dyslexia and ciliopathies associated with these genes.—Tammimies, K., Bieder, A., Lauter, G., Sugiaman-Trapman, D., Torchet, R., Hokkanen, M.-E., Burghoorn, J., Castrén, E., Kere, J., Tapia-Páez, I., Swoboda, P. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor (RF) X transcription factors through X-box promoter motifs. PMID:27451412

Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor X (RFX) transcription factors through X-box promoter motifs.

PubMed

Tammimies, Kristiina; Bieder, Andrea; Lauter, Gilbert; Sugiaman-Trapman, Debora; Torchet, Rachel; Hokkanen, Marie-Estelle; Burghoorn, Jan; Castrén, Eero; Kere, Juha; Tapia-Páez, Isabel; Swoboda, Peter

2016-10-01

DYX1C1, DCDC2, and KIAA0319 are three of the most replicated dyslexia candidate genes (DCGs). Recently, these DCGs were implicated in functions at the cilium. Here, we investigate the regulation of these DCGs by Regulatory Factor X transcription factors (RFX TFs), a gene family known for transcriptionally regulating ciliary genes. We identify conserved X-box motifs in the promoter regions of DYX1C1, DCDC2, and KIAA0319 and demonstrate their functionality, as well as the ability to recruit RFX TFs using reporter gene and electrophoretic mobility shift assays. Furthermore, we uncover a complex regulation pattern between RFX1, RFX2, and RFX3 and their significant effect on modifying the endogenous expression of DYX1C1 and DCDC2 in a human retinal pigmented epithelial cell line immortalized with hTERT (hTERT-RPE1). In addition, induction of ciliogenesis increases the expression of RFX TFs and DCGs. At the protein level, we show that endogenous DYX1C1 localizes to the base of the cilium, whereas DCDC2 localizes along the entire axoneme of the cilium, thereby validating earlier localization studies using overexpression models. Our results corroborate the emerging role of DCGs in ciliary function and characterize functional noncoding elements, X-box promoter motifs, in DCG promoter regions, which thus can be targeted for mutation screening in dyslexia and ciliopathies associated with these genes.-Tammimies, K., Bieder, A., Lauter, G., Sugiaman-Trapman, D., Torchet, R., Hokkanen, M.-E., Burghoorn, J., Castrén, E., Kere, J., Tapia-Páez, I., Swoboda, P. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor (RF) X transcription factors through X-box promoter motifs. © The Author(s).

Gene transfer of high-mobility group box 1 box-A domain in a rat acute liver failure model.

PubMed

Tanaka, Masayuki; Shinoda, Masahiro; Takayanagi, Atsushi; Oshima, Go; Nishiyama, Ryo; Fukuda, Kazumasa; Yagi, Hiroshi; Hayashida, Tetsu; Masugi, Yohei; Suda, Koichi; Yamada, Shingo; Miyasho, Taku; Hibi, Taizo; Abe, Yuta; Kitago, Minoru; Obara, Hideaki; Itano, Osamu; Takeuchi, Hiroya; Sakamoto, Michiie; Tanabe, Minoru; Maruyama, Ikuro; Kitagawa, Yuko

2015-04-01

High-mobility group box 1 (HMGB1) has recently been identified as an important mediator of various kinds of acute and chronic inflammation. The protein encoded by the box-A domain of the HMGB1 gene is known to act as a competitive inhibitor of HMGB1. In this study, we investigated whether box-A gene transfer results in box-A protein production in rats and assessed therapeutic efficacy in vivo using an acute liver failure (ALF) model. Three types of adenovirus vectors were constructed-a wild type and two mutants-and a mutant vector was then selected based on the secretion from HeLa cells. The secreted protein was subjected to a tumor necrosis factor (TNF) production inhibition test in vitro. The vector was injected via the portal vein in healthy Wistar rats to confirm box-A protein production in the liver. The vector was then injected via the portal vein in rats with ALF. Western blot analysis showed enhanced expression of box-A protein in HeLa cells transfected with one of the mutant vectors. The culture supernatant from HeLa cells transfected with the vector inhibited TNF-α production from macrophages. Expression of box-A protein was confirmed in the transfected liver at 72 h after transfection. Transfected rats showed decreased hepatic enzymes, plasma HMGB1, and hepatic TNF-α messenger RNA levels, and histologic findings and survival were significantly improved. HMGB1 box-A gene transfer results in box-A protein production in the liver and appears to have a beneficial effect on ALF in rats. Copyright © 2015 Elsevier Inc. All rights reserved.

The genetics of early telencephalon patterning: some assembly required

PubMed Central

Hébert, Jean M.; Fishell, Gord

2009-01-01

The immense range of human behaviours is rooted in the complex neural networks of the cerebrum. The creation of these networks depends on the precise integration of specific neuronal subtypes that are born in different regions of the telencephalon. Here, using the mouse as a model system, we review how these proliferative zones are established. Moreover, we discuss how these regions can be traced back in development to the function of a few key genes, including those that encode fibroblast growth factors (FGFs), sonic hedgehog (SHH), bone morphogenetic proteins (BMPs), forkhead box G1 (FoxG1), paired box 6 (PAX6) and LIM homeobox protein 2 (LHX2), that pattern the early telencephalon. PMID:19143049

Transcription Factor FoxO1 Is Essential for Enamel Biomineralization

PubMed Central

Poché, Ross A.; Sharma, Ramaswamy; Garcia, Monica D.; Wada, Aya M.; Nolte, Mark J.; Udan, Ryan S.; Paik, Ji-Hye; DePinho, Ronald A.; Bartlett, John D.; Dickinson, Mary E.

2012-01-01

The Transforming growth factor β (Tgf-β) pathway, by signaling via the activation of Smad transcription factors, induces the expression of many diverse downstream target genes thereby regulating a vast array of cellular events essential for proper development and homeostasis. In order for a specific cell type to properly interpret the Tgf-β signal and elicit a specific cellular response, cell-specific transcriptional co-factors often cooperate with the Smads to activate a discrete set of genes in the appropriate temporal and spatial manner. Here, via a conditional knockout approach, we show that mice mutant for Forkhead Box O transcription factor FoxO1 exhibit an enamel hypomaturation defect which phenocopies that of the Smad3 mutant mice. Furthermore, we determined that both the FoxO1 and Smad3 mutant teeth exhibit changes in the expression of similar cohort of genes encoding enamel matrix proteins required for proper enamel development. These data raise the possibility that FoxO1 and Smad3 act in concert to regulate a common repertoire of genes necessary for complete enamel maturation. This study is the first to define an essential role for the FoxO family of transcription factors in tooth development and provides a new molecular entry point which will allow researchers to delineate novel genetic pathways regulating the process of biomineralization which may also have significance for studies of human tooth diseases such as amelogenesis imperfecta. PMID:22291941

The cunning little vixen: Foxo and the cycle of life and death.

PubMed

Hedrick, Stephen M

2009-10-01

A screen for increased longevity in Caenorhabditis elegans has identified a transcription factor that programs cells for resistance to oxidative stress, DNA repair and cell cycle control. The mammalian orthologs of this factor are referred to as 'Foxo' for 'Forkhead box', with the second 'o' in the name denoting a subfamily of four members related by sequence. This family of factors is regulated by growth factors, oxidative stress or nutrient deprivation. Thus, it might readily control the inflammatory conflagration associated with infection-driven lymphocyte proliferation. Surprisingly, the first insights into Foxo-mediated immune regulation have instead revealed direct control of highly specialized genes of the adaptive immune system.

T-Box Genes in the Kidney and Urinary Tract.

PubMed

Kispert, A

2017-01-01

T-box (Tbx) genes encode an ancient group of transcription factors that play important roles in patterning, specification, proliferation, and differentiation programs in vertebrate organogenesis. This is testified by severe organ malformation syndromes in mice homozygous for engineered null alleles of specific T-box genes and by the large number of human inherited organ-specific diseases that have been linked to mutations in these genes. One of the organ systems that has not been associated with loss of specific T-box gene function in human disease for long is the excretory system. However, this has changed with the finding that mutations in TBX18, a member of a vertebrate-specific subgroup within the Tbx1-subfamily of T-box transcription factor genes, cause congenital anomalies of the kidney and urinary tract, predominantly hydroureter and ureteropelvic junction obstruction. Gene expression analyses, loss-of-function studies, and lineage tracing in the mouse suggest a primary role for this transcription factor in specifying the ureteric mesenchyme in the common anlage of the kidney, the ureter, and the bladder. We review the function of Tbx18 in ureterogenesis and discuss the body of evidence that Tbx18 and other members of the T-box gene family, namely, Tbx1, Tbx2, Tbx3, and Tbx20, play additional roles in development and homeostasis of other components of the excretory system in vertebrates. © 2017 Elsevier Inc. All rights reserved.

46 CFR 111.81-1 - Outlet boxes and junction boxes; general.

Code of Federal Regulations, 2010 CFR

2010-10-01

... fixture, wiring device, or similar item, including each separately installed connection and junction box... used. (d) As appropriate, each outlet-box or junction-box installation must meet the following...

Injury risk in professional boxing.

PubMed

Bledsoe, Gregory H; Li, Guohu; Levy, Fred

2005-10-01

Although a popular endeavor, boxing has fallen under increased scrutiny because of its association with traumatic brain injury. However, few studies have investigated the overall epidemiology of boxing injuries from representative samples, and no study has ever documented the incidence of injuries in female boxers. This study is a review of professional boxing data from the state of Nevada from September 2001 through March 2003. Medical and outcome data for all professional boxing matches occurring in Nevada between September 2001 and March 2003 (n = 524 matches) were analyzed on the basis of a pair-matched, case-control design. Cases were boxers who received an injury during the boxing matches. Boxers who were not injured served as control subjects. Both conditional and unconditional logistic regression models were used to assess risk factors for injury. The overall incidence rate of injury was 17.1 per 100 boxer-matches, or 3.4 per 100 boxer-rounds. Facial laceration accounted for 51% of all injuries, followed by hand injury (17%), eye injury (14%), and nose injury (5%). Male boxers were significantly more likely than female boxers to receive injuries (3.6 versus 1.2 per 100 boxer-rounds, P = 0.01). Male boxing matches also ended in knockouts and technical knockouts more often than did female matches (P < 0.001). The risk of injury for those who lost the matches was nearly twice the risk for the winners. Those who lost by knockout had double the risk of injury compared with those who lost by other means. Neither age nor weight was significantly associated with the risk of injury. The injury rate in professional boxing matches is high, particularly among male boxers. Superficial facial lacerations are the most common injury reported. Male boxers have a higher rate of knockout and technical knockouts than female boxers. Further research is necessary to determine the outcomes of injury, particularly the long-term neurologic outcome differences between sexes.

A holistic review on the autoimmune disease vitiligo with emphasis on the causal factors.

PubMed

Patel, Seema; Rauf, Abdur; Khan, Haroon; Meher, Biswa Ranjan; Hassan, Syed Shams Ul

2017-08-01

Vitiligo is an idiopathic systemic autoimmune disease affecting skin, hair and oral mucosa. This genetic yet acquired disease characterized by melanin loss is a cause of morbidity across all races. Though thyroid disturbance has been recognized as a key trigger of this pathology, an array of other factors plays critical role in its manifestation. Multiple hormones (corticotropin-releasing hormone, adrenocorticotropic hormone, α-melanocyte-stimulating hormone, melatonin, calcitriol, testosterone, estrogen), genes (Human leukocyte antigen (HLA), Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), Forkhead box D3 (FOXD3), Cluster of differentiation 117 (CD117), Estrogen receptor (ESR) 1, Cyclooxygenase-2 (COX2), Vitiligo-associated protein 1 (VIT1)), and lifestyle choices (stress, diet, cosmetic products, and medications) have been suspected as drivers of this disorder. The pathological mechanisms have been understood in recent times, with the aid of genomic studies; however a universally-effective therapy is yet to be achieved. This review discusses these under-investigated facets of vitiligo onset and progression; hence, it is expected to enrich vitiligo research. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Regulating the ethylene response of a plant by modulation of F-box proteins

DOEpatents

Guo, Hongwei [Beijing, CN; Ecker, Joseph R [Carlsbad, CA

2014-01-07

The relationship between F-box proteins and proteins invovled in the ethylene response in plants is described. In particular, F-box proteins may bind to proteins involved in the ethylene response and target them for degradation by the ubiquitin/proteasome pathway. The transcription factor EIN3 is a key transcription factor mediating ethylne-regulated gene expression and morphological responses. EIN3 is degraded through a ubiquitin/proteasome pathway mediated by F-box proteins EBF1 and EBF2. The link between F-box proteins and the ethylene response is a key step in modulating or regulating the response of a plant to ethylene. Described herein are transgenic plants having an altered sensitivity to ethylene, and methods for making transgenic plant haing an althered sensitivity to ethylene by modulating the level of activity of F-box proteins. Methods of altering the ethylene response in a plant by modulating the activity or expression of an F-box protein are described. Also described are methods of identifying compounds that modulate the ethylene response in plants by modulating the level of F-box protein expression or activity.

Prp43p Is a DEAH-Box Spliceosome Disassembly Factor Essential for Ribosome Biogenesis

PubMed Central

Combs, D. Joshua; Nagel, Roland J.; Ares, Manuel; Stevens, Scott W.

2006-01-01

The known function of the DEXH/D-box protein Prp43p is the removal of the U2, U5, and U6 snRNPs from the postsplicing lariat-intron ribonucleoprotein complex. We demonstrate that affinity-purified Prp43p-associated material includes the expected spliceosomal components; however, we also identify several preribosomal complexes that are specifically purified with Prp43p. Conditional prp43 mutant alleles confer a 35S pre-rRNA processing defect, with subsequent depletion of 27S and 20S precursors. Upon a shift to a nonpermissive temperature, both large and small-ribosomal-subunit proteins accumulate in the nucleolus of prp43 mutants. Pulse-chase analysis demonstrates delayed kinetics of 35S, 27S, and 20S pre-rRNA processing with turnover of these intermediates. Microarray analysis of pre-mRNA splicing defects in prp43 mutants shows a very mild effect, similar to that of nonessential pre-mRNA splicing factors. Prp43p is the first DEXH/D-box protein shown to function in both RNA polymerase I and polymerase II transcript metabolism. Its essential function is in its newly characterized role in ribosome biogenesis of both ribosomal subunits, positioning Prp43p to regulate both pre-mRNA splicing and ribosome biogenesis. PMID:16382144

Conserved composition of mammalian box H/ACA and box C/D small nucleolar ribonucleoprotein particles and their interaction with the common factor Nopp140.

PubMed

Yang, Y; Isaac, C; Wang, C; Dragon, F; Pogacic, V; Meier, U T

2000-02-01

Small nucleolar ribonucleoprotein particles (snoRNPs) mainly catalyze the modification of rRNA. The two major classes of snoRNPs, box H/ACA and box C/D, function in the pseudouridylation and 2'-O-methylation, respectively, of specific nucleotides. The emerging view based on studies in yeast is that each class of snoRNPs is composed of a unique set of proteins. Here we present a characterization of mammalian snoRNPs. We show that the previously characterized NAP57 is specific for box H/ACA snoRNPs, whereas the newly identified NAP65, the rat homologue of yeast Nop5/58p, is a component of the box C/D class. Using coimmunoprecipitation experiments, we show that the nucleolar and coiled-body protein Nopp140 interacts with both classes of snoRNPs. This interaction is corroborated in vivo by the exclusive depletion of snoRNP proteins from nucleoli in cells transfected with a dominant negative Nopp140 construct. Interestingly, RNA polymerase I transcription is arrested in nucleoli depleted of snoRNPs, raising the possibility of a feedback mechanism between rRNA modification and transcription. Moreover, the Nopp140-snoRNP interaction appears to be conserved in yeast, because depletion of Srp40p, the yeast Nopp140 homologue, in a conditional lethal strain induces the loss of box H/ACA small nucleolar RNAs. We propose that Nopp140 functions as a chaperone of snoRNPs in yeast and vertebrate cells.

Conserved Composition of Mammalian Box H/ACA and Box C/D Small Nucleolar Ribonucleoprotein Particles and Their Interaction with the Common Factor Nopp140

PubMed Central

Yang, Yunfeng; Isaac, Cynthia; Wang, Chen; Dragon, François; Pogac̆ić, Vanda; Meier, U. Thomas

2000-01-01

Small nucleolar ribonucleoprotein particles (snoRNPs) mainly catalyze the modification of rRNA. The two major classes of snoRNPs, box H/ACA and box C/D, function in the pseudouridylation and 2′-O-methylation, respectively, of specific nucleotides. The emerging view based on studies in yeast is that each class of snoRNPs is composed of a unique set of proteins. Here we present a characterization of mammalian snoRNPs. We show that the previously characterized NAP57 is specific for box H/ACA snoRNPs, whereas the newly identified NAP65, the rat homologue of yeast Nop5/58p, is a component of the box C/D class. Using coimmunoprecipitation experiments, we show that the nucleolar and coiled-body protein Nopp140 interacts with both classes of snoRNPs. This interaction is corroborated in vivo by the exclusive depletion of snoRNP proteins from nucleoli in cells transfected with a dominant negative Nopp140 construct. Interestingly, RNA polymerase I transcription is arrested in nucleoli depleted of snoRNPs, raising the possibility of a feedback mechanism between rRNA modification and transcription. Moreover, the Nopp140-snoRNP interaction appears to be conserved in yeast, because depletion of Srp40p, the yeast Nopp140 homologue, in a conditional lethal strain induces the loss of box H/ACA small nucleolar RNAs. We propose that Nopp140 functions as a chaperone of snoRNPs in yeast and vertebrate cells. PMID:10679015

Verification and Validation of Monte Carlo n-Particle Code 6 (MCNP6) with Neutron Protection Factor Measurements of an Iron Box

DTIC Science & Technology

2014-03-27

VERIFICATION AND VALIDATION OF MONTE CARLO N- PARTICLE CODE 6 (MCNP6) WITH NEUTRON PROTECTION FACTOR... PARTICLE CODE 6 (MCNP6) WITH NEUTRON PROTECTION FACTOR MEASUREMENTS OF AN IRON BOX THESIS Presented to the Faculty Department of Engineering...STATEMENT A. APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED iv AFIT-ENP-14-M-05 VERIFICATION AND VALIDATION OF MONTE CARLO N- PARTICLE CODE 6

The G-Box Transcriptional Regulatory Code in Arabidopsis1[OPEN

PubMed Central

Shepherd, Samuel J.K.; Brestovitsky, Anna; Dickinson, Patrick; Biswas, Surojit

2017-01-01

Plants have significantly more transcription factor (TF) families than animals and fungi, and plant TF families tend to contain more genes; these expansions are linked to adaptation to environmental stressors. Many TF family members bind to similar or identical sequence motifs, such as G-boxes (CACGTG), so it is difficult to predict regulatory relationships. We determined that the flanking sequences near G-boxes help determine in vitro specificity but that this is insufficient to predict the transcription pattern of genes near G-boxes. Therefore, we constructed a gene regulatory network that identifies the set of bZIPs and bHLHs that are most predictive of the expression of genes downstream of perfect G-boxes. This network accurately predicts transcriptional patterns and reconstructs known regulatory subnetworks. Finally, we present Ara-BOX-cis (araboxcis.org), a Web site that provides interactive visualizations of the G-box regulatory network, a useful resource for generating predictions for gene regulatory relations. PMID:28864470

Transcription factor ThWRKY4 binds to a novel WLS motif and a RAV1A element in addition to the W-box to regulate gene expression.

PubMed

Xu, Hongyun; Shi, Xinxin; Wang, Zhibo; Gao, Caiqiu; Wang, Chao; Wang, Yucheng

2017-08-01

WRKY transcription factors play important roles in many biological processes, and mainly bind to the W-box element to regulate gene expression. Previously, we characterized a WRKY gene from Tamarix hispida, ThWRKY4, in response to abiotic stress, and showed that it bound to the W-box motif. However, whether ThWRKY4 could bind to other motifs remains unknown. In this study, we employed a Transcription Factor-Centered Yeast one Hybrid (TF-Centered Y1H) screen to study the motifs recognized by ThWRKY4. In addition to the W-box core cis-element (termed W-box), we identified that ThWRKY4 could bind to two other motifs: the RAV1A element (CAACA) and a novel motif with sequence of GTCTA (W-box like sequence, WLS). The distributions of these motifs were screened in the promoter regions of genes regulated by some WRKYs. The results showed that the W-box, RAV1A, and WLS motifs were all present in high numbers, suggesting that they play key roles in gene expression mediated by WRKYs. Furthermore, five WRKY proteins from different WRKY subfamilies in Arabidopsis thaliana were selected and confirmed to bind to the RAV1A and WLS motifs, indicating that they are recognized commonly by WRKYs. These findings will help to further reveal the functions of WRKY proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

Genome-wide identification of the MADS-box transcription factor family in pear (Pyrus bretschneideri) reveals evolution and functional divergence.

PubMed

Wang, Runze; Ming, Meiling; Li, Jiaming; Shi, Dongqing; Qiao, Xin; Li, Leiting; Zhang, Shaoling; Wu, Jun

2017-01-01

MADS-box transcription factors play significant roles in plant developmental processes such as floral organ conformation, flowering time, and fruit development. Pear ( Pyrus ), as the third-most crucial temperate fruit crop, has been fully sequenced. However, there is limited information about the MADS family and its functional divergence in pear. In this study, a total of 95 MADS-box genes were identified in the pear genome, and classified into two types by phylogenetic analysis. Type I MADS-box genes were divided into three subfamilies and type II genes into 14 subfamilies. Synteny analysis suggested that whole-genome duplications have played key roles in the expansion of the MADS family, followed by rearrangement events. Purifying selection was the primary force driving MADS-box gene evolution in pear, and one gene pairs presented three codon sites under positive selection. Full-scale expression information for PbrMADS genes in vegetative and reproductive organs was provided and proved by transcriptional and reverse transcription PCR analysis. Furthermore, the PbrMADS11(12) gene, together with partners PbMYB10 and PbbHLH3 was confirmed to activate the promoters of the structural genes in anthocyanin pathway of red pear through dual luciferase assay. In addition, the PbrMADS11 and PbrMADS12 were deduced involving in the regulation of anthocyanin synthesis response to light and temperature changes. These results provide a solid foundation for future functional analysis of PbrMADS genes in different biological processes, especially of pigmentation in pear.

Cable Tester Box

NASA Technical Reports Server (NTRS)

Lee, Jason H.

2011-01-01

Cables are very important electrical devices that carry power and signals across multiple instruments. Any fault in a cable can easily result in a catastrophic outcome. Therefore, verifying that all cables are built to spec is a very important part of Electrical Integration Procedures. Currently, there are two methods used in lab for verifying cable connectivity. (1) Using a Break-Out Box and an ohmmeter this method is time-consuming but effective for custom cables and (2) Commercial Automated Cable Tester Boxes this method is fast, but to test custom cables often requires pre-programmed configuration files, and cables used on spacecraft are often uniquely designed for specific purposes. The idea is to develop a semi-automatic continuity tester that reduces human effort in cable testing, speeds up the electrical integration process, and ensures system safety. The JPL-Cable Tester Box is developed to check every single possible electrical connection in a cable in parallel. This system indicates connectivity through LED (light emitting diode) circuits. Users can choose to test any pin/shell (test node) with a single push of a button, and any other nodes that are shorted to the test node, even if they are in the same connector, will light up with the test node. The JPL-Cable Tester Boxes offers the following advantages: 1. Easy to use: The architecture is simple enough that it only takes 5 minutes for anyone to learn how operate the Cable Tester Box. No pre-programming and calibration are required, since this box only checks continuity. 2. Fast: The cable tester box checks all the possible electrical connections in parallel at a push of a button. If a cable normally takes half an hour to test, using the Cable Tester Box will improve the speed to as little as 60 seconds to complete. 3. Versatile: Multiple cable tester boxes can be used together. As long as all the boxes share the same electrical potential, any number of connectors can be tested together.

T-Box Genes in Drosophila Mesoderm Development.

PubMed

Reim, I; Frasch, M; Schaub, C

2017-01-01

In Drosophila there are eight genes encoding transcription factors of the T-box family, which are known to exert a variety of crucial developmental functions during ectodermal patterning processes, neuronal cell specification, mesodermal tissue development, and the development of extraembryonic tissues. In this review, we focus on the prominent roles of Drosophila T-box genes in mesodermal tissues. First, we describe the contributions of brachyenteron (byn) and optomotor-blind-related-gene-1 (org-1) to the development of the visceral mesoderm. Second, we provide an overview on the functions of the three Dorsocross paralogs (Doc1-3) and the two Tbx20-related paralogs (midline and H15) during Drosophila heart development. Third, we portray the roles of org-1 and midline/H15 in the specification of individual body wall and organ-attached muscles, including the function of org-1 in the transdifferentiation of certain heart-attached muscles during metamorphosis. The functional analysis of these evolutionarily conserved T-box genes, along with their interactions with other types of transcription factors and various signaling pathways, has provided key insights into the regulation of Drosophila visceral mesoderm, muscle, and heart development. © 2017 Elsevier Inc. All rights reserved.

MADS-box genes in maize: Frequent targets of selection during domestication

USDA-ARS?s Scientific Manuscript database

MADS-box genes encode transcription factors that are key regulators of plant inflorescence and flower development. We examined DNA sequence variation in 32 maize MADS-box genes and 32 random loci from the maize genome and investigated their involvement in maize domestication and improvement. Using n...

FoxM1 Promotes Glioma Cells Progression by Up-Regulating Anxa1 Expression

PubMed Central

Cheng, Shi-Xiang; Tu, Yue; Zhang, Sai

2013-01-01

Forkhead box M1 (FoxM1) is a member of the forkhead transcription factor family and is overexpression in malignant gliomas. However, the molecular mechanisms by which FoxM1lead to glioma carcinogenesis and progression are still not well known. In the present study, we show that Anxa1 was overexpression in gliomas and predicted the poor outcome. Furthermore, Anxa1 closely related to the FoxM1 expression and was a direct transcriptional target of FoxM1. Overexpression of FoxM1 up-regulated Anxa1 expression, whereas suppression of FoxM1 expression down-regulated Anxa1 expression in glioma cells. Finally, FoxM1 enhanced the proliferation, migration, and angiogenesis in Anxa1-dependent manner both in vitro and in vivo. Our findings provide both clinical and mechanistic evidences that FoxM1 contributes to glioma development by directly up-regulating Anxa1 expression. PMID:23991102

Transcriptional regulation of cellular ageing by the CCAAT box-binding factor CBF/NF-Y.

PubMed

Matuoka, Koozi; Chen, Kuang Yu

2002-09-01

Cellular ageing is a systematic process affecting the entirety of cell structure and function. Since changes in gene expression are extensive and global during ageing, involvement of general transcription regulators in the phenomenon is likely. Here, we focus on NF-Y, the major CCAAT box-binding factor, which exerts differential regulation on a wide variety of genes through its interaction with the CCAAT box present in as many as 25% of the eukaryotic genes. When a cell ages, senescing signals arise, typically through DNA damage due to oxidative stress or telomere shortening, and are transduced to proteins such as p53, retinoblastoma protein, and phosphatidylinositol 3-kinase. Among them, activated p53 family proteins suppress the function of NF-Y and thereby downregulate a set of cell cycle-related genes, including E2F1, which further leads to downregulation of E2F-regulated genes and cell cycle arrest. The p53 family also induces other ageing phenotypes such as morphological alterations and senescence-associated beta-galactosidase (SA-gal) presumably by upregulation of some genes through NF-Y suppression. In fact, the activities of NF-Y and E2F decrease during ageing and a dominant negative NF-YA induces SA-gal. Based on these observations, NF-Y appears to play an important role in the process of cellular ageing.

Looking Southwest at Reactor Box Furnaces With Reactor Boxes and ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Looking Southwest at Reactor Box Furnaces With Reactor Boxes and Repossessed Uranium in Recycle Recovery Building - Hematite Fuel Fabrication Facility, Recycle Recovery Building, 3300 State Road P, Festus, Jefferson County, MO

Cofactor-dependent specificity of a DEAD-box protein.

PubMed

Young, Crystal L; Khoshnevis, Sohail; Karbstein, Katrin

2013-07-16

DEAD-box proteins, a large class of RNA-dependent ATPases, regulate all aspects of gene expression and RNA metabolism. They can facilitate dissociation of RNA duplexes and remodeling of RNA-protein complexes, serve as ATP-dependent RNA-binding proteins, or even anneal duplexes. These proteins have highly conserved sequence elements that are contained within two RecA-like domains; consequently, their structures are nearly identical. Furthermore, crystal structures of DEAD-box proteins with bound RNA reveal interactions exclusively between the protein and the RNA backbone. Together, these findings suggest that DEAD-box proteins interact with their substrates in a nonspecific manner, which is confirmed in biochemical experiments. Nevertheless, this contrasts with the need to target these enzymes to specific substrates in vivo. Using the DEAD-box protein Rok1 and its cofactor Rrp5, which both function during maturation of the small ribosomal subunit, we show here that Rrp5 provides specificity to the otherwise nonspecific biochemical activities of the Rok1 DEAD-domain. This finding could reconcile the need for specific substrate binding of some DEAD-box proteins with their nonspecific binding surface and expands the potential roles of cofactors to specificity factors. Identification of helicase cofactors and their RNA substrates could therefore help define the undescribed roles of the 19 DEAD-box proteins that function in ribosome assembly.

Measure Guideline: Optimizing the Configuration of Flexible Duct Junction Boxes

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

Beach, R.; Burdick, A.

2014-03-01

This measure guideline offers additional recommendations to heating, ventilation, and air conditioning (HVAC) system designers for optimizing flexible duct, constant-volume HVAC systems using junction boxes within Air Conditioning Contractors of America (ACCA) Manual D guidance. IBACOS used computational fluid dynamics software to explore and develop guidance to better control the airflow effects of factors that may impact pressure losses within junction boxes among various design configurations. These recommendations can help to ensure that a system aligns more closely with the design and the occupants' comfort expectations. Specifically, the recommendations described herein show how to configure a rectangular box with fourmore » outlets, a triangular box with three outlets, metal wyes with two outlets, and multiple configurations for more than four outlets. Designers of HVAC systems, contractors who are fabricating junction boxes on site, and anyone using the ACCA Manual D process for sizing duct runs will find this measure guideline invaluable for more accurately minimizing pressure losses when using junction boxes with flexible ducts.« less

Genome-wide identification of the MADS-box transcription factor family in pear (Pyrus bretschneideri) reveals evolution and functional divergence

PubMed Central

Li, Jiaming; Shi, Dongqing; Qiao, Xin; Li, Leiting; Zhang, Shaoling

2017-01-01

MADS-box transcription factors play significant roles in plant developmental processes such as floral organ conformation, flowering time, and fruit development. Pear (Pyrus), as the third-most crucial temperate fruit crop, has been fully sequenced. However, there is limited information about the MADS family and its functional divergence in pear. In this study, a total of 95 MADS-box genes were identified in the pear genome, and classified into two types by phylogenetic analysis. Type I MADS-box genes were divided into three subfamilies and type II genes into 14 subfamilies. Synteny analysis suggested that whole-genome duplications have played key roles in the expansion of the MADS family, followed by rearrangement events. Purifying selection was the primary force driving MADS-box gene evolution in pear, and one gene pairs presented three codon sites under positive selection. Full-scale expression information for PbrMADS genes in vegetative and reproductive organs was provided and proved by transcriptional and reverse transcription PCR analysis. Furthermore, the PbrMADS11(12) gene, together with partners PbMYB10 and PbbHLH3 was confirmed to activate the promoters of the structural genes in anthocyanin pathway of red pear through dual luciferase assay. In addition, the PbrMADS11 and PbrMADS12 were deduced involving in the regulation of anthocyanin synthesis response to light and temperature changes. These results provide a solid foundation for future functional analysis of PbrMADS genes in different biological processes, especially of pigmentation in pear. PMID:28924499

Does previous use affect litter box appeal in multi-cat households?

PubMed

Ellis, J J; McGowan, R T S; Martin, F

2017-08-01

It is commonly assumed that cats actively avoid eliminated materials (especially in multi-cat homes), suggesting regular litter box cleaning as the best defense against out-of-box elimination. The relationship between previous use and litter box appeal to familiar subsequent users is currently unknown. The purpose of this study was to investigate the relationship between previous litter box use and the identity of the previous user, type of elimination, odor, and presence of physical/visual obstructions in a multi-cat household scenario. Cats preferred a clean litter box to a dirty one, but the identity of the previous user had no impact on preferences. While the presence of odor from urine and/or feces did not impact litter box preferences, the presence of odorless faux-urine and/or feces did - with the presence of faux-feces being preferred over faux-urine. Results suggest neither malodor nor chemical communication play a role in litter box preferences, and instead emphasize the importance of regular removal of physical/visual obstructions as the key factor in promoting proper litter box use. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

GLOVE BOX ATTACHMENT

DOEpatents

Butts, H.L.

1962-02-13

This invention comprises a housing unit to be fitted between a glove box port and a glove so that a slidable plate within the housing seals off the glove box port for evacuation of the glove box without damage to the glove. The housing and the glove may be evacuated without damage to the glove since movement of the glove is restricted during evacuation by the slidable plate. (AEC)

What's the FOX Got to Do with the KITten? Regulating the Lineage-Specific Transcriptional Landscape in GIST.

PubMed

Lee, Donna M; Duensing, Anette

2018-02-01

Transcriptional regulation of the KIT receptor tyrosine kinase, a master regulator in gastrointestinal stromal tumors (GIST) and their precursors, the interstitial cells of Cajal (ICC), is part of a positive feedback loop involving the transcription factor ETV1. A new study now shows that the forkhead box (FOX) family transcription factor FOXF1 not only is an upstream regulator of ETV1 and hence ICC/GIST lineage-specific gene transcription, but also functions as lineage-specific pioneer factor with an active role in chromatin rearrangement to facilitate ETV1 binding and transcriptional activity. Cancer Discov; 8(2); 146-9. ©2018 AACR See related article by Ran et al., p. 234 . ©2018 American Association for Cancer Research.

Automatic box loader

DOEpatents

Eldridge, Harry H.; Jones, Robert A.; Lindner, Gordon M.; Hight, Paul H.

1976-01-01

This invention relates to a system for repetitively forming an assembly consisting of a single layer of tubes and a row of ferromagnetic armatures underlying the same, electromagnetically conveying the resulting assembly to a position overlying a storage box, and depositing the assembly in the box. The system includes means for simultaneously depositing a row of the armatures on the inclined surface of a tube retainer. Tubes then are rolled down the surface to form a single tube layer bridging the armatures. A magnet assembly carrying electromagnets respectively aligned with the armatures is advanced close to the tube layer, and in the course of this advance is angularly displaced to bring the pole pieces of the electromagnets into parallelism with the tube layer. The magnets then are energized to pick up the assembly. The loaded magnet assembly is retracted to a position overlying the box, and during this retraction is again displaced to bring the pole pieces of the electromagnets into a horizontal plane. Means are provided for inserting the loaded electromagnets in the box and then de-energizing the electromagnets to deposit the assembly therein. The system accomplishes the boxing of fragile tubes at relatively high rates. Because the tubes are boxed as separated uniform layers, subsequent unloading operations are facilitated.

Conversion of a Replication Origin to a Silencer through a Pathway Shared by a Forkhead Transcription Factor and an S Phase Cyclin

PubMed Central

Casey, Laurieann; Patterson, Erin E.; Müller, Ulrika

2008-01-01

Silencing of the mating-type locus HMR in Saccharomyces cerevisiae requires DNA elements called silencers. To establish HMR silencing, the origin recognition complex binds the HMR-E silencer and recruits the silent information regulator (Sir)1 protein. Sir1 in turn helps establish silencing by stabilizing binding of the other Sir proteins, Sir2–4. However, silencing is semistable even in sir1Δ cells, indicating that SIR1-independent establishment mechanisms exist. Furthermore, the requirement for SIR1 in silencing a sensitized version of HMR can be bypassed by high-copy expression of FKH1 (FKH1hc), a conserved forkhead transcription factor, or by deletion of the S phase cyclin CLB5 (clb5Δ). FKH1hc caused only a modest increase in Fkh1 levels but effectively reestablished Sir2–4 chromatin at HMR as determined by Sir3-directed chromatin immunoprecipitation. In addition, FKH1hc prolonged the cell cycle in a manner distinct from deletion of its close paralogue FKH2, and it created a cell cycle phenotype more reminiscent to that caused by a clb5Δ. Unexpectedly, and in contrast to SIR1, both FKH1hc and clb5Δ established silencing at HMR using the replication origins, ARS1 or ARSH4, as complete substitutes for HMR-E (HMRΔE::ARS). HMRΔE::ARS1 was a robust origin in CLB5 cells. However, initiation by HMRΔE::ARS1 was reduced by clb5Δ or FKH1hc, whereas ARS1 at its native locus was unaffected. The CLB5-sensitivity of HMRΔE::ARS1 did not result from formation of Sir2–4 chromatin because sir2Δ did not rescue origin firing in clb5Δ cells. These and other data supported a model in which FKH1 and CLB5 modulated Sir2–4 chromatin and late-origin firing through opposing regulation of a common pathway. PMID:18045995

Medical and Safety Reforms in Boxing

PubMed Central

Jordan, Barry D.

1988-01-01

The continued existence of boxing as an accepted sport in civilized society has been long debated. The position of the American Medical Association (AMA) has evolved from promoting increased safety and medical reform to recommending total abolition of both amateur and professional boxing. In response to the AMA opposition to boxing, the boxing community has attempted to increase the safeguards in amateur and professional boxing. The United States of America Amateur Boxing Federation, which is the national regulatory agency for all amateur boxing in the United States, has taken several actions to prevent the occurrence of acute brain injury and is currently conducting epidemiologic studies to assess the long-term neuropsychologic consequences of amateur boxing. In professional boxing, state regulatory agencies such as the New York State Athletic Commission have introduced several medical interventions to prevent and reduce neurologic injury. The lack of a national regulatory agency to govern professional boxing has stimulated the formation of the Association of Boxing Commissions and potential legislation for the federal regulation of professional boxing by a federally chartered organization called the United States Boxing Commission. The AMA's opposition to boxing and the medical and safety reforms implemented by the proponents of boxing are discussed. PMID:3385788

Recognition of the Xenopus ribosomal core promoter by the transcription factor xUBF involves multiple HMG box domains and leads to an xUBF interdomain interaction.

PubMed

Leblanc, B; Read, C; Moss, T

1993-02-01

The interaction of the ribosomal transcription factor xUBF with the RNA polymerase I core promoter of Xenopus laevis has been studied both at the DNA and protein levels. It is shown that a single xUBF-DNA complex forms over the 40S initiation site (+1) and involves at least the DNA sequences between -20 and +60 bp. DNA sequences upstream of +10 and downstream of +18 are each sufficient to direct complex formation independently. HMG box 1 of xUBF independently recognizes the sequences -20 to -1 and +1 to +22 and the addition of the N-terminal dimerization domain to HMG box 1 stabilizes its interaction with these sequences approximately 10-fold. HMG boxes 2/3 interact with the DNA downstream of +22 and can independently position xUBF across the initiation site. The C-terminal segment of xUBF, HMG boxes 4, 5 or the acidic domain, directly or indirectly interact with HMG box 1, making the core promoter sequences between -11 and -15 hypersensitive to DNase. This interaction also requires the DNA sequences between +17 and +32, i.e. the HMG box 2/3 binding site. The data suggest extensive folding of the core promoter within the xUBF complex.

Intracellular distribution of a speech/language disorder associated FOXP2 mutant

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

Mizutani, Akifumi; Department of Pediatrics, Jichi Medical University, Yakushiji 3311-1, Shimotsukeshi, Tochigi 329-0498; Matsuzaki, Ayumi

Although a mutation (R553H) in the forkhead box (FOX)P2 gene is associated with speech/language disorder, little is known about the function of FOXP2 or its relevance to this disorder. In the present study, we identify the forkhead nuclear localization domains that contribute to the cellular distribution of FOXP2. Nuclear localization of FOXP2 depended on two distally separated nuclear localization signals in the forkhead domain. A truncated version of FOXP2 lacking the leu-zip, Zn{sup 2+} finger, and forkhead domains that was observed in another patient with speech abnormalities demonstrated an aggregated cytoplasmic localization. Furthermore, FOXP2 (R553H) mainly exhibited a cytoplasmic localizationmore » despite retaining interactions with nuclear transport proteins (importin {alpha} and {beta}). Interestingly, wild type FOXP2 promoted the transport of FOXP2 (R553H) into the nucleus. Mutant and wild type FOXP2 heterodimers in the nucleus or FOXP2 R553H in the cytoplasm may underlie the pathogenesis of the autosomal dominant speech/language disorder.« less

Bento Boxes

ERIC Educational Resources Information Center

Hasio, Cindy

2010-01-01

Bento boxes are common objects in Japanese culture, designed to hold enough lunch for one person. They have individual compartments and sometimes multiple tiers for rice, vegetables, and other side dishes. They are made of materials ranging from wood, cloth, aluminum, or plastic. In general, the greater the number of foods, the better the box is…

Ectromelia virus encodes a family of Ankyrin/F-box proteins that regulate NFκB

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

Burles, Kristin, E-mail: burles@ualberta.ca; Buuren, Nicholas van; Barry, Michele

2014-11-15

A notable feature of poxviruses is their ability to inhibit the antiviral response, including the nuclear factor kappa B (NFκB) pathway. NFκB is a transcription factor that is sequestered in the cytoplasm until cell stimulation, and relies on the SCF (Skp1, culllin-1, F-box) ubiquitin ligase to target its inhibitor, IκBα, for degradation. IκBα is recruited to the SCF by the F-box domain-containing protein βTrCP. Here, we show that ectromelia virus, the causative agent of mousepox, encodes four F-box-containing proteins, EVM002, EVM005, EVM154, and EVM165, all of which contain Ankyrin (Ank) domains. The Ank/F-box proteins inhibit NFκB nuclear translocation, and thismore » inhibition is dependent on the F-box domain. We also demonstrate that EVM002, EVM005, EVM154, and EVM165 prevent IκBα degradation, suggesting that they target the SCF. This study identifies a new mechanism by which ectromelia virus inhibits NFκB. - Highlights: • Ectromelia virus encodes four Ank/F-box proteins, EVM002, EVM005, EVM154 and EVM165. • The Ank/F-box proteins inhibit NFκB nuclear translocation, dependent on the F-box. • The Ank/F-box proteins prevent IκBα degradation, suggesting they target the SCF. • Deletion of a single Ank/F-box gene from ECTV does not prevent viral NFκB inhibition. • This study identifies a new mechanism by which ectromelia virus inhibits NFκB.« less

The immunosuppressives FK 506 and cyclosporin A inhibit the generation of protein factors binding to the two purine boxes of the interleukin 2 enhancer.

PubMed Central

Brabletz, T; Pietrowski, I; Serfling, E

1991-01-01

Like Cyclosporin A (CsA), the macrolide FK 506 is a potent immunosuppressive that inhibits early steps of T cell activation, including the synthesis of Interleukin 2 (II-2) and numerous other lymphokines. The block of II-2 synthesis occurs at the transcriptional level. At concentrations that block T cell activation, FK 506 and CsA inhibit the proto-enhancer activity of Purine boxes of the II-2 promoter and the generation of lymphocyte-specific factors binding to the Purine boxes. Under the same conditions, the DNA binding of other II-2 enhancer factors remains unaffected by both compounds. These results support the view that FK 506 and CsA, which both inhibit the activity of peptidylprolyl cis/trans isomerases, suppress T cell activation by a similar, if not identical mechanism. Images PMID:1707162

The immunosuppressives FK 506 and cyclosporin A inhibit the generation of protein factors binding to the two purine boxes of the interleukin 2 enhancer.

PubMed

Brabletz, T; Pietrowski, I; Serfling, E

1991-01-11

Like Cyclosporin A (CsA), the macrolide FK 506 is a potent immunosuppressive that inhibits early steps of T cell activation, including the synthesis of Interleukin 2 (II-2) and numerous other lymphokines. The block of II-2 synthesis occurs at the transcriptional level. At concentrations that block T cell activation, FK 506 and CsA inhibit the proto-enhancer activity of Purine boxes of the II-2 promoter and the generation of lymphocyte-specific factors binding to the Purine boxes. Under the same conditions, the DNA binding of other II-2 enhancer factors remains unaffected by both compounds. These results support the view that FK 506 and CsA, which both inhibit the activity of peptidylprolyl cis/trans isomerases, suppress T cell activation by a similar, if not identical mechanism.

EPA EcoBox

EPA Pesticide Factsheets

This tool box of ecological risk assessment (Eco-box) includes over 400+ links to tools, models, and databases found within EPA and our Government partners designed that can aid risk assessors with performing exposure assessments.

FOXO1, TGF-β Regulation and Wound Healing

PubMed Central

Hameedaldeen, Alhassan; Liu, Jian; Batres, Angelika; Graves, Gabrielle S.; Graves, Dana T.

2014-01-01

Re-epithelialization is a complex process that involves migration and proliferation of keratinocytes, in addition to the production of cytokines and growth factors that affect other cells. The induction of transcription factors during these processes is crucial for successful wound healing. The transcription factor forkhead boxO-1 (FOXO1) has recently been found to be an important regulator of wound healing. In particular, FOXO1 has significant effects through regulation of transforming growth factor-beta (TGF-β) expression and protecting keratinocytes from oxidative stress. In the absence of FOXO1, there is increased oxidative damage, reduced TGF-β1 expression, reduced migration and proliferation of keratinocytes and increased keratinocytes apoptosis leading to impaired re-epithelialization of wounds. PMID:25226535

PARylation of the forkhead-associated domain protein DAWDLE regulates plant immunity.

PubMed

Feng, Baomin; Ma, Shisong; Chen, Sixue; Zhu, Ning; Zhang, Shuxin; Yu, Bin; Yu, Yu; Le, Brandon; Chen, Xuemei; Dinesh-Kumar, Savithramma P; Shan, Libo; He, Ping

2016-12-01

Protein poly(ADP-ribosyl)ation (PARylation) primarily catalyzed by poly(ADP-ribose) polymerases (PARPs) plays a crucial role in controlling various cellular responses. However, PARylation targets and their functions remain largely elusive. Here, we deployed an Arabidopsis protein microarray coupled with in vitro PARylation assays to globally identify PARylation targets in plants. Consistent with the essential role of PARylation in plant immunity, the forkhead-associated (FHA) domain protein DAWDLE (DDL), one of PARP2 targets, positively regulates plant defense to both adapted and non-adapted pathogens. Arabidopsis PARP2 interacts with and PARylates DDL, which was enhanced upon treatment of bacterial flagellin. Mass spectrometry and mutagenesis analysis identified multiple PARylation sites of DDL by PARP2. Genetic complementation assays indicate that DDL PARylation is required for its function in plant immunity. In contrast, DDL PARylation appears to be dispensable for its previously reported function in plant development partially mediated by the regulation of microRNA biogenesis. Our study uncovers many previously unknown PARylation targets and points to the distinct functions of DDL in plant immunity and development mediated by protein PARylation and small RNA biogenesis, respectively. © 2016 The Authors.

The MADS-box transcription factor FgMcm1 regulates cell identity and fungal development in Fusarium graminearum.

PubMed

Yang, Cui; Liu, Huiquan; Li, Guotian; Liu, Meigang; Yun, Yingzi; Wang, Chenfang; Ma, Zhonghua; Xu, Jin-Rong

2015-08-01

In eukaryotic cells, MADS-box genes are known to play major regulatory roles in various biological processes by combinatorial interactions with other transcription factors. In this study, we functionally characterized the FgMCM1 MADS-box gene in Fusarium graminearum, the causal agent of wheat and barley head blight. Deletion of FgMCM1 resulted in the loss of perithecium production and phialide formation. The Fgmcm1 mutant was significantly reduced in virulence, deoxynivalenol biosynthesis and conidiation. In yeast two-hybrid assays, FgMcm1 interacted with Mat1-1-1 and Fst12, two transcription factors important for sexual reproduction. Whereas Fgmcm1 mutants were unstable and produced stunted subcultures, Fgmcm1 mat1-1-1 but not Fgmcm1 fst12 double mutants were stable. Furthermore, spontaneous suppressor mutations occurred frequently in stunted subcultures to recover growth rate. Ribonucleic acid sequencing analysis indicated that a number of sexual reproduction-related genes were upregulated in stunted subcultures compared with the Fgmcm1 mutant, which was downregulated in the expression of genes involved in pathogenesis, secondary metabolism and conidiation. We also showed that culture instability was not observed in the Fvmcm1 mutants of the heterothallic Fusarium verticillioides. Overall, our data indicate that FgMcm1 plays a critical role in the regulation of cell identity, sexual and asexual reproduction, secondary metabolism and pathogenesis in F. graminearum. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

The FOXP2 forkhead domain binds to a variety of DNA sequences with different rates and affinities.

PubMed

Webb, Helen; Steeb, Olga; Blane, Ashleigh; Rotherham, Lia; Aron, Shaun; Machanick, Philip; Dirr, Heini; Fanucchi, Sylvia

2017-07-01

FOXP2 is a member of the P subfamily of FOX transcription factors, the DNA-binding domain of which is the winged helix forkhead domain (FHD). In this work we show that the FOXP2 FHD is able to bind to various DNA sequences, including a novel sequence identified in this work, with different affinities and rates as detected using surface plasmon resonance. Combining the experimental work with molecular docking, we show that high-affinity sequences remain bound to the protein for longer, form a greater number of interactions with the protein and induce a greater structural change in the protein than low-affinity sequences. We propose a binding model for the FOXP2 FHD that involves three types of binding sequence: low affinity sites which allow for rapid scanning of the genome by the protein in a partially unstructured state; moderate affinity sites which serve to locate the protein near target sites and high-affinity sites which secure the protein to the DNA and induce a conformational change necessary for functional binding and the possible initiation of downstream transcriptional events. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Genome-wide analysis of the SBP-box gene family in Chinese cabbage (Brassica rapa subsp. pekinensis).

PubMed

Tan, Hua-Wei; Song, Xiao-Ming; Duan, Wei-Ke; Wang, Yan; Hou, Xi-Lin

2015-11-01

The SQUAMOSA PROMOTER BINDING PROTEIN (SBP)-box gene family contains highly conserved plant-specific transcription factors that play an important role in plant development, especially in flowering. Chinese cabbage (Brassica rapa subsp. pekinensis) is a leafy vegetable grown worldwide and is used as a model crop for research in genome duplication. The present study aimed to characterize the SBP-box transcription factor genes in Chinese cabbage. Twenty-nine SBP-box genes were identified in the Chinese cabbage genome and classified into six groups. We identified 23 orthologous and 5 co-orthologous SBP-box gene pairs between Chinese cabbage and Arabidopsis. An interaction network among these genes was constructed. Sixteen SBP-box genes were expressed more abundantly in flowers than in other tissues, suggesting their involvement in flowering. We show that the MiR156/157 family members may regulate the coding regions or 3'-UTR regions of Chinese cabbage SBP-box genes. As SBP-box genes were found to potentially participate in some plant development pathways, quantitative real-time PCR analysis was performed and showed that Chinese cabbage SBP-box genes were also sensitive to the exogenous hormones methyl jasmonic acid and salicylic acid. The SBP-box genes have undergone gene duplication and loss, evolving a more refined regulation for diverse stimulation in plant tissues. Our comprehensive genome-wide analysis provides insights into the SBP-box gene family of Chinese cabbage.

Small, Lightweight, Collapsible Glove Box

NASA Technical Reports Server (NTRS)

James, Jerry

2009-01-01

A small, lightweight, collapsible glove box enables its user to perform small experiments and other tasks. Originally intended for use aboard a space shuttle or the International Space Station (ISS), this glove box could also be attractive for use on Earth in settings in which work space or storage space is severely limited and, possibly, in which it is desirable to minimize weight. The development of this glove box was prompted by the findings that in the original space-shuttle or ISS setting, (1) it was necessary to perform small experiments in a large general-purpose work station, so that, in effect, they occupied excessive space; and it took excessive amounts of time to set up small experiments. The design of the glove box reflects the need to minimize the space occupied by experiments and the time needed to set up experiments, plus the requirement to limit the launch weight of the box and the space needed to store the box during transport into orbit. To prepare the glove box for use, the astronaut or other user has merely to insert hands through the two fabric glove ports in the side walls of the box and move two hinges to a locking vertical position (see figure). The user could do this while seated with the glove box on the user fs lap. When stowed, the glove box is flat and has approximately the thickness of two pieces of 8-in. (.20 cm) polycarbonate.

The influence of polarization on box air mass factors for UV/vis nadir satellite observations

NASA Astrophysics Data System (ADS)

Hilboll, Andreas; Richter, Andreas; Rozanov, Vladimir V.; Burrows, John P.

2015-04-01

Tropospheric abundances of pollutant trace gases like, e.g., NO2, are often derived by applying the differential optical absorption spectroscopy (DOAS) method to space-borne measurements of back-scattered and reflected solar radiation. The resulting quantity, the slant column density (SCD), subsequently has to be converted to more easily interpretable vertical column densities by means of the so-called box air mass factor (BAMF). The BAMF describes the ratio of SCD and VCD within one atmospheric layer and is calculated by a radiative transfer model. Current operational and scientific data products of satellite-derived trace gas VCDs do not include the effect of polarization in their radiative transfer models. However, the various scattering processes in the atmosphere do lead to a distinctive polarization pattern of the observed Earthshine spectra. This study investigates the influence of these polarization patterns on box air mass factors for satellite nadir DOAS measurements of NO2 in the UV/vis wavelength region. NO2 BAMFs have been simulated for a multitude of viewing geometries, surface albedos, and surface altitudes, using the radiative transfer model SCIATRAN. The results show a potentially large influence of polarization on the BAMF, which can reach 10% and more close to the surface. A simple correction for this effect seems not to be feasible, as it strongly depends on the specific measurement scenario and can lead to both high and low biases of the resulting NO2 VCD. We therefore conclude that all data products of NO2 VCDs derived from space-borne DOAS measurements should include polarization effects in their radiative transfer model calculations, or at least include the errors introduced by using linear models in their uncertainty estimates.

Measure Guideline: Optimizing the Configuration of Flexible Duct Junction Boxes

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

Beach, R.; Burdick, A.

2014-03-01

This measure guideline offers additional recommendations to heating, ventilation, and air conditioning (HVAC) system designers for optimizing flexible duct, constant-volume HVAC systems using junction boxes within Air Conditioning Contractors of America (ACCA) Manual D guidance (Rutkowski, H. Manual D -- Residential Duct Systems, 3rd edition, Version 1.00. Arlington, VA: Air Conditioning Contractors of America, 2009.). IBACOS used computational fluid dynamics software to explore and develop guidance to better control the airflow effects of factors that may impact pressure losses within junction boxes among various design configurations (Beach, R., Prahl, D., and Lange, R. CFD Analysis of Flexible Duct Junction Boxmore » Design. Golden, CO: National Renewable Energy Laboratory, submitted for publication 2013). These recommendations can help to ensure that a system aligns more closely with the design and the occupants' comfort expectations. Specifically, the recommendations described herein show how to configure a rectangular box with four outlets, a triangular box with three outlets, metal wyes with two outlets, and multiple configurations for more than four outlets. Designers of HVAC systems, contractors who are fabricating junction boxes on site, and anyone using the ACCA Manual D process for sizing duct runs will find this measure guideline invaluable for more accurately minimizing pressure losses when using junction boxes with flexible ducts.« less

The role of the RB tumour suppressor pathway in oxidative stress responses in the haematopoietic system

PubMed Central

Macleod, Kay F.

2010-01-01

Exposure to pro-oxidants and defects in the repair of oxidative base damage are associated with disease and ageing and also contribute to the development of anaemia, bone marrow failure and haematopoietic malignancies. This Review assesses emerging data indicative of a specific role for the RB tumour suppressor pathway in the response of the haematopoietic system to oxidative stress. This is mediated through signalling pathways that involve DNA damage sensors, forkhead box O (Foxo) transcription factors and p38 mitogen-activated protein kinases and has downstream consequences for cell cycle progression, antioxidant capacity, mitochondrial mass and cellular metabolism. PMID:18800074

Measuring Helicase Inhibition of the DEAD-box Protein Dbp2 by Yra1

PubMed Central

Ma, Wai Kit; Tran, Elizabeth J.

2016-01-01

Despite the highly conserved helicase core, individual DEAD-box proteins are specialized in diverse RNA metabolic processes. One mechanism that determines DEAD-box protein specificity is enzymatic regulation by other protein cofactors. In this chapter, we describe a protocol for purifying the Saccharomyces cerevisiae DEAD-box RNA helicase Dbp2 and RNA-binding protein Yra1 and subsequent analysis of helicase regulation. The experiments described here can be adapted to RNA helicase and purified co-factor. PMID:25579587

Glove box shield

DOEpatents

Brackenbush, L.W.; Hoenes, G.R.

A shield for a glove box housing radioactive material is comprised of spaced apart clamping members which maintain three overlapping flaps in place therebetween. There is a central flap and two side flaps, the side flaps overlapping at the interior edges thereof and the central flap extending past the intersection of the side flaps in order to insure that the shield is always closed when the user wthdraws his hand from the glove box. Lead loaded neoprene rubber is the preferred material for the three flaps, the extent of lead loading depending upon the radiation levels within the glove box.

Boxing-related head injuries.

PubMed

Jayarao, Mayur; Chin, Lawrence S; Cantu, Robert C

2010-10-01

Fatalities in boxing are most often due to traumatic brain injury that occurs in the ring. In the past 30 years, significant improvements in ringside and medical equipment, safety, and regulations have resulted in a dramatic reduction in the fatality rate. Nonetheless, the rate of boxing-related head injuries, particularly concussions, remains unknown, due in large part to its variability in clinical presentation. Furthermore, the significance of repeat concussions sustained when boxing is just now being understood. In this article, we identify the clinical manifestations, pathophysiology, and management of boxing-related head injuries, and discuss preventive strategies to reduce head injuries sustained by boxers.

Ectromelia virus encodes a family of Ankyrin/F-box proteins that regulate NFκB.

PubMed

Burles, Kristin; van Buuren, Nicholas; Barry, Michele

2014-11-01

A notable feature of poxviruses is their ability to inhibit the antiviral response, including the nuclear factor kappa B (NFκB) pathway. NFκB is a transcription factor that is sequestered in the cytoplasm until cell stimulation, and relies on the SCF (Skp1, culllin-1, F-box) ubiquitin ligase to target its inhibitor, IκBα, for degradation. IκBα is recruited to the SCF by the F-box domain-containing protein βTrCP. Here, we show that ectromelia virus, the causative agent of mousepox, encodes four F-box-containing proteins, EVM002, EVM005, EVM154, and EVM165, all of which contain Ankyrin (Ank) domains. The Ank/F-box proteins inhibit NFκB nuclear translocation, and this inhibition is dependent on the F-box domain. We also demonstrate that EVM002, EVM005, EVM154, and EVM165 prevent IκBα degradation, suggesting that they target the SCF. This study identifies a new mechanism by which ectromelia virus inhibits NFκB. Copyright © 2014 Elsevier Inc. All rights reserved.

Forkhead, a new cross regulator of metabolism and innate immunity downstream of TOR in Drosophila.

PubMed

Varma, Disha; Bülow, Margret H; Pesch, Yanina-Yasmin; Loch, Gerrit; Hoch, Michael

2014-10-01

Antimicrobial peptides (AMPs) are conserved cationic peptides which act both as defense molecules of the host immune system and as regulators of the commensal microbiome. Expression of AMPs is induced in response to infection by the Toll and Imd pathway. Under non-infected conditions, the transcription factor dFOXO directly regulates a set of AMP expression at low levels when nutrients are limited. Here we have analyzed whether target of rapamycin (TOR), another major regulator of growth and metabolism, also modulates AMP responses in Drosophila. We found that downregulation of TOR by feeding the drug rapamycin or by overexpressing the negative TOR regulators TSC1/TSC2, resulted in a specific induction of the AMPs Diptericin (Dpt) and Metchnikowin (Mtk). In contrast, overexpression of Rheb, which positively regulates TOR led to a repression of the two AMPs. Genetic and pharmacological experiments indicate that Dpt and Mtk activation is controlled by the transcription factor Forkhead (FKH), the founding member of the FoxO family. Shuttling of FKH from the cytoplasm to the nucleus is induced in the fat body and in the posterior midgut in response to TOR downregulation. The FKH-dependent induction of Dpt and Mtk can be triggered in dFOXO null mutants and in immune-compromised Toll and IMD pathway mutants indicating that FKH acts in parallel to these regulators. Together, we have discovered that FKH is the second conserved member of the FoxO family cross-regulating metabolism and innate immunity. dFOXO and FKH, which are activated upon downregulation of insulin or TOR activities, respectively, act in parallel to induce different sets of AMPs, thereby modulating the immune status of metabolic tissues such as the fat body or the gut in response to the oscillating energy status of the organism. Copyright © 2014 Elsevier Ltd. All rights reserved.

Exergaming boxing versus heavy-bag boxing: are these equipotent for individuals with spinal cord injury?

PubMed

Mat Rosly, Maziah; Mat Rosly, Hadi; Hasnan, Nazirah; Davis, Glen M; Husain, Ruby

2017-08-01

Current strategies for increased physical activity and exercise in individuals with spinal cord injury (SCI) face many challenges with regards to maintaining their continuity of participation. Barriers cited often include problems with accessing facilities, mundane, monotonous or boring exercises and expensive equipment that is often not adapted for wheelchair users. To compare the physiological responses and user preferences between conventional heavy-bag boxing against a novel form of video game boxing, known as exergaming boxing. Cross-sectional study. Exercise laboratory setting in a university medical center. Seventeen participants with SCI were recruited, of which sixteen were male and only one female. Their mean age was 35.6±10.2 years. All of them performed a 15-minute physical exercise session of exergaming and heavy-bag boxing in a sitting position. The study assessed physiological responses in terms of oxygen consumption, metabolic equivalent (MET) and energy expenditure between exergaming and heavy-bag boxing derived from open-circuit spirometry. Participants also rated their perceived exertion using Borg's category-ratio ratings of perceived exertion. Both exergaming (MET: 4.3±1.0) and heavy-bag boxing (MET: 4.4±1.0) achieved moderate exercise intensities in these participants with SCI. Paired t-test revealed no significant differences (P>0.05, Cohen's d: 0.02-0.49) in the physiological or perceived exertional responses between the two modalities of boxing. Post session user survey reported all the participants found exergaming boxing more enjoyable. Exergaming boxing, was able to produce equipotent physiological responses as conventional heavy-bag boxing. The intensity of both exercise modalities achieved recommended intensities for health and fitness benefits. Exergaming boxing have the potential to provide an enjoyable, self-competitive environment for moderate-vigorous exercise even at the comfort of their homes.

MADS-box genes and floral development: the dark side.

PubMed

Heijmans, Klaas; Morel, Patrice; Vandenbussche, Michiel

2012-09-01

The origin of the flower during evolution has been a crucial step in further facilitating plants to colonize a wide range of different niches on our planet. The >250 000 species of flowering plants existing today display an astonishing diversity in floral architecture. For this reason, the flower is a very attractive subject for evolutionary developmental (evo-devo) genetics studies. Research during the last two decades has provided compelling evidence that the origin and functional diversification of MIKC(c) MADS-box transcription factors has played a critical role during evolution of flowering plants. As master regulators of floral organ identity, MADS-box proteins are at the heart of the classic ABC model for floral development. Despite the enormous progress made in the field of floral development, there still remain aspects that are less well understood. Here we highlight some of the dark corners within our current knowledge on MADS-box genes and flower development, which would be worthwhile investigating in more detail in future research. These include the general question of to what extent MADS-box gene functions are conserved between species, the function of TM8-clade MADS-box genes which so far have remained uncharacterized, the divergence within the A-function, and post-transcriptional regulation of the ABC-genes.

Involvement of a banana MADS-box transcription factor gene in ethylene-induced fruit ripening.

PubMed

Liu, Juhua; Xu, Biyu; Hu, Lifang; Li, Meiying; Su, Wei; Wu, Jing; Yang, Jinghao; Jin, Zhiqiang

2009-01-01

To investigate the regulation of MADS-box genes in banana (Musa acuminata L. AAA group cv. Brazilian) fruit development and postharvest ripening, we isolated from banana fruit a MADS-box gene designated MuMADS1. Amino acid alignment indicated MuMADS1 belongs to the AGAMOUS subfamily, and phylogenetic analysis indicates that this gene is most similar to class D MADS-box genes. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that MuMADS1 is expressed in the stamen and pistil of male and female flowers and in the rhizome, the vegetative reproductive organ of the banana plant. In preharvest banana fruit, MuMADS1 is likely expressed throughout banana fruit development. In postharvest banana ripening, MuMADS1 is associated with ethylene biosynthesis. Expression patterns of MuMADS1 during postharvest ripening as determined by real-time RT-PCR suggest that differential expression of MuMADS1 may not only be induced by ethylene biosynthesis associated with postharvest banana ripening, but also may be induced by exogenous ethylene.

A FLEXIBLE POLYTHENE GLOVE BOX

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

Hughes, A.

1957-11-01

The need for a glove box capable of maintaining an inert atmosphere arose during the sampling and analysis of the alkali metals. The conventional rigid glove box was found to be unsuitable in practice and also inefficient in theory. The requirement was met by improvising a flexible glove box from thin polythene sheet. The alternative solution a this problem would have required an expensive vacuum glove box with its attendant pumping unit. (auth)

Surface reflectance drives nest box temperature profiles and thermal suitability for target wildlife.

PubMed

Griffiths, Stephen R; Rowland, Jessica A; Briscoe, Natalie J; Lentini, Pia E; Handasyde, Kathrine A; Lumsden, Linda F; Robert, Kylie A

2017-01-01

Thermal properties of tree hollows play a major role in survival and reproduction of hollow-dependent fauna. Artificial hollows (nest boxes) are increasingly being used to supplement the loss of natural hollows; however, the factors that drive nest box thermal profiles have received surprisingly little attention. We investigated how differences in surface reflectance influenced temperature profiles of nest boxes painted three different colors (dark-green, light-green, and white: total solar reflectance 5.9%, 64.4%, and 90.3% respectively) using boxes designed for three groups of mammals: insectivorous bats, marsupial gliders and brushtail possums. Across the three different box designs, dark-green (low reflectance) boxes experienced the highest average and maximum daytime temperatures, had the greatest magnitude of variation in daytime temperatures within the box, and were consistently substantially warmer than light-green boxes (medium reflectance), white boxes (high reflectance), and ambient air temperatures. Results from biophysical model simulations demonstrated that variation in diurnal temperature profiles generated by painting boxes either high or low reflectance colors could have significant ecophysiological consequences for animals occupying boxes, with animals in dark-green boxes at high risk of acute heat-stress and dehydration during extreme heat events. Conversely in cold weather, our modelling indicated that there are higher cumulative energy costs for mammals, particularly smaller animals, occupying light-green boxes. Given their widespread use as a conservation tool, we suggest that before boxes are installed, consideration should be given to the effect of color on nest box temperature profiles, and the resultant thermal suitability of boxes for wildlife, particularly during extremes in weather. Managers of nest box programs should consider using several different colors and installing boxes across a range of both orientations and shade profiles (i

Surface reflectance drives nest box temperature profiles and thermal suitability for target wildlife

PubMed Central

Rowland, Jessica A.; Briscoe, Natalie J.; Lentini, Pia E.; Handasyde, Kathrine A.; Lumsden, Linda F.; Robert, Kylie A.

2017-01-01

Thermal properties of tree hollows play a major role in survival and reproduction of hollow-dependent fauna. Artificial hollows (nest boxes) are increasingly being used to supplement the loss of natural hollows; however, the factors that drive nest box thermal profiles have received surprisingly little attention. We investigated how differences in surface reflectance influenced temperature profiles of nest boxes painted three different colors (dark-green, light-green, and white: total solar reflectance 5.9%, 64.4%, and 90.3% respectively) using boxes designed for three groups of mammals: insectivorous bats, marsupial gliders and brushtail possums. Across the three different box designs, dark-green (low reflectance) boxes experienced the highest average and maximum daytime temperatures, had the greatest magnitude of variation in daytime temperatures within the box, and were consistently substantially warmer than light-green boxes (medium reflectance), white boxes (high reflectance), and ambient air temperatures. Results from biophysical model simulations demonstrated that variation in diurnal temperature profiles generated by painting boxes either high or low reflectance colors could have significant ecophysiological consequences for animals occupying boxes, with animals in dark-green boxes at high risk of acute heat-stress and dehydration during extreme heat events. Conversely in cold weather, our modelling indicated that there are higher cumulative energy costs for mammals, particularly smaller animals, occupying light-green boxes. Given their widespread use as a conservation tool, we suggest that before boxes are installed, consideration should be given to the effect of color on nest box temperature profiles, and the resultant thermal suitability of boxes for wildlife, particularly during extremes in weather. Managers of nest box programs should consider using several different colors and installing boxes across a range of both orientations and shade profiles (i

Apple EIN3 BINDING F-box 1 inhibits the activity of three apple EIN3-like transcription factors

PubMed Central

Tacken, Emma J.; Ireland, Hilary S.; Wang, Yen-Yi; Putterill, Jo; Schaffer, Robert J.

2012-01-01

Background and aims Fruit ripening in Malus× domestica (apple) is controlled by ethylene. Work in model species has shown that following the detection of ethylene, the ETHYLENE INSENSITIVE 3 (EIN3) transcription factor is stabilized, leading to an increase in transcript accumulation of ethylene-responsive genes, such as POLYGALACTURONASE1 (PG1). In the absence of ethylene, the EIN3 BINDING F-box (EBF) proteins rapidly degrade EIN3 via the ubiquitination/SCF (Skp, Cullin, F-Box) proteasome pathway. In this study, we aim to identify and characterize the apple EBF genes, and test their activity against apple EIN3-like proteins (EILs). Methodology The apple genome sequence was mined for EBF-like genes. The expression of EBF-like genes was measured during fruit development. Using a transient assay in Nicotiana benthamiana leaves, the activity of three apple EILs was tested against the PG1 promoter, with and without ethylene and EBF1. Principal results Four EBF-like genes in apple were identified and grouped into two sub-clades. Sub-clade I genes had constant expression over fruit development while sub-clade II genes increased in expression at ripening. EBF1 was shown to reduce the transactivation of the apple PG1 promoter by the EIL1, EIL2 and EIL3 transcription factors in the presence of ethylene. Conclusions The apple EBF1 gene identified here is likely to be a functionally conserved EBF orthologue, modulating EIL activity in apples. The activity of EBF1 suggests that it is not specific to a single EIL, instead acting as a global regulator of apple EIL transcription factors. PMID:23585922

Glove box shield

DOEpatents

Brackenbush, Larry W.; Hoenes, Glenn R.

1981-01-01

According to the present invention, a shield for a glove box housing radioactive material is comprised of spaced apart clamping members which maintain three overlapping flaps in place therebetween. There is a central flap and two side flaps, the side flaps overlapping at the interior edges thereof and the central flap extending past the intersection of the side flaps in order to insure that the shield is always closed when the user withdraws his hand from the glove box. Lead loaded neoprene rubber is the preferred material for the three flaps, the extent of lead loading depending upon the radiation levels within the glove box.

Environmental Exchange Box

ERIC Educational Resources Information Center

Moseley, Christine

2003-01-01

In this activity, teachers in one state create and share an "exchange box" of environmental and cultural items with students of another state. The Environmental Exchange Box activity enables teachers to improve students' skills in scientific inquiry and develop attitudes and values conducive to science learning such as wonder, curiosity,…

Acute subdural hematoma because of boxing.

PubMed

Kushi, Hidehiko; Saito, Takeshi; Sakagami, Yuichiro; Ohtsuki, Jyoji; Tanjoh, Katsuhisa

2009-02-01

To identify factors determining the clinical characteristics and prognosis of acute subdural hematoma (ASDH) arising from boxing injuries by comparing with ASDH due to any nonboxing cause. Two groups were selected for this study: 10 patients with ASDH because of boxing injuries and 26 patients with nonboxer ASDH. All of the patients underwent neurologic examination by neurosurgeons. Primary resuscitation and stabilization as well as operative therapy were performed to all patients according to the European Brain Injury Consortium Guidelines. Two groups were compared in terms of age, the Glasgow Coma Scale at admission, neurologic findings, craniogram and brain computed tomography scan findings, operative findings, and prognosis. As potential prognostic indicators for boxers, the time interval until surgery, the Glasgow Outcome Scale, hematoma thickness, midline shift, and the site of bleeding were analyzed. The characteristics of patients because of boxing injuries are that patients were younger, had lucid interval, and had no cerebral contusion or contralateral brain injury. There was no significant difference in initial Glasgow Coma Scale, hematoma thickness, midline shift, and their prognosis. The most peculiar clinical presentation of boxers' ASDH was that all bleedings were limited from "bridging veins" or "cortical veins." The prognosis of boxers was most closely correlated with the site of bleeding (r2 = 0.81; p = 0.0001) and the midline shift (r2 = 0.67; p = 0.007). Our study shows that ASDH because of boxing is characterized by bleeding from bridging or cortical veins, and that the site of bleeding is a significant determinant of their prognosis.

Determination of DNA Binding Behavior of FoxA1 Constructs Using a Gold Nanoparticle-Based High Throughput Assay

NASA Astrophysics Data System (ADS)

Aung, Khin Moh Moh; Lim, Michelle Gek Liang; Hong, Shuzhen; Cheung, Edwin; Su, Xiaodi

Forkhead box protein 1 (FoxA1) is a member of the forkhead family of winged-helix transcription factors. It plays crucial roles in the development and differentiation of multiple organs and in the regulation of estrogen-stimulated genes. In this study, in order to determine the regions of FoxA1 necessary for efficient Deoxyribonucleic Acid (DNA) binding, we cloned, expressed and purified a series of FoxA1 constructs that contain either the DNA Binding Domain (DBD), the Transcription Activation Domain (TAD), or both. We determined the DNA binding behavior of these constructs using traditional electrophoretic mobility shift assay (EMSA) and a recently developed gold nanoparticles (AuNPs)-based fast screening method. We conclude that just the DBD region alone is not sufficient for protein-DNA binding activity. Amino acids flanking the upstream of the DBD region are required for maximal DNA binding activity. Through this study, we have also further validated the AuNPs assay for its generality and expanded the existing protocol for comparing the DNA binding behavior of multiple proteins of different charge properties and molecular weights.

Virulence factor NSs of rift valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH.

PubMed

Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas; Weber, Friedemann

2014-03-01

The nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. Rift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity.

Virulence Factor NSs of Rift Valley Fever Virus Recruits the F-Box Protein FBXO3 To Degrade Subunit p62 of General Transcription Factor TFIIH

PubMed Central

Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas

2014-01-01

ABSTRACT The nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. IMPORTANCE Rift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity. PMID:24403578

Track plate enclosures: Box designs affecting attractiveness to riparian mammals

USGS Publications Warehouse

Loukmas, J.J.; Mayack, D.T.; Richmond, M.E.

2003-01-01

We examined the efficacy of four track plate enclosure designs for monitoring the abundance of small and medium-sized mammals along 10 streams in New York State. Box size and clarity of view through the box were evaluated as factors affecting visitation. We checked track plate stations weekly from September 1999 to March 2000. Eleven mammalian species or species groups visited the track plate stations. Raccoons (Procyon lotor) (P = 0.020) and feral cats (Felis catus) (P = 0.008) visited large enclosures significantly more than small enclosures. Feral cats visited clear-view enclosures significantly more than obstructed-view enclosures (P = 0.025). Enclosure size and view did not significantly affect visitation by other species; however, a large box with a clear view was the most effective design.

A flexible system to capture sample vials in a storage box - the box vial scanner.

PubMed

Nowakowski, Steven E; Kressin, Kenneth R; Deick, Steven D

2009-01-01

Tracking sample vials in a research environment is a critical task and doing so efficiently can have a large impact on productivity, especially in high volume laboratories. There are several challenges to automating the capture process, including the variety of containers used to store samples. We developed a fast and robust system to capture the location of sample vials being placed in storage that allows the laboratories the flexibility to use sample containers of varying dimensions. With a single scan, this device captures the box identifier, the vial identifier and the location of each vial within a freezer storage box. The sample vials are tracked through a barcode label affixed to the cap while the boxes are tracked by a barcode label on the side of the box. Scanning units are placed at the point of use and forward data to a sever application for processing the scanned data. Scanning units consist of an industrial barcode reader mounted in a fixture positioning the box for scanning and providing lighting during the scan. The server application transforms the scan data into a list of storage locations holding vial identifiers. The list is then transferred to the laboratory database. The box vial scanner captures the IDs and location information for an entire box of sample vials into the laboratory database in a single scan. The system accommodates a wide variety of vials sizes by inserting risers under the sample box and a variety of storage box layouts are supported via the processing algorithm on the server.

Flutter analysis of composite box beams

NASA Technical Reports Server (NTRS)

Hodges, Dewey H.; Greenman, Matthew

1995-01-01

The dynamic aeroelastic instability of flutter is an important factor in the design of modern high-speed, flexible aircraft. The current trend is toward the creative use of composites to delay flutter. To obtain an optimum design, we need an accurate as well as efficient model. As a first step towards this goal, flutter analysis is carried out for an unswept composite box beam using a linear structural model and Theodorsen's unsteady aerodynamic theory. Structurally, the wing was modeled as a thin-walled box-beam of rectangular cross section. Theodorsen's theory was used to get 2-D unsteady aerodynamic forces, which were integrated over the span. A free-vibration analysis is carried out. These fundamental modes are used to get the flutter solution using the V-g method. Future work is intended to build on this foundation.

Early Cone Setting in Picea abies acrocona Is Associated with Increased Transcriptional Activity of a MADS Box Transcription Factor1[W][OA

PubMed Central

Uddenberg, Daniel; Reimegård, Johan; Clapham, David; Almqvist, Curt; von Arnold, Sara; Emanuelsson, Olof; Sundström, Jens F.

2013-01-01

Conifers normally go through a long juvenile period, for Norway spruce (Picea abies) around 20 to 25 years, before developing male and female cones. We have grown plants from inbred crosses of a naturally occurring spruce mutant (acrocona). One-fourth of the segregating acrocona plants initiate cones already in their second growth cycle, suggesting control by a single locus. The early cone-setting properties of the acrocona mutant were utilized to identify candidate genes involved in vegetative-to-reproductive phase change in Norway spruce. Poly(A+) RNA samples from apical and basal shoots of cone-setting and non-cone-setting plants were subjected to high-throughput sequencing (RNA-seq). We assembled and investigated 33,383 expressed putative protein-coding acrocona transcripts. Eight transcripts were differentially expressed between selected sample pairs. One of these (Acr42124_1) was significantly up-regulated in apical shoot samples from cone-setting acrocona plants, and the encoded protein belongs to the MADS box gene family of transcription factors. Using quantitative real-time polymerase chain reaction with independently derived plant material, we confirmed that the MADS box gene is up-regulated in both needles and buds of cone-inducing shoots when reproductive identity is determined. Our results constitute important steps for the development of a rapid cycling model system that can be used to study gene function in conifers. In addition, our data suggest the involvement of a MADS box transcription factor in the vegetative-to-reproductive phase change in Norway spruce. PMID:23221834

Cloning, Characterization, Regulation, and Function of Dormancy-Associated MADS-Box Genes from Leafy Spurge

USDA-ARS?s Scientific Manuscript database

DORMANCY-ASSOCIATED MADS-BOX (DAM) genes are SHORT VEGETATIVE PHASE–Like MADS box transcription factors linked to endodormancy induction. We have cloned and characterized several cDNA and genomic clones of DAM genes from the model perennial weed leafy spurge (Euphorbia esula). We present evidence fo...

Phylogenomics of MADS-Box Genes in Plants - Two Opposing Life Styles in One Gene Family.

PubMed

Gramzow, Lydia; Theißen, Günter

2013-09-12

The development of multicellular eukaryotes, according to their body plan, is often directed by members of multigene families that encode transcription factors. MADS (for MINICHROMOSOME MAINTENANCE1, AGAMOUS, DEFICIENS and SERUM RESPONSE FACTOR)-box genes form one of those families controlling nearly all major aspects of plant development. Knowing the complete complement of MADS-box genes in sequenced plant genomes will allow a better understanding of the evolutionary patterns of these genes and the association of their evolution with the evolution of plant morphologies. Here, we have applied a combination of automatic and manual annotations to identify the complete set of MADS-box genes in 17 plant genomes. Furthermore, three plant genomes were reanalyzed and published datasets were used for four genomes such that more than 2,600 genes from 24 species were classified into the two types of MADS-box genes, Type I and Type II. Our results extend previous studies, highlighting the remarkably different evolutionary patterns of Type I and Type II genes and provide a basis for further studies on the evolution and function of MADS-box genes.

Alterations of CHEK2 forkhead-associated domain increase the risk of Hodgkin lymphoma.

PubMed

Havranek, O; Spacek, M; Hubacek, P; Mocikova, H; Markova, J; Trneny, M; Kleibl, Z

2011-01-01

Checkpoint kinase 2 gene (CHEK2) codes for an important mediator of DNA damage response pathway. Mutations in the CHEK2 gene increase the risk of several cancer types, however, their role in Hodgkin lymphoma (HL) has not been studied so far. The most frequent CHEK2 alterations (including c.470T>C; p.I157T) cluster into the forkhead-associated (FHA) domain-coding region of the CHEK2 gene. We performed mutation analysis of the CHEK2 gene segment coding for FHA domain using denaturing high-performance liquid chromatography in 298 HL patients and analyzed the impact of characterized CHEK2 gene variants on the risk of HL development and progression-free survival (PFS). The overall frequency of CHEK2 alterations was significantly higher in HL patients (17/298; 5.7%) compared to the previously analyzed non-cancer controls (19/683; 2.8%; p= 0.04). Presence of any alteration within the analyzed region of the CHEK2 gene was associated with increased risk of HL development (OR = 2.11; 95% CI = 1.08 - 4.13; p= 0.04). The most frequent I157T mutation was found in 4.0% of HL patients and 2.5% of controls (p = 0.22), however, the frequency of 5 other alterations (excluding I157T) was significantly higher in HL cases and associated with increased risk of HL development (OR = 5.81; 95% CI = 1.12 - 30.12; p= 0.03). PFS in HL patients did not differ between CHEK2 mutation carriers and non-carriers. The predominant I157T mutation together with other alterations in its proximity represent moderate genetic predisposition factor increasing the risk of HL development.

Two high-mobility group box domains act together to underwind and kink DNA

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

Sánchez-Giraldo, R.; Acosta-Reyes, F. J.; Malarkey, C. S.

The crystal structure of HMGB1 box A bound to an unmodified AT-rich DNA fragment is reported at a resolution of 2 Å. A new mode of DNA recognition for HMG box proteins is found in which two box A domains bind in an unusual configuration generating a highly kinked DNA structure. High-mobility group protein 1 (HMGB1) is an essential and ubiquitous DNA architectural factor that influences a myriad of cellular processes. HMGB1 contains two DNA-binding domains, box A and box B, which have little sequence specificity but have remarkable abilities to underwind and bend DNA. Although HMGB1 box A ismore » thought to be responsible for the majority of HMGB1–DNA interactions with pre-bent or kinked DNA, little is known about how it recognizes unmodified DNA. Here, the crystal structure of HMGB1 box A bound to an AT-rich DNA fragment is reported at a resolution of 2 Å. Two box A domains of HMGB1 collaborate in an unusual configuration in which the Phe37 residues of both domains stack together and intercalate the same CG base pair, generating highly kinked DNA. This represents a novel mode of DNA recognition for HMGB proteins and reveals a mechanism by which structure-specific HMG boxes kink linear DNA.« less

A novel member of the SAF (scaffold attachment factor)-box protein family inhibits gene expression and induces apoptosis

PubMed Central

Chan, Ching Wan; Lee, Youn-Bok; Uney, James; Flynn, Andrea; Tobias, Jonathan H.; Norman, Michael

2007-01-01

The SLTM [SAF (scaffold attachment factor)-like transcription modulator] protein contains a SAF-box DNA-binding motif and an RNA-binding domain, and shares an overall identity of 34% with SAFB1 {scaffold attachment factor-B1; also known as SAF-B (scaffold attachment factor B), HET [heat-shock protein 27 ERE (oestrogen response element) and TATA-box-binding protein] or HAP (heterogeneous nuclear ribonucleoprotein A1-interacting protein)}. Here, we show that SLTM is localized to the cell nucleus, but excluded from nucleoli, and to a large extent it co-localizes with SAFB1. In the nucleus, SLTM has a punctate distribution and it does not co-localize with SR (serine/arginine) proteins. Overexpression of SAFB1 has been shown to exert a number of inhibitory effects, including suppression of oestrogen signalling. Although SLTM also suppressed the ability of oestrogen to activate a reporter gene in MCF-7 breast-cancer cells, inhibition of a constitutively active β-galactosidase gene suggested that this was primarily the consequence of a generalized inhibitory effect on transcription. Measurement of RNA synthesis, which showed a particularly marked inhibition of [3H]uridine incorporation into mRNA, supported this conclusion. In addition, analysis of cell-cycle parameters, chromatin condensation and cytochrome c release showed that SLTM induced apoptosis in a range of cultured cell lines. Thus the inhibitory effects of SLTM on gene expression appear to result from generalized down-regulation of mRNA synthesis and initiation of apoptosis consequent upon overexpressing the protein. While indicating a crucial role for SLTM in cellular function, these results also emphasize the need for caution when interpreting phenotypic changes associated with manipulation of protein expression levels. PMID:17630952

Heart Rate and Liking During "Kinect Boxing" Versus "Wii Boxing": The Potential for Enjoyable Vigorous Physical Activity Videogames.

PubMed

Sanders, Gabriel J; Peacock, Corey A; Barkley, Jacob E; Gish, Brian; Brock, Scott; Volpenhein, Josh

2015-08-01

Nintendo(®) (Kyoto, Japan) "Wii™ Sports Boxing" ("Wii Boxing") and Xbox(®) (Microsoft, Redmond, WA) "Kinect(®) Sports Boxing" ("Kinect Boxing") are both boxing simulation videogames that are available for two different active videogame (AVG) systems. Although these AVGs are similar, the style of gameplay required is different (i.e., upper body only versus total body movements) and may alter physical activity intensity and one's preference for playing one game over the other. AVGs that elicit the greatest physiologic challenge and are preferred by users should be identified in an effort to enhance the efficacy of physical activity interventions and programs that include AVGs. The mean heart rate (HRmean) and peak heart rate (HRpeak) for 27 adults (22.7±4.2 years old) were recorded during four 10-minute conditions: seated rest, treadmill walking at 3 miles/hour, "Wii Boxing," and "Kinect Boxing." Upon completion of all four conditions, participants indicated which condition they preferred, and HRmean and HRpeak were calculated as a percentage of age-predicted maximum heart rate to classify physical activity intensity for the three activity conditions (treadmill, "Wii Boxing," and "Kinect Boxing"). "Kinect Boxing" significantly (P<0.001) increased percentage HRmean (64.1±1.6 percent of age-predicted maximum) and percentage HRpeak (76.5±1.9 percent) above all other conditions: Wii HRmean, 53.0±1.2 percent; Wii HRpeak, 61.8±1.5 percent; treadmill HRmean, 52.4±1.2 percent; treadmill HRpeak, 55.2±2.2 percent. Percentage HRpeak for "Kinect Boxing" was great enough to be considered a vigorous-intensity physical activity. There was no difference (P=0.55) in percentage HRmean between "Wii Boxing" and treadmill walking. Participants also preferred "Kinect Boxing" (P<0.001; n=26) to all other conditions ("Wii Boxing," n=1; treadmill n=0). "Kinect Boxing" was the most preferred and the only condition that was physiologically challenging enough to be classified as a

Taking advantage from phenotype variability in a local animal genetic resource: identification of genomic regions associated with the hairless phenotype in Casertana pigs.

PubMed

Schiavo, G; Bertolini, F; Utzeri, V J; Ribani, A; Geraci, C; Santoro, L; Óvilo, C; Fernández, A I; Gallo, M; Fontanesi, L

2018-04-19

Casertana is an endangered autochthonous pig breed (raised in south-central Italy) that is considered to be the descendant of the influential Neapolitan pig population that was used to improve British breeds in the 19th century. Casertana pigs are characterized by a typical, almost complete, hairless phenotype, even though a few Casertana pigs are normal haired. In this work, using Illumina PorcineSNP60 BeadChip data, we carried out a genome-wide association study and an F ST analysis with this breed by comparing animals showing the classical hairless phenotype (n = 81) versus pigs classified as haired (n = 15). Combining the results obtained with the two approaches, we identified two significant regions: one on porcine chromosome (SSC) 7 and one on SSC15. The SSC7 region contains the forkhead box N3 (FOXN3) gene, the most plausible candidate gene of this region, considering that mutations in another gene of the same family (forkhead box N1; Foxn1 or FOXN1) are responsible for the nude locus in rodents and alopecia in humans. Another potential candidate gene, rho guanine nucleotide exchange factor 10 (ARHGEF10), is located in the SSC15 region. FOXN3 and ARHGEF10 have been detected as differentially expressed in androgenetic and senescent alopecia respectively. This study on an autochthonous pig breed contributes to shed some light on novel genes potentially involved in hair development and growth and demonstrates that local animal breeds can be valuable genetic resources for disclosing genetic factors affecting unique traits, taking advantage of phenotype variability segregating in small populations. © 2018 Stichting International Foundation for Animal Genetics.

Foxm1 transcription factor is required for lung fibrosis and epithelial-to-mesenchymal transition

PubMed Central

Balli, David; Ustiyan, Vladimir; Zhang, Yufang; Wang, I-Ching; Masino, Alex J; Ren, Xiaomeng; Whitsett, Jeffrey A; Kalinichenko, Vladimir V; Kalin, Tanya V

2013-01-01

Alveolar epithelial cells (AECs) participate in the pathogenesis of pulmonary fibrosis, producing pro-inflammatory mediators and undergoing epithelial-to-mesenchymal transition (EMT). Herein, we demonstrated the critical role of Forkhead Box M1 (Foxm1) transcription factor in radiation-induced pulmonary fibrosis. Foxm1 was induced in AECs following lung irradiation. Transgenic expression of an activated Foxm1 transcript in AECs enhanced radiation-induced pneumonitis and pulmonary fibrosis, and increased the expression of IL-1β, Ccl2, Cxcl5, Snail1, Zeb1, Zeb2 and Foxf1. Conditional deletion of Foxm1 from respiratory epithelial cells decreased radiation-induced pulmonary fibrosis and prevented the increase in EMT-associated gene expression. siRNA-mediated inhibition of Foxm1 prevented TGF-β-induced EMT in vitro. Foxm1 bound to and increased promoter activity of the Snail1 gene, a critical transcriptional regulator of EMT. Expression of Snail1 restored TGF-β-induced loss of E-cadherin in Foxm1-deficient cells in vitro. Lineage-tracing studies demonstrated that Foxm1 increased EMT during radiation-induced pulmonary fibrosis in vivo. Foxm1 is required for radiation-induced pulmonary fibrosis by enhancing the expression of genes critical for lung inflammation and EMT. PMID:23288041

UV light absorption parameters of the pathobiologically implicated bilirubin oxidation products, MVM, BOX A, and BOX B.

PubMed

Harris, Nathaniel A; Rapoport, Robert M; Zuccarello, Mario; Maggio, John E

2018-06-01

The formation of the bilirubin oxidation products (BOXes), BOX A ([4-methyl-5-oxo-3-vinyl-(1,5-dihydropyrrol-2-ylidene)acetamide]) and BOX B (3-methyl-5-oxo-4-vinyl-(1,5-dihydropyrrol-2-ylidene)acetamide), as well as MVM (4-methyl-3-vinylmaleimide) were synthesized by oxidation of bilirubin with H 2 O 2 without and with FeCl 3 , respectively. Compound identity was confirmed with NMR and mass spectrometry (MS; less than 1 ppm, tandem MS up to MS 4 ). UV absorption profiles, including λ max , and extinction coefficient (ε; estimated using NMR) for BOX A, BOX B, and MVM in H 2 O, 15% CH 3 CN plus 10 mM CF 3 CO 2 H, CH 3 CN, CHCl 3 , CH 2 Cl 2 , and 0.9% NaCl were determined. At longer wavelengths, λ max 's for 1) BOX A were little affected by the solvent, ranging from 295-297 nm; 2) BOX B, less polar solvent yielded λ max 's of lower wavelength, with values ranging from 308-313 nm, and 3) MVM, less polar solvent yielded λ max 's of higher wavelength, with values ranging from 318-327 nm. Estimated ε's for BOX A and BOX B were approximately 5- to 10-fold greater than for MVM.

Mortality of riparian box elder from sediment mobilization and extended inundation

USGS Publications Warehouse

Friedman, Jonathan M.; Auble, Gregor T.

1999-01-01

To explore how high flows limit the streamward extent of riparian vegetation we quantified the effects of sediment mobilization and extended inundation on box elder (Acer negundo) saplings along the cobble-bed Gunnison River in Black Canyon of the Gunnison National Monument, Colorado, USA. We counted and aged box elders in 144 plots of 37.2 m2, and combined a hydraulic model with the hydrologic record to determine the maximum shear stress and number of growing-season days inundated for each plot in each year of the record. We quantified the effects of the two mortality factors by calculating the extreme values survived during the lifetime of trees sampled in 1994 and by recounting box elders in the plots following a high flow in 1995. Both mortality factors can be modeled as threshold functions; box elders are killed either by inundation for more than 85 days during the growing season or by shear stress that exceeds the critical value for mobilization of the underlying sediment particles. Construction of upstream reservoirs in the 1960s and 1970s reduced the proportion of the canyon bottom annually cleared of box elders by high flows. Furthermore, because the dams decreased the magnitude of high flows more than their duration, flow regulation has decreased the importance of sediment mobilization relative to extended inundation. We use the threshold functions and cross-section data to develop a response surface predicting the proportion of the canyon bottom cleared at any combination of flow magnitude and duration. This response surface allows vegetation removal to be incorporated into quantitative multi-objective water management decisions.

GPS-ARM: Computational Analysis of the APC/C Recognition Motif by Predicting D-Boxes and KEN-Boxes

PubMed Central

Ren, Jian; Cao, Jun; Zhou, Yanhong; Yang, Qing; Xue, Yu

2012-01-01

Anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase incorporated with Cdh1 and/or Cdc20 recognizes and interacts with specific substrates, and faithfully orchestrates the proper cell cycle events by targeting proteins for proteasomal degradation. Experimental identification of APC/C substrates is largely dependent on the discovery of APC/C recognition motifs, e.g., the D-box and KEN-box. Although a number of either stringent or loosely defined motifs proposed, these motif patterns are only of limited use due to their insufficient powers of prediction. We report the development of a novel GPS-ARM software package which is useful for the prediction of D-boxes and KEN-boxes in proteins. Using experimentally identified D-boxes and KEN-boxes as the training data sets, a previously developed GPS (Group-based Prediction System) algorithm was adopted. By extensive evaluation and comparison, the GPS-ARM performance was found to be much better than the one using simple motifs. With this powerful tool, we predicted 4,841 potential D-boxes in 3,832 proteins and 1,632 potential KEN-boxes in 1,403 proteins from H. sapiens, while further statistical analysis suggested that both the D-box and KEN-box proteins are involved in a broad spectrum of biological processes beyond the cell cycle. In addition, with the co-localization information, we predicted hundreds of mitosis-specific APC/C substrates with high confidence. As the first computational tool for the prediction of APC/C-mediated degradation, GPS-ARM is a useful tool for information to be used in further experimental investigations. The GPS-ARM is freely accessible for academic researchers at: http://arm.biocuckoo.org. PMID:22479614

Characterization of an AGAMOUS-like MADS Box Protein, a Probable Constituent of Flowering and Fruit Ripening Regulatory System in Banana

PubMed Central

Roy Choudhury, Swarup; Roy, Sujit; Nag, Anish; Singh, Sanjay Kumar; Sengupta, Dibyendu N.

2012-01-01

The MADS-box family of genes has been shown to play a significant role in the development of reproductive organs, including dry and fleshy fruits. In this study, the molecular properties of an AGAMOUS like MADS box transcription factor in banana cultivar Giant governor (Musa sp, AAA group, subgroup Cavendish) has been elucidated. We have detected a CArG-box sequence binding AGAMOUS MADS-box protein in banana flower and fruit nuclear extracts in DNA-protein interaction assays. The protein fraction in the DNA-protein complex was analyzed by mass spectrometry and using this information we have obtained the full length cDNA of the corresponding protein. The deduced protein sequence showed ∼95% amino acid sequence homology with MA-MADS5, a MADS-box protein described previously from banana. We have characterized the domains of the identified AGAMOUS MADS-box protein involved in DNA binding and homodimer formation in vitro using full-length and truncated versions of affinity purified recombinant proteins. Furthermore, in order to gain insight about how DNA bending is achieved by this MADS-box factor, we performed circular permutation and phasing analysis using the wild type recombinant protein. The AGAMOUS MADS-box protein identified in this study has been found to predominantly accumulate in the climacteric fruit pulp and also in female flower ovary. In vivo and in vitro assays have revealed specific binding of the identified AGAMOUS MADS-box protein to CArG-box sequence in the promoters of major ripening genes in banana fruit. Overall, the expression patterns of this MADS-box protein in banana female flower ovary and during various phases of fruit ripening along with the interaction of the protein to the CArG-box sequence in the promoters of major ripening genes lead to interesting assumption about the possible involvement of this AGAMOUS MADS-box factor in banana fruit ripening and floral reproductive organ development. PMID:22984496

Characterization of an AGAMOUS-like MADS box protein, a probable constituent of flowering and fruit ripening regulatory system in banana.

PubMed

Roy Choudhury, Swarup; Roy, Sujit; Nag, Anish; Singh, Sanjay Kumar; Sengupta, Dibyendu N

2012-01-01

The MADS-box family of genes has been shown to play a significant role in the development of reproductive organs, including dry and fleshy fruits. In this study, the molecular properties of an AGAMOUS like MADS box transcription factor in banana cultivar Giant governor (Musa sp, AAA group, subgroup Cavendish) has been elucidated. We have detected a CArG-box sequence binding AGAMOUS MADS-box protein in banana flower and fruit nuclear extracts in DNA-protein interaction assays. The protein fraction in the DNA-protein complex was analyzed by mass spectrometry and using this information we have obtained the full length cDNA of the corresponding protein. The deduced protein sequence showed ~95% amino acid sequence homology with MA-MADS5, a MADS-box protein described previously from banana. We have characterized the domains of the identified AGAMOUS MADS-box protein involved in DNA binding and homodimer formation in vitro using full-length and truncated versions of affinity purified recombinant proteins. Furthermore, in order to gain insight about how DNA bending is achieved by this MADS-box factor, we performed circular permutation and phasing analysis using the wild type recombinant protein. The AGAMOUS MADS-box protein identified in this study has been found to predominantly accumulate in the climacteric fruit pulp and also in female flower ovary. In vivo and in vitro assays have revealed specific binding of the identified AGAMOUS MADS-box protein to CArG-box sequence in the promoters of major ripening genes in banana fruit. Overall, the expression patterns of this MADS-box protein in banana female flower ovary and during various phases of fruit ripening along with the interaction of the protein to the CArG-box sequence in the promoters of major ripening genes lead to interesting assumption about the possible involvement of this AGAMOUS MADS-box factor in banana fruit ripening and floral reproductive organ development.

Time course expression of Foxo transcription factors in skeletal muscle following corticosteroid administration

PubMed Central

Cho, John E.; Fournier, Mario; Da, Xiaoyu

2010-01-01

Increased expression of forkhead box O (Foxo) transcription factors were reported in cultured myotubes and mouse limb muscle with corticosteroid (CS) treatment. We previously reported that administration of CS to rats resulted in muscle fiber atrophy only by day 7. The aim of this study, therefore, was to evaluate the time-course changes in the expression of Foxo transcription factors and muscle-specific ubiquitin E3 ligases in rat limb muscle following CS administration. Triamcinolone (TRI; 1 mg · kg−1 · day−1 im) was administered for 1, 3, or 7 days. Control (CTL) rats were given saline. Muscle mRNA was analyzed by real-time RT-PCR. Compared with CTL, body weights of TRI-treated animals decreased by 3, 12, and 21% at days 1, 3, and 7, respectively. Muscle IGF-1 mRNA levels decreased by 33, 65, and 58% at days 1, 3, and 7 in TRI-treated rats compared with CTL. Levels of phosphorylated Akt were 28, 50, and 36% lower in TRI animals at these time points. Foxo1 mRNA increased progressively by 1.2-, 1.4-, and 2.5-fold at days 1, 3, and 7 in TRI animals. Similar changes were noted in the expression of Foxo3a mRNA (1.3-, 1.4-, and 2.6-fold increments). By contrast, Foxo4 mRNA was not significantly changed in TRI animals. With TRI, muscle atrophy F box/Atrogin-1 increased by 1.8-, 4.1-, and 7.5-fold at days 1, 3, and 7 compared with CTL rats. By contrast, muscle RING finger 1 increased only from day 7 (2.7-fold). Gradual reduction in IGF-I expression with TRI over the time series paralleled that of Akt. These findings are consistent with a progressive stimulus to muscle protein degradation and the need to process/remove disassembled muscle proteins via the ubiquitin-proteasome system. Elucidating the dynamic catabolic responses to CS challenge is important in understanding the mechanisms underlying muscle atrophy and therapeutic measures to offset this. PMID:19850732

Quantum transport in coupled Majorana box systems

NASA Astrophysics Data System (ADS)

Gau, Matthias; Plugge, Stephan; Egger, Reinhold

2018-05-01

We present a theoretical analysis of low-energy quantum transport in coupled Majorana box devices. A single Majorana box represents a Coulomb-blockaded mesoscopic superconductor proximitizing two or more long topological nanowires. The box thus harbors at least four Majorana zero modes (MZMs). Setups with several Majorana boxes, where MZMs on different boxes are tunnel coupled via short nanowire segments, are key ingredients to recent Majorana qubit and code network proposals. We construct and study the low-energy theory for multiterminal junctions with normal leads connected to the coupled box device by lead-MZM tunnel contacts. Transport experiments in such setups can test the nonlocality of Majorana-based systems and the integrity of the underlying Majorana qubits. For a single box, we recover the previously described topological Kondo effect which can be captured by a purely bosonic theory. For several coupled boxes, however, nonconserved local fermion parities require the inclusion of additional local sets of Pauli operators. We present a renormalization group analysis and develop a nonperturbative strong-coupling approach to quantum transport in such systems. Our findings are illustrated for several examples, including a loop qubit device and different two-box setups.

FOXP2 promotes the nuclear translocation of POT1, but FOXP2(R553H), mutation related to speech-language disorder, partially prevents it

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

Tanabe, Yuko; Fujita, Eriko; Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498

Highlights: {yields} We isolated protection of telomeres 1 (POT1) as a FOXP2-associated protein by a yeast two-hybrid. {yields} FOXP2 associated and co-localized with POT1 in the nuclei. {yields} FOXP2(R553H) also co-localized with POT1 in both the cytoplasm and nuclei. {yields} FOXP2(R553H) partially prevented the nuclear translocation of POT1. {yields} FOXP2(R553H) mutation may be associated with the pathogenesis of speech-language disorder. -- Abstract: FOXP2 is a forkhead box-containing transcription factor with several recognizable sequence motifs. However, little is known about the FOXP2-associated proteins except for C-terminal binding protein (CtBP). In the present study, we attempted to isolate the FOXP2-associated protein withmore » a yeast two-hybrid system using the C-terminal region, including the forkhead domain, as a bait probe, and identified protection of telomeres 1 (POT1) as a FOXP2-associated protein. Immunoprecipitation assay confirmed the association with FOXP2 and POT1. POT1 alone localized in the cytoplasm but co-localized with FOXP2 and the forkhead domain of FOXP2 in nuclei. However, both FOXP2 with mutated nuclear localization signals and (R553H) mutated forkhead, which is associated with speech-language disorder, prevented the nuclear translocation of POT1. These results suggest that FOXP2 is a binding partner for the nuclear translocation of POT1. As loss of POT1 function induces the cell arrest, the impaired nuclear translocation of POT1 in the developing neuronal cells may be associated with the pathogenesis of speech-language disorder with FOXP2(R553H) mutation.« less

Factors Affecting Microcuttings of Stevia Using a Mist-Chamber Propagation Box

PubMed Central

Osman, Mohamad; Samsudin, Nur Syamimi; Faruq, Golam

2013-01-01

Stevia rebaudiana Bertoni is a member of Compositae family. Stevia plant has zero calorie content and its leaves are estimated to be 300 times sweeter than sugar. This plant is believed to be the most ideal substitute for sugar and important to assist in medicinal value especially for diabetic patients. In this study, microcutting techniques using a mist-chamber propagation box were used as it was beneficial for propagation of Stevia and gave genetic uniformity to the plant. The effects of different treatments on root stimulation of Stevia in microcuttings technique were evaluated. Treatments studied were different sizes of shoot cuttings, plant growth regulators, lights, and shades. Data logger was used to record the mean value of humidity (>90% RH), light intensity (673–2045 lx), and temperature (28.6–30.1°C) inside the mist-chamber propagation box. From analysis of variance, there were significant differences between varieties and treatments in parameters studied (P < 0.05). For the size of shoot cuttings treatment, 6 nodes cuttings were observed to increase root number. As compared to control, shoot cuttings treated with indole butyric acid (IBA) had better performance regarding root length. Yellow light and 50% shade treatments showed higher root and leaf number and these conditions can be considered as crucial for potential propagation of Stevia. PMID:24470797

Factors affecting microcuttings of Stevia using a mist-chamber propagation box.

PubMed

Osman, Mohamad; Samsudin, Nur Syamimi; Faruq, Golam; Nezhadahmadi, Arash

2013-01-01

Stevia rebaudiana Bertoni is a member of Compositae family. Stevia plant has zero calorie content and its leaves are estimated to be 300 times sweeter than sugar. This plant is believed to be the most ideal substitute for sugar and important to assist in medicinal value especially for diabetic patients. In this study, microcutting techniques using a mist-chamber propagation box were used as it was beneficial for propagation of Stevia and gave genetic uniformity to the plant. The effects of different treatments on root stimulation of Stevia in microcuttings technique were evaluated. Treatments studied were different sizes of shoot cuttings, plant growth regulators, lights, and shades. Data logger was used to record the mean value of humidity (>90% RH), light intensity (673-2045 lx), and temperature (28.6-30.1°C) inside the mist-chamber propagation box. From analysis of variance, there were significant differences between varieties and treatments in parameters studied (P < 0.05). For the size of shoot cuttings treatment, 6 nodes cuttings were observed to increase root number. As compared to control, shoot cuttings treated with indole butyric acid (IBA) had better performance regarding root length. Yellow light and 50% shade treatments showed higher root and leaf number and these conditions can be considered as crucial for potential propagation of Stevia.

Deciphering the molecular mechanisms underlying the binding of the TWIST1/E12 complex to regulatory E-box sequences

PubMed Central

Bouard, Charlotte; Terreux, Raphael; Honorat, Mylène; Manship, Brigitte; Ansieau, Stéphane; Vigneron, Arnaud M.; Puisieux, Alain; Payen, Léa

2016-01-01

Abstract The TWIST1 bHLH transcription factor controls embryonic development and cancer processes. Although molecular and genetic analyses have provided a wealth of data on the role of bHLH transcription factors, very little is known on the molecular mechanisms underlying their binding affinity to the E-box sequence of the promoter. Here, we used an in silico model of the TWIST1/E12 (TE) heterocomplex and performed molecular dynamics (MD) simulations of its binding to specific (TE-box) and modified E-box sequences. We focused on (i) active E-box and inactive E-box sequences, on (ii) modified active E-box sequences, as well as on (iii) two box sequences with modified adjacent bases the AT- and TA-boxes. Our in silico models were supported by functional in vitro binding assays. This exploration highlighted the predominant role of protein side-chain residues, close to the heart of the complex, at anchoring the dimer to DNA sequences, and unveiled a shift towards adjacent ((-1) and (-1*)) bases and conserved bases of modified E-box sequences. In conclusion, our study provides proof of the predictive value of these MD simulations, which may contribute to the characterization of specific inhibitors by docking approaches, and their use in pharmacological therapies by blocking the tumoral TWIST1/E12 function in cancers. PMID:27151200

High-Density Terminal Box for Testing Wire Harness

NASA Technical Reports Server (NTRS)

Pierce, W. B.; Collins, W. G.

1982-01-01

Compact terminal box provides access to complex wiring harnesses for testing. Box accommodates more than twice as many wires as previous boxes. Box takes in wires via cable connectors and distributes them to contacts on box face. Instead of separate insulated jacks in metal face panel, box uses pairs of small military-standard metal sockets in precision-drilled plastic panel. Shorting plug provides continuity for wires when not being tested.

The Guide to the Ecology Box.

ERIC Educational Resources Information Center

Ontario Inst. for Studies in Education, Toronto.

Cooperating with the Canadian Commission for UNESCO, the Ontario Institute for Studies in Education has prepared boxes of experimental curriculum materials on the subject of ecology. This guide summarizes the design and contents of the boxes and provides instructions for those using the boxes--principals, teachers, parents, librarians, and…

Think Inside the Box

ERIC Educational Resources Information Center

Spencer, John

2017-01-01

Besides "thinking outside the box," the creativity needed to solve problems often involves thinking differently about the box, finding a new approach or off-beat way to use the materials, conditions, and even constraints that one has. Spencer discusses creative constraint--what happens when a problem solver runs into barriers that make…

Box-and-Whisker Plots.

ERIC Educational Resources Information Center

Larsen, Russell D.

1985-01-01

Box-and-whisker plots (which give rapid visualization of batches of data) can be effectively used to present diverse collections of data used in traditional first-year chemistry courses. Construction of box-and-whisker plots and their use with bond energy data and data on heats of formation and solution are discussed. (JN)

MADS-Box gene diversity in seed plants 300 million years ago.

PubMed

Becker, A; Winter, K U; Meyer, B; Saedler, H; Theissen, G

2000-10-01

MADS-box genes encode a family of transcription factors which control diverse developmental processes in flowering plants ranging from root development to flower and fruit development. Through phylogeny reconstructions, most of these genes can be subdivided into defined monophyletic gene clades whose members share similar expression patterns and functions. Therefore, the establishment of the diversity of gene clades was probably an important event in land plant evolution. In order to determine when these clades originated, we isolated cDNAs of 19 different MADS-box genes from Gnetum gnemon, a gymnosperm model species and thus a representative of the sister group of the angiosperms. Phylogeny reconstructions involving all published MADS-box genes were then used to identify gene clades containing putative orthologs from both angiosperm and gymnosperm lineages. Thus, the minimal number of MADS-box genes that were already present in the last common ancestor of extant gymnosperms and angiosperms was determined. Comparative expression studies involving pairs of putatively orthologous genes revealed a diversity of patterns that has been largely conserved since the time when the angiosperm and gymnosperm lineages separated. Taken together, our data suggest that there were already at least seven different MADS-box genes present at the base of extant seed plants about 300 MYA. These genes were probably already quite diverse in terms of both sequence and function. In addition, our data demonstrate that the MADS-box gene families of extant gymnosperms and angiosperms are of similar complexities.

Plate forming and break down pizza box

DOEpatents

Pantisano, Frank; Devine, Scott M.

1992-01-01

A standard corrugated paper pizza box is provided with slit cuts cut through the top panel of the pizza box in a shape to form four circular serving plates with a beveled raised edge and cross slit cuts through the bottom panel of the pizza box separating the box into four essentially equal portions for easy disposal.

Physcomitrella MADS-box genes regulate water supply and sperm movement for fertilization.

PubMed

Koshimizu, Shizuka; Kofuji, Rumiko; Sasaki-Sekimoto, Yuko; Kikkawa, Masahide; Shimojima, Mie; Ohta, Hiroyuki; Shigenobu, Shuji; Kabeya, Yukiko; Hiwatashi, Yuji; Tamada, Yosuke; Murata, Takashi; Hasebe, Mitsuyasu

2018-01-01

MIKC classic (MIKC C )-type MADS-box genes encode transcription factors that function in various developmental processes, including angiosperm floral organ identity. Phylogenetic analyses of the MIKC C -type MADS-box family, including genes from non-flowering plants, suggest that the increased numbers of these genes in flowering plants is related to their functional divergence; however, their precise functions in non-flowering plants and their evolution throughout land plant diversification are unknown. Here, we show that MIKC C -type MADS-box genes in the moss Physcomitrella patens function in two ways to enable fertilization. Analyses of protein localization, deletion mutants and overexpression lines of all six genes indicate that three MIKC C -type MADS-box genes redundantly regulate cell division and growth in the stems for appropriate external water conduction, as well as the formation of sperm with motile flagella. The former function appears to be maintained in the flowering plant lineage, while the latter was lost in accordance with the loss of sperm.

Thinking outside the Box

ERIC Educational Resources Information Center

Fanshawe, Simon; Sriskandarajah, Dhananjayan

2010-01-01

Britain is not only more diverse than ever before, but that diversity itself is growing more diverse. Britain's simplistic "tick-box" approach to identity is in danger of inhibiting the very equality it seeks to promote. To question the tick-box is not to accuse local authorities of "political correctness gone mad". The notion…

The Heuristic Interpretation of Box Plots

ERIC Educational Resources Information Center

Lem, Stephanie; Onghena, Patrick; Verschaffel, Lieven; Van Dooren, Wim

2013-01-01

Box plots are frequently used, but are often misinterpreted by students. Especially the area of the box in box plots is often misinterpreted as representing number or proportion of observations, while it actually represents their density. In a first study, reaction time evidence was used to test whether heuristic reasoning underlies this…

Freedom to box.

PubMed Central

Warburton, N

1998-01-01

The british Medical Association wants to criminalise all boxing. This article examines the logic of the arguments it uses and finds them wanting. The move from medical evidence about the risk of brain damage to the conclusion that boxing should be banned is not warranted. The BMA's arguments are a combination of inconsistent paternalism and legal moralism. Consistent application of the principles implicit in the BMA's arguments would lead to absurd consequences and to severe limitations being put on individual freedom. PMID:9549684

The Aspergillus fumigatus conidial melanin production is regulated by the bifunctional bHLH DevR and MADS-box RlmA transcription factors.

PubMed

Valiante, Vito; Baldin, Clara; Hortschansky, Peter; Jain, Radhika; Thywißen, Andreas; Straßburger, Maria; Shelest, Ekaterina; Heinekamp, Thorsten; Brakhage, Axel A

2016-10-01

Melanins play a crucial role in defending organisms against external stressors. In several pathogenic fungi, including the human pathogen Aspergillus fumigatus, melanin production was shown to contribute to virulence. A. fumigatus produces two different types of melanins, i.e., pyomelanin and dihydroxynaphthalene (DHN)-melanin. DHN-melanin forms the gray-green pigment characteristic for conidia, playing an important role in immune evasion of conidia and thus for fungal virulence. The DHN-melanin biosynthesis pathway is encoded by six genes organized in a cluster with the polyketide synthase gene pksP as a core element. Here, cross-species promoter analysis identified specific DNA binding sites in the DHN-melanin biosynthesis genes pksP-arp1 intergenic region that can be recognized by bHLH and MADS-box transcriptional regulators. Independent deletion of two genes coding for the transcription factors DevR (bHLH) and RlmA (MADS-box) interfered with sporulation and reduced the expression of the DHN-melanin gene cluster. In vitro and in vivo experiments proved that these transcription factors cooperatively regulate pksP expression acting both as repressors and activators in a mutually exclusive manner. The dual role executed by each regulator depends on specific DNA motifs recognized in the pksP promoter region. © 2016 John Wiley & Sons Ltd.

Math in the Box

ERIC Educational Resources Information Center

DeYoung, Mary J.

2009-01-01

This article describes how to make an origami paper box and explores the algebra, geometry, and other mathematics that unfolds. A set of origami steps that transforms the paper into an open box can hold mathematical surprises for both students and teachers. An origami lesson can engage students in an open-ended exploration of the relationship…

The Construction of the UCSC Econo-Box: An Inexpensive Yet Effective Glove Box

NASA Astrophysics Data System (ADS)

Suri, Jeff T.

2001-11-01

An inexpensive, acrylic dry (glove) box has been fabricated and utilized in the handling of water- and air-sensitive materials. Working drawings are provided and a complete layout of material costs is presented. The box was experimentally determined to be moisture-free for three days and critically oxygen-free for 20 minutes under an inert gas atmosphere.

Standards and interdisciplinary treatment of boxing injuries of the head in professional boxing on the basis of an IBF World Championship Fight.

PubMed

Dragu, Adrian; Unglaub, Frank; Radomirovic, Sinisa; Schnürer, Stefan; Wagner, Walter; Horch, Raymund E; Hell, Berthold

2010-12-01

Boxing injuries are well known in hobby boxing as well as in professional boxing. Especially in professional boxing it is of great importance to implement and follow prevention-, diagnosis- and therapy-standards in order to prevent or at least to minimize injuries of the athlete. The utmost aim would be to establish international prevention-, diagnosis- and therapy-standards for boxing injuries in professional boxing. However, this aim is on a short run unrealistic, as there are too many different professional boxing organisations with different regulations. A realistic short term aim would be to develop a national standard in order to unify the management and medical treatment of boxing injuries in professional boxing. We present the management and interdisciplinary treatment of a professional boxer with a bilateral open fracture of the mandible during a middle weight IBF World Championship Fight. On the basis of this case we want to present and discuss the possibilities of an interdisciplinary and successful medical treatment. In order to prevent or minimize boxing injuries of professional boxers, annual MRI-Scans of the head and neck have to be performed as prevention standard. Furthermore, neurocognitive tests must be performed on a regular basis. Boxing injuries in professional boxing need an interdisciplinary, unbiased and complex analysis directly at the boxing ring. The treatment of the injuries should be only performed in medical centres and thus under constant parameters. The needed qualifications must be learned in mandatory national licence courses of boxing physicians, referees and promoters.

Construction of anatase/rutile TiO2 hollow boxes for highly efficient photocatalytic performance

NASA Astrophysics Data System (ADS)

Jia, Changchao; Zhang, Xiao; Yang, Ping

2018-02-01

Hollow TiO2 hierarchical boxes with suitable anatase and rutile ratios were designed for photocatalysis. The unique hierarchical structure was fabricated via a Topotactic synthetic method. CaTiO3 cubes were acted as the sacrificial templates to create TiO2 hollow hierarchical boxes with well-defined phase distribution. The phase composition of the hollow TiO2 hierarchical boxes is similar to that of TiO2 P25 nanoparticles (∼80% anatase, and 20% rutile). Compared with nanaoparticles, TiO2 hollow boxes with hierarchical structures exhibited an excellent performance in the photocatalytic degradation of methylene blue organic pollutant. Quantificationally, the degradation rate of the hollow boxes is higher than that of TiO2 P25 nanoparticles by a factor of 2.7. This is ascribed that hollow structure provide an opportunity for using incident light more efficiently. The surface hierarchical and well-organized porous structures are beneficial to supply more active sites and enough transport channels for reactant molecules. The boxes consist of single crystal anatase and rutile combined well with each other, which gives photon-generated carriers transfer efficiently.

Nearly Seamless Vacuum-Insulated Boxes

NASA Technical Reports Server (NTRS)

Stepanian, Christopher J.; Ou, Danny; Hu, Xiangjun

2010-01-01

A design concept, and a fabrication process that would implement the design concept, have been proposed for nearly seamless vacuum-insulated boxes that could be the main structural components of a variety of controlled-temperature containers, including common household refrigerators and insulating containers for shipping foods. In a typical case, a vacuum-insulated box would be shaped like a rectangular parallelepiped conventional refrigerator box having five fully closed sides and a hinged door on the sixth side. Although it is possible to construct the five-closed-side portion of the box as an assembly of five unitary vacuum-insulated panels, it is not desirable to do so because the relatively high thermal conductances of the seams between the panels would contribute significant amounts of heat leakage, relative to the leakage through the panels themselves. In contrast, the proposal would make it possible to reduce heat leakage by constructing the five-closed-side portion of the box plus the stationary portion (if any) of the sixth side as a single, seamless unit; the only remaining seam would be the edge seal around the door. The basic cross-sectional configuration of each side of a vacuum-insulated box according to the proposal would be that of a conventional vacuum-insulated panel: a low-density, porous core material filling a partially evacuated space between face sheets. However, neither the face sheets nor the core would be conventional. The face sheets would be opposite sides of a vacuum bag. The core material would be a flexible polymer-modified silica aerogel of the type described in Silica/Polymer and Silica/Polymer/Fiber Composite Aero - gels (MSC-23736) in this issue of NASA Tech Briefs. As noted in that article, the stiffness of this core material against compression is greater than that of prior aerogels. This is an important advantage because it translates to greater retention of thickness and, hence, of insulation performance when pressure is

MADS-box transcription factor AGL21 regulates lateral root development and responds to multiple external and physiological signals.

PubMed

Yu, Lin-Hui; Miao, Zi-Qing; Qi, Guo-Feng; Wu, Jie; Cai, Xiao-Teng; Mao, Jie-Li; Xiang, Cheng-Bin

2014-11-01

Plant root system morphology is dramatically influenced by various environmental cues. The adaptation of root system architecture to environmental constraints, which mostly depends on the formation and growth of lateral roots, is an important agronomic trait. Lateral root development is regulated by the external signals coordinating closely with intrinsic signaling pathways. MADS-box transcription factors are known key regulators of the transition to flowering and flower development. However, their functions in root development are still poorly understood. Here we report that AGL21, an AGL17-clade MADS-box gene, plays a crucial role in lateral root development. AGL21 was highly expressed in root, particularly in the root central cylinder and lateral root primordia. AGL21 overexpression plants produced more and longer lateral roots while agl21 mutants showed impaired lateral root development, especially under nitrogen-deficient conditions. AGL21 was induced by many plant hormones and environmental stresses, suggesting a function of this gene in root system plasticity in response to various signals. Furthermore, AGL21 was found positively regulating auxin accumulation in lateral root primordia and lateral roots by enhancing local auxin biosynthesis, thus stimulating lateral root initiation and growth. We propose that AGL21 may be involved in various environmental and physiological signals-mediated lateral root development and growth. © The Author 2014. Published by Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.

Magnetorotational Dynamo Action in the Shearing Box

NASA Astrophysics Data System (ADS)

Walker, Justin; Boldyrev, Stanislav

2017-10-01

Magnetic dynamo action caused by the magnetorotational instability is studied in the shearing-box approximation with no imposed net magnetic flux. Consistent with recent studies, the dynamo action is found to be sensitive to the aspect ratio of the box: it is much easier to obtain in tall boxes (stretched in the direction normal to the disk plane) than in long boxes (stretched in the radial direction). Our direct numerical simulations indicate that the dynamo is possible in both cases, given a large enough magnetic Reynolds number. To explain the relatively larger effort required to obtain the dynamo action in a long box, we propose that the turbulent eddies caused by the instability most efficiently fold and mix the magnetic field lines in the radial direction. As a result, in the long box the scale of the generated strong azimuthal (stream-wise directed) magnetic field is always comparable to the scale of the turbulent eddies. In contrast, in the tall box the azimuthal magnetic flux spreads in the vertical direction over a distance exceeding the scale of the turbulent eddies. As a result, different vertical sections of the tall box are permeated by large-scale nonzero azimuthal magnetic fluxes, facilitating the instability. NSF AGS-1261659, Vilas Associates Award, NSF-Teragrid Project TG-PHY110016.

Gene Expression Dynamics in Major Endocrine Regulatory Pathways along the Transition from Solitary to Social Life in a Bumblebee, Bombus terrestris.

PubMed

Jedlička, Pavel; Ernst, Ulrich R; Votavová, Alena; Hanus, Robert; Valterová, Irena

2016-01-01

Understanding the social evolution leading to insect eusociality requires, among other, a detailed insight into endocrine regulatory mechanisms that have been co-opted from solitary ancestors to play new roles in the complex life histories of eusocial species. Bumblebees represent well-suited models of a relatively primitive social organization standing on the mid-way to highly advanced eusociality and their queens undergo both, a solitary and a social phase, separated by winter diapause. In the present paper, we characterize the gene expression levels of major endocrine regulatory pathways across tissues, sexes, and life-stages of the buff-tailed bumblebee, Bombus terrestris , with special emphasis on critical stages of the queen's transition from solitary to social life. We focused on fundamental genes of three pathways: (1) Forkhead box protein O and insulin/insulin-like signaling, (2) Juvenile hormone (JH) signaling, and (3) Adipokinetic hormone signaling. Virgin queens were distinguished by higher expression of forkhead box protein O and downregulated insulin-like peptides and JH signaling, indicated by low expression of methyl farnesoate epoxidase ( MFE ) and transcription factor Krüppel homolog 1 ( Kr-h1 ). Diapausing queens showed the expected downregulation of JH signaling in terms of low MFE and vitellogenin ( Vg ) expressions, but an unexpectedly high expression of Kr-h1 . By contrast, reproducing queens revealed an upregulation of MFE and Vg together with insulin signaling. Surprisingly, the insulin growth factor 1 (IGF-1) turned out to be a queen-specific hormone. Workers exhibited an expression pattern of MFE and Vg similar to that of reproducing queens. Males were characterized by high Kr-h1 expression and low Vg level. The tissue comparison unveiled an unexpected resemblance between the fat body and hypopharyngeal glands across all investigated genes, sexes, and life stages.

Equivalent missense variant in the FOXP2 and FOXP1 transcription factors causes distinct neurodevelopmental disorders.

PubMed

Sollis, Elliot; Deriziotis, Pelagia; Saitsu, Hirotomo; Miyake, Noriko; Matsumoto, Naomichi; Hoffer, Mariëtte J V; Ruivenkamp, Claudia A L; Alders, Mariëlle; Okamoto, Nobuhiko; Bijlsma, Emilia K; Plomp, Astrid S; Fisher, Simon E

2017-11-01

The closely related paralogues FOXP2 and FOXP1 encode transcription factors with shared functions in the development of many tissues, including the brain. However, while mutations in FOXP2 lead to a speech/language disorder characterized by childhood apraxia of speech (CAS), the clinical profile of FOXP1 variants includes a broader neurodevelopmental phenotype with global developmental delay, intellectual disability, and speech/language impairment. Using clinical whole-exome sequencing, we report an identical de novo missense FOXP1 variant identified in three unrelated patients. The variant, p.R514H, is located in the forkhead-box DNA-binding domain and is equivalent to the well-studied p.R553H FOXP2 variant that cosegregates with CAS in a large UK family. We present here for the first time a direct comparison of the molecular and clinical consequences of the same mutation affecting the equivalent residue in FOXP1 and FOXP2. Detailed functional characterization of the two variants in cell model systems revealed very similar molecular consequences, including aberrant subcellular localization, disruption of transcription factor activity, and deleterious effects on protein interactions. Nonetheless, clinical manifestations were broader and more severe in the three cases carrying the p.R514H FOXP1 variant than in individuals with the p.R553H variant related to CAS, highlighting divergent roles of FOXP2 and FOXP1 in neurodevelopment. © 2017 Wiley Periodicals, Inc.

Glove box for water pit applications

DOEpatents

Mills, William C [Richland, WA; Rabe, Richard A [North Fork, ID

2005-01-18

A glove box assembly that includes a glove box enclosure attached to a longitudinally extending hollow tube having an entranceway, wherein the portion of the tube is in a liquid environment. An elevator member is provided for raising an object that is introduced into the hollow tube from the liquid environment to a gas environment inside the glove box enclosure while maintaining total containment.

The DEAD-box helicase eIF4A: paradigm or the odd one out?

PubMed

Andreou, Alexandra Z; Klostermeier, Dagmar

2013-01-01

DEAD-box helicases catalyze the ATP-dependent unwinding of RNA duplexes. They share a helicase core formed by two RecA-like domains that carries a set of conserved motifs contributing to ATP binding and hydrolysis, RNA binding and duplex unwinding. The translation initiation factor eIF4A is the founding member of the DEAD-box protein family, and one of the few examples of DEAD-box proteins that consist of a helicase core only. It is an RNA-stimulated ATPase and a non-processive helicase that unwinds short RNA duplexes. In the catalytic cycle, a series of conformational changes couples the nucleotide cycle to RNA unwinding. eIF4A has been considered a paradigm for DEAD-box proteins, and studies of its function have revealed the governing principles underlying the DEAD-box helicase mechanism. However, as an isolated helicase core, eIF4A is rather the exception, not the rule. Most helicase modules in other DEAD-box proteins are modified, some by insertions into the RecA-like domains, and the majority by N- and C-terminal appendages. While the basic catalytic function resides within the helicase core, its modulation by insertions, additional domains or a network of interaction partners generates the diversity of DEAD-box protein functions in the cell. This review summarizes the current knowledge on eIF4A and its regulation, and discusses to what extent eIF4A serves as a model DEAD-box protein.

[Optimization of Polysaccharide Extraction from Spirodela polyrrhiza by Plackett-Burman Design Combined with Box-Behnken Response Surface Methodology].

PubMed

Jiang, Zheng; Wang, Hong; Wu, Qi-nan

2015-06-01

To optimize the processing of polysaccharide extraction from Spirodela polyrrhiza. Five factors related to extraction rate of polysaccharide were optimized by the Plackett-Burman design. Based on this study, three factors, including alcohol volume fraction, extraction temperature and ratio of material to liquid, were regarded as investigation factors by Box-Behnken response surface methodology. The effect order of three factors on the extraction rate of polysaccharide from Spirodela polyrrhiza were as follows: extraction temperature, alcohol volume fraction,ratio of material to liquid. According to Box-Behnken response, the best extraction conditions were: alcohol volume fraction of 81%, ratio of material to liquid of 1:42, extraction temperature of 100 degrees C, extraction time of 60 min for four times. Plackett-Burman design and Box-Behnken response surface methodology used to optimize the extraction process for the polysaccharide in this study is effective and stable.

Evaluation of bike boxes at signalized intersections.

DOT National Transportation Integrated Search

2011-01-01

This report presents a before-after study of bike boxes at 10 signalized intersections in Portland, Oregon. The bike boxes, also known as advanced stop lines or advanced stop boxes, were installed to increase visibility of cyclists and reduce conflic...

The lithium vapor box divertor

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

Goldston, R. J.; Myers, R.; Schwartz, J.

It has long been recognized that volumetric dissipation of the plasma heat flux from a fusion power system is preferable to its localized impingement on a material surface. Volumetric dissipation mitigates both the anticipated very high heat flux and intense particle-induced damage due to sputtering. Our recent projections to a tokamak demonstration power plant suggest an immense upstream parallel heat flux, of order 20 GW m -2, implying that fully detached operation may be a requirement for the success of fusion power. Building on pioneering work on the use of lithium by Nagayama et al and by Ono et almore » as well as earlier work on the gas box divertor by Watkins and Rebut, we present here a concept for a lithium vapor box divertor, in which lithium vapor extracts momentum and energy from a fusion-power-plant divertor plasma, using fully volumetric processes. Furthermore, at the high powers and pressures that are projected this requires a high density of lithium vapor, which must be isolated from the main plasma in order to avoid lithium build-up on the chamber walls or in the plasma. Isolation is achieved through a powerful multi-box differential pumping scheme available only for condensable vapors. The preliminary box-wise calculations are encouraging, but much more work is required in order to demonstrate the practical viability of this scheme, taking into account at least 2D plasma and vapor flows within and between the vapor boxes and out of the vapor boxes to the main plasma.« less

The lithium vapor box divertor

NASA Astrophysics Data System (ADS)

Goldston, R. J.; Myers, R.; Schwartz, J.

2016-02-01

It has long been recognized that volumetric dissipation of the plasma heat flux from a fusion power system is preferable to its localized impingement on a material surface. Volumetric dissipation mitigates both the anticipated very high heat flux and intense particle-induced damage due to sputtering. Recent projections to a tokamak demonstration power plant suggest an immense upstream parallel heat flux, of order 20 GW m-2, implying that fully detached operation may be a requirement for the success of fusion power. Building on pioneering work on the use of lithium by Nagayama et al and by Ono et al as well as earlier work on the gas box divertor by Watkins and Rebut, we present here a concept for a lithium vapor box divertor, in which lithium vapor extracts momentum and energy from a fusion-power-plant divertor plasma, using fully volumetric processes. At the high powers and pressures that are projected this requires a high density of lithium vapor, which must be isolated from the main plasma in order to avoid lithium build-up on the chamber walls or in the plasma. Isolation is achieved through a powerful multi-box differential pumping scheme available only for condensable vapors. The preliminary box-wise calculations are encouraging, but much more work is required to demonstrate the practical viability of this scheme, taking into account at least 2D plasma and vapor flows within and between the vapor boxes and out of the vapor boxes to the main plasma.

The lithium vapor box divertor

DOE PAGES

Goldston, R. J.; Myers, R.; Schwartz, J.

2016-01-13

It has long been recognized that volumetric dissipation of the plasma heat flux from a fusion power system is preferable to its localized impingement on a material surface. Volumetric dissipation mitigates both the anticipated very high heat flux and intense particle-induced damage due to sputtering. Our recent projections to a tokamak demonstration power plant suggest an immense upstream parallel heat flux, of order 20 GW m -2, implying that fully detached operation may be a requirement for the success of fusion power. Building on pioneering work on the use of lithium by Nagayama et al and by Ono et almore » as well as earlier work on the gas box divertor by Watkins and Rebut, we present here a concept for a lithium vapor box divertor, in which lithium vapor extracts momentum and energy from a fusion-power-plant divertor plasma, using fully volumetric processes. Furthermore, at the high powers and pressures that are projected this requires a high density of lithium vapor, which must be isolated from the main plasma in order to avoid lithium build-up on the chamber walls or in the plasma. Isolation is achieved through a powerful multi-box differential pumping scheme available only for condensable vapors. The preliminary box-wise calculations are encouraging, but much more work is required in order to demonstrate the practical viability of this scheme, taking into account at least 2D plasma and vapor flows within and between the vapor boxes and out of the vapor boxes to the main plasma.« less

A Role for the GCC-Box in Jasmonate-Mediated Activation of the PDF1.2 Gene of Arabidopsis1

PubMed Central

Brown, Rebecca L.; Kazan, Kemal; McGrath, Ken C.; Maclean, Don J.; Manners, John M.

2003-01-01

The PDF1.2 gene of Arabidopsis encoding a plant defensin is commonly used as a marker for characterization of the jasmonate-dependent defense responses. Here, using PDF1.2 promoter-deletion lines linked to the β-glucoronidase-reporter gene, we examined putative promoter elements associated with jasmonate-responsive expression of this gene. Using stably transformed plants, we first characterized the extended promoter region that positively regulates basal expression from the PDF1.2 promoter. Second, using promoter deletion constructs including one from which the GCC-box region was deleted, we observed a substantially lower response to jasmonate than lines carrying this motif. In addition, point mutations introduced into the core GCC-box sequence substantially reduced jasmonate responsiveness, whereas addition of a 20-nucleotide-long promoter element carrying the core GCC-box and flanking nucleotides provided jasmonate responsiveness to a 35S minimal promoter. Taken together, these results indicated that the GCC-box plays a key role in conferring jasmonate responsiveness to the PDF1.2 promoter. However, deletion or specific mutations introduced into the core GCC-box did not completely abolish the jasmonate responsiveness of the promoter, suggesting that the other promoter elements lying downstream from the GCC-box region may also contribute to jasmonate responsiveness. In other experiments, we identified a jasmonate- and pathogen-responsive ethylene response factor transcription factor, AtERF2, which when overexpressed in transgenic Arabidopsis plants activated transcription from the PDF1.2, Thi2.1, and PR4 (basic chitinase) genes, all of which contain a GCC-box sequence in their promoters. Our results suggest that in addition to their roles in regulating ethylene-mediated gene expression, ethylene response factors also appear to play important roles in regulating jasmonate-responsive gene expression, possibly via interaction with the GCC-box. PMID:12805630

The five-box method: The "four-box method" for the Catholic physician.

PubMed

Marugg, Lindsey; Atkinson, Marie-Noelle; Fernandes, Ashley

2014-11-01

The traditional ethical model of the "Four-Box Method" can be adapted to integrate the perspective of a Catholic physician. In an increasingly secularist environment, medical students and physicians are often asked to "leave religious beliefs at the door" and not consider the care and stewardship of our own morality and involvement as a provider. We reject this view. A patient's own religious and moral beliefs should be respected to the extent that they do not destroy our own; for us, the Catholic viewpoint can shine a light into dark corners and aid us in translating true things to patients of any religion. We analyzed a sample case in five different categories: medical indications, patient preferences, quality of life, contextual features, and the Catholic context. We explored how to methodically integrate the perspective of a Catholic physician into the analysis of this case to make the best decision for the patients. We felt that we were successfully able to integrate this perspective and create a "fifth box" based on the principles of Catholic social teaching. There were also points during the analysis that the perspective of the Catholic physician was integrated into the discussion of medical indications, proving to us that the "Catholic perspective" cannot be just put in one box either. The traditional ethical model of the "four-box method" can be adapted to integrate the perspective of a Catholic physician. In an increasingly secularist environment, medical students and physicians are often asked to "leave religious beliefs at the door" and not consider the care and stewardship of our own morality and involvement as a provider. We reject this view. A patient's own religious and moral beliefs should be respected to the extent that they do not destroy our own; for us, the Catholic viewpoint can shine a light into dark corners and aid us in translating true things to patients of any religion. By expanding to a "fifth box" of Catholic social teaching, the

Policy statement—Boxing participation by children and adolescents.

PubMed

Purcell, Laura; LeBlanc, Claire M A

2011-09-01

Thousands of boys and girls younger than 19 years participate in boxing in North America. Although boxing provides benefits for participants, including exercise, self-discipline, and self-confidence, the sport of boxing encourages and rewards deliberate blows to the head and face. Participants in boxing are at risk of head, face, and neck injuries, including chronic and even fatal neurologic injuries. Concussions are one of the most common injuries that occur with boxing. Because of the risk of head and facial injuries, the American Academy of Pediatrics and the Canadian Paediatric Society oppose boxing as a sport for children and adolescents. These organizations recommend that physicians vigorously oppose boxing in youth and encourage patients to participate in alternative sports in which intentional head blows are not central to the sport.

Spirit Boxes: Expressions of Culture.

ERIC Educational Resources Information Center

DeMuro, Ted

1984-01-01

After studying the culture and art of the ancient civilizations of South America, Mesopotamia, Greece, and Egypt, secondary level art students made spirit boxes as expressions of the various cultures. How to make the boxes and how to prepare the face molds are described. (RM)

Magnetorotational dynamo action in the shearing box

NASA Astrophysics Data System (ADS)

Walker, Justin; Boldyrev, Stanislav

2017-09-01

Magnetic dynamo action caused by the magnetorotational instability is studied in the shearing-box approximation with no imposed net magnetic flux. Consistent with recent studies, the dynamo action is found to be sensitive to the aspect ratio of the box: it is much easier to obtain in tall boxes (stretched in the direction normal to the disc plane) than in long boxes (stretched in the radial direction). Our direct numerical simulations indicate that the dynamo is possible in both cases, given a large enough magnetic Reynolds number. To explain the relatively larger effort required to obtain the dynamo action in a long box, we propose that the turbulent eddies caused by the instability most efficiently fold and mix the magnetic field lines in the radial direction. As a result, in the long box the scale of the generated strong azimuthal (stream-wise directed) magnetic field is always comparable to the scale of the turbulent eddies. In contrast, in the tall box the azimuthal magnetic flux spreads in the vertical direction over a distance exceeding the scale of the turbulent eddies. As a result, different vertical sections of the tall box are permeated by large-scale non-zero azimuthal magnetic fluxes, facilitating the instability. In agreement with this picture, the cases when the dynamo is efficient are characterized by a strong intermittency of the local azimuthal magnetic fluxes.

Computational Fluid Dynamics Analysis of Flexible Duct Junction Box Design

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

Beach, Robert; Prahl, Duncan; Lange, Rich

2013-12-01

IBACOS explored the relationships between pressure and physical configurations of flexible duct junction boxes by using computational fluid dynamics (CFD) simulations to predict individual box parameters and total system pressure, thereby ensuring improved HVAC performance. Current Air Conditioning Contractors of America (ACCA) guidance (Group 11, Appendix 3, ACCA Manual D, Rutkowski 2009) allows for unconstrained variation in the number of takeoffs, box sizes, and takeoff locations. The only variables currently used in selecting an equivalent length (EL) are velocity of air in the duct and friction rate, given the first takeoff is located at least twice its diameter away frommore » the inlet. This condition does not account for other factors impacting pressure loss across these types of fittings. For each simulation, the IBACOS team converted pressure loss within a box to an EL to compare variation in ACCA Manual D guidance to the simulated variation. IBACOS chose cases to represent flows reasonably correlating to flows typically encountered in the field and analyzed differences in total pressure due to increases in number and location of takeoffs, box dimensions, and velocity of air, and whether an entrance fitting is included. The team also calculated additional balancing losses for all cases due to discrepancies between intended outlet flows and natural flow splits created by the fitting. In certain asymmetrical cases, the balancing losses were significantly higher than symmetrical cases where the natural splits were close to the targets. Thus, IBACOS has shown additional design constraints that can ensure better system performance.« less

Film Boxes.

ERIC Educational Resources Information Center

Osterer, Irv

2002-01-01

Presents an art lesson in which students created three-dimensional designs for 35mm film packages to improve graphic arts learning. Describes how the students examined and created film boxes using QuarkXPress software. (CMK)

49 CFR 178.515 - Standards for reconstituted wood boxes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Standards for reconstituted wood boxes. 178.515... wood boxes. (a) The identification code for a reconstituted wood box is 4F. (b) Construction requirements for reconstituted wood boxes are as follows: (1) The walls of boxes must be made of water...

Ocular complications of boxing

PubMed Central

Bianco, M; Vaiano, A; Colella, F; Coccimiglio, F; Moscetti, M; Palmieri, V; Focosi, F; Zeppilli, P; Vinger, P

2005-01-01

Objectives: To investigate the prevalence of ocular injuries in a large population of boxers over a period of 16 years, in particular, the most severe lesions that may be vision threatening. Methods: Clinical records of the medical archive of the Italian Boxing Federation were analysed. A total of 1032 boxers were examined from February 1982 to October 1998. A complete ophthalmological history was available for 956, who formed the study population (a total of 10 697 examinations). The following data were collected: age when started boxing; duration of competitive boxing career (from the date of the first bout); weight category; a thorough ocular history. The following investigations were carried out: measurement of visual acuity and visual fields, anterior segment inspection, applanation tonometry, gonioscopy, and examination of ocular fundus. Eighty age matched healthy subjects, who had never boxed, formed the control group. Results: Of the 956 boxers examined, 428 were amateur (44.8%) and 528 professional (55.2%). The median age at first examination was 23.1 (4.3) years (range 15–36). The prevalence of conjunctival, corneal, lenticular, vitreal, ocular papilla, and retinal alterations in the study population was 40.9% compared with 3.1% in the control group (p⩽0.0001). The prevalence of serious ocular findings (angle, lens, macula, and peripheral retina alterations) was 5.6% in boxers and 3.1% in controls (NS). Conclusions: Boxing does not result in a higher prevalence of severe ocular lesions than in the general population. However, the prevalence of milder lesions (in particular with regard to the conjunctiva and cornea) is noteworthy, justifying the need for adequate ophthalmological surveillance. PMID:15665199

49 CFR 178.517 - Standards for plastic boxes.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Standards for plastic boxes. 178.517 Section 178...-bulk Performance-Oriented Packaging Standards § 178.517 Standards for plastic boxes. (a) The following are identification codes for plastic boxes: (1) 4H1 for an expanded plastic box; and (2) 4H2 for a...

49 CFR 178.517 - Standards for plastic boxes.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 3 2012-10-01 2012-10-01 false Standards for plastic boxes. 178.517 Section 178...-bulk Performance-Oriented Packaging Standards § 178.517 Standards for plastic boxes. (a) The following are identification codes for plastic boxes: (1) 4H1 for an expanded plastic box; and (2) 4H2 for a...

49 CFR 178.517 - Standards for plastic boxes.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 3 2014-10-01 2014-10-01 false Standards for plastic boxes. 178.517 Section 178...-bulk Performance-Oriented Packaging Standards § 178.517 Standards for plastic boxes. (a) The following are identification codes for plastic boxes: (1) 4H1 for an expanded plastic box; and (2) 4H2 for a...

49 CFR 178.517 - Standards for plastic boxes.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 3 2013-10-01 2013-10-01 false Standards for plastic boxes. 178.517 Section 178...-bulk Performance-Oriented Packaging Standards § 178.517 Standards for plastic boxes. (a) The following are identification codes for plastic boxes: (1) 4H1 for an expanded plastic box; and (2) 4H2 for a...

Ion-wake field inside a glass box.

PubMed

Chen, Mudi; Dropmann, Michael; Zhang, Bo; Matthews, Lorin S; Hyde, Truell W

2016-09-01

The confinement provided by a glass box is proving ideal for the formation of vertically aligned structures and a convenient method for controlling the number of dust particles comprising these dust structures as well as their sizes and shapes. In this paper, the electronic confinement of the glass box is mapped, and the particle interactions between the particle pairs inside the glass box are measured. The ion-wake field is shown to exist within the glass box, and its vertical and horizontal extents are measured.

49 CFR 178.517 - Standards for plastic boxes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Standards for plastic boxes. 178.517 Section 178... PACKAGINGS Non-bulk Performance-Oriented Packaging Standards § 178.517 Standards for plastic boxes. (a) The following are identification codes for plastic boxes: (1) 4H1 for an expanded plastic box; and (2) 4H2 for a...

Nonneurologic emergencies in boxing.

PubMed

Coletta, Domenic F

2009-10-01

Professional boxing has done an admirable job in promoting safety standards in its particular sport. However, injuries occur during the normal course of competition and, unfortunately, an occasional life-threatening emergency may arise. Although most common medical emergencies in boxing are injuries from closed head trauma, in this article those infrequent but potentially catastrophic nonneurologic conditions are reviewed along with some less serious emergencies that the physician must be prepared to address.

Identification and expression analysis of the SQUAMOSA promoter-binding protein (SBP)-box gene family in Prunus mume.

PubMed

Xu, Zongda; Sun, Lidan; Zhou, Yuzhen; Yang, Weiru; Cheng, Tangren; Wang, Jia; Zhang, Qixiang

2015-10-01

SQUAMOSA promoter-binding protein (SBP)-box family genes encode plant-specific transcription factors that play crucial roles in plant development, especially flower and fruit development. However, little information on this gene family is available for Prunus mume, an ornamental and fruit tree widely cultivated in East Asia. To explore the evolution of SBP-box genes in Prunus and explore their functions in flower and fruit development, we performed a genome-wide analysis of the SBP-box gene family in P. mume. Fifteen SBP-box genes were identified, and 11 of them contained an miR156 target site. Phylogenetic and comprehensive bioinformatics analyses revealed that different groups of SBP-box genes have undergone different evolutionary processes and varied in their length, structure, and motif composition. Purifying selection has been the main selective constraint on both paralogous and orthologous SBP-box genes. In addition, the sequences of orthologous SBP-box genes did not diverge widely after the split of P. mume and Prunus persica. Expression analysis of P. mume SBP-box genes revealed their diverse spatiotemporal expression patterns. Three duplicated SBP-box genes may have undergone subfunctionalization in Prunus. Most of the SBP-box genes showed high transcript levels in flower buds and young fruit. The four miR156-nontargeted genes were upregulated during fruit ripening. Together, these results provide information about the evolution of SBP-box genes in Prunus. The expression analysis lays the foundation for further research on the functions of SBP-box genes in P. mume and other Prunus species, especially during flower and fruit development.

Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation.

PubMed

Stennard, Fiona A; Costa, Mauro W; Lai, Donna; Biben, Christine; Furtado, Milena B; Solloway, Mark J; McCulley, David J; Leimena, Christiana; Preis, Jost I; Dunwoodie, Sally L; Elliott, David E; Prall, Owen W J; Black, Brian L; Fatkin, Diane; Harvey, Richard P

2005-05-01

The genetic hierarchies guiding lineage specification and morphogenesis of the mammalian embryonic heart are poorly understood. We now show by gene targeting that murine T-box transcription factor Tbx20 plays a central role in these pathways, and has important activities in both cardiac development and adult function. Loss of Tbx20 results in death of embryos at mid-gestation with grossly abnormal heart morphogenesis. Underlying these disturbances was a severely compromised cardiac transcriptional program, defects in the molecular pre-pattern, reduced expansion of cardiac progenitors and a block to chamber differentiation. Notably, Tbx20-null embryos showed ectopic activation of Tbx2 across the whole heart myogenic field. Tbx2 encodes a transcriptional repressor normally expressed in non-chamber myocardium, and in the atrioventricular canal it has been proposed to inhibit chamber-specific gene expression through competition with positive factor Tbx5. Our data demonstrate a repressive activity for Tbx20 and place it upstream of Tbx2 in the cardiac genetic program. Thus, hierarchical, repressive interactions between Tbx20 and other T-box genes and factors underlie the primary lineage split into chamber and non-chamber myocardium in the forming heart, an early event upon which all subsequent morphogenesis depends. Additional roles for Tbx20 in adult heart integrity and contractile function were revealed by in-vivo cardiac functional analysis of Tbx20 heterozygous mutant mice. These data suggest that mutations in human cardiac transcription factor genes, possibly including TBX20, underlie both congenital heart disease and adult cardiomyopathies.

Utilization of Boxes for Pesticide Storage in Sri Lanka.

PubMed

Pieris, Ravi; Weerasinghe, Manjula; Abeywickrama, Tharaka; Manuweera, Gamini; Eddleston, Michael; Dawson, Andrew; Konradsen, Flemming

2017-01-01

Pesticide self-poisoning is now considered one of the two most common methods of suicide worldwide. Encouraging safe storage of pesticides is one particular approach aimed at reducing pesticide self-poisoning. CropLife Sri Lanka (the local association of pesticide manufacturers), with the aid of the Department of Agriculture, distributed lockable in-house pesticide storage boxes free of charge to a farming community in a rural district of Sri Lanka. Padlocks were not provided with the boxes. These storage boxes were distributed to the farmers without prior education. The authors carried out a cross-sectional follow-up survey to assess the usage of boxes at 7 months after distribution. In an inspection of a sample of 239 box recipients' households, 142 households stored pesticides in the provided box at the time of survey. Among them, only 42 (42/142, 29.65%) households had locked the box; the remaining households (100/142, 70.4%) had not locked the box. A simple hand over of in-house pesticide storage boxes without awareness/education results in poor use of boxes. Additionally, providing in-house storage boxes may encourage farmers to store pesticides in and around houses and, if they are not locked, may lead to unplanned adverse effects.

Being Creative "Inside the Box"

ERIC Educational Resources Information Center

Tomascoff, Rocky

2011-01-01

Artist Joseph Cornell (1903-1972) created wonderful environments inside boxes using mostly found objects. They were often Surrealistic in nature. Some boxes were designed with glass fronts, and others were meant to be interactive with the viewer, wherein the objects could be handled. With Joseph Cornell in mind, the author introduces an art…

Litter box preference in domestic cats: covered versus uncovered.

PubMed

Grigg, Emma K; Pick, Lindsay; Nibblett, Belle

2013-04-01

Feline inappropriate elimination (periuria and/or perichezia) remains a very common behavioral complaint of cat owners. Treatment recommendations often include improving the attractiveness of the litter boxes available to the cat. One frequent recommendation is to avoid covered litter boxes, although this has not previously been tested experimentally. The goal of this study was to assess whether, all else being equal, cats preferentially used uncovered litter boxes over covered litter boxes. Twenty-eight cats were enrolled in the study and offered the choice of a covered or uncovered box. Waste was scooped daily from each box, and the weight of waste in the different box styles was compared and evaluated using paired t-tests and χ(2) analyses. Overall, there was no significant difference between use of the two box styles. Eight individual cats did exhibit a preference (four for covered, four for uncovered), but individual preference results are not evenly distributed, with more cats than expected showing no preference between litter box types. We postulate that, if boxes are kept sufficiently clean (ie, once daily minimum cleaning), most cats will not show a preference for either box type. The observation that a minority of cats in the study exhibited a preference supports the recommendation of providing individual cats with a 'cafeteria' of litter box styles, including a covered box, to determine whether such a preference exists. These findings add to existing literature on the topic of feline inappropriate elimination and provide additional information for clinicians recommending treatment options for cats exhibiting this behavior.

Amateur boxing: physical and physiological attributes.

PubMed

Chaabène, Helmi; Tabben, Montassar; Mkaouer, Bessem; Franchini, Emerson; Negra, Yassine; Hammami, Mehrez; Amara, Samiha; Chaabène, Raja Bouguezzi; Hachana, Younés

2015-03-01

Boxing is one of the oldest combat sports. The aim of the current review is to critically analyze the amateur boxer's physical and physiological characteristics and to provide practical recommendations for training as well as new areas of scientific research. High-level male and female boxers show a propensity for low body fat levels. Although studies on boxer somatotypes are limited, the available information shows that elite-level male boxers are characterized by a higher proportion of mesomorphy with a well-developed muscle mass and a low body fat level. To help support the overall metabolic demands of a boxing match and to accelerate the recovery process between rounds, athletes of both sexes require a high level of cardiorespiratory fitness. International boxers show a high peak and mean anaerobic power output. Muscle strength in both the upper and lower limbs is paramount for a fighter's victory and is one of the keys to success in boxing. As boxing punches are brief actions and very dynamic, high-level boxing performance requires well-developed muscle power in both the upper and lower limbs. Albeit limited, the available studies reveal that isometric strength is linked to high-level boxing performance. Future investigations into the physical and physiological attributes of boxers are required to enrich the current data set and to help create a suitable training program.

Reciprocal Loss of CArG-Boxes and Auxin Response Elements Drives Expression Divergence of MPF2-Like MADS-Box Genes Controlling Calyx Inflation

PubMed Central

Khan, Muhammad Ramzan; Hu, Jinyong; Ali, Ghulam Muhammad

2012-01-01

Expression divergence is thought to be a hallmark of functional diversification between homologs post duplication. Modification in regulatory elements has been invoked to explain expression divergence after duplication for several MADS-box genes, however, verification of reciprocal loss of cis-regulatory elements is lacking in plants. Here, we report that the evolution of MPF2-like genes has entailed degenerative mutations in a core promoter CArG-box and an auxin response factor (ARF) binding element in the large 1st intron in the coding region. Previously, MPF2-like genes were duplicated into MPF2-like-A and -B through genome duplication in Withania and Tubocapsicum (Withaninae). The calyx of Withania grows exorbitantly after pollination unlike Tubocapsicum, where it degenerates. Besides inflated calyx syndrome formation, MPF2-like transcription factors are implicated in functions both during the vegetative and reproductive development as well as in phase transition. MPF2-like-A of Withania (WSA206) is strongly expressed in sepals, while MPF2-like-B (WSB206) is not. Interestingly, their combined expression patterns seem to replicate the pattern of their closely related hypothetical progenitors from Vassobia and Physalis. Using phylogenetic shadowing, site-directed mutagenesis and motif swapping, we could show that the loss of a conserved CArG-box in MPF2-like-B of Withania is responsible for impeding its expression in sepals. Conversely, loss of an ARE in MPF2-like-A relaxed the constraint on expression in sepals. Thus, the ARE is an active suppressor of MPF2-like gene expression in sepals, which in contrast is activated via the CArG-box. The observed expression divergence in MPF2-like genes due to reciprocal loss of cis-regulatory elements has added to genetic and phenotypic variations in the Withaninae and enhanced the potential of natural selection for the adaptive evolution of ICS. Moreover, these results provide insight into the interplay of floral

Influence of dimension box differences and time differences during operations of red box for motorcycles at signalized intersection

NASA Astrophysics Data System (ADS)

Mulyadi, Agah Muhammad

2017-11-01

Performance of signalized intersection has declined due to a large number of motorcycles. The number of motorcycles reached 98.2 million units and the composition of motorcycles has reached around 81.7% of the total composition of vehicles in Indonesia (AISI, 2017). To solve that problem, the red box for motorcycles are provided at the signalized intersection. Red box for the motorcycle at signalized intersections was developed from the concept of Advance Stop Line (ASL) for bicycles. The Red Box was developed to split the queue between motorcycles and other vehicles when waiting at red light. This paper aims to evaluate the influence of the red box dimension and red time operation differences. The survey was conducted as many as 30 cycles of traffic signals per day. The data were analyzed using software IBM SPSS Statistics 20 by using Analysis of Variance (ANOVA) to obtain p-value (significant). The analysis shows that there are insignificant influences between the occupancy rates to the dimension of Red Box. Furthermore, that there is a significant difference that shows the dependency of only motorcycles in the Red Box Area towards red time operation.

MicroRNA-214 Suppresses Gluconeogenesis by Targeting Activating Transcriptional Factor 4*

PubMed Central

Li, Kai; Zhang, Jin; Yu, Junjie; Liu, Bin; Guo, Yajie; Deng, Jiali; Chen, Shanghai; Wang, Chunxia; Guo, Feifan

2015-01-01

Although the gluconeogenesis pathway is already a target for the treatment of type 2 diabetes, the potential role of microRNAs (miRNAs) in gluconeogenesis remains unclear. Here, we investigated the physiological functions of miR-214 in gluconeogenesis. The expression of miR-214 was suppressed by glucagon via protein kinase A signaling in primary hepatocytes, and miR-214 was down-regulated in the livers of fasted, high fat diet-induced diabetic and leptin receptor-mutated (db/db) mice. The overexpression of miR-214 in primary hepatocytes suppressed glucose production, and silencing miR-214 reversed this effect. Gluconeogenesis was suppressed in the livers of mice injected with an adenovirus expressing miR-214 (Ad-miR-214). Additionally, Ad-miR-214 alleviated high fat diet-induced elevation of gluconeogenesis and hyperglycemia. Furthermore, we found that activating transcription factor 4 (ATF4), a reported target of miR-214, can reverse the suppressive effect of miR-214 on gluconeogenesis in primary hepatocytes, and this suppressive effect was blocked in liver-specific ATF4 knock-out mice. ATF4 regulated gluconeogenesis via affecting forkhead box protein O1 (FOXO1) transcriptional activity. Finally, liver-specific miR-214 transgenic mice exhibited suppressed gluconeogenesis and reduced expression of ATF4, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in liver. Taken together, our results suggest that the miR-214-ATF4 axis is a novel pathway for the regulation of hepatic gluconeogenesis. PMID:25657009

Using a drug facts box to communicate drug benefits and harms: two randomized trials.

PubMed

Schwartz, Lisa M; Woloshin, Steven; Welch, H Gilbert

2009-04-21

side effects of a statin and clopidogrel. For example, 72% of the drug box group and 9% of the control group correctly quantified the benefit (absolute risk reduction) of the statin (P < 0.001). Most of the control participants overestimated this benefit, and 65% did so by a factor of 10 or more. The trials tested drug boxes in only 4 direct-to-consumer ads. If other direct-to-consumer ads were to communicate outcome data better, the effect of the drug box would be reduced. A drug facts box improved U.S. consumers' knowledge of prescription drug benefits and side effects. It resulted in better choices between drugs for current symptoms and corrected the overestimation of benefit in the setting of prevention. National Cancer Institute and Attorney General Consumer and Prescriber Education Program.

What Makes a Better Box?

ERIC Educational Resources Information Center

Moyer, Richard; Everett, Susan

2010-01-01

Every morning, many Americans start their day with a bowl of cereal. Some spend time while they eat breakfast reading the back of the cereal box, but few consider its size, shape, and construction, or realize that it was designed by an engineer. This article describes a lesson in which students design, build, and critique cereal boxes. The lesson…

Nopaline-type Ti plasmid of Agrobacterium encodes a VirF-like functional F-box protein.

PubMed

Lacroix, Benoît; Citovsky, Vitaly

2015-11-20

During Agrobacterium-mediated genetic transformation of plants, several bacterial virulence (Vir) proteins are translocated into the host cell to facilitate infection. One of the most important of such translocated factors is VirF, an F-box protein produced by octopine strains of Agrobacterium, which presumably facilitates proteasomal uncoating of the invading T-DNA from its associated proteins. The presence of VirF also is thought to be involved in differences in host specificity between octopine and nopaline strains of Agrobacterium, with the current dogma being that no functional VirF is encoded by nopaline strains. Here, we show that a protein with homology to octopine VirF is encoded by the Ti plasmid of the nopaline C58 strain of Agrobacterium. This protein, C58VirF, possesses the hallmarks of functional F-box proteins: it contains an active F-box domain and specifically interacts, via its F-box domain, with SKP1-like (ASK) protein components of the plant ubiquitin/proteasome system. Thus, our data suggest that nopaline strains of Agrobacterium have evolved to encode a functional F-box protein VirF.

The shear-lag effect of thin-walled box girder under vertical earthquake excitation

NASA Astrophysics Data System (ADS)

Zhai, Zhipeng; Li, Yaozhuang; Guo, Wei

2017-03-01

The variation method based on the energy variation principle is proved to be accurate and valid for analyzing the shear lag effect of box girder under static and dynamic load. Meanwhile, dynamic problems gradually become the key factors in engineering practice. Therefore, a method for calculating the shear lag effect in thin-walled box girder under vertical seismic excitation is proposed by applying Hamilton Principle in this paper. The Timoshenko shear deformation is taken into account. And a new definition of shear lag ratio for box girder is given. What's more, some conclusions are drawn by analysis of numerical example. The results show that small amplitude of earthquake ground motion can generate high stress and obvious shear lag, especially in the region of resonance. And the influence of rotary inertia cannot be ignored for analyzing the shear lag effect. With the increase of span to width ratio, shear lag effect becomes smaller and smaller. These research conclusions will be useful for the engineering practice and enrich the theoretical studies of box girders.

A Survey of MIKC Type MADS-Box Genes in Non-seed Plants: Algae, Bryophytes, Lycophytes and Ferns

PubMed Central

Thangavel, Gokilavani; Nayar, Saraswati

2018-01-01

MADS box transcription factors have been studied extensively in flowering plants but remain less studied in non-seed plants. MADS box is one such example of a gene which is prevalent across many classes of plants ranging from chlorophyta to embryophyta as well as fungi and animals. MADS box transcription factors are of two types, Type I and Type II. Type II transcription factors (TF) that consist of a MADS domain, I region, K domain, and C terminal domain are discussed in this review. The Type II/ MIKC class is widespread across charophytes and all major lineages of land plants but unknown in green and red algae. These transcription factors have been implicated in floral development in seed plants and thus the question arises, “What is their role in non-seed plants?” From the studies reviewed here it can be gathered that unlike seed plants, MIKCC genes in non-seed plants have roles in both gametophytic and sporophytic generations and contribute to the development of both vegetative and reproductive structures. On the other hand as previously observed in seed plants, MIKC* genes of non-seed plants have a conserved role during gametophyte development. With respect to evolution of MIKC genes in non-seed plants, the number of common ancestors is probably very few at each branch. The expansion of this gene family in seed plants and increased plant complexity seem to be correlated. As gradually the genomes of non-seed plants are becoming available it is worthwhile to gather the existing information about MADS box genes in non-seed plants. This review highlights various MIKC MADS box genes discovered so far in non-seed plants, their possible roles and an insight into their evolution. PMID:29720991

A Survey of MIKC Type MADS-Box Genes in Non-seed Plants: Algae, Bryophytes, Lycophytes and Ferns.

PubMed

Thangavel, Gokilavani; Nayar, Saraswati

2018-01-01

MADS box transcription factors have been studied extensively in flowering plants but remain less studied in non-seed plants. MADS box is one such example of a gene which is prevalent across many classes of plants ranging from chlorophyta to embryophyta as well as fungi and animals. MADS box transcription factors are of two types, Type I and Type II. Type II transcription factors (TF) that consist of a MADS domain, I region, K domain, and C terminal domain are discussed in this review. The Type II/ MIKC class is widespread across charophytes and all major lineages of land plants but unknown in green and red algae. These transcription factors have been implicated in floral development in seed plants and thus the question arises, "What is their role in non-seed plants?" From the studies reviewed here it can be gathered that unlike seed plants, MIKC C genes in non-seed plants have roles in both gametophytic and sporophytic generations and contribute to the development of both vegetative and reproductive structures. On the other hand as previously observed in seed plants, MIKC * genes of non-seed plants have a conserved role during gametophyte development. With respect to evolution of MIKC genes in non-seed plants, the number of common ancestors is probably very few at each branch. The expansion of this gene family in seed plants and increased plant complexity seem to be correlated. As gradually the genomes of non-seed plants are becoming available it is worthwhile to gather the existing information about MADS box genes in non-seed plants. This review highlights various MIKC MADS box genes discovered so far in non-seed plants, their possible roles and an insight into their evolution.

Differential effects of voluntary wheel running and toy rotation on the mRNA expression of neurotrophic factors and FKBP5 in a post-traumatic stress disorder rat model with the shuttle-box task.

PubMed

Tanichi, Masaaki; Toda, Hiroyuki; Shimizu, Kunio; Koga, Minori; Saito, Taku; Enomoto, Shingo; Boku, Shuken; Asai, Fumiho; Mitsui, Yumi; Nagamine, Masanori; Fujita, Masanori; Yoshino, Aihide

2018-06-18

Life-threatening experiences can result in the development of post-traumatic stress disorder. We have developed an animal model for post-traumatic stress disorder (PTSD) using a shuttle box in rats. In this paradigm, the rats were exposed to inescapable foot-shock stress (IS) in a shuttle box, and then an avoidance/escape task was performed in the same box 2 weeks after IS. A previous study using this paradigm revealed that environmental enrichment (EE) ameliorated avoidance/numbing-like behaviors, but not hyperarousal-like behaviors, and EE also elevated hippocampal brain-derived neurotrophic factor (BDNF) expression. However, the differential effects of EE components, i.e., running wheel (RW) or toy rotation, on PTSD-like behaviors has remained unclear. In this experiment, we demonstrated that RW, toy rotation, and EE (containing RW and toy rotation) ameliorated avoidance/numbing-like behaviors, induced learning of avoidance responses, and improved depressive-like behaviors in traumatized rats. The RW increased the hippocampal mRNA expression of neurotrophic factors, especially BDNF and glial-cell derived neurotrophic factor. Toy rotation influenced FK506 binding protein 5 mRNA expression, which is believed to be a regulator of the hypothalamic-pituitary-adrenal (HPA)-axis system, in the hippocampus and amygdala. This is the first report to elucidate the differential mechanistic effects of RW and toy rotation. The former appears to exert its effects via neurotrophic factors, while the latter exerts its effects via the HPA axis. Further studies will lead to a better understanding of the influence of environmental factors on PTSD. Copyright © 2018 Elsevier Inc. All rights reserved.

Sport medicine and the ethics of boxing.

PubMed

Leclerc, S; Herrera, C D

1999-12-01

In the light of medical evidence of the health risks associated with boxing, a watchful agnostic position among sport physicians is no longer justifiable. The normal activity in a boxing match places the athletes at risk of head injury, some of which may be difficult to detect and impossible to repair. This suggests that sport physicians and others expert in the prevention and diagnosis of such injuries should take a public stand against boxing, as other medical associations have. Although there is a need for continuing research into the health risks, doctors can in the interim take steps to increase public awareness of these risks. Sport physicians in particular can make a strong public statement by also ending their professional involvement with boxing. This need not be interpreted as paternalism; doctors are qualified neither to make laws nor to restrict private behaviour. Sport physicians are, however, well equipped to advise those who do make laws and those who choose to engage in boxing. In the end, because this stance against boxing will probably reduce the number of brain injuries in certain athletes, autonomy will be preserved, rather than restricted.

Sport medicine and the ethics of boxing

PubMed Central

Leclerc, S.; Herrera, C. D.

1999-01-01

In the light of medical evidence of the health risks associated with boxing, a watchful agnostic position among sport physicians is no longer justifiable. The normal activity in a boxing match places the athletes at risk of head injury, some of which may be difficult to detect and impossible to repair. This suggests that sport physicians and others expert in the prevention and diagnosis of such injuries should take a public stand against boxing, as other medical associations have. Although there is a need for continuing research into the health risks, doctors can in the interim take steps to increase public awareness of these risks. Sport physicians in particular can make a strong public statement by also ending their professional involvement with boxing. This need not be interpreted as paternalism; doctors are qualified neither to make laws nor to restrict private behaviour. Sport physicians are, however, well equipped to advise those who do make laws and those who choose to engage in boxing. In the end, because this stance against boxing will probably reduce the number of brain injuries in certain athletes, autonomy will be preserved, rather than restricted. 


 PMID:10597855

North American box turtles: A natural history

USGS Publications Warehouse

Dodd, C. Kenneth

2002-01-01

Once a familiar backyard visitor in many parts of the United States and Mexico, the box turtle is losing the battle against extinction. In North American Box Turtles, C. Kenneth Dodd, Jr., has written the first book-length natural history of the twelve species and subspecies of this endangered animal. This volume includes comprehensive information on the species’ evolution, behavior, courtship and reproduction, habitat use, diet, population structure, systematics, and disease. Special features include color photos of all species, subspecies, and their habitats; a simple identification guide to both living and fossil species; and a summary of information on fossil Terrapene and Native uses of box turtles. End-of-chapter sections highlight future research directions, including the need for long-term monitoring and observation of box turtles within their natural habitat and conservation applications. A glossary and a bibliography of literature on box turtles accompany the text.

Dynamics of TBP binding to the TATA box

NASA Astrophysics Data System (ADS)

Schluesche, Peter; Heiss, Gregor; Meisterernst, Michael; Lamb, Don C.

2008-02-01

Gene expression is highly controlled and regulated in living cells. One of the first steps in gene transcription is recognition of the promoter site by the TATA box Binding Protein (TBP). TBP recruits other transcriptions factors and eventually the RNA polymerase II to transcribe the DNA in mRNA. We developed a single pair Förster Resonance Energy Transfer (spFRET) assay to investigate the mechanism of gene regulation. Here, we apply this assay to investigate the initial binding process of TBP to the adenovirus major late (AdML) promoter site. From the spFRET measurements, we were able to identify two conformations of the TBP-DNA complex that correspond to TBP bound in the correct and the opposite orientation. Increased incubation times or the presence of the transcription factor TFIIA improved the alignment of TBP on the promoter site. Binding of TBP to the TATA box shows a rich dynamics with abrupt transitions between multiple FRET states. A frame-wise histogram analysis revealed the presence of at least six discrete states, showing that TBP binding is more complicated than previously thought. Hence, the spFRET assay is very sensitive to the conformation of the TBP-DNA complex and is very promising tool for investigating the pathway of TBP binding in detail.

Cardboard Boxes: Learning Concepts Galore!

ERIC Educational Resources Information Center

Warner, Laverne; Wilmoth, Linda

2007-01-01

Mrs. Keenan, a preschool teacher, observed her 3-year-old granddaughter Riley pull, tug, and stack piles of holiday boxes on the floor. She remembered that her child care director had suggested using boxes as a curriculum theme, but she hadn't given much thought about the idea until now. She said to herself, "I wonder if my children would be as…

Cosmetic Foot Surgery: Fashion's Pandora's Box

MedlinePlus

... Fashion’s Pandora’s Box? A A A | Print | Share Cosmetic Foot Surgery: Fashion’s Pandora’s Box? Foot and ankle surgeons warn ... extreme and imprudent as it may sound, the cosmetic surgery craze is not just for faces anymore—it ...

A New Set of ESTs from Chickpea (Cicer arietinum L.) Embryo Reveals Two Novel F-Box Genes, CarF-box_PP2 and CarF-box_LysM, with Potential Roles in Seed Development

PubMed Central

Gupta, Shefali; Garg, Vanika; Bhatia, Sabhyata

2015-01-01

Considering the economic importance of chickpea (C. arietinum L.) seeds, it is important to understand the mechanisms underlying seed development for which a cDNA library was constructed from 6 day old chickpea embryos. A total of 8,186 ESTs were obtained from which 4,048 high quality ESTs were assembled into 1,480 unigenes that majorly encoded genes involved in various metabolic and regulatory pathways. Of these, 95 ESTs were found to be involved in ubiquitination related protein degradation pathways and 12 ESTs coded specifically for putative F-box proteins. Differential transcript accumulation of these putative F-box genes was observed in chickpea tissues as evidenced by quantitative real-time PCR. Further, to explore the role of F-box proteins in chickpea seed development, two F-box genes were selected for molecular characterization. These were named as CarF-box_PP2 and CarF-box_LysM depending on their C-terminal domains, PP2 and LysM, respectively. Their highly conserved structures led us to predict their target substrates. Subcellular localization experiment revealed that CarF-box_PP2 was localized in the cytoplasm and CarF-box_LysM was localized in the nucleus. We demonstrated their physical interactions with SKP1 protein, which validated that they function as F-box proteins in the formation of SCF complexes. Sequence analysis of their promoter regions revealed certain seed specific cis-acting elements that may be regulating their preferential transcript accumulation in the seed. Overall, the study helped in expanding the EST database of chickpea, which was further used to identify two novel F-box genes having a potential role in seed development. PMID:25803812

Hypothalamic KLF4 mediates leptin's effects on food intake via AgRP

PubMed Central

Imbernon, Monica; Sanchez-Rebordelo, Estrella; Gallego, Rosalia; Gandara, Marina; Lear, Pamela; Lopez, Miguel; Dieguez, Carlos; Nogueiras, Ruben

2014-01-01

Krüppel-like factor 4 (KLF4) is a zinc-finger-type transcription factor expressed in a range of tissues that plays multiple functions. We report that hypothalamic KLF4 represents a new transcription factor specifically modulating agouti-related protein (AgRP) expression in vivo. Hypothalamic KLF4 colocalizes with AgRP neurons and is modulated by nutritional status and leptin. Over-expression of KLF4 in the hypothalamic arcuate nucleus (ARC) induces food intake and increases body weight through the specific stimulation of AgRP, as well as blunting leptin sensitivity in lean rats independent of forkhead box protein 01 (FoxO1). Down-regulation of KLF4 in the ARC inhibits fasting-induced food intake in both lean and diet-induced obese (DIO) rats. Silencing KLF4, however, does not, on its own, enhance peripheral leptin sensitivity in DIO rats. PMID:24944903

Hypothalamic KLF4 mediates leptin's effects on food intake via AgRP.

PubMed

Imbernon, Monica; Sanchez-Rebordelo, Estrella; Gallego, Rosalia; Gandara, Marina; Lear, Pamela; Lopez, Miguel; Dieguez, Carlos; Nogueiras, Ruben

2014-07-01

Krüppel-like factor 4 (KLF4) is a zinc-finger-type transcription factor expressed in a range of tissues that plays multiple functions. We report that hypothalamic KLF4 represents a new transcription factor specifically modulating agouti-related protein (AgRP) expression in vivo. Hypothalamic KLF4 colocalizes with AgRP neurons and is modulated by nutritional status and leptin. Over-expression of KLF4 in the hypothalamic arcuate nucleus (ARC) induces food intake and increases body weight through the specific stimulation of AgRP, as well as blunting leptin sensitivity in lean rats independent of forkhead box protein 01 (FoxO1). Down-regulation of KLF4 in the ARC inhibits fasting-induced food intake in both lean and diet-induced obese (DIO) rats. Silencing KLF4, however, does not, on its own, enhance peripheral leptin sensitivity in DIO rats.

Targeting the UPR transcription factor XBP1 protects against Huntington's disease through the regulation of FoxO1 and autophagy

PubMed Central

Vidal, Rene L.; Figueroa, Alicia; Court, Felipe A.; Thielen, Peter; Molina, Claudia; Wirth, Craig; Caballero, Benjamin; Kiffin, Roberta; Segura-Aguilar, Juan; Cuervo, Ana Maria; Glimcher, Laurie H.; Hetz, Claudio

2012-01-01

Mutations leading to expansion of a poly-glutamine track in Huntingtin (Htt) cause Huntington's disease (HD). Signs of endoplasmic reticulum (ER) stress have been recently reported in animal models of HD, associated with the activation of the unfolded protein response (UPR). Here we have investigated the functional contribution of ER stress to HD by targeting the expression of two main UPR transcription factors, XBP1 and ATF4 (activating transcription factor 4), in full-length mutant Huntingtin (mHtt) transgenic mice. XBP1-deficient mice were more resistant to developing disease features, associated with improved neuronal survival and motor performance, and a drastic decrease in mHtt levels. The protective effects of XBP1 deficiency were associated with enhanced macroautophagy in both cellular and animal models of HD. In contrast, ATF4 deficiency did not alter mHtt levels. Although, XBP1 mRNA splicing was observed in the striatum of HD transgenic brains, no changes in the levels of classical ER stress markers were detected in symptomatic animals. At the mechanistic level, we observed that XBP1 deficiency led to augmented expression of Forkhead box O1 (FoxO1), a key transcription factor regulating autophagy in neurons. In agreement with this finding, ectopic expression of FoxO1 enhanced autophagy and mHtt clearance in vitro. Our results provide strong evidence supporting an involvement of XBP1 in HD pathogenesis probably due to an ER stress-independent mechanism involving the control of FoxO1 and autophagy levels. PMID:22337954

Increased expression of high mobility group box protein 1 and vascular endothelial growth factor in placenta previa.

PubMed

Xie, Han; Qiao, Ping; Lu, Yi; Li, Ying; Tang, Yuping; Huang, Yiying; Bao, Yirong; Ying, Hao

2017-12-01

Placenta previa is often associated with preterm delivery, reduced birth weight, a higher frequency of placental accreta and postpartum haemorrhage, and increased likelihood of blood transfusion. The present study aimed to examine the expression of high mobility group box protein 1 (HMGB1) in the placenta of women with or without placenta previa. The study group consisted of placental tissues obtained from women with or without placenta previa. The expression levels of HMGB1 and vascular endothelial growth factor (VEGF) were evaluated in the placental tissues using reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemistry. The mRNA expression levels of HMGB1 and VEGF were significantly increased in the placenta previa group compared with in the normal group. In addition, the placenta previa group exhibited increased HMGB1 and VEGF staining in vascular endothelial cells and trophoblasts. There were no significant differences in the expression of HMGB1 or VEGF between groups with or without placenta accreta or postpartum haemorrhage. The present study hypothesised that the increased expression of HMGB1 in the placenta may be associated with the pathogenesis of placenta previa by regulating the expression of the proangiogenic factor VEGF.

KELCH F-BOX protein positively influences Arabidopsis seed germination by targeting PHYTOCHROME-INTERACTING FACTOR1

USDA-ARS?s Scientific Manuscript database

Seeds employ sensory systems that assess various environmental cues over time to maximize the successful transition from embryo to seedling. Here, we show that the Arabidopsis F-Box protein Cold Temperature-Germinating (CTG)-10, identified by activation tagging, is a positive regulator during this p...

MADS goes genomic in conifers: towards determining the ancestral set of MADS-box genes in seed plants.

PubMed

Gramzow, Lydia; Weilandt, Lisa; Theißen, Günter

2014-11-01

MADS-box genes comprise a gene family coding for transcription factors. This gene family expanded greatly during land plant evolution such that the number of MADS-box genes ranges from one or two in green algae to around 100 in angiosperms. Given the crucial functions of MADS-box genes for nearly all aspects of plant development, the expansion of this gene family probably contributed to the increasing complexity of plants. However, the expansion of MADS-box genes during one important step of land plant evolution, namely the origin of seed plants, remains poorly understood due to the previous lack of whole-genome data for gymnosperms. The newly available genome sequences of Picea abies, Picea glauca and Pinus taeda were used to identify the complete set of MADS-box genes in these conifers. In addition, MADS-box genes were identified in the growing number of transcriptomes available for gymnosperms. With these datasets, phylogenies were constructed to determine the ancestral set of MADS-box genes of seed plants and to infer the ancestral functions of these genes. Type I MADS-box genes are under-represented in gymnosperms and only a minimum of two Type I MADS-box genes have been present in the most recent common ancestor (MRCA) of seed plants. In contrast, a large number of Type II MADS-box genes were found in gymnosperms. The MRCA of extant seed plants probably possessed at least 11-14 Type II MADS-box genes. In gymnosperms two duplications of Type II MADS-box genes were found, such that the MRCA of extant gymnosperms had at least 14-16 Type II MADS-box genes. The implied ancestral set of MADS-box genes for seed plants shows simplicity for Type I MADS-box genes and remarkable complexity for Type II MADS-box genes in terms of phylogeny and putative functions. The analysis of transcriptome data reveals that gymnosperm MADS-box genes are expressed in a great variety of tissues, indicating diverse roles of MADS-box genes for the development of gymnosperms. This study is

MADS goes genomic in conifers: towards determining the ancestral set of MADS-box genes in seed plants

PubMed Central

Gramzow, Lydia; Weilandt, Lisa; Theißen, Günter

2014-01-01

Background and Aims MADS-box genes comprise a gene family coding for transcription factors. This gene family expanded greatly during land plant evolution such that the number of MADS-box genes ranges from one or two in green algae to around 100 in angiosperms. Given the crucial functions of MADS-box genes for nearly all aspects of plant development, the expansion of this gene family probably contributed to the increasing complexity of plants. However, the expansion of MADS-box genes during one important step of land plant evolution, namely the origin of seed plants, remains poorly understood due to the previous lack of whole-genome data for gymnosperms. Methods The newly available genome sequences of Picea abies, Picea glauca and Pinus taeda were used to identify the complete set of MADS-box genes in these conifers. In addition, MADS-box genes were identified in the growing number of transcriptomes available for gymnosperms. With these datasets, phylogenies were constructed to determine the ancestral set of MADS-box genes of seed plants and to infer the ancestral functions of these genes. Key Results Type I MADS-box genes are under-represented in gymnosperms and only a minimum of two Type I MADS-box genes have been present in the most recent common ancestor (MRCA) of seed plants. In contrast, a large number of Type II MADS-box genes were found in gymnosperms. The MRCA of extant seed plants probably possessed at least 11–14 Type II MADS-box genes. In gymnosperms two duplications of Type II MADS-box genes were found, such that the MRCA of extant gymnosperms had at least 14–16 Type II MADS-box genes. Conclusions The implied ancestral set of MADS-box genes for seed plants shows simplicity for Type I MADS-box genes and remarkable complexity for Type II MADS-box genes in terms of phylogeny and putative functions. The analysis of transcriptome data reveals that gymnosperm MADS-box genes are expressed in a great variety of tissues, indicating diverse roles of MADS-box

Models for nearly every occasion: Part I - One box models.

PubMed

Hewett, Paul; Ganser, Gary H

2017-01-01

The standard "well mixed room," "one box" model cannot be used to predict occupational exposures whenever the scenario involves the use of local controls. New "constant emission" one box models are proposed that permit either local exhaust or local exhaust with filtered return, coupled with general room ventilation or the recirculation of a portion of the general room exhaust. New "two box" models are presented in Part II of this series. Both steady state and transient models were developed. The steady state equation for each model, including the standard one box steady state model, is augmented with an additional factor reflecting the fraction of time the substance was generated during each task. This addition allows the easy calculation of the average exposure for cyclic and irregular emission patterns, provided the starting and ending concentrations are zero or near zero, or the cumulative time across all tasks is long (e.g., several tasks to a full shift). The new models introduce additional variables, such as the efficiency of the local exhaust to immediately capture freshly generated contaminant and the filtration efficiency whenever filtered exhaust is returned to the workspace. Many of the model variables are knowable (e.g., room volume and ventilation rate). A structured procedure for calibrating a model to a work scenario is introduced that can be applied to both continuous and cyclic processes. The "calibration" procedure generates estimates of the generation rate and all of remaining unknown model variables.

Light directs zebrafish period2 expression via conserved D and E boxes.

PubMed

Vatine, Gad; Vallone, Daniela; Appelbaum, Lior; Mracek, Philipp; Ben-Moshe, Zohar; Lahiri, Kajori; Gothilf, Yoav; Foulkes, Nicholas S

2009-10-01

For most species, light represents the principal environmental signal for entraining the endogenous circadian clock. The zebrafish is a fascinating vertebrate model for studying this process since unlike mammals, direct exposure of most of its tissues to light leads to local clock entrainment. Importantly, light induces the expression of a set of genes including certain clock genes in most zebrafish cell types in vivo and in vitro. However, the mechanism linking light to gene expression remains poorly understood. To elucidate this key mechanism, here we focus on how light regulates transcription of the zebrafish period2 (per2) gene. Using transgenic fish and stably transfected cell line-based assays, we define a Light Responsive Module (LRM) within the per2 promoter. The LRM lies proximal to the transcription start site and is both necessary and sufficient for light-driven gene expression and also for a light-dependent circadian clock regulation. Curiously, the LRM sequence is strongly conserved in other vertebrate per2 genes, even in species lacking directly light-sensitive peripheral clocks. Furthermore, we reveal that the human LRM can substitute for the zebrafish LRM to confer light-regulated transcription in zebrafish cells. The LRM contains E- and D-box elements that are critical for its function. While the E-box directs circadian clock regulation by mediating BMAL/CLOCK activity, the D-box confers light-driven expression. The zebrafish homolog of the thyrotroph embryonic factor binds efficiently to the LRM D-box and transactivates expression. We demonstrate that tef mRNA levels are light inducible and that knock-down of tef expression attenuates light-driven transcription from the per2 promoter in vivo. Together, our results support a model where a light-dependent crosstalk between E- and D-box binding factors is a central determinant of per2 expression. These findings extend the general understanding of the mechanism whereby the clock is entrained by light

Retraction: Myostatin Induces Degradation of Sarcomeric Proteins through a Smad3 Signaling Mechanism During Skeletal Muscle Wasting

PubMed Central

Lokireddy, Sudarsanareddy; McFarlane, Craig; Ge, Xiaojia; Zhang, Huoming; Sze, Siu Kwan; Sharma, Mridula

2011-01-01

Ubiquitination-mediated proteolysis is a hallmark of skeletal muscle wasting manifested in response to negative growth factors, including myostatin. Thus, the characterization of signaling mechanisms that induce the ubiquitination of intracellular and sarcomeric proteins during skeletal muscle wasting is of great importance. We have recently characterized myostatin as a potent negative regulator of myogenesis and further demonstrated that elevated levels of myostatin in circulation results in the up-regulation of the muscle-specific E3 ligases, Atrogin-1 and muscle ring finger protein 1 (MuRF1). However, the exact signaling mechanisms by which myostatin regulates the expression of Atrogin-1 and MuRF1, as well as the proteins targeted for degradation in response to excess myostatin, remain to be elucidated. In this report, we have demonstrated that myostatin signals through Smad3 (mothers against decapentaplegic homolog 3) to activate forkhead box O1 and Atrogin-1 expression, which further promotes the ubiquitination and subsequent proteasome-mediated degradation of critical sarcomeric proteins. Smad3 signaling was dispensable for myostatin-dependent overexpression of MuRF1. Although down-regulation of Atrogin-1 expression rescued approximately 80% of sarcomeric protein loss induced by myostatin, only about 20% rescue was seen when MuRF1 was silenced, implicating that Atrogin-1 is the predominant E3 ligase through which myostatin manifests skeletal muscle wasting. Furthermore, we have highlighted that Atrogin-1 not only associates with myosin heavy and light chain, but it also ubiquitinates these sarcomeric proteins. Based on presented data we propose a model whereby myostatin induces skeletal muscle wasting through targeting sarcomeric proteins via Smad3-mediated up-regulation of Atrogin-1 and forkhead box O1. PMID:21964591

SVP-like MADS-box protein from Carya cathayensis forms higher-order complexes.

PubMed

Wang, Jingjing; Hou, Chuanming; Huang, Jianqin; Wang, Zhengjia; Xu, Yingwu

2015-03-01

To properly regulate plant flowering time and construct floral pattern, MADS-domain containing transcription factors must form multimers including homo- and hetero-dimers. They are also active in forming hetero-higher-order complexes with three to five different molecules. However, it is not well known if a MADS-box protein can also form homo-higher-order complex. In this study a biochemical approach is utilized to provide insight into the complex formation for an SVP-like MADS-box protein cloned from hickory. The results indicated that the protein is a heterogeneous higher-order complex with the peak population containing over 20 monomers. Y2H verified the protein to form homo-complex in yeast cells. Western blot of the hickory floral bud sample revealed that the protein exists in higher-order polymers in native. Deletion assays indicated that the flexible C-terminal residues are mainly responsible for the higher-order polymer formation and the heterogeneity. Current results provide direct biochemical evidences for an active MADS-box protein to be a high order complex, much higher than a quartermeric polymer. Analysis suggests that a MADS-box subset may be able to self-assemble into large complexes, and thereby differentiate one subfamily from the other in a higher-order structural manner. Present result is a valuable supplement to the action of mechanism for MADS-box proteins in plant development. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Neurochemical aftermath of amateur boxing.

PubMed

Zetterberg, Henrik; Hietala, M Albert; Jonsson, Michael; Andreasen, Niels; Styrud, Ewa; Karlsson, Ingvar; Edman, Ake; Popa, Cornel; Rasulzada, Abdullah; Wahlund, Lars-Olof; Mehta, Pankaj D; Rosengren, Lars; Blennow, Kaj; Wallin, Anders

2006-09-01

Little solid information is available on the possible risks for neuronal injury in amateur boxing. To determine whether amateur boxing and severity of hits are associated with elevated levels of biochemical markers for neuronal injury in cerebrospinal fluid. Longitudinal study. Referral center specializing in evaluation of neurodegenerative disorders. Fourteen amateur boxers (11 men and 3 women) and 10 healthy male nonathletic control subjects. The boxers underwent lumbar puncture 7 to 10 days and 3 months after a bout. The control subjects underwent LP once. Neurofilament light protein, total tau, glial fibrillary acidic protein, phosphorylated tau, and beta-amyloid protein 1-40 (Abeta([1-40])) and 1-42 (Abeta([1-42])) concentrations in cerebrospinal fluid were measured. Increased levels after a bout compared with after 3 months of rest from boxing were found for 2 markers for neuronal and axonal injury, neurofilament light protein (mean +/- SD, 845 +/- 1140 ng/L vs 208 +/- 108 ng/L; P = .008) and total tau (mean +/- SD, 449 +/- 176 ng/L vs 306 +/- 78 ng/L; P = .006), and for the astroglial injury marker glial fibrillary acidic protein (mean +/- SD, 541 +/- 199 ng/L vs 405 +/- 138 ng/L; P = .003). The increase was significantly higher among boxers who had received many hits (>15) or high-impact hits to the head compared with boxers who reported few hits. In the boxers, concentrations of neurofilament light protein and glial fibrillary acidic protein, but not total tau, were significantly elevated after a bout compared with the nonathletic control subjects. With the exception of neurofilament light protein, there were no significant differences between boxers after 3 months of rest from boxing and the nonathletic control subjects. Amateur boxing is associated with acute neuronal and astroglial injury. If verified in longitudinal studies with extensive follow-up regarding the clinical outcome, analyses of cerebrospinal fluid may provide a scientific basis for

A winged helix forkhead (FOXD2) tunes sensitivity to cAMP in T lymphocytes through regulation of cAMP-dependent protein kinase RIalpha.

PubMed

Johansson, C Christian; Dahle, Maria K; Blomqvist, Sandra Rodrigo; Grønning, Line M; Aandahl, Einar M; Enerbäck, Sven; Taskén, Kjetil

2003-05-09

Forkhead/winged helix (FOX) transcription factors are essential for control of the cell cycle and metabolism. Here, we show that spleens from Mf2-/- (FOXD2-/-) mice have reduced mRNA (50%) and protein (35%) levels of the RIalpha subunit of the cAMP-dependent protein kinase. In T cells from Mf2-/- mice, reduced levels of RIalpha translates functionally into approximately 2-fold less sensitivity to cAMP-mediated inhibition of proliferation triggered through the T cell receptor-CD3 complex. In Jurkat T cells, FOXD2 overexpression increased the endogenous levels of RIalpha through induction of the RIalpha1b promoter. FOXD2 overexpression also increased the sensitivity of the promoter to cAMP. Finally, co-expression experiments demonstrated that protein kinase Balpha/Akt1 work together with FOXD2 to induce the RIalpha1b promoter (10-fold) and increase endogenous RIalpha protein levels further. Taken together, our data indicate that FOXD2 is a physiological regulator of the RIalpha1b promoter in vivo working synergistically with protein kinase B to induce cAMP-dependent protein kinase RIalpha expression, which increases cAMP sensitivity and sets the threshold for cAMP-mediated negative modulation of T cell activation.

30 CFR 18.49 - Connection boxes on machines.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Connection boxes on machines. 18.49 Section 18... Design Requirements § 18.49 Connection boxes on machines. Connection boxes used to facilitate replacement of cables or machine components shall be explosion-proof. Portable-cable terminals on cable reels...

Can the design of glove dispensing boxes influence glove contamination?

PubMed

Assadian, O; Leaper, D J; Kramer, A; Ousey, K J

2016-11-01

Few studies have explored the microbial contamination of glove boxes in clinical settings. The objective of this observational study was to investigate whether a new glove packaging system in which single gloves are dispensed vertically, cuff end first, has lower levels of contamination on the gloves and on the surface around the box aperture compared with conventional glove boxes. Seven participating sites were provided with vertical glove dispensing systems (modified boxes) and conventional boxes. Before opening glove boxes, the surface around the aperture was sampled microbiologically to establish baseline levels of superficial contamination. Once the glove boxes were opened, the first pair of gloves in each box was sampled for viable bacteria. Thereafter, testing sites were visited on a weekly basis over a period of six weeks and the same microbiological assessments were made. The surface near the aperture of the modified boxes became significantly less contaminated over time compared with the conventional boxes (P<0.001), with an average of 46.7% less contamination around the aperture. Overall, gloves from modified boxes showed significantly less colony-forming unit contamination than gloves from conventional boxes (P<0.001). Comparing all sites over the entire six-week period, gloves from modified boxes had 88.9% less bacterial contamination. This simple improvement to glove box design reduces contamination of unused gloves. Such modifications could decrease the risk of microbial cross-transmission in settings that use gloves. However, such advantages do not substitute for strict hand hygiene compliance and appropriate use of non-sterile, single-use gloves. Copyright © 2016 The Healthcare Infection Society. All rights reserved.

Box Plots in the Australian Curriculum

ERIC Educational Resources Information Center

Watson, Jane M.

2012-01-01

This article compares the definition of "box plot" as used in the "Australian Curriculum: Mathematics" with other definitions used in the education community; describes the difficulties students experience when dealing with box plots; and discusses the elaboration that is necessary to enable teachers to develop the knowledge…

Design procedures for fiber composite box beams

NASA Technical Reports Server (NTRS)

Chamis, Cristos C.; Murthy, Pappu L. N.

1989-01-01

Step-by-step procedures are described which can be used for the preliminary design of fiber composite box beams subjected to combined loadings. These procedures include a collection of approximate closed-form equations so that all the required calculations can be performed using pocket calculators. Included is an illustrative example of a tapered cantilever box beam subjected to combined loads. The box beam is designed to satisfy strength, displacement, buckling, and frequency requirements.

Design Procedures for Fiber Composite Box Beams

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Murthy, Pappu L. N.

1988-01-01

Step-by-step procedures are described which can be used for the preliminary design of fiber composite box beams subjected to combined loadings. These procedures include a collection of approximate closed-form equations so that all the required calculations can be performed using pocket calculators. Included is an illustrated example of a tapered cantilever box beam subjected to combined loads. The box beam is designed to satisfy strength, displacement, buckling, and frequency requirements.

ArduiPod Box: a low-cost and open-source Skinner box using an iPod Touch and an Arduino microcontroller.

PubMed

Pineño, Oskar

2014-03-01

This article introduces the ArduiPod Box, an open-source device built using two main components (i.e., an iPod Touch and an Arduino microcontroller), developed as a low-cost alternative to the standard operant conditioning chamber, or "Skinner box." Because of its affordability, the ArduiPod Box provides an opportunity for educational institutions with small budgets seeking to set up animal laboratories for research and instructional purposes. A pilot experiment is also presented, which shows that the ArduiPod Box, in spite of its extraordinary simplicity, can be effectively used to study animal learning and behavior.

NFI Transcription Factors Interact with FOXA1 to Regulate Prostate-Specific Gene Expression

PubMed Central

Elliott, Amicia D.; DeGraff, David J.; Anderson, Philip D.; Anumanthan, Govindaraj; Yamashita, Hironobu; Sun, Qian; Friedman, David B.; Hachey, David L.; Yu, Xiuping; Sheehan, Jonathan H.; Ahn, Jung-Mo; Raj, Ganesh V.; Piston, David W.; Gronostajski, Richard M.; Matusik, Robert J.

2014-01-01

Androgen receptor (AR) action throughout prostate development and in maintenance of the prostatic epithelium is partly controlled by interactions between AR and forkhead box (FOX) transcription factors, particularly FOXA1. We sought to identity additional FOXA1 binding partners that may mediate prostate-specific gene expression. Here we identify the nuclear factor I (NFI) family of transcription factors as novel FOXA1 binding proteins. All four family members (NFIA, NFIB, NFIC, and NFIX) can interact with FOXA1, and knockdown studies in androgen-dependent LNCaP cells determined that modulating expression of NFI family members results in changes in AR target gene expression. This effect is probably mediated by binding of NFI family members to AR target gene promoters, because chromatin immunoprecipitation (ChIP) studies found that NFIB bound to the prostate-specific antigen enhancer. Förster resonance energy transfer studies revealed that FOXA1 is capable of bringing AR and NFIX into proximity, indicating that FOXA1 facilitates the AR and NFI interaction by bridging the complex. To determine the extent to which NFI family members regulate AR/FOXA1 target genes, motif analysis of publicly available data for ChIP followed by sequencing was undertaken. This analysis revealed that 34.4% of peaks bound by AR and FOXA1 contain NFI binding sites. Validation of 8 of these peaks by ChIP revealed that NFI family members can bind 6 of these predicted genomic elements, and 4 of the 8 associated genes undergo gene expression changes as a result of individual NFI knockdown. These observations suggest that NFI regulation of FOXA1/AR action is a frequent event, with individual family members playing distinct roles in AR target gene expression. PMID:24801505

Brane boxes, anomalies, bending, and tadpoles

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

Leigh, R.G.; Rozali, M.

1999-01-01

Certain classes of chiral four-dimensional gauge theories may be obtained as the world volume theories of D5-branes are suspended between networks of NS5-branes, the so-called brane box models. In this paper, we derive the stringy consistency conditions placed on these models, and show that they are equivalent to an anomaly cancellation of the gauge theories. We derive these conditions in the orbifold theories which are {ital T} dual to the elliptic brane box models. Specifically, we show that the expression for tadpoles for unphysical twisted Ramond-Ramond 4-form fields in the orbifold theory are proportional to the gauge anomalies of themore » brane box theory. Thus string consistency is equivalent to world volume gauge anomaly cancellation. Furthermore, we find additional cylinder amplitudes which give the {beta} functions of the gauge theory. We show how these correspond to bending of the NS-branes in the brane box theory. {copyright} {ital 1998} {ital The American Physical Society}« less

Light Therapy Boxes for Seasonal Affective Disorder

MedlinePlus

Seasonal affective disorder treatment: Choosing a light therapy box Light therapy boxes can offer an effective treatment for seasonal affective disorder. Features such as light intensity, safety, cost and ...

21 CFR 864.9185 - Blood grouping view box.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood grouping view box. 864.9185 Section 864.9185...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Products Used In Establishments That Manufacture Blood and Blood Products § 864.9185 Blood grouping view box. (a) Identification. A blood grouping view box...

47 CFR 90.241 - Radio call box operations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Safety Pool for operation of radio call boxes to be used by the public to request fire, police, ambulance... Public Safety Pool for highway call box systems subject to the following requirements: (1) Call box...) above the ground, the natural formation, or the existing man-made structure (other than an antenna...

47 CFR 90.241 - Radio call box operations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Safety Pool for operation of radio call boxes to be used by the public to request fire, police, ambulance... Public Safety Pool for highway call box systems subject to the following requirements: (1) Call box...) above the ground, the natural formation, or the existing man-made structure (other than an antenna...

21 CFR 864.9185 - Blood grouping view box.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Blood grouping view box. 864.9185 Section 864.9185...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Products Used In Establishments That Manufacture Blood and Blood Products § 864.9185 Blood grouping view box. (a) Identification. A blood grouping view box...

21 CFR 864.9185 - Blood grouping view box.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Blood grouping view box. 864.9185 Section 864.9185...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Products Used In Establishments That Manufacture Blood and Blood Products § 864.9185 Blood grouping view box. (a) Identification. A blood grouping view box...

21 CFR 864.9185 - Blood grouping view box.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Blood grouping view box. 864.9185 Section 864.9185...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Products Used In Establishments That Manufacture Blood and Blood Products § 864.9185 Blood grouping view box. (a) Identification. A blood grouping view box...

21 CFR 864.9185 - Blood grouping view box.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Blood grouping view box. 864.9185 Section 864.9185...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Products Used In Establishments That Manufacture Blood and Blood Products § 864.9185 Blood grouping view box. (a) Identification. A blood grouping view box...

Therapeutic Strategies against Cyclin E1-Amplified Ovarian Cancers

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0566 TITLE : Therapeutic Strategies against Cyclin E1-Amplified Ovarian Cancers PRINCIPAL INVESTIGATOR: Dipanjan...RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2016 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2015 - 29 Sep 2016 4. TITLE AND...amplification, Homologous Recombination, Platinum analogues, MicroRNAs, Heat shock protein 90 inhibitors, Forkhead box protein M1, Retinoblastoma 16

NSs Virulence Factor of Rift Valley Fever Virus Engages the F-Box Proteins FBXW11 and β-TRCP1 To Degrade the Antiviral Protein Kinase PKR.

PubMed

Kainulainen, Markus; Lau, Simone; Samuel, Charles E; Hornung, Veit; Weber, Friedemann

2016-07-01

Rift Valley fever virus (RVFV, family Bunyaviridae, genus Phlebovirus) is a relevant pathogen of both humans and livestock in Africa. The nonstructural protein NSs is a major virulence factor known to suppress the type I interferon (IFN) response by inhibiting host cell transcription and by proteasomal degradation of a major antiviral IFN effector, the translation-inhibiting protein kinase PKR. Here, we identified components of the modular SCF (Skp1, Cul1, F-box protein)-type E3 ubiquitin ligases as mediators of PKR destruction by NSs. Small interfering RNAs (siRNAs) against the conserved SCF subunit Skp1 protected PKR from NSs-mediated degradation. Consequently, RVFV replication was severely reduced in Skp1-depleted cells when PKR was present. SCF complexes have a variable F-box protein subunit that determines substrate specificity for ubiquitination. We performed an siRNA screen for all (about 70) human F-box proteins and found FBXW11 to be involved in PKR degradation. The partial stabilization of PKR by FBXW11 depletion upregulated PKR autophosphorylation and phosphorylation of the PKR substrate eIF2α and caused a shutoff of host cell protein synthesis in RVFV-infected cells. To maximally protect PKR from the action of NSs, knockdown of structurally and functionally related FBXW1 (also known as β-TRCP1), in addition to FBXW11 deletion, was necessary. Consequently, NSs was found to interact with both FBXW11 and β-TRCP1. Thus, NSs eliminates the antiviral kinase PKR by recruitment of SCF-type E3 ubiquitin ligases containing FBXW11 and β-TRCP1 as substrate recognition subunits. This antagonism of PKR by NSs is essential for efficient RVFV replication in mammalian cells. Rift Valley fever virus is a pathogen of humans and animals that has the potential to spread from Africa and the Arabian Peninsula to other regions. A major virulence mechanism is the proteasomal degradation of the antiviral kinase PKR by the viral protein NSs. Here, we demonstrate that NSs

NSs Virulence Factor of Rift Valley Fever Virus Engages the F-Box Proteins FBXW11 and β-TRCP1 To Degrade the Antiviral Protein Kinase PKR

PubMed Central

Kainulainen, Markus; Lau, Simone; Samuel, Charles E.; Hornung, Veit

2016-01-01

ABSTRACT Rift Valley fever virus (RVFV, family Bunyaviridae, genus Phlebovirus) is a relevant pathogen of both humans and livestock in Africa. The nonstructural protein NSs is a major virulence factor known to suppress the type I interferon (IFN) response by inhibiting host cell transcription and by proteasomal degradation of a major antiviral IFN effector, the translation-inhibiting protein kinase PKR. Here, we identified components of the modular SCF (Skp1, Cul1, F-box protein)-type E3 ubiquitin ligases as mediators of PKR destruction by NSs. Small interfering RNAs (siRNAs) against the conserved SCF subunit Skp1 protected PKR from NSs-mediated degradation. Consequently, RVFV replication was severely reduced in Skp1-depleted cells when PKR was present. SCF complexes have a variable F-box protein subunit that determines substrate specificity for ubiquitination. We performed an siRNA screen for all (about 70) human F-box proteins and found FBXW11 to be involved in PKR degradation. The partial stabilization of PKR by FBXW11 depletion upregulated PKR autophosphorylation and phosphorylation of the PKR substrate eIF2α and caused a shutoff of host cell protein synthesis in RVFV-infected cells. To maximally protect PKR from the action of NSs, knockdown of structurally and functionally related FBXW1 (also known as β-TRCP1), in addition to FBXW11 deletion, was necessary. Consequently, NSs was found to interact with both FBXW11 and β-TRCP1. Thus, NSs eliminates the antiviral kinase PKR by recruitment of SCF-type E3 ubiquitin ligases containing FBXW11 and β-TRCP1 as substrate recognition subunits. This antagonism of PKR by NSs is essential for efficient RVFV replication in mammalian cells. IMPORTANCE Rift Valley fever virus is a pathogen of humans and animals that has the potential to spread from Africa and the Arabian Peninsula to other regions. A major virulence mechanism is the proteasomal degradation of the antiviral kinase PKR by the viral protein NSs. Here, we

Simplified method for the transverse bending analysis of twin celled concrete box girder bridges

NASA Astrophysics Data System (ADS)

Chithra, J.; Nagarajan, Praveen; S, Sajith A.

2018-03-01

Box girder bridges are one of the best options for bridges with span more than 25 m. For the study of these bridges, three-dimensional finite element analysis is the best suited method. However, performing three-dimensional analysis for routine design is difficult as well as time consuming. Also, software used for the three-dimensional analysis are very expensive. Hence designers resort to simplified analysis for predicting longitudinal and transverse bending moments. Among the many analytical methods used to find the transverse bending moments, SFA is the simplest and widely used in design offices. Results from simplified frame analysis can be used for the preliminary analysis of the concrete box girder bridges.From the review of literatures, it is found that majority of the work done using SFA is restricted to the analysis of single cell box girder bridges. Not much work has been done on the analysis multi-cell concrete box girder bridges. In this present study, a double cell concrete box girder bridge is chosen. The bridge is modelled using three- dimensional finite element software and the results are then compared with the simplified frame analysis. The study mainly focuses on establishing correction factors for transverse bending moment values obtained from SFA.

Validation of a noninvasive system for measuring head acceleration for use during boxing competition.

PubMed

Beckwith, Jonathan G; Chu, Jeffrey J; Greenwald, Richard M

2007-08-01

Although the epidemiology and mechanics of concussion in sports have been investigated for many years, the biomechanical factors that contribute to mild traumatic brain injury remain unclear because of the difficulties in measuring impact events in the field. The purpose of this study was to validate an instrumented boxing headgear (IBH) that can be used to measure impact severity and location during play. The instrumented boxing headgear data were processed to determine linear and rotational acceleration at the head center of gravity, impact location, and impact severity metrics, such as the Head Injury Criterion (HIC) and Gadd Severity Index (GSI). The instrumented boxing headgear was fitted to a Hybrid III (HIII) head form and impacted with a weighted pendulum to characterize accuracy and repeatability. Fifty-six impacts over 3 speeds and 5 locations were used to simulate blows most commonly observed in boxing. A high correlation between the HIII and instrumented boxing headgear was established for peak linear and rotational acceleration (r2= 0.91), HIC (r2 = 0.88), and GSI (r2 = 0.89). Mean location error was 9.7 +/- 5.2 masculine. Based on this study, the IBH is a valid system for measuring head acceleration and impact location that can be integrated into training and competition.

Boxing Injuries from an Instructional Program.

ERIC Educational Resources Information Center

Welch, Michael J.; And Others

1986-01-01

This paper describes the safeguards as well as the injury pattern of the boxing program at the US Military Academy at West Point from 1983 to 1985. About 2,100 cadets received boxing instruction during this period with an injury rate of less than four percent. (Author/MT)

Genome-wide identification and characterization of Fox genes in the silkworm, Bombyx mori.

PubMed

Song, JiangBo; Li, ZhiQuan; Tong, XiaoLing; Chen, Cong; Chen, Min; Meng, Gang; Chen, Peng; Li, ChunLin; Xin, YaQun; Gai, TingTing; Dai, FangYin; Lu, Cheng

2015-09-01

The forkhead box (Fox) transcription factor family has a characteristic of forkhead domain, a winged DNA-binding domain. The Fox genes have been classified into 23 subfamilies, designated FoxA to FoxS, of which the FoxR and FoxS subfamilies are specific to vertebrates. In this review, using whole-genome scanning, we identified 17 distinct Fox genes distributed on 13 chromosomes of the silkworm, Bombyx mori. A phylogenetic tree showed that the silkworm Fox genes could be classified into 13 subfamilies. The FoxK subfamily is specifically absent from the silkworm, although it is present in other lepidopteran insects, including Danaus plexippus and Heliconius melpomene. Microarray data revealed that the Fox genes have distinct expression patterns in the tissues on day 3 of the 5th instar larva. A Gene Ontology analysis suggested that the Fox genes have roles in cellular components, molecular functions, and biological processes, except in pore complex biogenesis. An analysis of the selective pressure on the proteins indicated that most of the amino acid sites in the Fox proteins are undergoing strong purifying selection. Here, we summarize the general characteristics of the Fox genes in the silkworm, which should support further functional studies of the silkworm Fox proteins.

AMP sensing by DEAD-box RNA helicases

PubMed Central

Putnam, Andrea A.; Jankowsky, Eckhard

2013-01-01

In eukaryotes, cellular levels of adenosine monophosphate (AMP) signal the metabolic state of the cell. AMP concentrations increase significantly upon metabolic stress, such as glucose deprivation in yeast. Here we show that several DEAD-box RNA helicases are sensitive to AMP, which is not produced during ATP hydrolysis by these enzymes. We find that AMP potently inhibits RNA binding and unwinding by the yeast DEAD-box helicases Ded1p, Mss116p, and eIF4A. However, the yeast DEAD-box helicases Sub2p and Dbp5p are not inhibited by AMP. Our observations identify a subset of DEAD-box helicases as enzymes with the capacity to directly link changes in AMP concentrations to RNA metabolism. PMID:23702290

Slat Heater Boxes for Thermal Vacuum Testing

NASA Technical Reports Server (NTRS)

Ungar, Eugene

2003-01-01

Slat heater boxes have been invented for controlling the sink temperatures of objects under test in a thermal vacuum chamber, the walls of which are cooled to the temperature of liquid nitrogen. A slat heater box (see Figure 1) includes a framework of struts that support electrically heated slats that are coated with a high-emissivity optically gray paint. The slats can be grouped together into heater zones for the purpose of maintaining an even temperature within each side. The sink temperature of an object under test is defined as the steady-state temperature of the object in the vacuum/ radiative environment during the absence of any internal heat source or sink. The slat heater box makes it possible to closely control the radiation environment to obtain a desired sink temperature. The slat heater box is placed inside the cold thermal vacuum chamber, and the object under test is placed inside (but not in contact with) the slat heater box. The slat heaters occupy about a third of the field of view from any point on the surface of the object under test, the remainder of the field of view being occupied by the cold chamber wall. Thus, the radiation environment is established by the combined effects of the slat heater box and the cold chamber wall. Given (1) the temperature of the chamber wall, (2) the fractions of the field of view occupied by the chamber wall and the slat heater box, and (3) the emissivities of the slats, chamber wall, and the surface of object under test, the slat temperature required to maintain a desired sink temperature can be calculated by solving the equations of gray-body radiation for the steady-state adiabatic case (equal absorption and emission by the object under test). Slat heater boxes offer an important advantage over the infrared lamps that have been previously used to obtain desired sink temperatures: In comparison with an infrared lamp, a slat heater box provides a greater degree of sink temperature uniformity for a test

Prohibiting Headgear for Safety in Amateur Boxing? Opinion of the Canadian Boxing Community: an Online Poll.

PubMed

Dickinson, Philip; Rempel, Philip

In 2013, the Amateur International Boxing Association (AIBA) introduced a rule banning headgear for male-senior open class boxers during competition. The AIBA has defended the rule change as motivated by safety and supported by internal unpublished studies. As a result, in 2018, the AIBA plans to universally prohibit headgear in competition: for all competitors (male and female), all ages and all levels. Within Canada, this ruling has generated controversy in the boxing community, yet there has been no overall measure of opinion. To address this, we instituted a voluntary, anonymous, online open-access poll to allow members of the boxing community to express their stance on headgear use in competition. In total, 636 responses were received. A total of 71.5 % of Canadian respondents believed headgear should be mandatory at all levels. Only 5.8 % agreed that headgear should be prohibited, as planned for 2018. Estimating results on a representative breakdown of boxing membership in Canada, a similar pattern emerged, whereby 68.2 % concurred with mandatory headgear while only 4.95 % supported its prohibition. Parents of boxers were almost unanimously against banning headgear, stating they would change sports as a result. Similarly, only 1.7 % of women believed headgear should be prohibited. The consensus of the Canadian boxing community largely opposes the rule changes that the AIBA has implemented. The results highlight risks posed to the long-term viability of the sport, if significant grassroots safety concerns are disregarded.

Redundant CArG Box Cis-motif Activity Mediates SHATTERPROOF2 Transcriptional Regulation during Arabidopsis thaliana Gynoecium Development

PubMed Central

Sehra, Bhupinder; Franks, Robert G.

2017-01-01

In the Arabidopsis thaliana seed pod, pod shatter and seed dispersal properties are in part determined by the development of a longitudinally orientated dehiscence zone (DZ) that derives from cells of the gynoecial valve margin (VM). Transcriptional regulation of the MADS protein encoding transcription factors genes SHATTERPROOF1 (SHP1) and SHATTERPROOF2 (SHP2) are critical for proper VM identity specification and later on for DZ development. Current models of SHP1 and SHP2 regulation indicate that the transcription factors FRUITFULL (FUL) and REPLUMLESS (RPL) repress these SHP genes in the developing valve and replum domains, respectively. Thus the expression of the SHP genes is restricted to the VM. FUL encodes a MADS-box containing transcription factor that is predicted to act through CArG-box containing cis-regulatory motifs. Here we delimit functional modules within the SHP2 cis-regulatory region and examine the functional importance of CArG box motifs within these regulatory regions. We have characterized a 2.2kb region upstream of the SHP2 translation start site that drives early and late medial domain expression in the gynoecium, as well as expression within the VM and DZ. We identified two separable, independent cis-regulatory modules, a 1kb promoter region and a 700bp enhancer region, that are capable of giving VM and DZ expression. Our results argue for multiple independent cis-regulatory modules that support SHP2 expression during VM development and may contribute to the robustness of SHP2 expression in this tissue. Additionally, three closely positioned CArG box motifs located in the SHP2 upstream regulatory region were mutated in the context of the 2.2kb reporter construct. Mutating simultaneously all three CArG boxes caused a moderate de-repression of the SHP2 reporter that was detected within the valve domain, suggesting that these CArG boxes are involved in SHP2 repression in the valve. PMID:29085379

Investigation of multiple mortality events in eastern box turtles (Terrapene carolina carolina).

PubMed

Adamovicz, Laura; Allender, Matthew C; Archer, Grace; Rzadkowska, Marta; Boers, Kayla; Phillips, Chris; Driskell, Elizabeth; Kinsel, Michael J; Chu, Caroline

2018-01-01

Wildlife mortality investigations are important for conservation, food safety, and public health; but they are infrequently reported for cryptic chelonian species. Eastern box turtles (Terrapene carolina carolina) are declining due to anthropogenic factors and disease, and while mortality investigations have been reported for captive and translocated individuals, few descriptions exist for free-living populations. We report the results of four natural mortality event investigations conducted during routine health surveillance of three Illinois box turtle populations in 2011, 2013, 2014, and 2015. In April 2011, over 50 box turtles were found dead and a polymicrobial necrotizing bacterial infection was diagnosed in five survivors using histopathology and aerobic/anaerobic culture. This represents the first reported occurrence of necrotizing bacterial infection in box turtles. In August 2013, paired histopathology and qPCR ranavirus detection in nine turtles was significantly associated with occupation of moist microhabitats, identification of oral plaques and nasal discharge on physical exam, and increases in the heterophil count and heterophil to lymphocyte ratio (p < 0.05). In July 2014 and 2015, ranavirus outbreaks reoccurred within a 0.2km radius of highly-disturbed habitat containing ephemeral ponds used by amphibians for breeding. qPCR ranavirus detection in five individuals each year was significantly associated with use of moist microhabitats (p < 0.05). Detection of single and co-pathogens (Terrapene herpesvirus 1, adenovirus, and Mycoplasma sp.) was common before, during, and after mortality events, but improved sample size would be necessary to determine the impacts of these pathogens on the occurrence and outcome of mortality events. This study provides novel information about the causes and predictors of natural box turtle mortality events. Continued investigation of health, disease, and death in free-living box turtles will improve baseline knowledge

Investigation of multiple mortality events in eastern box turtles (Terrapene carolina carolina)

PubMed Central

Allender, Matthew C.; Archer, Grace; Rzadkowska, Marta; Boers, Kayla; Phillips, Chris; Driskell, Elizabeth; Kinsel, Michael J.; Chu, Caroline

2018-01-01

Wildlife mortality investigations are important for conservation, food safety, and public health; but they are infrequently reported for cryptic chelonian species. Eastern box turtles (Terrapene carolina carolina) are declining due to anthropogenic factors and disease, and while mortality investigations have been reported for captive and translocated individuals, few descriptions exist for free-living populations. We report the results of four natural mortality event investigations conducted during routine health surveillance of three Illinois box turtle populations in 2011, 2013, 2014, and 2015. In April 2011, over 50 box turtles were found dead and a polymicrobial necrotizing bacterial infection was diagnosed in five survivors using histopathology and aerobic/anaerobic culture. This represents the first reported occurrence of necrotizing bacterial infection in box turtles. In August 2013, paired histopathology and qPCR ranavirus detection in nine turtles was significantly associated with occupation of moist microhabitats, identification of oral plaques and nasal discharge on physical exam, and increases in the heterophil count and heterophil to lymphocyte ratio (p < 0.05). In July 2014 and 2015, ranavirus outbreaks reoccurred within a 0.2km radius of highly-disturbed habitat containing ephemeral ponds used by amphibians for breeding. qPCR ranavirus detection in five individuals each year was significantly associated with use of moist microhabitats (p < 0.05). Detection of single and co-pathogens (Terrapene herpesvirus 1, adenovirus, and Mycoplasma sp.) was common before, during, and after mortality events, but improved sample size would be necessary to determine the impacts of these pathogens on the occurrence and outcome of mortality events. This study provides novel information about the causes and predictors of natural box turtle mortality events. Continued investigation of health, disease, and death in free-living box turtles will improve baseline knowledge

47 CFR 90.241 - Radio call box operations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Radio call box operations. 90.241 Section 90... PRIVATE LAND MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.241 Radio call box... Safety Pool for operation of radio call boxes to be used by the public to request fire, police, ambulance...

47 CFR 90.241 - Radio call box operations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Radio call box operations. 90.241 Section 90... PRIVATE LAND MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.241 Radio call box... Safety Pool for operation of radio call boxes to be used by the public to request fire, police, ambulance...

47 CFR 90.241 - Radio call box operations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Radio call box operations. 90.241 Section 90... PRIVATE LAND MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.241 Radio call box... Safety Pool for operation of radio call boxes to be used by the public to request fire, police, ambulance...

Transformative Environmental Education: Stepping Outside the Curriculum Box

ERIC Educational Resources Information Center

Johnston, Julie

2009-01-01

Environmental education has become trapped in the curriculum box. At a time when our students' generation is becoming trapped in a global warming box, their education needs to be rapidly adaptable to the changing state of their planet. Venturing outside the curriculum box takes courage, creativity, and a willingness to let nature serve as the…

A novel F-box protein CaF-box is involved in responses to plant hormones and abiotic stress in pepper (Capsicum annuum L.).

PubMed

Chen, Rugang; Guo, Weili; Yin, Yanxu; Gong, Zhen-Hui

2014-02-10

The F-box protein family is characterized by an F-box motif that has been shown to play an important role in regulating various developmental processes and stress responses. In this study, a novel F-box-containing gene was isolated from leaves of pepper cultivar P70 (Capsicum annuum L.) and designated CaF-box. The full-length cDNA is 2088 bp and contains an open reading frame of 1914 bp encoding a putative polypeptide of 638 amino acids with a mass of 67.8 kDa. CaF-box was expressed predominantly in stems and seeds, and the transcript was markedly upregulated in response to cold stress, abscisic acid (ABA) and salicylic acid (SA) treatment, and downregulated under osmotic and heavy metal stress. CaF-box expression was dramatically affected by salt stress, and was rapidly increased for the first hour, then sharply decreased thereafter. In order to further assess the role of CaF-box in the defense response to abiotic stress, a loss-of-function experiment in pepper plants was performed using a virus-induced gene silencing (VIGS) technique. Measurement of thiobarbituric acid reactive substances (TBARS) and electrolyte leakage revealed stronger lipid peroxidation and cell death in the CaF-box-silenced plants than in control plants, suggesting CaF-box plays an important role in regulating the defense response to abiotic stress resistance in pepper plants.

Genome-wide identification and analysis of the MADS-box gene family in bread wheat (Triticum aestivum L.)

PubMed Central

Yang, Congcong; Ding, Puyang; Liu, Yaxi; Qiao, Linyi; Chang, Zhijian; Geng, Hongwei; Wang, Penghao; Jiang, Qiantao; Wang, Jirui; Chen, Guoyue; Wei, Yuming; Zheng, Youliang; Lan, Xiujin

2017-01-01

The MADS-box genes encode transcription factors with key roles in plant growth and development. A comprehensive analysis of the MADS-box gene family in bread wheat (Triticum aestivum) has not yet been conducted, and our understanding of their roles in stress is rather limited. Here, we report the identification and characterization of the MADS-box gene family in wheat. A total of 180 MADS-box genes classified as 32 Mα, 5 Mγ, 5 Mδ, and 138 MIKC types were identified. Evolutionary analysis of the orthologs among T. urartu, Aegilops tauschii and wheat as well as homeologous sequences analysis among the three sub-genomes in wheat revealed that gene loss and chromosomal rearrangements occurred during and/or after the origin of bread wheat. Forty wheat MADS-box genes that were expressed throughout the investigated tissues and development stages were identified. The genes that were regulated in response to both abiotic stresses (i.e., phosphorus deficiency, drought, heat, and combined drought and heat) and biotic stresses (i.e., Fusarium graminearum, Septoria tritici, stripe rust and powdery mildew) were detected as well. A few notable MADS-box genes were specifically expressed in a single tissue and those showed relatively higher expression differences between the stress and control treatment. The expression patterns of considerable MADS-box genes differed from those of their orthologs in Brachypodium, rice, and Arabidopsis. Collectively, the present study provides new insights into the possible roles of MADS-box genes in response to stresses and will be valuable for further functional studies of important candidate MADS-box genes. PMID:28742823

Genome-wide identification and analysis of the MADS-box gene family in bread wheat (Triticum aestivum L.).

PubMed

Ma, Jian; Yang, Yujie; Luo, Wei; Yang, Congcong; Ding, Puyang; Liu, Yaxi; Qiao, Linyi; Chang, Zhijian; Geng, Hongwei; Wang, Penghao; Jiang, Qiantao; Wang, Jirui; Chen, Guoyue; Wei, Yuming; Zheng, Youliang; Lan, Xiujin

2017-01-01

The MADS-box genes encode transcription factors with key roles in plant growth and development. A comprehensive analysis of the MADS-box gene family in bread wheat (Triticum aestivum) has not yet been conducted, and our understanding of their roles in stress is rather limited. Here, we report the identification and characterization of the MADS-box gene family in wheat. A total of 180 MADS-box genes classified as 32 Mα, 5 Mγ, 5 Mδ, and 138 MIKC types were identified. Evolutionary analysis of the orthologs among T. urartu, Aegilops tauschii and wheat as well as homeologous sequences analysis among the three sub-genomes in wheat revealed that gene loss and chromosomal rearrangements occurred during and/or after the origin of bread wheat. Forty wheat MADS-box genes that were expressed throughout the investigated tissues and development stages were identified. The genes that were regulated in response to both abiotic stresses (i.e., phosphorus deficiency, drought, heat, and combined drought and heat) and biotic stresses (i.e., Fusarium graminearum, Septoria tritici, stripe rust and powdery mildew) were detected as well. A few notable MADS-box genes were specifically expressed in a single tissue and those showed relatively higher expression differences between the stress and control treatment. The expression patterns of considerable MADS-box genes differed from those of their orthologs in Brachypodium, rice, and Arabidopsis. Collectively, the present study provides new insights into the possible roles of MADS-box genes in response to stresses and will be valuable for further functional studies of important candidate MADS-box genes.

AMP sensing by DEAD-box RNA helicases.

PubMed

Putnam, Andrea A; Jankowsky, Eckhard

2013-10-23

In eukaryotes, cellular levels of adenosine monophosphate (AMP) signal the metabolic state of the cell. AMP concentrations increase significantly upon metabolic stress, such as glucose deprivation in yeast. Here, we show that several DEAD-box RNA helicases are sensitive to AMP, which is not produced during ATP hydrolysis by these enzymes. We find that AMP potently inhibits RNA binding and unwinding by the yeast DEAD-box helicases Ded1p, Mss116p, and eIF4A. However, the yeast DEAD-box helicases Sub2p and Dbp5p are not inhibited by AMP. Our observations identify a subset of DEAD-box helicases as enzymes with the capacity to directly link changes in AMP concentrations to RNA metabolism. Copyright © 2013 Elsevier Ltd. All rights reserved.

Design of housing file box of fire academy based on RFID

NASA Astrophysics Data System (ADS)

Li, Huaiyi

2018-04-01

This paper presents a design scheme of intelligent file box based on RFID. The advantages of RFID file box and traditional file box are compared and analyzed, and the feasibility of RFID file box design is analyzed based on the actual situation of our university. After introducing the shape and structure design of the intelligent file box, the paper discusses the working process of the file box, and explains in detail the internal communication principle of the RFID file box and the realization of the control system. The application of the RFID based file box will greatly improve the efficiency of our school's archives management.

Ctf4 Is a Hub in the Eukaryotic Replisome that Links Multiple CIP-Box Proteins to the CMG Helicase.

PubMed

Villa, Fabrizio; Simon, Aline C; Ortiz Bazan, Maria Angeles; Kilkenny, Mairi L; Wirthensohn, David; Wightman, Mel; Matak-Vinkovíc, Dijana; Pellegrini, Luca; Labib, Karim

2016-08-04

Replisome assembly at eukaryotic replication forks connects the DNA helicase to DNA polymerases and many other factors. The helicase binds the leading-strand polymerase directly, but is connected to the Pol α lagging-strand polymerase by the trimeric adaptor Ctf4. Here, we identify new Ctf4 partners in addition to Pol α and helicase, all of which contain a "Ctf4-interacting-peptide" or CIP-box. Crystallographic analysis classifies CIP-boxes into two related groups that target different sites on Ctf4. Mutations in the CIP-box motifs of the Dna2 nuclease or the rDNA-associated protein Tof2 do not perturb DNA synthesis genome-wide, but instead lead to a dramatic shortening of chromosome 12 that contains the large array of rDNA repeats. Our data reveal unexpected complexity of Ctf4 function, as a hub that connects multiple accessory factors to the replisome. Most strikingly, Ctf4-dependent recruitment of CIP-box proteins couples other processes to DNA synthesis, including rDNA copy-number regulation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The B-Box Domain Protein BBX21 Promotes Photomorphogenesis.

PubMed

Xu, Dongqing; Jiang, Yan; Li, Jian; Holm, Magnus; Deng, Xing Wang

2018-03-01

B-box-containing (BBX) proteins play critical roles in a variety of cellular and developmental processes in plants. BBX21 (also known as SALT TOLERANCE HOMOLOG2), which contains two B-box domains in tandem at the N terminus, has been previously demonstrated as a key component involved in the COP1-HY5 signaling hub. However, the exact molecular and physiological roles of B-box domains in BBX21 are largely unclear. Here, we found that structurally disruption of the second B-box domain, but not the first one, in BBX21 completely abolishes its biological and physiological activity in conferring hyperphotomorphogenetic phenotype in Arabidopsis ( Arabidopsis thaliana ). Intact B-box domains in BBX21 are not required for interaction with COP1 and its degradation by COP1 via the 26S proteasome system. However, disruption of the second B-box of BBX21 nearly impairs its ability for binding of T/G-box within the HY5 promoter both in vitro and in vivo, as well as controlling HY5 and HY5-regulated gene expression in Arabidopsis seedlings. Taken together, this study provides a mechanistic framework in which BBX21 directly binds to the T/G-box present in the HY5 promoter possibly through its second B-box domain, which in turn controls HY5 and HY5-regulated gene expression to promote photomorphogenesis. © 2018 American Society of Plant Biologists. All Rights Reserved.

Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators

NASA Technical Reports Server (NTRS)

Belaguli, N. S.; Sepulveda, J. L.; Nigam, V.; Charron, F.; Nemer, M.; Schwartz, R. J.

2000-01-01

Combinatorial interaction among cardiac tissue-restricted enriched transcription factors may facilitate the expression of cardiac tissue-restricted genes. Here we show that the MADS box factor serum response factor (SRF) cooperates with the zinc finger protein GATA-4 to synergistically activate numerous myogenic and nonmyogenic serum response element (SRE)-dependent promoters in CV1 fibroblasts. In the absence of GATA binding sites, synergistic activation depends on binding of SRF to the proximal CArG box sequence in the cardiac and skeletal alpha-actin promoter. GATA-4's C-terminal activation domain is obligatory for synergistic coactivation with SRF, and its N-terminal domain and first zinc finger are inhibitory. SRF and GATA-4 physically associate both in vivo and in vitro through their MADS box and the second zinc finger domains as determined by protein A pullout assays and by in vivo one-hybrid transfection assays using Gal4 fusion proteins. Other cardiovascular tissue-restricted GATA factors, such as GATA-5 and GATA-6, were equivalent to GATA-4 in coactivating SRE-dependent targets. Thus, interaction between the MADS box and C4 zinc finger proteins, a novel regulatory paradigm, mediates activation of SRF-dependent gene expression.

Delivery of the high-mobility group box 1 box A peptide using heparin in the acute lung injury animal models.

PubMed

Song, Ji Hyun; Kim, Ji Yeon; Piao, Chunxian; Lee, Seonyeong; Kim, Bora; Song, Su Jeong; Choi, Joon Sig; Lee, Minhyung

2016-07-28

In this study, the efficacy of the high-mobility group box-1 box A (HMGB1A)/heparin complex was evaluated for the treatment of acute lung injury (ALI). HMGB1A is an antagonist against wild-type high-mobility group box-1 (wtHMGB1), a pro-inflammatory cytokine that is involved in ALIs. HMGB1A has positive charges and can be captured in the mucus layer after intratracheal administration. To enhance the delivery and therapeutic efficiency of HMGB1A, the HMGB1A/heparin complex was produced using electrostatic interactions, with the expectation that the nano-sized complex with a negative surface charge could efficiently penetrate the mucus layer. Additionally, heparin itself had an anti-inflammatory effect. Complex formation with HMGB1A and heparin was confirmed by atomic force microscopy. The particle size and surface charge of the HMGB1A/heparin complex at a 1:1 weight ratio were 113nm and -25mV, respectively. Intratracheal administration of the complex was performed into an ALI animal model. The results showed that the HMGB1A/heparin complex reduced pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, more effectively than HMGB1A or heparin alone. Hematoxylin and eosin staining confirmed the decreased inflammatory reaction in the lungs after delivery of the HMGB1A/heparin complex. In conclusion, the HMGB1A/heparin complex might be useful to treat ALI. Copyright © 2016 Elsevier B.V. All rights reserved.

Human HMG box transcription factor HBP1: a role in hCD2 LCR function.

PubMed Central

Zhuma, T; Tyrrell, R; Sekkali, B; Skavdis, G; Saveliev, A; Tolaini, M; Roderick, K; Norton, T; Smerdon, S; Sedgwick, S; Festenstein, R; Kioussis, D

1999-01-01

The locus control region (LCR) of the human CD2 gene (hCD2) confers T cell-specific, copy-dependent and position-independent gene expression in transgenic mice. This LCR consists of a strong T cell-specific enhancer and an element without enhancer activity (designated HSS3), which is required for prevention of position effect variegation (PEV) in transgenic mice. Here, we identified the HMG box containing protein-1 (HBP1) as a factor binding to HSS3 of the hCD2 LCR. Within the LCR, HBP1 binds to a novel TTCATTCATTCA sequence that is higher in affinity than other recently reported HBP1-binding sites. Mice transgenic for a hCD2 LCR construct carrying a deletion of the HBP1-binding sequences show a propensity for PEV if the transgene integrates in a heterochromatic region of the chromosome such as the centromere or telomere. We propose that HBP1 plays an important role in chromatin opening and remodelling activities by binding to and bending the DNA, thus allowing DNA-protein and/or protein-protein interactions, which increase the probability of establishing an active locus. PMID:10562551

A Novel F-Box Protein CaF-Box Is Involved in Responses to Plant Hormones and Abiotic Stress in Pepper (Capsicum annuum L.)

PubMed Central

Chen, Rugang; Guo, Weili; Yin, Yanxu; Gong, Zhen-Hui

2014-01-01

The F-box protein family is characterized by an F-box motif that has been shown to play an important role in regulating various developmental processes and stress responses. In this study, a novel F-box-containing gene was isolated from leaves of pepper cultivar P70 (Capsicum annuum L.) and designated CaF-box. The full-length cDNA is 2088 bp and contains an open reading frame of 1914 bp encoding a putative polypeptide of 638 amino acids with a mass of 67.8 kDa. CaF-box was expressed predominantly in stems and seeds, and the transcript was markedly upregulated in response to cold stress, abscisic acid (ABA) and salicylic acid (SA) treatment, and downregulated under osmotic and heavy metal stress. CaF-box expression was dramatically affected by salt stress, and was rapidly increased for the first hour, then sharply decreased thereafter. In order to further assess the role of CaF-box in the defense response to abiotic stress, a loss-of-function experiment in pepper plants was performed using a virus-induced gene silencing (VIGS) technique. Measurement of thiobarbituric acid reactive substances (TBARS) and electrolyte leakage revealed stronger lipid peroxidation and cell death in the CaF-box-silenced plants than in control plants, suggesting CaF-box plays an important role in regulating the defense response to abiotic stress resistance in pepper plants. PMID:24518684

Genomic Organization, Phylogenetic Comparison and Differential Expression of the SBP-Box Family Genes in Grape

PubMed Central

Hou, Hongmin; Li, Jun; Gao, Min; Singer, Stacy D.; Wang, Hao; Mao, Linyong; Fei, Zhangjun; Wang, Xiping

2013-01-01

Background The SBP-box gene family is specific to plants and encodes a class of zinc finger-containing transcription factors with a broad range of functions. Although SBP-box genes have been identified in numerous plants including green algae, moss, silver birch, snapdragon, Arabidopsis, rice and maize, there is little information concerning SBP-box genes, or the corresponding miR156/157, function in grapevine. Methodology/Principal Findings Eighteen SBP-box gene family members were identified in Vitis vinifera, twelve of which bore sequences that were complementary to miRNA156/157. Phylogenetic reconstruction demonstrated that plant SBP-domain proteins could be classified into seven subgroups, with the V. vinifera SBP-domain proteins being more closely related to SBP-domain proteins from dicotyledonous angiosperms than those from monocotyledonous angiosperms. In addition, synteny analysis between grape and Arabidopsis demonstrated that homologs of several grape SBP genes were found in corresponding syntenic blocks of Arabidopsis. Expression analysis of the grape SBP-box genes in various organs and at different stages of fruit development in V. quinquangularis ‘Shang-24’ revealed distinct spatiotemporal patterns. While the majority of the grape SBP-box genes lacking a miR156/157 target site were expressed ubiquitously and constitutively, most genes bearing a miR156/157 target site exhibited distinct expression patterns, possibly due to the inhibitory role of the microRNA. Furthermore, microarray data mining and quantitative real-time RT-PCR analysis identified several grape SBP-box genes that are potentially involved in the defense against biotic and abiotic stresses. Conclusion The results presented here provide a further understanding of SBP-box gene function in plants, and yields additional insights into the mechanism of stress management in grape, which may have important implications for the future success of this crop. PMID:23527172

Exploding Boxes

ERIC Educational Resources Information Center

Kinney; Jan

2011-01-01

How do you teach the "same old, same old" in an interesting and inexpensive way? Art teachers are forever looking for new angles on the good-old elements and principles. And, as budgets tighten, they are trying to be as frugal as possible while still holding their students' attention. Enter exploding boxes! In conceptualizing the three types of…

BMI Sandwich Wing Box Analysis and Test

NASA Technical Reports Server (NTRS)

Palm, Tod; Mahler, Mary; Shah, Chandu; Rouse, Marshall; Bush, Harold; Wu, Chauncey; Small, William J.

2000-01-01

A composite sandwich single bay wing box test article was developed by Northrop Grumman and tested recently at NASA Langley Research Center. The objectives for the wing box development effort were to provide a demonstration article for manufacturing scale up of structural concepts related to a high speed transport wing, and to validate the structural performance of the design. The box concept consisted of highly loaded composite sandwich wing skins, with moderately loaded composite sandwich spars. The dimensions of the box were chosen to represent a single bay of the main wing box, with a spar spacing of 30 inches, height of 20 inches constant depth, and length of 64 inches. The bismaleimide facesheet laminates and titanium honeycomb core chosen for this task are high temperature materials able to sustain a 300F service temperature. The completed test article is shown in Figure 1. The tests at NASA Langley demonstrated the structures ability to sustain axial tension and compression loads in excess of 20,000 lb/in, and to maintain integrity in the thermal environment. Test procedures, analysis failure predictions, and test results are presented.

Eye trauma in boxing.

PubMed

Corrales, Gustavo; Curreri, Anthony

2009-10-01

In boxing, along with a few other sports, trauma is inherent to the nature of the sport; therefore it is considered a high-risk sport for ocular injuries. The long-term morbidity of ocular injuries suffered by boxers is difficult to estimate due to the lack of structured long-term follow-up of these athletes. Complications of blunt ocular trauma may develop years after the athlete has retired from the ring and is no longer considered to be at risk for boxing-related injuries. This article describes the wide range of eye injuries a boxer can sustain, and their immediate and long-term clinical management.

49 CFR 178.512 - Standards for steel or aluminum boxes.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 3 2012-10-01 2012-10-01 false Standards for steel or aluminum boxes. 178.512... PACKAGINGS Non-bulk Performance-Oriented Packaging Standards § 178.512 Standards for steel or aluminum boxes. (a) The following are identification codes for steel or aluminum boxes: (1) 4A for a steel box; and...

49 CFR 178.512 - Standards for steel or aluminum boxes.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Standards for steel or aluminum boxes. 178.512... PACKAGINGS Non-bulk Performance-Oriented Packaging Standards § 178.512 Standards for steel or aluminum boxes. (a) The following are identification codes for steel or aluminum boxes: (1) 4A for a steel box; and...

The regulatory mechanism of fruit ripening revealed by analyses of direct targets of the tomato MADS-box transcription factor RIPENING INHIBITOR

PubMed Central

Fujisawa, Masaki; Ito, Yasuhiro

2013-01-01

The developmental process of ripening is unique to fleshy fruits and a key factor in fruit quality. The tomato (Solanum lycopersicum) MADS-box transcription factor RIPENING INHIBITOR (RIN), one of the earliest-acting ripening regulators, is required for broad aspects of ripening, including ethylene-dependent and -independent pathways. However, our knowledge of direct RIN target genes has been limited, considering the broad effects of RIN on ripening. In a recent work published in The Plant Cell, we identified 241 direct RIN target genes by chromatin immunoprecipitation coupled with DNA microarray (ChIP-chip) and transcriptome analysis. Functional classification of the targets revealed that RIN participates in the regulation of many biological processes including well-known ripening processes such as climacteric ethylene production and lycopene accumulation. In addition, we found that ethylene is required for the full expression of RIN and several RIN-targeting transcription factor genes at the ripening stage. Here, based on our recently published findings and additional data, we discuss the ripening processes regulated by RIN and the interplay between RIN and ethylene. PMID:23518588

MicroRNA-214 suppresses gluconeogenesis by targeting activating transcriptional factor 4.

PubMed

Li, Kai; Zhang, Jin; Yu, Junjie; Liu, Bin; Guo, Yajie; Deng, Jiali; Chen, Shanghai; Wang, Chunxia; Guo, Feifan

2015-03-27

Although the gluconeogenesis pathway is already a target for the treatment of type 2 diabetes, the potential role of microRNAs (miRNAs) in gluconeogenesis remains unclear. Here, we investigated the physiological functions of miR-214 in gluconeogenesis. The expression of miR-214 was suppressed by glucagon via protein kinase A signaling in primary hepatocytes, and miR-214 was down-regulated in the livers of fasted, high fat diet-induced diabetic and leptin receptor-mutated (db/db) mice. The overexpression of miR-214 in primary hepatocytes suppressed glucose production, and silencing miR-214 reversed this effect. Gluconeogenesis was suppressed in the livers of mice injected with an adenovirus expressing miR-214 (Ad-miR-214). Additionally, Ad-miR-214 alleviated high fat diet-induced elevation of gluconeogenesis and hyperglycemia. Furthermore, we found that activating transcription factor 4 (ATF4), a reported target of miR-214, can reverse the suppressive effect of miR-214 on gluconeogenesis in primary hepatocytes, and this suppressive effect was blocked in liver-specific ATF4 knock-out mice. ATF4 regulated gluconeogenesis via affecting forkhead box protein O1 (FOXO1) transcriptional activity. Finally, liver-specific miR-214 transgenic mice exhibited suppressed gluconeogenesis and reduced expression of ATF4, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in liver. Taken together, our results suggest that the miR-214-ATF4 axis is a novel pathway for the regulation of hepatic gluconeogenesis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

49 CFR 230.103 - Tender roller bearing journal boxes.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Tender roller bearing journal boxes. 230.103... Locomotives and Tenders Running Gear § 230.103 Tender roller bearing journal boxes. Tender roller bearing journal boxes shall be maintained in a safe and suitable condition. ...

49 CFR 230.103 - Tender roller bearing journal boxes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Tender roller bearing journal boxes. 230.103... Locomotives and Tenders Running Gear § 230.103 Tender roller bearing journal boxes. Tender roller bearing journal boxes shall be maintained in a safe and suitable condition. ...

A Novel Sucrose-Regulatory MADS-Box Transcription Factor GmNMHC5 Promotes Root Development and Nodulation in Soybean (Glycine max [L.] Merr.).

PubMed

Liu, Wei; Han, Xiangdong; Zhan, Ge; Zhao, Zhenfang; Feng, Yongjun; Wu, Cunxiang

2015-08-31

The MADS-box protein family includes many transcription factors that have a conserved DNA-binding MADS-box domain. The proteins in this family were originally recognized to play prominent roles in floral development. Recent findings, especially with regard to the regulatory roles of the AGL17 subfamily in root development, have greatly broadened their known functions. In this study, a gene from soybean (Glycine max [L.] Merr.), GmNMHC5, was cloned from the Zigongdongdou cultivar and identified as a member of the AGL17 subfamily. Real-time fluorescence quantitative PCR analysis showed that GmNMHC5 was expressed at much higher levels in roots and nodules than in other organs. The activation of expression was first examined in leaves and roots, followed by shoot apexes. GmNMHC5 expression levels rose sharply when the plants were treated under short-day conditions (SD) and started to pod, whereas low levels were maintained in non-podding plants under long-day conditions (LD). Furthermore, overexpression of GmNMHC5 in transgenic soybean significantly promoted lateral root development and nodule building. Moreover, GmNMHC5 is upregulated by exogenous sucrose. These results indicate that GmNMHC5 can sense the sucrose signal and plays significant roles in lateral root development and nodule building.

Demographic consequences of nest box use for Red-footed Falcons Falco vespertinus in Central Asia

USGS Publications Warehouse

Bragin, Evgeny A.; Bragin, Alexander E.; Katzner, Todd

2017-01-01

Nest box programs are frequently implemented for the conservation of cavity-nesting birds, but their effectiveness is rarely evaluated in comparison to birds not using nest boxes. In the European Palearctic, Red-footed Falcon Falco vespertinus populations are both of high conservation concern and are strongly associated with nest box programs in heavily managed landscapes. We used a 21-year monitoring dataset collected on 753 nesting attempts by Red-footed Falcons in unmanaged natural or semi-natural habitats to provide basic information on this poorly known species; to evaluate long-term demographic trends; and to evaluate response of demographic parameters of Red-footed Falcons to environmental factors including use of nest boxes. We observed significant differences among years in laying date, offspring loss, and numbers of fledglings produced, but not in egg production. Of these four parameters, offspring loss and, to a lesser extent, number of fledglings exhibited directional trends over time. Variation in laying date and in numbers of eggs were not well explained by any one model, but instead by combinations of models, each with informative terms for nest type. Nevertheless, laying in nest boxes occurred 2.10 ± 0.70 days earlier than in natural nests. In contrast, variation in both offspring loss and numbers of fledglings produced were fairly well explained by a single model including terms for nest type, nest location, and an interaction between the two parameters (65% and 81% model weights respectively), with highest offspring loss in nest boxes on forest edges. Because, for other species, earlier laying dates are associated with more fit individuals, this interaction highlighted a possible ecological trap, whereby birds using nest boxes on forest edges lay eggs earlier but suffer greater offspring loss and produce lower numbers of fledglings than do those in other nesting settings. If nest boxes increase offspring loss for Red-footed Falcons in heavily

Design/Use of the Remotely Operated Bakeout Box Shutter (ROBBS)

NASA Technical Reports Server (NTRS)

Ottens, Brian P.

1999-01-01

A thermal vacuum box bakeout and certification allows orbital payloads to be cleaned and certified when the background TQCM measurements (a measure of how much molecular contamination is on a payload or chamber) are unacceptable or unmanageable in the standard thermal vacuum chamber. The box bakeout procedure is usually performed in 4 steps: bakeout the box, certify the box, bake out the payload, and finally certify the payload. In the procedure's current setup, the contaminant conduction hole ("lid") is initially open and a vacuum chamber break must occur between the bakeout and certification phases to close the box from the vacuum chamber. This exposure is necessary to allow the outgassed contaminants to escape the box's volume rapidly during bakeout phase, but payload certification isn't usually performed while the lid is still open, because it exposes the payload, TQCM, and box volume to chamber contaminants. The Remotely Operated Bakeout Box Shutter (ROBBS) is a new facility design and will allow the remote closure of the contamination hole while the chamber is still under vacuum, and with little or no time to do so.

Strong expression of the neuronal transcription factor FOXP2 is linked to an increased risk of early PSA recurrence in ERG fusion-negative cancers.

PubMed

Stumm, Laura; Burkhardt, Lia; Steurer, Stefan; Simon, Ronald; Adam, Meike; Becker, Andreas; Sauter, Guido; Minner, Sarah; Schlomm, Thorsten; Sirma, Hüseyin; Michl, Uwe

2013-07-01

Transcription factors of the forkhead box P (FOXP1-4) family have been implicated in various human cancer types before. The relevance and role of neuronal transcription factor FOXP2 in prostate cancer is unknown. A tissue microarray containing samples from more than 11 000 prostate cancers from radical prostatectomy specimens with clinical follow-up data was analysed for FOXP2 expression by immunohistochemistry. FOXP2 data were also compared with pre-existing ERG fusion (by fluorescence in situ hybridisation and immunohistochemistry) and cell proliferation (Ki67 labelling index) data. There was a moderate to strong FOXP2 protein expression in basal and secretory cells of normal prostatic glands. As compared with normal cells, FOXP2 expression was lost or reduced in 25% of cancers. Strong FOXP2 expression was linked to advanced tumour stage, high Gleason score, presence of lymph node metastases and early tumour recurrence (p<0.0001; each) in ERG fusion-negative, but not in ERG fusion-positive cancers. High FOXP2 expression was linked to high Ki67 labelling index (p<0.0001) in all cancers irrespective of ERG fusion status. These data demonstrate that similar high FOXP2 protein levels as in normal prostate epithelium exert a 'paradoxical' oncogenic role in 'non fusion-type' prostate cancer. It may be speculated that interaction of FOXP2 with members of pathways that are specifically activated in 'non fusion-type' cancers may be responsible for this phenomenon.

FOXF1 transcription factor is required for formation of embryonic vasculature by regulating VEGF signaling in endothelial cells.

PubMed

Ren, Xiaomeng; Ustiyan, Vladimir; Pradhan, Arun; Cai, Yuqi; Havrilak, Jamie A; Bolte, Craig S; Shannon, John M; Kalin, Tanya V; Kalinichenko, Vladimir V

2014-09-26

Inactivating mutations in the Forkhead Box transcription factor F1 (FOXF1) gene locus are frequently found in patients with alveolar capillary dysplasia with misalignment of pulmonary veins, a lethal congenital disorder, which is characterized by severe abnormalities in the respiratory, cardiovascular, and gastrointestinal systems. In mice, haploinsufficiency of the Foxf1 gene causes alveolar capillary dysplasia and developmental defects in lung, intestinal, and gall bladder morphogenesis. Although FOXF1 is expressed in multiple mesenchyme-derived cell types, cellular origins and molecular mechanisms of developmental abnormalities in FOXF1-deficient mice and patients with alveolar capillary dysplasia with misalignment of pulmonary veins remain uncharacterized because of lack of mouse models with cell-restricted inactivation of the Foxf1 gene. In the present study, the role of FOXF1 in endothelial cells was examined using a conditional knockout approach. A novel mouse line harboring Foxf1-floxed alleles was generated by homologous recombination. Tie2-Cre and Pdgfb-CreER transgenes were used to delete Foxf1 from endothelial cells. FOXF1-deficient embryos exhibited embryonic lethality, growth retardation, polyhydramnios, cardiac ventricular hypoplasia, and vascular abnormalities in the lung, placenta, yolk sac, and retina. Deletion of FOXF1 from endothelial cells reduced endothelial proliferation, increased apoptosis, inhibited vascular endothelial growth factor signaling, and decreased expression of endothelial genes critical for vascular development, including vascular endothelial growth factor receptors Flt1 and Flk1, Pdgfb, Pecam1, CD34, integrin β3, ephrin B2, Tie2, and the noncoding RNA Fendrr. Chromatin immunoprecipitation assay demonstrated that Flt1, Flk1, Pdgfb, Pecam1, and Tie2 genes are direct transcriptional targets of FOXF1. FOXF1 is required for the formation of embryonic vasculature by regulating endothelial genes critical for vascular development and

EPA ExpoBox

EPA Pesticide Factsheets

EPA ExpoBox is a toolbox for exposure assessors. Its purpose is to provide a compendium of exposure assessment and risk characterization tools that will present comprehensive step-by-step guidance and links to relevant exposure assessment data bases, mode

Phylogenetic and Structural Analysis of the Pluripotency Factor Sex-Determining Region Y box2 Gene of Camelus dromedarius (cSox2).

PubMed

Alawad, Abdullah; Alharbi, Sultan; Alhazzaa, Othman; Alagrafi, Faisal; Alkhrayef, Mohammed; Alhamdan, Ziyad; Alenazi, Abdullah; Al-Johi, Hasan; Alanazi, Ibrahim O; Hammad, Mohamed

2016-01-01

Although the sequencing information of Sox2 cDNA for many mammalian is available, the Sox2 cDNA of Camelus dromedaries has not yet been characterized. The objective of this study was to sequence and characterize Sox2 cDNA from the brain of C. dromedarius (also known as Arabian camel). A full coding sequence of the Sox2 gene from the brain of C. dromedarius was amplified by reverse transcription PCRjmc and then sequenced using the 3730XL series platform Sequencer (Applied Biosystem) for the first time. The cDNA sequence displayed an open reading frame of 822 nucleotides, encoding a protein of 273 amino acids. The molecular weight and the isoelectric point of the translated protein were calculated as 29.825 kDa and 10.11, respectively, using bioinformatics analysis. The predicted cSox2 protein sequence exhibited high identity: 99% for Homo sapiens, Mus musculus, Bos taurus, and Vicugna pacos; 98% for Sus scrofa and 93% for Camelus ferus. A 3D structure was built based on the available crystal structure of the HMG-box domain of human stem cell transcription factor Sox2 (PDB: 2 LE4) with 81 residues and predicting bioinformatics software for 273 amino acid residues. The comparison confirms the presence of the HMG-box domain in the cSox2 protein. The orthologous phylogenetic analysis showed that the Sox2 isoform from C. dromedarius was grouped with humans, alpacas, cattle, and pigs. We believe that this genetic and structural information will be a helpful source for the annotation. Furthermore, Sox2 is one of the transcription factors that contributes to the generation-induced pluripotent stem cells (iPSCs), which in turn will probably help generate camel induced pluripotent stem cells (CiPSCs).

The integrated endoplasmic reticulum stress response in Leishmania amazonensis macrophage infection: the role of X-box binding protein 1 transcription factor.

PubMed

Dias-Teixeira, Karina Luiza; Calegari-Silva, Teresa Cristina; dos Santos, Guilherme R R M; Vitorino Dos Santos, José; Lima, Carolina; Medina, Jorge Mansur; Aktas, Bertal Huseyin; Lopes, Ulisses G

2016-04-01

Endoplasmic reticulum (ER) stress triggers the integrated ER-stress response (IERSR) that ensures cellular survival of ER stress and represents a primordial form of innate immunity. We investigated the role of IERSR duringLeishmania amazonensisinfection. Treatment of RAW 264.7 infected macrophages with the ER stress-inducing agent thapsigargin (TG; 1 μM) increasedL. amazonensisinfectivity in an IFN1-α receptor (IFNAR)-dependent manner. In Western blot assays, we showed thatL. amazonensisactivates the inositol-requiring enzyme (IRE1)/ X-box binding protein (XBP)-1-splicing arms of the IERSR in host cells. In chromatin immunoprecipitation (ChIP) assays, we showed an increased occupancy of enhancer and promoter sequences for theIfnbgene by XBP1 in infected RAW 264.7 cells. Knocking down XBP1 expression by transducing RAW 264.7 cells with the short hairpin XBP1 lentiviral vector significantly reduced the parasite proliferation associated with impaired translocation of phosphorylated IFN regulatory transcription factor (IRF)-3 to the nucleus and a decrease in IFN1-β expression. Knocking down XBP1 expression also increased NO concentration, as determined by Griess reaction and reduced the expression of antioxidant genes, such as heme oxygenase (HO)-1, that protect parasites from oxidative stress. We conclude thatL. amazonensisactivation of XBP1 plays a critical role in infection by protecting the parasites from oxidative stress and increasing IFN1-β expression.-Dias-Teixeira, K. L., Calegari-Silva, T. C., Dos Santos, G. R. R. M., Vitorino dos Santos, J., Lima, C., Medina, J. M., Aktas, B. H., Lopes, U. G. The integrated endoplasmic reticulum stress response inLeishmania amazonensismacrophage infection: the role of X-box binding protein 1 transcription factor. © FASEB.

A Calculus for Boxes and Traits in a Java-Like Setting

NASA Astrophysics Data System (ADS)

Bettini, Lorenzo; Damiani, Ferruccio; de Luca, Marco; Geilmann, Kathrin; Schäfer, Jan

The box model is a component model for the object-oriented paradigm, that defines components (the boxes) with clear encapsulation boundaries. Having well-defined boundaries is crucial in component-based software development, because it enables to argue about the interference and interaction between a component and its context. In general, boxes contain several objects and inner boxes, of which some are local to the box and cannot be accessed from other boxes and some can be accessible by other boxes. A trait is a set of methods divorced from any class hierarchy. Traits can be composed together to form classes or other traits. We present a calculus for boxes and traits. Traits are units of fine-grained reuse, whereas boxes can be seen as units of coarse-grained reuse. The calculus is equipped with an ownership type system and allows us to combine coarse- and fine-grained reuse of code by maintaining encapsulation of components.

Crystal structure of human PCNA in complex with the PIP box of DVC1

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

Wang, Yong; University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing 100049; Xu, Min

2016-05-27

In higher eukaryotes, DVC1 (SPRTN, Spartan or C1orf124) is implicated in the translesion synthesis (TLS) pathway. DVC1 localizes to sites of DNA damage, binds to the proliferating cell nuclear antigen (PCNA) via its conserved PCNA-interacting motif (PIP box), and associates with ubiquitin selective segregase p97 and other factors, thus regulating translesion synthesis polymerases. Here, we report the crystal structure of human PCNA in complex with a peptide ({sup 321}SNSHQNVLSNYFPRVS{sup 336}) derived from human DVC1 that contains a unique YF type PIP box. Structural analysis reveals the detailed PIP box-PCNA interaction. Interestingly, substitution of Y331 with Phe severely reduces its PCNAmore » binding affinity. These findings offer new insights into the determinants of PIP box for PCNA binding. -- Highlights: •Crystal structure of PCNA in complex with DVC1{sup PIP} peptide was determined. •The Y331{sup P7}F mutation severely impairs DVC1's PCNA binding affinity. •The intramolecular hydrogen bond N326−Y331 in the 3{sub 10} helix affects DVC1's PCNA binding affinity.« less

49 CFR 178.515 - Standards for reconstituted wood boxes.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 3 2012-10-01 2012-10-01 false Standards for reconstituted wood boxes. 178.515... PACKAGINGS Non-bulk Performance-Oriented Packaging Standards § 178.515 Standards for reconstituted wood boxes. (a) The identification code for a reconstituted wood box is 4F. (b) Construction requirements for...

49 CFR 178.515 - Standards for reconstituted wood boxes.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 3 2013-10-01 2013-10-01 false Standards for reconstituted wood boxes. 178.515... PACKAGINGS Non-bulk Performance-Oriented Packaging Standards § 178.515 Standards for reconstituted wood boxes. (a) The identification code for a reconstituted wood box is 4F. (b) Construction requirements for...

49 CFR 178.515 - Standards for reconstituted wood boxes.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 3 2014-10-01 2014-10-01 false Standards for reconstituted wood boxes. 178.515... PACKAGINGS Non-bulk Performance-Oriented Packaging Standards § 178.515 Standards for reconstituted wood boxes. (a) The identification code for a reconstituted wood box is 4F. (b) Construction requirements for...

49 CFR 178.515 - Standards for reconstituted wood boxes.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Standards for reconstituted wood boxes. 178.515... PACKAGINGS Non-bulk Performance-Oriented Packaging Standards § 178.515 Standards for reconstituted wood boxes. (a) The identification code for a reconstituted wood box is 4F. (b) Construction requirements for...

A DNA-binding protein from Candida albicans that binds to the RPG box of Saccharomyces cerevisiae and the telomeric repeat sequence of C. albicans.

PubMed

Ishii, N; Yamamoto, M; Lahm, H W; Iizumi, S; Yoshihara, F; Nakayama, H; Arisawa, M; Aoki, Y

1997-02-01

Electromobility shift assays with a DNA probe containing the Saccharomyces cerevisiae ENO1 RPG box identified a specific DNA-binding protein in total protein extracts of Candida albicans. The protein, named Rbf1p (RPG-box-binding protein 1), bound to other S. cerevisiae RPG boxes, although the nucleotide recognition profile was not completely the same as that of S. cerevisiae Rap 1p (repressor-activator protein 1), an RPG-box-binding protein. The repetitive sequence of the C. albicans chromosomal telomere also competed with RPG-box binding to Rbf1p. For further analysis, we purified Rbf1p 57,600-fold from C. albicans total protein extracts, raised mAbs against the purified protein and immunologically cloned the gene, whose ORF specified a protein of 527 aa. The bacterially expressed protein showed RPG-box-binding activity with the same profile as that of the purified one. The Rbf1p, containing two glutamine-rich regions that are found in many transcription factors, showed transcriptional activation capability in S. cerevisiae and was predominantly observed in nuclei. These results suggest that Rbf1p is a transcription factor with telomere-binding activity in C. albicans.

Max-E47, a Designed Minimalist Protein that Targets the E-Box DNA Site In Vivo and In Vitro

PubMed Central

Xu, Jing; Chen, Gang; De Jong, Antonia T.; Shahravan, S. Hesam; Shin, Jumi A.

2009-01-01

Max-E47 is a designed hybrid protein comprising the Max DNA-binding basic region and E47 HLH dimerization subdomain. In the yeast one-hybrid system (Y1H), Max-E47 shows strong transcriptional activation from the E-box site, 5'-CACGTG, targeted by the Myc/Max/Mad network of transcription factors; two mutants, Max-E47Y and Max-E47YF, activate more weakly from the E-box in the Y1H. Quantitative fluorescence anisotropy titrations to gain free energies of protein:DNA binding gave low nM Kd values for the native MaxbHLHZ, Max-E47, and the Y and YF mutants binding to the E-box site (14 nM, 15 nM, 9 nM, and 6 nM, respectively), with no detectable binding to a nonspecific control duplex. Because these minimalist, E-box-binding hybrids have no activation domain and no interactions with the c-MycbHLHZ, as shown by the yeast two-hybrid assay, they can potentially serve as dominant-negative inhibitors that suppress activation of E-box-responsive genes targeted by transcription factors including the c-Myc/Max complex. As proof-of-principle, we used our modified Y1H, which allows direct competition between two proteins vying for a DNA target, to show that Max-E47 effectively outcompetes the native MaxbHLHZ for the E-box; weaker competition is observed from the two mutants, consistent with Y1H results. These hybrids provide a minimalist scaffold for further exploration of the relationship between protein structure and DNA-binding function and may have applications as protein therapeutics or biochemical probes capable of targeting the E-box site. PMID:19449889

Preload-Release Mechanism For Mounting Electronics Boxes

NASA Technical Reports Server (NTRS)

Generoli, Robert M.; Young, Harry J.

1995-01-01

Proposed mechanism applies spring preload to electrical connector only while needed during insertion of electronics box into supporting frame. Once connector fully mated, mechanism relieves preload. As result, supporting structure sized to handle only individual load applied briefly by each connector on box during insertion.

49 CFR 230.101 - Steam locomotive driving journal boxes.

Code of Federal Regulations, 2014 CFR

2014-10-01

... than one shim may be used between the box and bearing. (b) Broken bearings. Broken bearings shall be... 49 Transportation 4 2014-10-01 2014-10-01 false Steam locomotive driving journal boxes. 230.101... Locomotives and Tenders Running Gear § 230.101 Steam locomotive driving journal boxes. (a) Driving journal...

49 CFR 230.101 - Steam locomotive driving journal boxes.

Code of Federal Regulations, 2013 CFR

2013-10-01

... than one shim may be used between the box and bearing. (b) Broken bearings. Broken bearings shall be... 49 Transportation 4 2013-10-01 2013-10-01 false Steam locomotive driving journal boxes. 230.101... Locomotives and Tenders Running Gear § 230.101 Steam locomotive driving journal boxes. (a) Driving journal...

49 CFR 230.101 - Steam locomotive driving journal boxes.

Code of Federal Regulations, 2011 CFR

2011-10-01

... than one shim may be used between the box and bearing. (b) Broken bearings. Broken bearings shall be... 49 Transportation 4 2011-10-01 2011-10-01 false Steam locomotive driving journal boxes. 230.101... Locomotives and Tenders Running Gear § 230.101 Steam locomotive driving journal boxes. (a) Driving journal...

49 CFR 230.101 - Steam locomotive driving journal boxes.

Code of Federal Regulations, 2012 CFR

2012-10-01

... than one shim may be used between the box and bearing. (b) Broken bearings. Broken bearings shall be... 49 Transportation 4 2012-10-01 2012-10-01 false Steam locomotive driving journal boxes. 230.101... Locomotives and Tenders Running Gear § 230.101 Steam locomotive driving journal boxes. (a) Driving journal...

49 CFR 230.101 - Steam locomotive driving journal boxes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... than one shim may be used between the box and bearing. (b) Broken bearings. Broken bearings shall be... 49 Transportation 4 2010-10-01 2010-10-01 false Steam locomotive driving journal boxes. 230.101... Locomotives and Tenders Running Gear § 230.101 Steam locomotive driving journal boxes. (a) Driving journal...

30 CFR 77.1002 - Box cuts; spoil material placement.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Box cuts; spoil material placement. 77.1002 Section 77.1002 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE... COAL MINES Ground Control § 77.1002 Box cuts; spoil material placement. When box cuts are made...

30 CFR 77.1002 - Box cuts; spoil material placement.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Box cuts; spoil material placement. 77.1002 Section 77.1002 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE... COAL MINES Ground Control § 77.1002 Box cuts; spoil material placement. When box cuts are made...

Genome-wide identification, characterisation and expression analysis of the MADS-box gene family in Prunus mume.

PubMed

Xu, Zongda; Zhang, Qixiang; Sun, Lidan; Du, Dongliang; Cheng, Tangren; Pan, Huitang; Yang, Weiru; Wang, Jia

2014-10-01

MADS-box genes encode transcription factors that play crucial roles in plant development, especially in flower and fruit development. To gain insight into this gene family in Prunus mume, an important ornamental and fruit plant in East Asia, and to elucidate their roles in flower organ determination and fruit development, we performed a genome-wide identification, characterisation and expression analysis of MADS-box genes in this Rosaceae tree. In this study, 80 MADS-box genes were identified in P. mume and categorised into MIKC, Mα, Mβ, Mγ and Mδ groups based on gene structures and phylogenetic relationships. The MIKC group could be further classified into 12 subfamilies. The FLC subfamily was absent in P. mume and the six tandemly arranged DAM genes might experience a species-specific evolution process in P. mume. The MADS-box gene family might experience an evolution process from MIKC genes to Mδ genes to Mα, Mβ and Mγ genes. The expression analysis suggests that P. mume MADS-box genes have diverse functions in P. mume development and the functions of duplicated genes diverged after the duplication events. In addition to its involvement in the development of female gametophytes, type I genes also play roles in male gametophytes development. In conclusion, this study adds to our understanding of the roles that the MADS-box genes played in flower and fruit development and lays a foundation for selecting candidate genes for functional studies in P. mume and other species. Furthermore, this study also provides a basis to study the evolution of the MADS-box family.

BOX-DEATH HOLLOW ROADLESS AREA, UTAH.

USGS Publications Warehouse

Weir, Gordon W.; Lane, Michael

1984-01-01

Geologic mapping, geochemical sampling, and a search for prospects and mineralized rock in the Box-Death Hollow Roadless Area, Utah indicate that there is little promise for the occurrence of mineral or energy resources in the area. Additional exploratory drilling by industry seems warranted if wells elsewhere in the region find oil or gas in strata as yet untested in the Box-Death Hollow Roadless Area.

San Diego field operational test of smart call boxes : technical aspects

DOT National Transportation Integrated Search

1997-01-01

Smart call boxes are devices similar to those used as emergency call boxes in California. The basic call box consists of a microprocessor, a cellular transceiver, and a solar power source. The smart call box system also includes data-collection devic...

Lack of the central nervous system- and neural crest-expressed forkhead gene Foxs1 affects motor function and body weight.

PubMed

Heglind, Mikael; Cederberg, Anna; Aquino, Jorge; Lucas, Guilherme; Ernfors, Patrik; Enerbäck, Sven

2005-07-01

To gain insight into the expression pattern and functional importance of the forkhead transcription factor Foxs1, we constructed a Foxs1-beta-galactosidase reporter gene "knock-in" (Foxs1beta-gal/beta-gal) mouse, in which the wild-type (wt) Foxs1 allele has been inactivated and replaced by a beta-galactosidase reporter gene. Staining for beta-galactosidase activity reveals an expression pattern encompassing neural crest-derived cells, e.g., cranial and dorsal root ganglia as well as several other cell populations in the central nervous system (CNS), most prominently the internal granule layer of cerebellum. Other sites of expression include the lachrymal gland, outer nuclear layer of retina, enteric ganglion neurons, and a subset of thalamic and hypothalamic nuclei. In the CNS, blood vessel-associated smooth muscle cells and pericytes stain positive for Foxs1. Foxs1beta-gal/beta-gal mice perform significantly better (P < 0.01) on a rotating rod than do wt littermates. We have also noted a lower body weight gain (P < 0.05) in Foxs1beta-gal/lbeta-gal males on a high-fat diet, and we speculate that dorsomedial hypothalamic neurons, expressing Foxs1, could play a role in regulating body weight via regulation of sympathetic outflow. In support of this, we observed increased levels of uncoupling protein 1 mRNA in Foxs1beta-gal/beta-gal mice. This points toward a role for Foxs1 in the integration and processing of neuronal signals of importance for energy turnover and motor function.

Axisymmetric Shearing Box Models of Magnetized Disks

NASA Astrophysics Data System (ADS)

Guan, Xiaoyue; Gammie, Charles F.

2008-01-01

The local model, or shearing box, has proven a useful model for studying the dynamics of astrophysical disks. Here we consider the evolution of magnetohydrodynamic (MHD) turbulence in an axisymmetric local model in order to evaluate the limitations of global axisymmetric models. An exploration of the model parameter space shows the following: (1) The magnetic energy and α-decay approximately exponentially after an initial burst of turbulence. For our code, HAM, the decay time τ propto Res , where Res/2 is the number of zones per scale height. (2) In the initial burst of turbulence the magnetic energy is amplified by a factor proportional to Res3/4λR, where λR is the radial scale of the initial field. This scaling applies only if the most unstable wavelength of the magnetorotational instability is resolved and the final field is subthermal. (3) The shearing box is a resonant cavity and in linear theory exhibits a discrete set of compressive modes. These modes are excited by the MHD turbulence and are visible as quasi-periodic oscillations (QPOs) in temporal power spectra of fluid variables at low spatial resolution. At high resolution the QPOs are hidden by a noise continuum. (4) In axisymmetry disk turbulence is local. The correlation function of the turbulence is limited in radial extent, and the peak magnetic energy density is independent of the radial extent of the box LR for LR > 2H. (5) Similar results are obtained for the HAM, ZEUS, and ATHENA codes; ATHENA has an effective resolution that is nearly double that of HAM and ZEUS. (6) Similar results are obtained for 2D and 3D runs at similar resolution, but only for particular choices of the initial field strength and radial scale of the initial magnetic field.

49 CFR 230.102 - Tender plain bearing journal boxes.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Tender plain bearing journal boxes. 230.102... Locomotives and Tenders Running Gear § 230.102 Tender plain bearing journal boxes. Plain bearing journal boxes... expected to damage the bearing; or have a detrimental effect on the lubrication of the journal and bearing...

49 CFR 230.102 - Tender plain bearing journal boxes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Tender plain bearing journal boxes. 230.102... Locomotives and Tenders Running Gear § 230.102 Tender plain bearing journal boxes. Plain bearing journal boxes... expected to damage the bearing; or have a detrimental effect on the lubrication of the journal and bearing...

Minimum airflow reset of single-duct VAV terminal boxes

NASA Astrophysics Data System (ADS)

Cho, Young-Hum

Single duct Variable Air Volume (VAV) systems are currently the most widely used type of HVAC system in the United States. When installing such a system, it is critical to determine the minimum airflow set point of the terminal box, as an optimally selected set point will improve the level of thermal comfort and indoor air quality (IAQ) while at the same time lower overall energy costs. In principle, this minimum rate should be calculated according to the minimum ventilation requirement based on ASHRAE standard 62.1 and maximum heating load of the zone. Several factors must be carefully considered when calculating this minimum rate. Terminal boxes with conventional control sequences may result in occupant discomfort and energy waste. If the minimum rate of airflow is set too high, the AHUs will consume excess fan power, and the terminal boxes may cause significant simultaneous room heating and cooling. At the same time, a rate that is too low will result in poor air circulation and indoor air quality in the air-conditioned space. Currently, many scholars are investigating how to change the algorithm of the advanced VAV terminal box controller without retrofitting. Some of these controllers have been found to effectively improve thermal comfort, indoor air quality, and energy efficiency. However, minimum airflow set points have not yet been identified, nor has controller performance been verified in confirmed studies. In this study, control algorithms were developed that automatically identify and reset terminal box minimum airflow set points, thereby improving indoor air quality and thermal comfort levels, and reducing the overall rate of energy consumption. A theoretical analysis of the optimal minimum airflow and discharge air temperature was performed to identify the potential energy benefits of resetting the terminal box minimum airflow set points. Applicable control algorithms for calculating the ideal values for the minimum airflow reset were developed and

Information technology: opening the box.

PubMed

Nussbaum, G M

1998-09-01

If you thought managed care was a tough nut to crack, wait until you have to start making decisions about your organization's information technology (IT). Information systems are complex and expensive, they can take years to implement, and, once installed, they need costly and regular upgrades. But for a contemporary clinical organization to function, this technology is as essential as power and water. For many years, information technology was seen as a black box, impenetrable and beyond real understanding. If done with knowledge and care, however, cracking the box opens up possibilities, not ruin.

6. VIEW OF SPILLWAY TIMBERS AND WATER CONTROL BOX, SHOWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

6. VIEW OF SPILLWAY TIMBERS AND WATER CONTROL BOX, SHOWING WATER CONTROL BOX WITH LOWERED LAKE LEVEL - Three Bears Lake & Dams, Water Control Box, North of Marias Pass, East Glacier Park, Glacier County, MT

Cryogenic distribution box for Fermi National Accelerator Laboratory

NASA Astrophysics Data System (ADS)

Svehla, M. R.; Bonnema, E. C.; Cunningham, E. K.

2017-12-01

Meyer Tool & Mfg., Inc (Meyer Tool) of Oak Lawn, Illinois is manufacturing a cryogenic distribution box for Fermi National Accelerator Laboratory (FNAL). The distribution box will be used for the Muon-to-electron conversion (Mu2e) experiment. The box includes twenty-seven cryogenic valves, two heat exchangers, a thermal shield, and an internal nitrogen separator vessel, all contained within a six-foot diameter ASME coded vacuum vessel. This paper discusses the design and manufacturing processes that were implemented to meet the unique fabrication requirements of this distribution box. Design and manufacturing features discussed include: 1) Thermal strap design and fabrication, 2) Evolution of piping connections to heat exchangers, 3) Nitrogen phase separator design, 4) ASME code design of vacuum vessel, and 5) Cryogenic valve installation.

Box C/D sRNA stem ends act as stabilizing anchors for box C/D di-sRNPs

PubMed Central

Yip, W. S. Vincent; Shigematsu, Hideki; Taylor, David W.; Baserga, Susan J.

2016-01-01

Ribosomal RNA (rRNA) modifications are essential for ribosome function in all cellular organisms. Box C/D small (nucleolar) ribonucleoproteins [s(no)RNPs] catalyze 2′-O-methylation, one rRNA modification type in Eukarya and Archaea. Negatively stained electron microscopy (EM) models of archaeal box C/D sRNPs have demonstrated the dimeric sRNP (di-sRNP) architecture, which has been corroborated by nuclear magnetic resonance (NMR) studies. Due to limitations of the structural techniques, the orientation of the box C/D sRNAs has remained unclear. Here, we have used cryo-EM to elucidate the sRNA orientation in a M. jannaschii box C/D di-sRNP. The cryo-EM reconstruction suggests a parallel orientation of the two sRNAs. Biochemical and structural analyses of sRNPs assembled with mutant sRNAs indicate a potential interaction between the sRNA stem ends. Our results suggest that the parallel arrangement of the sRNAs juxtaposes their stem ends into close proximity to allow for a stabilizing interaction that helps maintain the di-sRNP architecture. PMID:27342279

CDL description of the CDC 6600 stunt box

NASA Technical Reports Server (NTRS)

Hertzog, J. B.

1971-01-01

The CDC 6600 central memory control (stunt box) is described utilizing CDL (Computer Design Language), block diagrams, and text. The stunt box is a clearing house for all central memory references from the 6600 central and peripheral processors. Since memory requests can be issued simultaneously, the stunt box must be capable of assigning priorities to requests, of labeling requests so that the data will be distributed correctly, and of remembering rejected addresses due to memory conflicts.

46 CFR 113.10-7 - Connection boxes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Connection boxes. 113.10-7 Section 113.10-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING COMMUNICATION AND ALARM SYSTEMS AND EQUIPMENT Fire and Smoke Detecting and Alarm Systems § 113.10-7 Connection boxes. Each...

46 CFR 113.10-7 - Connection boxes.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Connection boxes. 113.10-7 Section 113.10-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING COMMUNICATION AND ALARM SYSTEMS AND EQUIPMENT Fire and Smoke Detecting and Alarm Systems § 113.10-7 Connection boxes. Each...

46 CFR 113.10-7 - Connection boxes.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Connection boxes. 113.10-7 Section 113.10-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING COMMUNICATION AND ALARM SYSTEMS AND EQUIPMENT Fire and Smoke Detecting and Alarm Systems § 113.10-7 Connection boxes. Each...

46 CFR 113.10-7 - Connection boxes.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Connection boxes. 113.10-7 Section 113.10-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING COMMUNICATION AND ALARM SYSTEMS AND EQUIPMENT Fire and Smoke Detecting and Alarm Systems § 113.10-7 Connection boxes. Each...

46 CFR 113.10-7 - Connection boxes.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Connection boxes. 113.10-7 Section 113.10-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING COMMUNICATION AND ALARM SYSTEMS AND EQUIPMENT Fire and Smoke Detecting and Alarm Systems § 113.10-7 Connection boxes. Each...

Boxing It Up-a Cross-curricular Approach.

ERIC Educational Resources Information Center

Till, Wesley

1996-01-01

Reports on a class project that examined the manufacture of boxes and packaging to teach about design and technology. The class discovered basic manufacturing techniques by examining and disassembling cereal boxes. Field trips to stores provided more examples. Appraises the children's final projects and discusses acquiring materials. (MJP)

FOXO family in regulating cancer and metabolism.

PubMed

Ma, Jian; Matkar, Smita; He, Xin; Hua, Xianxin

2018-06-01

FOXO proteins are a sub-group of a superfamily of forkhead box (FOX)-containing transcription factors (TFs). FOXOs play an important role in regulating a plethora of biological activities ranging from development, cell signaling, and tumorigenesis to cell metabolism. Here we mainly focus on reviewing the role of FOXOs in regulating tumor and metabolism. Moreover, how crosstalk among various pathways influences the function of FOXOs will be reviewed. Further, the paradoxical role for FOXOs in controlling the fate of cancer and especially resistance/sensitivity of cancer to the class of drugs that target PI3K/AKT will also be reviewed. Finally, how FOXOs regulate crosstalk between common cancer pathways and cell metabolism pathways, and how these crosstalks affect the fate of the cancer will be discussed. Copyright © 2018. Published by Elsevier Ltd.

Structure and mechanism of the T-box riboswitches

PubMed Central

Zhang, Jinwei

2015-01-01

In most Gram-positive bacteria, including many clinically devastating pathogens from genera such as Bacillus, Clostridium, Listeria and Staphylococcus, T-box riboswitches sense and regulate intracellular availability of amino acids through a multipartite mRNA-tRNA interaction. The T-box mRNA leaders respond to nutrient starvation by specifically binding cognate tRNAs and sensing whether the bound tRNA is aminoacylated, as a proxy for amino acid availability. Based on this readout, T-boxes direct a transcriptional or translational switch to control the expression of downstream genes involved in various aspects of amino acid metabolism: biosynthesis, transport, aminoacylation, transamidation, etc. Two decades after its discovery, the structural and mechanistic underpinnings of the T-box riboswitch were recently elucidated, producing a wealth of insights into how two structured RNAs can recognize each other with robust affinity and exquisite selectivity. The T-box paradigm exemplifies how natural non-coding RNAs can interact not just through sequence complementarity, but can add molecular specificity by precisely juxtaposing RNA structural motifs, exploiting inherently flexible elements and the biophysical properties of post-transcriptional modifications, ultimately achieving a high degree of shape complementarity through mutually induced fit. The T-box also provides a proof-of-principle that compact RNA domains can recognize minute chemical changes (such as tRNA aminoacylation) on another RNA. The unveiling of the structure and mechanism of the T-box system thus expands our appreciation of the range of capabilities and modes of action of structured non-coding RNAs, and hints at the existence of networks of non-coding RNAs that communicate through both, structural and sequence specificity. PMID:25959893

Projection optics box

DOEpatents

Hale, Layton C.; Malsbury, Terry; Hudyma, Russell M.; Parker, John M.

2000-01-01

A projection optics box or assembly for use in an optical assembly, such as in an extreme ultraviolet lithography (EUVL) system using 10-14 nm soft x-ray photons. The projection optics box utilizes a plurality of highly reflective optics or mirrors, each mounted on a precision actuator, and which reflects an optical image, such as from a mask, in the EUVL system onto a point of use, such as a target or silicon wafer, the mask, for example, receiving an optical signal from a source assembly, such as a developed from laser system, via a series of highly reflective mirrors of the EUVL system. The plurality of highly reflective optics or mirrors are mounted in a housing assembly comprised of a series of bulkheads having wall members secured together to form a unit construction of maximum rigidity. Due to the precision actuators, the mirrors must be positioned precisely and remotely in tip, tilt, and piston (three degrees of freedom), while also providing exact constraint.

Wild-type offspring of heterozygous prolactin receptor-null female mice have maladaptive β-cell responses during pregnancy.

PubMed

Huang, Carol

2013-03-01

Abstract  β-Cell mass increases during pregnancy in adaptation to the insulin resistance of pregnancy. This increase is accompanied by an increase in β-cell proliferation, a process that requires intact prolactin receptor (Prlr) signalling. Previously, it was found that during pregnancy, heterozygous prolactin receptor-null (Prlr(+/-)) mice had lower number of β-cells, lower serum insulin and higher blood glucose levels than wild-type (Prlr(+/+)) mice. An unexpected observation was that the glucose homeostasis of the experimental mouse depends on the genotype of her mother, such that within the Prlr(+/+) group, the Prlr(+/+) offspring derived from Prlr(+/+) mothers (Prlr(+/+(+/+))) had higher β-cell mass and lower blood glucose than those derived from Prlr(+/-) mothers (Prlr(+/+(+/-))). Pathways that are known to regulate β-cell proliferation during pregnancy include insulin receptor substrate-2, Akt, menin, the serotonin synthetic enzyme tryptophan hydroxylase-1, Forkhead box M1 and Forkhead box D3. The aim of the present study was to determine whether dysregulation in these signalling molecules in the islets could explain the maternal effect on the phenotype of the offspring. It was found that the pregnancy-induced increases in insulin receptor substrate-2 and Akt expression in the islets were attenuated in the Prlr(+/+(+/-)) mice in comparison to the Prlr(+/+(+/+)) mice. The expression of Forkhead box D3, which plays a permissive role for β-cell proliferation during pregnancy, was also lower in the Prlr(+/+(+/-)) mice. In contrast, the pregnancy-induced increases in phospho-Jak2, tryptophan hydroxylase-1 and FoxM1, as well as the pregnancy-associated reduction in menin expression, were comparable between the two groups. There was also no difference in expression levels of genes that regulate insulin synthesis and secretion (i.e. glucose transporter 2, glucokinase and pancreatic and duodenal homeobox-1) between these two groups. Taken together, these

Laparoscopic virtual reality simulator and box trainer in gynecology.

PubMed

Akdemir, Ali; Sendağ, Fatih; Oztekin, Mehmet K

2014-05-01

To investigate whether a virtual reality simulator (LapSim) and traditional box trainer are effective tools for the acquisition of basic laparoscopic skills, and whether the LapSim is superior to the box trainer in surgical education. In a study at Ege University School of Medicine, Izmir, Turkey, between September 2008 and March 2013, 40 first- and second-year residents were randomized to train via the LapSim or box trainer for 4 weeks, and 20 senior residents were allocated to a control group. All 3 groups performed laparoscopic bilateral tubal ligation. Video records of each operation were assessed via the general rating scale of the Objective Structured Assessment of Laparoscopic Salpingectomy and by operation time in seconds. Compared with the control group, the LapSim and box trainer groups performed significantly better in total score (P<0.01 and P<0.01, respectively) and time (P=0.03 and P=0.01, respectively). There were no differences between the LapSim and box trainer groups. Novice residents who trained on a LapSim or box trainer performed better live laparoscopies than residents who trained via standard clinical surgical education. Training with a virtual reality simulator or box trainer should be considered before actual laparoscopic procedures are carried out. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Empirical and Perceived Utility of Text Boxes

ERIC Educational Resources Information Center

Benbassat, Danny; Underwood, Tim R.; Bailey, Brian P.; Albright, Charles; Chadwell, Brian J.

2008-01-01

This paper presents 2 studies that investigated the utility of textbook boxes. In the first study, 230 participants completed a perception questionnaire. The major finding was that professors and students rarely studied boxed text. In the second study, 177 participants read identical text with an insert that instructed them to stop reading and…

Meal box schemes a convenient way to avoid convenience food? Uses and understandings of meal box schemes among Danish consumers.

PubMed

Hertz, Frej Daniel; Halkier, Bente

2017-07-01

The term convenience food is subject to diversification, lack of clarity and moral ambiguity. In this paper we address these issues and critically discuss convenience food by using empirical findings from a Danish study that deals with practitioners' uses of meal box schemes. The methodological design consists of thirteen individual interviews, four focus groups and some observations of cooking practices. We combine the empirical findings with a particular definition of convenience food by Brunner et al. (2010) and selected practice theoretical concepts. This particular combination enables us to categorize meal box schemes as a new form of convenience food called convenient food. In addition, results suggest that meal box schemes reduce leftovers from dinner. Meal boxes also influence dinner related activities such as planning ahead in time and grocery shopping, which require less physical and mental effort. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ballast system for maintaining constant pressure in a glove box

NASA Technical Reports Server (NTRS)

Shlichta, Paul J. (Inventor)

1990-01-01

A ballast system for a glove box including a fixed platform on which is mounted an inflatable bag on top of which resides a cover and a weight. The variable gas volume of the inflatable bag communicates with that of the glove box via a valved tube. The weight and gas volume are selected to maintain a relatively constant pressure in the glove box despite variations in the glove box volume while avoiding the use of complicated valving apparatus.

A Group Action Method for Construction of Strong Substitution Box

NASA Astrophysics Data System (ADS)

Jamal, Sajjad Shaukat; Shah, Tariq; Attaullah, Atta

2017-06-01

In this paper, the method to develop cryptographically strong substitution box is presented which can be used in multimedia security and data hiding techniques. The algorithm of construction depends on the action of a projective general linear group over the set of units of the finite commutative ring. The strength of substitution box and ability to create confusion is assessed with different available analyses. Moreover, the ability of resistance against malicious attacks is also evaluated. The substitution box is examined by bit independent criterion, strict avalanche criterion, nonlinearity test, linear approximation probability test and differential approximation probability test. This substitution box is equated with well-recognized substitution boxes such as AES, Gray, APA, S8, prime of residue, Xyi and Skipjack. The comparison shows encouraging results about the strength of the proposed box. The majority logic criterion is also calculated to analyze the strength and its practical implementation.

Ignorance is a bliss: Mathematical structure of many-box models

NASA Astrophysics Data System (ADS)

Tylec, Tomasz I.; Kuś, Marek

2018-03-01

We show that the propositional system of a many-box model is always a set-representable effect algebra. In particular cases of 2-box and 1-box models, it is an orthomodular poset and an orthomodular lattice, respectively. We discuss the relation of the obtained results with the so-called Local Orthogonality principle. We argue that non-classical properties of box models are the result of a dual enrichment of the set of states caused by the impoverishment of the set of propositions. On the other hand, quantum mechanical models always have more propositions as well as more states than the classical ones. Consequently, we show that the box models cannot be considered as generalizations of quantum mechanical models and seeking additional principles that could allow us to "recover quantum correlations" in box models are, at least from the fundamental point of view, pointless.

Using rap music to promote adolescent health: pilot study of VoxBox.

PubMed

Paukste, Ernesta; Harris, Neil

2015-04-01

Alcohol, tobacco and other drugs (ATODs) usage among adolescents, particularly those living in lower socioeconomic communities, is a population health problem in Australia that requires innovative health promotion strategies. There is a growing recognition of the potential of arts-based approaches to engage youth in health promoting activities. This paper presents the process evaluation of the pilot VoxBox intervention that used rap to build adolescents' awareness of risks associated with ATODs. The VoxBox intervention was piloted in Logan, Queensland, at five high schools with 18 adolescents completing the intervention. Data collection methods included observation, focus groups, semi-structured interviews and a survey of adolescent participants. The intervention was well received by participants and stakeholders. Three factors characterising the project's successful engagement of adolescents were: participate - go with the flow, learning from the real deal and resourced to make some noise. In VoxBox, the emphasis on engaging adolescents in an activity of real interest that was appropriately resourced and delivered was central to credibility and success. SO WHAT?: The findings highlight the importance of interventions matching the interests of the targeted population group.

Convective Patterns under the Indo-Atlantic box

NASA Astrophysics Data System (ADS)

Davaille, A.; Stutzmann, E.; Silveira, G.; Besse, J.; Courtillot, V.

2005-12-01

Using recent fluid mechanics results as a framework, we reinterpret the images of the Indo-Atlantic mantle obtained from global and regional tomography studies together with geochemical, geological and paleomagnetic observations to unravel the pattern of convection in the Indo-Atlantic box and its temporal evolution over the last 260 Myr. Seismic tomography sections at different depths show that the Earth's mantle seems to be divided in two boxes by the subducted plates, the Pacific and the Indo-Atlantic boxes. The latter presently contains a) a broad slow seismic anomaly at the CMB which has a similar shape to Pangea 250 Myr ago, and which divides into several branches higher in the lower mantle, b) one superswell centered on the western edge of South Africa, c) at least 6 primary hotspots with long tracks related to traps, and d) numerous smaller hotspots. Moreover, in the last 260 Myr, this mantle box has undergone 10 traps events, 7 of them related to continental break up. Several of these past events are spatially correlated with present-day seismic anomalies and/or upwellings, suggesting episodicity. Laboratory experiments show that superswells, long-lived hotspot tracks and traps may represent three evolutionnary stages of the same phenomenon, i.e. the episodic destabilization of a hot, chemically heterogeneous thermal boundary layer, close to the bottom of the mantle. When scaled to the Earth's mantle, the recurrence time of this phenomenon is on the order of 100-200 Myr. Also, at any given time, the Indo-Atlantic box should contain 3 to 9 of these instabilities at different stages of their development. This is in agreement with observations. The return flow of the downwelling slabs, although confined to two main boxes by subduction zone geometry, may therefore not be passive, but rather take the form of active thermochemical instabilities.

Cereal Box Design: An Interdisciplinary Graphics Activity

ERIC Educational Resources Information Center

Fitzgerald, Mike; Tsosie, Teri

2004-01-01

This article describes cereal box design, an interdisciplinary graphics activity. The cereal box design activity is intriguing both for its simplicity and the resourcefulness that it can generate in young people. It lends itself to a variety of curriculums. It covers both consumerism and Design for the Environment (DfE) concepts broadly and in…

An amphioxus winged helix/forkhead gene, AmphiFoxD: insights into vertebrate neural crest evolution

NASA Technical Reports Server (NTRS)

Yu, Jr-Kai; Holland, Nicholas D.; Holland, Linda Z.

2002-01-01

During amphioxus development, the neural plate is bordered by cells expressing many genes with homologs involved in vertebrate neural crest induction. However, these amphioxus cells evidently lack additional genetic programs for the cell delaminations, migrations, and differentiations characterizing definitive vertebrate neural crest. We characterize an amphioxus winged helix/forkhead gene (AmphiFoxD) closely related to vertebrate FoxD genes. Phylogenetic analysis indicates that the AmphiFoxD is basal to vertebrate FoxD1, FoxD2, FoxD3, FoxD4, and FoxD5. One of these vertebrate genes (FoxD3) consistently marks neural crest during development. Early in amphioxus development, AmphiFoxD is expressed medially in the anterior neural plate as well as in axial (notochordal) and paraxial mesoderm; later, the gene is expressed in the somites, notochord, cerebral vesicle (diencephalon), and hindgut endoderm. However, there is never any expression in cells bordering the neural plate. We speculate that an AmphiFoxD homolog in the common ancestor of amphioxus and vertebrates was involved in histogenic processes in the mesoderm (evagination and delamination of the somites and notochord); then, in the early vertebrates, descendant paralogs of this gene began functioning in the presumptive neural crest bordering the neural plate to help make possible the delaminations and cell migrations that characterize definitive vertebrate neural crest. Copyright 2002 Wiley-Liss, Inc.

49 CFR 230.63 - Smoke box, steam pipes and pressure parts.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Smoke box, steam pipes and pressure parts. 230.63... Appurtenances Steam Pipes § 230.63 Smoke box, steam pipes and pressure parts. The smoke box, steam pipes and... individual conducting the inspection must enter the smoke box to conduct the inspection, looking for signs of...

49 CFR 230.63 - Smoke box, steam pipes and pressure parts.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Smoke box, steam pipes and pressure parts. 230.63... Appurtenances Steam Pipes § 230.63 Smoke box, steam pipes and pressure parts. The smoke box, steam pipes and... individual conducting the inspection must enter the smoke box to conduct the inspection, looking for signs of...

49 CFR 230.63 - Smoke box, steam pipes and pressure parts.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Smoke box, steam pipes and pressure parts. 230.63... Appurtenances Steam Pipes § 230.63 Smoke box, steam pipes and pressure parts. The smoke box, steam pipes and... individual conducting the inspection must enter the smoke box to conduct the inspection, looking for signs of...

49 CFR 230.63 - Smoke box, steam pipes and pressure parts.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Smoke box, steam pipes and pressure parts. 230.63... Appurtenances Steam Pipes § 230.63 Smoke box, steam pipes and pressure parts. The smoke box, steam pipes and... individual conducting the inspection must enter the smoke box to conduct the inspection, looking for signs of...

A Comparison of Energy Expenditure During "Wii Boxing" Versus Heavy Bag Boxing in Young Adults.

PubMed

Perusek, Kristen; Sparks, Kenneth; Little, Kathleen; Motley, Mary; Patterson, Sheila; Wieand, Jennifer

2014-02-01

Traditional computer videogames are sedentary, whereas new computer videogames, such as the Nintendo(®) (Redmond, WA) "Wii™ Sports" games, allow users to physically interact while playing the sport. Energy expenditure (EE), heart rate (HR), and rating of perceived exertion (RPE) during heavy bag boxing versus the Nintendo "Wii Boxing" game were compared. Fifteen males and 14 females (mean age, 25.6 years; height, 171.3 cm; weight, 71.8 kg) randomly selected (by a coin toss) heavy bag boxing or "Wii Boxing" for their first test session and completed the other protocol at their second session at least 2 days later. Each session lasted for a total duration of 30 minutes and consisted of 10 3-minute exercise bouts with measurements of HR, RPE, and EE obtained from indirect calorimetry. A paired-samples t test was used to analyze the results. Significant differences were found for HR (bag, 156 beats per minute; Wii, 138 beats per minute; P=0.001) and RPE (bag, 13.8; Wii, 11.4; P=0.0001) but not for EE (bag, 8.0 kcal/minute; Wii, 7.1 kcal/minute; bag, 241 total kcal; Wii, 213 total kcal; P=0.078). The results suggest that computer active videogames, such as the Nintendo Wii, have the potential to provide similar EE as their traditional forms of exercise and may be a sufficient replacement for traditional target HR zone activities, especially in less fit individuals. Further research is needed to compare EE for different "Wii Sports" games with those for their traditional forms of exercise.

Advances in the theory of box integrals

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

Bailey, David H.; Borwein, J.M.; Crandall, R.E.

2009-06-25

Box integrals - expectations <|{rvec r}|{sup s}> or <|{rvec r}-{rvec q}|{sup s}> over the unit n-cube (or n-box) - have over three decades been occasionally given closed forms for isolated n,s. By employing experimental mathematics together with a new, global analytic strategy, we prove that for n {le} 4 dimensions the box integrals are for any integer s hypergeometrically closed in a sense we clarify herein. For n = 5 dimensions, we show that a single unresolved integral we call K{sub 5} stands in the way of such hyperclosure proofs. We supply a compendium of exemplary closed forms that naturallymore » arise algorithmically from this theory.« less

Box C/D sRNA stem ends act as stabilizing anchors for box C/D di-sRNPs.

PubMed

Yip, W S Vincent; Shigematsu, Hideki; Taylor, David W; Baserga, Susan J

2016-10-14

Ribosomal RNA (rRNA) modifications are essential for ribosome function in all cellular organisms. Box C/D small (nucleolar) ribonucleoproteins [s(no)RNPs] catalyze 2'-O-methylation, one rRNA modification type in Eukarya and Archaea. Negatively stained electron microscopy (EM) models of archaeal box C/D sRNPs have demonstrated the dimeric sRNP (di-sRNP) architecture, which has been corroborated by nuclear magnetic resonance (NMR) studies. Due to limitations of the structural techniques, the orientation of the box C/D sRNAs has remained unclear. Here, we have used cryo-EM to elucidate the sRNA orientation in a M. jannaschii box C/D di-sRNP. The cryo-EM reconstruction suggests a parallel orientation of the two sRNAs. Biochemical and structural analyses of sRNPs assembled with mutant sRNAs indicate a potential interaction between the sRNA stem ends. Our results suggest that the parallel arrangement of the sRNAs juxtaposes their stem ends into close proximity to allow for a stabilizing interaction that helps maintain the di-sRNP architecture. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Interaction of MYC with host cell factor-1 is mediated by the evolutionarily conserved Myc box IV motif.

PubMed

Thomas, L R; Foshage, A M; Weissmiller, A M; Popay, T M; Grieb, B C; Qualls, S J; Ng, V; Carboneau, B; Lorey, S; Eischen, C M; Tansey, W P

2016-07-07

The MYC family of oncogenes encodes a set of three related transcription factors that are overexpressed in many human tumors and contribute to the cancer-related deaths of more than 70,000 Americans every year. MYC proteins drive tumorigenesis by interacting with co-factors that enable them to regulate the expression of thousands of genes linked to cell growth, proliferation, metabolism and genome stability. One effective way to identify critical co-factors required for MYC function has been to focus on sequence motifs within MYC that are conserved throughout evolution, on the assumption that their conservation is driven by protein-protein interactions that are vital for MYC activity. In addition to their DNA-binding domains, MYC proteins carry five regions of high sequence conservation known as Myc boxes (Mb). To date, four of the Mb motifs (MbI, MbII, MbIIIa and MbIIIb) have had a molecular function assigned to them, but the precise role of the remaining Mb, MbIV, and the reason for its preservation in vertebrate Myc proteins, is unknown. Here, we show that MbIV is required for the association of MYC with the abundant transcriptional coregulator host cell factor-1 (HCF-1). We show that the invariant core of MbIV resembles the tetrapeptide HCF-binding motif (HBM) found in many HCF-interaction partners, and demonstrate that MYC interacts with HCF-1 in a manner indistinguishable from the prototypical HBM-containing protein VP16. Finally, we show that rationalized point mutations in MYC that disrupt interaction with HCF-1 attenuate the ability of MYC to drive tumorigenesis in mice. Together, these data expose a molecular function for MbIV and indicate that HCF-1 is an important co-factor for MYC.

SUSCEPTIBILITY OF A GULF OF MEXICO ESTUARY TO HYPOXIA: AN ANALYSIS USING BOX MODELS

EPA Science Inventory

The extent of hypoxia and the physical factors affecting development and maintenance of hypoxia were examined for Pensacola Bay, Florida (USA) by conducting monthly water quality surveys for 3 years and by constructing salt-and-water balance box models using the resulting data. W...

Cloning, characterization, regulation, and function of dormancy-associated MADS-BOX genes from leafy spurge

USDA-ARS?s Scientific Manuscript database

DORMANCY-ASSOCIATED MADS-BOX (DAM) genes are transcription factors that have been linked to endodormancy induction. The evergrowing mutation in peach, which renders it incapable of entering endodormancy, resulted from a deletion in a series of DAM genes (Bielenberg et al. 2008). Likewise, DAM genes ...

Cloning, Characterization, Regulation, and Function of DORMANCY-ASSOCIATED MADS-BOX Genes from Leafy Spurge

USDA-ARS?s Scientific Manuscript database

DORMANCY-ASSOCIATED MADS-BOX (DAM) genes are transcription factors that have been linked to endodormancy induction. The evergrowing mutation in peach, which renders it incapable of entering endodormancy, resulted from a deletion in a series of DAM genes (Bielenberg et al. 2008). Likewise, DAM genes ...

Ballast system for maintaining constant pressure in a glove box

NASA Technical Reports Server (NTRS)

Shlichta, Paul J. (Inventor)

1989-01-01

A ballast system is disclosed for a glove box including a fixed platform on which is mounted an inflatable bag on top of which resides a cover and a weight. The variable gas volume of the inflatable bag communicates with that of the glove box via a valved tube. The weight and the gas volume are selected to maintain a relatively constant pressure in the glove box despite variations in the glove box volume while avoiding the use of complicated valving apparatus.

Ballast system for maintaining constant pressure in a glove box

NASA Astrophysics Data System (ADS)

Shlichta, Paul J.

1989-09-01

A ballast system is disclosed for a glove box including a fixed platform on which is mounted an inflatable bag on top of which resides a cover and a weight. The variable gas volume of the inflatable bag communicates with that of the glove box via a valved tube. The weight and the gas volume are selected to maintain a relatively constant pressure in the glove box despite variations in the glove box volume while avoiding the use of complicated valving apparatus.

Glove box on vehicular instrument panel

DOEpatents

Atarashi, Kazuya

1985-01-01

A glove box for the upper surface of an automobile dashboard whereby it may be positioned close to the driver. The glove box lid is pivotally supported by arms extending down either side to swing forwardly for opening. A hook is pivotally support adjacent an arm and weighted to swing into engagement with the arm to prevent opening of the lid during abrupt deceleration. A toggle spring assists in maintaining the lid in either the open or closed position.

Analysis of S-box in Image Encryption Using Root Mean Square Error Method

NASA Astrophysics Data System (ADS)

Hussain, Iqtadar; Shah, Tariq; Gondal, Muhammad Asif; Mahmood, Hasan

2012-07-01

The use of substitution boxes (S-boxes) in encryption applications has proven to be an effective nonlinear component in creating confusion and randomness. The S-box is evolving and many variants appear in literature, which include advanced encryption standard (AES) S-box, affine power affine (APA) S-box, Skipjack S-box, Gray S-box, Lui J S-box, residue prime number S-box, Xyi S-box, and S8 S-box. These S-boxes have algebraic and statistical properties which distinguish them from each other in terms of encryption strength. In some circumstances, the parameters from algebraic and statistical analysis yield results which do not provide clear evidence in distinguishing an S-box for an application to a particular set of data. In image encryption applications, the use of S-boxes needs special care because the visual analysis and perception of a viewer can sometimes identify artifacts embedded in the image. In addition to existing algebraic and statistical analysis already used for image encryption applications, we propose an application of root mean square error technique, which further elaborates the results and enables the analyst to vividly distinguish between the performances of various S-boxes. While the use of the root mean square error analysis in statistics has proven to be effective in determining the difference in original data and the processed data, its use in image encryption has shown promising results in estimating the strength of the encryption method. In this paper, we show the application of the root mean square error analysis to S-box image encryption. The parameters from this analysis are used in determining the strength of S-boxes

S-Boxes Based on Affine Mapping and Orbit of Power Function

NASA Astrophysics Data System (ADS)

Khan, Mubashar; Azam, Naveed Ahmed

2015-06-01

The demand of data security against computational attacks such as algebraic, differential, linear and interpolation attacks has been increased as a result of rapid advancement in the field of computation. It is, therefore, necessary to develop such cryptosystems which can resist current cryptanalysis and more computational attacks in future. In this paper, we present a multiple S-boxes scheme based on affine mapping and orbit of the power function used in Advanced Encryption Standard (AES). The proposed technique results in 256 different S-boxes named as orbital S-boxes. Rigorous tests and comparisons are performed to analyse the cryptographic strength of each of the orbital S-boxes. Furthermore, gray scale images are encrypted by using multiple orbital S-boxes. Results and simulations show that the encryption strength of the orbital S-boxes against computational attacks is better than that of the existing S-boxes.

The Twist Box Domain is Required for Twist1-induced Prostate Cancer Metastasis

PubMed Central

Gajula, Rajendra P.; Chettiar, Sivarajan T.; Williams, Russell D.; Thiyagarajan, Saravanan; Kato, Yoshinori; Aziz, Khaled; Wang, Ruoqi; Gandhi, Nishant; Wild, Aaron T.; Vesuna, Farhad; Ma, Jinfang; Salih, Tarek; Cades, Jessica; Fertig, Elana; Biswal, Shyam; Burns, Timothy F.; Chung, Christine H.; Rudin, Charles M.; Herman, Joseph M.; Hales, Russell K.; Raman, Venu; An, Steven S.; Tran, Phuoc T.

2013-01-01

Twist1, a basic helix-loop-helix transcription factor, plays a key role during development and is a master regulator of the epithelial-mesenchymal transition (EMT) that promotes cancer metastasis. Structure-function relationships of Twist1 to cancer-related phenotypes are underappreciated, so we studied the requirement of the conserved Twist box domain for metastatic phenotypes in prostate cancer (PCa). Evidence suggests that Twist1 is overexpressed in clinical specimens and correlated with aggressive/metastatic disease. Therefore, we examined a transactivation mutant, Twist1-F191G, in PCa cells using in vitro assays which mimic various stages of metastasis. Twist1 overexpression led to elevated cytoskeletal stiffness and cell traction forces at the migratory edge of cells based on biophysical single-cell measurements. Twist1 conferred additional cellular properties associated with cancer cell metastasis including increased migration, invasion, anoikis resistance, and anchorage-independent growth. The Twist box mutant was defective for these Twist1 phenotypes in vitro. Importantly, we observed a high frequency of Twist1-induced metastatic lung tumors and extra-thoracic metastases in vivo using the experimental lung metastasis assay. The Twist box was required for PCa cells to colonize metastatic lung lesions and extra-thoracic metastases. Comparative genomic profiling revealed transcriptional programs directed by the Twist box that were associated with cancer progression, such as Hoxa9. Mechanistically, Twist1 bound to the Hoxa9 promoter and positively regulated Hoxa9 expression in PCa cells. Finally, Hoxa9 was important for Twist1-induced cellular phenotypes associated with metastasis. These data suggest that the Twist box domain is required for Twist1 transcriptional programs and PCa metastasis. PMID:23982216

Contactin‑associated protein‑like 2 expression in SH‑SY5Y cells is upregulated by a FOXP2 mutant with a shortened poly‑glutamine tract.

PubMed

Zhao, Yunjing; Liu, Xiaoliang; Sun, Hongwei; Wang, Yueping; Yang, Wenzhu; Ma, Hongwei

2015-12-01

The forkhead box protein P2 (FOXP2) gene encodes an important transcription factor that contains a polyglutamine (poly‑Q) tract and a forkhead DNA binding domain. It has been observed that FOXP2 is associated with speech sound disorder (SSD), and mutations that decrease the length of the poly‑Q tract were identified in the FOXP2 gene of SSD patients. However, the exact role of poly‑Q reduction is not well understood. In the present study, constructs expressing wild‑type and poly‑Q reduction mutants of FOXP2 were generated by polymerase chain reaction (PCR) using lentiviral vectors and transfected into the SH‑SY5Y neuronal cell line. Quantitative reverse transcription (qRT)‑PCR and western blotting indicated that infected cells stably expressed high levels of FOXP2. Using this cell model, the impact of FOXP2 on the expression of contactin‑associated protein‑like 2 (CNTNAP2) were investigated, and CNTNAP2 mRNA expression levels were observed to be significantly higher in cells expressing poly‑Q‑reduced FOXP2. In addition, the expression level of CASPR2, a mammalian homolog of Drosophila Neurexin IV, was increased in cells expressing the FOXP2 mutant. Demonstration of regulation by FOXP2 indicates that CNTNAP2 may also be involved in SSD.

In vivo binding of hot pepper bZIP transcription factor CabZIP1 to the G-box region of pathogenesis-related protein 1 promoter

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

Lee, Boo-Ja; Park, Chang-Jin; Kim, Sung-Kyu

2006-05-26

We find that salicylic acid and ethephon treatment in hot pepper increases the expression of a putative basic/leucine zipper (bZIP) transcription factor gene, CabZIP1. CabZIP1 mRNA is expressed ubiquitously in various organs. The green fluorescent protein-fused transcription factor, CabZIP1::GFP, can be specifically localized to the nucleus, an action that is consistent with the presence of a nuclear localization signal in its protein sequence. Transient overexpression of the CabZIP1 transcription factor results in an increase in PR-1 transcripts level in Nicotiana benthamiana leaves. Using chromatin immunoprecipitation, we demonstrate that CabZIP1 binds to the G-box elements in native promoter of the hotmore » pepper pathogenesis-related protein 1 (CaPR-1) gene in vivo. Taken together, our results suggest that CabZIP1 plays a role as a transcriptional regulator of the CaPR-1 gene.« less

PCB-Based Break-Out Box

NASA Technical Reports Server (NTRS)

Lee, Jason H.

2011-01-01

Break-out boxes (BOBs) are necessary for all electrical integration/cable checkouts and troubleshooting. Because the price of a BOB is high, and no work can be done without one, often the procedure stops, simply waiting for a BOB. A less expensive BOB would take less time in the integration, testing, and troubleshooting process. The PCB-based BOB works and looks the same as a standard JPL BOB, called Gold Boxes. The only differences between the old BOB and the new PCB-based BOB is that the new one has 80 percent of its circuitry in a printed circuit board. This process reduces the time for fabrication, thus making the BOBs less expensive. Moreover, because of its unique design, the new BOBs can be easily assembled and fixed. About 80 percent of the new PCB-based BOB is in a $22 (at the time of this reporting) custom-designed, yet commercially available PCB. This device has been used successfully to verify that BOB cables were properly made. Also, upon completion, the BOB was beeped out via a multimeter to ensure that all sockets on the connectors were properly connected to the respective banana jack. When compared to the Gold Box BOBs, the new BOB has many advantages. It is much more cost efficient, it delivers equal usability at substantially lower cost of the BOB, and the Gold Box is much heavier when compared to the new BOB. The new BOB is also a bit longer and much more versatile in that connectors are easily changeable and if a banana jack is broken, it can be replaced instead of throwing away an entire BOB.

Study of Randomness in AES Ciphertexts Produced by Randomly Generated S-Boxes and S-Boxes with Various Modulus and Additive Constant Polynomials

NASA Astrophysics Data System (ADS)

Das, Suman; Sadique Uz Zaman, J. K. M.; Ghosh, Ranjan

2016-06-01

In Advanced Encryption Standard (AES), the standard S-Box is conventionally generated by using a particular irreducible polynomial {11B} in GF(28) as the modulus and a particular additive constant polynomial {63} in GF(2), though it can be generated by many other polynomials. In this paper, it has been shown that it is possible to generate secured AES S-Boxes by using some other selected modulus and additive polynomials and also can be generated randomly, using a PRNG like BBS. A comparative study has been made on the randomness of corresponding AES ciphertexts generated, using these S-Boxes, by the NIST Test Suite coded for this paper. It has been found that besides using the standard one, other moduli and additive constants are also able to generate equally or better random ciphertexts; the same is true for random S-Boxes also. As these new types of S-Boxes are user-defined, hence unknown, they are able to prevent linear and differential cryptanalysis. Moreover, they act as additional key-inputs to AES, thus increasing the key-space.

Sequence-specific DNA binding by MYC/MAX to low-affinity non-E-box motifs.

PubMed

Allevato, Michael; Bolotin, Eugene; Grossman, Mark; Mane-Padros, Daniel; Sladek, Frances M; Martinez, Ernest

2017-01-01

The MYC oncoprotein regulates transcription of a large fraction of the genome as an obligatory heterodimer with the transcription factor MAX. The MYC:MAX heterodimer and MAX:MAX homodimer (hereafter MYC/MAX) bind Enhancer box (E-box) DNA elements (CANNTG) and have the greatest affinity for the canonical MYC E-box (CME) CACGTG. However, MYC:MAX also recognizes E-box variants and was reported to bind DNA in a "non-specific" fashion in vitro and in vivo. Here, in order to identify potential additional non-canonical binding sites for MYC/MAX, we employed high throughput in vitro protein-binding microarrays, along with electrophoretic mobility-shift assays and bioinformatic analyses of MYC-bound genomic loci in vivo. We identified all hexameric motifs preferentially bound by MYC/MAX in vitro, which include the low-affinity non-E-box sequence AACGTT, and found that the vast majority (87%) of MYC-bound genomic sites in a human B cell line contain at least one of the top 21 motifs bound by MYC:MAX in vitro. We further show that high MYC/MAX concentrations are needed for specific binding to the low-affinity sequence AACGTT in vitro and that elevated MYC levels in vivo more markedly increase the occupancy of AACGTT sites relative to CME sites, especially at distal intergenic and intragenic loci. Hence, MYC binds diverse DNA motifs with a broad range of affinities in a sequence-specific and dose-dependent manner, suggesting that MYC overexpression has more selective effects on the tumor transcriptome than previously thought.

Small molecule therapeutics targeting F-box proteins in cancer.

PubMed

Liu, Yuan; Mallampalli, Rama K

2016-02-01

The ubiquitin proteasome system (UPS) plays vital roles in maintaining protein equilibrium mainly through proteolytic degradation of targeted substrates. The archetypical SCF ubiquitin E3 ligase complex contains a substrate recognition subunit F-box protein that recruits substrates to the catalytic ligase core for its polyubiquitylation and subsequent proteasomal degradation. Several well-characterized F-box proteins have been demonstrated that are tightly linked to neoplasia. There is mounting information characterizing F-box protein-substrate interactions with the rationale to develop unique therapeutics for cancer treatment. Here we review that how F-box proteins function in cancer and summarize potential small molecule inhibitors for cancer therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genome-wide survey and expression analysis of F-box genes in chickpea.

PubMed

Gupta, Shefali; Garg, Vanika; Kant, Chandra; Bhatia, Sabhyata

2015-02-13

The F-box genes constitute one of the largest gene families in plants involved in degradation of cellular proteins. F-box proteins can recognize a wide array of substrates and regulate many important biological processes such as embryogenesis, floral development, plant growth and development, biotic and abiotic stress, hormonal responses and senescence, among others. However, little is known about the F-box genes in the important legume crop, chickpea. The available draft genome sequence of chickpea allowed us to conduct a genome-wide survey of the F-box gene family in chickpea. A total of 285 F-box genes were identified in chickpea which were classified based on their C-terminal domain structures into 10 subfamilies. Thirteen putative novel motifs were also identified in F-box proteins with no known functional domain at their C-termini. The F-box genes were physically mapped on the 8 chickpea chromosomes and duplication events were investigated which revealed that the F-box gene family expanded largely due to tandem duplications. Phylogenetic analysis classified the chickpea F-box genes into 9 clusters. Also, maximum syntenic relationship was observed with soybean followed by Medicago truncatula, Lotus japonicus and Arabidopsis. Digital expression analysis of F-box genes in various chickpea tissues as well as under abiotic stress conditions utilizing the available chickpea transcriptome data revealed differential expression patterns with several F-box genes specifically expressing in each tissue, few of which were validated by using quantitative real-time PCR. The genome-wide analysis of chickpea F-box genes provides new opportunities for characterization of candidate F-box genes and elucidation of their function in growth, development and stress responses for utilization in chickpea improvement.

An effective box trap for capturing lynx

Treesearch

Jay A. Kolbe; John R. Squires; Thomas W. Parker

2003-01-01

We designed a box trap for capturing lynx (Lynx lynx) that is lightweight, safe, effective, and less expensive than many commercial models. It can be constructed in approximately 3-4 hours from readily available materials. We used this trap to capture 40 lynx 89 times (96% of lynx entering traps) and observed no trapping related injuries. We compare our box...

Fauna using nest boxes in four timber types in eastern Texas

Treesearch

Richard N. Conner; Daniel Saenz; D. Craig Rudolph

1995-01-01

Occupancy of 240 nest boxes in pure pine, pine-hardwood, upland hardwood, and bottomland hardwood forests (60 boxes in each forest type) were monitored for six years on the Stephen F. Austin Experimental Forest, Nacogdoches County in eastern Texas. Three boxes were placed at twenty sites in each forest type. Initially, each site had a box with 3.2, 4.7, or 5.7 cm...

49 CFR 178.512 - Standards for steel or aluminum boxes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Standards for steel or aluminum boxes. 178.512... FOR PACKAGINGS Non-bulk Performance-Oriented Packaging Standards § 178.512 Standards for steel or aluminum boxes. (a) The following are identification codes for steel or aluminum boxes: (1) 4A for a steel...

Non-local boxes and their implementation in Minecraft

NASA Astrophysics Data System (ADS)

Simnacher, Timo Yannick

PR-boxes are binary devices connecting two remote parties satisfying x AND y = a + b mod 2, where x and y denote the binary inputs and a and b are the respective outcomes without signaling. These devices are named after their inventors Sandu Popescu and Daniel Rohrlich and saturate the Clauser-Horne-Shimony-Holt (CHSH) inequality. This Bell-like inequality bounds the correlation that can exist between two remote, non-signaling, classical systems described by local hidden variable theories. Experiments have now convincingly shown that quantum entanglement cannot be explained by local hidden variable theories. Furthermore, the CHSH inequality provides a method to distinguish quantum systems from super-quantum correlations. The correlation between the outputs of the PR-box goes beyond any quantum entanglement. Though PR-boxes would have impressive consequences, as far as we know they are not physically realizable. However, by introducing PR-boxes to Minecraft as part of the redstone system, which simulates the electrical components for binary computing, we can experience the consequences of super-quantum correlations. For instance, Wim van Dam proved that two parties can use a sufficient number of PR-boxes to compute any Boolean function f(x,y) with only one bit of communication.

49 CFR 178.513 - Standards for boxes of natural wood.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 4C2 box must be one piece or equivalent. Parts are considered equivalent to one piece when one of the... 49 Transportation 3 2012-10-01 2012-10-01 false Standards for boxes of natural wood. 178.513... PACKAGINGS Non-bulk Performance-Oriented Packaging Standards § 178.513 Standards for boxes of natural wood...

49 CFR 178.513 - Standards for boxes of natural wood.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 4C2 box must be one piece or equivalent. Parts are considered equivalent to one piece when one of the... 49 Transportation 3 2014-10-01 2014-10-01 false Standards for boxes of natural wood. 178.513... PACKAGINGS Non-bulk Performance-Oriented Packaging Standards § 178.513 Standards for boxes of natural wood...

Shoe Box Circuits

ERIC Educational Resources Information Center

Sandifer, Cody

2009-01-01

Students' eyes grow wide with wonder as they get a motor to work or make a bulb light for the first time. As these daunting feats of electrical engineering remind us, teaching electricity is invariably rewarding and worthwhile. In this inquiry-based science project, elementary students work in pairs to design and wire a shoe box "room" that meets…

Acute Fasting Regulates Retrograde Synaptic Enhancement through a 4E-BP-Dependent Mechanism.

PubMed

Kauwe, Grant; Tsurudome, Kazuya; Penney, Jay; Mori, Megumi; Gray, Lindsay; Calderon, Mario R; Elazouzzi, Fatima; Chicoine, Nicole; Sonenberg, Nahum; Haghighi, A Pejmun

2016-12-21

While beneficial effects of fasting on organismal function and health are well appreciated, we know little about the molecular details of how fasting influences synaptic function and plasticity. Our genetic and electrophysiological experiments demonstrate that acute fasting blocks retrograde synaptic enhancement that is normally triggered as a result of reduction in postsynaptic receptor function at the Drosophila larval neuromuscular junction (NMJ). This negative regulation critically depends on transcriptional enhancement of eukaryotic initiation factor 4E binding protein (4E-BP) under the control of the transcription factor Forkhead box O (Foxo). Furthermore, our findings indicate that postsynaptic 4E-BP exerts a constitutive negative input, which is counteracted by a positive regulatory input from the Target of Rapamycin (TOR). This combinatorial retrograde signaling plays a key role in regulating synaptic strength. Our results provide a mechanistic insight into how cellular stress and nutritional scarcity could acutely influence synaptic homeostasis and functional stability in neural circuits. Copyright © 2016 Elsevier Inc. All rights reserved.

Regulatory T-cell stability and plasticity in mucosal and systemic immune systems.

PubMed

Murai, M; Krause, P; Cheroutre, H; Kronenberg, M

2010-09-01

Regulatory T cells (Treg) express the forkhead box p3 (Foxp3) transcription factor and suppress pathological immune responses against self and foreign antigens, including commensal microorganisms. Foxp3 has been proposed as a master key regulator for Treg, required for their differentiation, maintenance, and suppressive functions. Two types of Treg have been defined. Natural Treg (nTreg) are usually considered to be a separate sublineage arising during thymus differentiation. Induced Treg (iTreg) originate upon T cell receptor (TCR) stimulation in the presence of tumor growth factor beta. Although under homeostatic conditions most Treg in the periphery are nTreg, special immune challenges in the intestine promote more frequently the generation of iTreg. Furthermore, recent observations have challenged the notion that Treg are a stable sublineage, and they suggest that, particularly under lymphopenic and/or inflammatory conditions, Treg may lose Foxp3 and/or acquire diverse effector functions, especially in the intestine, which may contribute to uncontrolled inflammation.

Functional defect in regulatory T cells in myasthenia gravis

PubMed Central

Thiruppathi, Muthusamy; Rowin, Julie; Jiang, Qin Li; Sheng, Jian Rong; Prabhakar, Bellur S.; Meriggioli, Matthew N.

2012-01-01

Forkhead box P3 (FOXP3)+ is a transcription factor necessary for the function of regulatory T cells (Treg cells). Treg cells maintain immune homeostasis and self-tolerance, and play an important role in the prevention of autoimmune disease. Here, we discuss the role of Treg cells in the pathogenesis of myasthenia gravis (MG) and review evidence indicating that a significant defect in Treg cell in vitro suppressive function exists in MG patients, without an alteration in circulating frequency. This functional defect is associated with a reduced expression of key functional molecules such as FOXP3 on isolated Treg cells and appears to be more pronounced in immunosuppression-naive MG patients. In vitro administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced the suppressive function of Treg cells and up-regulated FOXP3 expression. These findings indicate a clinically relevant Treg cell–intrinsic defect in immune regulation in MG that may reveal a novel therapeutic target. PMID:23252899

Reliability of primary caregivers reports on lifestyle behaviours of European pre-school children: the ToyBox-study.

PubMed

González-Gil, E M; Mouratidou, T; Cardon, G; Androutsos, O; De Bourdeaudhuij, I; Góźdź, M; Usheva, N; Birnbaum, J; Manios, Y; Moreno, L A

2014-08-01

Reliable assessments of health-related behaviours are necessary for accurate evaluation on the efficiency of public health interventions. The aim of the current study was to examine the reliability of a self-administered primary caregivers questionnaire (PCQ) used in the ToyBox-intervention. The questionnaire consisted of six sections addressing sociodemographic and perinatal factors, water and beverages consumption, physical activity, snacking and sedentary behaviours. Parents/caregivers from six countries (Belgium, Bulgaria, Germany, Greece, Poland and Spain) were asked to complete the questionnaire twice within a 2-week interval. A total of 93 questionnaires were collected. Test-retest reliability was assessed using intra-class correlation coefficient (ICC). Reliability of the six questionnaire sections was assessed. A stronger agreement was observed in the questions addressing sociodemographic and perinatal factors as opposed to questions addressing behaviours. Findings showed that 92% of the ToyBox PCQ had a moderate-to-excellent test-retest reliability (defined as ICC values from 0.41 to 1) and less than 8% poor test-retest reliability (ICC < 0.40). Out of the total ICC values, 67% showed good-to-excellent reliability (ICC from 0.61 to 1). We conclude that the PCQ is a reliable tool to assess sociodemographic characteristics, perinatal factors and lifestyle behaviours of pre-school children and their families participating in the ToyBox-intervention. © 2014 World Obesity.

EPA ExpoBox Terminology

EPA Pesticide Factsheets

EPA-Expo-Box is a toolbox for exposure assessors. Its purpose is to provide a compendium of exposure assessment and risk characterization tools that will present comprehensive step-by-step guidance and links to relevant exposure assessment data bases,

Genome-wide identification and characterisation of F-box family in maize.

PubMed

Jia, Fengjuan; Wu, Bingjiang; Li, Hui; Huang, Jinguang; Zheng, Chengchao

2013-11-01

F-box-containing proteins, as the key components of the protein degradation machinery, are widely distributed in higher plants and are considered as one of the largest known families of regulatory proteins. The F-box protein family plays a crucial role in plant growth and development and in response to biotic and abiotic stresses. However, systematic analysis of the F-box family in maize (Zea mays) has not been reported yet. In this paper, we identified and characterised the maize F-box genes in a genome-wide scale, including phylogenetic analysis, chromosome distribution, gene structure, promoter analysis and gene expression profiles. A total of 359 F-box genes were identified and divided into 15 subgroups by phylogenetic analysis. The F-box domain was relatively conserved, whereas additional motifs outside the F-box domain may indicate the functional diversification of maize F-box genes. These genes were unevenly distributed in ten maize chromosomes, suggesting that they expanded in the maize genome because of tandem and segmental duplication events. The expression profiles suggested that the maize F-box genes had temporal and spatial expression patterns. Putative cis-acting regulatory DNA elements involved in abiotic stresses were observed in maize F-box gene promoters. The gene expression profiles under abiotic stresses also suggested that some genes participated in stress responsive pathways. Furthermore, ten genes were chosen for quantitative real-time PCR analysis under drought stress and the results were consistent with the microarray data. This study has produced a comparative genomics analysis of the maize ZmFBX gene family that can be used in further studies to uncover their roles in maize growth and development.

46. DETAIL VIEW OF THE MORTAR BOXES, STAMP BATTERIES AND ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

46. DETAIL VIEW OF THE MORTAR BOXES, STAMP BATTERIES AND AMALGAMATION TABLES. NOTE FULTON IRON WORKS, SAM FRANCISCO 1908 STAMPED INTO THE MORTAR BOX. ALSO NOTE THE DIES RESTING ON THE OUTSIDE OF THE MORTAR BOX BY THE SECOND STAMP BATTERY FROM THE CAMERA POSITION. - Standard Gold Mill, East of Bodie Creek, Northeast of Bodie, Bodie, Mono County, CA

Boxing injuries presenting to U.S. emergency departments, 1990-2008.

PubMed

Potter, Matthew R; Snyder, Ashley J; Smith, Gary A

2011-04-01

Boxing injuries can have serious consequences. To examine the epidemiology of boxing injuries in the U.S. with attention to head injuries and children. National estimates of boxing injuries were calculated using data from the National Electronic Injury Surveillance System. Injury rates per 1000 participants for the year 2003 were calculated using boxing participation data. Data analysis was conducted in 2009-2010. An estimated 165,602 individuals (95% CI=134891, 196313) sustained boxing injuries that resulted in a visit to a U.S. hospital emergency department from 1990 through 2008. An average of 8716 (95% CI=7078, 10354) injuries occurred annually, and there was a statistically significant increase in the annual number of injuries during the 19-year study period (slope=610, p<0.001). The rate of injury was 12.7 per 1000 participants. Those injured were predominately male (90.9%). The most common diagnosis was fracture (27.5%), and the most common body regions injured were the hand (33.0%) and head and neck (22.5%). Punching bag-related injuries accounted for 36.8% of boxing injuries. The percentage of injuries that were concussions/closed head injuries in the group aged 12-17 years (8.9%) was similar to that in the group aged 18-24 years (8.1%) and the group aged 25-34 years (8.5%). These findings, based on a nationally representative sample, indicate that injuries related to boxing are increasing in number. Increased efforts are needed to prevent boxing injuries. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Construction of an evidence-based, graduated training curriculum for D-box, a webcam-based laparoscopic basic skills trainer box.

PubMed

Debes, Anders J; Aggarwal, Rajesh; Balasundaram, Indran; Jacobsen, Morten B J

2012-06-01

Surgical training programs are now including simulators as training tools for teaching laparoscopic surgery. The aim of this study was to develop a standardized, graduated, and evidence-based curriculum for the newly developed D-box (D-box Medical, Lier, Norway) for training basic laparoscopic skills. Eighteen interns with no laparoscopic experience completed a training program on the D-box consisting of 8 sessions of 5 tasks with assessment on a sixth task. Performance was measured by the use of 3-dimensional electromagnetic tracking of hand movements, path length, and time taken. Ten experienced surgeons (>100 laparoscopic surgeries, median 250) were recruited for establishing benchmark criteria. Significant learning curves were obtained for all construct valid parameters for tasks 4 (P < .005) and 5 (P < .005) and reached plateau levels between the fifth and sixth session. Within the 8 sessions of this study, between 50% and 89% of the interns reached benchmark criteria on tasks 4 and 5. Benchmark criteria and an evidence-based curriculum have been developed for the D-box. The curriculum is aimed at training and assessing surgical novices in basic laparoscopic skills. Copyright © 2012 Elsevier Inc. All rights reserved.