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Sample records for b1 sox coordinate

  1. B1 SOX coordinate cell specification with patterning and morphogenesis in the early zebrafish embryo.

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    Yuichi Okuda

    2010-05-01

    Full Text Available The B1 SOX transcription factors SOX1/2/3/19 have been implicated in various processes of early embryogenesis. However, their regulatory functions in stages from the blastula to early neurula remain largely unknown, primarily because loss-of-function studies have not been informative to date. In our present study, we systematically knocked down the B1 sox genes in zebrafish. Only the quadruple knockdown of the four B1 sox genes sox2/3/19a/19b resulted in very severe developmental abnormalities, confirming that the B1 sox genes are functionally redundant. We characterized the sox2/3/19a/19b quadruple knockdown embryos in detail by examining the changes in gene expression through in situ hybridization, RT-PCR, and microarray analyses. Importantly, these phenotypic analyses revealed that the B1 SOX proteins regulate the following distinct processes: (1 early dorsoventral patterning by controlling bmp2b/7; (2 gastrulation movements via the regulation of pcdh18a/18b and wnt11, a non-canonical Wnt ligand gene; (3 neural differentiation by regulating the Hes-class bHLH gene her3 and the proneural-class bHLH genes neurog1 (positively and ascl1a (negatively, and regional transcription factor genes, e.g., hesx1, zic1, and rx3; and (4 neural patterning by regulating signaling pathway genes, cyp26a1 in RA signaling, oep in Nodal signaling, shh, and mdkb. Chromatin immunoprecipitation analysis of the her3, hesx1, neurog1, pcdh18a, and cyp26a1 genes further suggests a direct regulation of these genes by B1 SOX. We also found an interesting overlap between the early phenotypes of the B1 sox quadruple knockdown embryos and the maternal-zygotic spg embryos that are devoid of pou5f1 activity. These findings indicate that the B1 SOX proteins control a wide range of developmental regulators in the early embryo through partnering in part with Pou5f1 and possibly with other factors, and suggest that the B1 sox functions are central to coordinating cell fate

  2. SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.

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    Oosterveen, Tony; Kurdija, Sanja; Ensterö, Mats; Uhde, Christopher W; Bergsland, Maria; Sandberg, Magnus; Sandberg, Rickard; Muhr, Jonas; Ericson, Johan

    2013-04-30

    The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.

  3. Genovariation Analysis of Sox11 and CYP1B1 in Patients with Peter's Anormaly%Peters'异常患者Sox11及CYP1B1基因变异分析

    Institute of Scientific and Technical Information of China (English)

    贾秀华; 郭向明

    2013-01-01

    [Objective] To investigate the genovariation of Sox11 and CYP1B1 in Chinese population with Peters' anomaly.[Methods] 13 probands of Peters' anormaly and 100 normal controls were selected from our ocular genetic diseases bank.Cycle sequencing was used to analyze the exons and adjacent introns of Sox11 and CYP1B1.The variation detected was further evaluated in 100 normal controls using the heteroduplex analysis-single strand conformation polymorphism (HA-SSCP) methods.Screening the gene mutation of Sox11 and CYP1B1 in Chinese patients with Peters' anormaly,and the related phenotypes of them.[Results] One synonymous mutation of Sox11 and one missense mutation of CYP1B1 were detected in the 13 patients with Peters' anormaly.No such new mutation was found in 100 normal controls.[Conclusions] To our knowledge,it is the first time of Sox11 gene screening on patients with Peters' anormaly.And our finding support the role of CYP1B1 as a causative gene in Peters' anormaly and expand the mutation spectrum of CYP1B1.Furthermore,it enriches our knowledge of genotype-phenotype relation.Our results may provide basis for the functional and genomic study of this kind of disease.%[目的]研究中国人Peters’异常患者Sox11及CYP1B1基因变异情况.[方法]从眼遗传疾病库中选取13例Peters’异常的先证者以及100例正常对照,采用直接测序的方法分析Sox11及CYP1B1基因的外显子及其相邻内含子基因变异情况;通过测序识别的基因突变,使用HA-SSCP分析的方法,在100例正常对照中做进一步评估.筛查中国人群Peters’异常患者Sox11及CYP1B1基因基因变异,并研究其相关表型.[结果]在13例Peters’异常的患者中检测到一个Sox11同义突变,一个CYP1B1错义突变,在正常对照中未发现此基因突变.[结论]本研究首次对Peters’异常患者进行Sox11进行基因筛查,并验证了CYP1B1是Peters’异常的致病基因之一,进一步扩大了Peters’异常患者CYP1B1基因突变

  4. Formation of the embryonic organizer is restricted by the competitive influences of Fgf signaling and the SoxB1 transcription factors.

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    Cheng-Liang Kuo

    Full Text Available The organizer is one of the earliest structures to be established during vertebrate development and is crucial to subsequent patterning of the embryo. We have previously shown that the SoxB1 transcription factor, Sox3, plays a central role as a transcriptional repressor of zebrafish organizer gene expression. Recent data suggest that Fgf signaling has a positive influence on organizer formation, but its role remains to be fully elucidated. In order to better understand how Fgf signaling fits into the complex regulatory network that determines when and where the organizer forms, the relationship between the positive effects of Fgf signaling and the repressive effects of the SoxB1 factors must be resolved. This study demonstrates that both fgf3 and fgf8 are required for expression of the organizer genes, gsc and chd, and that SoxB1 factors (Sox3, and the zebrafish specific factors, Sox19a and Sox19b can repress the expression of both fgf3 and fgf8. However, we also find that these SoxB1 factors inhibit the expression of gsc and chd independently of their repression of fgf expression. We show that ectopic expression of organizer genes induced solely by the inhibition of SoxB1 function is dependent upon the activation of fgf expression. These data allow us to describe a comprehensive signaling network in which the SoxB1 factors restrict organizer formation by inhibiting Fgf, Nodal and Wnt signaling, as well as independently repressing the targets of that signaling. The organizer therefore forms only where Nodal-induced Fgf signaling overlaps with Wnt signaling and the SoxB1 proteins are absent.

  5. Sox9

    DEFF Research Database (Denmark)

    Seymour, Philip A

    2014-01-01

    Over the last decade, it has been discovered that the transcription factor Sox9 plays several critical roles in governing the development of the embryonic pancreas and the homeostasis of the mature organ. While analysis of pancreata from patients affected by the Sox9 haploinsufficiency syndrome...... tracing mouse models. Also, current controversies regarding Sox9 function in healthy and injured adult pancreas and unanswered questions and avenues of future study are discussed....

  6. DNA double-strand breaks coupled with PARP1 and HNRNPA2B1 binding sites flank coordinately expressed domains in human chromosomes.

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    Nickolai A Tchurikov

    2013-04-01

    Full Text Available Genome instability plays a key role in multiple biological processes and diseases, including cancer. Genome-wide mapping of DNA double-strand breaks (DSBs is important for understanding both chromosomal architecture and specific chromosomal regions at DSBs. We developed a method for precise genome-wide mapping of blunt-ended DSBs in human chromosomes, and observed non-random fragmentation and DSB hot spots. These hot spots are scattered along chromosomes and delimit protected 50-250 kb DNA domains. We found that about 30% of the domains (denoted forum domains possess coordinately expressed genes and that PARP1 and HNRNPA2B1 specifically bind DNA sequences at the forum domain termini. Thus, our data suggest a novel type of gene regulation: a coordinated transcription or silencing of gene clusters delimited by DSB hot spots as well as PARP1 and HNRNPa2B1 binding sites.

  7. EphrinB1/EphB3b Coordinate Bidirectional Epithelial-Mesenchymal Interactions Controlling Liver Morphogenesis and Laterality

    DEFF Research Database (Denmark)

    Cayuso, Jordi; Dzementsei, Aliaksandr; Fischer, Johanna C;

    2016-01-01

    and adjacent lateral plate mesoderm (LPM), resulting in asymmetric positioning of the zebrafish liver. EphrinB1 in hepatoblasts regulates directional migration and mediates interactions with the LPM, where EphB3b controls polarity and movement of the LPM. EphB3b in the LPM concomitantly repels hepatoblasts...

  8. Artificial induction of Sox21 regulates sensory cell formation in the embryonic chicken inner ear.

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    Stephen D Freeman

    Full Text Available During embryonic development, hair cells and support cells in the sensory epithelia of the inner ear derive from progenitors that express Sox2, a member of the SoxB1 family of transcription factors. Sox2 is essential for sensory specification, but high levels of Sox2 expression appear to inhibit hair cell differentiation, suggesting that factors regulating Sox2 activity could be critical for both processes. Antagonistic interactions between SoxB1 and SoxB2 factors are known to regulate cell differentiation in neural tissue, which led us to investigate the potential roles of the SoxB2 member Sox21 during chicken inner ear development. Sox21 is normally expressed by sensory progenitors within vestibular and auditory regions of the early embryonic chicken inner ear. At later stages, Sox21 is differentially expressed in the vestibular and auditory organs. Sox21 is restricted to the support cell layer of the auditory epithelium, while it is enriched in the hair cell layer of the vestibular organs. To test Sox21 function, we used two temporally distinct gain-of-function approaches. Sustained over-expression of Sox21 from early developmental stages prevented prosensory specification, and abolished the formation of both hair cells and support cells. However, later induction of Sox21 expression at the time of hair cell formation in organotypic cultures of vestibular epithelia inhibited endogenous Sox2 expression and Notch activity, and biased progenitor cells towards a hair cell fate. Interestingly, Sox21 did not promote hair cell differentiation in the immature auditory epithelium, which fits with the expression of endogenous Sox21 within mature support cells in this tissue. These results suggest that interactions among endogenous SoxB family transcription factors may regulate sensory cell formation in the inner ear, but in a context-dependent manner.

  9. A Systematic Survey and Characterization of Enhancers that Regulate Sox3 in Neuro-Sensory Development in Comparison with Sox2 Enhancers

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    Hisato Kondoh

    2012-11-01

    Full Text Available Development of neural and sensory primordia at the early stages of embryogenesis depends on the activity of two B1 Sox transcription factors, Sox2 and Sox3. The embryonic expression patterns of the Sox2 and Sox3 genes are similar, yet they show gene-unique features. We screened for enhancers of the 231-kb genomic region encompassing Sox3 of chicken, and identified 13 new enhancers that showed activity in different domains of the neuro-sensory primordia. Combined with the three Sox3-proximal enhancers determined previously, at least 16 enhancers were involved in Sox3 regulation. Starting from the NP1 enhancer, more enhancers with different specificities are activated in sequence, resulting in complex overlapping patterns of enhancer activities. NP1 was activated in the caudal lateral epiblast adjacent to the posterior growing end of neural plate, and by the combined action of Wnt and Fgf signaling, similar to the Sox2 N1 enhancer involved in neural/mesodermal dichotomous cell lineage segregation. The Sox3 D5 enhancer and Sox2 N3 enhancer were also activated similarly in the diencephalon, optic vesicle and lens placode, suggesting analogies in their regulation. In general, however, the specificities of the enhancers were not identical between Sox3 and Sox2, including the cases of the NP1 and D5 enhancers.

  10. A Systematic Survey and Characterization of Enhancers that Regulate Sox3 in Neuro-Sensory Development in Comparison with Sox2 Enhancers.

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    Nishimura, Naoko; Kamimura, Yoshifumi; Ishida, Yoshiko; Takemoto, Tatsuya; Kondoh, Hisato; Uchikawa, Masanori

    2012-11-22

    Development of neural and sensory primordia at the early stages of embryogenesis depends on the activity of two B1 Sox transcription factors, Sox2 and Sox3. The embryonic expression patterns of the Sox2 and Sox3 genes are similar, yet they show gene-unique features. We screened for enhancers of the 231-kb genomic region encompassing Sox3 of chicken, and identified 13 new enhancers that showed activity in different domains of the neuro-sensory primordia. Combined with the three Sox3-proximal enhancers determined previously, at least 16 enhancers were involved in Sox3 regulation. Starting from the NP1 enhancer, more enhancers with different specificities are activated in sequence, resulting in complex overlapping patterns of enhancer activities. NP1 was activated in the caudal lateral epiblast adjacent to the posterior growing end of neural plate, and by the combined action of Wnt and Fgf signaling, similar to the Sox2 N1 enhancer involved in neural/mesodermal dichotomous cell lineage segregation. The Sox3 D5 enhancer and Sox2 N3 enhancer were also activated similarly in the diencephalon, optic vesicle and lens placode, suggesting analogies in their regulation. In general, however, the specificities of the enhancers were not identical between Sox3 and Sox2, including the cases of the NP1 and D5 enhancers.

  11. SoxE function in vertebrate nervous system development.

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    Stolt, C Claus; Wegner, Michael

    2010-03-01

    Sox8, Sox9, and Sox10 as transcription factors of subgroup E of the Sox protein family are essential for many aspects of nervous system development. These SoxE proteins are already required for the initial neural crest induction, but also guarantee survival and maintenance of pluripotency in migrating neural crest stem cells. SoxE proteins are furthermore key regulators of glial specification in both the peripheral and the central nervous systems. At later stages of development, Sox10 plays crucial roles in Schwann cells and oligodendrocytes for terminal differentiation and myelin formation. In both glial cell types, Sox10 controls directly the expression of genes encoding the major myelin proteins. SoxE proteins are well-integrated components of regulatory networks and as such modulated in their activity by cooperating or antagonistic transcription factors such as SoxD or various bHLH proteins. The multiple functions in peripheral and central nervous system development also link SoxE proteins to various human diseases and identify these proteins as promising targets of future therapeutic approaches.

  12. Sox genes in grass carp (Ctenopharyngodon idella with their implications for genome duplication and evolution

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    Tong Jingou

    2006-11-01

    Full Text Available Abstract The Sox gene family is found in a broad range of animal taxa and encodes important gene regulatory proteins involved in a variety of developmental processes. We have obtained clones representing the HMG boxes of twelve Sox genes from grass carp (Ctenopharyngodon idella, one of the four major domestic carps in China. The cloned Sox genes belong to group B1, B2 and C. Our analyses show that whereas the human genome contains a single copy of Sox4, Sox11 and Sox14, each of these genes has two co-orthologs in grass carp, and the duplication of Sox4 and Sox11 occurred before the divergence of grass carp and zebrafish, which support the "fish-specific whole-genome duplication" theory. An estimation for the origin of grass carp based on the molecular clock using Sox1, Sox3 and Sox11 genes as markers indicates that grass carp (subfamily Leuciscinae and zebrafish (subfamily Danioninae diverged approximately 60 million years ago. The potential uses of Sox genes as markers in revealing the evolutionary history of grass carp are discussed.

  13. SOX9: a stem cell transcriptional regulator of secreted niche signaling factors.

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    Kadaja, Meelis; Keyes, Brice E; Lin, Mingyan; Pasolli, H Amalia; Genander, Maria; Polak, Lisa; Stokes, Nicole; Zheng, Deyou; Fuchs, Elaine

    2014-02-15

    Hair follicles (HFs) undergo cyclical periods of growth, which are fueled by stem cells (SCs) at the base of the resting follicle. HF-SC formation occurs during HF development and requires transcription factor SOX9. Whether and how SOX9 functions in HF-SC maintenance remain unknown. By conditionally targeting Sox9 in adult HF-SCs, we show that SOX9 is essential for maintaining them. SOX9-deficient HF-SCs still transition from quiescence to proliferation and launch the subsequent hair cycle. However, once activated, bulge HF-SCs begin to differentiate into epidermal cells, which naturally lack SOX9. In addition, as HF-SC numbers dwindle, outer root sheath production is not sustained, and HF downgrowth arrests prematurely. Probing the mechanism, we used RNA sequencing (RNA-seq) to identify SOX9-dependent transcriptional changes and chromatin immunoprecipitation (ChIP) and deep sequencing (ChIP-seq) to identify SOX9-bound genes in HF-SCs. Intriguingly, a large cohort of SOX9-sensitive targets encode extracellular factors, most notably enhancers of Activin/pSMAD2 signaling. Moreover, compromising Activin signaling recapitulates SOX9-dependent defects, and Activin partially rescues them. Overall, our findings reveal roles for SOX9 in regulating adult HF-SC maintenance and suppressing epidermal differentiation in the niche. In addition, our studies expose a role for SCs in coordinating their own behavior in part through non-cell-autonomous signaling within the niche.

  14. SOX genes: architects of development.

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    Prior, H M; Walter, M A

    1996-07-01

    Development in higher organisms involves complex genetic regulation at the molecular level. The emerging picture of development control includes several families of master regulatory genes which can affect the expression of down-stream target genes in developmental cascade pathways. One new family of such development regulators is the SOX gene family. The SOX genes are named for a shared motif called the SRY box a region homologous to the DNA-binding domain of SRY, the mammalian sex determining gene. Like SRY, SOX genes play important roles in chordate development. At least a dozen human SOX genes have been identified and partially characterized (Tables 1 and 2). Mutations in SOX9 have recently been linked to campomelic dysplasia and autosomal sex reversal, and other SOX genes may also be associated with human disease.

  15. Genome-wide mapping of Sox6 binding sites in skeletal muscle reveals both direct and indirect regulation of muscle terminal differentiation by Sox6

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    An Chung-Il

    2011-10-01

    Full Text Available Abstract Background Sox6 is a multi-faceted transcription factor involved in the terminal differentiation of many different cell types in vertebrates. It has been suggested that in mice as well as in zebrafish Sox6 plays a role in the terminal differentiation of skeletal muscle by suppressing transcription of slow fiber specific genes. In order to understand how Sox6 coordinately regulates the transcription of multiple fiber type specific genes during muscle development, we have performed ChIP-seq analyses to identify Sox6 target genes in mouse fetal myotubes and generated muscle-specific Sox6 knockout (KO mice to determine the Sox6 null muscle phenotype in adult mice. Results We have identified 1,066 Sox6 binding sites using mouse fetal myotubes. The Sox6 binding sites were found to be associated with slow fiber-specific, cardiac, and embryonic isoform genes that are expressed in the sarcomere as well as transcription factor genes known to play roles in muscle development. The concurrently performed RNA polymerase II (Pol II ChIP-seq analysis revealed that 84% of the Sox6 peak-associated genes exhibited little to no binding of Pol II, suggesting that the majority of the Sox6 target genes are transcriptionally inactive. These results indicate that Sox6 directly regulates terminal differentiation of muscle by affecting the expression of sarcomere protein genes as well as indirectly through influencing the expression of transcription factors relevant to muscle development. Gene expression profiling of Sox6 KO skeletal and cardiac muscle revealed a significant increase in the expression of the genes associated with Sox6 binding. In the absence of the Sox6 gene, there was dramatic upregulation of slow fiber-specific, cardiac, and embryonic isoform gene expression in Sox6 KO skeletal muscle and fetal isoform gene expression in Sox6 KO cardiac muscle, thus confirming the role Sox6 plays as a transcriptional suppressor in muscle development

  16. Sox2, a key factor in the regulation of pluripotency and neural differentiation

    Institute of Scientific and Technical Information of China (English)

    Shuchen; Zhang; Wei; Cui

    2014-01-01

    Sex determining region Y-box 2(Sox2), a member of the SoxB1 transcription factor family, is an important transcriptional regulator in pluripotent stem cells(PSCs). Together with octamer-binding transcription factor 4 and Nanog, they co-operatively control gene expression in PSCs and maintain their pluripotency. Furthermore, Sox2 plays an essential role in somatic cell reprogram-ming, reversing the epigenetic configuration of differ-entiated cells back to a pluripotent embryonic state. In addition to its role in regulation of pluripotency, Sox2 is also a critical factor for directing the differentiation of PSCs to neural progenitors and for maintaining the properties of neural progenitor stem cells. Here, we review recent findings concerning the involvement of Sox2 in pluripotency, somatic cell reprogramming and neural differentiation as well as the molecular mecha-nisms underlying these roles.

  17. Vitamin B1

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    ... Prize Alfred Nobel's Life and Work Teachers' Questionnaire Vitamin B1 - About The Chicken Farm educational game and ... the game window. Reading: "Christian Eijkman, Beriberi and Vitamin B1" - Who was Eijkman and why did he ...

  18. SOX4 expression in bladder carcinoma

    DEFF Research Database (Denmark)

    Aaboe, Mads; Birkenkamp-Demtroder, Karin; Wiuf, Carsten;

    2006-01-01

    The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors compared with normal tissue based on whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples. Using a SOX4-specific antibody, we found that the cancer cells expressed...... strongly impaired cell viability and promoted apoptosis. To characterize downstream target genes and SOX4-induced pathways, we used a time-course global expression study of the overexpressed SOX4. Analysis of the microarray data showed 130 novel SOX4-related genes, some involved in signal transduction (MAP......2K5), angiogenesis (NRP2), and cell cycle arrest (PIK3R3) and others with unknown functions (CGI-62). Among the genes regulated by SOX4, 25 contained at least one SOX4-binding motif in the promoter sequence, suggesting a direct binding of SOX4. The gene set identified in vitro was analyzed...

  19. MarA, SoxS and Rob of Escherichia coli - Global regulators of multidrug resistance, virulence and stress response.

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    Duval, Valérie; Lister, Ida M

    2013-01-01

    Bacteria have a great capacity for adjusting their metabolism in response to environmental changes by linking extracellular stimuli to the regulation of genes by transcription factors. By working in a co-operative manner, transcription factors provide a rapid response to external threats, allowing the bacteria to survive. This review will focus on transcription factors MarA, SoxS and Rob in Escherichia coli, three members of the AraC family of proteins. These homologous proteins exemplify the ability to respond to multiple threats such as oxidative stress, drugs and toxic compounds, acidic pH, and host antimicrobial peptides. MarA, SoxS and Rob recognize similar DNA sequences in the promoter region of more than 40 regulatory target genes. As their regulons overlap, a finely tuned adaptive response allows E. coli to survive in the presence of different assaults in a co-ordinated manner. These regulators are well conserved amongst Enterobacteriaceae and due to their broad involvement in bacterial adaptation in the host, have recently been explored as targets to develop new anti-virulence agents. The regulators are also being examined for their roles in novel technologies such as biofuel production.

  20. CYP7B1

    DEFF Research Database (Denmark)

    Roos, P; Svenstrup, K; Danielsen, E R

    2014-01-01

    UNLABELLED: The SPG5A subtype of Hereditary Spastic Paraplegia (HSP) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the CYP7B1 gene, which encodes a steroid cytochrome P450 7α-hydroxylase. This enzyme provides the primary metabolic route for neurosteroids. Clinica......UNLABELLED: The SPG5A subtype of Hereditary Spastic Paraplegia (HSP) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the CYP7B1 gene, which encodes a steroid cytochrome P450 7α-hydroxylase. This enzyme provides the primary metabolic route for neurosteroids...

  1. Sox31 is involved in central nervous system anteroposterior regionalization through regulating the organizer activity in zebrafish

    Institute of Scientific and Technical Information of China (English)

    Shengnan Hu; Zhili Wu; Yuanchang Yan; Yiping Li

    2011-01-01

    Sox superfamily proteins are DNA-binding transcriptional factors that contain highly conserved high-mobility group (HMG) box and take part in various development process.Sox31 is a maternal factor supplied in the oocyte and starts its zygotic expression during mid-blastula transition (MBT)From gastrulation stage, it mainly resides in neural tissue.Ectopically expression of Sox31 mRNA leads to cyclopia fusion eyes or totally loss of anterior head structure, in accompany with severe notochord defects. Molecular markers indicate that forebrain tissue reduces sharply while the posterior neural tissue expands anteriorly. In addition organizer specification is also suppressed. Oppositely, an antisense morpholino designed functionally knockdown Sox31 causes typically dorsalized phenotype and reversed central nervous system (CNS) anteroposterior (AP) patterning. Gain of function with chimeric construct, where Sox31 HMG DNA binding domain is fused to a transcription activation domain (VP16) or transcnption suppression domain (EnR), suggests that Sox31 acts as a transcriptional suppressor in vivo. The expression of Bozozok (Dharma), a direct target gene of pre-MBT Wnt/p-catenin signal is suppressed by Sox31 Thus, to unveil the relationship between Sox31 and β-catenin-related transcriptional activity, we designed Top/Fop luciferase assay in HEK293T cells, and found that Sox31 could indeed suppress Tcf/Lef-dependent transcriptional activity without influencing the stability of β-catenin.Moreover, post-MBT Wnt signal was reduced in Sox31 morphants corresponding to the suppressed hindbrain structure, while phenotypic defects caused by excessive Sox31 could be rescued by Wnt antagonist dkkl. Taken together, Sox31 functions as an essential CNS AP patterning determinant and coordinates the CNS AP patterning process with organizer specification.

  2. Remarkable evolutionary conservation of SOX14 orthologues

    Indian Academy of Sciences (India)

    Jelena Popovic; Milena Stevanovic

    2009-04-01

    SOX proteins constitute a large family of diverse, well-conserved transcription factors present in vertebrates and invertebrates, and also implicated in control of many developmental processes. Our objectives have been to identify Sox14 gene of goat (Capra hircus), cow (Bos taurus) and rat (Rattus norvegicus), and to perform comparative analyses and mapping of SOX14 orthologues from numerous vertebrate species. PCR based approach was used to identify Sox14 of goat, cow and rat, while nucleotide and amino acid sequence alignments and mapping were performed using information currently available in public database. Comparative sequence analysis revealed remarkable identity among Sox14 orthologues and helped us to identify highly conserved motifs that represent molecular signatures of SOX14 protein that might have structural or functional significance. Further, we determined chromosomal locations of numerous predicted group B Sox genes and their neighbouring genes using currently available genome database. In conclusion, our study has not only supported the proposed model of group B Sox genes evolution in chicken and mammals, but has also revealed that additional evolutionary events split Sox B genes into different chromosomes in some mammals. Mapping data presented in this study could help in refining the understanding of the evolution of group B Sox genes in vertebrates.

  3. Expression of Sox4 and Sox11 is regulated by multiple mechanisms during retinal development.

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    Usui, Ayumi; Iwagawa, Toshiro; Mochizuki, Yujin; Iida, Atsumi; Wegner, Michael; Murakami, Akira; Watanabe, Sumiko

    2013-02-14

    Sox11 and Sox4 play critical roles in retinal development, during which they display specific and unique expression patterns. The expression of Sox11 and Sox4 is temporally sequential, albeit spatially overlapping in some retinal subtypes. Gain-of-function and loss-of-function analyses suggested that Notch signaling suppresses Sox4 expression in the early developing retina but not during the later period of development. The levels of histone H3-acetylation and H3-lysine 4 tri-methylation at the Sox11 locus declined during development, as did the levels of Sox11. A similar but less marked change was seen for Sox4. For both genes, histone H3-lysine 27 methylation was low during development and increased markedly in the adult.

  4. [SOX2 defect and anophthalmia and microphthalmia].

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    Ye, Fu-xiang; Fan, Xian-qun

    2012-11-01

    As a severe congenital developmental disorder, anophthalmia and microphthalmia are usually accompanied with vision impairment and hypoevolutism of the orbit in the affected side. Many genes are involved in anophthalmia and microphthalmia, in which, SOX2 is an important one. The defect of SOX2 causes multiple system disorders, including anophthalmia and microphthalmia. We describe the relationship between the SOX2 defect and anophthalmia/microphthalmia, in order to offer some proposals for the differential diagnosis, treatment and research of anophthalmia and microphthalmia.

  5. Sox transcription in sarcosine utilization is controlled by Sigma(54) and SoxR in Bacillus thuringiensis HD73.

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    Peng, Qi; Liu, Chunxia; Wang, Bo; Yang, Min; Wu, Jianbo; Zhang, Jie; Song, Fuping

    2016-07-12

    Sarcosine oxidase catalyzes the oxidative demethylation of sarcosine to yield glycine, formaldehyde, and hydrogen peroxide. In this study, we analyzed the transcription and regulation of the sox locus, including the sarcosine oxidase-encoding genes in Bacillus thuringiensis (Bt). RT-PCR analysis revealed that the sox locus forms two opposing transcriptional units: soxB (soxB/E/F/G/H/I) and soxR (soxR/C/D/A). The typical -12/-24 consensus sequence was located 15 bp and 12 bp from the transcriptional start site (TSS) of soxB and soxC, respectively. Promoter-lacZ fusion assays showed that the soxB promoter is controlled by the Sigma(54) factor and is activated by the Sigma(54)-dependent transcriptional regulator SoxR. SoxR also inhibits its own expression. Expression from the PsoxCR promoter, which is responsible for the transcription of soxC, soxD, and soxA, is Sigma(54)-dependent and requires SoxR. An 11-bp inverted repeat sequence was identified as SoxR binding site upstream of the soxB TSS. Purified SoxR specifically bound a DNA fragment containing this region. Mutation or deletion of this sequence abolished the transcriptional activities of soxB and soxC. Thus, SoxR binds to the same sequence to activate the transcription of soxB and soxC. Sarcosine utilization was abolished in soxB and soxR mutants, suggesting that the sox locus is essential for sarcosine utilization.

  6. Sox transcription in sarcosine utilization is controlled by Sigma54 and SoxR in Bacillus thuringiensis HD73

    Science.gov (United States)

    Peng, Qi; Liu, Chunxia; Wang, Bo; Yang, Min; Wu, Jianbo; Zhang, Jie; Song, Fuping

    2016-01-01

    Sarcosine oxidase catalyzes the oxidative demethylation of sarcosine to yield glycine, formaldehyde, and hydrogen peroxide. In this study, we analyzed the transcription and regulation of the sox locus, including the sarcosine oxidase-encoding genes in Bacillus thuringiensis (Bt). RT-PCR analysis revealed that the sox locus forms two opposing transcriptional units: soxB (soxB/E/F/G/H/I) and soxR (soxR/C/D/A). The typical −12/−24 consensus sequence was located 15 bp and 12 bp from the transcriptional start site (TSS) of soxB and soxC, respectively. Promoter-lacZ fusion assays showed that the soxB promoter is controlled by the Sigma54 factor and is activated by the Sigma54-dependent transcriptional regulator SoxR. SoxR also inhibits its own expression. Expression from the PsoxCR promoter, which is responsible for the transcription of soxC, soxD, and soxA, is Sigma54-dependent and requires SoxR. An 11-bp inverted repeat sequence was identified as SoxR binding site upstream of the soxB TSS. Purified SoxR specifically bound a DNA fragment containing this region. Mutation or deletion of this sequence abolished the transcriptional activities of soxB and soxC. Thus, SoxR binds to the same sequence to activate the transcription of soxB and soxC. Sarcosine utilization was abolished in soxB and soxR mutants, suggesting that the sox locus is essential for sarcosine utilization. PMID:27404799

  7. B1 Aerogels

    DEFF Research Database (Denmark)

    Duer, Karsten; Svendsen, Sv Aa Højgaard

    1996-01-01

    , engineering and architectural basis which will support the appropriate use of aerogels in windows, solar collectors and passive solar applications, with the aim of saving or producing thermal energy for use in buildings".This objective is in very good agreement with the general scope of task 18 but where Task......The report summarizes the work that has been carried out within the project "B1 AEROGELS" as a part of the IEA SH&CP Task 18 "Advanced Glazing and Associated Materials For Solar And Building Applications".By providing at the same time thermal insulation and transparency the silica aerogel is a very...... of aerogel as a material for window applications. It was not a part of the project to make a further development of the aerogel material.The project was carried out in three main steps:1. Collection of information on aerogel production methods2. Measurements and evaluation of optical and thermal properties...

  8. mTOR inhibition decreases SOX2-SOX9 mediated glioma stem cell activity and temozolomide resistance

    Science.gov (United States)

    Garros-Regulez, Laura; Aldaz, Paula; Arrizabalaga, Olatz; Moncho-Amor, Veronica; Carrasco-Garcia, Estefania; Manterola, Lorea; Moreno-Cugnon, Leire; Barrena, Cristina; Villanua, Jorge; Ruiz, Irune; Pollard, Steven; Lovell-Badge, Robin; Sampron, Nicolas; Garcia, Idoia; Matheu, Ander

    2016-01-01

    ABSTRACT Background: SOX2 and SOX9 are commonly overexpressed in glioblastoma, and regulate the activity of glioma stem cells (GSCs). Their specific and overlapping roles in GSCs and glioma treatment remain unclear. Methods: SOX2 and SOX9 levels were examined in human biopsies. Gain and loss of function determined the impact of altering SOX2 and SOX9 on cell proliferation, senescence, stem cell activity, tumorigenesis and chemoresistance. Results: SOX2 and SOX9 expression correlates positively in glioma cells and glioblastoma biopsies. High levels of SOX2 bypass cellular senescence and promote resistance to temozolomide. Mechanistic investigations revealed that SOX2 acts upstream of SOX9. mTOR genetic and pharmacologic (rapamycin) inhibition decreased SOX2 and SOX9 expression, and reversed chemoresistance. Conclusions: Our findings reveal SOX2-SOX9 as an oncogenic axis that regulates stem cell properties and chemoresistance. We identify that rapamycin abrogate SOX protein expression and provide evidence that a combination of rapamycin and temozolomide inhibits tumor growth in cells with high SOX2/SOX9. PMID:26878385

  9. Molecular Cloning, Promoter Analysis and Expression Profiles of the sox3 Gene in Japanese Flounder, Paralichthys olivaceus

    Directory of Open Access Journals (Sweden)

    Jinning Gao

    2015-11-01

    Full Text Available Sox3, which belongs to the SoxB1 subgroup, plays major roles in neural and gonadal development. In the present study, Japanese flounder Paralichthys olivaceus sox3 gene (Posox3 and its promoter sequence were isolated and characterized. The deduced PoSox3 protein contained 298 amino acids with a characteristic HMG-box domain. Alignment and phylogenetic analyses indicated that PoSox3 shares highly identical sequence with Sox3 homologues from different species. The promoter region of Posox3 has many potential transcription factor (TF binding sites. The expression profiles of Posox3 in different developmental stages and diverse adult tissues were analyzed by quantitative real-time RT-PCR (qRT-PCR. Posox3 mRNA was maternally inherited, and maintained at a considerably high expression level between the blastula stage and the hatching stage during embryonic development. Posox3 was abundantly expressed in the adult brain and showed sexually dimorphic expression pattern. In situ hybridization (ISH was carried out to investigate the cellular distribution of Posox3 in the ovary, and results showed the uniform distribution of Posox3 throughout the cytoplasm of oogonia and stage I–III oocytes. These results indicate that Posox3 has potentially vital roles in embryonic and neural development and may be involved in the oogenesis process. Our work provides a fundamental understanding of the structure and potential functions of Sox3 in Paralichthys olivaceus.

  10. aflatoxina b1

    Directory of Open Access Journals (Sweden)

    A. Valdivia

    2004-01-01

    Full Text Available Con el objetivo de probar que la suplementación dietética de ácido elágico (AE o N-Acetilcisteína (NAC en pollos de engorda, atenúa los efectos de una intoxicación aguda por la aflatoxina B1 (AFB1, se intoxicaron con AFB1 pura, tres grupos de diez pollos cada uno (3.0 mb/kg pc, IP. Otros tres grupos recibieron solamente el vehículo (aceite de maíz 2.0 ml/kg pc, IP. Cuatro días antes se administró un alimento testigo, o bien, la misma dieta adicionada con AE (2.5 g/kg o NAC (200 mg/kg pc/6 h. A las 24 horas de la administración de AFB1, se cuantificaron las concentraciones hepáticas de glutatión (GSH, de actividad enzimática específica de la transferasa de glutatión (GST, alanina aminotransferasa, aspartato aminotransferasa y de proteínas hepáticas totales. Los resultados mostraron que NAC atenúa el impacto negativo de la AFB1 sobre el crecimiento corporal y al igual que AE, incrementa la GST y revierte parcialmente los efectos de AFB1 sobre GSH, lo cual sugiere que ambas sustancias pudieran conferir un efecto protector de las aves

  11. Cellular Reprogramming Employing Recombinant Sox2 Protein

    Directory of Open Access Journals (Sweden)

    Marc Thier

    2012-01-01

    Full Text Available Induced pluripotent stem (iPS cells represent an attractive option for the derivation of patient-specific pluripotent cells for cell replacement therapies as well as disease modeling. To become clinically meaningful, safe iPS cells need to be generated exhibiting no permanent genetic modifications that are caused by viral integrations of the reprogramming transgenes. Recently, various experimental strategies have been applied to accomplish transgene-free derivation of iPS cells, including the use of nonintegrating viruses, episomal expression, or excision of transgenes after reprogramming by site-specific recombinases or transposases. A straightforward approach to induce reprogramming factors is the direct delivery of either synthetic mRNA or biologically active proteins. We previously reported the generation of cell-permeant versions of Oct4 (Oct4-TAT and Sox2 (Sox2-TAT proteins and showed that Oct4-TAT is reprogramming-competent, that is, it can substitute for Oct4-encoding virus. Here, we explore conditions for enhanced Sox2-TAT protein stabilization and functional delivery into somatic cells. We show that cell-permeant Sox2 protein can be stabilized by lipid-rich albumin supplements in serum replacement or low-serum-supplemented media. Employing optimized conditions for protein delivery, we demonstrate that Sox2-TAT protein is able to substitute for viral Sox2. Sox2-piPS cells express pluripotency-associated markers and differentiate into all three germ layers.

  12. Genetics Home Reference: SOX2 anophthalmia syndrome

    Science.gov (United States)

    ... Kherani F, Katowitz J, Schimmenti LA, Hummel M, Fitzpatrick DR, Young TL. Familial recurrence of SOX2 anophthalmia ... Nov 5. Review. Citation on PubMed Verma AS, Fitzpatrick DR. Anophthalmia and microphthalmia. Orphanet J Rare Dis. ...

  13. Mesoderm-specific Stat3 deletion affects expression of Sox9 yielding Sox9-dependent phenotypes

    Science.gov (United States)

    Hall, Michael D.; Murray, Caroline A.; Perantoni, Alan O.

    2017-01-01

    To date, mutations within the coding region and translocations around the SOX9 gene both constitute the majority of genetic lesions underpinning human campomelic dysplasia (CD). While pathological coding-region mutations typically result in a non-functional SOX9 protein, little is known about what mechanism(s) controls normal SOX9 expression, and subsequently, which signaling pathways may be interrupted by alterations occurring around the SOX9 gene. Here, we report the identification of Stat3 as a key modulator of Sox9 expression in nascent cartilage and developing chondrocytes. Stat3 expression is predominant in tissues of mesodermal origin, and its conditional ablation using mesoderm-specific TCre, in vivo, causes dwarfism and skeletal defects characteristic of CD. Specifically, Stat3 loss results in the expansion of growth plate hypertrophic chondrocytes and deregulation of normal endochondral ossification in all bones examined. Conditional deletion of Stat3 with a Sox9Cre driver produces palate and tracheal irregularities similar to those described in Sox9+/- mice. Furthermore, mesodermal deletion of Stat3 causes global embryonic down regulation of Sox9 expression and function in vivo. Mechanistic experiments ex vivo suggest Stat3 can directly activate the expression of Sox9 by binding to its proximal promoter following activation. These findings illuminate a novel role for Stat3 in chondrocytes during skeletal development through modulation of a critical factor, Sox9. Importantly, they further provide the first evidence for the modulation of a gene product other than Sox9 itself which is capable of modeling pathological aspects of CD and underscore a potentially valuable therapeutic target for patients with the disorder. PMID:28166224

  14. Functional constraints on SoxE proteins in neural crest development: The importance of differential expression for evolution of protein activity.

    Science.gov (United States)

    Lee, Eric M; Yuan, Tian; Ballim, Reyna D; Nguyen, Kristy; Kelsh, Robert N; Medeiros, Daniel M; McCauley, David W

    2016-10-01

    Vertebrate SoxE genes (Sox8, 9, and 10) are key regulators of neural crest cell (NCC) development. These genes arose by duplication from a single SoxE gene in the vertebrate ancestor. Although SoxE paralogs are coexpressed early in NCC development, later, Sox9 is restricted to skeletogenic lineages in the head, and Sox10 to non-skeletogenic NCC in the trunk and head. When this subfunctionalization evolved and its possible role in the evolution of the neural crest are unknown. Sea lampreys are basal vertebrates that also possess three SoxE genes, while only a single SoxE is present in the cephalochordate amphioxus. In order to address the functional divergence of SoxE genes, and to determine if differences in their biochemical functions may be linked to changes in neural crest developmental potential, we examined the ability of lamprey and amphioxus SoxE genes to regulate differentiation of NCC derivatives in zebrafish colourless (cls) mutants lacking expression of sox10. Our findings suggest that the proto-vertebrate SoxE gene possessed both melanogenic and neurogenic capabilities prior to SoxE gene duplication. Following the agnathan-gnathostome split, lamprey SoxE1 and SoxE3 largely lost their melanogenic and/or enteric neurogenic properties, while gnathostome SoxE paralogs have retained functional conservation. We posit that this difference in protein subfunctionalization is a direct consequence of the independent regulation of SoxE paralog expression between the two lineages. Specifically, we propose that the overlapping expression of gnathostome SoxE paralogs in early neural crest largely constrained the function of gnathostome SoxE proteins. In contrast, the largely non-overlapping expression of lamprey SoxE paralogs allowed them to specialize with regard to their DNA-binding and/or protein interaction properties. Restriction of developmental potential among cranial and trunk neural crest in lampreys may be related to constraints on SoxE activity among

  15. 76 FR 4724 - Catawba Sox, LLC Formerly Known as Catawba Sox, Inc. Including Workers Whose Unemployment...

    Science.gov (United States)

    2011-01-26

    ... of Catawba Sox, LLC, formerly known as Catawba Sox, Inc., Newton, North Carolina. The notice was published in the Federal Register on August 2, 2010 (75 FR 45162). At the request of the State agency, the... Whose Unemployment Insurance UI) Wages Are Paid Through Ellis Hosiery Mill, LLC, Newton, NC;...

  16. SOX1 links the function of neural patterning and Notch signalling in the ventral spinal cord during the neuron-glial fate switch

    Energy Technology Data Exchange (ETDEWEB)

    Genethliou, Nicholas; Panayiotou, Elena [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Department of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus); Panayi, Helen; Orford, Michael; Mean, Richard; Lapathitis, George; Gill, Herman; Raoof, Sahir [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Gasperi, Rita De; Elder, Gregory [James J. Peters VA Medical Center, Research and Development (3F22), 130 West Kingsbridge Road, Bronx, NY 10468 (United States); Kessaris, Nicoletta; Richardson, William D. [Wolfson Institute for Biomedical Research and Research Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT (United Kingdom); Malas, Stavros, E-mail: smalas@cing.ac.cy [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Department of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus)

    2009-12-25

    During neural development the transition from neurogenesis to gliogenesis, known as the neuron-glial ({Nu}/G) fate switch, requires the coordinated function of patterning factors, pro-glial factors and Notch signalling. How this process is coordinated in the embryonic spinal cord is poorly understood. Here, we demonstrate that during the N/G fate switch in the ventral spinal cord (vSC) SOX1 links the function of neural patterning and Notch signalling. We show that, SOX1 expression in the vSC is regulated by PAX6, NKX2.2 and Notch signalling in a domain-specific manner. We further show that SOX1 regulates the expression of Hes1 and that loss of Sox1 leads to enhanced production of oligodendrocyte precursors from the pMN. Finally, we show that Notch signalling functions upstream of SOX1 during this fate switch and is independently required for the acquisition of the glial fate perse by regulating Nuclear Factor I A expression in a PAX6/SOX1/HES1/HES5-independent manner. These data integrate functional roles of neural patterning factors, Notch signalling and SOX1 during gliogenesis.

  17. Sox2 in Embryonic Stem Cells and Lung Development

    NARCIS (Netherlands)

    C.G. Pardo (Cristina Gontan)

    2009-01-01

    markdownabstract__Abstract__ Sox2 is a fascinating transcription factor with multiple roles during embryonic development. In early embryonic development, Sox2 is one of the key transcription factors in the maintenance of the pluripotent status of the cells of the inner cell mass (ICM). Sox2 is also

  18. Constitutive SoxS expression in a fluoroquinolone-resistant strain with a truncated SoxR protein and identification of a new member of the marA-soxS-rob regulon, mdtG.

    Science.gov (United States)

    Fàbrega, Anna; Martin, Robert G; Rosner, Judah L; Tavio, M Mar; Vila, Jordi

    2010-03-01

    Elevated levels of fluoroquinolone resistance are frequently found among Escherichia coli clinical isolates. This study investigated the antibiotic resistance mechanisms of strain NorE5, derived in vitro by exposing an E. coli clinical isolate, PS5, to two selection steps with increasing concentrations of norfloxacin. In addition to the amino acid substitution in GyrA (S83L) present in PS5, NorE5 has an amino acid change in ParC (S80R). Furthermore, we now find by Western blotting that NorE5 has a multidrug resistance phenotype resulting from the overexpression of the antibiotic resistance efflux pump AcrAB-TolC. Microarray and gene fusion analyses revealed significantly increased expression in NorE5 of soxS, a transcriptional activator of acrAB and tolC. The high soxS activity is attributable to a frameshift mutation that truncates SoxR, rendering it a constitutive transcriptional activator of soxS. Furthermore, microarray and reverse transcription-PCR analyses showed that mdtG (yceE), encoding a putative efflux pump, is overexpressed in the resistant strain. SoxS, MarA, and Rob activated an mdtG::lacZ fusion, and SoxS was shown to bind to the mdtG promoter, showing that mdtG is a member of the marA-soxS-rob regulon. The mdtG marbox sequence is in the backward or class I orientation within the promoter, and its disruption resulted in a loss of inducibility by MarA, SoxS, and Rob. Thus, chromosomal mutations in parC and soxR are responsible for the increased antibiotic resistance of NorE5.

  19. Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells.

    Science.gov (United States)

    Hutchins, Andrew Paul; Choo, Siew Hua; Mistri, Tapan Kumar; Rahmani, Mehran; Woon, Chow Thai; Ng, Calista Keow Leng; Jauch, Ralf; Robson, Paul

    2013-02-01

    Transcription factors (TF) often bind in heterodimeric complexes with each TF recognizing a specific neighboring cis element in the regulatory region of the genome. Comprehension of this DNA motif grammar is opaque, yet recent developments have allowed the interrogation of genome-wide TF binding sites. We reasoned that within this data novel motif grammars could be identified that controlled distinct biological programs. For this purpose, we developed a novel motif-discovery tool termed fexcom that systematically interrogates ChIP-seq data to discover spatially constrained TF-TF composite motifs occurring over short DNA distances. We applied this to the extensive ChIP-seq data available from mouse embryonic stem cells (ESCs). In addition to the well-known and most prevalent sox-oct motif, we also discovered a novel constrained spacer motif for Esrrb and Sox2 with a gap of between 2 and 8 bps that Essrb and Sox2 cobind in a selective fashion. Through the use of knockdown experiments, we argue that the Esrrb-Sox2 complex is an arbiter of gene expression differences between ESCs and epiblast stem cells (EpiSC). A number of genes downregulated upon dual Esrrb/Sox2 knockdown (e.g., Klf4, Klf5, Jam2, Pecam1) are similarly downregulated in the ESC to EpiSC transition and contain the esrrb-sox motif. The prototypical Esrrb-Sox2 target gene, containing an esrrb-sox element conserved throughout eutherian and metatherian mammals, is Nr0b1. Through positive regulation of this transcriptional repressor, we argue the Esrrb-Sox2 complex promotes the ESC state through inhibition of the EpiSC transcriptional program and the same trio may also function to maintain trophoblast stem cells.

  20. Testis development in the absence of SRY: chromosomal rearrangements at SOX9 and SOX3.

    Science.gov (United States)

    Vetro, Annalisa; Dehghani, Mohammad Reza; Kraoua, Lilia; Giorda, Roberto; Beri, Silvana; Cardarelli, Laura; Merico, Maurizio; Manolakos, Emmanouil; Parada-Bustamante, Alexis; Castro, Andrea; Radi, Orietta; Camerino, Giovanna; Brusco, Alfredo; Sabaghian, Marjan; Sofocleous, Crystalena; Forzano, Francesca; Palumbo, Pietro; Palumbo, Orazio; Calvano, Savino; Zelante, Leopoldo; Grammatico, Paola; Giglio, Sabrina; Basly, Mohamed; Chaabouni, Myriam; Carella, Massimo; Russo, Gianni; Bonaglia, Maria Clara; Zuffardi, Orsetta

    2015-08-01

    Duplications in the ~2 Mb desert region upstream of SOX9 at 17q24.3 may result in familial 46,XX disorders of sex development (DSD) without any effects on the XY background. A balanced translocation with its breakpoint falling within the same region has also been described in one XX DSD subject. We analyzed, by conventional and molecular cytogenetics, 19 novel SRY-negative unrelated 46,XX subjects both familial and sporadic, with isolated DSD. One of them had a de novo reciprocal t(11;17) translocation. Two cases carried partially overlapping 17q24.3 duplications ~500 kb upstream of SOX9, both inherited from their normal fathers. Breakpoints cloning showed that both duplications were in tandem, whereas the 17q in the reciprocal translocation was broken at ~800 kb upstream of SOX9, which is not only close to a previously described 46,XX DSD translocation, but also to translocations without any effects on the gonadal development. A further XX male, ascertained because of intellectual disability, carried a de novo cryptic duplication at Xq27.1, involving SOX3. CNVs involving SOX3 or its flanking regions have been reported in four XX DSD subjects. Collectively in our cohort of 19 novel cases of SRY-negative 46,XX DSD, the duplications upstream of SOX9 account for ~10.5% of the cases, and are responsible for the disease phenotype, even when inherited from a normal father. Translocations interrupting this region may also affect the gonadal development, possibly depending on the chromatin context of the recipient chromosome. SOX3 duplications may substitute SRY in some XX subjects.

  1. Emerging role of long non-coding RNA SOX2OT in SOX2 regulation in breast cancer.

    Directory of Open Access Journals (Sweden)

    Marjan E Askarian-Amiri

    Full Text Available The transcription factor SOX2 is essential for maintaining pluripotency in a variety of stem cells. It has important functions during embryonic development, is involved in cancer stem cell maintenance, and is often deregulated in cancer. The mechanism of SOX2 regulation has yet to be clarified, but the SOX2 gene lies in an intron of a long multi-exon non-coding RNA called SOX2 overlapping transcript (SOX2OT. Here, we show that the expression of SOX2 and SOX2OT is concordant in breast cancer, differentially expressed in estrogen receptor positive and negative breast cancer samples and that both are up-regulated in suspension culture conditions that favor growth of stem cell phenotypes. Importantly, ectopic expression of SOX2OT led to an almost 20-fold increase in SOX2 expression, together with a reduced proliferation and increased breast cancer cell anchorage-independent growth. We propose that SOX2OT plays a key role in the induction and/or maintenance of SOX2 expression in breast cancer.

  2. ompW is cooperatively upregulated by MarA and SoxS in response to menadione.

    Science.gov (United States)

    Collao, B; Morales, E H; Gil, F; Calderón, I L; Saavedra, C P

    2013-04-01

    OmpW is a minor porin whose biological function has not been clearly defined. Evidence obtained in our laboratory indicates that in Salmonella enterica serovar Typhimurium the expression of OmpW is activated by SoxS upon exposure to paraquat and it is required for resistance. SoxS belongs to the AraC family of transcriptional regulators, like MarA and Rob. Due to their high structural similarity, the genes under their control have been grouped in the mar/sox/rob regulon, which presents a DNA-binding consensus sequence denominated the marsox box. In this work, we evaluated the role of the transcription factors MarA, SoxS and Rob of S. enterica serovar Typhimurium in regulating ompW expression in response to menadione. We determined the transcript and protein levels of OmpW in different genetic backgrounds; in the wild-type and Δrob strains ompW was upregulated in response to menadione, while in the ΔmarA and ΔsoxS strains the induction was abolished. In a double marA soxS mutant, ompW transcript levels were lowered after exposure to menadione, and only complementation in trans with both genes restored the positive regulation. Using transcriptional fusions and electrophoretic mobility shift assays with mutant versions of the promoter region we demonstrated that two of the predicted sites were functional. Additionally, we demonstrated that MarA increases the affinity of SoxS for the ompW promoter region. In conclusion, our study shows that ompW is upregulated in response to menadione in a cooperative manner by MarA and SoxS through a direct interaction with the promoter region.

  3. Isolation and sequencing of the HMG domain of ten Sox genes from Odorrana schmackeri (Amphibia: Anura

    Directory of Open Access Journals (Sweden)

    Ning Wang

    2009-03-01

    Full Text Available Sox (SRY-related HMG-box genes encode a family of transcriptional regulators, which are characterized by a conserved 79-amino acid domain known as HMG-box. They play essential roles in a diverse range of processes including sex determination and the development of the central nervous system (CNS, neural crest and endoderm. In this paper, the HMG domain of ten distinct Sox gene family members (os-Sox2, os-Sox3a, os-Sox3b, os-Sox4, os-Sox11a, os-Sox11b, os-Sox14a, os-Sox14b, os-Sox21a, os-Sox21b were isolated from both male and female Odorrana schmackeri (Boettger, 1892 using PCR, and no sexual differences were found. Molecular phylogenetic analysis of the HMG domain suggested that these ten Sox genes are members of the SoxB and SoxC groups. In addition, sequence analysis suggested that four Sox genes (os-Sox3, os-Sox11, os-Sox14, os-Sox21 were duplicated. The duplication-degeneration-complementation model should be implied to explain the evolution and diversity of the Sox gene family in O. schmackeri.

  4. Differential expression of the transcription factors MarA, Rob, and SoxS of Salmonella Typhimurium in response to sodium hypochlorite: down-regulation of rob by MarA and SoxS.

    Science.gov (United States)

    Collao, B; Morales, E H; Gil, F; Polanco, R; Calderón, I L; Saavedra, C P

    2012-11-01

    To survive, Salmonella enterica serovar Typhimurium (S. Typhimurium) must sense signals found in phagocytic cells and modulate gene expression. In the present work, we evaluated the expression and cross-regulation of the transcription factors MarA, Rob, and SoxS in response to NaOCl. We generated strains ΔsoxS and ΔmarA, which were 20 times more sensitive to NaOCl as compared to the wild-type strain; while Δrob only 5 times. Subsequently, we determined that marA and soxS transcript and protein levels were increased while those of rob decreased in a wild-type strain treated with NaOCl. To assess if changes in S. Typhimurium after exposure to NaOCl were due to a cross-regulation, as in Escherichia coli, we evaluated the expression of marA, soxS, and rob in the different genetic backgrounds. The positive regulation observed in the wild-type strain of marA and soxS was retained in the Δrob strain. As in the wild-type strain, rob was down-regulated in the ΔmarA and ΔsoxS treated with NaOCl; however, this effect was decreased. Since rob was down-regulated by both factors, we generated a ΔmarA ΔsoxS strain finding that the negative regulation was abolished, confirming our hypothesis. Electrophoretic mobility shift assays using MarA and SoxS confirmed an interaction with the promoter of rob.

  5. Characterization of SoxB2 and SoxC genes in Amphioxus (Branchiostoma belcheri): Implications for their evolutionary conservation

    Institute of Scientific and Technical Information of China (English)

    LIN YuShuang; CHEN DongYan; FAN QiuSheng; ZHANG HongWei

    2009-01-01

    Most Sox genes directly affect cell fate determination and differentiation. In this study, we isolated two Sox genes: SoxB2 and SoxC from amphioxus (Branchiostoma belcheri), the closest living invertebrate relative of the vertebrates. Alignments of SoxB2 and SoxC protein sequences and their vertebrate homologs show high conservation of their HMG domains. Phylogenic analysis shows that amphioxus SoxB2 and SoxC fall out of the vertebrate branches, suggesting that vertebrate homologs might arise from gene duplications during evolution. The two genes possess similar spatial and temporal expression patterns during embryogenesis and in adults. They are both maternally inherited. During neurulation, they are expressed in the neural ectoderm and archenterons. In adults, they are expressed not only in the nerve cord, but also in the gut, midgut diverticulum, gill and oocytes. These results suggest that amphioxus SoxB2 and SoxC might co-function and have conserved functions in the nervous sys-tem and gonads as their vertebrate homologs.

  6. Expressions of SOX2 and CyclinD1 in epithelial ovarian cancer tissue%卵巢上皮性癌组织中 SOX2和 CyclinD1的表达

    Institute of Scientific and Technical Information of China (English)

    姚俊阁; 李红雨; 赵书君; 张慧; 张艳艳; 郭欢欢

    2014-01-01

    tissue . SOX2 may be in coordinated with CyclinD 1 in carcinogenesis and progression of epithelial ovarian cancer .

  7. SOX6 attenuates glucose-stimulated insulin secretion by repressing PDX1 transcriptional activity and is down-regulated in hyperinsulinemic obese mice.

    Science.gov (United States)

    Iguchi, Haruhisa; Ikeda, Yukio; Okamura, Masashi; Tanaka, Toshiya; Urashima, Yasuyo; Ohguchi, Hiroto; Takayasu, Shinobu; Kojima, Noriaki; Iwasaki, Satoshi; Ohashi, Riuko; Jiang, Shuying; Hasegawa, Go; Ioka, Ryoichi X; Magoori, Kenta; Sumi, Koichi; Maejima, Takashi; Uchida, Aoi; Naito, Makoto; Osborne, Timothy F; Yanagisawa, Masashi; Yamamoto, Tokuo T; Kodama, Tatsuhiko; Sakai, Juro

    2005-11-11

    In obesity-related insulin resistance, pancreatic islets compensate for insulin resistance by increasing secretory capacity. Here, we report the identification of sex-determining region Y-box 6 (SOX6), a member of the high mobility group box superfamily of transcription factors, as a co-repressor for pancreatic-duodenal homeobox factor-1 (PDX1). SOX6 mRNA levels were profoundly reduced by both a long term high fat feeding protocol in normal mice and in genetically obese ob/ob mice on a normal chow diet. Interestingly, we show that SOX6 is expressed in adult pancreatic insulin-producing beta-cells and that overexpression of SOX6 decreased glucose-stimulated insulin secretion, which was accompanied by decreased ATP/ADP ratio, Ca(2+) mobilization, proinsulin content, and insulin gene expression. In a complementary fashion, depletion of SOX6 by small interfering RNAs augmented glucose-stimulated insulin secretion in insulinoma mouse MIN6 and rat INS-1E cells. These effects can be explained by our mechanistic studies that show SOX6 acts to suppress PDX1 stimulation of the insulin II promoter through a direct protein/protein interaction. Furthermore, SOX6 retroviral expression decreased acetylation of histones H3 and H4 in chromatin from the promoter for the insulin II gene, suggesting that SOX6 may decrease PDX1 stimulation through changes in chromatin structure at specific promoters. These results suggest that perturbations in transcriptional regulation that are coordinated through SOX6 and PDX1 in beta-cells may contribute to the beta-cell adaptation in obesity-related insulin resistance.

  8. FCC DeSOx and DeNOx additive technology

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The fluid catalytic cracking(FCC) is the principal gasoline-producing process in the refinery. Considerable amounts of harmful sulfur oxides and nitrogen oxides (SOx and NOx ) are generated with the FCC operation. Impacted by strengthening environmental regulations and the current global emphasis on environmental protection and pollution abatement, refiners have been meaning to look for effective ways to control and reduce SOx and NOx emissions. FCC DeSOx and DeNOx additives is the most promising measure. The present paper reviews the developments in FCC DeSOx and DeNOx additive technology based on the respective authors' works, the future directions of the technology are also discussed.

  9. Sry and SoxE genes: How they participate in mammalian sex determination and gonadal development?

    Science.gov (United States)

    She, Zhen-Yu; Yang, Wan-Xi

    2017-03-01

    In mammals, sex determination defines the differentiation of the bipotential genital ridge into either testes or ovaries. Sry, the mammalian Y-chromosomal testis-determining gene, is a master regulator of male sex determination. It acts to switch the undifferentiated genital ridge towards testis development, triggering the adoption of a male fate. Sry initiates a cascade of gene networks through the direct regulation of Sox9 expression and promotes supporting cell differentiation, Leydig cell specification, vasculature formation and testis cord development. In the absence of Sry, alternative genetic cascades, including female sex-determining genes RSPO1, Wnt4/β-catenin and Foxl2, are involved in the formation of female genitalia and the maintenance of female ovarian development. The mutual antagonisms between male and female sex-determining pathways are crucial in not just the initiation but also the maintenance of the somatic sex of the gonad throughout the organism's lifetime. Any imbalances in above sex-determining genes can cause disorders of sex development in humans and mice. In this review, we provide a detailed summary of the expression profiles, biochemical properties and developmental functions of Sry and SoxE genes in embryonic testis development and adult gonadal development. We also briefly summarize the dedicate balances between male and female sex-determining genes in mammalian sex development, with particular highlights on the molecular actions of Sry and Sox9 transcription factors.

  10. SOX9 drives WNT pathway activation in prostate cancer.

    Science.gov (United States)

    Ma, Fen; Ye, Huihui; He, Housheng Hansen; Gerrin, Sean J; Chen, Sen; Tanenbaum, Benjamin A; Cai, Changmeng; Sowalsky, Adam G; He, Lingfeng; Wang, Hongyun; Balk, Steven P; Yuan, Xin

    2016-05-02

    The transcription factor SOX9 is critical for prostate development, and dysregulation of SOX9 is implicated in prostate cancer (PCa). However, the SOX9-dependent genes and pathways involved in both normal and neoplastic prostate epithelium are largely unknown. Here, we performed SOX9 ChIP sequencing analysis and transcriptome profiling of PCa cells and determined that SOX9 positively regulates multiple WNT pathway genes, including those encoding WNT receptors (frizzled [FZD] and lipoprotein receptor-related protein [LRP] family members) and the downstream β-catenin effector TCF4. Analyses of PCa xenografts and clinical samples both revealed an association between the expression of SOX9 and WNT pathway components in PCa. Finally, treatment of SOX9-expressing PCa cells with a WNT synthesis inhibitor (LGK974) reduced WNT pathway signaling in vitro and tumor growth in murine xenograft models. Together, our data indicate that SOX9 expression drives PCa by reactivating the WNT/β-catenin signaling that mediates ductal morphogenesis in fetal prostate and define a subgroup of patients who would benefit from WNT-targeted therapy.

  11. SOX7与SOX9在鉴别前列腺癌与前列腺增生中的作用%The role of SOX7 and SOX9 in differentiating prostate cancer from benign prostatic hyperplasia

    Institute of Scientific and Technical Information of China (English)

    许礼伟; 叶燕霞; 叶显明; 江福能; 秦国强; 钟惟德

    2014-01-01

    目的 探讨SOX7和SOX9在鉴别前列腺癌与前列腺增生中的临床意义.方法 收集147例前列腺癌与28例前列腺增生患者病理组织及临床资料,运用免疫组化实验分析SOX7与SOX9的表达及其作用.结果 SOX7在前列腺癌组织中表现为低表达(P=0.025),而SOX9为高表达(P=0.043),SOX7与SOX9呈负相关(r=-0.263,P=0.001).将SOX7与SOX9免疫组化评分与前列腺癌病理参数相结合进行分析,发现SOX7在血清PSA水平<10 ng/ml(P=0.048)、Gleason评分<7(P=0.018)、肿瘤TNM分期<T2a(P<0.001)和病理分期T2a~T2c(P=0.002)前列腺癌患者中有较高的表达,而SOX9在Gleason评分≥7(P=0.001)和肿瘤TNM分期≥T2a(P=0.005)的前列腺癌患者中有较高的表达,差异有统计学意义.结论 通过检测SOX7和SOX9的水平可鉴别前列腺癌与前列腺增生,并可以初步判断前列腺癌的恶性程度.

  12. Characterization, phylogeny, alternative splicing and expression of Sox30 gene

    Directory of Open Access Journals (Sweden)

    Huang Baofeng

    2010-12-01

    Full Text Available Abstract Background Members of the Sox gene family isolated from both vertebrates and invertebrates have been proved to participate in a wide variety of developmental processes, including sex determination and differentiation. Among these members, Sox30 had been considered to exist only in mammals since its discovery, and its exact function remains unclear. Results Sox30 cDNA was cloned from the Nile tilapia by RT-PCR and RACE. Screening of available genome and EST databases and phylogenetic analysis showed that Sox30 also exists in non-mammalian vertebrates and invertebrates, which was further supported by synteny analyses. Tissue expression in human, mouse and tilapia suggested that Sox30 was probably a gonad-specific gene, which was also supported by the fact that Sox30 EST sequences were obtained from gonads of the animal species. In addition, four alternatively spliced isoforms were isolated from tilapia gonad. Their temporal and spatial expression patterns during normal and sex reversed gonadal development were investigated by RT-PCR and in situ hybridization. Our data suggest that expressions of Sox30 isoforms are related to stage and phenotypic-sex, observed in the germ cells of male gonad and in somatic cells of the female gonad. Conclusions Sox30 is not a gene only existed in mammals, but exists widely throughout the animal kingdom as supported by our bioinformatic, phylogenetic and syntenic analyses. It is very likely that Sox30 is expressed exclusively in gonads. Expression analyses revealed that Sox30 may be involved in female and male gonadal development at different stages by alternative splicing.

  13. On Products of Property b1

    Institute of Scientific and Technical Information of China (English)

    Jianjun WANG; Peiyong ZHU

    2012-01-01

    In this note,we present that:(1) Let X=σ{Xα:α ∈ A} be |A|-paracompact (resp.,hereditarily |A|-paracompact).If every finite subproduct of {Xα:α ∈ A} has property b1 (resp.,hereditarily property b1),then so is X.(2) Let X be a P-space and Y a metric space.Then,X × Y has property b1 iff X has property b1.(3) Let X be a strongly zero-dimensional and compact space.Then,X × Y has property b1 iff Y has property b1.

  14. Sox11 Reduces Caspase-6 Cleavage and Activity.

    Directory of Open Access Journals (Sweden)

    Elaine Waldron-Roby

    Full Text Available The apoptotic cascade is an orchestrated event, whose final stages are mediated by effector caspases. Regulatory binding proteins have been identified for caspases such as caspase-3, -7, -8, and -9. Many of these proteins belong to the inhibitor of apoptosis (IAP family. By contrast, caspase-6 is not believed to be influenced by IAPs, and little is known about its regulation. We therefore performed a yeast-two-hybrid screen using a constitutively inactive form of caspase-6 for bait in order to identify novel regulators of caspase-6 activity. Sox11 was identified as a potential caspase-6 interacting protein. Sox11 was capable of dramatically reducing caspase-6 activity, as well as preventing caspase-6 self- cleavage. Several regions, including amino acids 117-214 and 362-395 within sox11 as well as a nuclear localization signal (NLS all contributed to the reduction in caspase-6 activity. Furthermore, sox11 was also capable of decreasing other effector caspase activity but not initiator caspases -8 and -9. The ability of sox11 to reduce effector caspase activity was also reflected in its capacity to reduce cell death following toxic insult. Interestingly, other sox proteins also had the ability to reduce caspase-6 activity but to a lesser extent than sox11.

  15. 34 CFR 5b.1 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... maintained by the Department, including but not limited to the individual's education, financial transactions... 34 Education 1 2010-07-01 2010-07-01 false Definitions. 5b.1 Section 5b.1 Education Office of the Secretary, Department of Education PRIVACY ACT REGULATIONS § 5b.1 Definitions. As used in this part:...

  16. 18 CFR 1b.1 - Definitions.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Definitions. 1b.1 Section 1b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.1 Definitions. For purposes of this part—...

  17. Clinicopathological significance of SOX4 expression in primary gallbladder carcinoma

    Directory of Open Access Journals (Sweden)

    Wang Chengguo

    2012-04-01

    Full Text Available Abstract Aim SOX4, as a member of the SRY-related HMG-box (SOX transcription factor family, has been demonstrated to be involved in tumorigenesis of many human malignancies; however, its role in primary gallbladder carcinoma (PGC is still largely unknown. The aim of this study was to investigate SOX4 expression in PGC and its prognostic significance. Methods From 1997 to 2006, 136 patients underwent resection for PGC. The median follow-up was 12.8 months. Immunostainings for SOX4 were performed on these archival tissues. The correlation of SOX4 expression with clinicopathological features including survival was analyzed. Results SOX4 was expressed in 75.0% (102/136 of PGC but not in the normal epithelium of the gallbladder. In addition, the over-expression of SOX4 was significantly associated with low histologic grade (P = 0.02, low pathologic T stage (P = 0.02, and early clinical stage (P = 0.03. The levels of SOX4 immunostainings in PGC tissues with positive nodal metastasis were also significantly lower than those without (P = 0.01. Moreover, Kaplan-Meier curves showed that SOX4 over-expression was significantly related to better overall (P = 0.008 and disease-free survival (P = 0.01. Furthermore, multivariate analyses showed that SOX4 expression was an independent risk factor for both overall (P = 0.03, hazard ratio, 3.682 and disease-free survival (P = 0.04, hazard ratio, 2.215. Conclusion Our data indicate for the first time that the over-expression of SOX4 in PGC was significantly correlated with favorable clinicopathologic features and was an independent prognostic factor for better overall and disease-free survival in patients. Therefore, SOX4 might be an auxiliary parameter for predicting malignant behavior for PGC. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1534825818694957.

  18. SOX9 Is a Progressive Factor in Prostate Cancer

    Science.gov (United States)

    2013-09-01

    implicated in supporting stem cells in small intestine and hair follicle (52–54). Recent lineage tracing studies found that SOX9 marks the adult stem cell... target . 15. SUBJECT TERMS SOX9, caner stem cells 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF...proliferate despite the castration level of circulating testosterone. Although enthusiasm for androgen receptor targeting approaches remains high

  19. MarA, SoxS and Rob function as virulence factors in an Escherichia coli murine model of ascending pyelonephritis.

    Science.gov (United States)

    Casaz, Paul; Garrity-Ryan, Lynne K; McKenney, David; Jackson, Caroline; Levy, Stuart B; Tanaka, S Ken; Alekshun, Michael N

    2006-12-01

    MarA, SoxS and Rob are transcription factors belonging to the AraC family. While these proteins have been associated historically with control of multiple antibiotic resistance, and tolerance to oxidative stress agents and organic solvents, only a paucity of experimental data support a role in regulating virulence. Clinical Escherichia coli isolates, and isogenic strains lacking marA, soxS and rob, were studied in a murine model of ascending pyelonephritis, which is a clinically relevant model of urinary tract infection. Organisms lacking all three transcription factors (triple knockouts) were significantly less virulent than parental strains, and complementation studies demonstrated that the addition of marA, soxS and rob individually restored wild-type virulence in the triple-knockout strain. Deletion of soxS or rob alone was more detrimental than the removal of marA. Thus, all three proteins contribute to virulence in vivo.

  20. Cloning and sequence analysis of Sox genes in a tetraploid cyprinid fish, Tor douronensis

    Institute of Scientific and Technical Information of China (English)

    GUO BaoCheng; LI JunBing; TONG ChaoBo; HE ShunPing

    2008-01-01

    A PCR survey for Sox genes in a young tetraploid fish Tor douronensis (Teleostei: Cyprinidae) was per-formed to access the evolutionary fates of important functional genes after genome duplication caused by polyploidization event. Totally 13 Sox genes were obtained in Tor douronensis, which represent SoxB, SoxC and SoxE groups. Phylogenetic analysis of Sox genes in Tor douronensis provided evidence for fish-specific genome duplication, and suggested that Sox19 might be a teleost specific Sox gene member. Sequence analysis revealed most of the nucleotide substitutions between duplicated copies of Sox genes caused by tetraploidization event or their orthologues in other species are silent substitutions. It would appear that the sequences are under purifying selective pressure, strongly suggesting that they repre- sent functional genes and supporting selection against all null allele at either of two duplicated loci of Sox4a, Sox9a and Sox9b. Surprising variations of the intron length and similarities of two duplicated copies of Sox9a and Sox9b, suggest that Tor douronensis might be an allotetraploidy.

  1. Cyclin B1 Vaccine Delays Spontaneous Tumors

    Science.gov (United States)

    Laura A, Vella; Min, Yu; Amy, Phillips; Olivera J, Finn

    2012-01-01

    We previously identified cyclin B1-specific T cells and antibodies in cancer patients with cyclin B1+ tumors and also in some healthy individuals. We also demonstrated that these responses may be important in cancer immunosurveillance by showing that vaccination against cyclin B1 prevents growth of transplantable cyclin B1+ tumors in mice. Constitutive overexpression of cyclin B1 was determined to correlate with the lack of p53 function. This allowed us to use p53−/− mice as a model that better approximates human disease. p53−/− mice spontaneously develop cyclin B1+ tumors. At 5–6 weeks of age, when the mice were still healthy with no evidence of tumor, they received the cyclin B1 vaccine and were then observed for tumor growth. We demonstrate that cyclin B1 vaccination can delay spontaneous cyclin B1+ tumor growth and increases median survival of tumor bearing p53−/− mice. PMID:19769738

  2. 18 CFR 3b.1 - Purpose.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Purpose. 3b.1 Section 3b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  3. Dual lineage-specific expression of Sox17 during mouse embryogenesis

    DEFF Research Database (Denmark)

    Choi, Eunyoung; Kraus, Marine R C; Lemaire, Laurence A

    2012-01-01

    Sox17 is essential for both endoderm development and fetal hematopoietic stem cell (HSC) maintenance. While endoderm-derived organs are well known to originate from Sox17-expressing cells, it is less certain whether fetal HSCs also originate from Sox17-expressing cells. By generating a Sox17(GFPCre......) allele and using it to assess the fate of Sox17-expressing cells during embryogenesis, we confirmed that both endodermal and a part of definitive hematopoietic cells are derived from Sox17-positive cells. Prior to E9.5, the expression of Sox17 is restricted to the endoderm lineage. However, at E9.5 Sox17...... is expressed in the endothelial cells (ECs) at the para-aortic splanchnopleural region that contribute to the formation of HSCs at a later stage. The identification of two distinct progenitor cell populations that express Sox17 at E9.5 was confirmed using fluorescence-activated cell sorting together with RNA...

  4. Pseudomonas aeruginosa SoxR does not conform to the archetypal paradigm for SoxR-dependent regulation of the bacterial oxidative stress adaptive response.

    Science.gov (United States)

    Palma, Marco; Zurita, Juan; Ferreras, Julian A; Worgall, Stefan; Larone, Davise H; Shi, Lei; Campagne, Fabien; Quadri, Luis E N

    2005-05-01

    SoxR is a transcriptional regulator that controls an oxidative stress response in Escherichia coli. The regulator is primarily activated by superoxide anion-dependent oxidation. Activated SoxR turns on transcription of a single gene, soxS, which encodes a transcriptional regulator that activates a regulon that includes dozens of oxidative stress response genes. SoxR homologues have been identified in many bacterial species, including the opportunistic pathogen Pseudomonas aeruginosa. However, the expected SoxR partner, SoxS, has not been found in P. aeruginosa. Thus, the primary gene target(s) of P. aeruginosa SoxR is unknown and the involvement of this regulator in the oxidative stress response of the bacterium remains unclear. We utilized transcriptome profiling to identify the P. aeruginosa SoxR regulon and constructed and characterized an unmarked P. aeruginosa DeltasoxR mutant. We provide evidence indicating that P. aeruginosa SoxR activates a six-gene regulon in response to O(2)(.-)-induced stress. The regulon includes three transcriptional units: (i) the recently identified mexGHI-ompD four-gene operon, which encodes a multidrug efflux pump system involved in quorum-sensing signal homeostasis; (ii) gene PA3718, encoding a probable efflux pump; and (iii) gene PA2274, encoding a probable monooxygenase. We also demonstrate that P. aeruginosa SoxR is not a key regulatory player in the oxidative stress response. Finally, we show that P. aeruginosa SoxR is required for virulence in a mouse model of intrapulmonary infection. These results demonstrate that the E. coli-based SoxRS paradigm does not hold in P. aeruginosa and foster new hypotheses for the possible physiological role of P. aeruginosa SoxR.

  5. Study of Microflares through SOXS Mission

    Indian Academy of Sciences (India)

    Rajmal Jain; Vishal Joshi; Yoichiro Hanaoka; T. Sakurai; Nipa Upadhyay

    2006-06-01

    We present a study of 10 microflares observed in 4–30 keV by SOXS mission simultaneously with H observations made at NAOJ, Japan during the interval between February and August 2004. The X-ray and H light curves showed that the lifetime of microflares varies between 4 and 25 min. We found that the X-ray emission in all microflares under study in the dynamic energy range of 4–30 keV can be fitted by thermal plus non-thermal components. The thermal spectrum appeared to start from almost 4 keV, low level discriminator (LLD) of both Si and CZT detectors, however it ends below 8 keV. We also observed the Fe line complex features at 6.7 keV in some microflares and attempted to fit this line by isothermal temperature assumption. The temperature of isothermal plasma of microflares varies in the range between 8.6 and 10.1 MK while emission measure between 0.5 and 2 × 1049 cm-3. Non-thermal (NT) emission appeared in the energy range 7–15 keV with exponent -6.8 ≤ ≤ -4.8. Our study of microflares that had occurred on 25 February 2004 showed that sometimes a given active region produces recurrent microflare activity of a similar nature.We concluded from X-ray and simultaneous H observations that the microflares are perhaps the result of the interaction of low lying loops. It appears that the electrons that accelerated during reconnection heat the ambient coronal plasma as well as interact with material while moving down along the loops and thereby produce H bright kernels.

  6. Study of impact of reduced Sox4 expression levels in homeostasis, cancer and ageing

    OpenAIRE

    Foronda Álvaro, Miguel

    2014-01-01

    Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 12-05-2014 Sox4 belongs to the SoxC class of transcription factors (encompassing Sox4, Sox11 and Sox12) within the Sry-related HMG box-containing superfamily of proteins. Sox4 expression peaks during embryonic development in neural crest and mesenchyme, where it regulates the differentiation and survival of mesenchymal and neural progeni...

  7. Targeting SOX2 as a therapeutic strategy in glioblastoma

    Directory of Open Access Journals (Sweden)

    Ander Matheu

    2016-10-01

    Full Text Available Glioblastoma is the most common and malignant brain cancer in adults. Current therapy consisting of surgery followed by radiation and temozolomide therapy has moderate success rate and the tumor reappears. Among the features that a cancer cell must have to survive the therapeutic treatment and reconstitute the tumor is the ability to self-renewal. Therefore, it is vital to identify the molecular mechanisms that regulate this activity.SOX2 is a transcription factor whose activity has been associated with the maintenance of the undifferentiated state of cancer stem cells in several tissues including the brain. Several groups have detected SOX2 levels increased in biopsies of glioblastoma patients, with highest levels associated to poor outcome. Therefore, SOX2 silencing might be a novel therapeutic approach to combat cancer and particularly brain tumors.In this review, we will summarize the current knowledge about SOX2 in glioblastoma and recapitulate several strategies, which have been recently described targeting SOX2 in this malignancy.

  8. The Function of HMG-Box Transcription Factors Sox4a and Sox4b in Zebrafish Bone Development and Homeostasis

    Science.gov (United States)

    Aceto, J.; Motte, P.; Martial, J. A.; Muller, M.

    2008-06-01

    In mammals, the Sox4 gene is involved in development of endocardial crests, the brain, the lung, teeth, gonads and lymphocytes. Recently, Sox4 was shown to control bone mass and mineralization in mice. In zebrafish, two homologs for the mammalian Sox4 are present, sox4a and sox4b. Here we investigate the function of the sox4a and sox4b genes in cartilage and bone development in zebrafish. Therefore, we focus our attention on the first bone structures to be formed, the head skeleton and more precisely the pharyngeal cartilage. We show that both genes are expressed in the pharyngeal region, albeit at different time points during development. Double in situ hybridization experiments are used to exactly define the particular tissues where they are expressed. Furthermore, microinjection experiments of antisense oligonucleotides are used to block translation of these specific genes and to define their precise function during cartilage and bone development.

  9. SOXE neofunctionalization and elaboration of the neural crest during chordate evolution

    Science.gov (United States)

    Tai, Andrew; Cheung, Martin; Huang, Yong-Heng; Jauch, Ralf; Bronner, Marianne E.; Cheah, Kathryn S. E.

    2016-01-01

    During chordate evolution, two genome-wide duplications facilitated acquisition of vertebrate traits, including emergence of neural crest cells (NCCs), in which neofunctionalization of the duplicated genes are thought to have facilitated development of craniofacial structures and the peripheral nervous system. How these duplicated genes evolve and acquire the ability to specify NC and their derivatives are largely unknown. Vertebrate SoxE paralogues, most notably Sox9/10, are essential for NC induction, delamination and lineage specification. In contrast, the basal chordate, amphioxus, has a single SoxE gene and lacks NC-like cells. Here, we test the hypothesis that duplication and divergence of an ancestral SoxE gene may have facilitated elaboration of NC lineages. By using an in vivo expression assay to compare effects of AmphiSoxE and vertebrate Sox9 on NC development, we demonstrate that all SOXE proteins possess similar DNA binding and homodimerization properties and can induce NCCs. However, AmphiSOXE is less efficient than SOX9 in transactivation activity and in the ability to preferentially promote glial over neuronal fate, a difference that lies within the combined properties of amino terminal and transactivation domains. We propose that acquisition of AmphiSoxE expression in the neural plate border led to NCC emergence while duplication and divergence produced advantageous mutations in vertebrate homologues, promoting elaboration of NC traits. PMID:27734831

  10. Histone Acetylation Influences the Activity of Sox9-related Transcriptional Complex

    Directory of Open Access Journals (Sweden)

    Furumatsu,Takayuki

    2010-12-01

    Full Text Available Chondrocyte differentiation is the fundamental process in skeletal development. From the mesenchymal condensation of chondroprogenitors to the hypertrophic maturation of chondrocytes, chondrogenesis is sequentially regulated by cross-talk among transcription factors, growth factors, and chromatin structure. The master transcription factor Sry-type HMG box (Sox 9 has an essential role in the expression of chondrogenic genes through the association with Sox9-binding sites on its target genes. Several transcription factors and coactivators, such as Scleraxis/E47 and p300, cooperatively modulate the Sox9-dependent transcription by interacting with Sox9. The Sox9-related transcriptional apparatus activates its target gene expression through p300-mediated histone acetylation on chromatin. The transforming growth factor (TGF-β superfamily also plays a key role in chondrocyte differentiation. The TGF-β-regulated Smad3/4 complex activates Sox9-dependent transcription on chromatin by associating with Sox9 itself, and by recruiting p300 onto Sox9. These findings suggest that the epigenetic status including histone modification and chromatin structure, directly influences Sox9-regulated chondrocyte differentiation. In this article, we review the regulators of Sox9 expression itself, modulators of posttranslational Sox9 function, and Sox9-associating factors in the Sox9-dependent epigenetic regulation during chondrogenesis.

  11. SOX9 is a novel cancer stem cell marker surrogated by osteopontin in human hepatocellular carcinoma

    Science.gov (United States)

    Kawai, Takayuki; Yasuchika, Kentaro; Ishii, Takamichi; Miyauchi, Yuya; Kojima, Hidenobu; Yamaoka, Ryoya; Katayama, Hokahiro; Yoshitoshi, Elena Yukie; Ogiso, Satoshi; Kita, Sadahiko; Yasuda, Katsutaro; Fukumitsu, Ken; Komori, Junji; Hatano, Etsuro; Kawaguchi, Yoshiya; Uemoto, Shinji

    2016-01-01

    The current lack of cancer stem cell (CSC) markers that are easily evaluated by blood samples prevents the establishment of new therapeutic strategies in hepatocellular carcinoma (HCC). Herein, we examined whether sex determining region Y-box 9 (SOX9) represents a new CSC marker, and whether osteopontin (OPN) can be used as a surrogate marker of SOX9 in HCC. In HCC cell lines transfected with a SOX9 promoter-driven enhanced green fluorescence protein gene, FACS-isolated SOX9+ cells were capable of self-renewal and differentiation into SOX9− cells, and displayed high proliferation capacity in vitro. Xenotransplantation experiments revealed that SOX9+ cells reproduced, differentiated into SOX9− cells, and generated tumors at a high frequency in vivo. Moreover, SOX9+ cells were found to be involved in epithelial-mesenchymal transition (EMT) and activation of TGFb/Smad signaling. Gain/loss of function experiments showed that SOX9 regulates Wnt/beta-catenin signaling, including cyclin D1 and OPN. Immunohistochemistry of 166 HCC surgical specimens and serum OPN measurements showed that compared to SOX9− patients, SOX9+ patients had significantly poorer recurrence-free survival, stronger venous invasion, and higher serum OPN levels. In conclusion, SOX9 is a novel HCC-CSC marker regulating the Wnt/beta-catenin pathway and its downstream target, OPN. OPN is a useful surrogate marker of SOX9 in HCC. PMID:27457505

  12. Observation of B Meson decays to b1pi and b1K.

    Science.gov (United States)

    Aubert, B; Bona, M; Boutigny, D; Karyotakis, Y; Lees, J P; Poireau, V; Prudent, X; Tisserand, V; Zghiche, A; Tico, J Garra; Grauges, E; Lopez, L; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Pegna, D Lopes; Lynch, G; Mir, L M; Orimoto, T J; Osipenkov, I L; Ronan, M T; Tackmann, K; Tanabe, T; Wenzel, W A; Del Amo Sanchez, P; Hawkes, C M; Watson, A T; Held, T; Koch, H; Pelizaeus, M; Schroeder, T; Steinke, M; Walker, D; Asgeirsson, D J; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Barrett, M; Khan, A; Saleem, M; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Liu, F; Long, O; Shen, B C; Zhang, L; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Schalk, T; Schumm, B A; Seiden, A; Wilson, M G; Winstrom, L O; Chen, E; Cheng, C H; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Gabareen, A M; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Klose, V; Kobel, M J; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Lombardo, V; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Watson, J E; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Franchini, P; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Santoro, V; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Chaisanguanthum, K S; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Dauncey, P D; Flack, R L; Nash, J A; Vazquez, W Panduro; Tibbetts, M; Behera, P K; Chai, X; Charles, M J; Mallik, U; Ziegler, V; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Lae, C K; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; George, K A; Di Lodovico, F; Menges, W; Sacco, R; Cowan, G; Flaecher, H U; Hopkins, D A; Paramesvaran, S; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Koeneke, K; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Zhao, M; Zheng, Y; McLachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; De Nardo, G; Fabozzi, F; Lista, L; Monorchio, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; Losecco, J M; Benelli, G; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Gagliardi, N; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Ben-Haim, E; Briand, H; Calderini, G; Chauveau, J; David, P; Del Buono, L; de la Vaissière, Ch; Hamon, O; Leruste, Ph; Malclès, J; Ocariz, J; Perez, A; Prendki, J; Gladney, L; Biasini, M; Covarelli, R; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Cenci, R; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Mazur, M A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Haire, M; Biesiada, J; Elmer, P; Lau, Y P; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Baracchini, E; Bellini, F; Cavoto, G; Del Re, D; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Gioi, L Li; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Castelli, G; Franek, B; Olaiya, E O; Ricciardi, S; Roethel, W; Wilson, F F; Emery, S; Escalier, M; Gaidot, A; Ganzhur, S F; de Monchenault, G Hamel; Kozanecki, W; Vasseur, G; Yèche, Ch; Zito, M; Chen, X R; Liu, H; Park, W; Purohit, M V; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Berger, N; Claus, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Glanzman, T; Gowdy, S J; Graham, M T; Grenier, P; Hast, C; Hryn'ova, T; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Luitz, S; Luth, V; Lynch, H L; Macfarlane, D B; Marsiske, H; Messner, R; Muller, D R; O'Grady, C P; Ofte, I; Perazzo, A; Perl, M; Pulliam, T; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Stelzer, J; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; van Bakel, N; Wagner, A P; Weaver, M; Wisniewski, W J; Wittgen, M; Wright, D H; Yarritu, A K; Yi, K; Young, C C; Burchat, P R; Edwards, A J; Majewski, S A; Petersen, B A; Wilden, L; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Jain, V; Pan, B; Saeed, M A; Wappler, F R; Zain, S B; Krishnamurthy, M; Spanier, S M; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Izen, J M; Lou, X C; Ye, S; Bianchi, F; Gallo, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Hamano, K; Kowalewski, R; Nugent, I M; Roney, J M; Sobie, R J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Dasu, S; Flood, K T; Hollar, J J; Kutter, P E; Pan, Y; Pierini, M; Prepost, R; Wu, S L; Neal, H

    2007-12-14

    We present the results of searches for decays of B mesons to final states with a b1 meson and a charged pion or kaon. The data, collected with the BABAR detector at the Stanford Linear Accelerator Center, represent 382x10(6) BB[over ] pairs produced in e+e- annihilation. The results for the branching fractions are, in units of 10(-6), B(B+-->b1(0)pi+)=6.7+/-1.7+/-1.0, B(B+-->b1(0)K+)=9.1+/-1.7+/-1.0, B(B0-->b1(-/+)pi(+/-))=10.9+/-1.2+/-0.9, and B(B0-->b1(-)K+)=7.4+/-1.0+/-1.0, with the assumption that B(b1-->omega pi)=1. We also measure charge and flavor asymmetries A(ch)(B+-->b1(0)pi+)=0.05+/-0.16+/-0.02, Ach(B+-->b1(0)K+)=-0.46+/-0.20+/-0.02, A(ch)(B0-->b1(-/+)pi(+/-))=-0.05+/-0.10+/-0.02, C(B0-->b1(-/+)pi(+/-))=-0.22+/-0.23+/-0.05, DeltaC(B0-->b1(-/+)pi(+/-))=-1.04+/-0.23+/-0.08, and A(ch)(B0-->b1(-)K+)=-0.07+/-0.12+/-0.02. The first error quoted is statistical, and the second systematic.

  13. A new SOx simulation model of coal combustion

    Energy Technology Data Exchange (ETDEWEB)

    Li Yonghua; Chen Hongwei; Zhen Zhi; Feng Zhaoxing; Dong Jianxun [North China Electric Power University, Baoding (China)

    2003-07-01

    It is very important to study the emission of pollutants from a coal combustion device, and we consider the best way is to use numerical simulation for such a study. By using a mathematical model with a post-processing method and based on combustion simulation, this paper reports the calculation of the SOx distribution in a power plant boiler furnace. For the formation of SOx, a conventional chemical reaction model is adopted, and according to the principles of reaction dynamics, a model for the SOx formation is also put forward. It is the first time the calculation and on-site testing an 800MW-unit boiler have been combined in China. The test and calculation results show that the model is reasonable, and such a study will be valuable as a reference for boiler design and clean operation. 5 refs., 1 fig., 3 tabs.

  14. Homologues of sox8 and sox10 in the orange-spotted grouper Epinephelus coioides: sequences, expression patterns, and their effects on cyp19a1a promoter activities in vitro.

    Science.gov (United States)

    Liu, Qiongyou; Lu, Huijie; Zhang, Lihong; Xie, Jun; Shen, Wenying; Zhang, Weimin

    2012-09-01

    Sox8 and Sox10 are members of group E Sox proteins involved in a wide range of developmental processes including sex determination and neurogenesis in vertebrates. The orange-spotted grouper sox8a and sox10a homologues were isolated and characterized in the present study. Both sox8a and sox10a genes contain three exons and two introns, and encode putative proteins with typical structures of group E Sox. Sox8a was expressed in diverse tissues including the central nervous system and some peripheral tissues. In contrast, sox10a mRNA was detected primarily in the central nervous system. During embryogenesis, sox8a mRNA seemed to be de novo synthesized in the embryos from otic vesicle stage. However, sox10a mRNA was only detectable in juvenile fish 35 days post hatching and thereafter. The mRNA levels of sox8a in the gonads were not significantly different among ovarian developmental stages but increased in the testis. In vitro transfection assays showed that the Sox10a but not Sox8a up-regulated cyp19a1a promoter activities. Taken together, these results suggested that the sox8a may play roles in diverse tissues and during embryogenesis, whereas sox10a may be mainly involved in the neural regulation of juvenile and adult fish, and that certain Sox homologues may regulate the orange-spotted grouper cyp19a1a promoter.

  15. Molecular analysis of the distribution and phylogeny of the soxB gene among sulfur-oxidizing bacteria - evolution of the Sox sulfur oxidation enzyme system.

    Science.gov (United States)

    Meyer, Birte; Imhoff, Johannes F; Kuever, Jan

    2007-12-01

    The soxB gene encodes the SoxB component of the periplasmic thiosulfate-oxidizing Sox enzyme complex, which has been proposed to be widespread among the various phylogenetic groups of sulfur-oxidizing bacteria (SOB) that convert thiosulfate to sulfate with and without the formation of sulfur globules as intermediate. Indeed, the comprehensive genetic and genomic analyses presented in the present study identified the soxB gene in 121 phylogenetically and physiologically divergent SOB, including several species for which thiosulfate utilization has not been reported yet. In first support of the previously postulated general involvement of components of the Sox enzyme complex in the thiosulfate oxidation process of sulfur-storing SOB, the soxB gene was detected in all investigated photo- and chemotrophic species that form sulfur globules during thiosulfate oxidation (Chromatiaceae, Chlorobiaceae, Ectothiorhodospiraceae, Thiothrix, Beggiatoa, Thiobacillus, invertebrate symbionts and free-living relatives). The SoxB phylogeny reflected the major 16S rRNA gene-based phylogenetic lineages of the investigated SOB, although topological discrepancies indicated several events of lateral soxB gene transfer among the SOB, e.g. its independent acquisition by the anaerobic anoxygenic phototrophic lineages from different chemotrophic donor lineages. A putative scenario for the proteobacterial origin and evolution of the Sox enzyme system in SOB is presented considering the phylogenetic, genomic (sox gene cluster composition) and geochemical data.

  16. Characterization of SoxB2 and SoxC genes in Amphi-oxus (Branchiostoma belcheri):Implications for their evolutionary conservation

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Most Sox genes directly affect cell fate determination and differentiation. In this study,we isolated two Sox genes:SoxB2 and SoxC from amphioxus (Branchiostoma belcheri),the closest living invertebrate relative of the vertebrates. Alignments of SoxB2 and SoxC protein sequences and their vertebrate homologs show high conservation of their HMG domains. Phylogenic analysis shows that amphioxus SoxB2 and SoxC fall out of the vertebrate branches,suggesting that vertebrate homologs might arise from gene duplications during evolution. The two genes possess similar spatial and temporal expression patterns during embryogenesis and in adults. They are both maternally inherited. During neurulation,they are expressed in the neural ectoderm and archenterons. In adults,they are expressed not only in the nerve cord,but also in the gut,midgut diverticulum,gill and oocytes. These results suggest that amphioxus SoxB2 and SoxC might co-function and have conserved functions in the nervous system and gonads as their vertebrate homologs.

  17. Activation of SoxR-dependent transcription in vitro by noncatalytic or NifS-mediated assembly of [2Fe-2S] clusters into apo-SoxR.

    Science.gov (United States)

    Hidalgo, E; Demple, B

    1996-03-29

    SoxR is a transcriptional activator that senses superoxide and nitric oxide stress in Escherichia coli. The active protein isolated from E. coli contains a pair of [2Fe-2S] clusters per SoxR dimer. We previously demonstrated that the iron-free protein (apo-SoxR), isolated during purification in thiol-containing buffers, binds soxS promoter DNA with an affinity equal to that of the metalloprotein (Fe-SoxR), but lacks significant ability to activate transcription in vitro. Here we demonstrate the reversibility of this process: the full transcriptional activity of SoxR can be restored by in vitro assembly of iron-sulfur clusters into the apoprotein. Two methods were used to synthesize the metallocenters of SoxR: (i) nonenzymatic, in which apo-SoxR, incubated in the presence of iron, inorganic sulfide, and a reducing agent, regained full transcriptional activity in 5-6 h; (ii) enzymatic, in which NifS protein of Azotobacter vinelandii regenerated active Fe-SoxR in as little as 2 min. Analysis by electron paramagnetic resonance spectroscopy indicated that binuclear [2Fe-2S] clusters were restored by both the enzymatic and nonenzymatic reconstitutions. A mutant SoxR protein missing one of its four cysteine residues failed to undergo either transcriptional activation or the formation of [2Fe-2S] centers, even in the presence of NifS. Thus, only the presence of an iron-sulfur center is required to restore transcriptional activity to apo-SoxR. Moreover, the catalytic generation of [2Fe-2S] centers extends the known specificity of this enzyme beyond that already shown for [4Fe-4S] centers. Catalytic generation of [2Fe-2S]-containing SoxR could allow for rapid activation of this transcription factor in vivo.

  18. The FCC Flue Gas SOx Transfer Additive RFS Developed by RIPP

    Institute of Scientific and Technical Information of China (English)

    Chen Beiyan; Jiang Wenbin; Song Haitao; Shen Ningyuan; Tian Huiping; He Mingyuan

    2007-01-01

    The present paper introduces the development of FCC flue gas SOx transfer additives by RIPP with a brief discussion of SOx transfer mechanism. The second-generation SOx transfer additives of the RFS series are RIPP's proprietary additives with significantly improved performances. The results of commercial tests indicate that the RFS additive can effectively control SOx emission of the FCC regenerator while maintaining product yields and product quality when the additive is used in a proper concentration range.

  19. SOX17 Regulates Cholangiocyte Differentiation and Acts as a Tumor Suppressor in Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Merino-Azpitarte, M; Lozano, E; Perugorria, M J

    2017-01-01

    BACKGROUND & AIMS: Cholangiocarcinoma (CCA) is a biliary malignancy linked to genetic and epigenetic abnormalities, such as hypermethylation of SOX17 promoter. Here, the role of SOX17 in cholangiocyte differentiation and cholangiocarcinogenesis was studied. METHODS: SOX17 expression/function was ...

  20. Sox2(+) adult stem and progenitor cells are important for tissue regeneration and survival of mice

    NARCIS (Netherlands)

    Arnold, K.; Sarkar, A.; Yram, M.A.; Polo, J.M.; Bronson, R.; Sengupta, S.; Seandel, M.; Geijsen, N.; Hochedlinger, K.

    2011-01-01

    The transcription factor Sox2 maintains the pluripotency of early embryonic cells and regulates the formation of several epithelia during fetal development. Whether Sox2 continues to play a role in adult tissues remains largely unknown. We show here that Sox2 marks adult cells in several epithelial

  1. The HMG box transcription factor Sox4 contributes to the development of the endocrine pancreas.

    NARCIS (Netherlands)

    Wilson, M.E.; Yang, K.Y.; Kalousova, A.; Janet, L.; Kosaka, Y.; Lynn, F.C.; Wang, J.; Mrejen, C.; Episkopou, V.; Clevers, J.C.; German, M.S.

    2005-01-01

    To investigate the role of the Sry/hydroxymethylglutaryl box (Sox) transcription factors in the development of the pancreas, we determined the expression pattern of Sox factors in the developing mouse pancreas. By RT-PCR, we detected the presence of multiple Sox family members in both the developing

  2. Sox9 expression in canine epithelial skin tumors

    Directory of Open Access Journals (Sweden)

    E. Fantinato

    2015-07-01

    Full Text Available Sox9 is a master regulatory gene involved in developmental processes, stem cells maintenance and tumorigenesis. This gene is expressed in healthy skin but even in several skin neoplasms, where its expression patterns often resembles those of the developing hair follicle. In this study, samples from eleven different types of canine skin neoplasms (squamous papilloma, squamous cell carcinoma, infundibular keratinizing acanthoma, inferior tricholemmoma, isthmic tricholemmoma, trichoblastoma, trichoepitelioma, malignant trichoepitelioma, pilomatricoma, subungual keratoacanthoma, subungual squamous cell carcinoma were immunohistochemically stained and evaluated for Sox9 with the aim to correlate tumor phenotype with molecular characteristics that may help to better define tumor development, contribute to its diagnosis and clinical management. Keratoacanthoma excluded, all the skin neoplasms examined showed a variable positivity to Sox9, especially in the basal layers, but with major intensity in neoplasms developing from the bulge region of the hair follicle, as trichoblastoma. According to our results, Sox9 could be employed as a stem cell marker to better assess the role of stem cells in canine epidermal and follicular tumors.

  3. SOX: search for short baseline neutrino oscillations with Borexino

    Science.gov (United States)

    Vivier, M.; Agostini, M.; Altenmüller, K.; Appel, S.; Bellini, G.; Benziger, J.; Berton, N.; Bick, D.; Bonfini, G.; Bravo, D.; Caccianiga, B.; Calaprice, F.; Caminata, A.; Cavalcante, P.; Chepurnov, A.; Choi, K.; Cribier, M.; D'Angelo, D.; Davini, S.; Derbin, A.; Di Noto, L.; Drachnev, I.; Durero, M.; Etenko, A.; Farinon, S.; Fischer, V.; Fomenko, K.; Franco, D.; Gabriele, F.; Gaffliot, J.; Galbiati, C.; Ghiano, C.; Giammarchi, M.; Goeger-Neff, M.; Goretti, A.; Gromov, M.; Hagner, C.; Houdy, T.; Hungerford, E.; Ianni, Aldo; Ianni, Andrea; Jonquàres, N.; Jedrzejczak, K.; Kaiser, M.; Kobychev, V.; Korablev, D.; Korga, G.; Kornoukhov, V.; Kryn, D.; Lachenmaier, T.; Lasserre, T.; Laubenstein, M.; Lehnert, B.; Link, J.; Litvinovich, E.; Lombardi, F.; Lombardi, P.; Ludhova, L.; Lukyanchenko, G.; Machulin, I.; Manecki, S.; Maneschg, W.; Marcocci, S.; Maricic, J.; Mention, G.; Meroni, E.; Meyer, M.; Miramonti, L.; Misiaszek, M.; Montuschi, M.; Mosteiro, P.; Muratova, V.; Musenich, R.; Neumair, B.; Oberauer, L.; Obolensky, M.; Ortica, F.; Pallavicini, M.; Papp, L.; Perasso, L.; Pocar, A.; Ranucci, G.; Razeto, A.; Re, A.; Romani, A.; Roncin, R.; Rossi, N.; Schönert, S.; Scola, L.; Semenov, D.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Sukhotin, S.; Suvorov, Y.; Tartaglia, R.; Testera, G.; Thurn, J.; Toropova, M.; Veyssiére, C.; Unzhakov, E.; Vogelaar, R. B.; von Feilitzsch, F.; Wang, H.; Weinz, S.; Winter, J.; Wojcik, M.; Wurm, M.; Yokley, Z.; Zaimidoroga, O.; Zavatarelli, S.; Zuber, K.; Zuzel, G.; Borexino Collaboration

    2016-05-01

    The Borexino detector has convincingly shown its outstanding performances in the low energy regime through its accomplishments in the observation and study of the solar and geo neutrinos. It is then an ideal tool to perform a state of the art source-based experiment for testing the longstanding hypothesis of a fourth sterile neutrino with ~ eV2 mass, as suggested by several anomalies accumulated over the past three decades in source, reactor, and accelerator-based experiments. The SOX project aims at successively deploying two intense radioactive sources, made of Cerium (antineutrino) and Chromium (neutrino), respectively, in a dedicated pit located beneath the detector. The existence of such an ~ eV2 sterile neutrino would then show up as an unambiguous spatial and energy distortion in the count rate of neutrinos interacting within the active detector volume. This article reports on the latest developments about the first phase of the SOX experiment, namely CeSOX, and gives a realistic projection of CeSOX sensitivity to light sterile neutrinos in a simple (3+1) model.

  4. Observation of B-meson decays to b_1 pi and b_1 K

    CERN Document Server

    Aubert, B; Boutigny, D; Karyotakis, Yu; Lees, J P; Poireau, V; Prudent, X; Tisserand, V; Zghiche, A; Garra Tico, J; Graugès-Pous, E; López, L; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lopes-Pegna, D; Lynch, G; Mir, L M; Orimoto, T J; Osipenkov, I L; Ronan, M T; Tackmann, K; Tanabé, T; Wenzel, W A; Del Amo-Sánchez, P; Hawkes, C M; Watson, A T; Held, T; Koch, H; Pelizaeus, M; Schröder, T; Steinke, M; Walker, D; Asgeirsson, D J; Çuhadar-Dönszelmann, T; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Khan, A; Saleem, M; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Liu, F; Long, O; Shen, B C; Zhang, L; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Schalk, T; Schumm, B A; Seiden, A; Wilson, M G; Winstrom, L O; Chen, E; Cheng, C H; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Gabareen, A M; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Klose, V; Kobel, M J; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Lombardo, V; Thiebaux, C; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Watson, J E; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Franchini, P; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Santoro, V; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; De Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Chaisanguanthum, K S; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Dauncey, P D; Flack, R L; Nash, J A; Panduro-Vazquez, W; Tibbetts, M; Behera, P K; Chai, X; Charles, M J; Mallik, U; Ziegler, V; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Lae, C K; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Bequilleux, J; D'Orazio, A; Davier, M; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; George, K A; Di Lodovico, F; Menges, W; Sacco, R; Cowan, G; Flächer, H U; Hopkins, D A; Paramesvaran, S; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Koeneke, K; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Zhao, M; Zheng, Y; Mclachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; De Nardo, Gallieno; Fabozzi, F; Lista, L; Monorchio, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; LoSecco, J M; Benelli, G; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Wong, Q K; Blount, N L; Brau, J E; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Gagliardi, N; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Ben-Haim, E; Briand, H; Calderini, G; Chauveau, J; David, P; Del Buono, L; De La Vaissière, C; Hamon, O; Leruste, P; Malcles, J; Ocariz, J; Pérez, A; Prendki, J; Gladney, L; Biasini, M; Covarelli, R; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Cenci, R; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Mazur, M A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Haire, M; Biesiada, J; Elmer, P; Lau, Y P; Lü, C; Olsen, J; Smith, A J S; Telnov, A V; Baracchini, E; Bellini, F; Cavoto, G; Del Re, D; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Li Gioi, L; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Castelli, G; Franek, B; Olaiya, E O; Ricciardi, S; Röthel, W; Wilson, F F; Emery, S; Escalier, M; Gaidot, A; Ganzhur, S F; Hamel de Monchenault, G; Kozanecki, W; Vasseur, G; Yéche, C; Zito, M; Chen, X R; Liu, H; Park, W; Purohit, M V; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Berger, N; Claus, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Glanzman, T; Gowdy, S J; Graham, M T; Grenier, P; Hast, C; Hrynóva, T; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Luitz, S; Lüth, V; Lynch, H L; MacFarlane, D B; Marsiske, H; Messner, R; Müller, D R; O'Grady, C P; Ofte, I; Perazzo, A; Perl, M; Pulliam, T; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Stelzer, J; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Vavra, J; Van Bakel, N; Wagner, A P; Weaver, M; Wisniewski, W J; Wittgen, M; Wright, D H; Yarritu, A K; Yi, K; Young, C C; Burchat, P R; Edwards, A J; Majewski, S A; Petersen, B A; Wilden, L; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Jain, V; Pan, B; Saeed, M A; Wappler, F R; Zain, S B; Krishnamurthy, M; Spanier, S M; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Izen, J M; Lou, X C; Ye, S; Bianchi, F; Gallo, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martínez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Hamano, K; Kowalewski, R; Nugent, I M; Roney, J M; Sobie, R J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Dasu, S; Flood, K T; Hollar, J J; Kutter, P E; Pan, Y; Pierini, M; Prepost, R; Wu, S L; Neal, H

    2007-01-01

    We present the results of searches for decays of B mesons to final states with a b_1 meson and a charged pion or kaon. The data, collected with the BaBar detector at the Stanford Linear Accelerator Center, represent 382 million B-Bbar pairs produced in e+e- annihilation. The results for the branching fractions are, in units of 10^{-6}, B(B+ -> b1^0 pi+) = 6.7 +/- 1.7 +/- 1.0 (4.0 sigma), B(B+ -> b1^0 K+ = 9.1+/- 1.7+/- 1.0 (5.3 sigma), B(B0 -> b1^-/+ pi^+/-) = 10.9 +/- 1.2 +/- 0.9 (8.9 sigma), and B(B0 -> b1^-K+) = 7.4 +/- 1.0 +/- 1.0 (6.1 sigma), with the assumption that B(b_1 -> omega pi)=1. We also measure charge and flavor asymmetries Ach(B+ -> b1^0 pi+) = 0.05 +/- 0.16 +/- 0.02, Ach(B+ -> b1^0 K+ = -0.46 +/- 0.20 +/- 0.02, Ach(B0 -> b1^-/+ pi^+/-) = -0.05 +/- 0.10 +/- 0.02, C(B0 -> b1^-/+ pi^+/-) = -0.22 +/- 0.23 +/- 0.05, deltaC(B0 -> b1^-/+ pi^+/-) = -1.04 +/- 0.23 +/- 0.08, and Ach(B0 -> b1^-K+) = -0.07 +/- 0.12 +/- 0.02, The first error quoted is statistical, the second systematic, and for the branch...

  5. Sox9基因的结构、功能及进化%Sox9 gene: structure, function and evolution

    Institute of Scientific and Technical Information of China (English)

    陈维; 王昌留; 王磊

    2012-01-01

    Sox9 is the first member of Sox gene family which has intron fragments after the discovery of SRY gene. About 671 Sox9 gene sequences are recorded in the Genebank, which are widely distributed in many species from mammals and bird to coelenterate. Sox9 is a multifunctional gene which takes part in sex determination, chondrogenesis, formation of nervous system and pancreas. Furthermore, this gene can also play roles in oncogenesis. This paper reviews the research progress of the structure, function and evolution of Sox9,to provide references for further study on Sox9 gene.%Sox9基因是继SRY基因之后人们发现的第一个具有内含子的Sox家族成员.在Genebank中可查的Sox9基因序列共671个,广泛分布于哺乳动物和鸟类直至水母等低等动物.近年来的研究发现,Sox9基因的功能呈现多样性,该基因在发育过程中参与性别的决定、软骨的形成以及神经系统和胰腺的形成,另外Sox9基因在肿瘤发生中也有一定的作用.本文从Sox9基因的结构、功能以及进化等方面进行了综述,为进一步研究Sox9基因提供参考资料.

  6. SOX9 Expression Predicts Relapse of Stage II Colon Cancer Patients

    DEFF Research Database (Denmark)

    Espersen, Maiken Lise Marcker; Linnemann, Dorte; Alamili, Mahdi;

    2016-01-01

    The aim of this study was to investigate if the protein expression of Sex-determining region y-box 9 (SOX9) in primary tumors could predict relapse of stage II colon cancer patients.144 patients with stage II primary colon cancer were retrospectively enrolledin the study. SOX9 expression...... high levels of SOX9 of primary stage II colon tumors predict low riskof relapse whereas low levels of SOX9 predict high risk of relapse. SOX9 may have an important value as a biomarker when evaluating risk of relapse for personalized treatment....

  7. SOX9 accelerates ESC differentiation to three germ layer lineages by repressing SOX2 expression through P21 (WAF1/CIP1).

    Science.gov (United States)

    Yamamizu, Kohei; Schlessinger, David; Ko, Minoru S H

    2014-11-01

    Upon removal of culture conditions that maintain an undifferentiated state, mouse embryonic stem cells (ESCs) differentiate into various cell types. Differentiation can be facilitated by forced expression of certain transcription factors (TFs), each of which can generally specify a particular developmental lineage. We previously established 137 mouse ESC lines, each of which carried a doxycycline-controllable TF. Among them, Sox9 has unique capacity: its forced expression accelerates differentiation of mouse ESCs into cells of all three germ layers. With the additional use of specific culture conditions, overexpression of Sox9 facilitated the generation of endothelial cells, hepatocytes and neurons from ESCs. Furthermore, Sox9 action increases formation of p21 (WAF1/CIP1), which then binds to the SRR2 enhancer of pluripotency marker Sox2 and inhibits its expression. Knockdown of p21 abolishes inhibition of Sox2 and Sox9-accelerated differentiation, and reduction of Sox2 2 days after the beginning of ESC differentiation can comparably accelerate mouse ESC formation of cells of three germ layers. These data implicate the involvement of the p21-Sox2 pathway in the mechanism of accelerated ESC differentiation by Sox9 overexpression. The molecular cascade could be among the first steps to program ESC differentiation.

  8. Organogenesis relies on SoxC transcription factors for the survival of neural and mesenchymal progenitors.

    Science.gov (United States)

    Bhattaram, Pallavi; Penzo-Méndez, Alfredo; Sock, Elisabeth; Colmenares, Clemencia; Kaneko, Kotaro J; Vassilev, Alex; Depamphilis, Melvin L; Wegner, Michael; Lefebvre, Véronique

    2010-04-12

    During organogenesis, neural and mesenchymal progenitor cells give rise to many cell lineages, but their molecular requirements for self-renewal and lineage decisions are incompletely understood. In this study, we show that their survival critically relies on the redundantly acting SoxC transcription factors Sox4, Sox11 and Sox12. The more SoxC alleles that are deleted in mouse embryos, the more severe and widespread organ hypoplasia is. SoxC triple-null embryos die at midgestation unturned and tiny, with normal patterning and lineage specification, but with massively dying neural and mesenchymal progenitor cells. Specific inactivation of SoxC genes in neural and mesenchymal cells leads to selective apoptosis of these cells, suggesting SoxC cell-autonomous roles. Tead2 functionally interacts with SoxC genes in embryonic development, and is a direct target of SoxC proteins. SoxC genes therefore ensure neural and mesenchymal progenitor cell survival, and function in part by activating this transcriptional mediator of the Hippo signalling pathway.

  9. Selective influence of Sox2 on POU transcription factor binding in embryonic and neural stem cells.

    Science.gov (United States)

    Mistri, Tapan Kumar; Devasia, Arun George; Chu, Lee Thean; Ng, Wei Ping; Halbritter, Florian; Colby, Douglas; Martynoga, Ben; Tomlinson, Simon R; Chambers, Ian; Robson, Paul; Wohland, Thorsten

    2015-09-01

    Embryonic stem cell (ESC) identity is orchestrated by co-operativity between the transcription factors (TFs) Sox2 and the class V POU-TF Oct4 at composite Sox/Oct motifs. Neural stem cells (NSCs) lack Oct4 but express Sox2 and class III POU-TFs Oct6, Brn1 and Brn2. This raises the question of how Sox2 interacts with POU-TFs to transcriptionally specify ESCs versus NSCs. Here, we show that Oct4 alone binds the Sox/Oct motif and the octamer-containing palindromic MORE equally well. Sox2 binding selectively increases the affinity of Oct4 for the Sox/Oct motif. In contrast, Oct6 binds preferentially to MORE and is unaffected by Sox2. ChIP-Seq in NSCs shows the MORE to be the most enriched motif for class III POU-TFs, including MORE subtypes, and that the Sox/Oct motif is not enriched. These results suggest that in NSCs, co-operativity between Sox2 and class III POU-TFs may not occur and that POU-TF-driven transcription uses predominantly the MORE cis architecture. Thus, distinct interactions between Sox2 and POU-TF subclasses distinguish pluripotent ESCs from multipotent NSCs, providing molecular insight into how Oct4 alone can convert NSCs to pluripotency.

  10. Effects of SOX2 on Proliferation, Migration and Adhesion of Human Dental Pulp Stem Cells.

    Directory of Open Access Journals (Sweden)

    Pengfei Liu

    Full Text Available As a key factor for cell pluripotent and self-renewing phenotypes, SOX2 has attracted scientists' attention gradually in recent years. However, its exact effects in dental pulp stem cells (DPSCs are still unclear. In this study, we mainly investigated whether SOX2 could affect some biological functions of DPSCs. DPSCs were isolated from the dental pulp of human impacted third molar. SOX2 overexpressing DPSCs (DPSCs-SOX2 were established through retroviral infection. The effect of SOX2 on cell proliferation, migration and adhesion ability was evaluated with CCK-8, trans-well system and fibronectin-induced cell attachment experiment respectively. Whole genome expression of DPSCs-SOX2 was analyzed with RNA microarray. Furthermore, a rescue experiment was performed with SOX2-siRNA in DPSC-SOX2 to confirm the effect of SOX2 overexpression in DPSCs. We found that SOX2 overexpression could result in the enhancement of cell proliferation, migration, and adhesion in DPSCs obviously. RNA microarray analysis indicated that some key genes in the signal pathways associated with cell cycle, migration and adhesion were upregulated in different degree, and the results were further confirmed with qPCR and western-blot. Finally, DPSC-SOX2 transfected with SOX2-siRNA showed a decrease of cell proliferation, migration and adhesion ability, which further confirmed the biological effect of SOX2 in human DPSCs. This study indicated that SOX2 could improve the cell proliferation, migration and adhesion ability of DPSCs through regulating gene expression about cell cycle, migration and adhesion, and provided a novel strategy to develop seed cells with strong proliferation, migration and adhesion ability for tissue engineering.

  11. Effects of SOX2 on Proliferation, Migration and Adhesion of Human Dental Pulp Stem Cells.

    Science.gov (United States)

    Liu, Pengfei; Cai, Jinglei; Dong, Delu; Chen, Yaoyu; Liu, Xiaobo; Wang, Yi; Zhou, Yulai

    2015-01-01

    As a key factor for cell pluripotent and self-renewing phenotypes, SOX2 has attracted scientists' attention gradually in recent years. However, its exact effects in dental pulp stem cells (DPSCs) are still unclear. In this study, we mainly investigated whether SOX2 could affect some biological functions of DPSCs. DPSCs were isolated from the dental pulp of human impacted third molar. SOX2 overexpressing DPSCs (DPSCs-SOX2) were established through retroviral infection. The effect of SOX2 on cell proliferation, migration and adhesion ability was evaluated with CCK-8, trans-well system and fibronectin-induced cell attachment experiment respectively. Whole genome expression of DPSCs-SOX2 was analyzed with RNA microarray. Furthermore, a rescue experiment was performed with SOX2-siRNA in DPSC-SOX2 to confirm the effect of SOX2 overexpression in DPSCs. We found that SOX2 overexpression could result in the enhancement of cell proliferation, migration, and adhesion in DPSCs obviously. RNA microarray analysis indicated that some key genes in the signal pathways associated with cell cycle, migration and adhesion were upregulated in different degree, and the results were further confirmed with qPCR and western-blot. Finally, DPSC-SOX2 transfected with SOX2-siRNA showed a decrease of cell proliferation, migration and adhesion ability, which further confirmed the biological effect of SOX2 in human DPSCs. This study indicated that SOX2 could improve the cell proliferation, migration and adhesion ability of DPSCs through regulating gene expression about cell cycle, migration and adhesion, and provided a novel strategy to develop seed cells with strong proliferation, migration and adhesion ability for tissue engineering.

  12. Genetic and epigenetic modifications of Sox2 contribute to the invasive phenotype of malignant gliomas.

    Directory of Open Access Journals (Sweden)

    Marta M Alonso

    Full Text Available We undertook this study to understand how the transcription factor Sox2 contributes to the malignant phenotype of glioblastoma multiforme (GBM, the most aggressive primary brain tumor. We initially looked for unbalanced genomic rearrangements in the Sox2 locus in 42 GBM samples and found that Sox2 was amplified in 11.5% and overexpressed in all the samples. These results prompted us to further investigate the mechanisms involved in Sox2 overexpression in GBM. We analyzed the methylation status of the Sox2 promoter because high CpG density promoters are associated with key developmental genes. The Sox2 promoter presented a CpG island that was hypomethylated in all the patient samples when compared to normal cell lines. Treatment of Sox2-negative glioma cell lines with 5-azacitidine resulted in the re-expression of Sox2 and in a change in the methylation status of the Sox2 promoter. We further confirmed these results by analyzing data from GBM cases generated by The Cancer Genome Atlas project. We observed Sox2 overexpression (86%; N = 414, Sox2 gene amplification (8.5%; N = 492, and Sox 2 promoter hypomethylation (100%; N = 258, suggesting the relevance of this factor in the malignant phenotype of GBMs. To further explore the role of Sox2, we performed in vitro analysis with brain tumor stem cells (BTSCs and established glioma cell lines. Downmodulation of Sox2 in BTSCs resulted in the loss of their self-renewal properties. Surprisingly, ectopic expression of Sox2 in established glioma cells was not sufficient to support self-renewal, suggesting that additional factors are required. Furthermore, we observed that ectopic Sox2 expression was sufficient to induce invasion and migration of glioma cells, and knockdown experiments demonstrated that Sox2 was essential for maintaining these properties. Altogether, our data underscore the importance of a pleiotropic role of Sox2 and suggest that it could be used as a therapeutic target in GBM.

  13. Genetic and Epigenetic Modifications of Sox2 Contribute to the Invasive Phenotype of Malignant Gliomas

    Science.gov (United States)

    Alonso, Marta M.; Diez-Valle, Ricardo; Manterola, Lorea; Rubio, Angel; Liu, Dan; Cortes-Santiago, Nahir; Urquiza, Leire; Jauregi, Patricia; de Munain, Adolfo Lopez; Sampron, Nicolás; Aramburu, Ander; Tejada-Solís, Sonia; Vicente, Carmen; Odero, María D.; Bandrés, Eva; García-Foncillas, Jesús; Idoate, Miguel A.; Lang, Frederick F.; Fueyo, Juan; Gomez-Manzano, Candelaria

    2011-01-01

    We undertook this study to understand how the transcription factor Sox2 contributes to the malignant phenotype of glioblastoma multiforme (GBM), the most aggressive primary brain tumor. We initially looked for unbalanced genomic rearrangements in the Sox2 locus in 42 GBM samples and found that Sox2 was amplified in 11.5% and overexpressed in all the samples. These results prompted us to further investigate the mechanisms involved in Sox2 overexpression in GBM. We analyzed the methylation status of the Sox2 promoter because high CpG density promoters are associated with key developmental genes. The Sox2 promoter presented a CpG island that was hypomethylated in all the patient samples when compared to normal cell lines. Treatment of Sox2-negative glioma cell lines with 5-azacitidine resulted in the re-expression of Sox2 and in a change in the methylation status of the Sox2 promoter. We further confirmed these results by analyzing data from GBM cases generated by The Cancer Genome Atlas project. We observed Sox2 overexpression (86%; N = 414), Sox2 gene amplification (8.5%; N = 492), and Sox 2 promoter hypomethylation (100%; N = 258), suggesting the relevance of this factor in the malignant phenotype of GBMs. To further explore the role of Sox2, we performed in vitro analysis with brain tumor stem cells (BTSCs) and established glioma cell lines. Downmodulation of Sox2 in BTSCs resulted in the loss of their self-renewal properties. Surprisingly, ectopic expression of Sox2 in established glioma cells was not sufficient to support self-renewal, suggesting that additional factors are required. Furthermore, we observed that ectopic Sox2 expression was sufficient to induce invasion and migration of glioma cells, and knockdown experiments demonstrated that Sox2 was essential for maintaining these properties. Altogether, our data underscore the importance of a pleiotropic role of Sox2 and suggest that it could be used as a therapeutic target in GBM. PMID:22069467

  14. SOX9 duplication linked to intersex in deer.

    Directory of Open Access Journals (Sweden)

    Regina Kropatsch

    Full Text Available A complex network of genes determines sex in mammals. Here, we studied a European roe deer with an intersex phenotype that was consistent with a XY genotype with incomplete male-determination. Whole genome sequencing and quantitative real-time PCR analyses revealed a triple dose of the SOX9 gene, allowing insights into a new genetic defect in a wild animal.

  15. 鳙Sox基因克隆及序列进化分析%CLONING AND SEQUENCE EVOLUTION ANALYSIS OF SOX GENES IN BIGHEAD CARP (ARISTICHTHYS NOBILIS)

    Institute of Scientific and Technical Information of China (English)

    郭稳杰; 俞小牧; 童金苟

    2014-01-01

    To amplify Sox genes from bighead carp genome, two pairs of degenerate primers (SoxN and Sox9) were de-signed for PCR amplification that were utilized for sequencing and analysis of sequence homology and phylogenetic relationships. The results showed that 15 distinct Sox genes encoding the HMG domains were identified in bighead carp, which were assigned to group B, C and E. According to their homology to orthologs of zebrafish, 15 Sox genes were designated as Sox1a, Sox1b, Sox2, Sox3, Sox4a, Sox4b, Sox9a, Sox9b, Sox10, Sox11b, Sox12, Sox14a, Sox14b, Sox19 and Sox21a, respectively. Phylogenetic tree of Sox1, Sox4 and Sox9 nucleotide sequences indicated that the duplication of these three Sox genes occurred before the divergence of bighead carp and zebrafish, and this observation supported the“fish-specific whole-genome duplication” theory. Using Sox1a, Sox1b and Sox4 as molecular clock markers in phy-logenetic analysis, the estimation of the divergence time between bighead carp and zebrafish demonstrated that in origi-nal Danioninae, a common ancestor appeared approximately 63.7 million years ago for bighead carp and zebrafish, both of which belong to Cyprinidae. This study would provide important information for further studies of Sox gene replica-tion and genome evolution in fish.%利用简并引物SoxN和Sox9在鳙基因组DNA中进行PCR扩增和产物克隆测序,并对序列进行同源性比较和系统进化分析。结果表明本文鉴定出鳙15个Sox基因HMG盒序列,分别属于 SoxB、SoxC和 SoxE组,依据斑马鱼同源基因将其分别命名为Sox1a、Sox1b、Sox2、Sox3、Sox4a、Sox4b、Sox9a、Sox9b、Sox10、Sox11b、Sox12、Sox14a、Sox14b、Sox19和Sox21a。基于鳙和斑马鱼 Sox1、Sox4和Sox9基因核苷酸序列构建的系统进化树显示这3个Sox基因的复制时间发生在鳙和斑马鱼的分化之前,结果支持了鱼类特异的基因组复制假说。以Sox1a、Sox1b和Sox4基因为分子钟标记构建系统

  16. Sox5 induces epithelial to mesenchymal transition by transactivation of Twist1

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Xin-Hong [Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan (China); Department of Pathology, The Basic Medical College of Zhengzhou University, Zhengzhou, Henan (China); Lv, Xin-Quan [Department of Pathology, The Basic Medical College of Zhengzhou University, Zhengzhou, Henan (China); Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan (China); Li, Hui-Xiang, E-mail: Lihuixiang1955@163.com [Department of Pathology, The Basic Medical College of Zhengzhou University, Zhengzhou, Henan (China); Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan (China)

    2014-03-28

    Highlights: • Depletion of Sox5 inhibits breast cancer proliferation, migration, and invasion. • Sox5 transactivates Twist1 expression. • Sox5 induces epithelial to mesenchymal transition through transactivation of Twist1 expression. - Abstract: The epithelial to mesenchymal transition (EMT), a highly conserved cellular program, plays an important role in normal embryogenesis and cancer metastasis. Twist1, a master regulator of embryonic morphogenesis, is overexpressed in breast cancer and contributes to metastasis by promoting EMT. In exploring the mechanism underlying the increased Twist1 in breast cancer cells, we found that the transcription factor SRY (sex-determining region Y)-box 5(Sox5) is up-regulation in breast cancer cells and depletion of Sox5 inhibits breast cancer cell proliferation, migration, and invasion. Furthermore, depletion of Sox5 in breast cancer cells caused a dramatic decrease in Twist1 and chromosome immunoprecipitation assay showed that Sox5 can bind directly to the Twist1 promoter, suggesting that Sox5 transactivates Twist1 expression. We further demonstrated that knockdown of Sox5 up-regulated epithelial phenotype cell biomarker (E-cadherin) and down-regulated mesenchymal phenotype cell biomarkers (N-cadherin, Vimentin, and Fibronectin 1), resulting in suppression of EMT. Our study suggests that Sox5 transactivates Twist1 expression and plays an important role in the regulation of breast cancer progression.

  17. Sox4 Links Tumor Suppression to Accelerated Aging in Mice by Modulating Stem Cell Activation

    Directory of Open Access Journals (Sweden)

    Miguel Foronda

    2014-07-01

    Full Text Available Sox4 expression is restricted in mammals to embryonic structures and some adult tissues, such as lymphoid organs, pancreas, intestine, and skin. During embryogenesis, Sox4 regulates mesenchymal and neural progenitor survival, as well as lymphocyte and myeloid differentiation, and contributes to pancreas, bone, and heart development. Aberrant Sox4 expression is linked to malignant transformation and metastasis in several types of cancer. To understand the role of Sox4 in the adult organism, we first generated mice with reduced whole-body Sox4 expression. These mice display accelerated aging and reduced cancer incidence. To specifically address a role for Sox4 in adult stem cells, we conditionally deleted Sox4 (Sox4cKO in stratified epithelia. Sox4cKO mice show increased skin stem cell quiescence and resistance to chemical carcinogenesis concomitantly with downregulation of cell cycle, DNA repair, and activated hair follicle stem cell pathways. Altogether, these findings highlight the importance of Sox4 in regulating adult tissue homeostasis and cancer.

  18. Sox2 expression in breast tumours and activation in breast cancer stem cells.

    Science.gov (United States)

    Leis, O; Eguiara, A; Lopez-Arribillaga, E; Alberdi, M J; Hernandez-Garcia, S; Elorriaga, K; Pandiella, A; Rezola, R; Martin, A G

    2012-03-15

    The cancer stem cell (CSC) model does not imply that tumours are generated from transformed tissue stem cells. The target of transformation could be a tissue stem cell, a progenitor cell, or a differentiated cell that acquires self-renewal ability. The observation that induced pluripotency reprogramming and cancer are related has lead to the speculation that CSCs may arise through a reprogramming-like mechanism. Expression of pluripotency genes (Oct4, Nanog and Sox2) was tested in breast tumours by immunohistochemistry and it was found that Sox2 is expressed in early stage breast tumours. However, expression of Oct4 or Nanog was not found. Mammosphere formation in culture was used to reveal stem cell properties, where expression of Sox2, but not Oct4 or Nanog, was induced. Over-expression of Sox2 increased mammosphere formation, effect dependent on continuous Sox2 expression; furthermore, Sox2 knockdown prevented mammosphere formation and delayed tumour formation in xenograft tumour initiation models. Induction of Sox2 expression was achieved through activation of the distal enhancer of Sox2 promoter upon sphere formation, the same element that controls Sox2 transcription in pluripotent stem cells. These findings suggest that reactivation of Sox2 represents an early step in breast tumour initiation, explaining tumour heterogeneity by placing the tumour-initiating event in any cell along the axis of mammary differentiation.

  19. The stem cell factor SOX2 regulates the tumorigenic potential in human gastric cancer cells.

    Science.gov (United States)

    Hütz, Katharina; Mejías-Luque, Raquel; Farsakova, Katarina; Ogris, Manfred; Krebs, Stefan; Anton, Martina; Vieth, Michael; Schüller, Ulrich; Schneider, Marlon R; Blum, Helmut; Wagner, Ernst; Jung, Andreas; Gerhard, Markus

    2014-04-01

    Gastric cancer (GC) is still one of the most common causes of cancer-related death worldwide, which is mainly attributable to late diagnosis and poor treatment options. Infection with Helicobacter pylori, different environmental factors and genetic alterations are known to influence the risk of developing gastric tumors. However, the molecular mechanisms involved in gastric carcinogenesis are still not fully understood, making it difficult to design targeted therapeutic approaches. Aberrant expression of the specific gastric differentiation marker SOX2 has been observed in stomach cancer. However, the role of SOX2 in gastric tumors has not been well established to date. To elucidate the role of SOX2 in gastric tumorigenesis, SOX2 transcriptional activity was blocked in AZ-521 cells. Interestingly, inhibition of SOX2 reduced cell proliferation and migration, increased apoptosis and induced changes in cell cycle. Blocking of SOX2 also reduced the tumorigenic potential of AZ-521 cells in vivo. In addition, correlation of SOX2 expression and proliferation was observed in a subset of human gastric tumors. Finally, target genes of SOX2 were for the first time identified by RNA microarray in GC cells. Taken together, the results presented here indicate that SOX2 controls several aspects related to GC development and progression by regulating the expression of members of important signaling pathways. These findings could provide new therapeutic options for a subset of GCs exhibiting SOX2 deregulation.

  20. Decreased expression of SOX17 is associated with tumor progression and poor prognosis in breast cancer.

    Science.gov (United States)

    Fu, De-Yuan; Tan, Hao-Sheng; Wei, Jin-Li; Zhu, Chang-Ren; Jiang, Ji-Xin; Zhu, Yu-Xiang; Cai, Feng-Lin; Chong, Mei-Hong; Ren, Chuan-Li

    2015-09-01

    The SOX17 (SRY-related HMG-box) transcription factor is involved in a variety of biological processes and is related to the tumorigenesis and progression of multiple tumors. However, the clinical application of SOX17 for breast cancer prognosis is currently limited. The aim of this study was to investigate the clinicopathologic and prognostic significance of SOX17 expression in human breast cancer. qPCR and western blot assays were performed to measure the expression of SOX17 in breast cancer cell lines and 30 matched pairs of breast cancer and corresponding noncancerous tissues. A SOX17 overexpression cell model was used to examine changes in cell growth in vitro. Immunohistochemical analyses were performed to retrospectively examine the prognostic impact of SOX17 expression in 187 additional breast cancer patients. Our results showed that SOX17 expression was decreased at both the messenger RNA (mRNA) and protein levels in the breast cancer cell lines and tissues, and that SOX17 overexpression could strongly suppress cell growth in vitro. Furthermore, the lack of SOX17 protein expression was strongly correlated with higher tumor grade (P = 0.002), lymph node metastasis (P breast cancer. Our findings indicate that SOX17 expression is a useful prognostic biomarker for breast cancer.

  1. Sox2 acts as a rheostat of epithelial to mesenchymal transition during neural crest development

    Directory of Open Access Journals (Sweden)

    Nikolaos eMandalos

    2014-09-01

    Full Text Available Precise control of self-renewal and differentiation of progenitor cells into the cranial neural crest (CNC pool ensures proper head development, guided by signaling pathways such as BMPs, FGFs, Shh and Notch. Here, we show that murine Sox2 plays an essential role in controlling progenitor cell behavior during craniofacial development. A Conditional by Inversion Sox2 allele (Sox2COIN has been employed to generate an epiblast ablation of Sox2 function (Sox2EpINV. Sox2EpINV/+(H haploinsufficient and conditional (Sox2EpINV/mosaic mutant embryos proceed beyond gastrulation and die around E11. These mutant embryos exhibit severe anterior malformations, with hydrocephaly and frontonasal truncations, which could be attributed to the deregulation of CNC progenitor cells during their epithelial to mesenchymal transition. This irregularity results in an exacerbated and aberrant migration of Sox10+ NCC in the branchial arches and frontonasal process of the Sox2 mutant embryos. These results suggest a novel role for Sox2 as a regulator of the epithelial to mesenchymal transitions that are important for the cell flow in the developing head.

  2. The Role of Sox Genes in Lung Morphogenesis and Cancer

    Directory of Open Access Journals (Sweden)

    Yongzhao Zhu

    2012-11-01

    Full Text Available The human lung consists of multiple cell types derived from early embryonic compartments. The morphogenesis of the lung, as well as the injury repair of the adult lung, is tightly controlled by a network of signaling pathways with key transcriptional factors. Lung cancer is the third most cancer-related death in the world, which may be developed due to the failure of regulating the signaling pathways. Sox (sex-determining region Y (Sry box-containing family transcriptional factors have emerged as potent modulators in embryonic development, stem cells maintenance, tissue homeostasis, and cancerogenesis in multiple processes. Recent studies demonstrated that the members of the Sox gene family played important roles in the development and maintenance of lung and development of lung cancer. In this context, we summarize our current understanding of the role of Sox family transcriptional factors in the morphogenesis of lung, their oncogenic potential in lung cancer, and their potential impact in the diagnosis, prognosis, and targeted therapy of lung cancer.

  3. Sox17 regulates liver lipid metabolism and adaptation to fasting.

    Science.gov (United States)

    Rommelaere, Samuel; Millet, Virginie; Vu Manh, Thien-Phong; Gensollen, Thomas; Andreoletti, Pierre; Cherkaoui-Malki, Mustapha; Bourges, Christophe; Escalière, Bertrand; Du, Xin; Xia, Yu; Imbert, Jean; Beutler, Bruce; Kanai, Yoshiakira; Malissen, Bernard; Malissen, Marie; Tailleux, Anne; Staels, Bart; Galland, Franck; Naquet, Philippe

    2014-01-01

    Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/- mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting.

  4. Sox17 regulates liver lipid metabolism and adaptation to fasting.

    Directory of Open Access Journals (Sweden)

    Samuel Rommelaere

    Full Text Available Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/- mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting.

  5. Sox2 promotes survival of satellite glial cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Koike, Taro, E-mail: koiket@hirakata.kmu.ac.jp; Wakabayashi, Taketoshi; Mori, Tetsuji; Hirahara, Yukie; Yamada, Hisao

    2015-08-14

    Sox2 is a transcriptional factor expressed in neural stem cells. It is known that Sox2 regulates cell differentiation, proliferation and survival of the neural stem cells. Our previous study showed that Sox2 is expressed in all satellite glial cells of the adult rat dorsal root ganglion. In this study, to examine the role of Sox2 in satellite glial cells, we establish a satellite glial cell-enriched culture system. Our culture method succeeded in harvesting satellite glial cells with the somata of neurons in the dorsal root ganglion. Using this culture system, Sox2 was downregulated by siRNA against Sox2. The knockdown of Sox2 downregulated ErbB2 and ErbB3 mRNA at 2 and 4 days after siRNA treatment. MAPK phosphorylation, downstream of ErbB, was also inhibited by Sox2 knockdown. Because ErbB2 and ErbB3 are receptors that support the survival of glial cells in the peripheral nervous system, apoptotic cells were also counted. TUNEL-positive cells increased at 5 days after siRNA treatment. These results suggest that Sox2 promotes satellite glial cell survival through the MAPK pathway via ErbB receptors. - Highlights: • We established satellite glial cell culture system. • Function of Sox2 in satellite glial cell was examined using siRNA. • Sox2 knockdown downregulated expression level of ErbB2 and ErbB3 mRNA. • Sox2 knockdown increased apoptotic satellite glial cell. • Sox2 promotes satellite glial cell survival through ErbB signaling.

  6. Establishment and initial characterization of SOX2-overexpressing NT2/D1 cell clones.

    Science.gov (United States)

    Drakulic, D; Krstic, A; Stevanovic, M

    2012-05-15

    SOX2, a universal marker of pluripotent stem cells, is a transcription factor that helps control embryonic development in vertebrates; its expression persists in neural stem/progenitor cells into adulthood. Considering the critical role of the SOX2 transcription factor in the regulation of genes required for self-renewal and pluripotency of stem cells, we developed and characterized SOX2-overexpressing NT2/D1 cell clones. Using Southern blot and semi-quantitative RT-PCR, we confirmed integration and expression of exogenous SOX2 in three NT2/D1 cell clones. Overexpression of the SOX2 gene was detected in two of these clones. SOX2 overexpression in NT2/D1 cell clones resulted in altered expression of key pluripotency genes OCT4 and NANOG. Furthermore, SOX2-overexpressing NT2/D1 cell clones entered into retinoic acid-dependent neural differentiation, even when there was elevated SOX2 expression. After 21 days of induction by retinoic acid, expression of neural markers (neuroD1 and synaptophysin) was higher in induced cell clones than in induced parental cells. The cell clone with SOX2 overexpression had an approximately 1.3-fold higher growth rate compared to parental cells. SOX2 overexpression did not increase the population of cells undergoing apoptosis. Taken together, we developed two SOX2-overexpressing cell clones, with constitutive SOX2 expression after three weeks of retinoic acid treatment. SOX2 overexpression resulted in altered expression of pluripotency-related genes, increased proliferation, and altered expression of neural markers after three weeks of retinoic acid treatment.

  7. Differential expression of ID4 and its association with TP53 mutation, SOX2, SOX4 and OCT-4 expression levels.

    Directory of Open Access Journals (Sweden)

    Thais Fernanda de Almeida Galatro

    Full Text Available Inhibitor of DNA Binding 4 (ID4 is a member of the helix-loop-helix ID family of transcription factors, mostly present in the central nervous system during embryonic development, that has been associated with TP53 mutation and activation of SOX2. Along with other transcription factors, ID4 has been implicated in the tumorigenic process of astrocytomas, contributing to cell dedifferentiation, proliferation and chemoresistance. In this study, we aimed to characterize the ID4 expression pattern in human diffusely infiltrative astrocytomas of World Health Organization (WHO grades II to IV of malignancy (AGII-AGIV; to correlate its expression level to that of SOX2, SOX4, OCT-4 and NANOG, along with TP53 mutational status; and to correlate the results with the clinical end-point of overall survival among glioblastoma patients. Quantitative real time PCR (qRT-PCR was performed in 130 samples of astrocytomas for relative expression, showing up-regulation of all transcription factors in tumor cases. Positive correlation was found when comparing ID4 relative expression of infiltrative astrocytomas with SOX2 (r = 0.50; p<0.005, SOX4 (r = 0.43; p<0.005 and OCT-4 (r = 0.39; p<0.05. The results from TP53 coding exon analysis allowed comparisons between wild-type and mutated status only in AGII cases, demonstrating significantly higher levels of ID4, SOX2 and SOX4 in mutated cases (p<0.05. This pattern was maintained in secondary GBM and further confirmed by immunohistochemistry, suggesting a role for ID4, SOX2 and SOX4 in early astrocytoma tumorigenesis. Combined hyperexpression of ID4, SOX4 and OCT-4 conferred a much lower (6 months median survival than did hypoexpression (18 months. Because both ID4 alone and a complex of SOX4 and OCT-4 activate SOX2 transcription, it is possible that multiple activation of SOX2 impair the prognosis of GBM patients. These observational results of associated expression of ID4 with SOX4 and OCT-4 may be used as a

  8. Preparation of Polyclonal Anti-Sox2 Antibody in Capra hircus%山羊SOX2多克隆抗体制备

    Institute of Scientific and Technical Information of China (English)

    刘平; 张明; 张昀; 郑喜邦; 李恭贺; 岑小妹; 岳磊磊; 宗自杰; 卢晟盛; 卢克焕

    2012-01-01

    [Objective] The present study was to construct a prokaryotic expression vector of Capra hircus Sox2 gene, pRSET-Sox2, to induce expression and purification of His-Sox2 fusion protein, which was used to immunize New Zeland white rabbits to prepare polyclonal anti-Sox2 antibody. [Method] Removed from plasmid pMD18-Sox2 by double digestion of BamH I and Xho I, Sox2 fragment was subcloned to pRSET-A vector to construct recombinant plasmid pRSET-Sox2. The plasmid was transformed into E. coli BL 21 (DE3), and His-Sox2 fusion protein was induced to expess with 1 mrnol·L-1 IPTG at 37℃ for 4 h, which was identified with SDS-PAGE analysis and Western blotting. In the same way, large volume of expressing culture was prepared to purify His-Sox2 fusion protein with NI-NTA argrose under denaturing condition. The refolded fusion protein in vitro was injected subcutaneously into New Zeland white rabbits for four times at intervals of 2-3 weeks. Seven days after the last injection, blood samples were collected, serum was isolated, and specificity of polyclonal anti-Sox2 antibody was determined by Western blotting assay. [Result] The prokaryotic expression vector pRSET-Sox2 was expressed efficiently in E. coli. BL21. The purified His-Sox2 was qualified for preparation of polyclonal antibody. The polyclonal anti-Sox2 antibody was prepared, and it could bind His-Sox2 fusion protein specifically, which was illustrated by Western blotting assay. [Conclusion] The polyclonal anti-Sox2 antibody with strong specificity was prepared, which will lay a solid biological foundation for study of Sox2, and for its application in detection of Capra hircus iPS cells (induced pluripotent stem cells).%[目的]构建山羊Sox2原核表达载体—pRSET-Sox2,并将诱导表达、纯化的His-Sox2融合蛋白免疫新西兰大白兔,制备Sox2多克隆抗体.[方法]从pMD18T-Sox2载体上以BamHI和XhoI双酶切截取Sox2 片段,然后将其亚克隆到pRSET-A表达载体上,获得pRSET-Sox2重组质粒.转化了pRSET-Sox

  9. Feasibility Study B-1 Power Controller.

    Science.gov (United States)

    1979-11-01

    Study performed by the Autonetics Strategic Systems Division ( ASSD ) of Rockwell International on Contract N62269-79-C-0294. The objective of this study...Modify the design of the ASSD B-1 SSPC, Part Number 12880-507-1, to be a 115 Vac quadruple SSPC unit, with a SOSTEL compatible interface. 3.1.2 115 Vac...Primary Power Modifications. The ASSD SSPC Unit, Appendix A, contains four identical PC’s operating from 230 Vac primary power. Referring to Figure 1

  10. Expression Detection of DMRTs and Two sox9 Genes in Takifugu rubripes (Tetraodontidae,Vertebrata)

    Institute of Scientific and Technical Information of China (English)

    SHEN Xueyan; CUI Jianzhou; YANG Guanpin; GONG Qingli; GU Qianqun

    2007-01-01

    Sex determination and sex differentiation are important phenomena in fish, but the mechanisms of sex determination in Takifugu rubripes are poorly understood. In our study, the expression patterns of genes for DMRTs (DMRT1, DMRT2 and DMRT3),sox9a and sox9b in T. rubripes tissues were verified with the Reverse Transcription (RT)-PCR detection. It is showed that DMRT1 expressions in testis and ovaries were much lower, and no expressions were fotmd in muscle, blood and tailfin. However, expressions for DMRT2 and DMRT3 were not found in the tissues stated above. Transcripts of sox9a were detected in muscle, fin, ovary and testis, but not in blood, whereas sox9b expression was only detected in ovary. The expression patterns of DMRTs, sox9a and sox9b in T. rubripes gonads suggest that these genes may not be sex-specific.

  11. Study on Mg/Fe Mixed Oxides Derived from Hydrotalite as De—SOx Catalyst

    Institute of Scientific and Technical Information of China (English)

    GuangLanZHUO; YinFeiCHEN; 等

    2002-01-01

    A novel class of desulfurization agent derived from hydrotalcite has been developed and its activity for SOx uptake have been investigated. The results showed that the Mg/Fe mixed oxide having high SOx uptake ability at a broad reaction temperature (e.g.673K-973K). The Mg/Fe ratio of the mixed oxide strongly affect the desulfurization role of the material and it can be used repeatly without much loss of SOx uptake ability.

  12. Study on Mg/Fe Mixed Oxides Derived from Hydrotalcite as De-SOx Catalyst

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A novel class of desulfurization agent derived from hydrotalcite has been developed and its activity for Sox uptake have been investigated. The results showed that the Mg/Fe mixed oxide having high Sox uptake ability at a broad reaction temperature (e.g. 673K ~ 973K). The Mg/Fe ratio of the mixed oxide strongly affect the desulfurization role of the material and it can be used repeatly without much loss of Sox uptake ability.

  13. Induction and selection of Sox17-expressing endoderm cells generated from murine embryonic stem cells.

    Science.gov (United States)

    Schroeder, Insa S; Sulzbacher, Sabine; Nolden, Tobias; Fuchs, Joerg; Czarnota, Judith; Meisterfeld, Ronny; Himmelbauer, Heinz; Wobus, Anna M

    2012-01-01

    Embryonic stem (ES) cells offer a valuable source for generating insulin-producing cells. However, current differentiation protocols often result in heterogeneous cell populations of various developmental stages. Here we show the activin A-induced differentiation of mouse ES cells carrying a homologous dsRed-IRES-puromycin knock-in within the Sox17 locus into the endoderm lineage. Sox17-expressing cells were selected by fluorescence-assisted cell sorting (FACS) and characterized at the transcript and protein level. Treatment of ES cells with high concentrations of activin A for 10 days resulted in up to 19% Sox17-positive cells selected by FACS. Isolated Sox17-positive cells were characterized by defini- tive endoderm-specific Sox17/Cxcr4/Foxa2 transcripts, but lacked pluripotency-associated Oct4 mRNA and protein. The Sox17-expressing cells showed downregulation of extraembryonic endoderm (Sox7, Afp, Sdf1)-, mesoderm (Foxf1, Meox1)- and ectoderm (Pax6, NeuroD6)-specific transcripts. The presence of Hnf4α, Hes1 and Pdx1 mRNA demonstrated the expression of primitive gut/foregut cell-specific markers. Ngn3, Nkx6.1 and Nkx2.2 transcripts in Sox17-positive cells were determined as properties of pancreatic endocrine progenitors. Immunocytochemistry of activin A-induced Sox17-positive embryoid bodies revealed coexpression of Cxcr4 and Foxa2. Moreover, the histochemical demonstration of E-cadherin-, Cxcr4-, Sox9-, Hnf1β- and Ngn3-positive epithelial-like structures underlined the potential of Sox17-positive cells to further differentiate into the pancreatic lineage. By reducing the heterogeneity of the ES cell progeny, Sox17-expressing cells are a suitable model to evaluate the effects of growth and differentiation factors and of culture conditions to delineate the differentiation process for the generation of pancreatic cells in vitro.

  14. SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells.

    Science.gov (United States)

    Klajn, A; Drakulic, D; Tosic, M; Pavkovic, Z; Schwirtlich, M; Stevanovic, M

    2014-11-01

    SOX2 is one of the key transcription factors involved in maintenance of neural progenitor identity. However, its function during the process of neural differentiation, including phases of lineage-specification and terminal differentiation, is still poorly understood. Considering growing evidence indicating that SOX2 expression level must be tightly controlled for proper neural development, the aim of this research was to analyze the effects of constitutive SOX2 overexpression on outcome of retinoic acid-induced neural differentiation of pluripotent NT2/D1 cells. We demonstrated that in spite of constitutive SOX2 overexpression, NT2/D1 cells were able to reach final phases of neural differentiation yielding both neuronal and glial cells. However, SOX2 overexpression reduced the number of mature MAP2-positive neurons while no difference in the number of GFAP-positive astrocytes was detected. In-depth analysis at single-cell level showed that SOX2 downregulation was in correlation with both neuronal and glial phenotype acquisitions. Interestingly, while in mature neurons SOX2 was completely downregulated, astrocytes with low level of SOX2 expression were detected. Nevertheless, cells with high level of SOX2 expression were incapable of entering in either of two differentiation pathways, neurogenesis or gliogenesis. Accordingly, our results indicate that fine balance between undifferentiated state and neural differentiation depends on SOX2 expression level. Unlike neurons, astrocytes could maintain low level of SOX2 expression after they acquired glial fate. Further studies are needed to determine whether differences in the level of SOX2 expression in GFAP-positive astrocytes are in correlation with their self-renewal capacity, differentiation status, and/or their phenotypic characteristics.

  15. SOX2 functions as a molecular rheostat to control the growth, tumorigenicity and drug responses of pancreatic ductal adenocarcinoma cells

    Science.gov (United States)

    Wuebben, Erin L.; Wilder, Phillip J.; Cox, Jesse L.; Grunkemeyer, James A.; Caffrey, Thomas; Hollingsworth, Michael A.; Rizzino, Angie

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is a highly deadly malignancy. Expression of the stem cell transcription factor SOX2 increases during progression of PDAC. Knockdown of SOX2 in PDAC cell lines decreases growth in vitro; whereas, stable overexpression of SOX2 in one PDAC cell line reportedly increases growth in vitro. Here, we reexamined the role of SOX2 in PDAC cells, because inducible SOX2 overexpression in other tumor cell types inhibits growth. In this study, four PDAC cell lines were engineered for inducible overexpression of SOX2 or inducible knockdown of SOX2. Remarkably, inducible overexpression of SOX2 in PDAC cells inhibits growth in vitro and reduces tumorigenicity. Additionally, inducible knockdown of SOX2 in PDAC cells reduces growth in vitro and in vivo. Thus, growth and tumorigenicity of PDAC cells is highly dependent on the expression of optimal levels of SOX2 – a hallmark of molecular rheostats. We also determined that SOX2 alters the responses of PDAC cells to drugs used in PDAC clinical trials. Increasing SOX2 reduces growth inhibition mediated by MEK and AKT inhibitors; whereas knockdown of SOX2 further reduces growth when PDAC cells are treated with these inhibitors. Thus, targeting SOX2, or its mode of action, could improve the treatment of PDAC. PMID:27145457

  16. SOX10 transactivates S100B to suppress Schwann cell proliferation and to promote myelination.

    Directory of Open Access Journals (Sweden)

    Sayaka Fujiwara

    Full Text Available Schwann cells are an important cell source for regenerative therapy for neural disorders. We investigated the role of the transcription factor sex determining region Y (SRY-box 10 (SOX10 in the proliferation and myelination of Schwann cells. SOX10 is predominantly expressed in rat sciatic nerve-derived Schwann cells and is induced shortly after birth. Among transcription factors known to be important for the differentiation of Schwann cells, SOX10 potently transactivates the S100B promoter. In cultures of Schwann cells, overexpressing SOX10 dramatically induces S100B expression, while knocking down SOX10 with shRNA suppresses S100B expression. Here, we identify three core response elements of SOX10 in the S100B promoter and intron 1 with a putative SOX motif. Knockdown of either SOX10 or S100B enhances the proliferation of Schwann cells. In addition, using dissociated cultures of dorsal root ganglia, we demonstrate that suppressing S100B with shRNA impairs myelination of Schwann cells. These results suggest that the SOX10-S100B signaling axis critically regulates Schwann cell proliferation and myelination, and therefore is a putative therapeutic target for neuronal disorders.

  17. Data Acquisition, Control, Communication and Computation System of Solar X-ray Spectrometer (SOXS) Mission

    Indian Academy of Sciences (India)

    Amish B. Shah; N. M. Vadher; Rajmal Jain; Hemant Dave; Vishal Shah; K. S. B. Manian; Satish Kayasth; Vinod Patel; Girish Ubale; Kirit Shah; Chirag Solanki; M. R. Deshpande; Ramkrishna Sharma; C. N. Umapathy; N. Viswanath; Ravi Kulkarni; P. S. Kumar

    2006-06-01

    The Solar X-ray Spectrometer (SOXS) mission onboard GSAT-2 Indian Spacecraft was launched on 08 May 2003 using GSLV–D2 rocket by Indian Space Research Organization (ISRO). SOXS aims to study solar flares, which are the most violent and energetic phenomena in the solar system, in the energy range of 4–56 keV with high spectral and temporal resolution. SOXS employs state-of-the-art semiconductor devices, viz., Si-Pin and CZT detectors to achieve sub-keV energy resolution requirements. In this paper, we present an overview of data acquisition, control, communication and computation of low energy payload of the SOXS mission.

  18. Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins.

    Science.gov (United States)

    Vilas, Jéssica M; Ferreirós, Alba; Carneiro, Carmen; Morey, Lluis; Da Silva-Álvarez, Sabela; Fernandes, Tânia; Abad, María; Di Croce, Luciano; García-Caballero, Tomás; Serrano, Manuel; Rivas, Carmen; Vidal, Anxo; Collado, Manuel

    2015-02-20

    Cellular reprogramming to iPSCs has uncovered unsuspected links between tumor suppressors and pluripotency factors. Using this system, it was possible to identify tumor suppressor p27 as a repressor of Sox2 during differentiation. This led to the demonstration that defects in the repression of Sox2 can contribute to tumor development. The members of the retinoblastoma family of pocket proteins, pRb, p107 and p130, are negative regulators of the cell cycle with tumor suppressor activity and with roles in differentiation. In this work we studied the relative contribution of the retinoblastoma family members to the regulation of Sox2 expression. We found that deletion of Rb or p130 leads to impaired repression of Sox2, a deffect amplified by inactivation of p53. We also identified binding of pRb and p130 to an enhancer with crucial regulatory activity on Sox2 expression. Using cellular reprogramming we tested the impact of the defective repression of Sox2 and confirmed that Rb deficiency allows the generation of iPSCs in the absence of exogenous Sox2. Finally, partial depletion of Sox2 positive cells reduced the pituitary tumor development initiated by Rb loss in vivo. In summary, our results show that Sox2 repression by pRb is a relevant mechanism of tumor suppression.

  19. Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins

    Science.gov (United States)

    Carneiro, Carmen; Morey, Lluis; Silva-Álvarez, Sabela Da; Fernandes, Tânia; Abad, María; Croce, Luciano Di; García-Caballero, Tomás; Serrano, Manuel; Rivas, Carmen; Vidal, Anxo; Collado, Manuel

    2015-01-01

    Cellular reprogramming to iPSCs has uncovered unsuspected links between tumor suppressors and pluripotency factors. Using this system, it was possible to identify tumor suppressor p27 as a repressor of Sox2 during differentiation. This led to the demonstration that defects in the repression of Sox2 can contribute to tumor development. The members of the retinoblastoma family of pocket proteins, pRb, p107 and p130, are negative regulators of the cell cycle with tumor suppressor activity and with roles in differentiation. In this work we studied the relative contribution of the retinoblastoma family members to the regulation of Sox2 expression. We found that deletion of Rb or p130 leads to impaired repression of Sox2, a deffect amplified by inactivation of p53. We also identified binding of pRb and p130 to an enhancer with crucial regulatory activity on Sox2 expression. Using cellular reprogramming we tested the impact of the defective repression of Sox2 and confirmed that Rb deficiency allows the generation of iPSCs in the absence of exogenous Sox2. Finally, partial depletion of Sox2 positive cells reduced the pituitary tumor development initiated by Rb loss in vivo. In summary, our results show that Sox2 repression by pRb is a relevant mechanism of tumor suppression. PMID:25576924

  20. LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression

    Science.gov (United States)

    Chen, Zhen-zhen; Huang, Lan; Wu, Ya-hong; Zhai, Wen-jie; Zhu, Ping-ping; Gao, Yan-feng

    2016-01-01

    Liver cancer has a tendency to develop asymptomatically in patients, so most patients are diagnosed at a later stage. Accumulating evidence implicates that liver tumour-initiating cells (TICs) as being responsible for liver cancer initiation and recurrence. However, the molecular mechanism of liver TIC self-renewal is poorly understood. Here we discover that a long noncoding RNA (lncRNA) termed LncSox4 is highly expressed in hepatocellular carcinoma (HCC) tissues and in liver TICs. We find that LncSox4 is required for liver TIC self-renewal and tumour initiation. LncSox4 interacts with and recruits Stat3 to the Sox4 promoter to initiate the expression of Sox4, which is highly expressed in liver TICs and required for liver TIC self-renewal. The expression level of Sox4 correlates with HCC development, clinical severity and prognosis of patients. Altogether, we find that LncSox4 is highly expressed in liver TICs and is required for their self-renewal. PMID:27553854

  1. AraC/XylS family stress response regulators Rob, SoxS, PliA, and OpiA in the fire blight pathogen Erwinia amylovora.

    Science.gov (United States)

    Pletzer, Daniel; Schweizer, Gabriel; Weingart, Helge

    2014-09-01

    Transcriptional regulators of the AraC/XylS family have been associated with multidrug resistance, organic solvent tolerance, oxidative stress, and virulence in clinically relevant enterobacteria. In the present study, we identified four homologous AraC/XylS regulators, Rob, SoxS, PliA, and OpiA, from the fire blight pathogen Erwinia amylovora Ea1189. Previous studies have shown that the regulators MarA, Rob, and SoxS from Escherichia coli mediate multiple-antibiotic resistance, primarily by upregulating the AcrAB-TolC efflux system. However, none of the four AraC/XylS regulators from E. amylovora was able to induce a multidrug resistance phenotype in the plant pathogen. Overexpression of rob led to a 2-fold increased expression of the acrA gene. However, the rob-overexpressing strain showed increased resistance to only a limited number of antibiotics. Furthermore, Rob was able to induce tolerance to organic solvents in E. amylovora by mechanisms other than efflux. We demonstrated that SoxS from E. amylovora is involved in superoxide resistance. A soxS-deficient mutant of Ea1189 was not able to grow on agar plates supplemented with the superoxide-generating agent paraquat. Furthermore, expression of soxS was induced by redox cycling agents. We identified two novel members of the AraC/XylS family in E. amylovora. PliA was highly upregulated during the early infection phase in apple rootstock and immature pear fruits. Multiple compounds were able to induce the expression of pliA, including apple leaf extracts, phenolic compounds, redox cycling agents, heavy metals, and decanoate. OpiA was shown to play a role in the regulation of osmotic and alkaline pH stress responses.

  2. The new SOXS instrument for the ESO NTT

    CERN Document Server

    Schipani, P; Campana, S; Baruffolo, A; Basa, S; Basso, S; Cappellaro, E; Cascone, E; Cosentino, R; DAlessio, F; De Caprio, V; Della Valle, M; Postigo, A de Ugarte; DOrsi, S; Franzen, R; Fynbo, J; Gal-Yam, A; Gardiol, D; Giro, E; Hamuy, M; Iuzzolino, M; Loreggia, D; Mattila, S; Munari, M; Pignata, G; Riva, M; Savarese, S; Schmidt, B; Scuderi, S; Smartt, S; Vitali, F

    2016-01-01

    SOXS (Son Of X-Shooter) will be a unique spectroscopic facility for the ESO-NTT 3.5-m telescope in La Silla (Chile), able to cover the optical/NIR band (350-1750 nm). The design foresees a high-efficiency spectrograph with a resolution-slit product of ~4,500, capable of simultaneously observing the complete spectral range 350 - 1750 nm with a good sensitivity, with light imaging capabilities in the visible band. This paper outlines the status of the project.

  3. RNA-Seq analysis reveals a six-gene SoxR regulon in Streptomyces coelicolor.

    Directory of Open Access Journals (Sweden)

    Nawar Naseer

    Full Text Available The redox-regulated transcription factor SoxR is conserved in diverse bacteria, but emerging studies suggest that this protein plays distinct physiological roles in different bacteria. SoxR regulates a global oxidative stress response (involving > 100 genes against exogenous redox-cycling drugs in Escherichia coli and related enterics. In the antibiotic producers Streptomyces coelicolor and Pseudomonas aeruginosa, however, SoxR regulates a smaller number of genes that encode membrane transporters and proteins with homology to antibiotic-tailoring enzymes. In both S. coelicolor and P. aeruginosa, SoxR-regulated genes are expressed in stationary phase during the production of endogenously-produced redox-active antibiotics. These observations suggest that SoxR evolved to sense endogenous secondary metabolites and activate machinery to process and transport them in antibiotic-producing bacteria. Previous bioinformatics analysis that searched the genome for SoxR-binding sites in putative promoters defined a five-gene SoxR regulon in S. coelicolor including an ABC transporter, two oxidoreductases, a monooxygenase and an epimerase/dehydratase. Since this in silico screen may have missed potential SoxR-targets, we conducted a whole genome transcriptome comparison of wild type S. coelicolor and a soxR-deficient mutant in stationary phase using RNA-Seq. Our analysis revealed a sixth SoxR-regulated gene in S. coelicolor that encodes a putative quinone oxidoreductase. Knowledge of the full complement of genes regulated by SoxR will facilitate studies to elucidate the function of this regulatory molecule in antibiotic producers.

  4. Molecular cloning and characterization of SoxB2 gene from Zhikong scallop Chlamys farreri

    Science.gov (United States)

    He, Yan; Bao, Zhenmin; Guo, Huihui; Zhang, Yueyue; Zhang, Lingling; Wang, Shi; Hu, Jingjie; Hu, Xiaoli

    2013-11-01

    The Sox proteins play critical roles during the development of animals, including sex determination and central nervous system development. In this study, the SoxB2 gene was cloned from a mollusk, the Zhikong scallop ( Chlamys farreri), and characterized with respect to phylogeny and tissue distribution. The full-length cDNA and genomic DNA sequences of C. farreri SoxB2 ( Cf SoxB2) were obtained by rapid amplification of cDNA ends and genome walking, respectively, using a partial cDNA fragment from the highly conserved DNA-binding domain, i.e., the High Mobility Group (HMG) box. The full-length cDNA sequence of Cf SoxB2 was 2 048 bp and encoded 268 amino acids protein. The genomic sequence was 5 551 bp in length with only one exon. Several conserved elements, such as the TATA-box, GC-box, CAAT-box, GATA-box, and Sox/sry-sex/testis-determining and related HMG box factors, were found in the promoter region. Furthermore, real-time quantitative reverse transcription PCR assays were carried out to assess the mRNA expression of Cf SoxB 2 in different tissues. SoxB2 was highly expressed in the mantle, moderately in the digestive gland and gill, and weakly expressed in the gonad, kidney and adductor muscle. In male and female gonads at different developmental stages of reproduction, the expression levels of Cf SoxB2 were similar. Considering the specific expression and roles of SoxB 2 in other animals, in particular vertebrates, and the fact that there are many pallial nerves in the mantle, cerebral ganglia in the digestive gland and gill nerves in gill, we propose a possible essential role in nervous tissue function for Sox B 2 in C. farreri.

  5. Sox11 is required to maintain proper levels of Hedgehog signaling during vertebrate ocular morphogenesis.

    Directory of Open Access Journals (Sweden)

    Lakshmi Pillai-Kastoori

    2014-07-01

    Full Text Available Ocular coloboma is a sight-threatening malformation caused by failure of the choroid fissure to close during morphogenesis of the eye, and is frequently associated with additional anomalies, including microphthalmia and cataracts. Although Hedgehog signaling is known to play a critical role in choroid fissure closure, genetic regulation of this pathway remains poorly understood. Here, we show that the transcription factor Sox11 is required to maintain specific levels of Hedgehog signaling during ocular development. Sox11-deficient zebrafish embryos displayed delayed and abnormal lens formation, coloboma, and a specific reduction in rod photoreceptors, all of which could be rescued by treatment with the Hedgehog pathway inhibitor cyclopamine. We further demonstrate that the elevated Hedgehog signaling in Sox11-deficient zebrafish was caused by a large increase in shha transcription; indeed, suppressing Shha expression rescued the ocular phenotypes of sox11 morphants. Conversely, over-expression of sox11 induced cyclopia, a phenotype consistent with reduced levels of Sonic hedgehog. We screened DNA samples from 79 patients with microphthalmia, anophthalmia, or coloboma (MAC and identified two novel heterozygous SOX11 variants in individuals with coloboma. In contrast to wild type human SOX11 mRNA, mRNA containing either variant failed to rescue the lens and coloboma phenotypes of Sox11-deficient zebrafish, and both exhibited significantly reduced transactivation ability in a luciferase reporter assay. Moreover, decreased gene dosage from a segmental deletion encompassing the SOX11 locus resulted in microphthalmia and related ocular phenotypes. Therefore, our study reveals a novel role for Sox11 in controlling Hedgehog signaling, and suggests that SOX11 variants contribute to pediatric eye disorders.

  6. cDNA cloning and expression analysis of two distinct Sox8 genes in Paramisgurnus dabryanus (Cypriniformes).

    Science.gov (United States)

    Xia, Xiaohua; Zhao, Jie; Du, Qiyan; Chang, Zhongjie

    2010-08-01

    The Sox9 gene attracts a lot of attention because of its connection with gonadal development and differentiation. However, Sox8, belonging to the same subgroup SoxE, has rarely been studied. To investigate the function as well as the evolutionary origin of SOXE subgroup, we amplified the genomic DNA of Paramisgurnus dabryanu using a pair of degenerate primers. Using rapid amplification of the cDNA ends (RACE), it was discovered that P. dabryanu has two duplicates: Sox8a and Sox8b. Each has an intron of different length in the conserved HMG-box region. The overall sequence similarity of the deduced amino acid of PdSox8a and PdSox8b was 46.26%, and only two amino acids changed in the HMG-box. This is the first evidence showing that there are two distinct duplications of Sox8 genes in Cypriniformes. Southern blot analysis showed only one hybrid band, with lengths 7.4 or 9.2 kb. Both semi-quantitative RT-PCR and real-time quantitative PCR assay displayed that both PdSox8a and PdSox8b are downregulated during early embryonic development. In adult tissues, the two Sox8 genes expressed ubiquitously, and expression levels are particularly high in the gonads and brain. In gonads, both PdSox8a and PdSox8b are expressed at a higher level in the tesis than in the ovary. PdSox8a and PdSox8b may have functional overlaps and are essential for the neuronal development and differentiation of gonads.

  7. cDNA cloning and expression analysis of two distinct Sox8 genes in Paramisgurnus dabryanus (Cypriniformes)

    Indian Academy of Sciences (India)

    Xiaohua Xia; Jie Zhao; Qiyan Du; Zhongjie Chang

    2010-08-01

    The Sox9 gene attracts a lot of attention because of its connection with gonadal development and differentiation. However, Sox8, belonging to the same subgroup SoxE, has rarely been studied. To investigate the function as well as the evolutionary origin of SOXE subgroup, we amplified the genomic DNA of Paramisgurnus dabryanu using a pair of degenerate primers. Using rapid amplification of the cDNA ends (RACE), it was discovered that P. dabryanu has two duplicates: Sox8a and Sox8b. Each has an intron of different length in the conserved HMG-box region. The overall sequence similarity of the deduced amino acid of PdSox8a and PdSox8b was 46.26%, and only two amino acids changed in the HMG-box. This is the first evidence showing that there are two distinct duplications of Sox8 genes in Cypriniformes. Southern blot analysis showed only one hybrid band, with lengths 7.4 or 9.2 kb. Both semi-quantitative RT-PCR and real-time quantitative PCR assay displayed that both PdSox8a and PdSox8b are downregulated during early embryonic development. In adult tissues, the two Sox8 genes expressed ubiquitously, and expression levels are particularly high in the gonads and brain. In gonads, both PdSox8a and PdSox8b are expressed at a higher level in the tesis than in the ovary. PdSox8a and PdSox8b may have functional overlaps and are essential for the neuronal development and differentiation of gonads.

  8. SOX9-mediated upregulation of LGR5 is important for glioblastoma tumorigenicity

    Energy Technology Data Exchange (ETDEWEB)

    Hiraoka, Koji; Hayashi, Tomoatsu; Kaneko, Ryusuke; Nasu-Nishimura, Yukiko; Koyama-Nasu, Ryo; Kawasaki, Yoshihiro; Akiyama, Tetsu, E-mail: akiyama@iam.u-tokyo.ac.jp

    2015-05-01

    LGR5 plays an important role in the self-renewal of stem cells and is used as a marker identifying self-renewing stem cells in small intestine and hair follicles. Moreover, LGR5 has been reported to be overexpressed in several cancers. SOX9 is a transcription factor that plays a key role in development, differentiation and lineage commitment in various tissues. It has also been reported that SOX9 is overexpressed in a variety of cancers and contributes to their malignant phenotype. Here we show that LGR5 is required for the tumorigenicity of glioblastoma cells. We further show that SOX9 is upregulated in glioblastoma cells and directly enhances the expression of LGR5. We also demonstrate that knockdown of SOX9 suppresses the proliferation and tumorigenicity of glioblastoma cells. These results suggest that SOX9-mediated transcriptional regulation of LGR5 is critical for the tumorigenicity of glioblastoma cells. We speculate that the SOX9-LGR5 pathway could be a potentially promising target for the therapy of glioblastoma. - Highlights: • LGR5 is required for the tumorigenicity of glioblastoma cells. • SOX9 directly enhances the expression of LGR5. • SOX9 is required for the tumorigenicity of glioblastoma cells.

  9. Spontaneous evolution of an unusual cortical malformation in SOX2 anophthalmia syndrome

    Directory of Open Access Journals (Sweden)

    Jay Desai

    2013-01-01

    Full Text Available Brain malformations such as agenesis and dysgenesis of corpus callosum, pituitary hypoplasia, hypothalamic hamartoma, mesial temporal periventricular heterotopia, and abnormally oriented and misshapen hippocampi have been described with SOX2 gene mutations. A neocortical malformation is presented here in association with SOX2 deletion that over time underwent spontaneous evolution and decrease in size.

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

    Science.gov (United States)

    2010-01-01

    January 15, 2009 and BMP-6 (40) to parathyroid hormone and progesterone (8). Previous work has shown that SOX4 directly signals from IL-5Ra (41), and here...stained section of SOX4 knockout mouse prostate (4x). Clear hyperplasia is seen in the uppermost gland however the majority of tissue appears normal. (C

  11. Analysis of SOX2 expression in developing human testis and germ cell neoplasia

    DEFF Research Database (Denmark)

    Sonne, Si Brask; Perrett, Rebecca M.; Nielsen, John Erik;

    2010-01-01

    The transcriptional regulators of pluripotency, POU5F1 (OCT4), NANOG and SOX2, are highly expressed in embryonal carcinoma (EC). In contrast to OCT4 and NANOG, SOX2 has not been demonstrated in the early human germ cell lineage or carcinoma in situ (CIS), the precursor for testicular germ cell tu...

  12. An Evolutionarily Conserved SoxB-Hdac2 Crosstalk Regulates Neurogenesis in a Cnidarian.

    Science.gov (United States)

    Flici, Hakima; Schnitzler, Christine E; Millane, R Cathriona; Govinden, Graham; Houlihan, Amy; Boomkamp, Stephanie D; Shen, Sanbing; Baxevanis, Andreas D; Frank, Uri

    2017-02-07

    SoxB transcription factors and histone deacetylases (HDACs) are each major players in the regulation of neurogenesis, but a functional link between them has not been previously demonstrated. Here, we show that SoxB2 and Hdac2 act together to regulate neurogenesis in the cnidarian Hydractinia echinata during tissue homeostasis and head regeneration. We find that misexpression of SoxB genes modifies the number of neural cells in all life stages and interferes with head regeneration. Hdac2 was co-expressed with SoxB2, and its downregulation phenocopied SoxB2 knockdown. We also show that SoxB2 and Hdac2 promote each other's transcript levels, but Hdac2 counteracts this amplification cycle by deacetylating and destabilizing SoxB2 protein. Finally, we present evidence for conservation of these interactions in human neural progenitors. We hypothesize that crosstalk between SoxB transcription factors and Hdac2 is an ancient feature of metazoan neurogenesis and functions to stabilize the correct levels of these multifunctional proteins.

  13. The versatile functions of Sox9 in development, stem cells, and human diseases

    Science.gov (United States)

    Jo, Alice; Denduluri, Sahitya; Zhang, Bosi; Wang, Zhongliang; Yin, Liangjun; Yan, Zhengjian; Kang, Richard; Shi, Lewis L.; Mok, James; Lee, Michael J.; Haydon, Rex C.

    2014-01-01

    The transcription factor Sox9 was first discovered in patients with campomelic dysplasia, a haploinsufficiency disorder with skeletal deformities caused by dysregulation of Sox9 expression during chondrogenesis. Since then, its role as a cell fate determiner during embryonic development has been well characterized; Sox9 expression differentiates cells derived from all three germ layers into a large variety of specialized tissues and organs. However, recent data has shown that ectoderm- and endoderm-derived tissues continue to express Sox9 in mature organs and stem cell pools, suggesting its role in cell maintenance and specification during adult life. The versatility of Sox9 may be explained by a combination of post-transcriptional modifications, binding partners, and the tissue type in which it is expressed. Considering its importance during both development and adult life, it follows that dysregulation of Sox9 has been implicated in various congenital and acquired diseases, including fibrosis and cancer. This review provides a summary of the various roles of Sox9 in cell fate specification, stem cell biology, and related human diseases. Ultimately, understanding the mechanisms that regulate Sox9 will be crucial for developing effective therapies to treat disease caused by stem cell dysregulation or even reverse organ damage. PMID:25685828

  14. Sox9 potentiates BMP2-induced chondrogenic differentiation and inhibits BMP2-induced osteogenic differentiation.

    Science.gov (United States)

    Liao, Junyi; Hu, Ning; Zhou, Nian; Lin, Liangbo; Zhao, Chen; Yi, Shixiong; Fan, Tingxu; Bao, Wei; Liang, Xi; Chen, Hong; Xu, Wei; Chen, Cheng; Cheng, Qiang; Zeng, Yongming; Si, Weike; Yang, Zhong; Huang, Wei

    2014-01-01

    Bone morphogenetic protein 2 (BMP2) is one of the key chondrogenic growth factors involved in the cartilage regeneration. However, it also exhibits osteogenic abilities and triggers endochondral ossification. Effective chondrogenesis and inhibition of BMP2-induced osteogenesis and endochondral ossification can be achieved by directing the mesenchymal stem cells (MSCs) towards chondrocyte lineage with chodrogenic factors, such as Sox9. Here we investigated the effects of Sox9 on BMP2-induced chondrogenic and osteogenic differentiation of MSCs. We found exogenous overexpression of Sox9 enhanced the BMP2-induced chondrogenic differentiation of MSCs in vitro. Also, it inhibited early and late osteogenic differentiation of MSCs in vitro. Subcutaneous stem cell implantation demonstrated Sox9 potentiated BMP2-induced cartilage formation and inhibited endochondral ossification. Mouse limb cultures indicated that BMP2 and Sox9 acted synergistically to stimulate chondrocytes proliferation, and Sox9 inhibited BMP2-induced chondrocytes hypertrophy and ossification. This study strongly suggests that Sox9 potentiates BMP2-induced MSCs chondrogenic differentiation and cartilage formation, and inhibits BMP2-induced MSCs osteogenic differentiation and endochondral ossification. Thus, exogenous overexpression of Sox9 in BMP2-induced mesenchymal stem cells differentiation may be a new strategy for cartilage tissue engineering.

  15. Cloning and study of adult-tissue-specific expression of Sox9 in Cyprinus carpio

    Indian Academy of Sciences (India)

    Du Qi-Yan; Wang Feng-Yu; Hua Hui-Ying; Chang Zhong-Jie

    2007-08-01

    The Sox9 gene is one of the important transcription factors in the development of many tissues and organs, particularly in sex determination and chondrogenesis. We amplified the genomic DNA of Cyprinus carpio using degenerate primers, and found that there were two versions of Sox9 in this species: Sox9a and Sox9b, that differ in having an intron of different length (704 bp and 616 bp, respectively) in the conserved HMG box region that codes for identical amino acid sequences. We used a two-phase rapid amplification of cDNA ends (RACE) for the isolation of full-length cDNA of Sox9b. Sequence analyses revealed a 2447-bp cDNA containing 233-bp 5′ untranslated region, a 927-bp 3′ untranslated region, including poly(A), and a 1287 bp open reading frame (ORF) encoding a protein of 428 amino acids. The HMG box of 79 amino acid motif was confirmed from positions 96–174. Sequence alignment showed that the identity of amino acids of Sox9 among ten animal species, including C. carpio, is 75%, indicating that the Sox9 gene is evolutionarily quite conserved. The expression level of Sox9b gene varied among several organs of adult C. carpio, with the level of expression being highest in the brain and testis.

  16. Molecular cloning and evolution analysis of the CaSox4 gene of Alligator sinensis%扬子鳄的CaSox4基因的分子克隆和进化分析

    Institute of Scientific and Technical Information of China (English)

    郑济芳; 朱睦元

    2003-01-01

    The completely identical HMG-box motif of CaSox4 gene from both male and female genomic DNA of the Chinese alligator (alligator sinensis) was cloned and sequenced by degenerate primer PCR.Compared with the human and mouse SRY,CaSox4 revealed 51% and 57% nucleotide homology respectively and 49% and 55% amino acid identity respectively,CaSox4 belongs to subgroup C of the Sox gene family.The GC content is 86% in the HMG-box region of the CaSox4 gene,Blast analysis showed that the CaSox4 gene shares 100 amino acid identity with human Sox4.bird SoxLF4,turtle Sra4 and lizard CvSox4 genes.Casox4 may be orthologous with the human SOx4 gene.This indicates that CaSox4 gene shows the remarkable evolutionary conservation during the evolution of Alligator Sinensis,The extensive sequence conservation of the Sox4 gene between reptiles,mammals and birds suggests major functional constraints[Acta Zoologica Sinica 49(3):404-407,2003].

  17. Haploinsufficiency of SOX5, a member of the SOX (SRY-related HMG-box) family of transcription factors is a cause of intellectual disability.

    Science.gov (United States)

    Schanze, Ina; Schanze, Denny; Bacino, Carlos A; Douzgou, Sofia; Kerr, Bronwyn; Zenker, Martin

    2013-02-01

    Intellectual disability (ID) is a clinically and genetically heterogeneous condition; the cause is unknown in most non-specific and sporadic cases. To establish an etiological basis in those patients represents a difficult challenge. Over the last years it has become apparent that chromosomal rearrangements below the detection level of conventional karyotyping contribute significantly to the cause of ID. We present three patients with non-specific intellectual disability who all have overlapping microdeletions in the chromosomal region 12p12.1. De novo occurrence of the deletion could be proven in the two cases from which parental samples were available. All three identified deletions have different breakpoints and range in size from 120 kb to 4.9 Mb. The smallest deletion helps to narrow down the critical region to a genomic segment (chr12:23,924,800-24,041,698, build 37/hg19) encompassing only one gene, SOX5. SOX5 is a member of the SOX (SRY-related HMG-box) family of transcription factors shown to play roles in chondroblast function, oligodendrocyte differentiation and migration, as well as ensuring proper development of specific neuronal cell types. Because of these biological functions, mutations in SOX5 are predicted to cause complex disease syndromes, as it is the case for other SOX genes, but such mutations have not yet been identified. Our findings indicate that haploinsufficiency of SOX5 is a cause of intellectual disability without any striking physical anomalies.

  18. Sox10 directs neural stem cells toward the oligodendrocyte lineage by decreasing Suppressor of Fused expression

    Science.gov (United States)

    Pozniak, Christine D.; Langseth, Abraham J.; Dijkgraaf, Gerrit J. P.; Choe, Youngshik; Werb, Zena; Pleasure, Samuel J.

    2010-01-01

    Oligodendrocyte precursor cells (OPCs) are lineage-restricted progenitors generally limited in vivo to producing oligodendrocytes. Mechanisms controlling genesis of OPCs are of interest because of their importance in myelin development and their potential for regenerative therapies in multiple sclerosis and dysmyelinating syndromes. We show here that the SoxE transcription factors (comprising Sox8, 9, and 10) induce multipotent neural precursor cells (NPCs) from the early postnatal subventricular zone (SVZ) to become OPCs in an autonomous manner. We performed a chromatin immunoprecipitation-based bioinformatic screen and identified Suppressor of Fused (Sufu) as a direct target of repression by Sox10. In vitro, overexpression of Sufu blocked OPC production, whereas RNAi-mediated inhibition augmented OPC production. Furthermore, mice heterozygous for Sufu have increased numbers of OPCs in the telencephalon during development. We conclude that Sox10 acts to restrict the potential of NPCs toward the oligodendrocyte lineage in part by regulating the expression of Sufu. PMID:21098272

  19. Fumonisin B(1): a neurotoxic mycotoxin.

    Science.gov (United States)

    Domijan, Ana-Marija

    2012-12-01

    Fumonisin B(1) (FB(1)) is a mycotoxin produced by Fusarium spp. moulds that contaminate crop, predominantly maize, all around the world. More than 15 types of fumonisins have been indentified so far, but FB(1) is the most abundant and toxicologically the most significant one. FB(1) has a wide range of toxic effects, depending on animal species. In horses FB(1) causes equine leukoencephalomalacia (ELEM), in pigs pulmonary oedema and in experimental rodents nephrotoxicity and hepatotoxicity. In humans exposure to FB(1) is linked with higher incidence of primary liver cancer and oesophageal cancer, which are frequent in certain regions of the world (such as Transkei region in South Africa) where maize is staple food. The occurrence of neural tube defect in children in some countries of Central America (such as Mexico and Honduras) is connected with the consumption of FB(1)-contaminated maize-based food. However, possible involvement of FB(1) in the development of human diseases is not clear. Nevertheless, the International Agency for Research on Cancer (IARC) has classified FB(1) as a possible carcinogen to humans (group 2B). FB(1) is a causative agent of ELEM, a brain disorder in equines, indicating that brain is a target organ of FB(1) toxicity. Several studies on experimental animals or on cell cultures of neural origin have established that FB(1) has a neurodegenerative potential, although the mechanism of its neurotoxicity is still vague. The aim of this article is to give an overview of available literature on FB(1) neurotoxicity and involved mechanisms, and to offer a new perspective for future studies.

  20. Clinical and Prognostic Implications of Transcription Factor SOX4 in Patients with Colon Cancer.

    Directory of Open Access Journals (Sweden)

    Chun-Mao Lin

    Full Text Available Colon cancer is one of the most common malignant cancers worldwide but the current therapeutic approaches for advanced colon cancer are less efficient. This study investigated associations between the expression of nuclear transcription factor SOX4 and various clinicopathologic parameters as well as patients' survival. Expression levels of nuclear SOX4 were analyzed by immunohistochemistry; the data comprised colon tissues from 263 patients with colon cancer. Paired t tests were used to analyze the differences in nuclear SOX4 expression between tumor and non-tumor tissues from each patient. Two-tailed Χ(2 tests were performed to determine whether the differences in nuclear SOX4 expression and clinicopathologic parameters were significant. Time-to-event endpoints for clinicopathologic parameters were plotted using the Kaplan-Meier method, and statistical significance was determined using univariate log-rank tests. Cox proportional hazard model was used for multivariate analysis to determine the independence of prognostic effects of nuclear SOX4 expression. Overexpression of nuclear SOX4 was significantly correlated with depth of invasion (P = 0.0041, distant metastasis (P<0.0001, and stage (P = 0.0001. Patients who displayed high expression levels of nuclear SOX4 achieved a significantly poorer disease-free survival rate, compared with patients with low SOX4 expression levels (P<0.001. Univariate Cox regression analysis showed that overexpression of nuclear SOX4 was a clear prognostic marker for colon cancer (P = 0.001. Overexpression of nuclear SOX4 may be used as a marker to predict the outcome of patients with colon cancer.

  1. Clinical and prognostic association of transcription factor SOX4 in gastric cancer.

    Directory of Open Access Journals (Sweden)

    Chia-Lang Fang

    Full Text Available Gastric cancer (GC is one of the most common malignant cancers worldwide. However, little is known about the molecular process by which this disease develops and progresses. This study investigated correlations between the expression of nuclear transcription factor SOX4 and various clinicopathologic parameters as well as patients' survival. Expression levels of nuclear SOX4 were analyzed by immunohistochemistry; the data comprised gastric tissues from 168 patients with GC. Paired t tests were used to analyze the differences in nuclear SOX4 expression between tumor and non-tumor tissues from each patient. Two-tailed Χ(2 tests were performed to determine whether the differences in nuclear SOX4 expression and clinicopathologic parameters were significant. Time-to-event endpoints for clinicopathologic parameters were plotted using the Kaplan-Meier method, and statistical significance was determined using univariate log-rank tests. Cox proportional hazard model was used for multivariate analysis to determine the independence of prognostic effects of nuclear SOX4 expression. Overexpression of nuclear SOX4 was significantly correlated with depth of invasion (P<0.0001, nodal status (P=0.0055, distant metastasis (P=0.0195, stage (P=0.0003, and vascular invasion (P=0.0383. Patients who displayed high expression levels of nuclear SOX4 achieved a significantly poorer disease-free survival rate, compared with patients with low SOX4 expression levels (P=0.003. Univariate Cox regression analysis showed that overexpression of nuclear SOX4 was a clear prognostic marker for GC (P=0.004. Overexpression of nuclear SOX4 can be used as a marker to predict the outcome of patients with GC.

  2. SOX9 indirectly regulates CEACAM1 expression and immune resistance in melanoma cells.

    Science.gov (United States)

    Ashkenazi, Shira; Ortenberg, Rona; Besser, Michal; Schachter, Jacob; Markel, Gal

    2016-05-24

    As melanoma cells are immunogenic, they instigate an adaptive immune response and production of anti-tumor T-cells. A central factor in this interaction is CEACAM1 (carcinoembryonic antigen cell adhesion molecule 1), a transmembrane glycoprotein previously shown in our lab to protect melanoma cells from T cell-mediated killing. In this study, we examine the role of transcription factor SOX9 in the regulation of CEACAM1 expression and immune resistance in melanoma cells. Knockdown of endogenous SOX9 results in CEACAM1 up-regulation, while its overexpression leads to the opposite effect. We show that SOX9 controls CEACAM1 expression at a transcriptional level, but in an indirect manner, as regulation of the CEACAM1 promoter remains intact even when all eight potential SOX9-binding sites are abolished. A series of promoter truncations localizes the SOX9-controlled area to the proximal 200bp of the promoter. Point mutations in putative Sp1 and ETS1 binding sites identify these transcription factors as the primary SOX9-controlled mediators. Co-immunoprecipitation studies show that SOX9 and Sp1 physically interact in melanoma cells, while silencing of SOX9 down-regulates ETS1, but not Sp1, in the same cells. Finally, knockdown of SOX9 indeed renders melanoma cells resistant to T cell-mediated killing, in line with the increased CEACAM1 expression. In conclusion, we show that SOX9 regulates CEACAM1 expression in melanoma cells, and thereby their immune resistance. As CEACAM1 is a pivotal protein in melanoma biology and immune crosstalk, further understanding of its regulation can provide new insights and contribute to the development of novel approaches to therapy.

  3. Synthesis of 5-Deoxy-5-Acyloxyiminoavermectin B1 Derivatives

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Four 5-deoxy-5-acyloxyiminoavermectin B1 derivatives 4a~d were synthesized via three steps from avermectin B1 and their biological activities were tested against Heliothis armigera,Laphygma exigua and Musca domestica.

  4. The early human germ cell lineage does not express SOX2 during in vivo development or upon in vitro culture

    DEFF Research Database (Denmark)

    Perrett, Rebecca M; Turnpenny, Lee; Eckert, Judith J

    2008-01-01

    of redundancy within the group B family of human SOX genes. Although lacking SOX2, proliferative human germ cells can still be identified in situ during early development and are capable of culture in vitro. Surprisingly, with the exception of FGF4, many stem cell-restricted SOX2 target genes remained detected...

  5. 26 CFR 301.7701(b)-1 - Resident alien.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Resident alien. 301.7701(b)-1 Section 301.7701... ADMINISTRATION PROCEDURE AND ADMINISTRATION Definitions § 301.7701(b)-1 Resident alien. (a) Scope. Section 301.7701(b)-1(b) provides rules for determining whether an alien individual is a lawful permanent...

  6. Compound list: aflatoxin B1 [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available aflatoxin B1 AFB1 00165 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/aflatoxin..._B1.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/aflatoxin_B1.Rat.in_vivo.Liver.Single.zip ...

  7. SWI/SNF enzymes promote SOX10- mediated activation of myelin gene expression.

    Science.gov (United States)

    Marathe, Himangi G; Mehta, Gaurav; Zhang, Xiaolu; Datar, Ila; Mehrotra, Aanchal; Yeung, Kam C; de la Serna, Ivana L

    2013-01-01

    SOX10 is a Sry-related high mobility (HMG)-box transcriptional regulator that promotes differentiation of neural crest precursors into Schwann cells, oligodendrocytes, and melanocytes. Myelin, formed by Schwann cells in the peripheral nervous system, is essential for propagation of nerve impulses. SWI/SNF complexes are ATP dependent chromatin remodeling enzymes that are critical for cellular differentiation. It was recently demonstrated that the BRG1 subunit of SWI/SNF complexes activates SOX10 expression and also interacts with SOX10 to activate expression of OCT6 and KROX20, two transcriptional regulators of Schwann cell differentiation. To determine the requirement for SWI/SNF enzymes in the regulation of genes that encode components of myelin, which are downstream of these transcriptional regulators, we introduced SOX10 into fibroblasts that inducibly express dominant negative versions of the SWI/SNF ATPases, BRM or BRG1. Dominant negative BRM and BRG1 have mutations in the ATP binding site and inhibit gene activation events that require SWI/SNF function. Ectopic expression of SOX10 in cells derived from NIH 3T3 fibroblasts led to the activation of the endogenous Schwann cell specific gene, myelin protein zero (MPZ) and the gene that encodes myelin basic protein (MBP). Thus, SOX10 reprogrammed these cells into myelin gene expressing cells. Ectopic expression of KROX20 was not sufficient for activation of these myelin genes. However, KROX20 together with SOX10 synergistically activated MPZ and MBP expression. Dominant negative BRM and BRG1 abrogated SOX10 mediated activation of MPZ and MBP and synergistic activation of these genes by SOX10 and KROX20. SOX10 was required to recruit BRG1 to the MPZ locus. Similarly, in immortalized Schwann cells, BRG1 recruitment to SOX10 binding sites at the MPZ locus was dependent on SOX10 and expression of dominant negative BRG1 inhibited expression of MPZ and MBP in these cells. Thus, SWI/SNF enzymes cooperate with SOX10 to

  8. SWI/SNF enzymes promote SOX10- mediated activation of myelin gene expression.

    Directory of Open Access Journals (Sweden)

    Himangi G Marathe

    Full Text Available SOX10 is a Sry-related high mobility (HMG-box transcriptional regulator that promotes differentiation of neural crest precursors into Schwann cells, oligodendrocytes, and melanocytes. Myelin, formed by Schwann cells in the peripheral nervous system, is essential for propagation of nerve impulses. SWI/SNF complexes are ATP dependent chromatin remodeling enzymes that are critical for cellular differentiation. It was recently demonstrated that the BRG1 subunit of SWI/SNF complexes activates SOX10 expression and also interacts with SOX10 to activate expression of OCT6 and KROX20, two transcriptional regulators of Schwann cell differentiation. To determine the requirement for SWI/SNF enzymes in the regulation of genes that encode components of myelin, which are downstream of these transcriptional regulators, we introduced SOX10 into fibroblasts that inducibly express dominant negative versions of the SWI/SNF ATPases, BRM or BRG1. Dominant negative BRM and BRG1 have mutations in the ATP binding site and inhibit gene activation events that require SWI/SNF function. Ectopic expression of SOX10 in cells derived from NIH 3T3 fibroblasts led to the activation of the endogenous Schwann cell specific gene, myelin protein zero (MPZ and the gene that encodes myelin basic protein (MBP. Thus, SOX10 reprogrammed these cells into myelin gene expressing cells. Ectopic expression of KROX20 was not sufficient for activation of these myelin genes. However, KROX20 together with SOX10 synergistically activated MPZ and MBP expression. Dominant negative BRM and BRG1 abrogated SOX10 mediated activation of MPZ and MBP and synergistic activation of these genes by SOX10 and KROX20. SOX10 was required to recruit BRG1 to the MPZ locus. Similarly, in immortalized Schwann cells, BRG1 recruitment to SOX10 binding sites at the MPZ locus was dependent on SOX10 and expression of dominant negative BRG1 inhibited expression of MPZ and MBP in these cells. Thus, SWI/SNF enzymes cooperate

  9. A Novel Regulatory Mechanism of Type II Collagen Expression via a SOX9-dependent Enhancer in Intron 6.

    Science.gov (United States)

    Yasuda, Hideyo; Oh, Chun-do; Chen, Di; de Crombrugghe, Benoit; Kim, Jin-Hoi

    2017-01-13

    Type II collagen α1 is specific for cartilaginous tissues, and mutations in its gene are associated with skeletal diseases. Its expression has been shown to be dependent on SOX9, a master transcription factor required for chondrogenesis that binds to an enhancer region in intron 1. However, ChIP sequencing revealed that SOX9 does not strongly bind to intron 1, but rather it binds to intron 6 and a site 30 kb upstream of the transcription start site. Here, we aimed to determine the role of the novel SOX9-binding site in intron 6. We prepared reporter constructs that contain a Col2a1 promoter, intron 1 with or without intron 6, and the luciferase gene. Although the reporter constructs were not activated by SOX9 alone, the construct that contained both introns 1 and 6 was activated 5-10-fold by the SOX9/SOX5 or the SOX9/SOX6 combination in transient-transfection assays in 293T cells. This enhancement was also observed in rat chondrosarcoma cells that stably expressed the construct. CRISPR/Cas9-induced deletion of intron 6 in RCS cells revealed that a 10-bp region of intron 6 is necessary both for Col2a1 expression and SOX9 binding. Furthermore, SOX9, but not SOX5, binds to this region as demonstrated in an electrophoretic mobility shift assay, although both SOX9 and SOX5 bind to a larger 325-bp fragment of intron 6 containing this small sequence. These findings suggest a novel mechanism of action of SOX5/6; namely, the SOX9/5/6 combination enhances Col2a1 transcription through a novel enhancer in intron 6 together with the enhancer in intron 1.

  10. Genome-wide analysis of the sox family in the calcareous sponge Sycon ciliatum: multiple genes with unique expression patterns

    Directory of Open Access Journals (Sweden)

    Fortunato Sofia

    2012-07-01

    Full Text Available Abstract Background Sox genes are HMG-domain containing transcription factors with important roles in developmental processes in animals; many of them appear to have conserved functions among eumetazoans. Demosponges have fewer Sox genes than eumetazoans, but their roles remain unclear. The aim of this study is to gain insight into the early evolutionary history of the Sox gene family by identification and expression analysis of Sox genes in the calcareous sponge Sycon ciliatum. Methods Calcaronean Sox related sequences were retrieved by searching recently generated genomic and transcriptome sequence resources and analyzed using variety of phylogenetic methods and identification of conserved motifs. Expression was studied by whole mount in situ hybridization. Results We have identified seven Sox genes and four Sox-related genes in the complete genome of Sycon ciliatum. Phylogenetic and conserved motif analyses showed that five of Sycon Sox genes represent groups B, C, E, and F present in cnidarians and bilaterians. Two additional genes are classified as Sox genes but cannot be assigned to specific subfamilies, and four genes are more similar to Sox genes than to other HMG-containing genes. Thus, the repertoire of Sox genes is larger in this representative of calcareous sponges than in the demosponge Amphimedon queenslandica. It remains unclear whether this is due to the expansion of the gene family in Sycon or a secondary reduction in the Amphimedon genome. In situ hybridization of Sycon Sox genes revealed a variety of expression patterns during embryogenesis and in specific cell types of adult sponges. Conclusions In this study, we describe a large family of Sox genes in Sycon ciliatum with dynamic expression patterns, indicating that Sox genes are regulators in development and cell type determination in sponges, as observed in higher animals. The revealed differences between demosponge and calcisponge Sox genes repertoire highlight the need to

  11. Aflatoxin B1: Mechanism of mutagenesis

    Directory of Open Access Journals (Sweden)

    Regina M. Santella

    2007-02-01

    Full Text Available

    Aflatoxins are a group of toxic and carcinogenic fungal metabolites that frequently contaminate corn, peanuts and other products. Aflatoxin B1 (AFB1, the most potent of these, is metabolized by the cytochrome P450 system into a number of hydroxylated metabolites and glutathione conjugates in the process of conversion to more hydrophilic forms for urinary excretion. Unfortunately, one of these metabolites is the aflatoxin-8,9-epoxide that is produced in two forms, endo and exo. Glutathione S-transferases (GST are able to conjugate and detoxify this reactive intermediate. Species differences in susceptibility to the effects of AFB1 are partially related to differences in expression of specific GSTs that are able to conjugate the epoxide to glutathione. The exo epoxide is able to intercalate into DNA and this is followed by reaction of the C8 position of the epoxide with the N7 position of guanine.

    NMR studies of oligonucleotide duplexes containing the adduct have demonstrated that the adduct exists with the aromatic portion intercalated on the 5' face of the guanine residue with Watson-Crick base pairing maintained.

    However, this covalent adduct is chemically unstable due to the charge on the ribose ring. As a result, the guanine can be released from the DNA leaving an apurinic site. This released guanine adduct can be detected in the urine and serves as a biomarker of exposure to AFB1. Alternatively, the ribose ring opens forming a stable formamidopyrimidine (FAPY adduct. This adduct somewhat stabilizes the DNA duplex. Time course studies in animals have demonstrated that the N7 adduct is rapidly removed, probably because it causes more distortion in the helix, while the FAPY adduct is more

  12. Profiling of Sox4-dependent transcriptome in skin links tumour suppression and adult stem cell activation

    Directory of Open Access Journals (Sweden)

    Miguel Foronda

    2015-12-01

    Full Text Available Adult stem cells (ASCs reside in specific niches in a quiescent state in adult mammals. Upon specific cues they become activated and respond by self-renewing and differentiating into newly generated specialised cells that ensure appropriate tissue fitness. ASC quiescence also serves as a tumour suppression mechanism by hampering cellular transformation and expansion (White AC et al., 2014. Some genes restricted to early embryonic development and adult stem cell niches are often potent modulators of stem cell quiescence, and derailed expression of these is commonly associated to cancer (Vervoort SJ et al., 2013. Among them, it has been shown that recommissioned Sox4 expression facilitates proliferation, survival and migration of malignant cells. By generating a conditional Knockout mouse model in stratified epithelia (Sox4cKO mice, we demonstrated a delayed plucking-induced Anagen in the absence of Sox4. Skin global transcriptome analysis revealed a prominent defect in the induction of transcriptional networks that control hair follicle stem cell (HFSC activation such as those regulated by Wnt/Ctnnb1, Shh, Myc or Sox9, cell cycle and DNA damage response-associated pathways. Besides, Sox4cKO mice are resistant to skin carcinogenesis, thus linking Sox4 to both normal and pathological HFSC activation (Foronda M et al., 2014. Here we provide additional details on the analysis of Sox4-regulated transcriptome in Telogen and Anagen skin. The raw and processed microarray data is deposited in GEO under GSE58155.

  13. SOX2 redirects the developmental fate of the intestinal epithelium toward a premature gastric phenotype

    Institute of Scientific and Technical Information of China (English)

    Lalini Raghoebir; Dick Tibboel; Ron Smits; Robbert J. Rottier; Elvira RM. Bakker; Jason C. Mills; Sigrid Swagemakers; Marjon Buscop-van Kempen; Anne Boerema-de Munck; Siska Driegen; Dies Meijer; Frank Grosveld

    2012-01-01

    Various factors play an essential role in patterning the digestive tract.During development,Sox2 and Cdx2 are exclusively expressed in the anterior and the posterior parts of the primitive gut,respectively.However,it is unclear whether these transcription factors influence each other in determining specification of the na(i)ve gut endoderm.We therefore investigated whether Sox2 redirects the fate of the prospective intestinal part of the primitive gut.Ectopic expression of Sox2 in the posterior region of the primitive gut caused anteriorization of the gut toward a gastric-like phenotype.Sox2 activated the foregut transcriptional program,in spite of sustained co-expression of endogenous Cdx2.However,binding of Cdx2 to its genomic targets and thus its transcriptional activity was strongly reduced.Recent findings indicate that endodermal Cdx2 is required to initiate the intestinal program and to suppress anterior cell fate.Our findings suggest that reduced Cdx2 expression by itself is not sufficient to cause anteriorization,but that Sox2 expression is also required.Moreover,it indicates that the balance between Sox2 and Cdx2 function is essential for proper specification of the primitive gut and that Sox2 may overrule the initial patterning of the primitive gut,emphasizing the plasticity of the primitive gut.

  14. The role of SOX9 transcription factor in pancreatic and duodenal development.

    Science.gov (United States)

    Belo, Jamie; Krishnamurthy, Mansa; Oakie, Amanda; Wang, Rennian

    2013-11-15

    Progenitor expansion during development is a highly regulated process dictating the final organ size, while expansion of specific progenitor populators can adjust the final cellular composition of the organ. Understanding factors involved in these pathways is required to develop cell-based therapies such as β-cell transplantation for conditions such as diabetes mellitus. One versatile factor controlling both processes as well as a network of other proteins involved in pancreatic and duodenal development is the transcription factor SOX9. This review will focus on a comparison of SOX9 function during progenitor expansion and differentiation in the developing pancreas and duodenum with specific focus on endocrine development. During human pancreatic development, SOX9 functions in a dose-dependent manner to regulate epithelial progenitor expansion and endocrine differentiation. SOX9 expression is eventually limited to a subset of ductal and centroacinar cells, hypothesized to be the pancreatic stem cell compartment. Similarly, during duodenal development, SOX9 is expressed in most early epithelial progenitors and becomes gradually restricted to proliferative progenitors in the lower crypts, as well as mature Paneth and enteroendocrine cells indicating some differences in functional roles. However, in both developmental contexts, SOX9 is involved in pathways responsible for cellular proliferation and differentiation, such as Notch and Wnt. With its adaptable and central function in progenitor control, SOX9 represents an attractive target for manipulation for in vitro progenitor expansion and differentiation meriting further investigation.

  15. SOX7 is involved in aspirin-mediated growth inhibition of human colorectal cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xin Zhou; Shu-Yan Huang; Jing-Xin Feng; Yan-Yan Gao; Li Zhao; Jun Lu; Bai-Qu Huang; Yu Zhang

    2011-01-01

    AIM: To confirm the role of sex-determining region Y-box 7 (Sox7) in aspirin-mediated growth inhibition of COX-independent human colorectal cancer cells.METHODS: The cell survival percentage was examined by MTT (Moto-nuclear cell direc cytotoxicity) assay.SOX7 expression was assessed by using reverse transcription-polymerase chain reaction and Western blotting. SB203580 was used to inhibit the p38MAPK signal pathway. SOX7 promoter activity was detected by Luciferase reporter assay.RESULTS: SOX7 was upregulated by aspirin and was involved in aspirin-mediated growth inhibition of SW480 human colorectal cancer cells. The p38MAPK pathway played a role in aspirin-induced SOX7 expression, during which the AP1 transcription factors c-Jun and c-Fos upregulated SOX7 promoter activities.RESULTS: SOX7 is upregulated by aspirin and is involved in aspirin-mediated growth inhibition of human colorectal cancer SW480 cells.

  16. Expression of the stem cell marker, SOX2, in ameloblastoma and dental epithelium.

    Science.gov (United States)

    Juuri, Emma; Isaksson, Sanna; Jussila, Maria; Heikinheimo, Kristiina; Thesleff, Irma

    2013-12-01

    Ameloblastomas are locally invasive odontogenic tumors that exhibit a high rate of recurrence and often associate with the third molars. They are suggested to originate from dental epithelium because the tumor cells resemble epithelial cells of developing teeth. Expression of the transcription factor SOX2 has been previously localized in epithelial stem and progenitor cells in developing teeth as well as in various tumors. Here, we show that SOX2 is expressed in the epithelial cells of follicular and plexiform ameloblastomas. SOX2 was localized in the dental lamina of developing human primary molars. It was also expressed in the fragmented dental lamina associated with the third molars and in the epithelium budding from its posterior aspect in mice. However, no SOX2 expression was detected in either Hertwig's epithelial root sheath directing the formation of roots or in the epithelial cell rests of Malassez covering the completed roots. SOX2 was associated with supernumerary tooth formation in odontoma-like tumors induced by Wnt signal activation in mice. We propose that SOX2 functions in maintaining the progenitor state of epithelium in ameloblastomas and that ameloblastomas may originate from SOX2-expressing dental lamina epithelium.

  17. Sox9 plays multiple roles in the lung epithelium during branching morphogenesis.

    Science.gov (United States)

    Rockich, Briana E; Hrycaj, Steven M; Shih, Hung Ping; Nagy, Melinda S; Ferguson, Michael A H; Kopp, Janel L; Sander, Maike; Wellik, Deneen M; Spence, Jason R

    2013-11-19

    Lung branching morphogenesis is a highly orchestrated process that gives rise to the complex network of gas-exchanging units in the adult lung. Intricate regulation of signaling pathways, transcription factors, and epithelial-mesenchymal cross-talk are critical to ensuring branching morphogenesis occurs properly. Here, we describe a role for the transcription factor Sox9 during lung branching morphogenesis. Sox9 is expressed at the distal tips of the branching epithelium in a highly dynamic manner as branching occurs and is down-regulated starting at embryonic day 16.5, concurrent with the onset of terminal differentiation of type 1 and type 2 alveolar cells. Using epithelial-specific genetic loss- and gain-of-function approaches, our results demonstrate that Sox9 controls multiple aspects of lung branching. Fine regulation of Sox9 levels is required to balance proliferation and differentiation of epithelial tip progenitor cells, and loss of Sox9 leads to direct and indirect cellular defects including extracellular matrix defects, cytoskeletal disorganization, and aberrant epithelial movement. Our evidence shows that unlike other endoderm-derived epithelial tissues, such as the intestine, Wnt/β-catenin signaling does not regulate Sox9 expression in the lung. We conclude that Sox9 collectively promotes proper branching morphogenesis by controlling the balance between proliferation and differentiation and regulating the extracellular matrix.

  18. Search for B-meson decays to b1ρ and b1K*

    Science.gov (United States)

    Aubert, B.; Karyotakis, Y.; Lees, J. P.; Poireau, V.; Prencipe, E.; Prudent, X.; Tisserand, V.; Garra Tico, J.; Grauges, E.; Martinelli, M.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Battaglia, M.; Brown, D. N.; Hooberman, B.; Kerth, L. T.; Kolomensky, Yu. G.; Lynch, G.; Osipenkov, I. L.; Tackmann, K.; Tanabe, T.; Hawkes, C. M.; Soni, N.; Watson, A. T.; Koch, H.; Schroeder, T.; Asgeirsson, D. J.; Hearty, C.; Mattison, T. S.; McKenna, J. A.; Barrett, M.; Khan, A.; Randle-Conde, A.; Blinov, V. E.; Bukin, A. D.; Buzykaev, A. R.; Druzhinin, V. P.; Golubev, V. B.; Onuchin, A. P.; Serednyakov, S. I.; Skovpen, Yu. I.; Solodov, E. P.; Todyshev, K. Yu.; Bondioli, M.; Curry, S.; Eschrich, I.; Kirkby, D.; Lankford, A. J.; Lund, P.; Mandelkern, M.; Martin, E. C.; Stoker, D. P.; Atmacan, H.; Gary, J. W.; Liu, F.; Long, O.; Vitug, G. M.; Yasin, Z.; Sharma, V.; Campagnari, C.; Hong, T. M.; Kovalskyi, D.; Mazur, M. A.; Richman, J. D.; Beck, T. W.; Eisner, A. M.; Heusch, C. A.; Kroseberg, J.; Lockman, W. S.; Martinez, A. J.; Schalk, T.; Schumm, B. A.; Seiden, A.; Wang, L.; Winstrom, L. O.; Cheng, C. H.; Doll, D. A.; Echenard, B.; Fang, F.; Hitlin, D. G.; Narsky, I.; Ongmongkolkul, P.; Piatenko, T.; Porter, F. C.; Andreassen, R.; Mancinelli, G.; Meadows, B. T.; Mishra, K.; Sokoloff, M. D.; Bloom, P. C.; Chavez, A.; Ford, W. T.; Gaz, A.; Hirschauer, J. F.; Nagel, M.; Nauenberg, U.; Smith, J. G.; Wagner, S. R.; Ayad, R.; Toki, W. H.; Wilson, R. J.; Feltresi, E.; Hauke, A.; Jasper, H.; Karbach, T. M.; Merkel, J.; Petzold, A.; Spaan, B.; Wacker, K.; Kobel, M. J.; Nogowski, R.; Schubert, K. R.; Schwierz, R.; Bernard, D.; Latour, E.; Verderi, M.; Clark, P. J.; Playfer, S.; Watson, J. E.; Andreotti, M.; Bettoni, D.; Bozzi, C.; Calabrese, R.; Cecchi, A.; Cibinetto, G.; Fioravanti, E.; Franchini, P.; Luppi, E.; Munerato, M.; Negrini, M.; Petrella, A.; Piemontese, L.; Santoro, V.; Baldini-Ferroli, R.; Calcaterra, A.; de Sangro, R.; Finocchiaro, G.; Pacetti, S.; Patteri, P.; Peruzzi, I. M.; Piccolo, M.; Rama, M.; Zallo, A.; Contri, R.; Guido, E.; Lo Vetere, M.; Monge, M. R.; Passaggio, S.; Patrignani, C.; Robutti, E.; Tosi, S.; Chaisanguanthum, K. S.; Morii, M.; Adametz, A.; Marks, J.; Schenk, S.; Uwer, U.; Bernlochner, F. U.; Klose, V.; Lacker, H. M.; Lueck, T.; Volk, A.; Bard, D. J.; Dauncey, P. D.; Tibbetts, M.; Behera, P. K.; Charles, M. J.; Mallik, U.; Cochran, J.; Crawley, H. B.; Dong, L.; Eyges, V.; Meyer, W. T.; Prell, S.; Rosenberg, E. I.; Rubin, A. E.; Gao, Y. Y.; Gritsan, A. V.; Guo, Z. J.; Arnaud, N.; Béquilleux, J.; D'Orazio, A.; Davier, M.; Derkach, D.; Firmino da Costa, J.; Grosdidier, G.; Le Diberder, F.; Lepeltier, V.; Lutz, A. M.; Malaescu, B.; Pruvot, S.; Roudeau, P.; Schune, M. H.; Serrano, J.; Sordini, V.; Stocchi, A.; Wormser, G.; Lange, D. J.; Wright, D. M.; Bingham, I.; Burke, J. P.; Chavez, C. A.; Fry, J. R.; Gabathuler, E.; Gamet, R.; Hutchcroft, D. E.; Payne, D. J.; Touramanis, C.; Bevan, A. J.; Clarke, C. K.; di Lodovico, F.; Sacco, R.; Sigamani, M.; Cowan, G.; Paramesvaran, S.; Wren, A. C.; Brown, D. N.; Davis, C. L.; Denig, A. G.; Fritsch, M.; Gradl, W.; Hafner, A.; Alwyn, K. E.; Bailey, D.; Barlow, R. J.; Jackson, G.; Lafferty, G. D.; West, T. J.; Yi, J. I.; Anderson, J.; Chen, C.; Jawahery, A.; Roberts, D. A.; Simi, G.; Tuggle, J. M.; Dallapiccola, C.; Salvati, E.; Cowan, R.; Dujmic, D.; Fisher, P. H.; Henderson, S. W.; Sciolla, G.; Spitznagel, M.; Yamamoto, R. K.; Zhao, M.; Patel, P. M.; Robertson, S. H.; Schram, M.; Biassoni, P.; Lazzaro, A.; Lombardo, V.; Palombo, F.; Stracka, S.; Cremaldi, L.; Godang, R.; Kroeger, R.; Sonnek, P.; Summers, D. J.; Zhao, H. W.; Simard, M.; Taras, P.; Nicholson, H.; de Nardo, G.; Lista, L.; Monorchio, D.; Onorato, G.; Sciacca, C.; Raven, G.; Snoek, H. L.; Jessop, C. P.; Knoepfel, K. J.; Losecco, J. M.; Wang, W. F.; Corwin, L. A.; Honscheid, K.; Kagan, H.; Kass, R.; Morris, J. P.; Rahimi, A. M.; Sekula, S. J.; Wong, Q. K.; Blount, N. L.; Brau, J.; Frey, R.; Igonkina, O.; Kolb, J. A.; Lu, M.; Rahmat, R.; Sinev, N. B.; Strom, D.; Strube, J.; Torrence, E.; Castelli, G.; Gagliardi, N.; Margoni, M.; Morandin, M.; Posocco, M.; Rotondo, M.; Simonetto, F.; Stroili, R.; Voci, C.; Del Amo Sanchez, P.; Ben-Haim, E.; Bonneaud, G. R.; Briand, H.; Chauveau, J.; Hamon, O.; Leruste, Ph.; Marchiori, G.; Ocariz, J.; Perez, A.; Prendki, J.; Sitt, S.; Gladney, L.; Biasini, M.; Manoni, E.; Angelini, C.; Batignani, G.; Bettarini, S.; Calderini, G.; Carpinelli, M.; Cervelli, A.; Forti, F.; Giorgi, M. A.; Lusiani, A.; Morganti, M.; Neri, N.; Paoloni, E.; Rizzo, G.; Walsh, J. J.; Lopes Pegna, D.; Lu, C.; Olsen, J.; Smith, A. J. S.; Telnov, A. V.; Anulli, F.; Baracchini, E.; Cavoto, G.; Faccini, R.; Ferrarotto, F.; Ferroni, F.; Gaspero, M.; Jackson, P. D.; Li Gioi, L.

    2009-09-01

    We present a search for decays of B mesons to final states with a b1 meson and a ρ or K*(892) meson. The search is based on a data sample consisting of 465 million B Bmacr pairs collected by the BABAR detector at the SLAC National Accelerator Laboratory. We do not observe any statistically significant signal. The upper limits we set on the branching fractions range from 1.4 to 8.0×10-6 at the 90% confidence level, including systematic uncertainties.

  19. Sox10 expressing cells in the lateral wall of the aged mouse and human cochlea.

    Directory of Open Access Journals (Sweden)

    Xinping Hao

    Full Text Available Age-related hearing loss (presbycusis is a common human disorder, affecting one in three Americans aged 60 and over. Previous studies have shown that presbyacusis is associated with a loss of non-sensory cells in the cochlear lateral wall. Sox10 is a transcription factor crucial to the development and maintenance of neural crest-derived cells including some non-sensory cell types in the cochlea. Mutations of the Sox10 gene are known to cause various combinations of hearing loss and pigmentation defects in humans. This study investigated the potential relationship between Sox10 gene expression and pathological changes in the cochlear lateral wall of aged CBA/CaJ mice and human temporal bones from older donors. Cochlear tissues prepared from young adult (1-3 month-old and aged (2-2.5 year-old mice, and human temporal bone donors were examined using quantitative immunohistochemical analysis and transmission electron microscopy. Cells expressing Sox10 were present in the stria vascularis, outer sulcus and spiral prominence in mouse and human cochleas. The Sox10(+ cell types included marginal and intermediate cells and outer sulcus cells, including those that border the scala media and those extending into root processes (root cells in the spiral ligament. Quantitative analysis of immunostaining revealed a significant decrease in the number of Sox10(+ marginal cells and outer sulcus cells in aged mice. Electron microscopic evaluation revealed degenerative alterations in the surviving Sox10(+ cells in aged mice. Strial marginal cells in human cochleas from donors aged 87 and older showed only weak immunostaining for Sox10. Decreases in Sox10 expression levels and a loss of Sox10(+ cells in both mouse and human aged ears suggests an important role of Sox10 in the maintenance of structural and functional integrity of the lateral wall. A loss of Sox10(+ cells may also be associated with a decline in the repair capabilities of non-sensory cells in the

  20. [Microdeletion 12p12 involving SOX5 gene: a new syndrome with developmental delay].

    Science.gov (United States)

    Arroyo-Carrera, Ignacio; de Zaldívar-Tristancho, M Solo; Martín-Fernández, Rebeca; Hernández-Martín, Raquel; López-Lafuente, Amparo; Rodríguez-Revenga, Laia

    2015-05-16

    Introduccion. El gen SOX5 codifica un factor de transcripcion implicado en la regulacion de la condrogenia y el desarrollo del sistema nervioso. Caso clinico. Niña de 10 anos con discapacidad intelectual, alteracion conductual y malformaciones menores de este nuevo sindrome con alteracion en el neurodesarrollo, con una delecion 12p12 que incluye el gen SOX5. Conclusiones. Se revisan los casos publicados tanto de deleciones intragenicas de SOX5 como de deleciones mas grandes que incluyen este gen, y se analizan las correlaciones genotipo-fenotipo y los genes implicados en esta paciente.

  1. Poisson Coordinates.

    Science.gov (United States)

    Li, Xian-Ying; Hu, Shi-Min

    2013-02-01

    Harmonic functions are the critical points of a Dirichlet energy functional, the linear projections of conformal maps. They play an important role in computer graphics, particularly for gradient-domain image processing and shape-preserving geometric computation. We propose Poisson coordinates, a novel transfinite interpolation scheme based on the Poisson integral formula, as a rapid way to estimate a harmonic function on a certain domain with desired boundary values. Poisson coordinates are an extension of the Mean Value coordinates (MVCs) which inherit their linear precision, smoothness, and kernel positivity. We give explicit formulas for Poisson coordinates in both continuous and 2D discrete forms. Superior to MVCs, Poisson coordinates are proved to be pseudoharmonic (i.e., they reproduce harmonic functions on n-dimensional balls). Our experimental results show that Poisson coordinates have lower Dirichlet energies than MVCs on a number of typical 2D domains (particularly convex domains). As well as presenting a formula, our approach provides useful insights for further studies on coordinates-based interpolation and fast estimation of harmonic functions.

  2. Construction of HEK293 cells stably expressing wild-type organic anion transporting polypeptide 1B1 (OATP1B1*1a) and variant OATP1B1*1b and OATP1B1*15.

    Science.gov (United States)

    Chen, M; Qu, B X; Chen, X L; Hu, H H; Jiang, H D; Yu, L S; Zhou, Q; Zeng, S

    2016-06-01

    A transgenic cell line stably expressing the human organic anion transporting polypeptide (OATP1B1) was established. Human Embryonic Kidney 293 (HEK293) cell line stably expressing OATP1B1*1a sequence was amplified through PCR with the extracted total RNA as templates from human liver, then subcloned into the plasmid pMD19-T and verified by sequencing. OATP1B1*1b/OATP1B1*15 mutant sequences were obtained by site-directed mutation PCR with pMD19-T/ OATP1B1*1a as templates. The plasmids pcDNA3.1(+)/OATP1B1*1a, *1b and *15 were constructed and transfected into HEK293 cell line using Lipofectamine 2000 transfection reagent. Several stable transfected clones were obtained after selection with G418. Using rosuvastatin as a probe substrate of OATP1B1, the intracellular rosuvastatin accumulation in HEK293 and HEK-OATP1B1*1a, *1b and *15 monoclone cells were validated by a ultra-performance liquid chromatography-tandem mass spectrometry. OATP1B1 mRNA and protein expression were detected by RT-PCR and Western blot, respectively. The results from RT-PCR, rosuvastatin uptake and Western blot assay indicated that human OATP1B1 was highly expressed in transfected cells compared with controls. The HEK-293 cell lines stably expressing human OATP1B1-wild and variant (HEK-OATP1B1, *1b and *15) are potential models to study drug transport in vitro.

  3. MAN1B1 deficiency: an unexpected CDG-II.

    Directory of Open Access Journals (Sweden)

    Daisy Rymen

    Full Text Available Congenital disorders of glycosylation (CDG are a group of rare metabolic diseases, due to impaired protein and lipid glycosylation. In the present study, exome sequencing was used to identify MAN1B1 as the culprit gene in an unsolved CDG-II patient. Subsequently, 6 additional cases with MAN1B1-CDG were found. All individuals presented slight facial dysmorphism, psychomotor retardation and truncal obesity. Generally, MAN1B1 is believed to be an ER resident alpha-1,2-mannosidase acting as a key factor in glycoprotein quality control by targeting misfolded proteins for ER-associated degradation (ERAD. However, recent studies indicated a Golgi localization of the endogenous MAN1B1, suggesting a more complex role for MAN1B1 in quality control. We were able to confirm that MAN1B1 is indeed localized to the Golgi complex instead of the ER. Furthermore, we observed an altered Golgi morphology in all patients' cells, with marked dilatation and fragmentation. We hypothesize that part of the phenotype is associated to this Golgi disruption. In conclusion, we linked mutations in MAN1B1 to a Golgi glycosylation disorder. Additionally, our results support the recent findings on MAN1B1 localization. However, more work is needed to pinpoint the exact function of MAN1B1 in glycoprotein quality control, and to understand the pathophysiology of its deficiency.

  4. An excretory function for the Escherichia coli outer membrane pore TolC: upregulation of marA and soxS transcription and Rob activity due to metabolites accumulated in tolC mutants.

    Science.gov (United States)

    Rosner, Judah L; Martin, Robert G

    2009-08-01

    Efflux pumps function to rid bacteria of xenobiotics, including antibiotics, bile salts, and organic solvents. TolC, which forms an outer membrane channel, is an essential component of several efflux pumps in Escherichia coli. We asked whether TolC has a role during growth in the absence of xenobiotics. Because tolC transcription is activated by three paralogous activators, MarA, SoxS, and Rob, we examined the regulation of these activators in tolC mutants. Using transcriptional fusions, we detected significant upregulation of marRAB and soxS transcription and Rob protein activity in tolC mutants. Three mechanisms could be distinguished: (i) activation of marRAB transcription was independent of marRAB, soxR, and rob functions; (ii) activation of soxS transcription required SoxR, a sensor of oxidants; and (iii) Rob protein was activated posttranscriptionally. This mechanism is similar to the mechanisms of upregulation of marRAB, soxS, and Rob by treatment with certain phenolics, superoxides, and bile salts, respectively. The transcription of other marA/soxS/rob regulon promoters, including tolC itself, was also elevated in tolC mutants. We propose that TolC is involved in the efflux of certain cellular metabolites, not only xenobiotics. As these metabolites accumulate during growth, they trigger the upregulation of MarA, SoxS, and Rob, which in turn upregulate tolC and help rid the bacteria of these metabolites, thereby restoring homeostasis.

  5. Analysis of the zebrafish sox9b promoter: Identification of elements that recapitulate organ-specific expression of sox9b.

    Science.gov (United States)

    Burns, Felipe R; Lanham, Kevin A; Xiong, Kong M; Gooding, Alex J; Peterson, Richard E; Heideman, Warren

    2016-03-10

    The SRY-related high-mobility box 9 (SOX9) gene is expressed in many different tissues. To better understand the DNA elements that control tissue-specific expression, we cloned and sequenced a 2.5 kb fragment lying 5' to the zebrafish sox9b gene transcriptional start site. Three regions of this clone contained stable secondary structures that hindered cloning, sequencing, and amplification. This segment and smaller fragmentswere inserted 5' of an EGFP reporter and transgenic fish were raised with the different reporters. Reporter expression was also observed in embryos directly injected with the constructs to transiently express the reporter. Heart expression required only a very short 5' sequence, as a 0.6 kb sox9b fragment produced reporter expression in heart in transgenic zebrafish, and transient experiments showed heart expression from a minimal sox9b promoter region containing a conserved TATA box and an EGR2 element (-74/+29 bp). Reporter expression in transgenic skeletal muscle was consistently lower than in other tissues. Jaw, brain, and notochord expression was strong with the full-length clone, but was dramatically reduced as the size of the fragment driving the reporter decreased from approximately 1.8 to 0.9 kb. The 2.5 kb region 5' of the sox9b contained 7 conserved non-coding elements (CNEs) that included putative hypoxia inducible factor 1α (HIF1α), CAAT box (CCAAT), early growth response protein 2 (EGR2), and core promoter elements. While a synthetic fragment containing all 7 CNEs produced some degree of reporter expression in muscle, jaw, heart and brain, the degree of reporter expression was considerably lower than that produced by the full length clone. These results can account for the tissue-specific expression of sox9b in the developing zebrafish.

  6. Sox9 Modulates Proliferation and Expression of Osteogenic Markers of Adipose-Derived Stem Cells (ASC

    Directory of Open Access Journals (Sweden)

    Sabine Stöckl

    2013-05-01

    Full Text Available Background: Mesenchymal stem cells (MSC are promising tools for tissue-engineering and musculoskeletal regeneration. They reside within various tissues, like adipose tissue, periosteum, synovia, muscle, dermis, blood and bone marrow, latter being the most common tissue used for MSC isolation. A promising alternative source for MSC is adipose tissue due to better availability and higher yield of MSC in comparison to bone marrow. A drawback is the yet fragmentary knowledge of adipose-derived stem cell (ASC physiology in order to make them a safe tool for in vivo application. Methods/Results: Here, we identified Sox9 as a highly expressed and crucial transcription factor in undifferentiated rat ASC (rASC. In comparison to rat bone marrow-derived stem cells (rBMSC, mRNA and protein levels of Sox9 were significantly higher in rASC. To study the role of Sox9 in detail, we silenced Sox9 with shRNA in rASC and examined proliferation, apoptosis and the expression of osteogenic differentiation markers. Our results clearly point to a difference in the expression profile of osteogenic marker genes between undifferentiated rASC and rBMSC in early passages. Sox9 silencing induced the expression of osteocalcin, Vegfα and Mmp13, and decreased rASC proliferation accompanied with an induction of p21 and cyclin D1 expression and delayed S-phase entry. Conclusions: We suggest a pro-proliferative role for Sox9 in undifferentiated rASC which may explain the higher proliferation rate of rASC compared to rBMSC. Moreover, we propose an osteogenic differentiation delaying role of Sox9 in rASC which suggests that Sox9 expression is needed to maintain rASC in an undifferentiated, proliferative state.

  7. High expression of Sox10 correlates with tumor aggressiveness and poor prognosis in human nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2016-03-01

    Full Text Available Yu Zhao,1,* Zhi-gang Liu,1,* Jiao Tang,1 Ren-fang Zou,1 Xiao-yan Chen,2 Guan-min Jiang,3 Yan-fang Qiu,1 Hui Wang11Key Laboratory of Translational Radiation Oncology, Department of Radiation Oncology, 2Department of Pathology, 3Department of Clinical Laboratory, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China*These authors contributed equally to this workPurpose: The aim of the study was to detect the expression of Sox10 in human nasopharyngeal carcinoma (NPC and investigate the relationship between its expression and the clinicopathological characteristics of NPC patients.Patients and methods: Tumor specimens (n=105 were retrospectively collected from patients with NPC diagnosed between 2004 and 2005 who presented at Hunan Cancer Hospital. Immunohistochemistry analyses were performed to characterize the expression of Sox10 in NPC. Kaplan–Meier survival and Cox regression analyses were employed to evaluate the prognosis of 105 NPC patients.Results: The results showed that Sox10 was markedly overexpressed in human NPC tissues. Analysis of clinicopathological parameters showed that high Sox10 expression was significantly correlated with the clinical stage (P=0.032, T classification (P=0.034, and lymph node metastasis (P=0.03. Cox regression analyses further showed that Sox10 expression was an independent prognostic factor for overall survival (P=0.005. This is the first time Sox10 has shown its importance in predicting NPC progressiveness and survival outcomes.Conclusion: Sox10 serves as a potential biomarker for NPC patients. It may hopefully become a novel therapeutic target for NPC patients.Keywords: Sox10, NPC, prognosis

  8. Silencing of SOX12 by shRNA suppresses migration, invasion and proliferation of breast cancer cells

    Science.gov (United States)

    Ding, Hanzhi; Quan, Hong; Yan, Weiguo; Han, Jing

    2016-01-01

    Sex determining region Y-box protein 12 (SOX12) is essential for embryonic development and cell-fate determination. The role of SOX12 in tumorigenesis of breast cancer is not well-understood. Here, we found that SOX12 mRNA expression was up-regulated in human breast cancer tissues. To clarify the roles of SOX12 in breast cancer, we used lentiviral shRNAs to suppress its expression in two breast cancer cells with relatively higher expression of SOX12 (BT474 and MCF-7). Our findings strongly suggested that SOX12 was critical for cell migration and invasion of breast cancer cells. We found that silencing of SOX12 significantly decreased the mRNA and protein levels of MMP9 and Twist, while notably increased E-cadherin. Moreover, SOX12 knockdown significantly inhibited the proliferation of breast cancer cells in vitro and the growth of xenograft tumours in vivo. Flow cytometry analysis revealed that breast cancer cells with SOX12 knockdown showed cell cycle arrest and decreased mRNA and protein levels of proliferating cell nuclear antigen (PCNA), CDK2 and Cyclin D1. Taken together, SOX12 plays an important role in growth inhibition through cell-cycle arrest, as well as migration and invasion of breast cancer cells. PMID:27582508

  9. Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis.

    Science.gov (United States)

    Driskell, Ryan R; Giangreco, Adam; Jensen, Kim B; Mulder, Klaas W; Watt, Fiona M

    2009-08-01

    The dermal papilla comprises the specialised mesenchymal cells at the base of the hair follicle. Communication between dermal papilla cells and the overlying epithelium is essential for differentiation of the hair follicle lineages. We report that Sox2 is expressed in all dermal papillae at E16.5, but from E18.5 onwards expression is confined to a subset of dermal papillae. In postnatal skin, Sox2 is only expressed in the dermal papillae of guard/awl/auchene follicles, whereas CD133 is expressed both in guard/awl/auchene and in zigzag dermal papillae. Using transgenic mice that express GFP under the control of the Sox2 promoter, we isolated Sox2(+) (GFP(+)) CD133(+) cells and compared them with Sox2(-) (GFP(-)) CD133(+) dermal papilla cells. In addition to the 'core' dermal papilla gene signature, each subpopulation expressed distinct sets of genes. GFP(+) CD133(+) cells had upregulated Wnt, FGF and BMP pathways and expressed neural crest markers. In GFP(-) CD133(+) cells, the hedgehog, IGF, Notch and integrin pathways were prominent. In skin reconstitution assays, hair follicles failed to form when dermis was depleted of both GFP(+) CD133(+) and GFP(-) CD133(+) cells. In the absence of GFP(+) CD133(+) cells, awl/auchene hairs failed to form and only zigzag hairs were found. We have thus demonstrated a previously unrecognised heterogeneity in dermal papilla cells and shown that Sox2-positive cells specify particular hair follicle types.

  10. Sox5 functions as a fate switch in medaka pigment cell development.

    Directory of Open Access Journals (Sweden)

    Yusuke Nagao

    2014-04-01

    Full Text Available Mechanisms generating diverse cell types from multipotent progenitors are crucial for normal development. Neural crest cells (NCCs are multipotent stem cells that give rise to numerous cell-types, including pigment cells. Medaka has four types of NCC-derived pigment cells (xanthophores, leucophores, melanophores and iridophores, making medaka pigment cell development an excellent model for studying the mechanisms controlling specification of distinct cell types from a multipotent progenitor. Medaka many leucophores-3 (ml-3 mutant embryos exhibit a unique phenotype characterized by excessive formation of leucophores and absence of xanthophores. We show that ml-3 encodes sox5, which is expressed in premigratory NCCs and differentiating xanthophores. Cell transplantation studies reveal a cell-autonomous role of sox5 in the xanthophore lineage. pax7a is expressed in NCCs and required for both xanthophore and leucophore lineages; we demonstrate that Sox5 functions downstream of Pax7a. We propose a model in which multipotent NCCs first give rise to pax7a-positive partially fate-restricted intermediate progenitors for xanthophores and leucophores; some of these progenitors then express sox5, and as a result of Sox5 action develop into xanthophores. Our results provide the first demonstration that Sox5 can function as a molecular switch driving specification of a specific cell-fate (xanthophore from a partially-restricted, but still multipotent, progenitor (the shared xanthophore-leucophore progenitor.

  11. Ablation of the Sox11 Gene Results in Clefting of the Secondary Palate Resembling the Pierre Robin Sequence.

    Science.gov (United States)

    Huang, Huarong; Yang, Xiaojuan; Bao, Meiling; Cao, Huanhuan; Miao, Xiaoping; Zhang, Xiaoyun; Gan, Lin; Qiu, Mengsheng; Zhang, Zunyi

    2016-03-25

    Mouse gene inactivation has shown that the transcription factor Sox11 is required for mouse palatogenesis. However, whether Sox11 is primarily involved in the regulation of palatogenesis still remains elusive. In this study, we explored the role ofSox11in palatogenesis by analyzing the developmental mechanism in cleft palate formation in mutants deficient in Sox11. Sox11 is expressed both in the developing palatal shelf and in the surrounding structures, including the mandible. We found that cleft palate occurs only in the mutant in which Sox11is directly deleted. As in the wild type, the palatal shelves in the Sox11 mutant undergo outgrowth in a downward direction and exhibit potential for fusion and elevation. However, mutant palatal shelves encounter clefting, which is associated with a malpositioned tongue that results in physical obstruction of palatal shelf elevation at embryonic day 14.5 (E14.5). We found that loss of Sox11led to reduced cell proliferation in the developing mandibular mesenchyme via Cyclin D1, leading to mandibular hypoplasia, which blocks tongue descent. Extensive analyses of gene expression inSox11 deficiency identified FGF9 as a potential candidate target of Sox11 in the modulation of cell proliferation both in the mandible and the palatal shelf between E12.5 and E13.5. Finally we show, using in vitro assays, that Sox11 directly regulates the expression of Fgf9 and that application of FGF9 protein to Sox11-deficient palatal shelves restores the rate of BrdU incorporation. Taken together, the palate defects presented in the Sox11 loss mutant mimic the clefting in the Pierre Robin sequence in humans.

  12. Sox10 contributes to the balance of fate choice in dorsal root ganglion progenitors

    Science.gov (United States)

    Madelaine, Romain; Busolin, Giorgia; Nikaido, Masataka; Colanesi, Sarah; Camargo-Sosa, Karen; Toppo, Stefano; Blader, Patrick; Tiso, Natascia; Kelsh, Robert N.

    2017-01-01

    The development of functional peripheral ganglia requires a balance of specification of both neuronal and glial components. In the developing dorsal root ganglia (DRGs), these components form from partially-restricted bipotent neuroglial precursors derived from the neural crest. Work in mouse and chick has identified several factors, including Delta/Notch signaling, required for specification of a balance of these components. We have previously shown in zebrafish that the Sry-related HMG domain transcription factor, Sox10, plays an unexpected, but crucial, role in sensory neuron fate specification in vivo. In the same study we described a novel Sox10 mutant allele, sox10baz1, in which sensory neuron numbers are elevated above those of wild-types. Here we investigate the origin of this neurogenic phenotype. We demonstrate that the supernumerary neurons are sensory neurons, and that enteric and sympathetic neurons are almost absent just as in classical sox10 null alleles; peripheral glial development is also severely abrogated in a manner similar to other sox10 mutant alleles. Examination of proliferation and apoptosis in the developing DRG reveals very low levels of both processes in wild-type and sox10baz1, excluding changes in the balance of these as an explanation for the overproduction of sensory neurons. Using chemical inhibition of Delta-Notch-Notch signaling we demonstrate that in embryonic zebrafish, as in mouse and chick, lateral inhibition during the phase of trunk DRG development is required to achieve a balance between glial and neuronal numbers. Importantly, however, we show that this mechanism is insufficient to explain quantitative aspects of the baz1 phenotype. The Sox10(baz1) protein shows a single amino acid substitution in the DNA binding HMG domain; structural analysis indicates that this change is likely to result in reduced flexibility in the HMG domain, consistent with sequence-specific modification of Sox10 binding to DNA. Unlike other Sox10

  13. 1 Cases of Allergic Shock Induced by Vitamin B1%维生素B1致过敏性休克1例

    Institute of Scientific and Technical Information of China (English)

    贾春燕; 贾春娟; 李延龙

    2014-01-01

    维生素B1是多种酶系统的辅酶,由此通常在临床消化系统疾病和神经损伤方面应用,维生素B1可以有效的促进消化系统功能正常协调,在临床治疗中起到辅助治疗的作用。但是在临床应用中,我们应该采用肌肉注射,因为静脉注射会发生过敏,甚至由于个体不同会发生休克或更严重导致死亡,由此在维生素B1用药过程中,一定要避免医疗事故的发生,在进行肌肉注射时应先皮试,皮试结果为阴性时再进行用药。对于维生素B1的应用我们要谨慎,在用药前一定要做好对患者各项生命体征的检测和观察,严谨用药程序,减少医疗纠纷的发生。并且在用药期间,护理人员一定要做好巡查工作,发现不良反映,应及时处理并向医生反映,并要向患者交代清楚维生素B1的禁忌和注意事项,确保用药的安全性。%Vitamin B1 enzymes system, which usual y in clinical diseases of digestive system and nerve injury, vitamin B1 can promote digestive system normal coordinate ef ective, play the role of adjuvant therapy in clinical treatment. But in practice, we should adopt the intramuscular injection, intravenous injection of al ergy occurs because, even because of dif erent individual wil shock or a more serious cause death, resulting in the process of vitamin B1 medication, must avoid medical accidents, should first skin test in intramuscular injection, skin test result is negative in medicine.The application of vitamin B1 we need to be cautious, before administration must do the detection and observation of the patient vital signs, rigorous treatment procedures, reduce medical disputes.And during the treatment, the nursing staf must do inspections, found adverse reactions, should be promptly dealt with and to reflect the doctor, and to explain clearly to the patient of vitamin B1 taboos and mat ers needing at ention, to ensure the safety of drug use.

  14. SOX2 and SOX2-MYC Reprogramming Process of Fibroblasts to the Neural Stem Cells Compromised by Senescence.

    Directory of Open Access Journals (Sweden)

    Marta Winiecka-Klimek

    Full Text Available Tumorigenic potential of induced pluripotent stem cells (iPSCs infiltrating population of induced neural stem cells (iNSCs generated from iPSCs may limit their medical applications. To overcome such a difficulty, direct reprogramming of adult somatic cells into iNSCs was proposed. The aim of this study was the systematic comparison of induced neural cells (iNc obtained with different methods-direct reprogramming of human adult fibroblasts with either SOX2 (SiNSc-like or SOX2 and c-MYC (SMiNSc-like and induced pluripotent stem cells differentiation to ebiNSc-in terms of gene expression profile, differentiation potential as well as proliferation properties. Immunocytochemistry and real-time PCR analyses were used to evaluate gene expression profile and differentiation potential of various iNc types. Bromodeoxyuridine (BrdU incorporation and senescence-associated beta-galactosidase (SA-β-gal assays were used to estimate proliferation potential. All three types of iNc were capable of neuronal differentiation; however, astrocytic differentiation was possible only in case of ebiNSc. Contrary to ebiNSc generation, the direct reprogramming was rarely a propitious process, despite 100% transduction efficiency. The potency of direct iNSCs-like cells generation was lower as compared to iNSCs obtained by iPSCs differentiation, and only slightly improved when c-MYC was added. Directly reprogrammed iNSCs-like cells were lacking the ability to differentiate into astrocytic cells and characterized by poor efficiency of neuronal cells formation. Such features indicated that these cells could not be fully reprogrammed, as confirmed mainly with senescence detection. Importantly, SiNSc-like and SMiNSc-like cells were unable to achieve the long-term survival and became senescent, which limits their possible therapeutic applicability. Our results suggest that iNSCs-like cells, generated in the direct reprogramming attempts, were either not fully reprogrammed or

  15. SerpinB1 Promotes Pancreatic β Cell Proliferation

    Energy Technology Data Exchange (ETDEWEB)

    El Ouaamari, Abdelfattah; Dirice, Ercument; Gedeon, Nicholas; Hu, Jiang; Zhou, Jian-Ying; Shirakawa, Jun; Hou, Lifei; Goodman, Jessica; Karampelias, Christos; Qiang, Guifeng; Boucher, Jeremie; Martinez, Rachael; Gritsenko, Marina A.; De Jesus, Dario F.; Kahraman, Sevim; Bhatt, Shweta; Smith, Richard D.; Beer, Hans-Dietmar; Jungtrakoon, Prapaporn; Gong, Yanping; Goldfine, Allison B.; Liew, Chong Wee; Doria, Alessandro; Andersson, Olov; Qian, Wei-Jun; Remold-O’Donnell, Eileen; Kulkarni, Rohit N.

    2016-01-01

    Compensatory β-cell growth in response to insulin resistance is a common feature in diabetes. We recently reported that liver-derived factors participate in this compensatory response in the liver insulin receptor knockout (LIRKO) mouse, a model of significant islet hyperplasia. Here we show that serpinB1 is a liver-derived secretory protein that controls β-cell proliferation. SerpinB1 is abundant in the hepatocyte secretome and sera derived from LIRKO mice. SerpinB1 and small molecule compounds that partially mimic serpinB1 activity enhanced proliferation of zebrafish, mouse and human β-cells. We report that serpinB1-induced β-cell replication requires protease inhibition activity and mice lacking serpinB1 exhibit attenuated β-cell replication in response to insulin resistance. Finally, SerpinB1-treatment of islets modulated signaling proteins in growth and survival pathways such as MAPK, PKA and GSK3. Together, these data implicate SerpinB1 as a protein that can potentially be harnessed to enhance functional β-cell mass in patients with diabetes.

  16. 26 CFR 1.7702B-1 - Consumer protection provisions.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Consumer protection provisions. 1.7702B-1 Section 1.7702B-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME...-Term Care Insurance Model Act (Model Act) and Long-Term Care Insurance Model Regulation...

  17. 77 FR 52698 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-08-30

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of...: 18 AGM-65K2 MAVERICK All-Up- Round Missiles, 36 TGM-65K2 Captive Air Training Missiles, 3...

  18. 26 CFR 301.269B-1 - Stapled foreign corporations.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Stapled foreign corporations. 301.269B-1....269B-1 Stapled foreign corporations. In accordance with section 269B(a)(1), a stapled foreign corporation is subject to the same taxes that apply to a domestic corporation under Title 26 of the...

  19. 26 CFR 1.269B-1 - Stapled foreign corporations.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Stapled foreign corporations. 1.269B-1 Section 1... (CONTINUED) INCOME TAXES Items Not Deductible § 1.269B-1 Stapled foreign corporations. (a) Treatment as a domestic corporation—(1) General rule. Except as otherwise provided, if a foreign corporation is a...

  20. CYP1B1 and hormone-induced cancer.

    Science.gov (United States)

    Gajjar, Ketan; Martin-Hirsch, Pierre L; Martin, Francis L

    2012-11-01

    Cancers in hormone-responsive tissues (e.g., breast, ovary, endometrium, prostate) occur at high incidence rates worldwide. However, their genetic basis remains poorly understood. Studies to date suggest that endogenous/exogenous oestrogen and environmental carcinogens may play a role in development and/or progression of hormone-induced cancers via oxidative oestrogen metabolism. Cytochrome P450 1B1 is a key enzyme in its oestrogen metabolism pathway, giving rise to hydroxylation and conjugation. Although CYP1B1 is expressed in many cancers, particularly high levels of expression are observed in oestrogen-mediated disease. CYP1B1 is more readily found in tumour tissue compared to normal. Given the role of CYP1B1 in pro-carcinogen and oestrogen metabolism, polymorphisms in CYP1B1 could result in modifications in its enzyme activity and subsequently lead to hormone-mediated carcinogenesis. CYP1B1 may also be involved in progression of the disease by altering the tissue response to hormones and clinical response to chemotherapy. The exact mechanism behind these events is complex and unclear. Only a few functional single nucleotide polymorphisms of CYP1B1 are known to result in amino acid substitutions and have been extensively investigated. Studies examining the contribution of different CYP1B1 alleles to hormone-mediated cancer risks are inconsistent. The main focus of this review is to appraise the available studies linking the pathogenesis of the hormone-induced cancers to various CYP1B1 polymorphisms. Additionally, we explore the role of a neuronal protein, γ-synuclein, in CYP1B1-mediated pathogenesis.

  1. Context-dependent wiring of Sox2 regulatory networks for self-renewal of embryonic and trophoblast stem cells.

    Science.gov (United States)

    Adachi, Kenjiro; Nikaido, Itoshi; Ohta, Hiroshi; Ohtsuka, Satoshi; Ura, Hiroki; Kadota, Mitsutaka; Wakayama, Teruhiko; Ueda, Hiroki R; Niwa, Hitoshi

    2013-11-07

    Sox2 is a transcription factor required for the maintenance of pluripotency. It also plays an essential role in different types of multipotent stem cells, raising the possibility that Sox2 governs the common stemness phenotype. Here we show that Sox2 is a critical downstream target of fibroblast growth factor (FGF) signaling, which mediates self-renewal of trophoblast stem cells (TSCs). Sustained expression of Sox2 together with Esrrb or Tfap2c can replace FGF dependency. By comparing genome-wide binding sites of Sox2 in embryonic stem cells (ESCs) and TSCs combined with inducible knockout systems, we found that, despite the common role in safeguarding the stem cell state, Sox2 regulates distinct sets of genes with unique functions in these two different yet developmentally related types of stem cells. Our findings provide insights into the functional versatility of transcription factors during embryogenesis, during which they can be recursively utilized in a variable manner within discrete network structures.

  2. Structural Stability, Transitions, and Interactions within SoxYZCD-Thiosulphate from Sulfurimonas denitrificans: An In Silico Molecular Outlook for Maintaining Environmental Sulphur Cycle

    Science.gov (United States)

    Banerjee, Arundhati

    2016-01-01

    Thiosulphate oxidation (an essential mechanism) serves to maintain the global sulphur cycle. Earlier experimental and computational studies dealt with environmental thiosulphate oxidation but none dealt with thiosulphate oxidation from deep ocean belts. Wet-laboratory experimental research shows that epsilon-proteobacteria Sulfurimonas denitrificans possess sox (sulphur-oxidizing) operon and perform thiosulphate oxidation efficiently underneath the oceans. From this specific sox operon, SoxCD complex recycles the thiosulphate-bound SoxY from SoxYZ complex to balance the environmental sulphur cycle. So, four chief proteins were variedly modeled and relevant simulated interactive structures were obtained. The final simulated tetraprotein complex (SoxYZCD) from docked SoxYZ and SoxCD complexes was disclosed to be a highly interactive one with predominant ionic residues. Free energy of folding, solvent accessibility, and conformational shifts (coil-like conformation to helices and sheets) were observed in SoxYZ complex after interacting with SoxCD. The stability of the complex (SoxYZCD) after simulation was also observed through the electrostatic surface potential values. These evaluations were rationalized via biostatistics. This aids SoxCD for recycling SoxY along with thiosulphate, which remains interconnected by four H-bonds with SoxY. Therefore, this novel exploration is endowed with the detailed molecular viewpoint for maintaining the sulphur cycle (globally) including the ocean belts. PMID:27777586

  3. Identification of direct regulatory targets of the transcription factor Sox10 based on function and conservation

    Directory of Open Access Journals (Sweden)

    Lee Sanghyuk

    2008-09-01

    Full Text Available Abstract Background Sox10, a member of the Sry-related HMG-Box gene family, is a critical transcription factor for several important cell lineages, most notably the neural crest stem cells and the derivative peripheral glial cells and melanocytes. Thus far, only a handful of direct target genes are known for this transcription factor limiting our understanding of the biological network it governs. Results We describe identification of multiple direct regulatory target genes of Sox10 through a procedure based on function and conservation. By combining RNA interference technique and DNA microarray technology, we have identified a set of genes that show significant down-regulation upon introduction of Sox10 specific siRNA into Schwannoma cells. Subsequent comparative genomics analyses led to potential binding sites for Sox10 protein conserved across several mammalian species within the genomic region proximal to these genes. Multiple sites belonging to 4 different genes (proteolipid protein, Sox10, extracellular superoxide dismutase, and pleiotrophin were shown to directly interact with Sox10 by chromatin immunoprecipitation assay. We further confirmed the direct regulation through the identified cis-element for one of the genes, extracellular superoxide dismutase, using electrophoretic mobility shift assay and reporter assay. Conclusion In sum, the process of combining differential expression profiling and comparative genomics successfully led to further defining the role of Sox10, a critical transcription factor for the development of peripheral glia. Our strategy utilizing relatively accessible techniques and tools should be applicable to studying the function of other transcription factors.

  4. CYP1B1: a unique gene with unique characteristics.

    Science.gov (United States)

    Faiq, Muneeb A; Dada, Rima; Sharma, Reetika; Saluja, Daman; Dada, Tanuj

    2014-01-01

    CYP1B1, a recently described dioxin inducible oxidoreductase, is a member of the cytochrome P450 superfamily involved in the metabolism of estradiol, retinol, benzo[a]pyrene, tamoxifen, melatonin, sterols etc. It plays important roles in numerous physiological processes and is expressed at mRNA level in many tissues and anatomical compartments. CYP1B1 has been implicated in scores of disorders. Analyses of the recent studies suggest that CYP1B1 can serve as a universal/ideal cancer marker and a candidate gene for predictive diagnosis. There is plethora of literature available about certain aspects of CYP1B1 that have not been interpreted, discussed and philosophized upon. The present analysis examines CYP1B1 as a peculiar gene with certain distinctive characteristics like the uniqueness in its chromosomal location, gene structure and organization, involvement in developmentally important disorders, tissue specific, not only expression, but splicing, potential as a universal cancer marker due to its involvement in key aspects of cellular metabolism, use in diagnosis and predictive diagnosis of various diseases and the importance and function of CYP1B1 mRNA in addition to the regular translation. Also CYP1B1 is very difficult to express in heterologous expression systems, thereby, halting its functional studies. Here we review and analyze these exceptional and startling characteristics of CYP1B1 with inputs from our own experiences in order to get a better insight into its molecular biology in health and disease. This may help to further understand the etiopathomechanistic aspects of CYP1B1 mediated diseases paving way for better research strategies and improved clinical management.

  5. SOX2 defect and anophthalmia and microphthalmia%SOX2基因缺陷与先天性小眼球和无眼球

    Institute of Scientific and Technical Information of China (English)

    叶福相; 范先群

    2012-01-01

    As a severe congenital developmental disorder,anophthalmia and microphthalmia are usually accompanied with vision impairment and hypoevolutism of the orbit in the affected side.Many genes are involved in anophthalmia and microphthalmia,in which,SOX2 is an important one.The defect of SOX2 causes multiple system disorders,including anophthalmia and microphthalmia.We describe the relationship between the SOX2 defect and anophthalmia/microphthalmia,in order to offer some proposals for the differential diagnosis,treatment and research of anophthalmia and microphthalmia.%先天性小眼球和无眼球是一种严重眼球先天性发育疾病,患侧通常有严重的视力障碍,同时伴有患侧眼眶发育迟缓.先天性小眼球和无眼球的发病与诸多基因相关,其中,较为重要的是SOX2基因,其缺陷可导致包括先天性无眼球和小眼球在内的多系统异常.本文对SOX2基因缺陷与先天性小眼球和无眼球之间的关系进行简要综述,为先天性小眼球和无眼球的鉴别、诊治和研究提供一定的参考.

  6. Pluripotency transcription factor Sox2 is strongly adsorbed by heparin but requires a protein transduction domain for cell internalization

    Energy Technology Data Exchange (ETDEWEB)

    Albayrak, Cem [Department of Chemical Engineering, Stanford University, 381 North-South Mall, Stanford, CA 94305 (United States); Yang, William C. [Department of Bioengineering, Stanford University, 318 Campus Drive, Stanford, CA 94305 (United States); Swartz, James R., E-mail: jswartz@stanford.edu [Department of Chemical Engineering, Stanford University, 381 North-South Mall, Stanford, CA 94305 (United States); Department of Bioengineering, Stanford University, 318 Campus Drive, Stanford, CA 94305 (United States)

    2013-02-15

    Highlights: ► Both R9Sox2 and Sox2 bind heparin with comparable affinity. ► Both R9Sox2 and Sox2 bind to fibroblasts, but only R9Sox2 is internalized. ► Internalization efficiency of R9Sox2 is 0.3% of the administered protein. ► Heparan sulfate adsorption may be part of a mechanism for managing cell death. -- Abstract: The binding of protein transduction domain (PTD)-conjugated proteins to heparan sulfate is an important step in cellular internalization of macromolecules. Here, we studied the pluripotency transcription factor Sox2, with or without the nonaarginine (R9) PTD. Unexpectedly, we observed that Sox2 is strongly adsorbed by heparin and by the fibroblasts without the R9 PTD. However, only the R9Sox2 fusion protein is internalized by the cells. These results collectively show that binding to heparan sulfate is not sufficient for cellular uptake, thereby supporting a recent hypothesis that other proteins play a role in cell internalization of PTD-conjugated proteins.

  7. TG-interacting Factor (TGIF) Downregulates SOX3 Gene Expression in the NT2/D1 Cell Line

    Institute of Scientific and Technical Information of China (English)

    Marija Mojsin; Jelena Popovic; Natasa Kovacevic Gruiicic; Milena Stevanovic

    2012-01-01

    SOX3 is a member of the Sox gene family implicated in brain formation and cognitive function.It is considered to be one of the earliest neural markers in vertebrates,playing a role in specifying neuronal fate.Recently,we have established the first link between TALE (threeamino-acid loop extension) proteins,PBX1 (pre-B-cell leukemia homeobox 1) and MEIS1 (myeloid ecotropic viral integration site 1homologue),and the expression of the human SOX3 gene.Here we present the evidence that TGIF (TG-interacting factor) is an additional TALE superfamily member involved in the regulation of human SOX3 gene expression in NT2/D1 cells by direct interaction with the consensus binding site that is conserved in primate orthologue promoters.Functional analysis demonstrated that mutation of the TGIF binding site resulted in the activation of SOX3 promoter.TGIF overexpression downregulates SOX3 promoter activity and decreases endogenous SOX3 protein expression in both uninduced and refinoic acid (RA)-induced NT2/D1 cells.Up to now,this is the first transcription factor identified as a negative regulator of SOX3 gene expression.The obtained results further underscore the significance of TALE proteins as important transcriptional regulators of SOX3 gene expression.

  8. Coordination using Implicit Communication

    CERN Document Server

    Cuff, Paul

    2011-01-01

    We explore a basic noise-free signaling scenario where coordination and communication are naturally merged. A random signal X_1,...,X_n is processed to produce a control signal or action sequence A_1,...,A_n, which is observed and further processed (without access to X_1,...,X_n) to produce a third sequence B_1,...,B_n. The object of interest is the set of empirical joint distributions p(x,a,b) that can be achieved in this setting. We show that H(A) >= I(X;A,B) is the necessary and sufficient condition for achieving p(x,a,b) when no causality constraints are enforced on the encoders. We also give results for various causality constraints. This setting sheds light on the embedding of digital information in analog signals, a concept that is exploited in digital watermarking, steganography, cooperative communication, and strategic play in team games such as bridge.

  9. Mir-21–Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact

    Science.gov (United States)

    Sathyan, Pratheesh; Zinn, Pascal O.; Marisetty, Anantha L.; Liu, Bin; Kamal, Mohamed Mostafa; Singh, Sanjay K.; Bady, Pierre; Lu, Li; Wani, Khalida M.; Veo, Bethany L.; Gumin, Joy; Kassem, Dina Hamada; Robinson, Frederick; Weng, Connie; Baladandayuthapani, Veerabhadran; Suki, Dima; Colman, Howard; Bhat, Krishna P.; Sulman, Erik P.; Aldape, Ken; Colen, Rivka R.; Verhaak, Roel G.W.; Lu, Zhimin; Fuller, Gregory N.; Huang, Suyun; Lang, Frederick F.; Sawaya, Raymond; Hegi, Monika

    2015-01-01

    Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21–Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21–Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21–Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes. SIGNIFICANCE STATEMENT Molecular profiling-based classification of glioblastoma (GBM) into four subtypes has substantially increased our understanding of the biology of the disease and has pointed to the heterogeneous nature of GBM. However, this classification is not

  10. Supercritical Fluid Extraction of Aflatoxin B 1 from Soil

    Science.gov (United States)

    This research describes the development of a Supercritical Fluid Extraction (SFE) method to recover aflatoxin B1 from fortified soil. The effects of temperature, pressure, modifier (identity and percentage), and extraction type were assessed. Using the optimized SFE conditions, ...

  11. Analysis of CYP27B1 in multiple sclerosis

    Science.gov (United States)

    Ross, Jay P; Bernales, Cecily Q; Lee, Joshua D; Sadovnick, A Dessa; Traboulsee, Anthony L; Vilariño-Güell, Carles

    2016-01-01

    The analysis of genetic variability in CYP27B1 and its effect on risk of multiple sclerosis (MS) has yielded conflicting results. Here we describe a study to genetically characterize CYP27B1 and elucidate its role on MS risk in the Canadian population. Sequencing CYP27B1 failed to identify mutations known to cause loss of enzymatic activity, however genotyping of p.R389H in cases and controls identified the mutation in one multi-incident family (allele frequency = 0.03%) in which the p.R389H mutation segregates with disease in five family members diagnosed with MS, thus providing additional support for CYP27B1 p.R389H in the pathogenicity of MS. PMID:24308945

  12. Autophagy and cellular senescence mediated by Sox2 suppress malignancy of cancer cells.

    Directory of Open Access Journals (Sweden)

    Yong-Yeon Cho

    Full Text Available Autophagy is a critical cellular process required for maintaining cellular homeostasis in health and disease states, but the molecular mechanisms and impact of autophagy on cancer is not fully understood. Here, we found that Sox2, a key transcription factor in the regulation of the "stemness" of embryonic stem cells and induced-pluripotent stem cells, strongly induced autophagic phenomena, including intracellular vacuole formation and lysosomal activation in colon cancer cells. The activation occurred through Sox2-mediated ATG10 gene expression and resulted in the inhibition of cell proliferation and anchorage-independent colony growth ex vivo and tumor growth in vivo. Further, we found that Sox2-induced-autophagy enhanced cellular senescence by up-regulating tumor suppressors or senescence factors, including p16(INK4a, p21 and phosphorylated p53 (Ser15. Notably, knockdown of ATG10 in Sox2-expressing colon cancer cells restored cancer cell properties. Taken together, our results demonstrated that regulation of autophagy mediated by Sox2 is a mechanism-driven novel strategy to treat human colon cancers.

  13. Differential Nucleosome Occupancies across Oct4-Sox2 Binding Sites in Murine Embryonic Stem Cells.

    Science.gov (United States)

    Sebeson, Amy; Xi, Liqun; Zhang, Quanwei; Sigmund, Audrey; Wang, Ji-Ping; Widom, Jonathan; Wang, Xiaozhong

    2015-01-01

    The binding sequence for any transcription factor can be found millions of times within a genome, yet only a small fraction of these sequences encode functional transcription factor binding sites. One of the reasons for this dichotomy is that many other factors, such as nucleosomes, compete for binding. To study how the competition between nucleosomes and transcription factors helps determine a functional transcription factor site from a predicted transcription factor site, we compared experimentally-generated in vitro nucleosome occupancy with in vivo nucleosome occupancy and transcription factor binding in murine embryonic stem cells. Using a solution hybridization enrichment technique, we generated a high-resolution nucleosome map from targeted regions of the genome containing predicted sites and functional sites of Oct4/Sox2 regulation. We found that at Pax6 and Nes, which are bivalently poised in stem cells, functional Oct4 and Sox2 sites show high amounts of in vivo nucleosome displacement compared to in vitro. Oct4 and Sox2, which are active, show no significant displacement of in vivo nucleosomes at functional sites, similar to nonfunctional Oct4/Sox2 binding. This study highlights a complex interplay between Oct4 and Sox2 transcription factors and nucleosomes among different target genes, which may result in distinct patterns of stem cell gene regulation.

  14. Differential Nucleosome Occupancies across Oct4-Sox2 Binding Sites in Murine Embryonic Stem Cells.

    Directory of Open Access Journals (Sweden)

    Amy Sebeson

    Full Text Available The binding sequence for any transcription factor can be found millions of times within a genome, yet only a small fraction of these sequences encode functional transcription factor binding sites. One of the reasons for this dichotomy is that many other factors, such as nucleosomes, compete for binding. To study how the competition between nucleosomes and transcription factors helps determine a functional transcription factor site from a predicted transcription factor site, we compared experimentally-generated in vitro nucleosome occupancy with in vivo nucleosome occupancy and transcription factor binding in murine embryonic stem cells. Using a solution hybridization enrichment technique, we generated a high-resolution nucleosome map from targeted regions of the genome containing predicted sites and functional sites of Oct4/Sox2 regulation. We found that at Pax6 and Nes, which are bivalently poised in stem cells, functional Oct4 and Sox2 sites show high amounts of in vivo nucleosome displacement compared to in vitro. Oct4 and Sox2, which are active, show no significant displacement of in vivo nucleosomes at functional sites, similar to nonfunctional Oct4/Sox2 binding. This study highlights a complex interplay between Oct4 and Sox2 transcription factors and nucleosomes among different target genes, which may result in distinct patterns of stem cell gene regulation.

  15. The Expression of NP847 and Sox2 after TBI and Its Influence on NSCs

    Science.gov (United States)

    Gu, Jun; Bao, Yifeng; Chen, Jian; Huang, Chuanjun; Zhang, Xinghua; Jiang, Rui; Liu, Qianqian; Liu, Yonghua; Xu, Xide; Shi, Wei

    2016-01-01

    The proliferation and differentiation of neural stem cells (NSCs) is important for neural regeneration after cerebral injury. Here, for the first time, we show that phosphorylated (p)-ser847-nNOS (NP847), rather than nNOS, may play a major role in NSC proliferation after traumatic brain injury (TBI). Western blot results demonstrated that the expression of NP847 and Sox2 in the hippocampus is up-regulated after TBI, and they both peak 3 days after brain injury. In addition, an immunofluorescence experiment indicated that NP847 and Sox2 partly co-localize in the nuclei of NSCs after TBI. Further immunoprecipitation experiments found that NP847 and Sox2 can directly interact with each other in NSCs. Moreover, in an OGD model of NSCs, NP847 expression is decreased, which is followed by the down-regulation of Sox2. Interestingly, in this study, we did not observe changes in the expression of nNOS in the OGD model. Further research data suggest that the NP847-Sox2 complex may play a major role in NSCs through the Shh/Gli signaling pathway in a CaMKII-dependent manner after brain injury. PMID:28066182

  16. Sox10 Regulates Stem/Progenitor and Mesenchymal Cell States in Mammary Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Christopher Dravis

    2015-09-01

    Full Text Available To discover mechanisms that mediate plasticity in mammary cells, we characterized signaling networks that are present in the mammary stem cells responsible for fetal and adult mammary development. These analyses identified a signaling axis between FGF signaling and the transcription factor Sox10. Here, we show that Sox10 is specifically expressed in mammary cells exhibiting the highest levels of stem/progenitor activity. This includes fetal and adult mammary cells in vivo and mammary organoids in vitro. Sox10 is functionally relevant, as its deletion reduces stem/progenitor competence whereas its overexpression increases stem/progenitor activity. Intriguingly, we also show that Sox10 overexpression causes mammary cells to undergo a mesenchymal transition. Consistent with these findings, Sox10 is preferentially expressed in stem- and mesenchymal-like breast cancers. These results demonstrate a signaling mechanism through which stem and mesenchymal states are acquired in mammary cells and suggest therapeutic avenues in breast cancers for which targeted therapies are currently unavailable.

  17. Synthesis of 4"-benzyloxyimino-4"-deoxyavermectin B1a derivatives

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Six new 4"-benzyloxyimino-4"-deoxyavermectin B1a derivatives were synthesized from avermectin B1a by the selective protection of C-5-hydroxy group, oxidation of C-4"-hydroxy group, and deprotection followed by reaction with O-substituted hydroxylamine hydrochlorides. Their structures were confirmed by IR, 1H NMR, 13C NMR and MS. Insecticidal activities of the derivatives against Phopalosiphum pseudobrassicae, Spodoptera exigua and Pluteua xylosteua were evaluated.

  18. CIAE Signs Contract on B1/B2 Project

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    CIAE signed Contract on Design,Commissioning and Technology Service for B1/B2 Project of Birine Reactor with CZEC in December,2015.The B1/B2 project which was won over by CZEC is PhaseⅠand PhaseⅡof an Algeria project which aimed to upgrade and rebuild Algeria Birine Nuclear Research Center.According to the contract with total fund amounting to 110million Yuan,CIAE will provide

  19. CYP1B1-mediated Pathobiology of Primary Congenital Glaucoma.

    Science.gov (United States)

    Faiq, Muneeb A; Dada, Rima; Qadri, Rizwana; Dada, Tanuj

    2015-01-01

    CYP1B1 is a dioxin-inducible enzyme belonging to the cytochrome P450 superfamily. It has been observed to be important in a variety of developmental processes including in utero development of ocular structures. Owing to its role in the developmental biology of eye, its dysfunction can lead to ocular developmental defects. This has been found to be true and CYP1B1 mutations have been observed in a majority of primary congenital glaucoma (PCG) patients from all over the globe. Primary congenital glaucoma is an irreversibly blinding childhood disorder (onset at birth or early infancy) typified by anomalous development of trabecular meshwork (TM). How CYP1B1 causes PCG is not known; however, some basic investigations have been reported. Understanding the CYP1B1 mediated etiopathomechanism of PCG is very important to identify targets for therapy and preventive management. In this perspective, we will make an effort to reconstruct the pathomechanism of PCG in the light of already reported information about the disease and the CYP1B1 gene. How to cite this article: Faiq MA, Dada R, Qadri R, Dada T. CYP1 B1-mediated Pathobiology of Primary Congenital Glaucoma. J Curr Glaucoma Pract 2015;9(3):77-80.

  20. Ectopic expression and knockdown of a zebrafish sox21 reveal its role as a transcriptional repressor in early development.

    Science.gov (United States)

    Argenton, Francesco; Giudici, Simona; Deflorian, Gianluca; Cimbro, Simona; Cotelli, Franco; Beltrame, Monica

    2004-02-01

    Sox proteins are DNA-binding proteins belonging to the HMG box superfamily and they play key roles in animal embryonic development. Zebrafish Sox21a is part of group B Sox proteins and its chicken and mouse orthologs have been described as transcriptional repressor and activator, respectively, in two different target gene contexts. Zebrafish sox21a is present as a maternal transcript in the oocyte and is mainly expressed at the developing midbrain-hindbrain boundary from the onset of neurulation. In order to understand its role in vivo, we ectopically expressed sox21a by microinjection. Ectopic expression of full length sox21a leads to dorsalization of the embryos. A subset of the dorsalized embryos shows a partial axis splitting, and hence an ectopic neural tube, as an additional phenotype. At gastrulation, injected embryos show expansion of the expression domains of organizer-specific genes, such as chordin and goosecoid. Molecular markers used in somitogenesis highlight that sox21a-injected embryos have shortened AP axis, undulating axial structures, enlarged or even radialized paraxial territory. The developmental abnormalities caused by ectopic expression of sox21a are suggestive of defects in convergence-extension morphogenetic movements. Antisense morpholino oligonucleotides, designed to functionally knockdown sox21a, cause ventralization of the embryos. Moreover, gain-of-function experiments with chimeric constructs, where Sox21a DNA-binding domain is fused to a transcriptional activator (VP16) or repressor (EnR) domain, suggests that zebrafish Sox21a acts as a repressor in dorso-ventral patterning.

  1. TECHNICAL COORDINATION

    CERN Multimedia

    A. Ball

    Overview From a technical perspective, CMS has been in “beam operation” state since 6th November. The detector is fully closed with all components operational and the magnetic field is normally at the nominal 3.8T. The UXC cavern is normally closed with the radiation veto set. Access to UXC is now only possible during downtimes of LHC. Such accesses must be carefully planned, documented and carried out in agreement with CMS Technical Coordination, Experimental Area Management, LHC programme coordination and the CCC. Material flow in and out of UXC is now strictly controlled. Access to USC remains possible at any time, although, for safety reasons, it is necessary to register with the shift crew in the control room before going down.It is obligatory for all material leaving UXC to pass through the underground buffer zone for RP scanning, database entry and appropriate labeling for traceability. Technical coordination (notably Stephane Bally and Christoph Schaefer), the shift crew and run ...

  2. Sox9 Expression in Amniotes: Species-Specific Differences in the Formation of Digits

    Science.gov (United States)

    Montero, Juan A.; Lorda-Diez, Carlos I.; Francisco-Morcillo, Javier; Chimal-Monroy, Jesus; Garcia-Porrero, Juan A.; Hurle, Juan M.

    2017-01-01

    In tetrapods the digit pattern has evolved to adapt to distinct locomotive strategies. The number of digits varies between species or even between hindlimb and forelimb within the same species. These facts illustrate the plasticity of embryonic limb autopods. Sox9 is a precocious marker of skeletal differentiation of limb mesenchymal cells. Its pattern of expression in the developing limb has been widely studied and reflects the activity of signaling cascades responsible for skeletogenesis. In this assay we stress previously overlooked differences in the pattern of expression of Sox9 in limbs of avian, mouse and turtle embryos which may reflect signaling differences associated with distinct limb skeletal morphologies observed in these species. Furthermore, we show that Sox9 gene expression is higher and maintained in the interdigital region in species with webbed digits in comparison with free digit animals. PMID:28386540

  3. Sox2 transcription network acts as a molecular switch to regulate properties of neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Koji; Shimozaki

    2014-01-01

    Neural stem cells(NSCs) contribute to ontogeny by producing neurons at the appropriate time and location. Neurogenesis from NSCs is also involved in various biological functions in adults. Thus, NSCs continue to exert their effects throughout the lifespan of the organism. The mechanism regulating the core functional properties of NSCs is governed by intra- and extracellular signals. Among the transcription factors that serve as molecular switches, Sox2 is considered a key factor in NSCs. Sox2 forms a core network with partner factors, thereby functioning as a molecular switch. This review discusses how the network of Sox2 partner and target genes illustrates the molecular characteristics of the mechanism underlying the self-renewal and multipotency of NSCs.

  4. Genome duplication, subfunction partitioning, and lineage divergence: Sox9 in stickleback and zebrafish.

    Science.gov (United States)

    Cresko, William A; Yan, Yi-Lin; Baltrus, David A; Amores, Angel; Singer, Amy; Rodríguez-Marí, Adriana; Postlethwait, John H

    2003-11-01

    Teleosts are the most species-rich group of vertebrates, and a genome duplication (tetraploidization) event in ray-fin fish appears to have preceded this remarkable explosion of biodiversity. What is the relationship of the ray-fin genome duplication to the teleost radiation? Genome duplication may have facilitated lineage divergence by partitioning different ancestral gene subfunctions among co-orthologs of tetrapod genes in different teleost lineages. To test this hypothesis, we investigated gene expression patterns for Sox9 gene duplicates in stickleback and zebrafish, teleosts whose lineages diverged early in Euteleost evolution. Most expression domains appear to have been partitioned between Sox9a and Sox9b before the divergence of stickleback and zebrafish lineages, but some ancestral expression domains were distributed differentially in each lineage. We conclude that some gene subfunctions, as represented by lineage-specific expression domains, may have assorted differently in separate lineages and that these may have contributed to lineage diversification during teleost evolution.

  5. Evidence for the eta_b(1S) in the Decay Upsilon(2S)-> gamma eta_b(1S)

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B.; Bona, M.; Karyotakis, Y.; Lees, J.P.; Poireau, V.; Prencipe, E.; Prudent, X.; Tisserand, V.; /Annecy, LAPP; Garra Tico, J.; Grauges, E.; /Barcelona U., ECM; Lopez, L.; Palano, A.; Pappagallo, M.; /INFN, Bari /Bari U.; Eigen, G.; Stugu, B.; Sun, L.; /Bergen U.; Battaglia, M.; Brown, D.N.; Kerth, L.T.; Kolomensky, Yu.G.; Lynch, G.; /LBL, Berkeley /UC, Berkeley /Birmingham U. /Ruhr U., Bochum /British Columbia U. /Brunel U. /Novosibirsk, IYF /UC, Irvine /UCLA /UC, Riverside /UC, San Diego /UC, Santa Barbara /UC, Santa Cruz /Caltech /Cincinnati U. /Colorado U. /Colorado State U. /Dortmund U. /Dresden, Tech. U. /Ecole Polytechnique /Edinburgh U. /INFN, Ferrara /Ferrara U. /INFN, Ferrara /INFN, Ferrara /Ferrara U. /INFN, Ferrara /INFN, Ferrara /Ferrara U. /Frascati /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /Harvard U. /Heidelberg U. /Humboldt U., Berlin /Imperial Coll., London /Iowa U. /Iowa State U. /Johns Hopkins U. /Orsay, LAL /LLNL, Livermore /Liverpool U. /Queen Mary, U. of London /Royal Holloway, U. of London /Louisville U. /Karlsruhe U., EKP /Manchester U. /Maryland U. /Massachusetts U., Amherst /MIT, LNS /McGill U. /INFN, Milan /Milan U. /INFN, Milan /INFN, Milan /Milan U. /Mississippi U. /Montreal U. /Mt. Holyoke Coll. /INFN, Naples /Naples U. /INFN, Naples /INFN, Naples /Naples U. /NIKHEF, Amsterdam /Notre Dame U. /Ohio State U. /Oregon U. /INFN, Padua /Padua U. /INFN, Padua /INFN, Padua /Padua U. /Paris U., VI-VII /Pennsylvania U. /INFN, Perugia /Perugia U. /INFN, Pisa /Pisa U. /INFN, Pisa /Pisa, Scuola Normale Superiore /INFN, Pisa /Pisa U. /INFN, Pisa /Princeton U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /Rostock U. /Rutherford /DSM, DAPNIA, Saclay /South Carolina U. /SLAC /Stanford U., Phys. Dept. /SUNY, Albany /Tennessee U. /Texas U. /Texas U., Dallas /INFN, Turin /Turin U. /INFN, Trieste /Trieste U. /Valencia U., IFIC /Victoria U. /Warwick U. /Wisconsin U., Madison

    2009-12-14

    We have performed a search for the {eta}{sub b}(1S) meson in the radiative decay of the {Upsilon}(2S) resonance using a sample of 91.6 million {Upsilon}(2S) events recorded with the BABAR detector at the PEP-II B factory at the SLAC National Accelerator Laboratory. We observe a peak in the photon energy spectrum at E{sub {gamma}} = 610.5{sub -4.3}{sup +4.5}(stat) {+-} 1.8(syst) MeV, corresponding to an {eta}{sub b}(1S) mass of 9392.9{sub -4.8}{sup +4.6}(stat) {+-} 1.9(syst) MeV/c{sup 2}. The branching fraction for the decay {Upsilon}(2S) {yields} {gamma}{eta}{sub b}(1S) is determined to be (4.2{sub -1.0}{sup +1.1}(stat) {+-} 0.9(syst)) x 10{sup -4}. The ratio {Beta}({Upsilon}(2S) {yields} {gamma}{eta}{sub b}(1S))/{Beta}({Upsilon}(3S) {yields} {gamma}{eta}{sub b}(1S)) = 0.89{sub -0.23}{sup +0.25}(stat){sub -0.16}{sup +0.12}(syst) is consistent with the ratio expected for magnetic dipole transitions to the {eta}{sub b}(1S) meson.

  6. Occurrence of aflatoxin B1 in natural products

    Directory of Open Access Journals (Sweden)

    Guilherme Prado

    2012-12-01

    Full Text Available The media claims for the consumption of natural resource-based food have gradually increased in both developing and developed countries. The interest in the safety of these products is partially due to the possible presence of toxigenic fungi acting as mycotoxin producers, such as aflatoxins produced during the secondary metabolism of Aspergillus flavus, A. parasiticus and A. nomius. Aflatoxins, mainly aflatoxin B1, are directly associated with liver cancer in human beings. This paper is aimed at evaluating the presence of aflatoxin B1 in a few vegetable drugs, dried plant extracts and industrialized products traded in 2010 in the city of Belo Horizonte, State of Minas Gerais, Brazil. The method used for the quantification of aflatoxin B1 was based on extraction through acetone:water (85:15, immunoaffinity column purification followed by separation and detection in high efficiency liquid chromatography. Under the conditions of analysis, the Limits of Detection and Quantification were 0.6 µg kg-1 and 1.0 µg kg-1respectively. The complete sets of analyses were carried out in duplicate. Aflatoxin B1 was noticed in a single sample (< 1.0 µg kg-1. The results revealed low aflatoxin B1contamination in the products under analysis. However, it is required to establish a broad monitoring program in order to obtain additional data and check up on the actual extension of contamination.

  7. SerpinB1 Promotes Pancreatic β Cell Proliferation.

    Science.gov (United States)

    El Ouaamari, Abdelfattah; Dirice, Ercument; Gedeon, Nicholas; Hu, Jiang; Zhou, Jian-Ying; Shirakawa, Jun; Hou, Lifei; Goodman, Jessica; Karampelias, Christos; Qiang, Guifeng; Boucher, Jeremie; Martinez, Rachael; Gritsenko, Marina A; De Jesus, Dario F; Kahraman, Sevim; Bhatt, Shweta; Smith, Richard D; Beer, Hans-Dietmar; Jungtrakoon, Prapaporn; Gong, Yanping; Goldfine, Allison B; Liew, Chong Wee; Doria, Alessandro; Andersson, Olov; Qian, Wei-Jun; Remold-O'Donnell, Eileen; Kulkarni, Rohit N

    2016-01-12

    Although compensatory islet hyperplasia in response to insulin resistance is a recognized feature in diabetes, the factor(s) that promote β cell proliferation have been elusive. We previously reported that the liver is a source for such factors in the liver insulin receptor knockout (LIRKO) mouse, an insulin resistance model that manifests islet hyperplasia. Using proteomics we show that serpinB1, a protease inhibitor, which is abundant in the hepatocyte secretome and sera derived from LIRKO mice, is the liver-derived secretory protein that regulates β cell proliferation in humans, mice, and zebrafish. Small-molecule compounds, that partially mimic serpinB1 effects of inhibiting elastase activity, enhanced proliferation of β cells, and mice lacking serpinB1 exhibit attenuated β cell compensation in response to insulin resistance. Finally, SerpinB1 treatment of islets modulated proteins in growth/survival pathways. Together, these data implicate serpinB1 as an endogenous protein that can potentially be harnessed to enhance functional β cell mass in patients with diabetes.

  8. Glaucoma and Cytochrome P4501B1 Gene Mutations

    Directory of Open Access Journals (Sweden)

    Mukesh Tanwar

    2010-01-01

    Full Text Available Developmental anomalies of the ocular anterior chamber angle may lead to an incomplete development of the structures that form the conventional aqueous outflow pathway. Thus, disorders that present with such dysfunction tend to be associated with glaucoma. Among them, Axenfeld-Rieger (ARS malformation is a rare clinical entity with an estimated prevalence of one in every 200,000 individuals. The changes in eye morphogenesis in ARS are highly penetrant and are associated with 50% risk of development of glaucoma. Mutations in the cytochrome P4501B1 (CYP1B1 gene have been reported to be associated with primary congenital glaucoma and other forms of glaucoma and mutations in pituitary homeobox 2 (PITX2 gene have been identified in ARS in various studies. This case was negative for PITX2 mutations and compound heterozygote for CYP1B1 mutations. Clinical manifestations of this patient include bilateral elevated intraocular pressure (>40 mmHg with increased corneal diameter (>14 mm and corneal opacity. Patient also had iridocorneal adhesions, anteriorly displaced Schwalbe line, anterior insertion of iris, broad nasal bridge and protruding umbilicus. This is the first study from north India reporting CYP1B1 mutations in Axenfeld-Rieger syndrome with bilateral buphthalmos and early onset glaucoma. Result of this study supports the role of CYP1B1 as a causative gene in ASD disorders and its role in oculogenesis.

  9. Elevated Levels of SOX10 in Serum from Vitiligo and Melanoma Patients, Analyzed by Proximity Ligation Assay.

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    Andries Blokzijl

    Full Text Available The diagnosis of malignant melanoma currently relies on clinical inspection of the skin surface and on the histopathological status of the excised tumor. The serum marker S100B is used for prognostic estimates at later stages of the disease, but analyses are marred by false positives and inadequate sensitivity in predicting relapsing disorder.To investigate SOX10 as a potential biomarker for melanoma and vitiligo.In this study we have applied proximity ligation assay (PLA to detect the transcription factor SOX10 as a possible serum marker for melanoma. We studied a cohort of 110 melanoma patients. We further investigated a second cohort of 85 patients with vitiligo, which is a disease that also affects melanocytes.The specificity of the SOX10 assay in serum was high, with only 1% of healthy blood donors being positive. In contrast, elevated serum SOX10 was found with high frequency among vitiligo and melanoma patients. In patients with metastases, lack of SOX10 detection was associated with treatment benefit. In two responding patients, a change from SOX10 positivity to undetectable levels was seen before the response was evident clinically.We show for the first time that SOX10 represents a promising new serum melanoma marker for detection of early stage disease, complementing the established S100B marker. Our findings imply that SOX10 can be used to monitor responses to treatment and to assess if the treatment is of benefit at stages earlier than what is possible radiologically.

  10. The transcription factor SOX18 regulates the expression of matrix metalloproteinase 7 and guidance molecules in human endothelial cells.

    Directory of Open Access Journals (Sweden)

    Martina Hoeth

    Full Text Available Mutations in the transcription factor SOX18 are responsible for specific cardiovascular defects in humans and mice. In order to gain insight into the molecular basis of its action, we identified target genes of SOX18 and analyzed one, MMP7, in detail.SOX18 was expressed in HUVEC using a recombinant adenoviral vector and the altered gene expression profile was analyzed using microarrays. Expression of several regulated candidate SOX18 target genes was verified by real-time PCR. Knock-down of SOX18 using RNA interference was then used to confirm the effect of the transcription factor on selected genes that included the guidance molecules ephrin B2 and semaphorin 3G. One gene, MMP7, was chosen for further analysis, including detailed promoter studies using reporter gene assays, electrophoretic mobility shift analysis and chromatin-immunoprecipitation, revealing that it responds directly to SOX18. Immunohistochemical analysis demonstrated the co-expression of SOX18 and MMP7 in blood vessels of human skin.The identification of MMP7 as a direct SOX18 target gene as well as other potential candidates including guidance molecules provides a molecular basis for the proposed function of this transcription factor in the regulation of vessel formation.

  11. Sox17-Mediated XEN Cell Conversion Identifies Dynamic Networks Controlling Cell-Fate Decisions in Embryo-Derived Stem Cells

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    Angela C.H. McDonald

    2014-10-01

    Full Text Available Little is known about the gene regulatory networks (GRNs distinguishing extraembryonic endoderm (ExEn stem (XEN cells from those that maintain the extensively characterized embryonic stem cell (ESC. An intriguing network candidate is Sox17, an essential transcription factor for XEN derivation and self-renewal. Here, we show that forced Sox17 expression drives ESCs toward ExEn, generating XEN cells that contribute to ExEn when placed back into early mouse embryos. Transient Sox17 expression is sufficient to drive this fate change during which time cells transit through distinct intermediate states prior to the generation of functional XEN-like cells. To orchestrate this conversion process, Sox17 acts in autoregulatory and feedforward network motifs, regulating dynamic GRNs directing cell fate. Sox17-mediated XEN conversion helps to explain the regulation of cell-fate changes and reveals GRNs regulating lineage decisions in the mouse embryo.

  12. Over-expression of Sox4 and β-catenin is associated with a less favorable prognosis of osteosarcoma.

    Science.gov (United States)

    Bao, Zheng-Qi; Zhang, Chang-chun; Xiao, Yu-zhou; Zhou, Jian-sheng; Tao, Yi-sheng; Chai, Da-min

    2016-04-01

    The purpose of this study was to examine the association of the expression of Sox4 and β-catenin with the prognosis of osteosarcoma. A total of 108 cases of conventional osteosarcoma were involved in this study and 28 cases of osteochondroma served as controls. The expression of Sox4 and β-catenin was detected by using immunohistochemical staining and Western blotting. The results showed that Sox4 and β-catenin were over-expressed in 67 (62.03%) and 62 (57.41%) of 108 osteosarcoma cases, while in only 3 (10.71%) and 5 (17.86%) of 28 controls, respectively (Posteosarcoma (Posteosarcoma patients with Sox4 and β-catenin over-expressed were significantly reduced as compared with those in Sox4 and β-catenin low-expression group (Posteosarcoma (Posteosarcoma.

  13. Transmission and Demographic Dynamics of Coxsackievirus B1.

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    Pei-Yu Chu

    Full Text Available The infectious activity of coxsackievirus B1 (CV-B1 in Taiwan was high from 2008 to 2010, following an alarming increase in severe neonate disease in the United States (US. To examine the relationship between CV-B1 strains isolated in Taiwan and those from other parts of the world, we performed a phylodynamic study using VP1 and partial 3Dpol (414 nt sequences from 22 strains of CV-B1 isolated in Taiwan (1989-2010 and compared them to sequences from strains isolated worldwide. Phylogenetic trees were constructed by neighbor-joining, maximum likelihood, and Bayesian Monte Carlo Markov Chain methods. Four genotypes (GI-IV in the VP1 region of CV-B1 and three genotypes (GA-C in the 3Dpol region of enterovirus B were identified and had high support values. The phylogenetic analysis indicates that the GI and GIII strains in VP1 were geographically distributed in Taiwan (1993-1994 and in India (2007-2009. On the other hand, the GII and GIV strains appear to have a wider spatiotemporal distribution and ladder-like topology A stair-like phylogeny was observed in the VP1 region indicating that the phylogeny of the virus may be affected by different selection pressures in the specified regions. Further, most of the GI and GII strains in the VP1 tree were clustered together in GA in the 3D tree, while the GIV strains diverged into GB and GC. Taken together, these data provide important insights into the population dynamics of CV-B1 and indicate that incongruencies in specific gene regions may contribute to spatiotemporal patterns of epidemicity for this virus.

  14. TECHNICAL COORDINATION

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    A. Ball

    2010-01-01

    Operational Experience At the end of the first full-year running period of LHC, CMS is established as a reliable, robust and mature experiment. In particular common systems and infrastructure faults accounted for <0.6 % CMS downtime during LHC pp physics. Technical operation throughout the entire year was rather smooth, the main faults requiring UXC access being sub-detector power systems and rack-cooling turbines. All such problems were corrected during scheduled technical stops, in the shadow of tunnel access needed by the LHC, or in negotiated accesses or access extensions. Nevertheless, the number of necessary accesses to the UXC averaged more than one per week and the technical stops were inevitably packed with work packages, typically 30 being executed within a few days, placing a high load on the coordination and area management teams. It is an appropriate moment for CMS Technical Coordination to thank all those in many CERN departments and in the Collaboration, who were involved in CMS techni...

  15. Construction of recombinant baculovirus Ac-CMV-hSox9 for gene therapy of intervertebral disc degeneration

    Institute of Scientific and Technical Information of China (English)

    LIU Xiao-yun; YANG Shu-hua; LIANG Chang-yong; SONG Jian-hua; LI Kang-hua; CHEN Xin-wen

    2007-01-01

    Objective: To construct the recombinant baculovirus Ac-cytomegalovirus (CMV)-hSox9 for gene therapy of intervertebral disc degeneration. Methods: Bac-to-Bac system was used for the construction of baculovirus Ac-CMV-hSox9. The cDNA of hSox9 was first cloned into a plasmid vector under the control of CMV promotor to generate the donor plasmid pFastBacDul-green fluorescene protein (GFP)-CMV (pFGC)-hSox9.The resultant plasmid was transformed into DH10Bac cells and then the transformation mixture was spread on Luria-Bertani (LB) agarose culture medium containing isopropyl-β-D-thiogalactoside (IPTG), X-gal, gentamicin, kanamycin and tetracycline.The white colonies were selected and cultured for amplification, and the hSox9Bacmid DNA was extracted. After verification, recombinant baculovirus Ac-CMV-hSox9 was obtained through transfecting Sf 21 cells.The expression of hSox9 gene in the intervertebral disc cells in rabbits was determined by Western blotting and immunohistochemical staining.Results: Polymerase chain reaction (PCR) confirmed the presence of hSox9 gene in the recombinant baculovirus and the Sf 21 cells transfected by the baculovirus showed the expression of fluorescence protein.Western blotting and immunohistochemical staining analysis indicated that exogenous hSox9 gene was expressed in the disc cells.Conclusions: The successful construction of the recombinant baculovirus Ac-CMV-hSox9 and the confirmation of the target gene expression provides a novel expression vector system for basic research and clinical treatment of intervertebral degenerative disc disease.

  16. SOX2 gene regulates the transcriptional network of oncogenes and affects tumorigenesis of human lung cancer cells.

    Science.gov (United States)

    Chen, Si; Xu, Yingxi; Chen, Yanan; Li, Xuefei; Mou, Wenjun; Wang, Lina; Liu, Yanhua; Reisfeld, Ralph A; Xiang, Rong; Lv, Dan; Li, Na

    2012-01-01

    Recent studies demonstrated that cancer stem cells (CSCs) have higher tumorigenesis properties than those of differentiated cancer cells and that transcriptional factor-SOX2 plays a vital role in maintaining the unique properties of CSCs; however, the function and underlying mechanism of SOX2 in carcinogenesis of lung cancer are still elusive. This study applied immunohistochemistry to analyze the expression of SOX2 in human lung tissues of normal individuals as well as patients with adenocarcinoma, squamous cell carcinoma, and large cell and small cell carcinoma and demonstrated specific overexpression of SOX2 in all types of lung cancer tissues. This finding supports the notion that SOX2 contributes to the tumorigenesis of lung cancer cells and can be used as a diagnostic probe. In addition, obviously higher expression of oncogenes c-MYC, WNT1, WNT2, and NOTCH1 was detected in side population (SP) cells than in non-side population (NSP) cells of human lung adenocarcinoma cell line-A549, revealing a possible mechanism for the tenacious tumorigenic potential of CSCs. To further elucidate the function of SOX2 in tumorigenesis of cancer cells, A549 cells were established with expression of luciferase and doxycycline-inducible shRNA targeting SOX2. We found silencing of SOX2 gene reduces the tumorigenic property of A549 cells with attenuated expression of c-MYC, WNT1, WNT2, and NOTCH1 in xenografted NOD/SCID mice. By using the RNA-Seq method, an additional 246 target cancer genes of SOX2 were revealed. These results present evidence that SOX2 may regulate the expression of oncogenes in CSCs to promote the development of human lung cancer.

  17. 5-Azacytidine suppresses EC9706 cell proliferation and metastasis by upregulating the expression of SOX17 and CDH1.

    Science.gov (United States)

    Li, Wenli; Wu, Dan; Niu, Ziyu; Jiang, Dalei; Ma, Huan; He, Heming; Zuo, Xiuli; Xie, Xiangjun; He, Yuanlong

    2016-10-01

    5-Azacytidine is a well-known anticancer drug that is clinically used in the treatment of breast cancer, melanoma and colon cancer. It has been reported that 5-azacytidine suppresses the biological behavior of esophageal cancer cells. However, corresponding mechanisms remain unclear. In this study, using Transwell invasion and cell proliferation assays, we demonstrated that 5-azacytidine significantly inhibited the metastasis and proliferation of EC9706 cells, and upregulated the expression of cadherin 1 (CDH1) and SRY-box containing gene 17 (SOX17). Moreover, the inhibition of the metastasis of the 5-azacytidine-treated EC9706 cells was impaired following transfection with siRNA targeting CDH1 (CDH1 siRNA), and the inhibition of cell proliferation was attenuated following the downregulation of SOX17 by siRNA targeting SOX17 (SOX17 siRNA). Furthermore, 5-azacytidine remarkably reduced the CDH1 and SOX17 promoter methylation levels, suggesting that 5-azacytidine upregulates the expression of SOX17 and CDH1 by inhibiting the methylation of the SOX17 and CDH1 promoter. The findings of our study confirm that 5-azacytidine suppresses the proliferation and metastasis of EC9706 esophageal cancer cells by upregulating the expression of CDH1 and SOX17. The expression levels of CDH1 and SOX17 negatively correlate with the promoter methylation levels. CDH1 and SOX17 are potential indicators of the clinical application of 5-azacytidine.

  18. SOX2 gene regulates the transcriptional network of oncogenes and affects tumorigenesis of human lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Si Chen

    Full Text Available Recent studies demonstrated that cancer stem cells (CSCs have higher tumorigenesis properties than those of differentiated cancer cells and that transcriptional factor-SOX2 plays a vital role in maintaining the unique properties of CSCs; however, the function and underlying mechanism of SOX2 in carcinogenesis of lung cancer are still elusive. This study applied immunohistochemistry to analyze the expression of SOX2 in human lung tissues of normal individuals as well as patients with adenocarcinoma, squamous cell carcinoma, and large cell and small cell carcinoma and demonstrated specific overexpression of SOX2 in all types of lung cancer tissues. This finding supports the notion that SOX2 contributes to the tumorigenesis of lung cancer cells and can be used as a diagnostic probe. In addition, obviously higher expression of oncogenes c-MYC, WNT1, WNT2, and NOTCH1 was detected in side population (SP cells than in non-side population (NSP cells of human lung adenocarcinoma cell line-A549, revealing a possible mechanism for the tenacious tumorigenic potential of CSCs. To further elucidate the function of SOX2 in tumorigenesis of cancer cells, A549 cells were established with expression of luciferase and doxycycline-inducible shRNA targeting SOX2. We found silencing of SOX2 gene reduces the tumorigenic property of A549 cells with attenuated expression of c-MYC, WNT1, WNT2, and NOTCH1 in xenografted NOD/SCID mice. By using the RNA-Seq method, an additional 246 target cancer genes of SOX2 were revealed. These results present evidence that SOX2 may regulate the expression of oncogenes in CSCs to promote the development of human lung cancer.

  19. Effect of sox19b gene knockdown on the eyes development in zebra fish%sox19b在斑马鱼胚胎眼睛发育中的作用

    Institute of Scientific and Technical Information of China (English)

    高明; 杨阳; 陈学冉; 史玮; 林浴霜; 郝爱军

    2013-01-01

    Objective To explore the function of sox19b on the eye development in zebrafish by knockdown of sox19b. Methods To inhibit the expression of sox196 by microinjection of soxl9b morpholinos( MO)and then observe the effect of the development of the eyes in zebrafish by RT-PCR and the whole-mount in situ hybridization. Results The development of the eyes was abnormal after knockdown of sox 196, mainly showed small eyes or eye deficiency and the abnormal retina and lens( n = 57/93 ) . The expression of some important genes during the development of the eyes, such as rx3, pax2a and vsx2, was decreased apparently in the sox19b morphant. Conclusion The transcription factor, sox196 is critical for the development of the eyes via the regulation of the important eye-field transcription factors, EFTEs in early zebrafish embryos.%目的 通过抑制sox19b基因的表达,探讨sox19b基因在斑马鱼胚胎眼睛发育和形成中的作用.方法 通过显微注射sox19b吗啉寡聚核苷酸(MO)抑制sox19b基因的表达,观察胚胎发育过程中表型的变化;采用石蜡包埋组织切片及HE染色、RT-PCR和整封原位杂交等方法探讨敲除sox19b后对斑马鱼胚胎眼睛发育的调控机制.结果 敲除sox19b基因后,斑马鱼胚胎眼睛发育受到影响,表现为眼睛变小或缺失,视网膜及晶状体结构发育异常(n=57/93);眼睛发育过程中重要调控基因rx3、pax2a及vsx2等表达明显降低,进而影响眼睛的发育和形成.结论 sox19b基因作为转录调控因子,可以通过调节眼区转录因子的表达进而影响斑马鱼胚胎早期眼睛的发育和形成.

  20. Derivation of an endogenous small RNA from double-stranded Sox4 sense and natural antisense transcripts in the mouse brain.

    Science.gov (United States)

    Ling, King-Hwa; Brautigan, Peter J; Moore, Sarah; Fraser, Rachel; Cheah, Pike-See; Raison, Joy M; Babic, Milena; Lee, Young Kyung; Daish, Tasman; Mattiske, Deidre M; Mann, Jeffrey R; Adelson, David L; Thomas, Paul Q; Hahn, Christopher N; Scott, Hamish S

    2016-03-01

    Natural antisense transcripts (NATs) are involved in cellular development and regulatory processes. Multiple NATs at the Sox4 gene locus are spatiotemporally regulated throughout murine cerebral corticogenesis. In the study, we evaluated the potential functional role of Sox4 NATs at Sox4 gene locus. We demonstrated Sox4 sense and NATs formed dsRNA aggregates in the cytoplasm of brain cells. Over expression of Sox4 NATs in NIH/3T3 cells generally did not alter the level of Sox4 mRNA expression or protein translation. Upregulation of a Sox4 NAT known as Sox4ot1 led to the production of a novel small RNA, Sox4_sir3. Its biogenesis is Dicer1-dependent and has characteristics resemble piRNA. Expression of Sox4_sir3 was observed in the marginal and germinative zones of the developing and postnatal brains suggesting a potential role in regulating neurogenesis. We proposed that Sox4 sense-NATs serve as Dicer1-dependent templates to produce a novel endo-siRNA- or piRNA-like Sox4_sir3.

  1. Coordination Capacity

    CERN Document Server

    Cuff, Paul; Cover, Thomas

    2009-01-01

    We develop elements of a theory of cooperation and coordination in networks. Rather than considering a communication network as a means of distributing information, or of reconstructing random processes at remote nodes, we ask what dependence can be established among the nodes given the communication constraints. Specifically, in a network with communication rates between the nodes, we ask what is the set of all achievable joint distributions p(x1, ..., xm) of actions at the nodes on the network. Several networks are solved, including arbitrarily large cascade networks. Distributed cooperation can be the solution to many problems such as distributed games, distributed control, and establishing mutual information bounds on the influence of one part of a physical system on another.

  2. 78 FR 699 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-01-04

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... goals and national security objectives of the United States by meeting the legitimate security and... dissemination. It can be either fixed or mobile. In addition to the shelter housing the operator...

  3. βB1-crystallin: thermodynamic profiles of molecular interactions.

    Directory of Open Access Journals (Sweden)

    Monika B Dolinska

    Full Text Available BACKGROUND: β-Crystallins are structural proteins maintaining eye lens transparency and opacification. Previous work demonstrated that dimerization of both βA3 and βB2 crystallins (βA3 and βB2 involves endothermic enthalpy of association (∼8 kcal/mol mediated by hydrophobic interactions. METHODOLOGY/PRINCIPAL FINDINGS: Thermodynamic profiles of the associations of dimeric βA3 and βB1 and tetrameric βB1/βA3 were measured using sedimentation equilibrium. The homo- and heteromolecular associations of βB1 crystallin are dominated by exothermic enthalpy (-13.3 and -24.5 kcal/mol, respectively. CONCLUSIONS/SIGNIFICANCE: Global thermodynamics of βB1 interactions suggest a role in the formation of stable protein complexes in the lens via specific van der Waals contacts, hydrogen bonds and salt bridges whereas those β-crystallins which associate by predominately hydrophobic forces participate in a weaker protein associations.

  4. 78 FR 36536 - 36(b)(1) Arms Sales Notification

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    2013-06-18

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... Department: Navy (GGW) (v) Prior Related Cases, if any: Multiple FMS cases dating back to 1997 (vi)...

  5. 76 FR 72180 - 36(b)(1) Arms Sales Notification

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    2011-11-22

    ... require travel of U.S. Government or contractor representatives to Malaysia on a temporary basis for... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense...

  6. 78 FR 62600 - 36(b)(1) Arms Sales Notification

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    2013-10-22

    ... circuits are classified Secret. The hardware, software, and data identified are classified to protect... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... data, U.S. Government and contractor technical assistance and other related logistics support,...

  7. 77 FR 13564 - 36(b)(1) Arms Sales Notification

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    2012-03-07

    .... The hardware, software, and data identified are classified to protect vulnerabilities, design and... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... data, U.S. Government and contractor technical assistance and other related logistics support. \\*\\...

  8. 76 FR 61673 - 36(b)(1) Arms Sales Notification

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    2011-10-05

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security..., APX-72 Transponder, AN/ARN-147 VOR/ILS, AN/ARN-149 Receiver (ADF), HF-9000 HF Radio, ASN-150 Tactical... RADAR, ARC-210 UHF Radio, APX-72 Transponder, AN/ARN- 147 VOR/ILS, AN/ARN-149 Receiver (ADF), HF-9000...

  9. 78 FR 36534 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-06-18

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... representatives to travel to Thailand for a period of five weeks for equipment de-processing/fielding,...

  10. 78 FR 41040 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-07-09

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency.... Government and contractor representatives to travel to the region to support the program. There will be...

  11. 26 CFR 31.3306(b)-1 - Wages.

    Science.gov (United States)

    2010-04-01

    ... Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Federal Unemployment Tax Act (Chapter 23, Internal Revenue Code of 1954) § 31.3306(b)-1 Wages. (a) Applicable law...

  12. 26 CFR 1.167(b)-1 - Straight line method.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Straight line method. 1.167(b)-1 Section 1.167(b... Straight line method. (a) In general. Under the straight line method the cost or other basis of the... may be reduced to a percentage or fraction. The straight line method may be used in determining...

  13. 78 FR 62592 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-10-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... Republic of Singapore to contribute to regional security. Its contributions to counter-piracy...

  14. 78 FR 22848 - 36(b)(1) Arms Sales Notification

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    2013-04-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... regional security. Its contributions to counter-piracy and counterterrorism efforts continue to stabilize...

  15. 78 FR 50045 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-08-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... its borders and littoral waters, as well as conduct counter- terrorism/counter-piracy operations....

  16. 78 FR 22850 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-04-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... contributions to counter-piracy and counterterrorism efforts continue to stabilize a critical chokepoint...

  17. 78 FR 50047 - 36(b)(1) Arms Sales Notification

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    2013-08-16

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... for Purchase: 19 Mobile Troposcatter Radio Systems, 10 Mobile Microwave Radio Systems, spare and... Technology Contained in the Defense Article or Defense Services Proposed to be Sold: None (viii) Date...

  18. 78 FR 15004 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-03-08

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... Representatives, Transmittals 12-60 with attached transmittal, policy justification, and Sensitivity of Technology... RAPISCAN Mobile Eagle High Energy Mobile System Vehicles, 40 M60 RAPISCAN Mobile Eagle High Energy...

  19. 76 FR 66048 - 36(b)(1) Arms Sales Notification

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    2011-10-25

    ... Technology: 1. The AVENGER system is a lightweight, highly mobile, and transportable surface-to-air missile... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... Representatives, Transmittals 11-38 with attached transmittal, policy justification, and Sensitivity of...

  20. 78 FR 50043 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-08-16

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... Representatives, Transmittals 12-67 with attached transmittal, policy justification, and Sensitivity of Technology... Illuminator Radars, 216 MIM-23P HAWK Tactical Missiles, 2 Mobile Battalion Operation Centers (BOC), 3 HAWK...

  1. 78 FR 41036 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-07-09

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... Representatives, Transmittal 13-40 with attached transmittal, policy justification, and Sensitivity of Technology... Reaper Remotely Piloted Aircraft 8 Mobile Ground Control Stations 48 Honeywell TPE331-10T...

  2. Dynamic distribution and stem cell characteristics of Sox1-expressing cells in the cerebellar cortex

    Institute of Scientific and Technical Information of China (English)

    Joelle Alcock; Virginie Sottile

    2009-01-01

    Bergmann glia cells are a discrete radial glia population surrounding Purkinje cells in the cerebellar cortex. Al-though Bergmann glia are essential for the development and correct arborization of Purkinje cells, little is known about the regulation of this cell population after the developmental phase. In an effort to characterize this population at the molecular level, we have analyzed marker expression and established that adult Bergmann glia express Soxl, Sox2 and Sox9, a feature otherwise associated with neural stem cells (NSCs). In the present study, we have further analyzed the developmental pattern of Soxl-expressing cells in the developing cerebellum. We report that before be-coming restricted to the Purkinje cell layer, Soxl-positive cells are present throughout the immature tissue, and that these cells show characteristics of Bergmann glia progenitors. Our study shows that these progenitors express Soxl, Sox2 and Sox9, a signature maintained throughout cerebellar maturation into adulthood. When isolated in culture, the Soxl-expressing cerebellar population exhibited neurosphere-forming ability, NSC-marker characteristics, and demonstrated multipotency at the clonal level. Our results show that the Bergmann glia population expresses Soxl during cerebellar development, and that these cells can be isolated and show stem cell characteristics in vitro, sug-gesting that they could hold a broader potential than previously thought.

  3. Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice.

    Directory of Open Access Journals (Sweden)

    Kristie Lee

    Full Text Available Congenital hydrocephalus (CH is a life-threatening medical condition in which excessive accumulation of CSF leads to ventricular expansion and increased intracranial pressure. Stenosis (blockage of the Sylvian aqueduct (Aq; the narrow passageway that connects the third and fourth ventricles is a common form of CH in humans, although the genetic basis of this condition is unknown. Mouse models of CH indicate that Aq stenosis is associated with abnormal development of the subcommmissural organ (SCO a small secretory organ located at the dorsal midline of the caudal diencephalon. Glycoproteins secreted by the SCO generate Reissner's fibre (RF, a thread-like structure that descends into the Aq and is thought to maintain its patency. However, despite the importance of SCO function in CSF homeostasis, the genetic program that controls SCO development is poorly understood. Here, we show that the X-linked transcription factor SOX3 is expressed in the murine SCO throughout its development and in the mature organ. Importantly, overexpression of Sox3 in the dorsal diencephalic midline of transgenic mice induces CH via a dose-dependent mechanism. Histological, gene expression and cellular proliferation studies indicate that Sox3 overexpression disrupts the development of the SCO primordium through inhibition of diencephalic roof plate identity without inducing programmed cell death. This study provides further evidence that SCO function is essential for the prevention of hydrocephalus and indicates that overexpression of Sox3 in the dorsal midline alters progenitor cell differentiation in a dose-dependent manner.

  4. Studying the expression patterns of OCT4 and SOX2 proteins in regenerating rabbit ear tissue

    Directory of Open Access Journals (Sweden)

    A. S. Javanmard

    2016-06-01

    Full Text Available Epimorphic regeneration in New Zealand rabbit ear is an interesting example of mammalian wound healing in which blastema formation is involved in replacement of injured tissues. It has been suggested that isolated cells from regenerating rabbit ear possess stem-like properties. In this study, we aimed to determine the expression of stemness markers, OCT4 and SOX2 proteins, in regenerating rabbit tissues by immunohistochemistry. Results indicated that both proteins could be detected in epithelial cells, hair follicle cells and perichondrium cells. Expression pattern analysis of OCT4 and SOX2 proteins showed no clear differences between regenerative and non-regenerative control tissues. According to several reports of OCT4 and SOX2 proteins expression in adult stem cells, it could be proposed that OCT4 and SOX2 expressing cells in regenerating rabbit ear tissues are progenitor/adult stem cells which are resident in these tissues, and other markers should be used for detection of blastema cells.

  5. Sorting live stem cells based on Sox2 mRNA expression.

    Directory of Open Access Journals (Sweden)

    Hans M Larsson

    Full Text Available While cell sorting usually relies on cell-surface protein markers, molecular beacons (MBs offer the potential to sort cells based on the presence of any expressed mRNA and in principle could be extremely useful to sort rare cell populations from primary isolates. We show here how stem cells can be purified from mixed cell populations by sorting based on MBs. Specifically, we designed molecular beacons targeting Sox2, a well-known stem cell marker for murine embryonic (mES and neural stem cells (NSC. One of our designed molecular beacons displayed an increase in fluorescence compared to a nonspecific molecular beacon both in vitro and in vivo when tested in mES and NSCs. We sorted Sox2-MB(+SSEA1(+ cells from a mixed population of 4-day retinoic acid-treated mES cells and effectively isolated live undifferentiated stem cells. Additionally, Sox2-MB(+ cells isolated from primary mouse brains were sorted and generated neurospheres with higher efficiency than Sox2-MB(- cells. These results demonstrate the utility of MBs for stem cell sorting in an mRNA-specific manner.

  6. A mechanism regulating the onset of Sox2 expression in the embryonic neural plate.

    Directory of Open Access Journals (Sweden)

    Costis Papanayotou

    2008-01-01

    Full Text Available In vertebrate embryos, the earliest definitive marker for the neural plate, which will give rise to the entire central nervous system, is the transcription factor Sox2. Although some of the extracellular signals that regulate neural plate fate have been identified, we know very little about the mechanisms controlling Sox2 expression and thus neural plate identity. Here, we use electroporation for gain- and loss-of-function in the chick embryo, in combination with bimolecular fluorescence complementation, two-hybrid screens, chromatin immunoprecipitation, and reporter assays to study protein interactions that regulate expression of N2, the earliest enhancer of Sox2 to be activated and which directs expression to the largest part of the neural plate. We show that interactions between three coiled-coil domain proteins (ERNI, Geminin, and BERT, the heterochromatin proteins HP1alpha and HP1gamma acting as repressors, and the chromatin-remodeling enzyme Brm acting as activator control the N2 enhancer. We propose that this mechanism regulates the timing of Sox2 expression as part of the process of establishing neural plate identity.

  7. Sixteen additional enhancers associated with the chicken Sox2 locus outside the central 50-kb region.

    Science.gov (United States)

    Okamoto, Ryuji; Uchikawa, Masanori; Kondoh, Hisato

    2015-01-01

    The transcription factor Sox2 plays a central role in the regulation of neuro-sensory development, and many other developmental processes. To gain an in depth understanding of the Sox2 gene regulation, we previously investigated the Sox2-proximal 50-kb region of the chicken genome to determine enhancers based on functional assays using chicken embryo electroporation. We identified 11 enhancers with specificity for neuro-sensory tissues. In this study, we extended the analysis of Sox2 locus-associated enhancers to a 200-kb region and identified 16 additional enhancers with functions in neuro-sensory development. These enhancers roughly correspond to a fraction of the sequence blocks that are highly conserved between chicken and mammalian genomes. The neural enhancers were activated in sequence, thereby creating a complex pattern of functional overlaps in the developing central nervous system (CNS). The variations in the specificities of the sensory enhancers also reflected the intermediate steps of sensory tissue development. This study provides an example where a single transcription factor gene has numerous regulatory elements that allow it to fulfill many functional roles in different biological contexts.

  8. Aflatoxin B1content in patients with hepatic diseases Aflatoxina B1 en pacientes con enfermedades hepáticas

    Directory of Open Access Journals (Sweden)

    Clara López

    2002-08-01

    Full Text Available Aflatoxins are toxic metabolites of some Aspergillus flavus, A. parasiticus and A. nomius strains that occur in many foods and feeds. There are four major natural occurring aflatoxins: B1, B2, G1 and G2. These toxins can cause illness in human beings and animals. Aflatoxin B1 is the most abundant and toxic member of the family, and it is also the most potent hepatocarcinogen known. In order to estimate the potential human health risk of AFB1, it is useful to measure blood concentration. The presence of aflatoxin B1 in patients was evaluated by high-performance liquid chromatography, in serum samples, obtained from 20 patient volunteers with hepatic disease. Out of the 20 patients, the presence of AFB1 was detected in only one of them, in a concentration of 0.47 ng/cm³. Nevertheless, this result should draw the attention of control organizations in Argentina to the need for a thorough food and feed inspection.Las aflatoxinas son metabolitos tóxicos producidos por cepas de Aspergillus flavus, A. parasiticus y A. nomius, presentes en alimentos y piensos. Las cuatro aflatoxinas principales son: aflatoxina B1, B2, G1 y G2. Dichas toxinas pueden causar enfermedades tanto en seres humanos como en animales. La aflatoxina B1 es la más abundante y la más tóxica del grupo y es también el más potente hepatocarcinógeno conocido. El objetivo de este trabajo fue detectar la presencia de aflatoxina B1 en sangre humana para estimar el riesgo potencial de la salud. La determinación de aflatoxina B1 fue realizada por cromatografía líquida de alto rendimiento, en suero de 20 pacientes voluntarios con enfermedades hepáticas. En sólo uno de estos pacientes se detectó la presencia de aflatoxina B1, en una concentración de 0.47ng/cm³. Estos resultados deberían ser tenidos en cuenta por los responsables de la vigilancia y control de los alimentos en la Argentina.

  9. Effects of Aflatoxin B1 and Fumonisin B1 on the Viability and Induction of Apoptosis in Rat Primary Hepatocytes

    Science.gov (United States)

    Ribeiro, Deise H. B.; Ferreira, Fabiane L.; da Silva, Valéria N.; Aquino, Simone; Corrêa, Benedito

    2010-01-01

    The present study evaluated the effect of aflatoxin B1 (AFB1) and fumonisin B1 (FB1) either alone, or in association, on rat primary hepatocyte cultures. Cell viability was assessed by flow cytometry after propidium iodine intercalation. DNA fragmentation and apoptosis were assessed by agarose gel electrophoresis and acridine orange and ethidium bromide staining. At the concentrations of AFB1 and FB1 used, the toxins did not decrease cell viability, but did induce apoptosis in a concentration and time-dependent manner. PMID:20480051

  10. The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation

    LENUS (Irish Health Repository)

    Sernbo, Sandra

    2011-09-24

    Abstract Background The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking. Methods SOX11 expression and clinicopathological data was compared using χ2 test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier analysis and the log rank test were applied to evaluate ovarian cancer-specific survival (OCSS) and overall survival (OS) in strata, according to SOX11 expression. Also, the methylation status of the SOX11 promoter was determined by sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the effect of ectopic overexpression of SOX11 on proliferation was studied through [3H]-thymidine incorporation. Results SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were expressed in two of five cell lines, correlating with promoter methylation status. Demethylation was successfully performed using 5\\'-Aza-2\\'deoxycytidine (5-Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed the growth regulatory role of SOX11. Conclusions SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. Re-expression of SOX11 in EOC indicates a potential use of epigenetic drugs to affect cellular growth in SOX11-negative tumours.

  11. 绵羊Sox2基因逆转录病毒载体的构建与检测%Construction and Detection of Retrovirus Vector with Ovine Sox2 Gene

    Institute of Scientific and Technical Information of China (English)

    赵健灵; 安铁洙; 张志人; 王子竹; 朴善花; 王春生

    2012-01-01

    In order to construct the retroviral vector with sheep Sox2 to induce ovine somatic cell to iPS, sheep Sox2 gene was cloned, and then linked with retroviral vector pMXs. 293GP cells were co-transfected by the vector and pVSV-G. Viral supernatant was infected sheep fibroblast cells in order to detect the expression of Sox2. The results were showed as followed. PCR and restriction enzyme digestion revealed that pMXs-Sox2 plasmid was constructed successfully. Expression of Sox2 was detected in sheep fibroblasts cell after being infected by the viral supernatant obtained. The results indicated that the vector obtained could be used to induce sheep somatic cell reprogramming.%为建立利用内源诱导因子诱导绵羊体细胞为多能干细胞(induced pluripotent stem cell,iPS)的方法,对绵羊Sox2基因进行克隆,并与pMXs连接构建逆转录病毒载体,将构建的载体转染293GP细胞以获得假病毒上清,利用假病毒上清侵染绵羊胎儿成纤维细胞以检测细胞中的Sox2表达变化.PCR和酶切鉴定结果显示,成功构建了pMXs-Sox2重组质粒,该质粒具有转染293GP细胞的能力,所获得的假病毒上清侵染绵羊胎儿成纤维细胞后,可诱导细胞表达Sox2基因.本研究为开展绵羊iPS的相关研究提供依据.

  12. Ewing sarcoma ewsa protein regulates chondrogenesis of Meckel's cartilage through modulation of Sox9 in zebrafish.

    Directory of Open Access Journals (Sweden)

    Chris Merkes

    Full Text Available Ewing sarcoma is the second most common skeletal (bone and cartilage cancer in adolescents, and it is characterized by the expression of the aberrant chimeric fusion gene EWS/FLI1. Wild-type EWS has been proposed to play a role in mitosis, splicing and transcription. We have previously shown that EWS/FLI1 interacts with EWS, and it inhibits EWS activity in a dominant manner. Ewing sarcoma is a cancer that specifically develops in skeletal tissues, and although the above data suggests the significance of EWS, its role in chondrogenesis/skeletogenesis is not understood. To elucidate the function of EWS in skeletal development, we generated and analyzed a maternal zygotic (MZ ewsa/ewsa line because the ewsa/wt and ewsa/ewsa zebrafish appeared to be normal and fertile. Compared with wt/wt, the Meckel's cartilage of MZ ewsa/ewsa mutants had a higher number of craniofacial prehypertrophic chondrocytes that failed to mature into hypertrophic chondrocytes at 4 days post-fertilization (dpf. Ewsa interacted with Sox9, which is the master transcription factor for chondrogenesis. Sox9 target genes were either upregulated (ctgfa, ctgfb, col2a1a, and col2a1b or downregulated (sox5, nog1, nog2, and bmp4 in MZ ewsa/ewsa embryos compared with the wt/wt zebrafish embryos. Among these Sox9 target genes, the chromatin immunoprecipitation (ChIP experiment demonstrated that Ewsa directly binds to ctgfa and ctgfb loci. Consistently, immunohistochemistry showed that the Ctgf protein is upregulated in the Meckel's cartilage of MZ ewsa/ewsa mutants. Together, we propose that Ewsa promotes the differentiation from prehypertrophic chondrocytes to hypertrophic chondrocytes of Meckel's cartilage through inhibiting Sox9 binding site of the ctgf gene promoter. Because Ewing sarcoma specifically develops in skeletal tissue that is originating from chondrocytes, this new role of EWS may provide a potential molecular basis of its pathogenesis.

  13. Nac1 Coordinates a Sub-network of Pluripotency Factors to Regulate Embryonic Stem Cell Differentiation.

    Science.gov (United States)

    Malleshaiah, Mohan; Padi, Megha; Rué, Pau; Quackenbush, John; Martinez-Arias, Alfonso; Gunawardena, Jeremy

    2016-02-01

    Pluripotent cells give rise to distinct cell types during development and are regulated by often self-reinforcing molecular networks. How such networks allow cells to differentiate is less well understood. Here, we use integrative methods to show that external signals induce reorganization of the mouse embryonic stem cell pluripotency network and that a sub-network of four factors, Nac1, Oct4, Tcf3, and Sox2, regulates their differentiation into the alternative mesendodermal and neuroectodermal fates. In the mesendodermal fate, Nac1 and Oct4 were constrained within quantitative windows, whereas Sox2 and Tcf3 were repressed. In contrast, in the neuroectodermal fate, Sox2 and Tcf3 were constrained while Nac1 and Oct4 were repressed. In addition, we show that Nac1 coordinates differentiation by activating Oct4 and inhibiting both Sox2 and Tcf3. Reorganization of progenitor cell networks around shared factors might be a common differentiation strategy and our integrative approach provides a general methodology for delineating such networks.

  14. Nac1 Coordinates a Sub-network of Pluripotency Factors to Regulate Embryonic Stem Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Mohan Malleshaiah

    2016-02-01

    Full Text Available Pluripotent cells give rise to distinct cell types during development and are regulated by often self-reinforcing molecular networks. How such networks allow cells to differentiate is less well understood. Here, we use integrative methods to show that external signals induce reorganization of the mouse embryonic stem cell pluripotency network and that a sub-network of four factors, Nac1, Oct4, Tcf3, and Sox2, regulates their differentiation into the alternative mesendodermal and neuroectodermal fates. In the mesendodermal fate, Nac1 and Oct4 were constrained within quantitative windows, whereas Sox2 and Tcf3 were repressed. In contrast, in the neuroectodermal fate, Sox2 and Tcf3 were constrained while Nac1 and Oct4 were repressed. In addition, we show that Nac1 coordinates differentiation by activating Oct4 and inhibiting both Sox2 and Tcf3. Reorganization of progenitor cell networks around shared factors might be a common differentiation strategy and our integrative approach provides a general methodology for delineating such networks.

  15. Filtration of SOX9 Genes Mutation and Analyses of Its Function in Colorectal Cancer%结直肠癌中SOX9基因突变的筛选及其功能解析

    Institute of Scientific and Technical Information of China (English)

    汪丽佩; 李天一

    2013-01-01

    [目的]观察结直肠癌(colorectalcancer,CRC)中是否存在SOX9基因的突变位点.[方法]通过PCR及直接测序的方法,检测5个结肠癌细胞系DNA(HT29、SW480、SW620、RKO、Hce8693)和20个结肠癌组织DNA中的SOX9基因全部编码区段、启动子、核心区域及增强子区域的突变情况.[结果]在SOX9基因Intron 4的3519bp处发现SNPs位点1个(A/C),包括A/C杂合型、C/C纯合型以及A/A纯合型,但在全部的关键区域未发现突变热点.[结论]SOX9基因在CRC中不存在突变位点,但其在表达水平上明显升高,可推测SOX9基因不是在基因水平上,而是由表达水平的改变直接参与CRC的发生.%[Objective] To find the mutation hot point of SOX9 gene in colorectal cancer. [Methods] Amplification of 5 colorectal cancer cell lines DNA HT29 ,SW480,SW620,RKO,Hce8693 and 20 colorectal cancer tissue DNA through PCR at SOX9's coding region, core region, Promotor and En-hancer.PCR coupled with sequencing was used to detect whether any mutations exist in the sequence of SOX9 gene. [Result] One SNP site was fount at the Intron4(3519bp) of SOX9 gene, including A/C heterozygous type, C/C homozygous type and A/A homozygous type, but no mutation hot point was founc in all the important regions of SOX9.[Conclusion]The mutation hot point didn't exist in the SOX9 gene of colorectal cancer, but its expression was strong in this cancer, which could be deduced that SOX9 doesn't function on colorectal cancer at genomic level, but at expression level.

  16. Cartilage development requires the function of Estrogen-related receptor alpha that directly regulates sox9 expression in zebrafish.

    Science.gov (United States)

    Kim, Yong-Il; No Lee, Joon; Bhandari, Sushil; Nam, In-Koo; Yoo, Kyeong-Won; Kim, Se-Jin; Oh, Gi-Su; Kim, Hyung-Jin; So, Hong-Seob; Choe, Seong-Kyu; Park, Raekil

    2015-12-10

    Estrogen-related receptor alpha (ESRRa) regulates a number of cellular processes including development of bone and muscles. However, direct evidence regarding its involvement in cartilage development remains elusive. In this report, we establish an in vivo role of Esrra in cartilage development during embryogenesis in zebrafish. Gene expression analysis indicates that esrra is expressed in developing pharyngeal arches where genes necessary for cartilage development are also expressed. Loss of function analysis shows that knockdown of esrra impairs expression of genes including sox9, col2a1, sox5, sox6, runx2 and col10a1 thus induces abnormally formed cartilage in pharyngeal arches. Importantly, we identify putative ESRRa binding elements in upstream regions of sox9 to which ESRRa can directly bind, indicating that Esrra may directly regulate sox9 expression. Accordingly, ectopic expression of sox9 rescues defective formation of cartilage induced by the knockdown of esrra. Taken together, our results indicate for the first time that ESRRa is essential for cartilage development by regulating sox9 expression during vertebrate development.

  17. CRISPR reveals a distal super-enhancer required for Sox2 expression in mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Yan Li

    Full Text Available The pluripotency of embryonic stem cells (ESCs is maintained by a small group of master transcription factors including Oct4, Sox2 and Nanog. These core factors form a regulatory circuit controlling the transcription of a number of pluripotency factors including themselves. Although previous studies have identified transcriptional regulators of this core network, the cis-regulatory DNA sequences required for the transcription of these key pluripotency factors remain to be defined. We analyzed epigenomic data within the 1.5 Mb gene-desert regions around the Sox2 gene and identified a 13kb-long super-enhancer (SE located 100kb downstream of Sox2 in mouse ESCs. This SE is occupied by Oct4, Sox2, Nanog, and the mediator complex, and physically interacts with the Sox2 locus via DNA looping. Using a simple and highly efficient double-CRISPR genome editing strategy we deleted the entire 13-kb SE and characterized transcriptional defects in the resulting monoallelic and biallelic deletion clones with RNA-seq. We showed that the SE is responsible for over 90% of Sox2 expression, and Sox2 is the only target gene along the chromosome. Our results support the functional significance of a SE in maintaining the pluripotency transcription program in mouse ESCs.

  18. Identification of novel craniofacial regulatory domains located far upstream of SOX9 and disrupted in Pierre Robin sequence.

    Science.gov (United States)

    Gordon, Christopher T; Attanasio, Catia; Bhatia, Shipra; Benko, Sabina; Ansari, Morad; Tan, Tiong Y; Munnich, Arnold; Pennacchio, Len A; Abadie, Véronique; Temple, I Karen; Goldenberg, Alice; van Heyningen, Veronica; Amiel, Jeanne; FitzPatrick, David; Kleinjan, Dirk A; Visel, Axel; Lyonnet, Stanislas

    2014-08-01

    Mutations in the coding sequence of SOX9 cause campomelic dysplasia (CD), a disorder of skeletal development associated with 46,XY disorders of sex development (DSDs). Translocations, deletions, and duplications within a ∼2 Mb region upstream of SOX9 can recapitulate the CD-DSD phenotype fully or partially, suggesting the existence of an unusually large cis-regulatory control region. Pierre Robin sequence (PRS) is a craniofacial disorder that is frequently an endophenotype of CD and a locus for isolated PRS at ∼1.2-1.5 Mb upstream of SOX9 has been previously reported. The craniofacial regulatory potential within this locus, and within the greater genomic domain surrounding SOX9, remains poorly defined. We report two novel deletions upstream of SOX9 in families with PRS, allowing refinement of the regions harboring candidate craniofacial regulatory elements. In parallel, ChIP-Seq for p300 binding sites in mouse craniofacial tissue led to the identification of several novel craniofacial enhancers at the SOX9 locus, which were validated in transgenic reporter mice and zebrafish. Notably, some of the functionally validated elements fall within the PRS deletions. These studies suggest that multiple noncoding elements contribute to the craniofacial regulation of SOX9 expression, and that their disruption results in PRS.

  19. Sox7-sustained expression alters the balance between proliferation and differentiation of hematopoietic progenitors at the onset of blood specification.

    Science.gov (United States)

    Gandillet, Arnaud; Serrano, Alicia G; Pearson, Stella; Lie-A-Ling, Michael; Lacaud, Georges; Kouskoff, Valerie

    2009-11-26

    The molecular mechanisms that regulate the balance between proliferation and differentiation of precursors at the onset of hematopoiesis specification are poorly understood. By using a global gene expression profiling approach during the course of embryonic stem cell differentiation, we identified Sox7 as a potential candidate gene involved in the regulation of blood lineage formation from the mesoderm germ layer. In the present study, we show that Sox7 is transiently expressed in mesodermal precursors as they undergo specification to the hematopoietic program. Sox7 knockdown in vitro significantly decreases the formation of both primitive erythroid and definitive hematopoietic progenitors as well as endothelial progenitors. In contrast, Sox7-sustained expression in the earliest committed hematopoietic precursors promotes the maintenance of their multipotent and self-renewing status. Removal of this differentiation block driven by Sox7-enforced expression leads to the efficient differentiation of hematopoietic progenitors to all erythroid and myeloid lineages. This study identifies Sox7 as a novel and important player in the molecular regulation of the first committed blood precursors. Furthermore, our data demonstrate that the mere sustained expression of Sox7 is sufficient to completely alter the balance between proliferation and differentiation at the onset of hematopoiesis.

  20. Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex

    DEFF Research Database (Denmark)

    Lukas, C; Sørensen, Claus Storgaard; Kramer, E;

    1999-01-01

    genes beyond the G1/S transition is required for coordinating S-phase progression with cell division, a process driven by cyclin-B-dependent kinase and anaphase-promoting complex (APC)-mediated proteolysis. How E2F-dependent events at G1/S transition are orchestrated with cyclin B and APC activity...... in the timely accumulation of cyclin B1 and the coordination of cell-cycle progression during the post-restriction point period....

  1. SOX2 expression is upregulated in adult spinal cord after contusion injury in both oligodendrocyte lineage and ependymal cells.

    Science.gov (United States)

    Lee, Hyun Joon; Wu, Junfang; Chung, Jumi; Wrathall, Jean R

    2013-02-01

    The upregulation of genes normally associated with development may occur in the adult after spinal cord injury (SCI). To test this, we performed real-time RT-PCR array analysis of mouse spinal cord mRNAs comparing embryonic day (E)14.5 spinal cord with intact adult and adult cord 1 week after a clinically relevant standardized contusion SCI. We found significantly increased expression of a large number of neural development- and stem cell-associated genes after SCI. These included Sox2 (sex determining region Y-box 2), a transcription factor that regulates self-renewal and potency of embryonic neural stem cells and is one of only a few key factors needed to induce pluripotency. In adult spinal cord of Sox2-EGFP mice, Sox2-EGFP was found mainly in the ependymal cells of the central canal. After SCI, both mRNA and protein levels of Sox2 were significantly increased at and near the injury site. By 1 day, Sox2 was upregulated in NG2(+) oligodendrocyte progenitor cells (OPC) in the spared white matter. By 3 days, Sox2-EGFP ependymal cells had increased proliferation and begun to form multiple layers and clusters of cells in the central lesion zone of the cord. Expression of Sox2 by NG2(+) cells had declined by 1 week, but increased numbers of other Sox2-expressing cells persisted for at least 4 weeks after SCI in both mouse and rat models. Thus, SCI upregulates many genes associated with development and neural stem cells, including the key transcription factor Sox2, which is expressed in a pool of cells that persists for weeks after SCI.

  2. SOX2 co-occupies distal enhancer elements with distinct POU factors in ESCs and NPCs to specify cell state.

    Directory of Open Access Journals (Sweden)

    Michael A Lodato

    Full Text Available SOX2 is a master regulator of both pluripotent embryonic stem cells (ESCs and multipotent neural progenitor cells (NPCs; however, we currently lack a detailed understanding of how SOX2 controls these distinct stem cell populations. Here we show by genome-wide analysis that, while SOX2 bound to a distinct set of gene promoters in ESCs and NPCs, the majority of regions coincided with unique distal enhancer elements, important cis-acting regulators of tissue-specific gene expression programs. Notably, SOX2 bound the same consensus DNA motif in both cell types, suggesting that additional factors contribute to target specificity. We found that, similar to its association with OCT4 (Pou5f1 in ESCs, the related POU family member BRN2 (Pou3f2 co-occupied a large set of putative distal enhancers with SOX2 in NPCs. Forced expression of BRN2 in ESCs led to functional recruitment of SOX2 to a subset of NPC-specific targets and to precocious differentiation toward a neural-like state. Further analysis of the bound sequences revealed differences in the distances of SOX and POU peaks in the two cell types and identified motifs for additional transcription factors. Together, these data suggest that SOX2 controls a larger network of genes than previously anticipated through binding of distal enhancers and that transitions in POU partner factors may control tissue-specific transcriptional programs. Our findings have important implications for understanding lineage specification and somatic cell reprogramming, where SOX2, OCT4, and BRN2 have been shown to be key factors.

  3. Activation of the Escherichia coli marA/soxS/rob regulon in response to transcriptional activator concentration.

    Science.gov (United States)

    Martin, Robert G; Bartlett, Emily S; Rosner, Judah L; Wall, Michael E

    2008-07-04

    The paralogous transcriptional activators MarA, SoxS, and Rob activate a common set of promoters, the marA/soxS/rob regulon of Escherichia coli, by binding a cognate site (marbox) upstream of each promoter. The extent of activation varies from one promoter to another and is only poorly correlated with the in vitro affinity of the activator for the specific marbox. Here, we examine the dependence of promoter activation on the level of activator in vivo by manipulating the steady-state concentrations of MarA and SoxS in Lon protease mutants and by measuring promoter activation using lacZ transcriptional fusions. We found that: (i) the MarA concentrations needed for half-maximal stimulation varied by at least 19-fold among the 10 promoters tested; (ii) most marboxes were not saturated when there were 24,000 molecules of MarA per cell; (iii) the correlation between the MarA concentration needed for half-maximal promoter activity in vivo and marbox binding affinity in vitro was poor; and (iv) the two activators differed in their promoter activation profiles. The marRAB and sodA promoters could both be saturated by MarA and SoxS in vivo. However, saturation by MarA resulted in greater marRAB and lesser sodA transcription than did saturation by SoxS, implying that the two activators interact with RNA polymerase in different ways at the different promoters. Thus, the concentration and nature of activator determine which regulon promoters are activated, as well as the extent of their activation.

  4. Irx3 and Bmp2 Regulate Mouse Mesenchymal Cell Chondrogenic Differentiation in Both a Sox9-Dependent and -Independent Manner.

    Science.gov (United States)

    Tamamura, Yoshihiro; Katsube, Kenichi; Mera, Hisashi; Itokazu, Maki; Wakitani, Shigeyuki

    2017-01-06

    Sox9, a master regulator of cartilage development, controls the cell fate decision to differentiate from mesenchymal to chondrogenic cells. In addition, Sox9 regulates the proliferation and differentiation of chondrocytes, as well as the production of cartilage-specific proteoglycans. The existence of Sox9-independent mechanisms in cartilage development remains to be determined. Here, we attempted to identify genes involved in such putative mechanisms via microarray analysis using a mouse chondrogenic cell line, N1511. We first focused on transcription factors that exhibited upregulated expression following Bmp2 treatment, which was not altered by subsequent treatment with Sox9 siRNA. Among these, we selected positive regulators for chondrogenesis and identified Iroquois-related homeobox 3 (Irx3) as one of the candidate genes. Irx3 expression gradually increased with chondrocyte terminal differentiation in a reciprocal manner to Sox9 expression, and promoted the chondrogenic differentiation of mesenchymal cells upon Bmp2 treatment. Furthermore, Irx3 partially rescued impaired chondrogenesis by upregulating the expression of epiphycan and lumican under reduced Sox9 expression. Finally, Irx3 was shown to act in concert with Bmp2 signaling to activate the p38 MAPK pathway, which in turn stimulated Sox9 expression, as well as the expression of epiphycan and lumican in a Sox9-independent manner. These results indicate that Irx3 represents a novel chondrogenic factor of mesenchymal cells, acts synergistically with Bmp2-mediated signaling, and regulates chondrogenesis independent of the transcriptional machinery associated with Sox9-mediated regulation. This article is protected by copyright. All rights reserved.

  5. RUN COORDINATION

    CERN Multimedia

    C. Delaere

    2013-01-01

    Since the LHC ceased operations in February, a lot has been going on at Point 5, and Run Coordination continues to monitor closely the advance of maintenance and upgrade activities. In the last months, the Pixel detector was extracted and is now stored in the pixel lab in SX5; the beam pipe has been removed and ME1/1 removal has started. We regained access to the vactank and some work on the RBX of HB has started. Since mid-June, electricity and cooling are back in S1 and S2, allowing us to turn equipment back on, at least during the day. 24/7 shifts are not foreseen in the next weeks, and safety tours are mandatory to keep equipment on overnight, but re-commissioning activities are slowly being resumed. Given the (slight) delays accumulated in LS1, it was decided to merge the two global runs initially foreseen into a single exercise during the week of 4 November 2013. The aim of the global run is to check that we can run (parts of) CMS after several months switched off, with the new VME PCs installed, th...

  6. RUN COORDINATION

    CERN Multimedia

    Christophe Delaere

    2013-01-01

    The focus of Run Coordination during LS1 is to monitor closely the advance of maintenance and upgrade activities, to smooth interactions between subsystems and to ensure that all are ready in time to resume operations in 2015 with a fully calibrated and understood detector. After electricity and cooling were restored to all equipment, at about the time of the last CMS week, recommissioning activities were resumed for all subsystems. On 7 October, DCS shifts began 24/7 to allow subsystems to remain on to facilitate operations. That culminated with the Global Run in November (GriN), which   took place as scheduled during the week of 4 November. The GriN has been the first centrally managed operation since the beginning of LS1, and involved all subdetectors but the Pixel Tracker presently in a lab upstairs. All nights were therefore dedicated to long stable runs with as many subdetectors as possible. Among the many achievements in that week, three items may be highlighted. First, the Strip...

  7. SOX9 regulates microRNA miR-202-5p/3p expression during mouse testis differentiation

    DEFF Research Database (Denmark)

    Wainwright, Elanor N; Jorgensen, Joan S; Kim, Youngha;

    2013-01-01

    . Expression of the primary transcript of miR-202-5p/3p remained low in XY gonads in a conditional Sox9-null mouse model, suggesting that pri-miR-202 transcription is downstream of SOX9, a transcription factor that is both necessary and sufficient for male sex determination. We identified the pri-miR-202...... findings indicate that expression of the conserved gonad microRNA, miR-202-5p/3p, is downstream of the testis-determining factor SOX9, suggesting an early role in testis development....

  8. 78 FR 76114 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-12-16

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... spares 16 AN/ARC-220 HF Radios 32 AN/ARC-186 VHF AM/FM Radios 16 AN/ARN 123 VOR ILS Marker Beacons 14 AN..., 2 per aircraft (14 ac x 2=28 engines) 5 T55-GA-714A Turbine to be used as spares. 16 AN/ARC-220...

  9. Genome-wide Reconstruction of OxyR and SoxRS Transcriptional Regulatory Networks under Oxidative Stress in Escherichia coli K-12 MG1655

    DEFF Research Database (Denmark)

    Seo, Sang Woo; Kim, Donghyuk; Szubin, Richard;

    2015-01-01

    Three transcription factors (TFs), OxyR, SoxR, and SoxS, play a critical role in transcriptional regulation of the defense system for oxidative stress in bacteria. However, their full genome-wide regulatory potential is unknown. Here, we perform a genome-scale reconstruction of the OxyR, SoxR, an...

  10. [Pyrido[2,3-b][1,4]diazepinones with CNS activity].

    Science.gov (United States)

    Savelli, F; Boido, A; Pirisino, G; Piu, L; Satta, M; Manca, P

    1987-11-01

    In the interests of developing our research on compounds with a pyrazinone nucleus, cyclohomologues, characterised by the presence of one diazepinone nucleus, were prepared. The 5-[(dialkylamino)alkyl]-3,5-dihydro-2-methyl/phenyl-4H-pyrido[2,3- b][1,4]diazepin-4-ones obtained by means of condensation of the 2-(dialkylamino)alkylamino-3-aminopyridines with ethyl acetyl- or benzoyl- acetate, were subjected to pharmacological experimentation in order to evaluate their effect upon mice with regard to exploratory activity, motor coordination, and spontaneous activity. In addition their analgesic activity was evaluated and also their anti-strychnine, anti-cardiazole, anti-amphetamine and anti-reserpine activities.

  11. First observation of the hadronic transition $ \\Upsilon(4S) \\to \\eta h_{b}(1P)$ and new measurement of the $h_b(1P)$ and $\\eta_b(1S)$ parameters

    CERN Document Server

    Tamponi, U; Abdesselam, A; Aihara, H; Arinstein, K; Asner, D M; Atmacan, H; Aushev, T; Ayad, R; Badhrees, I; Bakich, A M; Barberio, E; Bhardwaj, V; Bhuyan, B; Biswal, J; Bondar, A; Bonvicini, G; Bozek, A; Bračko, M; Browder, T E; Červenkov, D; Chen, A; Cheon, B G; Cho, K; Chobanova, V; Choi, S -K; Choi, Y; Cinabro, D; Danilov, M; Doležal, Z; Drásal, Z; Drutskoy, A; Eidelman, S; Epifanov, D; Farhat, H; Fast, J E; Ferber, T; Fulsom, B G; Gaur, V; Gabyshev, N; Garmash, A; Getzkow, D; Gillard, R; Goh, Y M; Golob, B; Haba, J; Hayasaka, K; Hayashii, H; He, X H; Hedges, M T; Hou, W -S; Iijima, T; Inami, K; Ishikawa, A; Jaegle, I; Joffe, D; Julius, T; Kato, E; Katrenko, P; Kichimi, H; Kiesling, C; Kim, D Y; Kim, H J; Kim, J H; Kim, K T; Kim, S H; Kinoshita, K; Kodyš, P; Korpar, S; Križan, P; Krokovny, P; Kumita, T; Kuzmin, A; Lange, J S; Lewis, P; Libby, J; Lukin, P; Matvienko, D; Miyabayashi, K; Miyata, H; Mizuk, R; Mohanty, G B; Moll, A; Mori, T; Nakano, E; Nakao, M; Nanut, T; Natkaniec, Z; Nayak, M; Nisar, N K; Nishida, S; Ogawa, S; Okuno, S; Olsen, S L; Ostrowicz, W; Oswald, C; Pakhlova, G; Pal, B; Park, H; Pedlar, T K; Pesántez, L; Pestotnik, R; Petriřc, M; Piilonen, L E; Ribežl, E; Ritter, M; Rostomyan, A; Ryu, S; Sakai, Y; Sandilya, S; Santelj, L; Sanuki, T; Sato, Y; Savinov, V; Schneider, O; Schnell, G; Schwanda, C; Semmler, D; Senyo, K; Sevior, M E; Shapkin, M; Shebalin, V; Shen, C P; Shibata, T -A; Shiu, J -G; Shwartz, B; Sibidanov, A; Simon, F; Sohn, Y -S; Sokolov, A; Starič, M; Steder, M; Stypula, J; Tanida, K; Teramoto, Y; Trabelsi, K; Uchida, M; Uglov, T; Unno, Y; Uno, S; Urquijo, P; Van Hulse, C; Vanhoefer, P; Varner, G; Vinokurova, A; Vossen, A; Wagner, M N; Wang, M -Z; Wang, X L; Watanabe, Y; Williams, K M; Won, E; Yamaoka, J; Yashchenko, S; Zhang, Z P; Zhilich, V; Zhulanov, V; Zupanc, A

    2015-01-01

    Using a sample of $771.6 \\times 10^{6}$ $\\Upsilon(4S)$ decays collected by the Belle experiment at the KEKB $e^+e^-$ collider, we observe for the first time the transition $\\Upsilon(4S) \\to \\eta h_b(1P)$ with the branching fraction ${\\cal B}[\\Upsilon(4S) \\to \\eta h_b(1P)]= (2.18 \\pm 0.11 \\pm 0.18) \\times 10^{-3}$ and we measure the $h_b(1P)$ mass $M_{h_{b}(1P)} = (9899.3 \\pm 0.4 \\pm 1.0)$ MeV/$c^{2}$, corresponding to the hyperfine splitting $\\Delta M_{\\mathrm HF}(1P) = (0.6 \\pm 0.4 \\pm 1.0)$ MeV/$c^{2}$. Using the transition $h_b(1P) \\to \\gamma \\eta_b(1S)$, we measure the $\\eta_b(1S)$ mass $M_{\\eta_{b}(1S)} = (9400.7 \\pm 1.7 \\pm 1.6)$ MeV/$c^{2}$, corresponding to $\\Delta M_{\\mathrm HF}(1S) = (59.6 \\pm 1.7 \\pm 1.6)$ MeV/$c^{2}$, the $\\eta_b(1S)$ width $\\Gamma_{\\eta_{b}(1S)} = (8 ^{+6}_{-5} \\pm 5)$ MeV/$c^{2}$ and the branching fraction ${\\cal B}[h_b(1P) \\to \\gamma \\eta_b(1S)]= (56 \\pm 8 \\pm 4) \\%$.

  12. Sox9基因参与动物性别决定与分化的分子机制%Molecular Mechanisms of Sox9 Gene in Regulating Sex Determination and Differentiation of Animals

    Institute of Scientific and Technical Information of China (English)

    陈维; 王昌留

    2012-01-01

    Sox9基因参与动物多种生理活动的调控,其最主要的功能还是性别决定.笔者通过阅读大量文献,分析不同物种的性别决定分子机制,对Sox9参与动物的性别决定和分化进行了综述,为进一步研究Sox9基因在性别决定和分化中的作用提供参考.%Sox9 gene can take part in many physiological activities of gene regulations.Its most important role is involved in sex determination.The molecular mechanisms of sex determination and differentiation regulated by Sox9 gene in different species are reviewed,which is expected to provide reference materials for further study on sex determination and differentiation of Sox9 gene.

  13. Crystal structure of a KSHV-SOX-DNA complex: insights into the molecular mechanisms underlying DNase activity and host shutoff.

    Science.gov (United States)

    Bagnéris, Claire; Briggs, Louise C; Savva, Renos; Ebrahimi, Bahram; Barrett, Tracey E

    2011-07-01

    The early lytic phase of Kaposi's sarcoma herpesvirus infection is characterized by viral replication and the global degradation (shutoff) of host mRNA. Key to both activities is the virally encoded alkaline exonuclease KSHV SOX. While the DNase activity of KSHV SOX is required for the resolution of viral genomic DNA as a precursor to encapsidation, its exact involvement in host shutoff remains to be determined. We present the first crystal structure of a KSHV SOX-DNA complex that has illuminated the catalytic mechanism underpinning both its endo and exonuclease activities. We further illustrate that KSHV SOX, similar to its Epstein-Barr virus homologue, has an intrinsic RNase activity in vitro that although an element of host shutoff, cannot solely account for the phenomenon.

  14. Yin Yang 1 is associated with cancer stem cell transcription factors (SOX2, OCT4, BMI1) and clinical implication.

    Science.gov (United States)

    Kaufhold, Samantha; Garbán, Hermes; Bonavida, Benjamin

    2016-05-25

    The transcription factor Yin Yang 1 (YY1) is frequently overexpressed in cancerous tissues compared to normal tissues and has regulatory roles in cell proliferation, cell viability, epithelial-mesenchymal transition, metastasis and drug/immune resistance. YY1 shares many properties with cancer stem cells (CSCs) that drive tumorigenesis, metastasis and drug resistance and are regulated by overexpression of certain transcription factors, including SOX2, OCT4 (POU5F1), BMI1 and NANOG. Based on these similarities, it was expected that YY1 expression would be associated with SOX2, OCT4, BMI1, and NANOG's expressions and activities. Data mining from the proteomic tissue-based datasets from the Human Protein Atlas were used for protein expression patterns of YY1 and the four CSC markers in 17 types of cancer, including both solid and hematological malignancies. A close association was revealed between the frequency of expressions of YY1 and SOX2 as well as SOX2 and OCT4 in all cancers analyzed. Two types of dynamics were identified based on the nature of their association, namely, inverse or direct, between YY1 and SOX2. These two dynamics define distinctive patterns of BMI1 and OCT4 expressions. The relationship between YY1 and SOX2 expressions as well as the expressions of BMI1 and OCT4 resulted in the classification of four groups of cancers with distinct molecular signatures: (1) Prostate, lung, cervical, endometrial, ovarian and glioma cancers (YY1(lo)SOX2(hi)BMI1(hi)OCT4(hi)) (2) Skin, testis and breast cancers (YY1(hi)SOX2(lo)BMI1(hi)OCT4(hi)) (3) Liver, stomach, renal, pancreatic and urothelial cancers (YY1(lo)SOX2(lo)BMI1(hi)OCT4(hi)) and (4) Colorectal cancer, lymphoma and melanoma (YY1(hi)SOX2(hi)BMI1(lo)OCT4(hi)). A regulatory loop is proposed consisting of the cross-talk between the NF-kB/PI3K/AKT pathways and the downstream inter-regulation of target gene products YY1, OCT4, SOX2 and BMI1.

  15. Cytochrome P1B1 (CYP1B1) polymorphisms and ovarian cancer risk: a meta-analysis.

    Science.gov (United States)

    Gajjar, Ketan; Owens, Gemma; Sperrin, Matthew; Martin-Hirsch, Pierre L; Martin, Francis L

    2012-12-16

    CYP1B1 is a key P450 enzyme involved in the metabolism of exogenous and endogenous substrates and plays a key role in hormone-induced carcinogenesis. Risk factors for ovarian cancer are related to hormonal exposure and reproduction, and polymorphisms within genes involved in metabolism of oestrogen and certain xenobiotics may influence the risk of developing ovarian cancer. Current meta-analysis evaluated four CYP1B1 polymorphisms (Leu432Val, Arg48Gly, Ala119Ser and Asn453Ser) for their association with ovarian cancer risk. A search of the MEDLINE bibliographic database for the period up to April 2012 identified five relevant studies. With regards to Leu432Val polymorphism, all of the five studies were eligible (1199 cases and 2596 controls) for analysis, while for Arg48Gly (799 cases and 1169 controls), Ala119Ser (799 cases and 1172 controls) and Asn453Ser (361cases and 1577 controls) only two studies were eligible for analysis. Fixed-effect models were used to estimate pooled odds ratios (OR) with 95% confidence intervals (95% CI) and chi-square based Q-test was used to test for heterogeneity. The pooled OR (95% CI) for CYP1B1_Leu432Val polymorphism were 1.1 (0.84-1.31) for heterozygous subjects and 0.82 (0.57-1.17) for homozygous Val subjects. In a recessive model, homozygous carriers of Leu432Val showed a weak trend towards reduced risk as compared to 'wild type' and heterozygous carriers (OR 0.8, 95% CI; 0.66-0.99); however, this association was of limited significance. Regarding Arg48Gly, the pooled OR (95% CI) were 1.06 (0.89-1.27) for heterozygous and 0.98 (1.72-1.33) for homozygous Gly subjects. With respect to Ala119Ser and Asn453Ser, the pooled OR were 1.06 (0.87-1.29) and 1.24 (0.94-1.63) for heterozygous and 1.1 (0.8-1.52) and 1.09 (0.5-2.34) for homozygous respectively. In conclusion, this meta-analysis suggests that CYP1B1 polymorphisms are not associated with ovarian cancer risk. Studies evaluating CYP1B1_Leu432Val polymorphism are required to

  16. Cytochrome P1B1 (CYP1B1) polymorphisms and cancer risk: a meta-analysis of 52 studies.

    Science.gov (United States)

    Li, Cuiping; Long, Bingshuang; Qin, Xianjing; Li, Weixiong; Zhou, Yang

    2015-01-02

    CYP1B1 plays a critical role in the oxidative metabolism of a variety of exogenous compounds, including carcinogenic compounds, which may be activated during metabolism. There are only a few studies that have examined the association between the two polymorphisms and cancer, and that these studies have been inconclusive. Hence, the aim of the present meta-analysis was to evaluate the relationship between polymorphisms in CYP1B1 G119T and A453G and cancer risk. We performed a detailed search using the PubMed and EMBASE libraries to obtain all relevant published reports on the relationship between the G119T and A453G polymorphisms in CYP1B1 and cancer risk. Combined odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by Stata version 11.2. We conducted stratified analyses based on cancer types, ethnicity, source of controls, and quality assessments. We also made assessments of heterogeneity tests, sensitivity analyses, and publication bias. There were a total of 25 articles with 15,376 cases and 18,382 controls concerning CYP1B1 G119T and 40 articles with 27,983 cases and 35,839 controls concerning A453G polymorphisms. Regarding G119T, the combined results indicate that the variant genotypes were significantly associated with a slightly increased cancer risk in comparison to the homozygote (TT versus GG: p=0.006, OR=1.231, 95% CI: 1.061-1.428), especially for breast cancer and prostate cancer. Moreover, significantly increased associations with cancer risk were demonstrated in Asians in all genetic models. The combined results indicated no association of A453G with cancer risk; however, an association was observed specifically for prostate cancer. This meta-analysis suggests that the CYP1B1 G119T polymorphism may confer to genetic susceptibility to cancer in Asians, especially to breast cancer and prostate cancer. The A453G polymorphism was found to modify the risk of prostate cancer.

  17. Motor coordination: a local hub for coordination.

    Science.gov (United States)

    Calabrese, Ronald L

    2014-03-31

    A local interneuron of a crayfish central pattern generator serves as a hub that integrates ascending and descending coordinating information and passes it on to a local oscillatory microcircuit to coordinate a series of segmental appendages known as swimmerets.

  18. Argumentative SOX Compliant and Quality Decision Support Intelligent Expert System over the Suppliers Selection Process

    Directory of Open Access Journals (Sweden)

    Jesus Angel Fernandez Canelas

    2013-01-01

    Full Text Available The objective of this paper is to define a decision support system over SOX (Sarbanes-Oxley Act compatibility and quality of the Suppliers Selection Process based on Artificial Intelligence and Argumentation Theory knowledge and techniques. The present SOX Law, in effect nowadays, was created to improve financial government control over US companies. This law is a factor standard out United States due to several factors like present globalization, expansion of US companies, or key influence of US stock exchange markets worldwide. This paper constitutes a novel approach to this kind of problems due to following elements: (1 it has an optimized structure to look for the solution, (2 it has a dynamic learning method to handle court and control gonvernment bodies decisions, (3 it uses fuzzy knowledge to improve its performance, and (4 it uses its past accumulated experience to let the system evolve far beyond its initial state.

  19. SuFEx Click: New Materials from SOx F and Silyl Ethers.

    Science.gov (United States)

    Yatvin, Jeremy; Brooks, Karson; Locklin, Jason

    2016-11-07

    New forms of click chemistry present new opportunities in materials science. Sulfur(VI) fluoride exchange (SuFEx) is a recently discovered click reaction between molecules containing SOx F groups and silyl ethers, two functionalities that are orthogonal to all other known click chemistries, that generates sulfate or sulfonate connections upon the addition of certain organobases or fluoride sources. SuFEx also has several important advantages over other click reactions in that it is insensitive to ambient oxygen and water, and its precursor materials, especially SOx F, are chemically, UV, and thermally inert. This Concept article focuses on the unique reactivity of SuFEx and its relation to building high molecular weight polymers and surface coatings, both of which make it a powerful new tool for materials science.

  20. Stemness of the organ of Corti relates to the epigenetic status of Sox2 enhancers.

    Directory of Open Access Journals (Sweden)

    Jörg Waldhaus

    Full Text Available In the adult mammalian auditory epithelium, the organ of Corti, loss of sensory hair cells results in permanent hearing loss. The underlying cause for the lack of regenerative response is the depletion of otic progenitors in the cell pool of the sensory epithelium. Here, we show that an increase in the sequence-specific methylation of the otic Sox2 enhancers NOP1 and NOP2 is correlated with a reduced self-renewal potential in vivo and in vitro; additionally, the degree of methylation of NOP1 and NOP2 is correlated with the dedifferentiation potential of postmitotic supporting cells into otic stem cells. Thus, the stemness the organ of Corti is related to the epigenetic status of the otic Sox2 enhancers. These observations validate the continued exploration of treatment strategies for dedifferentiating or reprogramming of differentiated supporting cells into progenitors to regenerate the damaged organ of Corti.

  1. Identification of novel craniofacial regulatory domains located far upstream ofSOX9and disrupted in Pierre Robin sequence

    OpenAIRE

    2014-01-01

    Mutations in the coding sequence of SOX9 cause campomelic dysplasia (CD), a disorder of skeletal development associated with 46,XY disorders of sex development (DSDs). Translocations, deletions and duplications within a ~2 Mb region upstream of SOX9 can recapitulate the CD-DSD phenotype fully or partially, suggesting the existence of an unusually large cis-regulatory control region. Pierre Robin sequence (PRS) is a craniofacial disorder that is frequently an endophenotype of CD and a locus fo...

  2. 3B1 beam line and its physical properties

    Science.gov (United States)

    Yi, Futing; Wang, Peiwei; Jin, Ming; Wu, Jianwu

    1995-02-01

    The 3B1 beam line is in the hall of 13# on BSRF, and is used for the lithography, biology and multilayer reflection research. On the line, there are a cylinder mirror system, a vacuum control system, an exposure chamber and a beryllium window for lithography research. The mirror coated with gold receives the synchrotron radiation at a glance angle of 1.5°, and scans in the vertical for lithography. The light, reflected by the scanning mirror and absorbed by the window, produces a spectrum of 4-20 Å and a uniformity spot for the lithography.

  3. Premalignant SOX2 overexpression in the fallopian tubes of ovarian cancer patients: Discovery and validation studies

    Directory of Open Access Journals (Sweden)

    Karin Hellner

    2016-08-01

    Full Text Available Current screening methods for ovarian cancer can only detect advanced disease. Earlier detection has proved difficult because the molecular precursors involved in the natural history of the disease are unknown. To identify early driver mutations in ovarian cancer cells, we used dense whole genome sequencing of micrometastases and microscopic residual disease collected at three time points over three years from a single patient during treatment for high-grade serous ovarian cancer (HGSOC. The functional and clinical significance of the identified mutations was examined using a combination of population-based whole genome sequencing, targeted deep sequencing, multi-center analysis of protein expression, loss of function experiments in an in-vivo reporter assay and mammalian models, and gain of function experiments in primary cultured fallopian tube epithelial (FTE cells. We identified frequent mutations involving a 40 kb distal repressor region for the key stem cell differentiation gene SOX2. In the apparently normal FTE, the region was also mutated. This was associated with a profound increase in SOX2 expression (p < 2−16, which was not found in patients without cancer (n = 108. Importantly, we show that SOX2 overexpression in FTE is nearly ubiquitous in patients with HGSOCs (n = 100, and common in BRCA1-BRCA2 mutation carriers (n = 71 who underwent prophylactic salpingo-oophorectomy. We propose that the finding of SOX2 overexpression in FTE could be exploited to develop biomarkers for detecting disease at a premalignant stage, which would reduce mortality from this devastating disease.

  4. SOx-NOx-Rox Box{trademark} flue gas clean-up demonstration. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    Babcock and Wilcox`s (B and W) SOx-NOx-Rox Box{trademark} process effectively removes SOx, NOx and particulate (Rox) from flue gas generated from coal-fired boilers in a single unit operation, a high temperature baghouse. The SNRB technology utilizes dry sorbent injection upstream of the baghouse for removal of SOx and ammonia injection upstream of a zeolitic selective catalytic reduction (SCR) catalyst incorporated in the baghouse to reduce NOx emissions. Because the SOx and NOx removal processes require operation at elevated gas temperatures (800--900 F) for high removal efficiency, high-temperature fabric filter bags are used in the baghouse. The SNRB technology evolved from the bench and laboratory pilot scale to be successfully demonstrated at the 5-MWe field scale. This report represents the completion of Milestone M14 as specified in the Work Plan. B and W tested the SNRB pollution control system at a 5-MWe demonstration facility at Ohio Edison`s R.E. Burger Plant located near Shadyside, Ohio. The design and operation were influenced by the results from laboratory pilot testing at B and W`s Alliance Research Center. The intent was to demonstrate the commercial feasibility of the SNRB process. The SNRB facility treated a 30,000 ACFM flue gas slipstream from Boiler No. 8. Operation of the facility began in May 1992 and was completed in May 1993. About 2,300 hours of high-temperature operation were achieved. The main emissions control performance goals of: greater than 70% SO{sub 2} removal using a calcium-based sorbent; greater than 90% NOx removal with minimal ammonia slip; and particulate emissions in compliance with the New Source Performance Standards (NSPS) of 0.03 lb/million Btu were exceeded simultaneously in the demonstration program when the facility was operated at optimal conditions. Testing also showed significant reductions in emissions of some hazardous air pollutants.

  5. Sox10 gain-of-function causes XX sex reversal in mice: implications for human 22q-linked disorders of sex development.

    Science.gov (United States)

    Polanco, Juan Carlos; Wilhelm, Dagmar; Davidson, Tara-Lynne; Knight, Deon; Koopman, Peter

    2010-02-01

    Male development in mammals is normally initiated by the Y-linked gene Sry, which activates expression of Sox9, leading to a cascade of gene activity required for testis formation. Although defects in this genetic cascade lead to human disorders of sex development (DSD), only a dozen DSD genes have been identified, and causes of 46,XX DSD (XX maleness) other than SRY translocation are almost completely unknown. Here, we show that transgenic expression of Sox10, a close relative of Sox9, in gonads of XX mice resulted in development of testes and male physiology. The degree of sex reversal correlated with levels of Sox10 expression in different transgenic lines. Sox10 was expressed at low levels in primordial gonads of both sexes during normal mouse development, becoming male-specific during testis differentiation. SOX10 protein was able to activate transcriptional targets of SOX9, explaining at a mechanistic level its ability to direct male development. Because over-expression of SOX10 alone is able to mimic the XX DSD phenotypes associated with duplication of human chromosome 22q13, and given that human SOX10 maps to 22q13.1, our results functionally implicate SOX10 in the etiology of these DSDs.

  6. SOX2 O-GlcNAcylation alters its protein-protein interactions and genomic occupancy to modulate gene expression in pluripotent cells

    Science.gov (United States)

    Myers, Samuel A; Peddada, Sailaja; Chatterjee, Nilanjana; Friedrich, Tara; Tomoda, Kiichrio; Krings, Gregor; Thomas, Sean; Maynard, Jason; Broeker, Michael; Thomson, Matthew; Pollard, Katherine; Yamanaka, Shinya; Burlingame, Alma L; Panning, Barbara

    2016-01-01

    The transcription factor SOX2 is central in establishing and maintaining pluripotency. The processes that modulate SOX2 activity to promote pluripotency are not well understood. Here, we show SOX2 is O-GlcNAc modified in its transactivation domain during reprogramming and in mouse embryonic stem cells (mESCs). Upon induction of differentiation SOX2 O-GlcNAcylation at serine 248 is decreased. Replacing wild type with an O-GlcNAc-deficient SOX2 (S248A) increases reprogramming efficiency. ESCs with O-GlcNAc-deficient SOX2 exhibit alterations in gene expression. This change correlates with altered protein-protein interactions and genomic occupancy of the O-GlcNAc-deficient SOX2 compared to wild type. In addition, SOX2 O-GlcNAcylation impairs the SOX2-PARP1 interaction, which has been shown to regulate ESC self-renewal. These findings show that SOX2 activity is modulated by O-GlcNAc, and provide a novel regulatory mechanism for this crucial pluripotency transcription factor. DOI: http://dx.doi.org/10.7554/eLife.10647.001 PMID:26949256

  7. The overexpression of SOX2 affects the migration of human teratocarcinoma cell line NT2/D1

    Directory of Open Access Journals (Sweden)

    DANIJELA DRAKULIC

    2015-03-01

    Full Text Available The altered expression of the SOX2 transcription factor is associated with oncogenic or tumor suppressor functions in human cancers. This factor regulates the migration and invasion of different cancer cells. In this study we investigated the effect of constitutive SOX2 overexpression on the migration and adhesion capacity of embryonal teratocarcinoma NT2/D1 cells derived from a metastasis of a human testicular germ cell tumor. We detected that increased SOX2 expression changed the speed, mode and path of cell migration, but not the adhesion ability of NT2/D1 cells. Additionally, we demonstrated that SOX2 overexpression increased the expression of the tumor suppressor protein p53 and the HDM2 oncogene. Our results contribute to the better understanding of the effect of SOX2 on the behavior of tumor cells originating from a human testicular germ cell tumor. Considering that NT2/D1 cells resemble cancer stem cells in many features, our results could contribute to the elucidation of the role of SOX2 in cancer stem cells behavior and the process of metastasis.

  8. The overexpression of SOX2 affects the migration of human teratocarcinoma cell line NT2/D1.

    Science.gov (United States)

    Drakulic, Danijela; Vicentic, Jelena Marjanovic; Schwirtlich, Marija; Tosic, Jelena; Krstic, Aleksandar; Klajn, Andrijana; Stevanovic, Milena

    2015-03-01

    The altered expression of the SOX2 transcription factor is associated with oncogenic or tumor suppressor functions in human cancers. This factor regulates the migration and invasion of different cancer cells. In this study we investigated the effect of constitutive SOX2 overexpression on the migration and adhesion capacity of embryonal teratocarcinoma NT2/D1 cells derived from a metastasis of a human testicular germ cell tumor. We detected that increased SOX2 expression changed the speed, mode and path of cell migration, but not the adhesion ability of NT2/D1 cells. Additionally, we demonstrated that SOX2 overexpression increased the expression of the tumor suppressor protein p53 and the HDM2 oncogene. Our results contribute to the better understanding of the effect of SOX2 on the behavior of tumor cells originating from a human testicular germ cell tumor. Considering that NT2/D1 cells resemble cancer stem cells in many features, our results could contribute to the elucidation of the role of SOX2 in cancer stem cells behavior and the process of metastasis.

  9. The prognostic value of SOX2 expression in non-small cell lung cancer: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yansu Chen

    Full Text Available OBJECTIVE: To investigate the association of SOX2 expression in tumor with clinicopathological features and survival of non-small-cell lung carcinoma (NSCLC patients. METHODS: Publications assessing the clinicopathological characteristics and prognostic significance of SOX2 in NSCLC were identified up to May 2013. A meta-analysis of eligible studies was performed using standard statistical methods to clarify the association between SOX2 expression and these clinical parameters. RESULTS: A total of eight studies met the inclusion criteria. Analysis of these data showed that SOX2 expression was positively associated with squamous histology, (pooled OR = 5.26, 95% CI: 1.08-25.6, P = 0.040. Simultaneously, we also found that SOX2 expression was positively associated with overall survival (pooled HR = 0.65, 95% CI: 0.47-0.89, P = 0.007, random-effect. CONCLUSIONS: SOX2 expression in tumor is a candidate positive prognostic biomarker for NSCLC patients.

  10. The exonuclease and host shutoff functions of the SOX protein of Kaposi's sarcoma-associated herpesvirus are genetically separable.

    Science.gov (United States)

    Glaunsinger, Britt; Chavez, Leonard; Ganem, Don

    2005-06-01

    The Kaposi's sarcoma-associated herpesvirus (KSHV) SOX protein, encoded by ORF37, promotes shutoff of host cell gene expression during lytic viral replication by dramatically impairing mRNA accumulation. SOX is the KSHV homolog of the alkaline exonuclease of other herpesviruses, which has been shown to function as a DNase involved in processing and packaging the viral genome. Although the exonuclease activity of these proteins is widely conserved across all herpesviruses, the host shutoff activity observed for KSHV SOX is not. We show here that SOX expression sharply reduces the half-life of target mRNAs. Extensive mutational analysis reveals that the DNase and host shutoff activities of SOX are genetically separable. Lesions affecting the DNase activity cluster in conserved regions of the protein, but residues critical for mRNA degradation are not conserved across the viral family. Additionally, we present evidence suggesting that the two different functions of SOX occur within distinct cellular compartments-DNase activity in the nucleus and host shutoff activity in the cytoplasm.

  11. Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects.

    Science.gov (United States)

    Bauters, Marijke; Frints, Suzanna G; Van Esch, Hilde; Spruijt, Liesbeth; Baldewijns, Marcella M; de Die-Smulders, Christine E M; Fryns, Jean-Pierre; Marynen, Peter; Froyen, Guy

    2014-08-01

    Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X;22)(q27;q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects.

  12. 3D imaging of Sox2 enhancer clusters in embryonic stem cells.

    Science.gov (United States)

    Liu, Zhe; Legant, Wesley R; Chen, Bi-Chang; Li, Li; Grimm, Jonathan B; Lavis, Luke D; Betzig, Eric; Tjian, Robert

    2014-12-24

    Combinatorial cis-regulatory networks encoded in animal genomes represent the foundational gene expression mechanism for directing cell-fate commitment and maintenance of cell identity by transcription factors (TFs). However, the 3D spatial organization of cis-elements and how such sub-nuclear structures influence TF activity remain poorly understood. Here, we combine lattice light-sheet imaging, single-molecule tracking, numerical simulations, and ChIP-exo mapping to localize and functionally probe Sox2 enhancer-organization in living embryonic stem cells. Sox2 enhancers form 3D-clusters that are segregated from heterochromatin but overlap with a subset of Pol II enriched regions. Sox2 searches for specific binding targets via a 3D-diffusion dominant mode when shuttling long-distances between clusters while chromatin-bound states predominate within individual clusters. Thus, enhancer clustering may reduce global search efficiency but enables rapid local fine-tuning of TF search parameters. Our results suggest an integrated model linking cis-element 3D spatial distribution to local-versus-global target search modalities essential for regulating eukaryotic gene transcription.

  13. Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice

    Science.gov (United States)

    Overman, Jeroen; Fontaine, Frank; Moustaqil, Mehdi; Mittal, Deepak; Sierecki, Emma; Sacilotto, Natalia; Zuegg, Johannes; Robertson, Avril AB; Holmes, Kelly; Salim, Angela A; Mamidyala, Sreeman; Butler, Mark S; Robinson, Ashley S; Lesieur, Emmanuelle; Johnston, Wayne; Alexandrov, Kirill; Black, Brian L; Hogan, Benjamin M; Val, Sarah De; Capon, Robert J; Carroll, Jason S; Bailey, Timothy L; Koopman, Peter; Jauch, Ralf; Smyth, Mark J; Cooper, Matthew A; Gambin, Yann; Francois, Mathias

    2017-01-01

    Pharmacological targeting of transcription factors holds great promise for the development of new therapeutics, but strategies based on blockade of DNA binding, nuclear shuttling, or individual protein partner recruitment have yielded limited success to date. Transcription factors typically engage in complex interaction networks, likely masking the effects of specifically inhibiting single protein-protein interactions. Here, we used a combination of genomic, proteomic and biophysical methods to discover a suite of protein-protein interactions involving the SOX18 transcription factor, a known regulator of vascular development and disease. We describe a small-molecule that is able to disrupt a discrete subset of SOX18-dependent interactions. This compound selectively suppressed SOX18 transcriptional outputs in vitro and interfered with vascular development in zebrafish larvae. In a mouse pre-clinical model of breast cancer, treatment with this inhibitor significantly improved survival by reducing tumour vascular density and metastatic spread. Our studies validate an interactome-based molecular strategy to interfere with transcription factor activity, for the development of novel disease therapeutics. DOI: http://dx.doi.org/10.7554/eLife.21221.001 PMID:28137359

  14. SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia.

    Science.gov (United States)

    Mauri, Lucia; Franzoni, Alessandra; Scarcello, Manuela; Sala, Stefano; Garavelli, Livia; Modugno, Alessandra; Grammatico, Paola; Patrosso, Maria Cristina; Piozzi, Elena; Del Longo, Alessandra; Gesu, Giovanni P; Manfredini, Emanuela; Primignani, Paola; Damante, Giuseppe; Penco, Silvana

    2015-02-01

    Anophthalmia (A) and microphthalmia (M) are rare developmental anomalies that have significant effects on visual activity. In fraction of A/M subjects, single genetic defects have been identified as causative. In this study we analysed 65 Italian A/M patients, 21 of whom are syndromic, for mutations in SOX2, OTX2 and PAX6 genes. In syndromic patients the presence of genome imbalances through array CGH was also investigated. No mutations were found for OTX2 and PAX6 genes. Three causative SOX2 mutations were found in subjects with syndromic A. In a subject with syndromic signs and monolateral M, two de novo 6.26 Mb and 1.37 Mb deletions in 4q13.2q13.3 have been identified. A SOX2 missense (p.Ala161Ser) mutation was found in 1 out of 39 a subject with non-syndromic monolateral M. Alanine at position 161 is conserved along phylogeny and the p.Ala161Ser mutation is estimated pathogenic by in silico analysis. However, this mutation was also present in the unaffected patient's daughter.

  15. The HMG-box transcription factor Sox4b is required for pituitary expression of gata2a and specification of thyrotrope and gonadotrope cells in zebrafish.

    Science.gov (United States)

    Quiroz, Yobhana; Lopez, Mauricio; Mavropoulos, Anastasia; Motte, Patrick; Martial, Joseph A; Hammerschmidt, Matthias; Muller, Marc

    2012-06-01

    The pituitary is a complex gland comprising different cell types each secreting specific hormones. The extensive network of signaling molecules and transcription factors required for determination and terminal differentiation of specific cell types is still not fully understood. The SRY-like HMG-box (SOX) transcription factor Sox4 plays important roles in many developmental processes and has two homologs in zebrafish, Sox4a and Sox4b. We show that the sox4b gene is expressed in the pituitary anlagen starting at 24 h after fertilization (hpf) and later in the entire head region including the pituitary. At 48 hpf, sox4b mRNA colocalizes with that for TSH (tshβ), glycoprotein subunit α (gsuα), and the Zn finger transcription factor Gata2a. Loss of Sox4b function, using morpholino knockdown or expression of a dominant-negative Sox4 mutant, leads to a drastic decrease in tshβ and gsuα expression and reduced levels of gh, whereas other anterior pituitary gland markers including prl, slβ, pomc, and lim3 are not affected. Sox4b is also required for expression of gata2a in the pituitary. Knockdown of gata2a leads to decreased tshβ and gsuα expression at 48 hpf, similar to sox4b morphants. Injection of gata2a mRNA into sox4b morphants rescued tshβ and gsuα expression in thyrotrope cells. Finally, sox4b or gata2a knockdown causes a significant decrease of gonadotropin expression (lhβ and fshβ) at 4 d after fertilization. In summary, our results indicate that Sox4b is expressed in zebrafish during pituitary development and plays a crucial role in the differentiation of thyrotrope and gonadotrope cells through induction of gata2a expression in the developing pituitary.

  16. Enhancement of neural and thermal vasoconstriction by prostaglandin B1.

    Science.gov (United States)

    Engelbrecht, J A; Greenberg, S; Wilson, W R

    1975-03-01

    The vascular effects of prostaglandin B1 (PGB1) were studied during constant-flow perfusion of the canine hindpaw. The effects of PGB1 (50-200 ng/kg/min ia) on systemic and hindpaw perfusion pressures and on responses to local cooling (4 degrees C for 90 sec) and local heating (45 degrees C for 60 sec) were measured in 15 dogs. PGB1 (50-100 ng/kg/min) decreased perfusion pressure without any significant effect on systemic arterial pressure. Higher concentrations of PGB1 (200 ng/kg/min) elevated perfusion pressure to control values. The pressor responses to local cooling were increased from 11 to 32 mmHg while the dilator responses to local heating and nitroglycerin were reduced during infusions of PGB1. PGB1 also enhanced the pressor responses to norepinephrine or tyramine. These findings support the conclusions that (1) low concentrations of prostaglandin B1 enhance neurotransmitter release with minimal effects on vascular smooth muscle cells and (2) these effects are not secondary to increased perfusion pressures or vascular wall stresses since infusions of PGB1 resulted in vasodilation.

  17. Synthesis of Polyclonal Antibodies against Aflatoxin B1

    Directory of Open Access Journals (Sweden)

    Wiyogo Prio Wicaksono

    2015-09-01

    Full Text Available Polyclonal antibodies of aflatoxin B1 were successfully produced from New Zealand White female rabbits after immunization by the hapten of aflatoxin B1-carboxymethyl hydroxylamine hemihydrochloride (AFB1-CMO conjugated with bovine serum albumin (BSA as the antigen. The hapten was synthesized using the carbodiimide method with CMO as a linker. Absorption peaks at 362, 264, and 218 nm were observed as a result of characterization with UV-Vis spectroscopy, while IR spectroscopy showed peaks at 3448 cm-1 and 1642 cm-1 attributable to the hydroxyl and nitrile groups, respectively. Furthermore, mass spectrometry showed fragmentation at the m/z of 386, 368.2, and 310, which confirms that the hapten of AFB1-CMO was successfully synthesized. The hapten was then conjugated with BSA to serve as an antigen of AFB1 when it was injected into the rabbits. The specificity of the antigen towards its antibody and the confirmation of hapten-BSA conjugation were characterized using the dot blot immunoassay, which showed a BSA concentration of 1.74 mg/mL. Two weeks after the primary immunization by its antigen, agar gel precipitation testing showed that the rabbit blood serum had positive results for polyclonal antibodiest against AFB1 with the highest concentration of antibodiest of 2.19 mg/mL.

  18. DELF B1 200 activités

    CERN Document Server

    Bloomfield, Anatole

    2006-01-01

    L'ouvrage est organisé par compétences de réception et de production. Chaque partie propose d'abord une présentation de l'épreuve correspondante, puis les activités de préparation suivies d'épreuves-types et d'une auto-évaluation. Dans le cadre d'une approche actionnelle, les activités fournissent les outils nécessaires à la préparation des examens. Elles donnent des exemples concrets répondant aux attentes des candidats comme à celle des examinateurs. LeNouveau DELF B1 propose des activités précises en vue d'atteindre les compétences nécessaires aux épreuves (oral, écrit, réception, production); sa simplicité et sa pédagogie en font une méthode complète. Dans la tradition de la collection Nouvel Entraînez-vous, cet ouvrage est pratique, didactique et se prête à une utilisation en autonomie ou en classe.Le niveau B1 dit " avancé " évalue un niveau de compétence où l'apprenant peut se considérer comme étant indépendant. Arrivé à ce stade, il est apte de comprendre l'inform...

  19. SOX9基因判断前列腺癌恶性程度及生化复发的预测%SOX9 gene for judgment of malignancy and prediction of biochemical relapse of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    秦国强; 江福能; 毕学成; 韩兆冬; 何慧婵; 钟惟德

    2012-01-01

    Objective:To investigate the role of SOX9 gene for judgment of malignancy and prediction of biochemical relapse of prostate cancer after castration. Methods: Inquiry of SOX9 expression in prostate cancer tissues was conducted in Oncomine,the public Database. Expression of SOX9 in DU145,LNCap and PC3, cell lines of prostate cancer, and RWPE-1, the normal prostate cell line, was detected using reverse transcription-quantitative polymerase chain reaction ( RT-QPCR). Immunohistochemical assay was employed to detect SOX9 expression in 106 prostate cancer tissues and adjacent tissues for further clinical analysis of pathologic parameters. Surgical SD rat castration models were constructed to detect SOX9 expression in prostate tissues. Results: Marked SOX9 expression was presented in prostate cancer tissues. The PC3 cell line was noted as having considerably higher S0X9 expression than RWPE-1 (P =0.004). Of 106 tissues,prostate cancer tissues yielded significantly higher level of S0X9 positive expression (n = 62 ) than adjacent cancerous tissues ( n =26) ( P = 0. 000). Intense SOX9 expression was positively correlated with serum PSA ( P = 0. 007 ) , Gleason score (P =0.034) and tumor TNM stage (P =0.004) ,but not with age (P=0. 179). The distinction in the number of SD rats with SOX9 positively stained prostate cancer tissues between control group ( n = 2 ) and model group ( n = 9) reached statistical significance (P < 0. 05 ). Conclusion; Intense SOX9 expression is correlated with malignancy of prostate cancer. In addition to predicting the progress of biochemical relapse, it is possible to offer early diagnosis and judgment of malignancy via determination of SOX9 expression and serum PSA concentration.%目的:探讨SOX9基因在判断前列腺癌恶性程度及预测前列腺癌去势后生化复发的作用.方法:通过Oncomine公共数据库查询SOX9基因在前列腺癌中的表达情况;RT-QPCR法检测SOX9基因在前列腺癌细胞株DU145、LNCap、PC3和

  20. SOX9 governs differentiation stage-specific gene expression in growth plate chondrocytes via direct concomitant transactivation and repression.

    Directory of Open Access Journals (Sweden)

    Victor Y L Leung

    2011-11-01

    Full Text Available Cartilage and endochondral bone development require SOX9 activity to regulate chondrogenesis, chondrocyte proliferation, and transition to a non-mitotic hypertrophic state. The restricted and reciprocal expression of the collagen X gene, Col10a1, in hypertrophic chondrocytes and Sox9 in immature chondrocytes epitomise the precise spatiotemporal control of gene expression as chondrocytes progress through phases of differentiation, but how this is achieved is not clear. Here, we have identified a regulatory element upstream of Col10a1 that enhances its expression in hypertrophic chondrocytes in vivo. In immature chondrocytes, where Col10a1 is not expressed, SOX9 interacts with a conserved sequence within this element that is analogous to that within the intronic enhancer of the collagen II gene Col2a1, the known transactivation target of SOX9. By analysing a series of Col10a1 reporter genes in transgenic mice, we show that the SOX9 binding consensus in this element is required to repress expression of the transgene in non-hypertrophic chondrocytes. Forced ectopic Sox9 expression in hypertrophic chondrocytes in vitro and in mice resulted in down-regulation of Col10a1. Mutation of a binding consensus motif for GLI transcription factors, which are the effectors of Indian hedgehog signaling, close to the SOX9 site in the Col10a1 regulatory element, also derepressed transgene expression in non-hypertrophic chondrocytes. GLI2 and GLI3 bound to the Col10a1 regulatory element but not to the enhancer of Col2a1. In addition to Col10a1, paired SOX9-GLI binding motifs are present in the conserved non-coding regions of several genes that are preferentially expressed in hypertrophic chondrocytes and the occurrence of pairing is unlikely to be by chance. We propose a regulatory paradigm whereby direct concomitant positive and negative transcriptional control by SOX9 ensures differentiation phase-specific gene expression in chondrocytes. Discrimination between

  1. Preliminary screening of downstream proteins of Sox2 and role of Sox2 in colonic cancer cell migration and invasion%Sox2下游调控蛋白的筛选及其对大肠癌细胞增殖、迁移的影响

    Institute of Scientific and Technical Information of China (English)

    周敏; 陆滟霞; 袁理; 郑林; 刘燕; 洪敏; 张超; 李学农

    2014-01-01

    Objective To screen the down-stream proteins of transcription factor Sox2 and explore the role of Sox2 in the proliferation and migration of colonic cancer cells in vitro. Methods The cellular proteins were separated by SDS-PAGE electrophoresis and stained with Coomassie blue and amine plated silver. The differentially expressed proteins was identified by mass spectrometry and verified by QPCR and Western blotting. A cell counting kit-8 (CCK8) assay was performed to evaluate the cell proliferation, and the cell migration was assessed using Transwell assay. Results S3a was identified by proteomics technology as a Sox2-downregulated protein while ENO1 and gama-actin the up-regulated proteins. QPCR and Western blotting analyses showed that overexpression of Sox2 significantly decreased the expression of S3a (P<0.005) and increased the expression of ENO1(P<0.05), but had no significant effect on gama-actin expression. Sox2 overexpression obviously promoted cell proliferation and migration (P<0.05), while inhibition of Sox2 produced contrary effects (P<0.05). Conclusion Sox2 negatively regulates S3a expression and positively regulates ENO1 expression to promot the proliferation and migration of colonic cancer cells.%目的:分析大肠癌细胞转录因子Sox2对大肠癌细胞增殖及迁移的影响。方法应用SDS-PAGE蛋白电泳,结合考马斯亮蓝及镀胺银染色方法,筛选差异蛋白。质谱分析筛选Sox2下游调控蛋白,应用定量PCR(QPCR)及Western blotting验证和鉴定下游调控蛋白。Cell Counting Kit-8(CCK8)观察Sox2对大肠癌细胞增殖的影响,Transwell实验观察Sox2对迁移能力的影响。结果应用蛋白组学技术成功筛选出Sox2下调蛋白S3a、上调蛋白ENO1、Gama-actin。QPCR和Western blotting显示,Sox2过表达后,大肠癌细胞S3a表达减少(P<0.005),ENO1表达增加(P<0.05),Gama-actin表达无明显差异,细胞增殖及迁移能力提高(P<0.05);Sox2

  2. Effectiveness of compression stockings to prevent the post-thrombotic syndrome (The SOX Trial and Bio-SOX biomarker substudy: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Rodger Marc A

    2007-07-01

    Full Text Available Abstract Background Post thrombotic syndrome (PTS is a burdensome and costly complication of deep venous thrombosis (DVT that develops in 20–40% of patients within 1–2 years after symptomatic DVT. Affected patients have chronic leg pain and swelling and may develop ulcers. Venous valve disruption from the thrombus itself or thrombus-associated mediators of inflammation is considered to be a key initiating event for the development of venous hypertension that often underlies PTS. As existing treatments for PTS are extremely limited, strategies that focus on preventing the development of PTS in patients with DVT are more likely to be effective and cost-effective in reducing its burden. Elastic compression stockings (ECS could be helpful in preventing PTS; however, data on their effectiveness are scarce and conflicting. Methods/Design The SOX Trial is a randomized, allocation concealed, double-blind multicenter clinical trial. The objective of the study is to evaluate ECS to prevent PTS. A total of 800 patients with proximal DVT will be randomized to one of 2 treatment groups: ECS or placebo (inactive stockings worn on the DVT-affected leg daily for 2 years. The primary outcome is the incidence of PTS during follow-up. Secondary outcomes are severity of PTS, venous thromboembolism (VTE recurrence, death from VTE, quality of life and cost-effectiveness. Outcomes will be evaluated during 6 clinic visits and 2 telephone follow ups. At baseline, 1 and 6 months, blood samples will be obtained to evaluate the role of inflammatory mediators and genetic markers of thrombophilia in the development of PTS (Bio-SOX substudy. Discussion The SOX Trial will be the largest study and the first with a placebo control to evaluate the effectiveness of ECS to prevent PTS. It is designed to provide definitive data on the effects of ECS on the occurrence and severity of PTS, as well as DVT recurrence, cost-effectiveness and quality of life. This study will also

  3. 16 CFR Appendix B1 to Part 305 - Upright Freezers With Manual Defrost

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Upright Freezers With Manual Defrost B1 Appendix B1 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF...) Pt. 305, App. B1 Appendix B1 to Part 305—Upright Freezers With Manual Defrost Range...

  4. Performance of an activated carbon made from waste palm shell in simultaneous adsorption of SO_x and NO_x of flue gas at low temperature

    Institute of Scientific and Technical Information of China (English)

    S.; SUMATHI; S.; BHATIA; K.T.; LEE; A.; R.; MOHAMED

    2009-01-01

    This study examined the individual and simultaneous adsorption of SOx (SO2) and NOx (NO-NO2) on activated carbon prepared from waste palm shell. The adsorption process was examined in a fixed bed reactor at low temperatures (100―300℃). For individual adsorption without any catalytic activation, SOx showed good adsorption whereas NOx was very much poor. In the simultaneous adsorption of SOx and NOx, SOx showed greater adsorption affinity than NOx. For palm shell activated carbon (PSAC) impregnated with metal catalyst (Ni and Ce) the concentration adsorbed profile showed that the amount of SOx adsorbed decreased regularly, while the amount of the adsorbed NOx increased irregularly. The properties of the pure and impregnated PSAC were analyzed by BET, SEM and EDX. These investiga-tions indicated that PSAC impregnated with metal catalyst is the determining factor in the adsorption of SOx and NOx simultaneously.

  5. Mecanismos moleculares envolvidos na mutagenicidade induzida pela aflatoxina B1

    OpenAIRE

    2012-01-01

    La aflatoxina B1 (AFB1) es una micotoxina identificada como el más potente hepatocarcinógeno. El metabolito que resulta del proceso de detoxificación de la AFB1 en el hígado tiene la capacidad de reaccionar con el ADN genómico, generando el aducto AFB1-ADN; durante la replicación del ADN este aducto induce la transversión G:C→T:A. Polimorfismos en los genes que codifican las enzimas encargadas de la activación y detoxificación de la AFB1 y enzimas de reparación del ADN han sido asociados con ...

  6. Characterization of TetD as a transcriptional activator of a subset of genes of the Escherichia coli SoxS/MarA/Rob regulon.

    Science.gov (United States)

    Griffith, Kevin L; Becker, Stephen M; Wolf, Richard E

    2005-05-01

    In Escherichia coli, SoxS, MarA and Rob form a closely related subset of the AraC/XylS family of positive regulators, sharing approximately 42% amino acid sequence identity over the length of SoxS and the ability to activate transcription of a common set of target genes that provide resistance to redox-cycling compounds and antibiotics. On the basis of its approximately 43% amino acid sequence identity with SoxS, MarA and Rob, TetD, encoded by transposon Tn10, appears to be a fourth member of the subset. However, although its expression has been shown to be negatively regulated by TetC and not inducible by tetracycline, the physiological function of TetD is unknown. Accordingly, in the work presented here, we initiate a molecular characterization of TetD. We show that expression of TetD activates transcription of a subset of the SoxS/MarA/Rob regulon genes and confers resistance to redox-cycling compounds and antibiotics. We show that mutations in the putative TetD binding site of a TetD-activatable promoter and a mutation in the protein's N-terminal DNA recognition helix interfere with transcription activation, thereby indicating that TetD directly activates target gene transcription. Finally, we show that TetD, like SoxS and MarA, is intrinsically unstable; however, unlike SoxS and MarA, TetD is not degraded by Lon or any of the cell's known cytoplasmic ATP-dependent proteases. Thus, we conclude that TetD is a bona fide member of the SoxS/MarA/Rob subfamily of positive regulators.

  7. Luteolin and apigenin activate the Oct-4/Sox2 signal via NFATc1 in human periodontal ligament cells.

    Science.gov (United States)

    Liu, Lu; Peng, Zhengjun; Huang, Haoquan; Xu, Zhezhen; Wei, Xi

    2016-10-01

    Identifying small molecules to activate the Oct-4/Sox2-derived pluripotency network represents a hopeful and safe method to pluripotency without genetic manipulation. Luteolin and apigenin, two major bioactive flavonoids, enhance reprogramming efficiency and increase expression of Oct-4/Sox2/c-Myc, albeit the detailed mechanism regulating pluripotency in dental-derived cells remains unknown. In the present study, to elucidate the effect of luteolin/apigenin on pluripotency of periodontal ligament cells (PDLCs) through interaction with downstream signals, we examined cell cycle, proliferation, apoptosis, expression of Oct-4/Sox2/c-Myc, and multilineage differentiation of PDLCs with luteolin/apigenin treatment. Moreover, we profiled the differentially expressed pluripotency genes by PCR arrays. Our results demonstrated that luteolin/apigenin restrained cell proliferation, increased apoptosis, and arrested PDLCs in G2/M and S phase. Luteolin and apigenin activated expression of Oct-4, Sox2, and c-Myc in a time- and dose-dependent pattern, and repressed lineage-specific differentiation. PCR arrays profiled multiple signals in PDLCs with luteolin/apigenin treatment, among which NFATc1 was the major upregulated gene. Notably, blocking of the NFATc1 signal with INCA-6 significantly decreased mRNA and protein expression of Oct-4, Sox2, and c-Myc in PDLCs with luteolin/apigenin treatment, indicating that NFATc1 may act as an upstream modulator of Oct-4/Sox2 signal. Taken together, this study showed that luteolin and apigenin effectively maintain pluripotency of PDLCs through activation of Oct-4/Sox2 signal via NFATc1.

  8. Sox9 drives columnar differentiation of esophageal squamous epithelium: a possible role in the pathogenesis of Barrett's esophagus.

    Science.gov (United States)

    Clemons, Nicholas J; Wang, David H; Croagh, Daniel; Tikoo, Anjali; Fennell, Christina M; Murone, Carmel; Scott, Andrew M; Watkins, D Neil; Phillips, Wayne A

    2012-12-15

    The molecular mechanism underlying the development of Barrett's esophagus (BE), the precursor to esophageal adenocarcinoma, remains unknown. Our previous work implicated sonic hedgehog (Shh) signaling as a possible driver of BE and suggested that bone morphogenetic protein 4 (Bmp4) and Sox9 were downstream mediators. We have utilized a novel in vivo tissue reconstitution model to investigate the relative roles of Bmp4 and Sox9 in driving metaplasia. Epithelia reconstituted from squamous epithelial cells or empty vector-transduced cells had a stratified squamous phenotype, reminiscent of normal esophagus. Expression of Bmp4 in the stromal compartment activated signaling in the epithelium but did not alter the squamous phenotype. In contrast, expression of Sox9 in squamous epithelial cells induced formation of columnar-like epithelium with expression of the columnar differentiation marker cytokeratin 8 and the intestinal-specific glycoprotein A33. In patient tissue, A33 protein was expressed specifically in BE, but not in normal esophagus. Expression of Cdx2, another putative driver of BE, alone had no effect on reconstitution of a squamous epithelium. Furthermore, epithelium coexpressing Cdx2 and Sox9 had a phenotype similar to epithelium expressing Sox9 alone. Our results demonstrate that Sox9 is sufficient to drive columnar differentiation of squamous epithelium and expression of an intestinal differentiation marker, reminiscent of BE. These data suggest that Shh-mediated expression of Sox9 may be an important early event in the development of BE and that the potential for inhibitors of the hedgehog pathway to be used in the treatment of BE and/or esophageal adenocarcinoma could be tested in the near future.

  9. HIPPO pathway members restrict SOX2 to the inner cell mass where it promotes ICM fates in the mouse blastocyst.

    Directory of Open Access Journals (Sweden)

    Eryn Wicklow

    2014-10-01

    Full Text Available Pluripotent epiblast (EPI cells, present in the inner cell mass (ICM of the mouse blastocyst, are progenitors of both embryonic stem (ES cells and the fetus. Discovering how pluripotency genes regulate cell fate decisions in the blastocyst provides a valuable way to understand how pluripotency is normally established. EPI cells are specified by two consecutive cell fate decisions. The first decision segregates ICM from trophectoderm (TE, an extraembryonic cell type. The second decision subdivides ICM into EPI and primitive endoderm (PE, another extraembryonic cell type. Here, we investigate the roles and regulation of the pluripotency gene Sox2 during blastocyst formation. First, we investigate the regulation of Sox2 patterning and show that SOX2 is restricted to ICM progenitors prior to blastocyst formation by members of the HIPPO pathway, independent of CDX2, the TE transcription factor that restricts Oct4 and Nanog to the ICM. Second, we investigate the requirement for Sox2 in cell fate specification during blastocyst formation. We show that neither maternal (M nor zygotic (Z Sox2 is required for blastocyst formation, nor for initial expression of the pluripotency genes Oct4 or Nanog in the ICM. Rather, Z Sox2 initially promotes development of the primitive endoderm (PE non cell-autonomously via FGF4, and then later maintains expression of pluripotency genes in the ICM. The significance of these observations is that 1 ICM and TE genes are spatially patterned in parallel prior to blastocyst formation and 2 both the roles and regulation of Sox2 in the blastocyst are unique compared to other pluripotency factors such as Oct4 or Nanog.

  10. Limitations of Radar Coordinates

    OpenAIRE

    Bini, Donato; Lusanna, Luca; Mashhoon, Bahram

    2004-01-01

    The construction of a radar coordinate system about the world line of an observer is discussed. Radar coordinates for a hyperbolic observer as well as a uniformly rotating observer are described in detail. The utility of the notion of radar distance and the admissibility of radar coordinates are investigated. Our results provide a critical assessment of the physical significance of radar coordinates.

  11. SOX9 directly Regulates CTGF/CCN2 Transcription in Growth Plate Chondrocytes and in Nucleus Pulposus Cells of Intervertebral Disc.

    Science.gov (United States)

    Oh, Chun-do; Yasuda, Hideyo; Zhao, Weiwei; Henry, Stephen P; Zhang, Zhaoping; Xue, Ming; de Crombrugghe, Benoit; Chen, Di

    2016-07-20

    Several lines of evidence indicate that connective tissue growth factor (CTGF/CCN2) stimulates chondrocyte proliferation and maturation. Given the fact that SOX9 is essential for several steps of the chondrocyte differentiation pathway, we asked whether Ctgf (Ccn2) is the direct target gene of SOX9. We found that Ctgf mRNA was down-regulated in primary sternal chondrocytes from Sox9(flox/flox) mice infected with Ad-CMV-Cre. We performed ChIP-on-chip assay using anti-SOX9 antibody, covering the Ctgf gene from 15 kb upstream of its 5'-end to 10 kb downstream of its 3'-end to determine SOX9 interaction site. One high-affinity interaction site was identified in the Ctgf proximal promoter by ChIP-on-chip assay. An important SOX9 regulatory element was found to be located in -70/-64 region of the Ctgf promoter. We found the same site for SOX9 binding to the Ctgf promoter in nucleus pulposus (NP) cells. The loss of Sox9 in growth plate chondrocytes in knee joint and in NP cells in intervertebral disc led to the decrease in CTGF expression. We suggest that Ctgf is the direct target gene of SOX9 in chondrocytes and NP cells. Our study establishes a strong link between two regulatory molecules that have a major role in cartilaginous tissues.

  12. On the active site of mononuclear B1 metallo β-lactamases: a computational study

    Science.gov (United States)

    Sgrignani, Jacopo; Magistrato, Alessandra; Dal Peraro, Matteo; Vila, Alejandro J.; Carloni, Paolo; Pierattelli, Roberta

    2012-04-01

    Metallo-β-lactamases (MβLs) are Zn(II)-based bacterial enzymes that hydrolyze β-lactam antibiotics, hampering their beneficial effects. In the most relevant subclass (B1), X-ray crystallography studies on the enzyme from Bacillus Cereus point to either two zinc ions in two metal sites (the so-called `3H' and `DCH' sites) or a single Zn(II) ion in the 3H site, where the ion is coordinated by Asp120, Cys221 and His263 residues. However, spectroscopic studies on the B1 enzyme from B. Cereus in the mono-zinc form suggested the presence of the Zn(II) ion also in the DCH site, where it is bound to an aspartate, a cysteine, a histidine and a water molecule. A structural model of this enzyme in its DCH mononuclear form, so far lacking, is therefore required for inhibitor design and mechanistic studies. By using force field based and mixed quantum-classical (QM/MM) molecular dynamics (MD) simulations of the protein in aqueous solution we constructed such structural model. The geometry and the H-bond network at the catalytic site of this model, in the free form and in complex with two common β-lactam drugs, is compared with experimental and theoretical findings of CphA and the recently solved crystal structure of new B2 MβL from Serratia fonticola (Sfh-I). These are MβLs from the B2 subclass, which features an experimentally well established mono-zinc form, in which the Zn(II) is located in the DCH site. From our simulations the ɛɛδ and δɛδ protomers emerge as possible DCH mono-zinc reactive species, giving a novel contribution to the discussion on the MβL reactivity and to the drug design process.

  13. Porcine SOX9 Gene Expression Is Influenced by an 18 bp Indel in the 5'-Untranslated Region.

    Directory of Open Access Journals (Sweden)

    Bertram Brenig

    Full Text Available Sex determining region Y-box 9 (SOX9 is an important regulator of sex and skeletal development and is expressed in a variety of embryonal and adult tissues. Loss or gain of function resulting from mutations within the coding region or chromosomal aberrations of the SOX9 locus lead to a plethora of detrimental phenotypes in humans and animals. One of these phenotypes is the so-called male-to-female or female-to-male sex-reversal which has been observed in several mammals including pig, dog, cat, goat, horse, and deer. In 38,XX sex-reversal French Large White pigs, a genome-wide association study suggested SOX9 as the causal gene, although no functional mutations were identified in affected animals. However, besides others an 18 bp indel had been detected in the 5'-untranslated region of the SOX9 gene by comparing affected animals and controls. We have identified the same indel (Δ18 between position +247 bp and +266 bp downstream the transcription start site of the porcine SOX9 gene in four other pig breeds; i.e., German Large White, Laiwu Black, Bamei, and Erhualian. These animals have been genotyped in an attempt to identify candidate genes for porcine inguinal and/or scrotal hernia. Because the 18 bp segment in the wild type 5'-UTR harbours a highly conserved cAMP-response element (CRE half-site, we analysed its role in SOX9 expression in vitro. Competition and immunodepletion electromobility shift assays demonstrate that the CRE half-site is specifically recognized by CREB. Both binding of CREB to the wild type as well as the absence of the CRE half-site in Δ18 reduced expression efficiency in HEK293T, PK-15, and ATDC5 cells significantly. Transfection experiments of wild type and Δ18 SOX9 promoter luciferase constructs show a significant reduction of RNA and protein levels depending on the presence or absence of the 18 bp segment. Hence, the data presented here demonstrate that the 18 bp indel in the porcine SOX9 5'-UTR is of functional

  14. Porcine SOX9 Gene Expression Is Influenced by an 18 bp Indel in the 5'-Untranslated Region.

    Science.gov (United States)

    Brenig, Bertram; Duan, Yanyu; Xing, Yuyun; Ding, Nengshui; Huang, Lusheng; Schütz, Ekkehard

    2015-01-01

    Sex determining region Y-box 9 (SOX9) is an important regulator of sex and skeletal development and is expressed in a variety of embryonal and adult tissues. Loss or gain of function resulting from mutations within the coding region or chromosomal aberrations of the SOX9 locus lead to a plethora of detrimental phenotypes in humans and animals. One of these phenotypes is the so-called male-to-female or female-to-male sex-reversal which has been observed in several mammals including pig, dog, cat, goat, horse, and deer. In 38,XX sex-reversal French Large White pigs, a genome-wide association study suggested SOX9 as the causal gene, although no functional mutations were identified in affected animals. However, besides others an 18 bp indel had been detected in the 5'-untranslated region of the SOX9 gene by comparing affected animals and controls. We have identified the same indel (Δ18) between position +247 bp and +266 bp downstream the transcription start site of the porcine SOX9 gene in four other pig breeds; i.e., German Large White, Laiwu Black, Bamei, and Erhualian. These animals have been genotyped in an attempt to identify candidate genes for porcine inguinal and/or scrotal hernia. Because the 18 bp segment in the wild type 5'-UTR harbours a highly conserved cAMP-response element (CRE) half-site, we analysed its role in SOX9 expression in vitro. Competition and immunodepletion electromobility shift assays demonstrate that the CRE half-site is specifically recognized by CREB. Both binding of CREB to the wild type as well as the absence of the CRE half-site in Δ18 reduced expression efficiency in HEK293T, PK-15, and ATDC5 cells significantly. Transfection experiments of wild type and Δ18 SOX9 promoter luciferase constructs show a significant reduction of RNA and protein levels depending on the presence or absence of the 18 bp segment. Hence, the data presented here demonstrate that the 18 bp indel in the porcine SOX9 5'-UTR is of functional importance and may

  15. Effect of SOX13 antibody on islet β cell function in ketosis-prone diabetes%SOX13抗体对酮症倾向糖尿病患者胰岛功能的影响

    Institute of Scientific and Technical Information of China (English)

    李莉蓉; 上官海燕; 沈山梅; 胡云; 黄干; 周智广; 朱大龙

    2010-01-01

    目的 探讨SOX13抗体(sry related HMG box 13-antibody,SOX13-Ab)对酮症倾向糖尿病(KPD)患者胰岛功能的影响,进一步确定SOX13-Ab在KPD患者中的自身免疫反应特征.方法 2005年1月至2009年11月对南京鼓楼医院内分泌科就诊的245例KPD患者[男138例,女107例,年龄33(1~80)岁]均检测SOX13-Ab、谷氨酸脱羧酶抗体(GAD-Ab)和蛋白酪氨酸磷酸酶抗体(IA-2A),以SOX13-Ab单一阳性患者为病例组,以GAD-Ab、IA-2A单一阳性及抗体均阴性组患者为对照组,比较4组患者的胰岛功能.各组平均C肽水平采用中位数(四分位数间距)表示,经自然对数转化后进一步采用方差分析比较组间差异.结果 (1)女性患者中SOX13-Ab单一阳性、GAD-Ab单一阳性组空腹C肽(FCP)和餐后2 h C肽(PCP)水平分别为166.0(300.0)和166.5(159.3)、285.0(527.0)和231.0(502.5)pmol/L,均显著低于抗体阴性组[FCP为287.5(302.7)pmol/L、PCP为528.0(774.0)pmol/L;均P<0.05];(2)发病年龄≤40岁或病程≤5年的KPD患者中,其FCP水平SOX13-Ab组[166.0(56.0)vs 228.0(250.0)pmol/L]、GAD-Ab单一阳性组[191.0(137.5)vs 324.0(340.0)pmol/L]均显著低于抗体阴性组[167.1(223.1)vs 324.0(340.0)pmol/L];而在病程>5年的KPD患者中,GAD-Ab单一阳性组FCP水平为130.0(458.8)pmol/L、SOX13-Ab单一阳性组为189.5(357.7)pmol/L,两组比较差异有统计学意义(P<0.05);(3)协方差分析显示SOX13-Ab单一阳性与抗体阴性组之间FCP、PCP比较差异无统计学意义(P>0.05);而GAD-Ab/SOX13-Ab双阳性组FCP与抗体阴性组比较差异有统计学意义(P<0.05);(4)GAD-Ab、IA-2A单一阳性组内FCP与病程均呈显著负相关(r值分别为-0.500、-0.821,P值分别为0.007、0.023),而SOX13-Ab单一阳性组内FCP与病程之间无显著负相关性(r=-0.104,P=0.606).结论 SOX13-Ab对KPD患者胰岛功能的影响弱于GAD-Ab.%Objective To explore the effect of SOX13 antibody(sry related HMG box 13-antibody,SOX13-Ab)on islet β cell function and to

  16. A genome-wide association analysis implicates SOX6 as a candidate gene for wrist bone mass

    Institute of Scientific and Technical Information of China (English)

    Shawn; LEVY

    2010-01-01

    Osteoporosis is a highly heritable common bone disease leading to fractures that severely impair the life quality of patients.Wrist fractures caused by osteoporosis are largely due to the scarcity of wrist bone mass.Here we report the results of a genome-wide association study (GWAS) of wrist bone mineral density (BMD).We examined ~500000 SNP markers in 1000 unrelated homogeneous Caucasian subjects and found a novel allelic association with wrist BMD at rs11023787 in the SOX6 (SRY (sex determining region Y)-box 6) gene (P=9.00×10-5).Subjects carrying the C allele of rs11023787 in SOX6 had significantly higher mean wrist BMD values than those with the T allele (0.485:0.462 g cm-2 for C allele vs.T allele carriers).For validation,we performed SOX6 association for BMD in an independent Chinese sample and found that SNP rs11023787 was significantly associated with wrist BMD in the Chinese sample (P=6.41×10-3).Meta-analyses of the GWAS scan and the replication studies yielded P-values of 5.20×10-6 for rs11023787.Results of this study,together with the functional relevance of SOX6 in cartilage formation,support the SOX6 gene as an important gene for BMD variation.

  17. Growth factors and medium hyperglycemia induce Sox9+ ductal cell differentiation into β cells in mice with reversal of diabetes.

    Science.gov (United States)

    Zhang, Mingfeng; Lin, Qing; Qi, Tong; Wang, Tiankun; Chen, Ching-Cheng; Riggs, Arthur D; Zeng, Defu

    2016-01-19

    We previously reported that long-term administration of a low dose of gastrin and epidermal growth factor (GE) augments β-cell neogenesis in late-stage diabetic autoimmune mice after eliminating insulitis by induction of mixed chimerism. However, the source of β-cell neogenesis is still unknown. SRY (sex-determining region Y)-box 9(+) (Sox9(+)) ductal cells in the adult pancreas are clonogenic and can give rise to insulin-producing β cells in an in vitro culture. Whether Sox9(+) ductal cells in the adult pancreas can give rise to β cells in vivo remains controversial. Here, using lineage-tracing with genetic labeling of Insulin- or Sox9-expressing cells, we show that hyperglycemia (>300 mg/dL) is required for inducing Sox9(+) ductal cell differentiation into insulin-producing β cells, and medium hyperglycemia (300-450 mg/dL) in combination with long-term administration of low-dose GE synergistically augments differentiation and is associated with normalization of blood glucose in nonautoimmune diabetic C57BL/6 mice. Short-term administration of high-dose GE cannot augment differentiation, although it can augment preexisting β-cell replication. These results indicate that medium hyperglycemia combined with long-term administration of low-dose GE represents one way to induce Sox9(+) ductal cell differentiation into β cells in adult mice.

  18. Histological and Pathological Assessment of miR-204 and SOX4 Levels in Gastric Cancer Patients.

    Science.gov (United States)

    Yuan, Xiao; Wang, Shuanhu; Liu, Mulin; Lu, Zhen; Zhan, Yanqing; Wang, Wenbin; Xu, A-Man

    2017-01-01

    Gastric cancer is one of the most common cancers and the efficient therapeutic methods are limited. Further study of the exact molecular mechanism of gastric cancer to develop novel targeted therapies is necessary and urgent. We herein systematically examined that miR-204 suppressed both proliferation and metastasis of gastric cancer AGS cells. miR-204 directly targeted SOX4. In clinical tissue research, we determined that miR-204 was expressed much lower and SOX4 expressed much higher in gastric cancer tissues compared with normal gastric tissues. Associated analysis with clinicopathological parameters in gastric cancer patients showed miR-204 was associated with no lymph node metastasis and early tumor stages whereas SOX4 was associated with lymph node metastasis and advanced tumor stages. In addition, miR-204 and SOX4 were negatively correlated in tissues from gastric cancer patients. Our findings examined the important role of miR-204 and SOX4 played in gastric cancer, and they could be used as candidate therapeutic targets for gastric cancer therapy.

  19. The Impact of SOX Adoption on the Compensation of Non-US Companies’ Boards: The Case of Canadian Companies

    Directory of Open Access Journals (Sweden)

    Nadejda SERDIUC

    2015-11-01

    Full Text Available The purpose of this article is to study the relationship between the adoption of the Sarbanes-Oxley Act (SOX and the compensation of the board of directors of Canadian companies listed on US stock markets. The SOX act, promulgated on 30 July 2002 and the rules adopted by the Securities and Exchange Commission (SEC require, among furthermore, a majority of independent directors on boards. The literature focuses on two main differences between US companies and Canadian companies: more concentrated ownership and the smaller market capitalization of Canadian companies. Therefore, a consistent application of SOX on all the companies that differ at the base, in their size and structure, may have a different impact on the costs of compliance. Using a sample of 17 Canadian companies listed on US stock exchanges from 2001 to 2004, our analysis show that there is a link between the adoption of SOX and the increased in the cash compensation of the board of directors. The results also show that the effect of SOX is different depending on the company’s size.

  20. Cyclin-dependent kinase inhibitor p21 controls adult neural stem cell expansion by regulating Sox2 gene expression.

    Science.gov (United States)

    Marqués-Torrejón, M Ángeles; Porlan, Eva; Banito, Ana; Gómez-Ibarlucea, Esther; Lopez-Contreras, Andrés J; Fernández-Capetillo, Oscar; Vidal, Anxo; Gil, Jesús; Torres, Josema; Fariñas, Isabel

    2013-01-01

    In the adult brain, continual neurogenesis of olfactory neurons is sustained by the existence of neural stem cells (NSCs) in the subependymal niche. Elimination of the cyclin-dependent kinase inhibitor 1A (p21) leads to premature exhaustion of the subependymal NSC pool, suggesting a relationship between cell cycle control and long-term self-renewal, but the molecular mechanisms underlying NSC maintenance by p21 remain unexplored. Here we identify a function of p21 in the direct regulation of the expression of pluripotency factor Sox2, a key regulator of the specification and maintenance of neural progenitors. We observe that p21 directly binds a Sox2 enhancer and negatively regulates Sox2 expression in NSCs. Augmented levels of Sox2 in p21 null cells induce replicative stress and a DNA damage response that leads to cell growth arrest mediated by increased levels of p19(Arf) and p53. Our results show a regulation of NSC expansion driven by a p21/Sox2/p53 axis.

  1. In depth analysis of the Sox4 gene locus that consists of sense and natural antisense transcripts.

    Science.gov (United States)

    Ling, King-Hwa; Brautigan, Peter J; Moore, Sarah; Fraser, Rachel; Leong, Melody Pui-Yee; Leong, Jia-Wen; Zainal Abidin, Shahidee; Lee, Han-Chung; Cheah, Pike-See; Raison, Joy M; Babic, Milena; Lee, Young Kyung; Daish, Tasman; Mattiske, Deidre M; Mann, Jeffrey R; Adelson, David L; Thomas, Paul Q; Hahn, Christopher N; Scott, Hamish S

    2016-06-01

    SRY (Sex Determining Region Y)-Box 4 or Sox4 is an important regulator of the pan-neuronal gene expression during post-mitotic cell differentiation within the mammalian brain. Sox4 gene locus has been previously characterized with multiple sense and overlapping natural antisense transcripts [1], [2]. Here we provide accompanying data on various analyses performed and described in Ling et al. [2]. The data include a detail description of various features found at Sox4 gene locus, additional experimental data derived from RNA-Fluorescence in situ Hybridization (RNA-FISH), Western blotting, strand-specific reverse-transcription quantitative polymerase chain reaction (RT-qPCR), gain-of-function and in situ hybridization (ISH) experiments. All the additional data provided here support the existence of an endogenous small interfering- or PIWI interacting-like small RNA known as Sox4_sir3, which origin was found within the overlapping region consisting of a sense and a natural antisense transcript known as Sox4ot1.

  2. Transcription factor Sox4 is required for PUMA-mediated apoptosis induced by histone deacetylase inhibitor, TSA.

    Science.gov (United States)

    Jang, Sang-Min; Kang, Eun-Jin; Kim, Jung-Woong; Kim, Chul-Hong; An, Joo-Hee; Choi, Kyung-Hee

    2013-08-23

    PUMA is a crucial regulator of apoptotic cell death mediated by p53-dependent and p53-independent mechanisms. In many cancer cells, PUMA expression is induced in response to DNA-damaging reagent in a p53-dependent manner. However, few studies have investigated transcription factors that lead to the induction of PUMA expression via p53-independent apoptotic signaling. In this study, we found that the transcription factor Sox4 increased PUMA expression in response to trichostatin A (TSA), a histone deacetylase inhibitor in the p53-null human lung cancer cell line H1299. Ectopic expression of Sox4 led to the induction of PUMA expression at the mRNA and protein levels, and TSA-mediated up-regulation of PUMA transcription was repressed by the knockdown of Sox4. Using luciferase assays and chromatin immunoprecipitation, we also determined that Sox4 recruits p300 on the PUMA promoter region and increases PUMA gene expression in response to TSA treatment. Taken together, these results suggest that Sox4 is required for p53-independent apoptotic cell death mediated by PUMA induction via TSA treatment.

  3. In depth analysis of the Sox4 gene locus that consists of sense and natural antisense transcripts

    Directory of Open Access Journals (Sweden)

    King-Hwa Ling

    2016-06-01

    Full Text Available SRY (Sex Determining Region Y-Box 4 or Sox4 is an important regulator of the pan-neuronal gene expression during post-mitotic cell differentiation within the mammalian brain. Sox4 gene locus has been previously characterized with multiple sense and overlapping natural antisense transcripts [1,2]. Here we provide accompanying data on various analyses performed and described in Ling et al. [2]. The data include a detail description of various features found at Sox4 gene locus, additional experimental data derived from RNA-Fluorescence in situ Hybridization (RNA-FISH, Western blotting, strand-specific reverse-transcription quantitative polymerase chain reaction (RT-qPCR, gain-of-function and in situ hybridization (ISH experiments. All the additional data provided here support the existence of an endogenous small interfering- or PIWI interacting-like small RNA known as Sox4_sir3, which origin was found within the overlapping region consisting of a sense and a natural antisense transcript known as Sox4ot1.

  4. Sox2+ progenitors in sharks link taste development with the evolution of regenerative teeth from denticles

    Science.gov (United States)

    Martin, Kyle J.; Rasch, Liam J.; Cooper, Rory L.; Johanson, Zerina; Fraser, Gareth J.

    2016-01-01

    Teeth and denticles belong to a specialized class of mineralizing epithelial appendages called odontodes. Although homology of oral teeth in jawed vertebrates is well supported, the evolutionary origin of teeth and their relationship with other odontode types is less clear. We compared the cellular and molecular mechanisms directing development of teeth and skin denticles in sharks, where both odontode types are retained. We show that teeth and denticles are deeply homologous developmental modules with equivalent underlying odontode gene regulatory networks (GRNs). Notably, the expression of the epithelial progenitor and stem cell marker sex-determining region Y-related box 2 (sox2) was tooth-specific and this correlates with notable differences in odontode regenerative ability. Whereas shark teeth retain the ancestral gnathostome character of continuous successional regeneration, new denticles arise only asynchronously with growth or after wounding. Sox2+ putative stem cells associated with the shark dental lamina (DL) emerge from a field of epithelial progenitors shared with anteriormost taste buds, before establishing within slow-cycling cell niches at the (i) superficial taste/tooth junction (T/TJ), and (ii) deep successional lamina (SL) where tooth regeneration initiates. Furthermore, during regeneration, cells from the superficial T/TJ migrate into the SL and contribute to new teeth, demonstrating persistent contribution of taste-associated progenitors to tooth regeneration in vivo. This data suggests a trajectory for tooth evolution involving cooption of the odontode GRN from nonregenerating denticles by sox2+ progenitors native to the oral taste epithelium, facilitating the evolution of a novel regenerative module of odontodes in the mouth of early jawed vertebrates: the teeth. PMID:27930309

  5. Aflatoxin B1 in poultry: toxicology, metabolism and prevention.

    Science.gov (United States)

    Rawal, Sumit; Kim, Ji Eun; Coulombe, Roger

    2010-12-01

    Aflatoxins (AF) are ubiquitous in corn-based animal feed and causes hepatotoxic and hepatocarcinogenic effects. The most important AF in terms of toxic potency and occurrence is aflatoxin B1 (AFB1). Poultry, especially turkeys, are extremely sensitive to the toxic and carcinogenic action of AFB1, resulting in millions of dollars in annual losses to producers due to reduced growth rate, increased susceptibility to disease, reduced egg production and other adverse effects. The extreme sensitivity of turkeys and other poultry to AFB1 is associated with efficient hepatic cytochrome P450-mediated bioactivation and deficient detoxification by glutathione S-transferases (GST). Discerning the biochemical and molecular mechanisms of this extreme sensitivity of poultry to AFB1, will contribute in the development of novel strategies to increase aflatoxin resistance. Since AFB1 is an unavoidable contaminant of corn-based poultry feed, chemoprevention strategies aimed at reducing AFB1 toxicity in poultry and in other animals have been the subject of numerous studies. This brief review summarizes many of the key recent findings regarding the action of aflatoxins in poultry.

  6. Aflatoxin B1 transfer and metabolism in human placenta.

    Science.gov (United States)

    Partanen, Heidi A; El-Nezami, Hani S; Leppänen, Jukka M; Myllynen, Päivi K; Woodhouse, Heather J; Vähäkangas, Kirsi H

    2010-01-01

    Aflatoxin B1 (AFB1), a common dietary contaminant, is a major risk factor of hepatocellular carcinoma (HCC). Early onset of HCC in some countries in Africa and South-East Asia indicates the importance of early life exposure. Placenta is the primary route for various compounds, both nutrients and toxins, from the mother to the fetal circulation. Furthermore, placenta contains enzymes for xenobiotic metabolism. AFB1, AFB1-metabolites, and AFB1-albumin adducts have been detected in cord blood of babies after maternal exposure during pregnancy. However, the role that the placenta plays in the transfer and metabolism of AFB1 is not clear. In this study, placental transfer and metabolism of AFB1 were investigated in human placental perfusions and in in vitro studies. Eight human placentas were perfused with 0.5 or 5microM AFB1 for 2-4 h. In vitro incubations with placental microsomal and cytosolic proteins from eight additional placentas were also conducted. Our results from placental perfusions provide the first direct evidence of the actual transfer of AFB1 and its metabolism to aflatoxicol (AFL) by human placenta. In vitro incubations with placental cytosolic fraction confirmed the capacity of human placenta to form AFL. AFL was the only metabolite detected in both perfusions and in vitro incubations. Since AFL is less mutagenic, but putatively as carcinogenic as AFB1, the formation of AFL may not protect the fetus from the toxicity of AFB1.

  7. Genotoxicity of aflatoxin B1 and its ammonium derivatives.

    Science.gov (United States)

    Márquez Márquez, R; Tejada de Hernandez, I; Madrigal Bujaidar, E

    1995-01-01

    Aflatoxin (AF) B1 is a main contaminant in diverse agricultural products. In an attempt to reduce this problem and the hazards to human health, an AFB1 inactivating system with ammonia has been developed. In this work we evaluated the efficiency of the system in mice using micronucleus (MN) and sister chromatid exchange (SCE) analysis. Four groups of animals were fed for 8 weeks with a special diet mainly composed of maize: (1) uncontaminated; (2) uncontaminated/inactivated; (3) contaminated/inactivated; and (4) contaminated. We evaluated MN at weekly intervals in peripheral blood, and in weeks 4 and 8 SCE frequencies were quantified in bone marrow cells. The results shows that animals fed with AFB1 contaminated/inactivated maize had a 45% lower level of induced cytogenetic damage than those animals fed with AFB1 contaminated but not inactivated maize. A residual amount of AFB1 after the inactivating treatment and reconversion back to AFB1 in the organism may account for the remaining increased levels of SCE and MN.

  8. Molecular ions in the protostellar shock L1157-B1

    CERN Document Server

    Podio, L; Ceccarelli, C; Codella, C; Bachiller, R

    2014-01-01

    We perform a complete census of molecular ions with an abundance larger than 1e-10 in the protostellar shock L1157-B1 by means of an unbiased high-sensitivity survey obtained with the IRAM-30m and Herschel/HIFI. By means of an LVG radiative transfer code the gas physical conditions and fractional abundances of molecular ions are derived. The latter are compared with estimates of steady-state abundances in the cloud and their evolution in the shock calculated with the chemical model Astrochem. We detect emission from HCO+, H13CO+, N2H+, HCS+, and, for the first time in a shock, from HOCO+, and SO+. The bulk of the emission peaks at blueshifted velocity, ~ 0.5-3 km/s with respect to systemic, has a width of ~ 4-8 km/s, and is associated with the outflow cavities (T_kin ~ 20-70 K, n(H2) ~ 1e5 cm-3). Observed HCO+ and N2H+ abundances are in agreement with steady-state abundances in the cloud and with their evolution in the compressed and heated gas in the shock for cosmic rays ionization rate Z = 3e-16 s-1. HOCO+...

  9. Regulation of nucleotide excision repair by nuclear lamin b1.

    Directory of Open Access Journals (Sweden)

    Veronika Butin-Israeli

    Full Text Available The nuclear lamins play important roles in the structural organization and function of the metazoan cell nucleus. Recent studies on B-type lamins identified a requirement for lamin B1 (LB1 in the regulation of cell proliferation in normal diploid cells. In order to further investigate the function of LB1 in proliferation, we disrupted its normal expression in U-2 OS human osteosarcoma and other tumor cell lines. Silencing LB1 expression induced G1 cell cycle arrest without significant apoptosis. The arrested cells are unable to mount a timely and effective response to DNA damage induced by UV irradiation. Several proteins involved in the detection and repair of UV damage by the nucleotide excision repair (NER pathway are down-regulated in LB1 silenced cells including DDB1, CSB and PCNA. We propose that LB1 regulates the DNA damage response to UV irradiation by modulating the expression of specific genes and activating persistent DNA damage signaling. Our findings are relevant to understanding the relationship between the loss of LB1 expression, DNA damage signaling, and replicative senescence.

  10. 甲状腺乳头状癌组织中SOX2和 CyclinD1的表达及相关性%Expressions of SOX2 and CyclinD1 in the Papillary Thyroid Carcinoma

    Institute of Scientific and Technical Information of China (English)

    董斌

    2016-01-01

    目的:探讨甲状腺乳头状癌组织中性别决定区 Y 框蛋白(SOX2)和细胞周期素 D1(CyclinD1)的表达及相关性。方法采用免疫组化 S-P 法检测100例甲状腺乳头状癌和50例癌旁正常甲状腺组织中 SOX2和 CyclinD1的表达,并分析两者与甲状腺乳头状癌患者临床病理参数的关系。结果甲状腺乳头状癌组织中 SOX2和 CyclinD1的阳性率分别为80.0%和73.0%,均高于癌旁正常甲状腺组织的10.0%和4.0%,差异有统计学意义(P <0.05)。甲状腺乳头状癌组织中 SOX2和 CyclinD1的表达与其临床分期、淋巴结转移关系密切(P <0.05)。甲状腺乳头状癌组织中 SOX2和 CyclinD1的表达呈正相关(r =0.597,P <0.05)。结论甲状腺乳头状癌组织中 SOX2和 CyclinD1存在表达,两者可能共同参与了甲状腺乳头状癌的疾病进展。%Objective To investigate the expressions of sex determining region Y-box(SOX2)and CyclinD1 in the patients with papillary thyroid carcinoma and the correlation. Methods Immunohistochemical S-P method was used to detect the expressions of SOX2 and CyclinD1 in the 100 patients with papillary thyroid carcinoma and 50 pa-tients with paraneoplastic normal thyroid tissues,their relationship with clinicopathological parameters were ana-lyzed. Results The positive rates of SOX2 and CyclinD1 in the papillary thyroid carcinoma were 80. 0% and 73. 0% ,and were 10. 0% and 4. 0% in the paraneoplastic normal thyroid tissues(P < 0. 05). The expressions of SOX2 and CyclinD1 in the papillary thyroid carcinoma were related with clinical stage and lymph node metastasis (P < 0. 05). In the papillary thyroid carcinoma,the expression of SOX2 was positively related with CyclinD1(r =0. 597,P < 0. 05). Conclusion high expressions of SOX2 and CyclinD1 are observed in the papillary thyroid carci-noma,and may be related to the development of papillary thyroid carcinoma.

  11. Análisis del gen SOX-2 en carcinoma escamoso de cabeza y cuello

    OpenAIRE

    González Márquez, Rocío

    2015-01-01

    El carcinoma escamoso de cabeza y cuello es la sexta neoplasia más frecuente en el mundo. El origen de dichos tumores implica gran numero de alteraciones genéticas y moleculares, siendo recientemente estudiado el gen SOX2. Se estudiaron las muestras procedentes de 220 pacientes con carcinoma escamoso de hipofaringe, laringe y senos paranasales. En el estudio inmunohistoquímico apareció un grado de sobreexpresión similar en tumores faringeos y laríngeos, así como relación significativa con...

  12. Análisis del gen SOX-2 en carcinoma escamoso de cabeza y cuello

    OpenAIRE

    González Márquez, Rocío

    2014-01-01

    El carcinoma escamoso de cabeza y cuello es la sexta neoplasia más frecuente en el mundo. El origen de dichos tumores implica gran numero de alteraciones genéticas y moleculares, siendo recientemente estudiado el gen SOX2. Se estudiaron las muestras procedentes de 220 pacientes con carcinoma escamoso de hipofaringe, laringe y senos paranasales. En el estudio inmunohistoquímico apareció un grado de sobreexpresión similar en tumores faringeos y laríngeos, así como relación significativa con...

  13. A novel SoxB2 gene is required for maturation of sperm nucleus during spermiogenesis in the Chinese mitten crab, Eriocheir sinensis

    Science.gov (United States)

    Liu, Zhi-Qiang; Jiang, Xue-Hui; Qi, Hai-Yan; Xiong, Liang-Wei; Qiu, Gao-Feng

    2016-01-01

    SRY-related HMG box (Sox) genes are characterized by the presence of a DNA-binding HMG domain and involved in a diverse range of developmental processes. In this study, we identified a novel Sox gene, designated as EsSoxB2-1, from the Chinese mitten crab Eriocheir sinensis. The EsSoxB2-1 encodes a protein of 259 amino acids, sharing the highest identity with the beetle Tribolium castaneum SOX21b. Unlike insect Sox21b, however, EsSoxB2-1 is intronless and exhibits a gonad-specific expression pattern at both mRNA and protein level. Two core promoters in 5′ flanking region were demonstrated to be essential for inducing transcriptional regulatory activity. The transcription of EsSoxB2-1 mRNA begins in spermatogonia stage, while the translation of EsSOXB2-1 protein initiates at spermiogenesis stage. Interestingly, EsSOXB2-1 protein was exclusively localized in the nucleus of spermatid and spermatozoa even at the end of acrosome reaction, and was bound to the uncondensed chromatin in nucleoplasm of mature spermatozoa. Knockdown of EsSoxB2-1 by RNAi leads to abnormal transformation of the nucleus during spermiogenesis. Together, these findings demonstrated the requirement of EsSoxB2-1 for the spermatozoa nucleus maturation and also suggested that EsSoxB2-1 would be delivered into fertilized eggs along with chromatins as a paternal transcription factor for regulating early embryonic development. PMID:27561408

  14. Sox17 promotes cell cycle progression and inhibits TGF-beta/Smad3 signaling to initiate progenitor cell behavior in the respiratory epithelium.

    Directory of Open Access Journals (Sweden)

    Alexander W Lange

    Full Text Available The Sry-related high mobility group box transcription factor Sox17 is required for diverse developmental processes including endoderm formation, vascular development, and fetal hematopoietic stem cell maintenance. Expression of Sox17 in mature respiratory epithelial cells causes proliferation and lineage respecification, suggesting that Sox17 can alter adult lung progenitor cell fate. In this paper, we identify mechanisms by which Sox17 influences lung epithelial progenitor cell behavior and reprograms cell fate in the mature respiratory epithelium. Conditional expression of Sox17 in epithelial cells of the adult mouse lung demonstrated that cell cluster formation and respecification of alveolar progenitor cells toward proximal airway lineages were rapidly reversible processes. Prolonged expression of Sox17 caused the ectopic formation of bronchiolar-like structures with diverse respiratory epithelial cell characteristics in alveolar regions of lung. During initiation of progenitor cell behavior, Sox17 induced proliferation and increased the expression of the progenitor cell marker Sca-1 and genes involved in cell cycle progression. Notably, Sox17 enhanced cyclin D1 expression in vivo and activated cyclin D1 promoter activity in vitro. Sox17 decreased the expression of transforming growth factor-beta (TGF-beta-responsive cell cycle inhibitors in the adult mouse lung, including p15, p21, and p57, and inhibited TGF-beta1-mediated transcriptional responses in vitro. Further, Sox17 interacted with Smad3 and blocked Smad3 DNA binding and transcriptional activity. Together, these data show that a subset of mature respiratory epithelial cells retains remarkable phenotypic plasticity and that Sox17, a gene required for early endoderm formation, activates the cell cycle and reinitiates multipotent progenitor cell behavior in mature lung cells.

  15. PENGARUH KETEBALAN SUBSTRAT PADA FERMENTASI TEMPE TERHADAP KADAR VITAMIN B1 (THE INFLUENCE OF SUBSTRATE THICKNESS DURING TEMPE FERMENTATION ON VITAMINS B1 LEVEL

    Directory of Open Access Journals (Sweden)

    Fifi Retiaty

    2012-12-01

    Full Text Available ABSTRACT The level of vitamin B1 in tempe could be increased by modifying the surface of substrate during soybean fermentation. This research aimed to know the influence of substrate thickness during soybean fermentation into tempe to the levels of vitamin B1. The design of this research was completed randomized design with two replication. Vitamin B1 content was analyzed on raw soybeans, boiled soybeans, and tempe using spectrophotometer methods. The substrate thicknesses examined were 0.25 cm, 0.50 cm and 1.00cm. Vitamin B1 level on raw soybean was 0.7436 mg percent and on boiled soybean was 0.4898 mg percent, while in tempe with substrate thickness  0.25 cm, 0.50 cm and 1.00 cm, the vitamin B1 contents were 1.1413, 0.9044, and 0.7130 mg percent respectively. The thickness of tempe substrate affected on vitamin B1 content. A thinner substrate resulted on higher vitamin B1 level. Keywords: fermentation, tempe, vitamin B1   ABSTRAK Kadar vitamin B1 pada tempe dapat ditingkatkan dengan memodifikasi permukaan dari substrat dalam fermentasi kedelai. Tujuan penelitian ini adalah untuk mengetahui pengaruh ketebalan substrat pada fermentasi kedelai menjadi tempe terhadap kadar vitamin B1. Disain penelitian ini adalah Rancangan Acak Lengkap dengan dua kali ulangan. Kadar vitamin B1 dianalisis pada kedelai mentah, kedelai rebus, dan tempe dengan menggunakan metode spektrofotometri. Ketebalan substrat yang diteliti adalah 0.25 cm, 0,50 cm, 1,00 cm. Kadar vitamin B1 pada  kedelai mentah adalah 0,7436 mg persen dan pada kedelai rebus adalah 0.4898 mg persen. Sedangkan kadar vitamin B1 pada tempe dengan ketebalan 0,25, 0,5 dan 1 cm secara berturut-turut adalah 1,1413 mg persen , 0,9044 mg persen dan 0,7130 mg persen. Ketebalan substar tempe berpengaruh pada kandungan vitamin B1. Semakin tipis substrat, akan menghasilkan vitamin B1 yang semakin tinggi. [Penel Gizi Makan 2012, 35(2: 182-188]   Kata Kunci: fermentasi, tempe, vitamin B1

  16. Screening of CYP1B1 and MYOC in Moroccan families with primary congenital glaucoma: Three novel mutations in CYP1B1

    OpenAIRE

    Hilal, Latifa; Boutayeb, Soraya; Serrou, Aziza; Refass-Buret, Loubna; Shisseh, Hafsa; Bencherifa, Fatiha; El Mzibri, Mohammed; Benazzouz, Bouchra; Berraho, Amina

    2010-01-01

    Purpose To investigate the contribution of cytochrome P4501B1 (CYP1B1) and myocillin (MYOC) mutations to primary congenital glaucoma (PCG) in Moroccan families. Methods This study included 90 unrelated families with PCG and 100 normal control individuals. Two previously reported CYP1B1 mutations (g.4339delG and p.G61E) were first screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The coding exons of CYP1B1 were sequenced in g.4339delG- and p.G61E-negati...

  17. A novel temperature-gradient Na±β-alumina solid electrolyte based SOx gas sensor without gaseous reference electrode

    DEFF Research Database (Denmark)

    Rao, N.; Bleek, C.M. Van den; Schoonman, J.

    1992-01-01

    electrodes. The EMF of this so-called TGNB (Temperature Gradient Na+-beta"-alumina) SOx sensor is in good agreement with the theoretical prediction. The consistence of the experimental results with the theoretical values and the simple construction of this type of SOx sensor indicate its potential......An electrochemical SOx ps sensor with a tubular Na+-beta"-alumina solid electrolyte has been fabricated and tested under non-isothermal conditions. The temperature difference between the reference and working electrode of the sensor cell is about 100-degrees-C, which causes a serious deviation...... of the experimental EMF response from the value as calculated using the Nernst equation for an isothermal system. The experimental results are Consistent with the theoretical prediction for a non-isothermal system. The response time is usually less then 10 min. SEM and EDX have been employed to investigate the sensor...

  18. [A Case of Sigmoid Colon Cancer with Synchronous Liver Metastasis, Treated with Laparoscopic Liver Resection after SOX plus BV Chemotherapy].

    Science.gov (United States)

    Shimizu, Yasuhito; Ando, Katsuhiko; Oda, Kenji; Kubosawa, Hitoshi; Miyazaki, Masaru

    2015-11-01

    We performed laparoscopic liver resection in a patient with synchronous liver metastasis from advanced sigmoid colon cancer after induction with S-1 plus oxaliplatin (SOX) plus bevacizumab (BV) chemotherapy. A 61-year-old woman underwent laparoscopy-assisted sigmoidectomy for locally advanced sigmoid colon cancer with synchronous liver metastasis. SOX plus BV chemotherapy was initiated. After 3 courses, the liver tumor was downsized, and metastasectomy was performed laparoscopically with R0 resection. The postoperative course was uneventful and the patient was discharged on the 11th postoperative day. She has been free from recurrence. Induction with SOX plus BV chemotherapy is considered to be not only effective, but also beneficial for maintaining the quality of life (QOL) in patients with advanced colorectal cancer.

  19. Aflatoxin B1 is toxic to porcine oocyte maturation.

    Science.gov (United States)

    Liu, Jun; Wang, Qiao-Chu; Han, Jun; Xiong, Bo; Sun, Shao-Chen

    2015-07-01

    As a toxic secondary metabolite of Aspergillus species, Aflatoxin B1 (AFB1) is a major food and feed contaminant in tropical and sub-tropical regions with high temperature and humidity. It has been reported to be toxic to the female reproductive system in laboratory and domestic animals. In the present study, the influence of acute exposure to AFB1 (10 and 50 μM, 44h) on porcine oocyte maturation and its possible mechanism were investigated. The maturation rates of oocytes decreased significantly in the presence of 50 μM of AFB1. Cell cycle analysis showed that most oocytes were arrested at germinal vesicle breakdown or meosis I stage. However, actin assembly, spindle structure and chromosome alignment were not disrupted after exposure to 50 μM AFB1. Further study showed that DNA methylation levels increased in treated oocytes (50 μM). Histone methylation levels were also analysed after treatment (50 μM): H3K27me3 and H3K4me2 levels decreased, whereas H3K9me3 level increased, indicating that epigenetic modification was affected. AFB1 treatment (50 μM) also induced oxidative stress and further led to autophagy, as shown by accumulation of reactive oxygen species, up-regulated LC3 protein expression and increased mRNA levels of ATG3, ATG5 and ATG7. Annexin V-FITC staining assay revealed that AFB1 treatment (50 μM) resulted in oocyte early apoptosis, which was confirmed by increased Bak, Bax, Bcl-xl mRNA levels. Collectively, our results suggest that AFB1 disrupts porcine oocyte maturation through changing epigenetic modifications as well as inducing oxidative stress, excessive autophagy and apoptosis.

  20. Aflatoxin B1 Degradation by a Pseudomonas Strain

    Science.gov (United States)

    Sangare, Lancine; Zhao, Yueju; Folly, Yawa Minnie Elodie; Chang, Jinghua; Li, Jinhan; Selvaraj, Jonathan Nimal; Xing, Fuguo; Zhou, Lu; Wang, Yan; Liu, Yang

    2014-01-01

    Aflatoxin B1 (AFB1), one of the most potent naturally occurring mutagens and carcinogens, causes significant threats to the food industry and animal production. In this study, 25 bacteria isolates were collected from grain kernels and soils displaying AFB1 reduction activity. Based on its degradation effectiveness, isolate N17-1 was selected for further characterization and identified as Pseudomonas aeruginosa. P. aeruginosa N17-1 could degrade AFB1, AFB2 and AFM1 by 82.8%, 46.8% and 31.9% after incubation in Nutrient Broth (NB) medium at 37 °C for 72 h, respectively. The culture supernatant of isolate N17-1 degraded AFB1 effectively, whereas the viable cells and intra cell extracts were far less effective. Factors influencing AFB1 degradation by the culture supernatant were investigated. Maximum degradation was observed at 55 °C. Ions Mn2+ and Cu2+ were activators for AFB1 degradation, however, ions Mg2+, Li+, Zn2+, Se2+, Fe3+ were strong inhibitors. Treatments with proteinase K and proteinase K plus SDS significantly reduced the degradation activity of the culture supernatant. No degradation products were observed based on preliminary LC-QTOF/MS analysis, indicating AFB1 was metabolized to degradation products with chemical properties different from that of AFB1. The results indicated that the degradation of AFB1 by P. aeruginosa N17-1 was enzymatic and could have a great potential in industrial applications. This is the first report indicating that the isolate of P. aeruginosa possesses the ability to degrade aflatoxin. PMID:25341538

  1. AFLATOXIN B1 RESIDUES IN EGGS AND FLESH OF LAYING HENS FED AFLATOXIN B1 CONTAMINATED DIET

    Directory of Open Access Journals (Sweden)

    Saqer Mohammad Herzallah

    2013-01-01

    Full Text Available Aflatoxin B1(AFB1 and total Aflatoxins (AFT contaminated feed effect on aflatoxins residue level in eggs, muscles (breast, leg, organs (liver, kidney, gizzard and excreted aflatoxins in chicken litter of layer hens were monitored. Laying hens were on four levels of aflatoxins for 6 weeks and monitored weekly for the change in both AFB1 and AFT levels. Pronouncedly, the AFB1 and AFT were detected in eggs, muscles (legs, breast, organs (liver, kidney and gizzard and litter in noticeable amounts. Total Aflatoxin (AFT level was lowest in chicken breast (0.63 ppb and highest in liver (2.12 ppb and gizzard (1.22 ppb of chicken fed diet with 965.12 ppb. Whereas, AFB1 residue was 0.66 ppb in eggs, 1.59 ppb in liver tissues of hens given feed contaminated with 894.12 ppb. Residue level of AFB1 was high in liver and kidney of all treatments. The chicken breast tissues were lowest in AFB1 and AFT of values 0.72 and 0.63, respectively. Eggs production was significantly (p<0.05 affected with AFB1 contaminated feed and egg production was decreased by more than 30%.

  2. Use of methanol as cryoprotectant and its effect on sox genes and proteins in chilled zebrafish embryos.

    Science.gov (United States)

    Desai, Kunjan; Spikings, Emma; Zhang, Tiantian

    2015-08-01

    Methanol is a widely used cryoprotectant (CPA) in cryopreservation of fish embryos, however little is known about its effect at the molecular level. This study investigated the effect of methanol on sox gene and protein expression in zebrafish embryos (50% epiboly) when they were chilled for 3 h and subsequently warmed and cultured to the hatching stages. Initial experiments were carried out to evaluate the chilling tolerance of 50% epiboly embryos which showed no significant differences in hatching rates for up to 6 h chilling in methanol (0.2-, 0.5- and 1 M). Subsequent experiments in embryos that had been chilled for 3 h in 1 M methanol and warmed and cultured up to the hatching stages found that sox2 and sox3 gene expression were increased significantly in hatched embryos that had been chilled compared to non-chilled controls. Sox19a gene expression also remained above control levels in the chilled embryos at all developmental stages tested. Whilst stable sox2 protein expression was observed between non-chilled controls and embryos chilled for 3 h with or without MeOH, a surge in sox19a protein expression was observed in embryos chilled for 3 h in the presence of 1 M MeOH compared to non-chilled controls and then returned to control levels by the hatching stage. The protective effect of MeOH was increased with increasing concentrations. Effect of methanol at molecular level during chilling was reported here first time which could add new parameter in selection of cryoprotectant while designing cryopreservation protocol.

  3. The transcription factor SOX17 is involved in the transcriptional control of the uteroglobin gene in rabbit endometrium.

    Science.gov (United States)

    Garcia, Carlos; Calvo, Enrique; Nieto, Antonio

    2007-10-15

    The transcription of the uteroglobin gene (ug) is induced by progesterone in the rabbit endometrium, primarily through the binding of the progesterone receptor to the distal region of the ug promoter. However, other transcription factors participate in the progesterone action. The proximal ug promoter contains several putative consensus sequences for the binding of various progesterone-dependent endometrial nuclear factors (Perez Martinez et al. [1996] Arch Biochem Biophys 333: 12-18), suggesting that several transcription factors might be implicated in the hormonal induction of ug. We report here that one of these progesterone-dependent factors specifically binds to the sequence CACAATG (-183/-177) of the rabbit ug promoter. This sequence (hereafter called element G') is very similar to the consensus sequence for binding of the SOX family of transcription factors. Mutation of the element G' reduced transcription from the ug promoter in transient expression experiments. The endometrial factor was purified and analyzed by nano-liquid chromatography and ion trap coupled mass spectrometry yielding two partial amino acid sequences corresponding to a region of SOX17 that is highly conserved inter-species. This identification was confirmed by immunological techniques using a specific anti-SOX17 antibody. In agreement with the above findings, overexpression of SOX17 in transfected endometrial cells increased transcription from the ug promoter. SOX17 gradually accumulated in the nucleus in vivo concomitant with the induction of ug expression by progesterone in the endometrium. Thus, these findings implicate, for the first time, SOX17 in the transcriptional control of rabbit ug.

  4. Profiling spermatogenic failure in adult testes bearing Sox9-deficient Sertoli cells identifies genes involved in feminization, inflammation and stress

    Directory of Open Access Journals (Sweden)

    Barrionuevo Francisco

    2010-12-01

    Full Text Available Abstract Background Sox9 (Sry box containing gene 9 is a DNA-binding transcription factor involved in chondrocyte development and sex determination. The protein's absence in testicular Sertoli nurse cells has been shown to disrupt testicular function in adults but little is known at the genome-wide level about molecular events concomitant with testicular break-down. Methods To determine the genome-wide effect on mRNA concentrations triggered by the absence of Sox9 in Sertoli cells we analysed adult testicular tissue from wild-type versus mutant mice with high-density oligonucleotide microarrays and integrated the output of this experiment with regulatory motif predictions and protein-protein network data. Results We report the genome-wide mRNA signature of adult testes lacking Sox9 in Sertoli cells before and after the onset of late spermatogenic failure as compared to fertile controls. The GeneChip data integrated with evolutionarily conserved Sox9 DNA binding motifs and regulatory network data identified genes involved in feminization, stress response and inflammation. Conclusions Our results extend previous observations that genes required for female gonadogenesis are up-regulated in the absence of Sox9 in fetal Sertoli cells to the adult stage. Importantly, we identify gene networks involved in immunological processes and stress response which is reminiscent of a phenomenon occurring in a sub-group of infertile men. This suggests mice lacking Sox9 in their Sertoli cells to be a potentially useful model for adult human testicular failure.

  5. Activated WNT signaling in postnatal SOX2-positive dental stem cells can drive odontoma formation.

    Science.gov (United States)

    Xavier, Guilherme M; Patist, Amanda L; Healy, Chris; Pagrut, Ankita; Carreno, Gabriela; Sharpe, Paul T; Martinez-Barbera, Juan Pedro; Thavaraj, Selvam; Cobourne, Martyn T; Andoniadou, Cynthia L

    2015-09-28

    In common with most mammals, humans form only two dentitions during their lifetime. Occasionally, supernumerary teeth develop in addition to the normal complement. Odontoma represent a small group of malformations containing calcified dental tissues of both epithelial and mesenchymal origin, with varying levels of organization, including tooth-like structures. The specific cell type responsible for the induction of odontoma, which retains the capacity to re-initiate de novo tooth development in postnatal tissues, is not known. Here we demonstrate that aberrant activation of WNT signaling by expression of a non-degradable form of β-catenin specifically in SOX2-positive postnatal dental epithelial stem cells is sufficient to generate odontoma containing multiple tooth-like structures complete with all dental tissue layers. Genetic lineage-tracing confirms that odontoma form in a similar manner to normal teeth, derived from both the mutation-sustaining epithelial stem cells and adjacent mesenchymal tissues. Activation of the WNT pathway in embryonic SOX2-positive progenitors results in ectopic expression of secreted signals that promote odontogenesis throughout the oral cavity. Significantly, the inductive potential of epithelial dental stem cells is retained in postnatal tissues, and up-regulation of WNT signaling specifically in these cells is sufficient to promote generation and growth of ectopic malformations faithfully resembling human odontoma.

  6. SOX2+ cell population from normal human brain white matter is able to generate mature oligodendrocytes.

    Directory of Open Access Journals (Sweden)

    Jorge Oliver-De La Cruz

    Full Text Available OBJECTIVES: A number of neurodegenerative diseases progress with a loss of myelin, which makes them candidate diseases for the development of cell-replacement therapies based on mobilisation or isolation of the endogenous neural/glial progenitor cells, in vitro expansion, and further implantation. Cells expressing A2B5 or PDGFRA/CNP have been isolated within the pool of glial progenitor cells in the subcortical white matter of the normal adult human brain, all of which demonstrate glial progenitor features. However, the heterogeneity and differentiation potential of this pool of cells is not yet well established. METHODS: We used diffusion tensor images, histopathology, and immunostaining analysis to demonstrate normal cytoarchitecture and the absence of abnormalities in human temporal lobe samples from patients with mesial temporal sclerosis. These samples were used to isolate and enrich glial progenitor cells in vitro, and later to detect such cells in vivo. RESULTS: We have identified a subpopulation of SOX2+ cells, most of them co-localising with OLIG2, in the white matter of the normal adult human brain in vivo. These cells can be isolated and enriched in vitro, where they proliferate and generate immature (O4+ and mature (MBP+ oligodendrocytes and, to a lesser extent, astrocytes (GFAP+. CONCLUSION: Our results demonstrate the existence of a new glial progenitor cell subpopulation that expresses SOX2 in the white matter of the normal adult human brain. These cells might be of use for tissue regeneration procedures.

  7. RIT1 GTPase Regulates Sox2 Transcriptional Activity and Hippocampal Neurogenesis.

    Science.gov (United States)

    Mir, Sajad; Cai, Weikang; Andres, Douglas A

    2017-02-10

    Adult neurogenesis, the process of generating mature neurons from neuronal progenitor cells, makes critical contributions to neural circuitry and brain function in both healthy and disease states. Neurogenesis is a highly regulated process in which diverse environmental and physiological stimuli are relayed to resident neural stem cell populations to control the transcription of genes involved in self-renewal and differentiation. Understanding the molecular mechanisms governing neurogenesis is necessary for the development of translational strategies to harness this process for neuronal repair. Here we report that the Ras-related GTPase RIT1 serves to control the sequential proliferation and differentiation of adult hippocampal neural progenitor cells, with in vivo expression of active RIT1 driving robust adult neurogenesis. Gene expression profiling analysis demonstrates increased expression of a specific set of transcription factors known to govern adult neurogenesis in response to active RIT1 expression in the hippocampus, including sex-determining region Y-related HMG box 2 (Sox2), a well established regulator of stem cell self-renewal and neurogenesis. In adult hippocampal neuronal precursor cells, RIT1 controls an Akt-dependent signaling cascade, resulting in the stabilization and transcriptional activation of phosphorylated Sox2. This study supports a role for RIT1 in relaying niche-derived signals to neural/stem progenitor cells to control transcription of genes involved in self-renewal and differentiation.

  8. Audit Fee Premiums: Pre and Post the Andersen Scandal and SOX

    Directory of Open Access Journals (Sweden)

    Nancy Manzhen Fan

    2014-10-01

    Full Text Available Purpose – This paper aims to examine audit fee premiums along the timeline from 2000 through 2005, a turbulent period of time in audit market with the demise of Author Anderson and passage of Sarbanes-Oxley Act (SOX. Design/methodology/approach – The paper employs the treatment effects model. Audit firms are classified into three segments: Big 5 (4 auditors, second-tier auditors (Grant Thornton and BDO Seidman, and third-tier auditors (others. Findings -- Before the demise of Andersen and the passage of SOX, there were no audit fee premiums, but there was a reverse trend afterward. While Big 4 auditors do not charge fee premiums over the second-tier auditors, the second-tier auditors’ charges audit fee premiums over the third-tier auditors. In addition, our findings show a selectivity bias between Big 5 (4 auditors and the second-tier auditors but no selectivity bias between the second- and third-tier auditors. Research limitations/implications – The paper focuses on the cost efficiency of auditor selection only and future research should explore the effects of auditor reputation, monopoly power and product differentiation of Big 4 auditors on audit fee premiums. Originality/value – The paper contributes to the extant audit premiums literature by utilizing treatment effect model in examining three tiers of auditors.

  9. Sox10-dependent neural crest origin of olfactory microvillous neurons in zebrafish.

    Science.gov (United States)

    Saxena, Ankur; Peng, Brian N; Bronner, Marianne E

    2013-03-19

    The sense of smell in vertebrates is detected by specialized sensory neurons derived from the peripheral nervous system. Classically, it has been presumed that the olfactory placode forms all olfactory sensory neurons. In contrast, we show that the cranial neural crest is the primary source of microvillous sensory neurons within the olfactory epithelium of zebrafish embryos. Using photoconversion-based fate mapping and live cell tracking coupled with laser ablation, we followed neural crest precursors as they migrated from the neural tube to the nasal cavity. A subset that coexpressed Sox10 protein and a neurogenin1 reporter ingressed into the olfactory epithelium and differentiated into microvillous sensory neurons. Timed loss-of-function analysis revealed a critical role for Sox10 in microvillous neurogenesis. Taken together, these findings directly demonstrate a heretofore unknown contribution of the cranial neural crest to olfactory sensory neurons in zebrafish and provide important insights into the assembly of the nascent olfactory system. DOI:http://dx.doi.org/10.7554/eLife.00336.001.

  10. Data of evolutionary structure change: 1CLMA-2B1UA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1CLMA-2B1UA 1CLM 2B1U A A LTEEQIAEFKEAFALFD-KDGDGTITTKELGTVMRSLGQ...NPTEAELQDMINEVDADGNGTIDFPEFLSLMARKMKEQDSEEELIEAFKVFDRDGNGLISAAELRHVMTNLGEKLTDDEVDEMIREADIDGDGHINYEEFVRMMVS 1CLM A 1CLMA FALFD-KDGDG

  11. Phenotypic variability in Waardenburg syndrome resulting from a 22q12.3-q13.1 microdeletion involving SOX10.

    Science.gov (United States)

    Jelena, Brezo; Christina, Lam; Eric, Vilain; Fabiola, Quintero-Rivera

    2014-06-01

    Waardenburg syndrome (WS) is a neurocristopathy characterized by pigmentation abnormalities of the skin, hair, and iris, as well as sensorineural hearing loss. Contiguous gene deletions encompassing SOX10 are rare, which limits conclusions about genotype-phenotype correlation regarding patient prognosis and management. This study adds to the existing body of knowledge by characterizing a 2.4 Mb deletion [arr[hg19] 22q12.3-q13.1 (36467502-38878207)x1] encompassing SOX10 and 53 additional RefSeq genes in a 15-year-old female with atypical WS. The patient presented with developmental delay, profound bilateral sensorineural hearing loss, heterochromia iridis, hypotonia, and bilateral finger contractures. Published genomic and phenotypic profiles of patients with SOX10-encompassing deletions point toward several plausible candidate gene that could account for the considerable clinical heterogeneity. These studies suggest the existence of modifiers among the co-deleted, dosage-sensitive genes (e.g., MYH9) and among genes whose effect may depend on the unmasking of recessive mutations (e.g., PLA2G6). Finally, we highlight evidence illustrating extensive interconnectivity of SOX10-hypothesizing that haploinsufficiency of SOX10 may "unmask" subtler effects on expression or epistasis associated with variants in SOX10 targets (e.g., DHH), in its partners (e.g., PAX3, EGR2), and in genes with functional overlap (e.g., SOX8, SOX9).

  12. Genome-Wide Identification and Transcriptome-Based Expression Profiling of the Sox Gene Family in the Nile Tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Wei, Ling; Yang, Chao; Tao, Wenjing; Wang, Deshou

    2016-02-23

    The Sox transcription factor family is characterized with the presence of a Sry-related high-mobility group (HMG) box and plays important roles in various biological processes in animals, including sex determination and differentiation, and the development of multiple organs. In this study, 27 Sox genes were identified in the genome of the Nile tilapia (Oreochromis niloticus), and were classified into seven groups. The members of each group of the tilapia Sox genes exhibited a relatively conserved exon-intron structure. Comparative analysis showed that the Sox gene family has undergone an expansion in tilapia and other teleost fishes following their whole genome duplication, and group K only exists in teleosts. Transcriptome-based analysis demonstrated that most of the tilapia Sox genes presented stage-specific and/or sex-dimorphic expressions during gonadal development, and six of the group B Sox genes were specifically expressed in the adult brain. Our results provide a better understanding of gene structure and spatio-temporal expression of the Sox gene family in tilapia, and will be useful for further deciphering the roles of the Sox genes during sex determination and gonadal development in teleosts.

  13. Sex-determining region Y-box3 (SOX3) functions as an oncogene in promoting epithelial ovarian cancer by targeting Src kinase.

    Science.gov (United States)

    Yan, Qin; Wang, Fangyuan; Miao, Yi; Wu, Xiaomei; Bai, Mingzhu; Xi, Xiaowei; Feng, Youji

    2016-09-01

    Ovarian cancer is one of the most common cancers which cause female mortality. The knowledge of ovarian cancer initiation and progression is critical to develop new therapeutic strategies to treat and prevent it. Recently, SOX3 has been reported to play a pivotal role in tumor progression. However, the clinical significance of SOX3 in human ovarian cancer remains elusive, and the identity of SOX3 in ovarian cancer initiation, progression, and the related underlying mechanism is unknown. In this study, we showed that SOX3 expression increased from benign and borderline to malignant ovarian tumors. Subsequently, we found that overexpression of SOX3 in EOC cells promoted proliferation, migration, and invasion, while restrained apoptosis and adhesion of ovarian cancer cells. In contrast, silencing of SOX3 gained the opposite results. Finally, we discovered SOX3 targeted Src kinase in EOC cells. These data imply that SOX3, acting as an oncogene in EOC, is not only a crucial factor in the carcinogenesis but also a promising therapeutic target for EOC.

  14. SOX10 mutation is relevant to inner ear malformation in patients with Waardenburg syndrome%SOX10基因突变对Waardenburg综合征患者内耳发育的影响

    Institute of Scientific and Technical Information of China (English)

    徐广雨; 郝青青; 钟玲玲; 任巍; 闫艳; 刘日渊; 李佳楠; 郭维维; 赵辉

    2016-01-01

    目的 通过对SOX10基因突变Waardenburg综合征(Waardenburg syndrome,WS)患者的内耳影像学分析和分子遗传学分析,研究SOX10基因突变与WS患者发生内耳畸形的相关性.方法 收集2001-2015年解放军总医院耳鼻咽喉头颈外科收治的WS患者36例的临床资料.通过颞骨高分辨率CT、头颅MRI、内听道磁共振水成像等影像学检查,全面评估每位患者内耳发育情况.并对每位患者筛查WS常见致病基因SOX10、MITF、PAX3的突变情况.按SOX10基因是否突变分为2组,以Fisher精确检验法比较两组间内耳畸形发生率的差异.结果 36例WS患者中,共发现12例内耳畸形(33.3%),其中后半规管畸形发生率最高(12例),可合并前庭扩大及耳蜗畸形.36例患者中9例检出SOX10基因杂合突变,其中6例出现双侧内耳畸形.36例患者中27例无SOX10基因突变,其中6例出现双侧内耳畸形.Fisher精确检验法比较SOX10基因突变组与非SOX10基因突变组间内耳畸形发生率差异有统计学意义(P =0.036).结论 WS患者中如为SOX10基因突变,则出现内耳畸形的可能性较大,并且趋向于双侧耳蜗、前庭及半规管同时畸形.%Objective To determine the relevance between the SOX10 mutation and Waardenburg syndrome (WS) accompanied with inner ear abnormality by analyzing the inner ear imaging results and molecular and genetic results of the WS patients with the SOX10 mutation.Methods This study included 36 WS in patients during 2001 and 2015 in the department of otorhinolaryngology head and neck surgery,Chinese Peoples's Liberation Army General Hospital.The condition of the inner ear of each patient was assessed by analyzing HRCT scans of the temporal bone and MRI scans of the brain and internal auditory canal.Meanwhile,the possible pathogenic genes of WS,including SOX10,MITF,and PAX3,were also screened.Patients were divided into two groups according to SOX10 mutation.The Fisher accuracy test was used to determine

  15. Coordination and Cooperation

    OpenAIRE

    Janssen, Maarten

    2003-01-01

    textabstractThis comment makes four related points. First, explaining coordination is different from explaining cooperation. Second, solving the coordination problem is more important for the theory of games than solving the cooperation problem. Third, a version of the Principle of Coordination can be rationalized on individualistic grounds. Finally, psychological game theory should consider how players perceive their gaming situation. ---------------------------------------------------------...

  16. Processing Coordination Ambiguity

    Science.gov (United States)

    Engelhardt, Paul E.; Ferreira, Fernanda

    2010-01-01

    We examined temporarily ambiguous coordination structures such as "put the butter in the bowl and the pan on the towel." Minimal Attachment predicts that the ambiguous noun phrase "the pan" will be interpreted as a noun-phrase coordination structure because it is syntactically simpler than clausal coordination. Constraint-based theories assume…

  17. Coordination and Cooperation

    NARCIS (Netherlands)

    M.C.W. Janssen (Maarten)

    2003-01-01

    textabstractThis comment makes four related points. First, explaining coordination is different from explaining cooperation. Second, solving the coordination problem is more important for the theory of games than solving the cooperation problem. Third, a version of the Principle of Coordination can

  18. Regularized estimation of magnitude and phase of multi-coil b1 field via Bloch-Siegert B1 mapping and coil combination optimizations.

    Science.gov (United States)

    Zhao, Feng; Fessler, Jeffrey A; Wright, Steven M; Noll, Douglas C

    2014-10-01

    Parallel excitation requires fast and accurate B1 map estimation. Bloch-Siegert (BS) B1 mapping is very fast and accurate over a large dynamic range. When applied to multi-coil systems, however, this phase-based method may produce low signal-to-noise ratio estimates in low magnitude regions due to localized excitation patterns of parallel excitation systems. Also, the imaging time increases with the number of coils. In this work, we first propose to modify the standard BS B1 mapping sequence so that it avoids the scans required by previous B1 phase estimation methods. A regularized method is then proposed to jointly estimate the magnitude and phase of multi-coil B1 maps from BS B1 mapping data, improving estimation quality by using the prior knowledge of the smoothness of B1 magnitude and phase. Lastly, we use Cramer-Rao lower bound analysis to optimize the coil combinations, to improve the quality of the raw data for B1 estimation. The proposed methods are demonstrated by simulations and phantom experiments.

  19. Hyperglycemic activity of the recombinant crustacean hyperglycemic hormone B1 isoform (CHH-B1) of the Pacific white shrimp Litopenaeus vannamei.

    Science.gov (United States)

    Camacho-Jiménez, Laura; Sánchez-Castrejón, Edna; Ponce-Rivas, Elizabeth; Muñoz-Márquez, Ma Enriqueta; Aguilar, Manuel B; Re, Ana Denisse; Díaz, Fernando

    2015-09-01

    Crustacean hyperglycemic hormone (CHH) is the most abundant neuropeptide produced by the X-organ/sinus gland (XO/SG) complex in the crustacean eyestalk. CHH plays a principal role in the control of glucose metabolism. The CHH-B1 isoform is produced in the eyestalk of Litopenaeus vannamei by alternative splicing of the chhB gene and its cDNA sequence has revealed that this isoform has a non-amidated C-terminal residue (CHH-like peptide). In this work, a recombinant CHH-B1 (rCHH-B1) with a sequence identical to the native hormone was expressed in the methylotrophic yeast Pichia pastoris X-33 and purified from the culture medium by RP-HPLC. The identity of the purified rCHH-B1 was confirmed by N-terminal sequencing and by using an anti-CHH-B1 polyclonal antibody. An in vivo assay showed that the hyperglycemic effect was dependant of the dosage of rCHH-B1, and the maximal hyperglycemic response was obtained with 250pmol treatment. These results suggest that the amino acid sequence of the C-terminus and its correct structure are both important for the hyperglycemic activity of naturally occurring non-amidated CHH peptides, such as CHH-B1. CHH-B1 appears to be the first reported CHH-like peptide with significant hyperglycemic activity produced in the sinus gland of a penaeid shrimp.

  20. EphB1 Suppression in Acute Myelogenous Leukemia : Regulating the DNA Damage Control System

    NARCIS (Netherlands)

    Kampen, K. R.; Scherpen, F. J. G.; Garcia-Manero, G.; Yang, H.; Kaspers, G. J. L.; Cloos, J.; Zwaan, C. M.; van den Heuvel-Eibrink, M. M.; Kornblau, S. M.; De Bont, E. S. J. M.

    2015-01-01

    Loss of ephrin receptor (EphB1) expression may associate with aggressive cancer phenotypes; however, the mechanism of action remains unclear. To gain detailed insight into EphB1 function in acute myelogenous leukemia (AML), comprehensive analysis of EphB1 transcriptional regulation was conducted. In

  1. 22 CFR 9b.1 - Press access to the Department of State.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Press access to the Department of State. 9b.1 Section 9b.1 Foreign Relations DEPARTMENT OF STATE GENERAL REGULATIONS GOVERNING DEPARTMENT OF STATE PRESS BUILDING PASSES § 9b.1 Press access to the Department of State. (a) Media correspondents without...

  2. Data of evolutionary structure change: 1DJ2B-1ADIB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1DJ2B-1ADIB 1DJ2 1ADI B B IGSLSQVSGVLGCQWGDEGKGKLVDILAQHFDIVARCQG...LLSEACPLILDYHVALDNAREKARGAKAIGTTGRGIGPAYEDKVARRGLRVGDLFDKETFAEKLKEVMEYHNFQLVNYYKAEAVDYQKVLDDTMAVADI...LY CA 195 PHE CA 263 LYS CA 227 TYR CA 251 1ADI B 1ADIB 1 1ADI B 1ADI

  3. Strain background modifies phenotypes in the ATP8B1-deficient mouse

    NARCIS (Netherlands)

    Shah, S.; Sanford, U.R.; Vargas, J.C.; Xu, H.; Groen, A.; Paulusma, C.C.; Grenert, J.P.; Pawlikowska, L.; Sen, S.; Oude Elferink, R.P.J.; Bull, L.N.

    2010-01-01

    BACKGROUND: Mutations in ATP8B1 (FIC1) underlie cases of cholestatic disease, ranging from chronic and progressive (progressive familial intrahepatic cholestasis) to intermittent (benign recurrent intrahepatic cholestasis). The ATP8B1-deficient mouse serves as an animal model of human ATP8B1 deficie

  4. Performance of an activated carbon made from waste palm shell in simultaneous adsorption of SOx and NOx of flue gas at low temperature

    Institute of Scientific and Technical Information of China (English)

    S.SUMATHI; S.BHATIA; K.T.LEE; A.R.MOHAMED

    2009-01-01

    This study examined the individual and simultaneous adsorption of SOx (SO2) and NOx (NO-NO2) on activated carbon prepared from waste palm shell. The adsorption process was examined in a fixed bed reactor at low temperatures (100-300℃). For individual adsorption without any catalytic activation, SOx showed good adsorption whereas NOx was very much poor. In the simultaneous adsorption of SOx and NOx, SOx showed greater adsorption affinity than NOx. For palm shell activated carbon (PSAC) im-pregnated with metal catalyst (Ni and Ce) the concentration adsorbed profile showed that the amount of SOx adsorbed decreased regularly, while the amount of the adsorbed NOx increased irregularly. The properties of the pure and impregnated PSAC were analyzed by BET, SEM and EDX. These investiga-tions indicated that PSAC impregnated with metal catalyst is the determining factor in the adsorption of SOxand NOx simultaneously.

  5. Members of the CREB/ATF and AP1 family of transcription factors are involved in the regulation of SOX18 gene expression

    Directory of Open Access Journals (Sweden)

    Petrović Isidora

    2011-01-01

    Full Text Available The SOX18 transcription factor plays an important role in endothelial cell specification, angiogenesis and atherogenesis. By profiling transcription factor interactions (TranSignal TM TF Protein Array we identified several transcription factors implicated in angiogenesis that have the ability to bind to the SOX18 optimal promoter region in vitro. In this report we focused our attention on distinct transcription factors identified by the array as belonging to AP-1 and CREB/ATF protein families. In particular, we analyzed the effects of CREB, JunB, c-Jun and ATF3 on SOX18 gene expression. Functional analysis revealed that CREB acts as a repressor, while JunB, c-Jun and ATF3 act as activators of SOX18 promoter activity. Our findings indicate that a transcriptional network that includes CREB, JunB, c-Jun and ATF3 could be involved in angiogenesis-related transcriptional regulation of the SOX18 gene.

  6. Normal Levels of Sox9 Expression in the Developing Mouse Testis Depend on the TES/TESCO Enhancer, but This Does Not Act Alone

    Science.gov (United States)

    O’Neill, Helen C.; Koopman, Peter; Lovell-Badge, Robin

    2017-01-01

    During mouse sex determination, transient expression of the Y-linked gene Sry up-regulates its direct target gene Sox9, via a 3.2 kb testis specific enhancer of Sox9 (TES), which includes a core 1.4 kb element, TESCO. SOX9 activity leads to differentiation of Sertoli cells, rather than granulosa cells from the bipotential supporting cell precursor lineage. Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh. Although human patients heterozygous for null mutations in SOX9, which are assumed to have 50% of normal expression, often show XY female sex reversal, mice deleted for one copy of Sox9 do not. Consistent with this, we did not observe sex reversal in either TESCO-/- or TES-/- XY embryos or adult mice. However, embryos carrying both a conditional Sox9 null allele and the TES deletion developed ovotestes. Quantitative analysis of these revealed levels of 23% expression of Sox9 compared to wild type, and a significant increase in the expression of the granulosa cell marker Foxl2. This indicates that the threshold in mice where sex reversal begins to be seen is about half that of the ~50% levels predicted in humans. Our results demonstrate that TES/TESCO is a crucial enhancer regulating Sox9 expression in the gonad, but point to the existence of additional enhancers that act redundantly. PMID:28045957

  7. Different effects of transcriptional regulators MarA, SoxS and Rob on susceptibility of Escherichia coli to cationic antimicrobial peptides (CAMPs): Rob-dependent CAMP induction of the marRAB operon.

    Science.gov (United States)

    Warner, Douglas M; Levy, Stuart B

    2010-02-01

    Cationic antimicrobial peptides (CAMPs), a component of the mammalian immune system, protect the host from bacterial infections. The roles of the Escherichia coli transcriptional regulators MarA, SoxS and Rob in susceptibility to these peptides were examined. Overexpression of marA, either in an antibiotic-resistant marR mutant or from a plasmid, decreased bacterial susceptibility to CAMPs. Overexpression of the soxS gene from a plasmid, which decreased susceptibility to antibiotics, unexpectedly caused no decrease in CAMP susceptibility; instead it produced increased susceptibility to different CAMPs. Deletion or overexpression of rob had little effect on CAMP susceptibility. The marRAB operon was upregulated when E. coli was incubated in sublethal amounts of CAMPs polymyxin B, LL-37 or human beta-defensin-1; however, this upregulation required Rob. Deletion of acrAB increased bacterial susceptibility to polymyxin B, LL-37 and human beta-defensin-1 peptides. Deletion of tolC yielded an even greater increase in susceptibility to these peptides and also led to increased susceptibility to human alpha-defensin-2. Inhibition of cellular proton-motive force increased peptide susceptibility for wild-type and acrAB deletion strains; however, it decreased susceptibility of tolC mutants. These findings demonstrate that CAMPs are both inducers of marA-mediated drug resistance through interaction with Rob and also substrates for efflux in E. coli. The three related transcriptional regulators show different effects on bacterial cell susceptibility to CAMPs.

  8. Important roles of multiple Sp1 binding sites and epigenetic modifications in the regulation of the methionine sulfoxide reductase B1 (MsrB1 promoter

    Directory of Open Access Journals (Sweden)

    Favaloro Bartolo

    2007-05-01

    Full Text Available Abstract Background Methionine sulfoxide reductases (Msrs are enzymes that catalyze the reduction of oxidized methionine residues. Most organisms that were genetically modified to lack the MsrA gene have shown shortening of their life span. Methionine sulfoxide reductases B (MsrB proteins codified by three separate genes, named MsrB1, MsrB2, and MsrB3, are included in the Msrs system. To date, the mechanisms responsible for the transcriptional regulation of MsrB genes have not been reported. The aim of this study was to investigate the regulation of MsrB1 selenoprotein levels through transcriptional regulation of the MsrB1 gene in MDA-MB231 and MCF-7 breast carcinoma cell lines. Results A MsrB1 gene promoter is located 169 base pairs upstream from the transcription start site. It contains three Sp1 binding sites which are sufficient for maximal promoter activity in transient transfection experiments. High levels of MsrB1 transcript, protein and promoter activity were detected in low metastatic MCF7 human breast cancer cells. On the contrary, very low levels of both MsrB1 transcript and promoter activity were detected in the highly metastatic counterpart MDA-MB231 cells. A pivotal role for Sp1 in the constitutive expression of the MsrB1 gene was demonstrated through transient expression of mutant MsrB1 promoter-reporter gene constructs and chromatin immunoprecipitation experiments. Since Sp1 is ubiquitously expressed, these sites, while necessary, are not sufficient to explain the patterns of gene expression of MsrB1 in various human breast cancer cells. MDA-MB231 cells can be induced to express MsrB1 by treatment with 5-Aza-2'-deoxycytidine, a demethylating agent. Therefore, the MsrB1 promoter is controlled by epigenetic modifications. Conclusion The results of this study provide the first insights into the transcriptional regulation of the human MsrB1 gene, including the discovery that the Sp1 transcription factor may play a central role in its

  9. CYP1B1 expression, a potential risk factor for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Goth-Goldstein, Regine; Erdmann, Christine A.; Russell, Marion

    2001-05-31

    CYP1B1 expression in non-tumor breast tissue from breast cancer patients and cancer-free individuals was determined to test the hypothesis that high CYP1B1 expression is a risk factor for breast cancer. Large interindividual variations in CYP1B1 expression were found with CYP1B1 levels notably higher in breast cancer patients than cancer-free individuals. The results indicate that CYP1B1 might play a role in breast cancer either through increased PAH activation or through metabolism of endogenous estrogen to a carcinogenic derivative.

  10. Herschel observations of B1-bS and B1-bN: two first hydrostatic core candidates in the Perseus star-forming cloud

    CERN Document Server

    Pezzuto, Stefano; Schisano, E; Strafella, F; Di Francesco, J; Sadavoy, S; André, P; Benedettini, M; Bernard, J P; di Giorgio, A M; Facchini, A; Hennemann, M; Hill, T; Könyves, V; Molinari, S; Motte, F; Nguyen-Luong, Q; Peretto, N; Pestalozzi, M; Polychroni, D; Rygl, K L J; Saraceno, P; Schneider, N; Spinoglio, L; Testi, L; Ward-Thompson, D; White, G J

    2012-01-01

    We report far-IR Herschel observations obtained between 70 $\\mu$m and 500 $\\mu$m of two star-forming dusty condensations, B1-bS and B1-bN, in the B1 region of the Perseus star-forming cloud. In the Western part of the Perseus cloud, B1-bS is the only source detected in all of the 6 PACS and SPIRE photometric bands without being visible in the Spitzer map at 24 $\\mu$m. B1-bN is clearly detected between 100 $\\mu$m and 250 $\\mu$m. We have fitted the spectral energy distributions of these sources to derive their physical properties, and find that a simple greybody model fails to reproduce the observed SEDs. At least a two-component model, consisting of a central source surrounded by a dusty envelope is required. The properties derived from the fit, however, suggest that the central source is not a Class 0 object. We then conclude that while B1-bS and B1-bN appear to be more evolved than a pre-stellar core, the best-fit models suggest that their central objects are younger than a Class 0 source. Hence, they may be...

  11. Dependence of B1+ and B1− Field Patterns of Surface Coils on the Electrical Properties of the Sample and the MR Operating Frequency

    Science.gov (United States)

    Vaidya, Manushka V.; Collins, Christopher M.; Sodickson, Daniel K.; Brown, Ryan; Wiggins, Graham C.; Lattanzi, Riccardo

    2016-01-01

    In high field MRI, the spatial distribution of the radiofrequency magnetic (B1) field is usually affected by the presence of the sample. For hardware design and to aid interpretation of experimental results, it is important both to anticipate and to accurately simulate the behavior of these fields. Fields generated by a radiofrequency surface coil were simulated using dyadic Green’s functions, or experimentally measured over a range of frequencies inside an object whose electrical properties were varied to illustrate a variety of transmit (B1+) and receive (B1−) field patterns. In this work, we examine how changes in polarization of the field and interference of propagating waves in an object can affect the B1 spatial distribution. Results are explained conceptually using Maxwell’s equations and intuitive illustrations. We demonstrate that the electrical conductivity alters the spatial distribution of distinct polarized components of the field, causing “twisted” transmit and receive field patterns, and asymmetries between |B1+| and |B1−|. Additionally, interference patterns due to wavelength effects are observed at high field in samples with high relative permittivity and near-zero conductivity, but are not present in lossy samples due to the attenuation of propagating EM fields. This work provides a conceptual framework for understanding B1 spatial distributions for surface coils and can provide guidance for RF engineers.

  12. CYP1B1 is polymorphic in cynomolgus and rhesus macaques.

    Science.gov (United States)

    Uno, Yasuhiro; Matsushita, Akinori; Yamazaki, Hiroshi

    2011-09-01

    Cytochrome P450 (CYP) 1B1 is involved in the metabolic activation of various procarcinogens, and some CYP1B1 genetic variants alter CYP1B1-dependent procarcinogen metabolism. Cynomolgus and rhesus macaques are frequently used in toxicity tests due to their evolutionary closeness to humans. In this study, we attempted to identify CYP1B1 genetic variants in 13 cynomolgus and 4 rhesus macaques. A total of 17 genetic variants were identified, including 8 non-synonymous genetic variants, indicating that, similar to humans, CYP1B1 is polymorphic in macaques. These CYP1B1 genetic variants could be the basis for understanding potential inter-animal differences in macaque CYP1B1-dependent metabolism of promutagens.

  13. Significance of Sox9 mRNA in dedifferentiation process of chondrosarcoma%Sox9 mRNA在软骨肉瘤去分化过程中的意义

    Institute of Scientific and Technical Information of China (English)

    刘百奇; 孟祥龙; 张昊; 车德馨; 王国文; 韩金刚

    2016-01-01

    目的:探讨Sox9 mRNA在软骨肉瘤去分化过程中所起的作用,并分析其与各临床病理参数的关系。方法利用免疫组织化学方法检测Sox9 mRNA在人普通软骨肉瘤与去分化软骨肉瘤间的差异表达及其与临床病理参数的关系。结果与正常软骨组织比较,Sox9 mRNA 在普通软骨肉瘤中表达上调,在去分化软骨肉瘤中表达下调;Sox9 mRNA在软骨肉瘤各分级之间表达水平比较,差异有统计学意义(P0.05),而与肺转移、有无复发有关,且肺转移及复发者阳性率明显高于无肺转移、无复发者,差异有统计学意义(P0.05),while had relation with the lung metastasis and recurrence,moreover the positive rate in the patients with lung metastasis and recurrence was significantly higher than that in the patients without lung metastasis and recurrence ,the difference was statistically significant(P<0.01). Conclusion Sox9 mRNA is related with occurrence,progression,metastasis and prognosis of chondrosarcoma.

  14. A Sox Transcription Factor Is a Critical Regulator of Adult Stem Cell Proliferation in the Drosophila Intestine

    Directory of Open Access Journals (Sweden)

    Fanju W. Meng

    2015-11-01

    Full Text Available Adult organs and their resident stem cells are constantly facing the challenge of adapting cell proliferation to tissue demand, particularly in response to environmental stresses. Whereas most stress-signaling pathways are conserved between progenitors and differentiated cells, stem cells have the specific ability to respond by increasing their proliferative rate, using largely unknown mechanisms. Here, we show that a member of the Sox family of transcription factors in Drosophila, Sox21a, is expressed in intestinal stem cells (ISCs in the adult gut. Sox21a is essential for the proliferation of these cells during both normal epithelium turnover and repair. Its expression is induced in response to tissue damage, downstream of the Jun N-terminal kinase (JNK and extracellular signal-regulated kinase (ERK pathways, to promote ISC proliferation. Although short-lived, Sox21a mutant flies show no developmental defects, supporting the notion that this factor is a specific regulator of adult stem cell proliferation.

  15. Chronic constipation recognized as a sign of a SOX10 mutation in a patient with Waardenburg syndrome.

    Science.gov (United States)

    Arimoto, Yukiko; Namba, Kazunori; Nakano, Atsuko; Matsunaga, Tatsuo

    2014-05-01

    Waardenburg syndrome is characterized by hearing loss, pigmentation abnormalities, dysmorphologic features, and neurological phenotypes. Waardenburg syndrome consists of four distinct subtypes, and SOX10 mutations have been identified in type II and type IV. Type IV differs from type II owing to the presence of Hirschsprung disease. We identified a de novo nonsense mutation in SOX10 (p.G39X) in a female pediatric patient with Waardenburg syndrome with heterochromia iridis, profound bilateral sensorineural hearing loss, inner ear malformations, and overall hypopigmentation of the hair without dystopia canthorum. This patient has experienced chronic constipation since she was a neonate, but anorectal manometry showed a normal anorectal reflex. Chronic constipation in this patient was likely to be a consequence of a mild intestinal disorder owing to the SOX10 mutation, and this patient was considered to have a clinical phenotype intermediate between type II and type IV of the syndrome. Chronic constipation may be recognized as indicative of a SOX10 mutation in patients with Waardenburg syndrome.

  16. Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects

    NARCIS (Netherlands)

    Bauters, M.; Frints, S.G.; Esch, H. van; Spruijt, L.; Baldewijns, M.M.; Die-Smulders, C.E.M. de; Fryns, J.P.; Marynen, P.; Froyen, G.

    2014-01-01

    Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from

  17. CD44, SHH and SOX2 as novel biomarkers in esophageal cancer patients treated with neoadjuvant chemoradiotherapy

    NARCIS (Netherlands)

    Honing, Judith; Pavlov, Kirill V.; Mul, Veronique E. M.; Karrenbeld, Arend; Meijer, Coby; Faiz, Zohra; Smit, Justin K.; Hospers, Geke A. P.; Burgerhof, Johannes G. M.; Kruyt, Frank A. E.; Kleibeuker, Jan H.; Plukker, John T. M.

    2015-01-01

    Background and purpose: Neoadjuvant chemoradiotherapy (nCRT) improves survival in esophageal cancer (EC) patients, but the response to treatment is heterogeneous and little is known regarding prognostic and predictive markers in these patients. CD44, SOX2 and SHH have been implicated in resistance t

  18. SOX6 and PDCD4 enhance cardiomyocyte apoptosis through LPS-induced miR-499 inhibition.

    Science.gov (United States)

    Jia, Zhuqing; Wang, Jiaji; Shi, Qiong; Liu, Siyu; Wang, Weiping; Tian, Yuyao; Lu, Qin; Chen, Ping; Ma, Kangtao; Zhou, Chunyan

    2016-02-01

    Sepsis-induced cardiac apoptosis is one of the major pathogenic factors in myocardial dysfunction. As it enhances numerous proinflammatory factors, lipopolysaccharide (LPS) is considered the principal mediator in this pathological process. However, the detailed mechanisms involved are unclear. In this study, we attempted to explore the mechanisms involved in LPS-induced cardiomyocyte apoptosis. We found that LPS stimulation inhibited microRNA (miR)-499 expression and thereby upregulated the expression of SOX6 and PDCD4 in neonatal rat cardiomyocytes. We demonstrate that SOX6 and PDCD4 are target genes of miR-499, and they enhance LPS-induced cardiomyocyte apoptosis by activating the BCL-2 family pathway. The apoptosis process enhanced by overexpression of SOX6 or PDCD4, was rescued by the cardiac-abundant miR-499. Overexpression of miR-499 protected the cardiomyocytes against LPS-induced apoptosis. In brief, our results demonstrate the existence of a miR-499-SOX6/PDCD4-BCL-2 family pathway in cardiomyocytes in response to LPS stimulation.

  19. Effects of GABA agonists on body temperature regulation in GABA(B(1))-/- mice.

    Science.gov (United States)

    Quéva, Christophe; Bremner-Danielsen, Marianne; Edlund, Anders; Ekstrand, A Jonas; Elg, Susanne; Erickson, Sven; Johansson, Thore; Lehmann, Anders; Mattsson, Jan P

    2003-09-01

    1. Activation of GABA(B) receptors evokes hypothermia in wildtype (GABA(B(1))+/+) but not in GABA(B) receptor knockout (GABA(B(1))-/-) mice. The aim of the present study was to determine the hypothermic and behavioural effects of the putative GABA(B) receptor agonist gamma-hydroxybutyrate (GHB), and of the GABA(A) receptor agonist muscimol. In addition, basal body temperature was determined in GABA(B(1))+/+, GABA(B(1))+/- and GABA(B(1))-/- mice. 2. GABA(B(1))-/- mice were generated by homologous recombination in embryonic stem cells. Correct gene targeting was assessed by Southern blotting, PCR and Western blotting. GABA(B) receptor-binding sites were quantified with radioligand binding. Measurement of body temperature was done using subcutaneous temperature-sensitive chips, and behavioural changes after drug administration were scored according to a semiquantitative scale. 3. GABA(B(1))-/- mice had a short lifespan, probably caused by generalised seizure activity. No histopathological or blood chemistry changes were seen, but the expression of GABA(B(2)) receptor protein was below the detection limit in brains from GABA(B(1))-/- mice, in the absence of changes in mRNA levels. 4. GABA(B) receptor-binding sites were absent in brain membranes from GABA(B(1))-/- mice. 5. GABA(B(1))-/- mice were hypothermic by approximately 1 degrees C compared to GABA(B(1))+/+ and GABA(B(1))+/- mice. 6. Injection of baclofen (9.6 mg kg-1) produced a large reduction in body temperature and behavioural effects in GABA(B(1))+/+ and in GABA(B(1))+/- mice, but GABA(B(1))-/- mice were unaffected. The same pattern was seen after administration of GHB (400 mg kg-1). The GABA(A) receptor agonist muscimol (2 mg kg-1), on the other hand, produced a more pronounced hypothermia in GABA(B(1))-/-mice. In GABA(B(1))+/+ and GABA(B(1))+/- mice, muscimol induced sedation and reduced locomotor activity. However, when given to GABA(B(1))-/- mice, muscimol triggered periods of intense jumping and wild

  20. CYP1B1 mRNA inducibility due to benzo(a)pyrene is modified by the CYP1B1 L432V gene polymorphism.

    Science.gov (United States)

    Helmig, Simone; Wenzel, Sibylle; Maxeiner, Hagen; Schneider, Joachim

    2014-07-01

    Benzo(a)pyrene (BaP), a primary component of tobacco smoke, is activated by cytochrome P450 1B1 (CYP1B1). Smokers homozygous for the C-allele (*1/*1) at the CYP1B1 Leu432Val polymorphism have shown increased CYP1B1 expression, compared to smokers homozygous for the G-allele *3/*3. Since no difference has been shown in CYP1B1 expression between both genotypes in non-smokers, we assumed that the genetic impact is produced in combination with an exogenous induction (e.g. BaP). To confirm this theory and to quantify the effect, we induced human leucocytes with increasing BaP concentrations and determined CYP1B1 mRNA expression with real-time polymerase chain reaction (PCR). We incubated human leucocytes from 27 healthy donors with BaP concentrations ranging from 2.5 to 250 µM. We identified the CYP1B1 genotypes by melting curve analysis and assessed relative CYP1B1 mRNA expression using real-time PCR. Expression was related to β-2-microglobulin with the 2(-ΔΔCT) method. Inducibility of CYP1B1 mRNA by BaP was higher in leucocytes carrying the CYP1B1*1/*1 genotype than in leucocytes carrying the CYP1B1*3/*3 genotype (P = 0.012). We revealed significant differences, with BaP concentrations of 2.5 µM (P = 0.0094), 5 µM (P = 0.027), 10 µM (P = 0.0006), 25 µM (P = 0.0007) and 50 µM (P = 0.017). Homozygous carriers of the C-allele (*1/*1) at the CYP1B1 Leu432Val polymorphism show a higher response to environmental factors, such as carcinogenic BaP, than homozygous carriers of the G-allele *3/*3.

  1. FUNCION DE SOX2 EN LA REGENERACION DE LA MEDULA ESPINAL DE XENOPUS LAEVIS

    OpenAIRE

    2010-01-01

    Los mamíferos presentan una limitada capacidad de regeneración frente a una lesión de la médula espinal, lo que impide una correcta recuperación locomotriz. Sin embargo, los renacuajos de Xenopus laevis sí son capaces de regenerar la médula espinal, pero se desconocen los mecanismos involucrados en este proceso. Es posible que esta regeneración proceda a través de la activación de células madre y progenitores neurales. Sox2 es un factor de transcripción que se expresa en las células mad...

  2. FUNCION DE SOX2 EN LA REGENERACION DE LA MEDULA ESPINAL DE XONOPUS LAEVIS

    OpenAIRE

    2010-01-01

    Los mamíferos presentan una limitada capacidad de regeneración frente a una lesión de la médula espinal, lo que impide una correcta recuperación locomotriz. Sin embargo, los renacuajos de Xenopus laevis sí son capaces de regenerar la médula espinal, pero se desconocen los mecanismos involucrados en este proceso. Es posible que esta regeneración proceda a través de la activación de células madre y progenitores neurales. Sox2 es un factor de transcripción que se expresa en las cé...

  3. AudioRegent: Exploiting SimpleADL and SoX for Digital Audio Delivery

    Directory of Open Access Journals (Sweden)

    Nitin Arora

    2010-06-01

    Full Text Available AudioRegent is a command-line Python script currently being used by the University of Alabama Libraries’ Digital Services to create web-deliverable MP3s from regions within archival audio files. In conjunction with a small-footprint XML file called SimpleADL and SoX, an open-source command-line audio editor, AudioRegent batch processes archival audio files, allowing for one or many user-defined regions, particular to each audio file, to be extracted with additional audio processing in a transparent manner that leaves the archival audio file unaltered. Doing so has alleviated many of the tensions of cumbersome workflows, complicated documentation, preservation concerns, and reliance on expensive closed-source GUI audio applications.

  4. Calorimetric measurement of the SOX anti-neutrino source for sterile neutrino search

    Energy Technology Data Exchange (ETDEWEB)

    Altenmueller, Konrad; Agostini, Matteo; Papp, Laszlo; Schoenert, Stefan [Physik Department and Excellence Cluster Universe, Technische Universitaet Muenchen (Germany); Collaboration: Borexino-Collaboration

    2015-07-01

    A thermal calorimeter is under development to measure with <1% accuracy the heat release of the Cerium anti-neutrino source for the SOX experiment, which is looking for eV-scale sterile neutrinos. The heat release is proportional to the source activity and thus to the emitted neutrino flux, which is an important parameter of the experiment. The calorimeter design is based on a copper heat exchanger mounted around the source with integrated water lines for the heat extraction. Heat loss through conduction and radiation is minimized by suspending the set-up through Kevlar ropes and inserting it inside a thermalized vacuum tank with radiation shields. The device is currently being assembled and tested at TUM in Garching.

  5. Effect of microRNA-101 on apoptosis of rabbit condylar cartilage cells by inhibiting target gene SOX9

    Institute of Scientific and Technical Information of China (English)

    Xin Li; Zi-Xin Wang; Zi-Sheng Wang; Quan-Fang Li

    2015-01-01

    Objective:To explore the effect of microRNA-101 on apoptosis of condylar cartilage cells and the specific mechanism of molecular biology. Methods: IL-1 was used to stimulate and establish the model of apoptosis of condylar cartilage cells. The expression change of miR-101 in control group was compared with that in IL-1 stimulation group by qRT-PCR. Overexpression and down-regulation models of miR-101 were established by transfecting Mimics and Inhibitor and verified by qRT-PCR. Flow cytometry was used to detect the effect of miR-101 overexpression and down-regulation on apoptosis. Target gene of miR-101 was analyzed and calculated through bioinformatics. Western blot and Luciferase report assay were used to detect whether Sox9 could become the target gene of miR-101. Results:qRT-PCR results showed that IL-1 stimulation could cause the increase of miR-101 expression. After the transfection of rabbit condylar cartilage cells by Mimics and Inhibitor, qRT-PCR results confirmed the significant effect of miR-101 overexpression and down-regulation. It was confirmed by flow cytometry that overexpression of miR-101 could promote the apoptosis of condylar cartilage cells, and down-regulation of miR-101 could reduce the apoptosis. It was confirmed by Western blot and Luciferase report assay that Sox9 was the target gene of miR-101, and miR-101 inhibited SOX9 expression through complementary pairing with 3’UTR of Sox9 mRNA. Conclusions:miR-101 can promote the apoptosis of condylar cartilage cells through inhibiting the protein level of target gene SOX9.

  6. Sox2 regulates cholinergic amacrine cell positioning and dendritic stratification in the retina.

    Science.gov (United States)

    Whitney, Irene E; Keeley, Patrick W; St John, Ace J; Kautzman, Amanda G; Kay, Jeremy N; Reese, Benjamin E

    2014-07-23

    The retina contains two populations of cholinergic amacrine cells, one positioned in the ganglion cell layer (GCL) and the other in the inner nuclear layer (INL), that together comprise ∼1/2 of a percent of all retinal neurons. The present study examined the genetic control of cholinergic amacrine cell number and distribution between these two layers. The total number of cholinergic amacrine cells was quantified in the C57BL/6J and A/J inbred mouse strains, and in 25 recombinant inbred strains derived from them, and variations in their number and ratio (GCL/INL) across these strains were mapped to genomic loci. The total cholinergic amacrine cell number was found to vary across the strains, from 27,000 to 40,000 cells, despite little variation within individual strains. The number of cells was always lower within the GCL relative to the INL, and the sizes of the two populations were strongly correlated, yet there was variation in their ratio between the strains. Approximately 1/3 of that variation in cell ratio was mapped to a locus on chromosome 3, where Sex determining region Y box 2 (Sox2) was identified as a candidate gene due to the presence of a 6-nucleotide insertion in the protein-coding sequence in C57BL/6J and because of robust and selective expression in cholinergic amacrine cells. Conditionally deleting Sox2 from the population of nascent cholinergic amacrine cells perturbed the normal ratio of cells situated in the GCL versus the INL and induced a bistratifying morphology, with dendrites distributed to both ON and OFF strata within the inner plexiform layer.

  7. Enhanced time overcurrent coordination

    Energy Technology Data Exchange (ETDEWEB)

    Enriquez, Arturo Conde; Martinez, Ernesto Vazquez [Universidad Autonoma de Nuevo Leon, Facultad de Ingenieria Mecanica y Electrica, Apdo. Postal 114-F, Ciudad Universitaria, CP 66450 San Nicolas de los Garza, Nuevo Leon (Mexico)

    2006-04-15

    In this paper, we recommend a new coordination system for time overcurrent relays. The purpose of the coordination process is to find a time element function that allows it to operate using a constant back-up time delay, for any fault current. In this article, we describe the implementation and coordination results of time overcurrent relays, fuses and reclosers. Experiments were carried out in a laboratory test situation using signals of a power electrical system physics simulator. (author)

  8. Overexpression of SULT2B1b Promotes Angiogenesis in Human Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Wen Chen

    2016-03-01

    Full Text Available Background/Aims: Overexpression of cytosolic sulfotransferase 2B1b (SULT2B1b has been commonly found in colorectal and hepatocellular carcinoma, suggesting that SULT2B1b might act as a potential oncogenic protein. However, its clinical significance and biological role in gastric cancer progression remain largely unknown. Methods: Expressions of SULT2B1b in clinical gastric cancer (GC samples were examined using qRT-PCR and Western blot. Results: SULT2B1b was markedly overexpressed in human GC samples, and positively correlated with vessel density and associated with poor clinical features. We also demonstrated that overexpression of SULT2B1b resulted in increased tumor angiogenesis and tumor growth in mouse GC models. In addition, ablation of SULT2B1b in human GC cells lines BGC823 and MKN45 decreased the capability of the cells to recruit endothelial cells. Moreover, depletion of SULT2B1b in GC cells reduced VEGF-A expression by downregulating SP1 and AP2. Conclusion: Our results suggested that the SULT2B1b-mediated angiogenic pathway could serve as biomarkers for GC diagnosis and prognosis, and suppressing SULT2B1b-mediated angiogenic signaling might be a promising strategy for developing novel GC treatment.

  9. Observations and light curve solutions of the eclipsing binaries USNO-B1.0 1395-0370184 and USNO-B1.0 1395-0370731

    Directory of Open Access Journals (Sweden)

    Kjurkchieva D.

    2016-01-01

    Full Text Available We present follow-up photometric observations in Sloan filters g', i' of the newly discovered eclipsing stars USNO-B1.0 1395-0370184 and USNO-B1.0 1395-0370731. Our data revealed that their orbital periods are considerably bigger than the previous values. This result changed the classification of USNO-B1.0 1395-0370184 from ultrashort-period binary (P=0.197 d to short-period system (P=0.251 d. The light curve solutions of our observations revealed that USNOB1.0 1395-0370184 and USNO-B1.0 1395-0370731 are overcontact binaries in which components are K dwarfs, close in masses and radii. The light curve distortions were reproduced by cool spots with angular radius of around 20°.

  10. NOAA Climate Data Record (CDR) of Gridded Satellite Data from ISCCP B1 (GridSat-B1) Infrared Channel Brightness Temperature, Version 2

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Gridded Satellite (GridSat-B1) data provides a uniform set of quality controlled geostationary satellite observations for the visible, infrared window and...

  11. Cell stress promotes the association of phosphorylated HspB1 with F-actin.

    Directory of Open Access Journals (Sweden)

    Joseph P Clarke

    Full Text Available Previous studies have suggested that the small heat shock protein, HspB1, has a direct influence on the dynamics of cytoskeletal elements, in particular, filamentous actin (F-actin polymerization. In this study we have assessed the influence of HspB1 phosphorylation on its interaction(s with F-actin. We first determined the distribution of endogenous non-phosphorylated HspB1, phosphorylated HspB1 and F-actin in neuroendocrine PC12 cells by immunocytochemistry and confocal microscopy. We then investigated a potential direct interaction between HspB1 with F-actin by precipitating F-actin directly with biotinylated phalloidin followed by Western analyses; the reverse immunoprecipitation of HspB1 was also carried out. The phosphorylation influence of HspB1 in this interaction was investigated by using pharmacologic inhibition of p38 MAPK. In control cells, HspB1 interacts with F-actin as a predominantly non-phosphorylated protein, but subsequent to stress there is a redistribution of HspB1 to the cytoskeletal fraction and a significantly increased association of pHspB1 with F-actin. Our data demonstrate HspB1 is found in a complex with F-actin both in phosphorylated and non-phosphorylated forms, with an increased association of pHspB1 with F-actin after heat stress. Overall, our study combines both cellular and biochemical approaches to show cellular localization and direct demonstration of an interaction between endogenous HspB1 and F-actin using methodolgy that specifically isolates F-actin.

  12. Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Z.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Li, X.L. [Department of Dermatology, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); He, X.J. [Department of Orthopedics, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Wu, B.J.; Xu, M. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Chang, H.M. [Department of Otolaryngology - Head and Neck Surgery, Affiliated Hospital of Xi' an Medical University, Xi' an (China); Zhang, X.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Xing, Z. [Department of Clinical Dentistry, Faculty of Dentistry, Center for Clinical Dental Research, University of Bergen, Bergen (Norway); Jing, X.H.; Kong, D.M.; Kou, X.H.; Yang, Y.Y. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China)

    2014-03-18

    SRY-related high-mobility-group box 9 (Sox9) gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs). After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering.

  13. The transcription factor protein Sox11 enhances early osteoblast differentiation by facilitating proliferation and the survival of mesenchymal and osteoblast progenitors.

    Science.gov (United States)

    Gadi, Jogeswar; Jung, Seung-Hyun; Lee, Min-Jung; Jami, Ajita; Ruthala, Kalyani; Kim, Kyoung-Min; Cho, Nam-Hoon; Jung, Han-Sung; Kim, Cheol-Hee; Lim, Sung-Kil

    2013-08-30

    Sox11 deletion mice are known to exhibit developmental defects of craniofacial skeletal malformations, asplenia, and hypoplasia of the lung, stomach, and pancreas. Despite the importance of Sox11 in the developing skeleton, the role of Sox11 in osteogenesis has not been studied yet. In this study, we identified that Sox11 is an important transcription factor for regulating the proliferation and survival of osteoblast precursor cells as well as the self-renewal potency of mesenchymal progenitor cells via up-regulation of Tead2. Furthermore, Sox11 also plays an important role in the segregation of functional osteoblast lineage progenitors from osteochondrogenic progenitors. Facilitation of osteoblast differentiation from mesenchymal cells was achieved by enhanced expression of the osteoblast lineage specific transcription factors Runx2 and Osterix. Morpholino-targeted disruption of Sox11 in zebrafish impaired organogenesis, including the bones, which were under mineralized. These results indicated that Sox11 plays a crucial role in the proliferation and survival of mesenchymal and osteoblast precursors by Tead2, and osteogenic differentiation by regulating Runx2 and Osterix.

  14. Montelukast Disposition: No Indication of Transporter-Mediated Uptake in OATP2B1 and OATP1B1 Expressing HEK293 Cells

    Science.gov (United States)

    Brännström, Marie; Nordell, Pär; Bonn, Britta; Davis, Andrew M.; Palmgren, Anna-Pia; Hilgendorf, Constanze; Rubin, Katarina; Grime, Ken

    2015-01-01

    Clinical studies with montelukast show variability in effect and polymorphic OATP2B1-dependent absorption has previously been implicated as a possible cause. This claim has been challenged with conflicting data and here we used OATP2B1-transfected HEK293 cells to clarify the mechanisms involved. For montelukast, no significant difference in cell uptake between HEK-OATP2B1 and empty vector cell lines was observed at pH 6.5 or pH 7.4, and no concentration-dependent uptake was detected. Montelukast is a carboxylic acid, a relatively potent inhibitor of OATP1B1, OATP1B3, and OATP2B1, and has previously been postulated to be actively transported into human hepatocytes. Using OATP1B1-transfected HEK293 cells and primary human hepatocytes in the presence of OATP inhibitors we demonstrate for the first time that active OATP-dependent transport is unlikely to play a significant role in the human disposition of montelukast. PMID:26694455

  15. SOX10 is a novel marker of acinus and intercalated duct differentiation in salivary gland tumors: a clue to the histogenesis for tumor diagnosis.

    Science.gov (United States)

    Ohtomo, Rie; Mori, Taisuke; Shibata, Shinsuke; Tsuta, Koji; Maeshima, Akiko M; Akazawa, Chihiro; Watabe, Yukio; Honda, Kazufumi; Yamada, Tesshi; Yoshimoto, Seiichi; Asai, Masao; Okano, Hideyuki; Kanai, Yae; Tsuda, Hitoshi

    2013-08-01

    Salivary gland tumors are relatively rare and morphologically diverse and heterogeneous tumors; therefore, histogenesis-based tumor markers are sorely needed to aid in diagnosing and determining the cell type of origin. SRY-related HMG-box 10 (SOX10) protein is a transcription factor known to be crucial in the specification of the neural crest and maintenance of Schwann cells and melanocytes. In addition, positive expression has also been implicated in the major salivary gland. Here, we examined SOX10 expression in various salivary gland tumors to correlate this expression with myoepithelial markers. Overall, 76 malignant and 14 benign tumors were examined. SOX10 expression clearly delineated two distinct subtypes of human salivary gland tumors; acinic cell carcinomas, adenoid cystic carcinomas, epithelial-myoepithelial carcinomas, myoepithelial carcinomas, and pleomorphic adenomas, including the pleomorphic adenoma component of carcinoma, were SOX10 positive, while salivary duct carcinomas, mucoepidermoid carcinomas, an oncocytic carcinoma, Oncocytomas, and Warthin tumors were SOX10 negative. Also, SOX10 was expressed in solid-type or non-specific morphology salivary gland tumors, but was not expressed in poorly differentiated squamous cell carcinomas. In normal human salivary gland tissue, SOX10 expression was specific to the nuclei of acini and both luminal and abluminal cells of intercalated ducts but not in other sites. Moreover, the murine model suggested that SOX10 continued to be expressed from the developmental stage to adulthood in the acinar and both luminal and abluminal intercalated ducts in the major salivary gland. Thus, SOX10 is a novel marker for diagnosing and understanding the histogenesis of salivary gland tumors.

  16. RAR agonists stimulate SOX9 gene expression in breast cancer cell lines: evidence for a role in retinoid-mediated growth inhibition.

    Science.gov (United States)

    Afonja, Olubunmi; Raaka, Bruce M; Huang, Ambrose; Das, Sharmistha; Zhao, Xinyu; Helmer, Elizabeth; Juste, Dominique; Samuels, Herbert H

    2002-11-01

    Retinoic acid receptors (RARs) are ligand-dependent transcription factors which are members of the steroid/thyroid hormone receptor gene family. RAR-agonists inhibit the proliferation of many human breast cancer cell lines, particularly those whose growth is stimulated by estradiol (E2) or growth factors. PCR-amplified subtractive hybridization was used to identify candidate retinoid-regulated genes that may be involved in growth inhibition. One candidate gene identified was SOX9, a member of the high mobility group (HMG) box gene family of transcription factors. SOX9 gene expression is rapidly stimulated by RAR-agonists in T-47D cells and other retinoid-inhibited breast cancer cell lines. In support of this finding, a database search indicates that SOX9 is expressed as an EST in breast tumor cells. SOX9 is known to be expressed in chondrocytes where it regulates the transcription of type II collagen and in testes where it plays a role in male sexual differentiation. RAR pan-agonists and the RARalpha-selective agonist Am580, but not RXR agonists, stimulate the expression of SOX9 in a wide variety of retinoid-inhibited breast cancer cell lines. RAR-agonists did not stimulate SOX9 in breast cancer cell lines which were not growth inhibited by retinoids. Expression of SOX9 in T-47D cells leads to cycle changes similar to those found with RAR-agonists while expression of a dominant negative form of SOX9 blocks RA-mediated cell cycle changes, suggesting a role for SOX9 in retinoid-mediated growth inhibition.

  17. Flavonoids exhibit diverse effects on CYP11B1 expression and cortisol synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Li-Chuan; Li, Lih-Ann, E-mail: lihann@nhri.org.tw

    2012-02-01

    CYP11B1 catalyzes the final step of cortisol biosynthesis. The effects of flavonoids on transcriptional expression and enzyme activity of CYP11B1 were investigated using the human adrenocortical H295R cell model. All tested nonhydroxylated flavones including 3′,4′-dimethoxyflavone, α-naphthoflavone, and β-naphthoflavone upregulated CYP11B1 expression and cortisol production, whereas apigenin and quercetin exhibited potent cytotoxicity and CYP11B1 repression at high concentrations. Nonhydroxylated flavones stimulated CYP11B1-catalyzed cortisol formation at transcriptional level. Resveratrol increased endogenous and substrate-supported cortisol production like nonhydroxylated flavones tested, but it had no effect on CYP11B1 gene expression and enzyme activity. Resveratrol appeared to alter cortisol biosynthesis at an earlier step. The Ad5 element situated in the − 121/− 106 region was required for basal and flavone-induced CYP11B1 expression. Overexpression of COUP-TFI did not improve the responsiveness of Ad5 to nonhydroxylated flavones. Although COUP-TFI overexpression increased CYP11B1 and CYP11B2 promoter activation, its effect was not mediated through the common Ad5 element. Treating cells with PD98059 (a flavone-type MEK1 inhibitor) increased CYP11B1 promoter activity, but not involving ERK signaling because phosphorylation of ERK1/2 remained unvarying throughout the course of treatment. Likewise, AhR was not responsible for the CYP11B1-modulating effects of flavonoids because inconsistency with their effects on AhR activation. 3′,4′-dimethoxyflavone and 8-Br-cAMP additively activated CYP11B1 promoter activity. H-89 reduced 3′,4′-dimethoxyflavone-induced CYP11B1 promoter activation but to a lesser extent as compared to its inhibition on cAMP-induced transactivation. Our data suggest that constant exposure to nonhydroxylated flavones raises a potential risk of high basal and cAMP-induced cortisol synthesis in consequence of increased CYP11B1

  18. Transcriptomic Characterization of SF3B1 Mutation Reveals Its Pleiotropic Effects in Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Wang, Lili; Brooks, Angela N; Fan, Jean; Wan, Youzhong; Gambe, Rutendo; Li, Shuqiang; Hergert, Sarah; Yin, Shanye; Freeman, Samuel S; Levin, Joshua Z; Fan, Lin; Seiler, Michael; Buonamici, Silvia; Smith, Peter G; Chau, Kevin F; Cibulskis, Carrie L; Zhang, Wandi; Rassenti, Laura Z; Ghia, Emanuela M; Kipps, Thomas J; Fernandes, Stacey; Bloch, Donald B; Kotliar, Dylan; Landau, Dan A; Shukla, Sachet A; Aster, Jon C; Reed, Robin; DeLuca, David S; Brown, Jennifer R; Neuberg, Donna; Getz, Gad; Livak, Kenneth J; Meyerson, Matthew M; Kharchenko, Peter V; Wu, Catherine J

    2016-11-14

    Mutations in SF3B1, which encodes a spliceosome component, are associated with poor outcome in chronic lymphocytic leukemia (CLL), but how these contribute to CLL progression remains poorly understood. We undertook a transcriptomic characterization of primary human CLL cells to identify transcripts and pathways affected by SF3B1 mutation. Splicing alterations, identified in the analysis of bulk cells, were confirmed in single SF3B1-mutated CLL cells and also found in cell lines ectopically expressing mutant SF3B1. SF3B1 mutation was found to dysregulate multiple cellular functions including DNA damage response, telomere maintenance, and Notch signaling (mediated through KLF8 upregulation, increased TERC and TERT expression, or altered splicing of DVL2 transcript, respectively). SF3B1 mutation leads to diverse changes in CLL-related pathways.

  19. Expression of SOX2 in gastric carcinoma tissues and its clinicopathologic significance%SOX2在胃癌组织中的表达与临床意义

    Institute of Scientific and Technical Information of China (English)

    陈淑贞; 许玲; 刘凤军; 宋燕燕; 薛凤华; 张建平

    2012-01-01

    Objective:To investigate the expression of SO×2 in gastric carcinoma and analyze its relationship with clinicopathologic characteristics. Methods:Tissue microarray and immunohis-tochemical methods were performed to detect the expression of SO×2 in 130 cases of gastric carcinoma and 20 cases normal gastric mucosa. Results:The positive expression rate of SO×2 in gastric carcinoma (67.7%) was obviously down regulated than in normal gastric mucosa (90.0%). The expression of SOX2 was not related to the age and sex of the patients, but significantly associated with histological type, differentiation, depth of invasion, lymph node metastasis and TNM stage of the tumor. The statistical significance in the each group was assessed by P<0.05. Conclusion: The results suggest the expression of SO×2 is closely related to the genesis, invasion and metastasis of gastric carcinoma, and may provide a potential role for prognosis.%目的:探讨SOX2在胃癌组织中的表达情况及与临床病理特征的关系.方法:应用组织芯片技术及免疫组织化学PV-9000通用二步法检测130例胃癌组织及20例正常胃黏膜中SOX2的表达情况.结果:SOX2在胃癌组织中的阳性表达率(67.7%)低于较正常胃黏膜阳性率(90.0%,P<0.05).SOX2的表达与患者的年龄、性别无关,与肿瘤的组织学类型、分化程度、浸润深度、淋巴结转移及TNM分期相关,差异均有统计学意义(P<0.05).结论:SOX2与胃癌的发生、浸润和转移过程有密切关系,可为胃癌早期诊断、治疗、预后判断提供依据.

  20. SOX2在非小细胞肺癌,肺腺癌和肺鳞癌中的作用

    Institute of Scientific and Technical Information of China (English)

    Niki Karachaliou; Rafael Rosell; Santiago Viteri; 刘红兵

    2015-01-01

    SOX2是在胚胎发育中发挥关键作用的干细胞转录因子,它是一组能使人类体细胞转化成多能干细胞的因子(Oct4,SOX2,Nanog)的基因之一.SOX2的过度表达在各种肺癌组织类型如肺小细胞肺癌,肺鳞癌及肺腺癌.肺小细胞肺癌基因组改变频谱已经确认SOX2是潜在治疗干预靶点.3q扩增是肺鳞癌的最普遍的基因变异,并参与原位鳞癌演变也提示SOX2是肿瘤演变的关键靶点,因而SOX2及其下游效应物成为鳞癌生物治疗的潜在靶点.近20%的肺腺癌表达SOX2,且预后更差.SOX2并不导致细胞分化缺失,而是促进鳞状上皮识别,这也与SOX2是谱系生存原癌基因相一致.有趣的是,SOX2转录因子是EGFR信号通路的主要下游靶点,在自我更新生长及SP细胞扩增中发挥主要作用.鉴于SOX2在正常发育和肿瘤发展中的复杂作用,阐明SOX2依赖通路可提供新的肺癌治疗途径,并揭示肿瘤发展,正常发育,维持多能性的其他共同通路.

  1. Involvement of ubiquitous and tale transcription factors, as well as liganded RXRα, in the regulation of human SOX2 gene expression in the NT2/D1 embryonal carcinoma cell line

    Directory of Open Access Journals (Sweden)

    Milivojević Milena

    2010-01-01

    Full Text Available SOX2 is a key transcription factor in embryonic development representing a universal marker of pluripotent stem cells. Based on the functional redundancy and overlapping expression patterns of SOXB1 subgroup members during development, the goal of this study has been to analyze if some aspects of regulation of expression are preserved between human SOX2 and SOX3 genes. Thus, we have tested several transcription factors previously demonstrated to play roles in controlling SOX3 gene activity for potential participation in the regulation of SOX2 gene expression in NT2/D1 cells. Here we report on the activation of SOX2 expression by ubiquitous transcription factors (NF-Y, Sp1 and MAZ, TALE family members (Pbx1 and Meis1, as well as liganded RXRα. Elucidating components involved in the regulation of SOX gene expression represent a valuable contribution in unraveling the regulatory networks operating in pluripotent embryonic cells.

  2. 26 CFR 1.50B-1 - Definitions of WIN expenses and WIN employees.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Definitions of WIN expenses and WIN employees. 1.50B-1 Section 1.50B-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY INCOME TAX INCOME TAXES Rules for Computing Credit for Expenses of Work Incentive Programs § 1.50B-1 Definitions of WIN expenses and WIN employees. (a)...

  3. Transcriptional Response of Yeast to Aflatoxin B1: Recombinational Repair Involving RAD51 and RAD1

    OpenAIRE

    2004-01-01

    The potent carcinogen aflatoxin B1 is a weak mutagen but a strong recombinagen in Saccharomyces cerevisiae. Aflatoxin B1 exposure greatly increases frequencies of both heteroallelic recombination and chromosomal translocations. We analyzed the gene expression pattern of diploid cells exposed to aflatoxin B1 using high-density oligonucleotide arrays comprising specific probes for all 6218 open reading frames. Among 183 responsive genes, 46 are involved in either DNA repair or in control of cel...

  4. Coordination failure caused by sunspots

    DEFF Research Database (Denmark)

    Beugnot, Julie; Gürgüç, Zeynep; Øvlisen, Frederik Roose;

    2012-01-01

    In a coordination game with Pareto-ranked equilibria, we study whether a sunspot can lead to either coordination on an inferior equilibrium (mis-coordination) or to out-of equilibrium behavior (dis-coordination). While much of the literature searches for mechanisms to attain coordination on the e......In a coordination game with Pareto-ranked equilibria, we study whether a sunspot can lead to either coordination on an inferior equilibrium (mis-coordination) or to out-of equilibrium behavior (dis-coordination). While much of the literature searches for mechanisms to attain coordination...

  5. Social Postural Coordination

    Science.gov (United States)

    Varlet, Manuel; Marin, Ludovic; Lagarde, Julien; Bardy, Benoit G.

    2011-01-01

    The goal of the current study was to investigate whether a visual coupling between two people can produce spontaneous interpersonal postural coordination and change their intrapersonal postural coordination involved in the control of stance. We examined the front-to-back head displacements of participants and the angular motion of their hip and…

  6. Coordinate measuring machines

    DEFF Research Database (Denmark)

    De Chiffre, Leonardo

    This document is used in connection with three exercises of 2 hours duration as a part of the course GEOMETRICAL METROLOGY AND MACHINE TESTING. The exercises concern three aspects of coordinate measuring: 1) Measuring and verification of tolerances on coordinate measuring machines, 2) Traceabilit...

  7. Team coordination dynamics.

    Science.gov (United States)

    Gorman, Jamie C; Amazeen, Polemnia G; Cooke, Nancy J

    2010-07-01

    Team coordination consists of both the dynamics of team member interaction and the environmental dynamics to which a team is subjected. Focusing on dynamics, an approach is developed that contrasts with traditional aggregate-static concepts of team coordination as characterized by the shared mental model approach. A team coordination order parameter was developed to capture momentary fluctuations in coordination. Team coordination was observed in three-person uninhabited air vehicle teams across two experimental sessions. The dynamics of the order parameter were observed under changes of a team familiarity control parameter. Team members returned for the second session to either the same (Intact) or different (Mixed) team. 'Roadblock' perturbations, or novel changes in the task environment, were introduced in order to probe the stability of team coordination. Nonlinear dynamic methods revealed differences that a traditional approach did not: Intact and Mixed team coordination dynamics looked very different; Mixed teams were more stable than Intact teams and explored the space of solutions without the need for correction. Stability was positively correlated with the number of roadblock perturbations that were overcome successfully. The novel and non-intuitive contribution of a dynamical analysis was that Mixed teams, who did not have a long history working together, were more adaptive. Team coordination dynamics carries new implications for traditional problems such as training adaptive teams.

  8. Coordination models and languages

    NARCIS (Netherlands)

    Papadopoulos, G.A.; Arbab, F.

    1998-01-01

    A new class of models, formalisms and mechanisms has recently evolved for describing concurrent and distributed computations based on the concept of ``coordination''. The purpose of a coordination model and associated language is to provide a means of integrating a number of possibly heterogeneous c

  9. Tobacco smoke induces CYP1B1 in the aerodigestive tract.

    Science.gov (United States)

    Port, Jeffrey L; Yamaguchi, Kentaro; Du, Baoheng; De Lorenzo, Mariana; Chang, Mindy; Heerdt, Paul M; Kopelovich, Levy; Marcus, Craig B; Altorki, Nasser K; Subbaramaiah, Kotha; Dannenberg, Andrew J

    2004-11-01

    Several members of the P450 family, including cytochrome P450 1B1 (CYP1B1), can convert tobacco smoke (TS) procarcinogens, including benzo[a]pyrene (B[a]P), to carcinogenic intermediates. In this study we investigated the effects of TS condensate and B[a]P on the expression of CYP1B1 in vitro and in vivo. CYP1B1 mRNA and protein were induced by both TS condensate and B[a]P in cell lines derived from the human aerodigestive tract. Treatment with TS condensate stimulated binding of the aryl hydrocarbon receptor (AhR) to an oligonucleotide containing a canonical xenobiotic response element (XRE) site and induced XRE-luciferase activity. These findings are consistent with prior evidence that polycyclic aromatic hydrocarbons, known ligands of the AhR, stimulate CYP1B1 transcription by an XRE-dependent mechanism. To determine whether these in vitro findings applied in vivo, both murine and human studies were carried out. Short-term exposure to TS induced CYP1B1 in the tongue, esophagus, lung and colon of experimental mice. In contrast, CYP1B1 was not induced by TS in the aorta of these mice. Levels of CYP1B1 mRNA were also elevated in the bronchial mucosa of human tobacco smokers versus never smokers (P CYP1B1 in TS-induced carcinogenesis in the aerodigestive tract.

  10. Apoptotic extinction of germ cells in testes of Cyp26b1 knockout mice.

    Science.gov (United States)

    MacLean, Glenn; Li, Hui; Metzger, Daniel; Chambon, Pierre; Petkovich, Martin

    2007-10-01

    Cyp26b1 encodes a retinoic acid (RA) metabolizing cytochrome P450 enzyme that is expressed in embryonic tissues undergoing morphogenesis, including the testes. We have generated transgenic mice lacking Cyp26b1 and have observed increased RA levels in embryonic testes. Cyp26b1(-/-) germ cells prematurely enter meiosis at embryonic d 13.5 and appear to arrest at pachytene stage. Furthermore, after embryonic d 13.5, a rapid increase in apoptosis is observed in male germ cells derived from Cyp26b1(-/-) embryos; germ cells are essentially absent in mutant male neonates. In contrast, testicular somatic cells appear to develop normally in the absence of Cyp26b1. Moreover, ovarian germ and somatic cells appear unaffected by the lack of CYP26B1. We also show that the synthetic retinoid Am580, which is resistant to CYP26 metabolism, induces meiosis of male germ cells in cultured gonads, suggesting that abnormal development of germ cells in the Cyp26b1(-/-) testes results from excess RA rather than the absence of CYP26B1-generated metabolites of RA. These results provide evidence that CYP26B1 maintains low levels of RA in the developing testes that blocks entry into meiosis and acts as a survival factor to prevent apoptosis of male germ cells.

  11. Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol

    Directory of Open Access Journals (Sweden)

    Strebhardt Klaus

    2008-12-01

    Full Text Available Abstract Background Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1, is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers. Methods In order to explore cyclin B1 as a potential target for gynecological cancer therapy, we studied the effect of small interfering RNA (siRNA on different gynecological cancer cell lines by monitoring their proliferation rate, cell cycle profile, protein expression and activity, apoptosis induction and colony formation. Tumor formation in vivo was examined using mouse xenograft models. Results Downregulation of cyclin B1 inhibited proliferation of several breast and cervical cancer cell lines including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1 siRNA with taxol, we observed an increased apoptotic rate accompanied by an enhanced antiproliferative effect in breast cancer cells. Furthermore, control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo. Conclusion Our data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1 sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1 targeting is an attractive strategy for the combination with conventionally used agents in gynecological cancer therapy.

  12. Global gene profiling of aging lungs in Atp8b1 mutant mice

    Science.gov (United States)

    Soundararajan, Ramani; Stearns, Timothy M.; Czachor, Alexander; Fukumoto, Jutaro; Turn, Christina; Westermann-Clark, Emma; Breitzig, Mason; Tan, Lee; Lockey, Richard F.; King, Benjamin L.; Kolliputi, Narasaiah

    2016-01-01

    Objective Recent studies implicate cardiolipin oxidation in several age-related diseases. Atp8b1 encoding Type 4 P-type ATPases is a cardiolipin transporter. Mutation in Atp8b1 gene or inflammation of the lungs impairs the capacity of Atp8b1 to clear cardiolipin from lung fluid. However, the link between Atp8b1 mutation and age-related gene alteration is unknown. Therefore, we investigated how Atp8b1 mutation alters age-related genes. Methods We performed Affymetrix gene profiling of lungs isolated from young (7-9 wks, n=6) and aged (14 months, 14 M, n=6) C57BL/6 and Atp8b1 mutant mice. In addition, Ingenuity Pathway Analysis (IPA) was performed. Differentially expressed genes were validated by quantitative real-time PCR (qRT-PCR). Results Global transcriptome analysis revealed 532 differentially expressed genes in Atp8b1 lungs, 157 differentially expressed genes in C57BL/6 lungs, and 37 overlapping genes. IPA of age-related genes in Atp8b1 lungs showed enrichment of Xenobiotic metabolism and Nrf2-mediated signaling pathways. The increase in Adamts2 and Mmp13 transcripts in aged Atp8b1 lungs was validated by qRT-PCR. Similarly, the decrease in Col1a1 and increase in Cxcr6 transcripts was confirmed in both Atp8b1 mutant and C57BL/6 lungs. Conclusion Based on transcriptome profiling, our study indicates that Atp8b1 mutant mice may be susceptible to age-related lung diseases. PMID:27689529

  13. Strain background modifies phenotypes in the ATP8B1-deficient mouse.

    Directory of Open Access Journals (Sweden)

    Sohela Shah

    Full Text Available BACKGROUND: Mutations in ATP8B1 (FIC1 underlie cases of cholestatic disease, ranging from chronic and progressive (progressive familial intrahepatic cholestasis to intermittent (benign recurrent intrahepatic cholestasis. The ATP8B1-deficient mouse serves as an animal model of human ATP8B1 deficiency. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effect of genetic background on phenotypes of ATP8B1-deficient and wild-type mice, using C57Bl/6 (B6, 129, and (B6-129 F1 strain backgrounds. B6 background resulted in greater abnormalities in ATP8B1-deficient mice than did 129 and/or F1 background. ATP8B1-deficient pups of B6 background gained less weight. In adult ATP8B1-deficient mice at baseline, those of B6 background had lower serum cholesterol levels, higher serum alkaline phosphatase levels, and larger livers. After challenge with cholate-supplemented diet, these mice exhibited higher serum alkaline phosphatase and bilirubin levels, greater weight loss and larger livers. ATP8B1-deficient phenotypes in mice of F1 and 129 backgrounds are usually similar, suggesting that susceptibility to manifestations of ATP8B1 deficiency may be recessive. We also detected differences in hepatobiliary phenotypes between wild-type mice of differing strains. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the ATP8B1-deficient mouse in a B6 background may be a better model of human ATP8B1 deficiency and highlight the importance of informed background strain selection for mouse models of liver disease.

  14. Measuring electron-impact cross sections of water: elastic scattering and electronic excitation of the ã3B1 and Ã1B1 states

    Science.gov (United States)

    Matsui, Midori; Hoshino, Masamitsu; Kato, Hidetoshi; Ferreira da Silva, Fillipe; Limão-Vieira, Paulo; Tanaka, Hiroshi

    2016-04-01

    Here, we report elastic differential cross sections (DCSs) for electron scattering from water in the incident energy range of 2-100 eV. Furthermore, we present a complete study on the electronic excitation of the ã3B1 and Ã1B1 states at electron impact energies of 15, 20, and 30 eV and in the scattering angle range of 10° - 130°. Integral cross sections (ICSs) are determined from the DCSs. Measuring elastic DCSs in various experimental conditions confirmed the reproducibility of the data. The present results agree with the data previously obtained from a conventional collimating tube gas source. Ambiguities associated with the unfolding procedure of the electron energy loss (EEL) spectra for the electronic excitations have been reduced by comparison against the EEL spectrum at high electron impact energy and for small scattering angle. The reliability of the extracted DCSs is improved significantly for optically forbidden contributions from the overlap of the ã3B1 and Ã1B1 electronic states. The BEf-scaling model is also confirmed to produce the integral cross section for the optical allowed transition of the Ã1B1 state in the intermediate electron energy region above 15 eV.

  15. Metabolism of aflatoxin B1 and identification of the major aflatoxin B1-DNA adducts formed in cultured human bronchus and colon

    DEFF Research Database (Denmark)

    1979-01-01

    compared to aflatoxin B1, the binding level of benzo(a)pyrene to both bronchial and colonic DNA was generally higher. The major adducts formed in both tissues by the interaction of aflatoxin B1 and DNA were chromatographically identical to 2,3-dihydro-2-(N7-guanyl)-3-hydroxyaflatoxin B1 (Structure 1......) with the guanyl group and hydroxy group in trans-position and an adduct which has been tentatively identified by other investigators as 2,3-dihydro-2-(N5-formyl-2',5',6'-triamino-4'-oxo-N5-pyrimidyl)-3-hydroxyaflatoxin B1 (Structure 11). Seventy % of the radioactivity associated with bronchial DNA was found...... in these two peaks, and the ratio of radioactivity between the peaks was nearly 1. In colonic DNA, the ratio between Structures 1 and 11 was approximately 2. These observations add aflatoxin B1 to the list of chemical procarcinogens metabolized by cultured human tissues and in which the carcinogen-DNA adducts...

  16. Observation of B+->b_1+K0 and search for B-meson decays to b_10K0 and b_1pi0

    CERN Document Server

    Aubert, B; Bóna, M; Karyotakis, Yu; Lees, J P; Poireau, V; Prencipe, E; Prudent, X; Tisserand, V; Garra Tico, J; Graugès-Pous, E; Lopezab, L; Palanoab, A; Pappagalloab, M; Eigen, G; Stugu, B; Sun, L; Abrams, G S; Battaglia, M; Brown, D N; Cahn, R N; Jacobsen, R G; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lynch, G; Osipenkov, I L; Ronan, M T; Tackmann, K; Tanabé, T; Hawkes, C M; Soni, N; Watson, A T; Koch, H; Schröder, T; Walker, D; Asgeirsson, D J; Çuhadar-Dönszelmann, T; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Barrett, M; Khan, A; Teodorescu, L; Blinov, V E; Bukin, A D; Buzykaev, A R; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Gary, J W; Liu, F; Long, O; Shen, B C; Vitug, G M; Yasin, Z; Zhang, L; Sharma, V; Campagnari, C; Hong, T M; Kovalskyi, D; Mazur, M A; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Schalk, T; Schumm, B A; Seiden, A; Wang, L; Wilson, M G; Winstrom, L O; Cheng, C H; Doll, D A; Echenard, B; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Clifton, Z C; Ford, W T; Gaz, A; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Smith, J G; Ulmer, K A; Wagner, S R; Ayad, R; Soffer, A; Toki, W H; Wilson, R J; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Karbach, M; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Kobel, M J; Mader, W F; Nogowski, R; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Thiebaux, C; Verderi, M; Clark, P J; Gradl, W; Playfer, S; Watson, J E; Andreottiab, M; Bettonia, D; Bozzia, C; Calabreseab, R; Cecchiab, A; Cibinettoab, G; Franchiniab, P; Luppiab, E; Negriniab, M; Petrellaab, A; Piemontesea, L; Santoroab, V; Baldini-Ferroli, R; Calcaterra, A; De Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzoa, A; Contriab, R; Lo Vetereab, M; Macria, M M; Mongeab, M R; Passaggioa, S; Patrignaniab, C; Robuttia, E; Santroniab, A; Tosiab, S; Chaisanguanthum, K S; Morii, M; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Klose, V; Lacker, H M; De Nardoab, G; Listaa, L; Monorchioab, D; Onoratoab, G; Sciaccaab, C; Bard, D J; Dauncey, P D; Nash, J A; Panduro-Vazquez, W; Tibbetts, M; Behera, P K; Chai, X; Charles, M J; Mallik, U; Cochran, J; Crawley, H B; Dong, L; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Lae, C K; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Bquilleux, J; D'Orazio, A; Davier, M; Firminoda Costa, J; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Touramanis, C; Bevan, A J; George, K A; Di Lodovico, F; Sacco, R; Sigamani, M; Cowan, G; Flächer, H U; Hopkins, D A; Paramesvaran, S; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Alwyn, K E; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Dallapiccola, C; Hertzbach, S S; Li, X; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Koeneke, K; Sciolla, G; Spitznagel, M; Taylor, F; Yamamoto, R K; Zhao, M; Mclachlin, S E; Patel, P M; Robertson, S H; Lazzaroab, A; Lombardoa, V; Palomboab, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Simard, M; Taras, P; Viaud, F B; Nicholson, H; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; LoSecco, J M; Wang, W F; Benelli, G; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Sekula, S J; Wong, Q K; Blount, N L; Brau, J E; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Castelliab, G; Gagliardiab, N; Margoniab, M; Morandina, M; Posoccoa, M; Rotondoa, M; Simonettoab, F; Stroiliab, R; Vociab, C; Del Amo-Sánchez, P; Ben-Haim, E; Briand, H; Calderini, G; Chauveau, J; David, P; Del Buono, L; Hamon, O; Leruste, P; Ocariz, J; Pérez, A; Prendki, J; Gladney, L; Biasiniab, M; Covarelliab, R; Manoniab, E; Angeliniab, C; Batignaniab, G; Bettariniab, S; Carpinelliab, M; Cervelliab, A; Fortiab, F; Giorgiab, M A; Lusianiac, A; Marchioriab, G; Morgantiab, M; Neriab, N; Paoloniab, E; Rizzoab, G; Walsha, J J; Biesiada, J; Lopes-Pegna, D; Lü, C; Olsen, J; Smith, A J S; Telnov, A V; Anullia, F; Baracchiniab, E; Cavotoa, G; del Reab, D; Di Marcoab, E; Facciniab, R; Ferrarottoa, F; Ferroniab, F; Gasperoab, M; Jacksona, P D; Li Gioia, L; Mazzonia, M A; Morgantia, S; Pireddaa, G; Polciab, F; Rengaab, F; Voenaa, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Franek, B; Olaiya, E O; Röthel, W; Wilson, F F; Emery, S; Escalier, M; Esteve, L; Gaidot, A; Ganzhur, S F; Hamel de Monchenault, G; Kozanecki, W; Vasseur, G; Y`che, C; Zito, M; Chen, X R; Liu, H; Park, e W; Purohit, M V; White, R M; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Benitez, J F; Cenci, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Gabareen, A M; Gowdy, S J; Graham, M T; Grenier, P; Hast, C; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Lindquist, B; Luitz, S; Lüth, V; Lynch, H L; MacFarlane, D B; Marsiske, H; Messner, R; Müller, D R; Neal, H; Nelson, S; O'Grady, C P; Ofte, I; Perazzo, A; Perl, M; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Vavra, J; Wagner, A P; Weaver, M; West, C A; Wisniewski, W J; Wittgen, M; Wright, D H; Wulsin, H W; Yarritu, A K; Yi, K; Young, C C; Ziegler, V; Burchat, P R; Edwards, A J; Majewski, S A; Miyashita, T S; Petersen, B A; Wilden, L; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Pan, B; Saeed, M A; Zain, S B; Spanier, S M; Wogsland, B J; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Drummond, B W; Izen, J M; Lou, X C; Bianchiab, F; Gambaab, D; Pelliccioniab, M; Bombenab, M; Bosisioab, L; Cartaroab, C; Della Riccaab, G; Lanceriab, L; Vitaleab, L; Azzolini, V; Lopez-March, N; Martínez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, S; Bhuyan, B; Choi, H H F; Hamano, K; Kowalewski, R; Lewczuk, M J; Nugent, I M; Roney, J M; Sobie, R J; Gershon, T J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Dasu, S; Flood, K T; Pan, Y; Pierini, M; Prepost, R; Vuosalo, C O; Wu, S L

    2008-01-01

    We present the results of searches for decays of B mesons to final states with a b_1 meson and a neutral pion or kaon. The data, collected with the BABAR detector at the Stanford Linear Accelerator Center, represent 465 million BBbar pairs produced in e+e- annihilation. The results for the branching fractions are, in units of 1e-6, BR(B+ to b_1+K0) = 9.6+/-1.7+/-0.9, BR(B0 to b_10K0) = 5.1+/-1.8+/-0.5 (<7.8), BR(B+ to b_1+pi0) = 1.8+/-0.9+/-0.2 (<3.3), and BR(B0 to b_10pi0) = 0.4+/-0.8+/-0.2 (<1.9), with the assumption that BR(B_1 to omega pi)=1. We also measure the charge asymmetry A_ch(B+ to b_1+K0) = -0.03+/-0.15+/-0.02. The first error quoted is statistical, the second systematic, and the upper limits in parentheses indicate the 90% confidence level.

  17. Fat-Dachsous signaling coordinates cartilage differentiation and polarity during craniofacial development.

    Directory of Open Access Journals (Sweden)

    Pierre Le Pabic

    2014-10-01

    Full Text Available Organogenesis requires coordinated regulation of cellular differentiation and morphogenesis. Cartilage cells in the vertebrate skeleton form polarized stacks, which drive the elongation and shaping of skeletal primordia. Here we show that an atypical cadherin, Fat3, and its partner Dachsous-2 (Dchs2, control polarized cell-cell intercalation of cartilage precursors during craniofacial development. In zebrafish embryos deficient in Fat3 or Dchs2, chondrocytes fail to stack and misregulate expression of sox9a. Similar morphogenetic defects occur in rerea/atr2a-/- mutants, and Fat3 binds REREa, consistent with a model in which Fat3, Dchs2 and REREa interact to control polarized cell-cell intercalation and simultaneously control differentiation through Sox9. Chimaeric analyses support such a model, and reveal long-range influences of all three factors, consistent with the activation of a secondary signal that regulates polarized cell-cell intercalation. This coordinates the spatial and temporal morphogenesis of chondrocytes to shape skeletal primordia and defects in these processes underlie human skeletal malformations. Similar links between cell polarity and differentiation mechanisms are also likely to control organ formation in other contexts.

  18. The role of SOX10 in the pathogenesis of Hirschsprung's disease associated enterocolitis%SOX10在先天性巨结肠相关性小肠结肠炎发病中的作用

    Institute of Scientific and Technical Information of China (English)

    郑辉明; 向磊; 李宁; 韦佳; 郑帅玉; 邱银荣; 冯杰雄

    2011-01-01

    目的 探讨SOX10、潘氏细胞发育及分泌防御素-5与先天性巨结肠相关性小肠结肠炎的关系.方法 收集50例先天性巨结肠病变肠管,根据术前是否发生小肠结肠炎分为HAFC组(n=14)和HD组(n=36),并以20例正常结肠标本作对照组.采用免疫组织化学方法观察结肠中防御素-5蛋白质表达、潘氏细胞发育情况以及SOX10蛋白质表达情况.采用实时荧光定量PCR技术检测防御素-5 mRNA及Sox 10 mRNA表达情况.结果 防御素-5在正常肠管中不表达,HAEC组和HD组在肠腺隐窝基底处呈不同程度阳性表达.但前者阳性区域平均光密度值明显增高(0.33±0.039比0.10±0.031,P<0.05),HAEC组防御素-5mRNA亦呈显著增高趋势(2.72±0.80比0.78±0.21,P<0.05).对结肠组织同层切片进行潘氏细胞特异性产物溶菌酶免疫组化染色发现,对照组肠管中除1例存在弱阳性外其他均无阳性表达.HD组和HAEC组结肠中同样在隐窝基底处存在溶菌酶阳性细胞,可鉴别为化生的潘氏细胞,但HAEC组在发生率(78.6%)和细胞个数(2.97±0.80)明显高于HD组(27.8%,0.43±0.85)(P<0.05).SOX10免疫产物主要在结肠神经节细胞膜及胞浆中表达,对照组、HAEC组、HD组阳性区域的平均光密度值递减(0.75±0.041,0.61±0.048,0.35±0.025),差异具有统计学意义(P<0.05),同时RT-PCR检测显示Sox10 mRNA在各组中的表达与蛋白质水平呈平行结果.结论 SOX10可能通过影响潘氏细胞发育及分泌防御素-5在先天性巨结肠相关性小肠结肠炎的发生发展中起一定作用.%Objective To study the expression of SOX10 and Human α-defensins-5(HD-5 )in Hirschsprung's disease associated enterocolitis(HAEC) and expore the possible relationship between SOX10 and HAEC.Methods Fifty pathological colons of Hirschsprung's disease (HD) were divided into HAEC group (n = 14) and HD group(n = 36) according to the presence of preoperative enterocolitis,Twenty normal colons as control

  19. Uranyl ion coordination

    Science.gov (United States)

    Evans, H.T.

    1963-01-01

    A review of the known crystal structures containing the uranyl ion shows that plane-pentagon coordination is equally as prevalent as plane-square or plane-hexagon. It is suggested that puckered-hexagon configurations of OH - or H2O about the uranyl group will tend to revert to plane-pentagon coordination. The concept of pentagonal coordination is invoked for possible explanations of the complex crystallography of the natural uranyl hydroxides and the unusual behavior of polynuclear ions in hydrolyzed uranyl solutions.

  20. The SH2B1 obesity locus and abnormal glucose homeostasis

    DEFF Research Database (Denmark)

    Prudente, S; Copetti, M; Morini, E

    2013-01-01

    affecting risk of obesity and insulin resistance might also modulate risk of T2D. Recently, 32 loci have been associated with body mass index (BMI) by genome-wide studies, including one locus on chromosome 16p11 containing the SH2B1 gene. Animal studies have suggested that SH2B1 is a physiological enhancer...

  1. Preparation and application of new fluorescein-labeled fumonisins B1 in fluorescence polarization analysis technique

    Science.gov (United States)

    Objective: To prepare a new fluorescent tracer against common mycotoxins such as fumonisin B1 in order to replace 6-(4,6-Dichlorotriazinyl) aminofluorescein (6-DTAF), an expensive marker, and to develop a technique for quick detection of fumonisin B1 based on the principle of fluorescence polarizati...

  2. Tumor-specific expression of cytochrome P450 CYP1B1.

    Science.gov (United States)

    Murray, G I; Taylor, M C; McFadyen, M C; McKay, J A; Greenlee, W F; Burke, M D; Melvin, W T

    1997-07-15

    Cytochrome P450 CYP1B1 is a recently cloned dioxin-inducible form of the cytochrome P450 family of xenobiotic metabolizing enzymes. An antibody raised against a peptide specific for CYP1B1 was found to recognize CYP1B1 expressed in human lymphoblastoid cells but not to recognize other forms of cytochrome P450, particularly CYP1A1 and CYP1A2. Using this antibody, the cellular distribution and localization of CYP1B1 were investigated by immunohistochemistry in a range of malignant tumors and corresponding normal tissues. CYP1B1 was found to be expressed at a high frequency in a wide range of human cancers of different histogenetic types, including cancers of the breast, colon, lung, esophagus, skin, lymph node, brain, and testis. There was no detectable immunostaining for CYP1B1 in normal tissues. These results provide the basis for the development of novel methods of cancer diagnosis based on the identification of CYP1B1 in tumor cells and the development of anticancer drugs that are selectively activated in tumors by CYP1B1.

  3. 26 CFR 1.666(b)-1A - Total taxes deemed distributed.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Total taxes deemed distributed. 1.666(b)-1A Section 1.666(b)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning Before January 1, 1969 §...

  4. 26 CFR 1.666(b)-1 - Total taxes deemed distributed.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Total taxes deemed distributed. 1.666(b)-1 Section 1.666(b)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning Before January 1, 1969 §...

  5. Data of evolutionary structure change: 1B1GA-1CLMA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B1GA-1CLMA 1B1G 1CLM A A KSPEELKGIFEKYAAK-EGDPNQLSKEELKLLLQTEFPS...-- LTEEQIAEFKEAFALFDKDGDGTITTKELGTVMRSL-----GQNPTEAELQDMINEVDADGNGTIDFPEFLSLMARKMKEQDSEEELIEAFK...SN CA 464 1CLM A 1CLMA...dbChain> 1CLMA LQDMINEVDADGN HHHHHH 2 1CLM A 1CLMA

  6. UNC93B1 mediates host resistance to infection with Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Mariane B Melo

    Full Text Available UNC93B1 associates with Toll-Like Receptor (TLR 3, TLR7 and TLR9, mediating their translocation from the endoplasmic reticulum to the endolysosome, hence allowing proper activation by nucleic acid ligands. We found that the triple deficient '3d' mice, which lack functional UNC93B1, are hyper-susceptible to infection with Toxoplasma gondii. We established that while mounting a normal systemic pro-inflammatory response, i.e. producing abundant MCP-1, IL-6, TNFα and IFNγ, the 3d mice were unable to control parasite replication. Nevertheless, infection of reciprocal bone marrow chimeras between wild-type and 3d mice with T. gondii demonstrated a primary role of hemopoietic cell lineages in the enhanced susceptibility of UNC93B1 mutant mice. The protective role mediated by UNC93B1 to T. gondii infection was associated with impaired IL-12 responses and delayed IFNγ by spleen cells. Notably, in macrophages infected with T. gondii, UNC93B1 accumulates on the parasitophorous vacuole. Furthermore, upon in vitro infection the rate of tachyzoite replication was enhanced in non-activated macrophages carrying mutant UNC93B1 as compared to wild type gene. Strikingly, the role of UNC93B1 on intracellular parasite growth appears to be independent of TLR function. Altogether, our results reveal a critical role for UNC93B1 on induction of IL-12/IFNγ production as well as autonomous control of Toxoplasma replication by macrophages.

  7. Data of evolutionary structure change: 1DTGA-1B1XA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1DTGA-1B1XA 1DTG 1B1X A A ---KTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPSVAC...VVRKSDADLTWNSLSGKKSCHTGVGRTAAWNIPMGLLFNQTGSCKFDKFFSQSCAPGADPQSSLCALCVGNNENENKCMPNSEERYYGYTGAFRCLAEKAGDVAFVKD...ndex>0 1DTG A 1DTGA A 1DTGA CQLCP-----GCGCS 2 1DTG A 1DTGA

  8. DREAM - A Novel Approach for Robust, Ultra-Fast, Multi-Slice B1 Mapping

    NARCIS (Netherlands)

    Nehrke, K.; Boernert, P.

    2012-01-01

    Fast and robust in vivo B1 mapping is an essential prerequisite forquantitative MRI or multi-element transmit applications like RF-shimming or accelerated multi-dimensional RF pulses. However, especially at higher field strength, the acquisition speed of current B1-mapping approaches is typicall

  9. Immunosuppressive effects of fumonisin B1 in the Trichinella spiralis model

    NARCIS (Netherlands)

    Nijs M de; Egmond HP van; Jong WH de; Loveren H van; LPI; ARO; MGB

    2002-01-01

    Fumonisine B1 is een mycotoxine geproduceerd door Fusarium moniliforme en wordt vooral gevonden in mais. Fumonisine B1 veroorzaakt oesophaguskanker in de mens, longoedeem in het varken en leuko-encephalomalacie in het paard. Effecten van dit mycotoxine op het immuunsysteem werden waargenomen in

  10. 26 CFR 1.802(b)-1 - Tax on life insurance companies.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Tax on life insurance companies. 1.802(b)-1...) INCOME TAX (CONTINUED) INCOME TAXES Life Insurance Companies § 1.802(b)-1 Tax on life insurance companies... August 16, 1954, section 802(b) imposes a tax on the 1954 life insurance company taxable income of...

  11. Construction and Virulence of Filamentous Hemagglutinin Protein B1 Mutant of Pasteurella multocida in Chickens

    Institute of Scientific and Technical Information of China (English)

    GUO Dong-chun; QU Lian-dong; SUN Yan; ZHANG Ai-qin; LIU Jia-sen; LU Yan; LIU Pei-xin; YUAN Dong-wei; JIANG Qian; SI Chang-de

    2014-01-01

    Pasteurella multocida, a Gram-negative nonmotile coccobacillus, is the causative agent of fowl cholera, bovine hemorrhagic septicemia, enzoonotic pneumonia and swine atropic rhinitis. Two iflamentous hemagglutinin genes, fhaB1 and fhaB2, are the potential virulence factors. In this study, an inactivation fhaB1 mutant of P. multocida in avian strain C48-102 was constructed by a kanamycin-resistance cassette. The virulence of the fhaB1 mutant and the wild type strain was assessed in chickens by intranasal and intramuscular challenge. The inactivation of fhaB1 resulted in a high degree of attenuation when the chickens were challenged intranasally and a lesser degree when challenged intramuscularly. The fhaB1 mutant and the wild type strain were investigated their sensitivity to the antibody-dependent classical complement-mediated killing pathway in 90%convalescent chicken serum. The fhaB1 mutant was serum sensitive as the viability has reduced between untreated serum and heat inactivated chicken serum (P<0.007). These results conifrmed that FhaB1 played the critical roles in the bacterial pathogenesis and further studies were needed to investigate the mechanism which caused reduced virulence of the fhaB1 mutant.

  12. Data of evolutionary structure change: 1B1ZA-2NTSA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B1ZA-2NTSA 1B1Z 2NTS A A DPDPSQLHRSSLVKNLQNIYFLYE-GDPVTHENVKSVDQ...ELDYKVRKYLTDNKQLYTN--------------GPSKYETGYIKFIPKNKESFWFDFF-PEPEFTQSKYLMIYKDNETLDSNTSQIEVYLTT-- ...ine> 2NTS A 2NTSA 2NTS A 2NTS.../line> PHE CA 274 2NTS A 2NTS

  13. Data of evolutionary structure change: 1B1ZC-2NTSA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B1ZC-2NTSA 1B1Z 2NTS C A DPDPSQLHRSSLVKNLQNIYFLYE-GDPVTHENVKSVDQ...ELDYKVRKYLTDNKQLYTNG--------------PSKYETGYIKFIPKNKESFWFDFFP-EPEFTQSKYLMIYKDNETLDSNTSQIEVYLTT-- ...e>THR CA 392 2NTS A 2NTS...CA 343 LYS CA 296 2NTS A 2NTS...208 PHE CA 276 THR CA 304 2NTS

  14. Data of evolutionary structure change: 1B1ZD-2NTSA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B1ZD-2NTSA 1B1Z 2NTS D A DPDPSQLHRSSLVKNLQNIYFLYE-GDPVTHENVKSVDQ...ELDYKVRKYLTDNKQLYT--------------NGPSKYETGYIKFIPKNKESFWFDFFP-EPEFTQSKYLMIYKDNETLDSNTSQIEVYLTT-- ...R CA 395 2NTS A 2NTS... LYS CA 294 2NTS A 2NTS...e>PHE CA 282 THR CA 304 2NTS

  15. Data of evolutionary structure change: 1B1ZB-2NTSA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B1ZB-2NTSA 1B1Z 2NTS B A DPDPSQLHRSSLVKNLQNIYFLYE-GDPVTHENVKSVDQ...ELDYKVRKYLTDNKQLYT--------------NGPSKYETGYIKFIPKNKESFWFDFF-PEPEFTQSKYLMIYKDNETLDSNTSQIEVYLTT-- ...4 2NTS A 2NTSA 2NTS A 2NTSAPHE CA 283 2NTS A 2NTS

  16. 26 CFR 1.668(b)-1A - Tax on distribution.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Tax on distribution. 1.668(b)-1A Section 1.668(b... (CONTINUED) INCOME TAXES Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning Before January 1, 1969 § 1.668(b)-1A Tax on distribution. (a) In general. The partial tax imposed on...

  17. 26 CFR 1.669(b)-1A - Tax on distribution.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Tax on distribution. 1.669(b)-1A Section 1.669(b... (CONTINUED) INCOME TAXES Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning Before January 1, 1969 § 1.669(b)-1A Tax on distribution. (a) In general. The partial tax imposed on...

  18. 26 CFR 1.6038B-1 - Reporting of certain transfers to foreign corporations.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Reporting of certain transfers to foreign corporations. 1.6038B-1 Section 1.6038B-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... either: (1) The transferor (or one or more successors) properly entered into a gain recognition...

  19. Solar X-ray Spectrometer (SOXS) Mission – Low Energy Payload – First Results

    Indian Academy of Sciences (India)

    Rajmal Jain; Vishal Joshi; S. L. Kayasth; Hemant Dave; M. R. Deshpande

    2006-06-01

    We present the first results from the ‘Low Energy Detector’ payload of ‘Solar X-ray Spectrometer (SOXS)’ mission, which was launched onboard GSAT-2 Indian spacecraft on 08 May 2003 by GSLV-D2 rocket to study the solar flares. The SOXS Low Energy Detector (SLD) payload was designed, developed and fabricated by Physical Research Laboratory (PRL) in collaboration with Space Application Centre (SAC), Ahmedabad and ISRO Satellite Centre (ISAC), Bangalore of the Indian Space Research Organization (ISRO). The SLD payload employs the state-of-the-art solid state detectors viz., Si PIN and Cadmium-Zinc-Telluride (CZT) devices that operate at near room temperature (-20° C). The dynamic energy range of Si PIN and CZT detectors are 4–25 keV and 4–56 keV respectively. The Si PIN provides sub-keV energy resolution while CZT reveals ∼ 1.7 keV energy resolution throughout the dynamic range. The high sensitivity and sub-keV energy resolution of Si PIN detector allows the measuring of the intensity, peak energy and equivalent width of the Fe-line complex at approximately 6.7 keV as a function of time in all 8 M-class flares studied in this investigation. The peak energy () of Fe-line feature varies between 6.4 and 6.8 keV with increase in temperature from 9 to 34 MK. We found that the equivalent width () of Fe-line feature increases exponentially with temperature up to 20 MK but later it increases very slowly up to 28 MK and then it remains uniform around 1.55 keV up to 34 MK. We compare our measurements of with calculations made earlier by various investigators and propose that these measurements may improve theoretical models. We interpret the variation of both and with temperature as the changes in the ionization and recombination conditions in the plasma during the flare interval and as a consequence the contribution from different ionic emission lines also varies.

  20. Genome wide binding (ChIP-Seq) of murine Bapx1 and Sox9 proteins in vivo and in vitro.

    Science.gov (United States)

    Chatterjee, Sumantra; Kraus, Petra; Sivakamasundari, V; Yap, Sook Peng; Kumar, Vibhor; Prabhakar, Shyam; Lufkin, Thomas

    2016-12-01

    This work pertains to GEO submission GSE36672, in vivo and in vitro genome wide binding (ChIP-Seq) of Bapx1/Nkx3.2 and Sox9 proteins. We have previously shown that data from a genome wide binding assay combined with transcriptional profiling is an insightful means to divulge the mechanisms directing cell type specification and the generation of tissues and subsequent organs [1]. Our earlier work identified the role of the DNA-binding homeodomain containing protein Bapx1/Nkx3.2 in midgestation murine embryos. Microarray analysis of EGFP-tagged cells (both wildtype and null) was integrated using ChIP-Seq analysis of Bapx1/Nkx3.2 and Sox9 DNA-binding proteins in living tissue.

  1. Cytochrome 450 1B1 (CYP1B1 polymorphisms associated with response to docetaxel in Castration-Resistant Prostate Cancer (CRPC patients

    Directory of Open Access Journals (Sweden)

    Price Douglas K

    2010-09-01

    Full Text Available Abstract Background The selection of patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in Castration-Resistant Prostate Cancer (CRPC patients. Functional polymorphisms within the cytochrome P450 1B1 (CYP1B1 gene have been associated with alterations in enzymatic expression and activity and may change sensitivity to the widely used docetaxel regimen. Methods CYP1B1 genotyping was performed on blood samples of 60 CRPC patients treated with docetaxel, using TaqMan probes-based assays. Association between CYP1B1-142C>G (leading to the 48ArgGly transition, 4326C>G (432LeuVal, and 4390A>G (453AsnSer polymorphisms and treatment response, progression-free-survival (PFS and overall-survival (OS was estimated using Pearson χ2 test, Kaplan-Meier curves and Log-rank test. Results Patients carrying the CYP1B1-432ValVal genotype experienced a significantly lower response-rate (P = 0.014, shorter progression-free-survival (P = 0.032 and overall-survival (P Conclusions CYP1B1-4326C>G (432LeuVal polymorphism emerged as possible predictive marker of response and clinical outcome to docetaxel in CRPC patients and may represent a potential new tool for treatment optimization. Larger prospective trials are warranted to validate these findings, which might be applied to the future practice of CRPC treatment.

  2. FoxM1 Promotes Stemness and Radio-Resistance of Glioblastoma by Regulating the Master Stem Cell Regulator Sox2.

    Science.gov (United States)

    Lee, Yeri; Kim, Kang Ho; Kim, Dong Geon; Cho, Hee Jin; Kim, Yeonghwan; Rheey, Jinguen; Shin, Kayoung; Seo, Yun Jee; Choi, Yeon-Sook; Lee, Jung-Il; Lee, Jeongwu; Joo, Kyeung Min; Nam, Do-Hyun

    2015-01-01

    Glioblastoma (GBM) is the most aggressive and most lethal brain tumor. As current standard therapy consisting of surgery and chemo-irradiation provides limited benefit for GBM patients, novel therapeutic options are urgently required. Forkhead box M1 (FoxM1) transcription factor is an oncogenic regulator that promotes the proliferation, survival, and treatment resistance of various human cancers. The roles of FoxM1 in GBM remain incompletely understood, due in part to pleotropic nature of the FoxM1 pathway. Here, we show the roles of FoxM1 in GBM stem cell maintenance and radioresistance. ShRNA-mediated FoxM1 inhibition significantly impeded clonogenic growth and survival of patient-derived primary GBM cells with marked downregulation of Sox2, a master regulator of stem cell phenotype. Ectopic expression of Sox2 partially rescued FoxM1 inhibition-mediated effects. Conversely, FoxM1 overexpression upregulated Sox2 expression and promoted clonogenic growth of GBM cells. These data, with a direct binding of FoxM1 in the Sox2 promoter region in GBM cells, suggest that FoxM1 regulates stemness of primary GBM cells via Sox2. We also found significant increases in FoxM1 and Sox2 expression in GBM cells after irradiation both in vitro and in vivo orthotopic tumor models. Notably, genetic or a small-molecule FoxM1 inhibitor-mediated FoxM1 targeting significantly sensitized GBM cells to irradiation, accompanying with Sox2 downregulation. Finally, FoxM1 inhibition combined with irradiation in a patient GBM-derived orthotopic model significantly impeded tumor growth and prolonged the survival of tumor bearing mice. Taken together, these results indicate that the FoxM1-Sox2 signaling axis promotes clonogenic growth and radiation resistance of GBM, and suggest that FoxM1 targeting combined with irradiation is a potentially effective therapeutic approach for GBM.

  3. Sulfolobus Replication Factor C stimulates the activity of DNA Polymerase B1

    DEFF Research Database (Denmark)

    Xing, Xuanxuan; Zhang, Likui; Guo, Li;

    2014-01-01

    Replication factor C (RFC) is known to function in loading proliferating cell nuclear antigen (PCNA) onto primed DNA, allowing PCNA to tether DNA polymerase for highly processive DNA synthesis in eukaryotic and archaeal replication. In this report, we show that an RFC complex from...... with the ability of RFC to facilitate DNA binding by PolB1 through protein-protein interaction. These results suggest that Sulfolobus RFC may play a role in recruiting DNA polymerase for efficient primer extension, in addition to clamp loading, during DNA replication....... the hyperthermophilic archaea of the genus Sulfolobus physically interacts with DNA polymerase B1 (PolB1) and enhances both the polymerase and 3'-5' exonuclease activities of PolB1 in an ATP-independent manner. Stimulation of the PolB1 activity by RFC is independent of the ability of RFC to bind DNA but is consistent...

  4. Yin Yang 1 is associated with cancer stem cell transcription factors (SOX2, OCT4, BMI1) and clinical implication

    OpenAIRE

    Kaufhold, Samantha; Garbán, Hermes; Bonavida, Benjamin

    2016-01-01

    The transcription factor Yin Yang 1 (YY1) is frequently overexpressed in cancerous tissues compared to normal tissues and has regulatory roles in cell proliferation, cell viability, epithelial-mesenchymal transition, metastasis and drug/immune resistance. YY1 shares many properties with cancer stem cells (CSCs) that drive tumorigenesis, metastasis and drug resistance and are regulated by overexpression of certain transcription factors, including SOX2, OCT4 (POU5F1), BMI1 and NANOG. Based on t...

  5. A Gene Regulatory Network Cooperatively Controlled by Pdx1 and Sox9 Governs Lineage Allocation of Foregut Progenitor Cells

    DEFF Research Database (Denmark)

    Shih, Hung Ping; Seymour, Philip A; Patel, Nisha A;

    2015-01-01

    The generation of pancreas, liver, and intestine from a common pool of progenitors in the foregut endoderm requires the establishment of organ boundaries. How dorsal foregut progenitors activate pancreatic genes and evade the intestinal lineage choice remains unclear. Here, we identify Pdx1 and Sox...... pancreatic fate and sheds light on the gene regulatory circuitry that governs the development of distinct organs from multi-lineage-competent foregut progenitors....

  6. Evaluated kinetic and photochemical data for atmospheric chemistry: Volume I - gas phase reactions of Ox, HOx, NOx and SOx species

    OpenAIRE

    2004-01-01

    This article, the first in the series, presents kinetic and photochemical data evaluated by the IUPAC Subcommittee on GasKinetic Data Evaluation for Atmospheric Chemistry. It covers the gas phase and photochemical reactions of Ox, HOx, NOx and SOx species, which were last published in 1997, and were updated on the IUPAC website in late 2001. The article consists of a summary sheet, containing the recommended kinetic parameters for the evaluated reactions, and five appendi...

  7. Cytochrome P450 CYP1B1 activity in renal cell carcinoma.

    Science.gov (United States)

    McFadyen, M C E; Melvin, W T; Murray, G I

    2004-08-31

    Renal cell carcinoma (RCC) is the most common malignancy of the kidney and has a poor prognosis due to its late presentation and resistance to current anticancer drugs. One mechanism of drug resistance, which is potentially amenable to therapeutic intervention, is based on studies in our laboratory. CYP1B1 is a cytochrome P450 enzyme overexpressed in a variety of malignant tumours. Our studies are now elucidating a functional role for CYP1B1 in drug resistance. Cytochrome P450 reductase (P450R) is required for optimal metabolic activity of CYP1B1. Both CYP1B1 and P450R can catalyse the biotransformation of anticancer drugs at the site of the tumour. In this investigation, we determined the expression of CYP1B1 and P450R in samples of normal kidney and RCC (11 paired normal and tumour and a further 15 tumour samples). The O-deethylation of ethoxyresorufin to resorufin was used to measure CYP1B1 activity in RCC. Cytochrome P450 reductase activity was determined by following the reduction of cytochrome c at 550 nm. The key finding of this study was the presence of active CYP1B1 in 70% of RCC. Coincubation with the CYP1B1 inhibitor alpha-naphthoflavone (10 nM) inhibited this activity. No corresponding CYP1B1 activity was detected in any of the normal tissue examined (n=11). Measurable levels of active P450R were determined in all normal (n=11) and tumour samples (n=26). The presence of detectable CYP1B1, which is capable of metabolising anticancer drugs in tumour cells, highlights a novel target for therapeutic intervention.

  8. Cyp26b1 within the growth plate regulates bone growth in juvenile mice

    Energy Technology Data Exchange (ETDEWEB)

    Minegishi, Yoshiki [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Department of Plastic and Reconstructive Surgery, University of Fukui Hospital, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan); Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Sakai, Yasuo [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Department of Plastic Surgery, Bellland General Hospital, 500-3 Higashiyama Naka-ku, Sakai, Osaka 599-8247 (Japan); Yahara, Yasuhito [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Akiyama, Haruhiko [Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagito, Gifu 501-1194 (Japan); Yoshikawa, Hideki [Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Hosokawa, Ko [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tsumaki, Noriyuki, E-mail: ntsumaki@cira.kyoto-u.ac.jp [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Japan Science and Technology Agency, CREST, Tokyo 102-0075 (Japan)

    2014-11-07

    Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1{sup Δchon} cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone.

  9. Key role for spinal dorsal horn microglial kinin B1 receptor in early diabetic pain neuropathy

    Directory of Open Access Journals (Sweden)

    Couture Réjean

    2010-06-01

    Full Text Available Abstract Background The pro-nociceptive kinin B1 receptor (B1R is upregulated on sensory C-fibres, astrocytes and microglia in the spinal cord of streptozotocin (STZ-diabetic rat. This study aims at defining the role of microglial kinin B1R in diabetic pain neuropathy. Methods Sprague-Dawley rats were made diabetic with STZ (65 mg/kg, i.p., and 4 days later, two specific inhibitors of microglial cells (fluorocitrate, 1 nmol, i.t.; minocycline, 10 mg/kg, i.p. were administered to assess the impact on thermal hyperalgesia, allodynia and mRNA expression (qRT-PCR of B1R and pro-inflammatory markers. Spinal B1R binding sites ((125I-HPP-desArg10-Hoe 140 were also measured by quantitative autoradiography. Inhibition of microglia was confirmed by confocal microscopy with the specific marker Iba-1. Effects of intrathecal and/or systemic administration of B1R agonist (des-Arg9-BK and antagonists (SSR240612 and R-715 were measured on neuropathic pain manifestations. Results STZ-diabetic rats displayed significant tactile and cold allodynia compared with control rats. Intrathecal or peripheral blockade of B1R or inhibition of microglia reversed time-dependently tactile and cold allodynia in diabetic rats without affecting basal values in control rats. Microglia inhibition also abolished thermal hyperalgesia and the enhanced allodynia induced by intrathecal des-Arg9-BK without affecting hyperglycemia in STZ rats. The enhanced mRNA expression (B1R, IL-1β, TNF-α, TRPV1 and Iba-1 immunoreactivity in the STZ spinal cord were normalized by fluorocitrate or minocycline, yet B1R binding sites were reduced by 38%. Conclusion The upregulation of kinin B1R in spinal dorsal horn microglia by pro-inflammatory cytokines is proposed as a crucial mechanism in early pain neuropathy in STZ-diabetic rats.

  10. 两个Sox9基因在斑马鱼胚胎发育和成体性腺中的动态表达特征%Dynamic Expression Patterns of Two Sox9 Genes in Developing Embryo and Gonads of Zebrafish

    Institute of Scientific and Technical Information of China (English)

    梁清仪; 王心仪; 孙冬捷; 严继舟

    2014-01-01

    通过整体原位杂交和切片原位杂交技术系统全面地比较分析了斑马鱼胚胎四个发育时期(12、24、48 hpf和4 dpf)和成熟性腺中Sox9a和Sox9b基因的表达模式。结果显示,两个Sox9基因在脑和眼中持续表达,但在耳囊、头部软骨、胸鳍芽和体节中差异性表达。 Sox9a特异性地在侧线、尾部神经嵴、原肾管和精巢支持细胞中表达,而Sox9b在卵巢的卵黄颗粒中大量表达。与已发表的研究结果相比,本研究更广泛地揭示了Sox9a和Sox9b的动态差异表达模式,且更清楚地显示了其在性腺中的表达特征。%Using whole mount and tissue section in situ hybridization techniques , the expression patterns of two Sox9 homologues genes ,Sox9a and Sox9b,were comprehensively compared and analyzed in four stages of developing embryo (12, 24, 48 hpf and 4 dpf) and mature gonads of zebrafish (Danio rerio).The two genes were persistently expressed in brain and eyes ,but differentially expressed in otic vesicle , head cartilage , pectoral fin buds and somites .Distinct from high expression of Sox9b in the yolk granules of oocytes, Sox9a was specifically expressed in lateral line , tail neural crest , primary renal tubular and Sertoli cells in testis . Compared with other published results , the present data revealed a more extensive differential expression pro-file of two Sox9 genes in the developing embryo and gonads of zebrafish .

  11. Supercritical Airfoil Coordinates

    Data.gov (United States)

    National Aeronautics and Space Administration — Rectangular Supercritical Wing (Ricketts) - design and measured locations are provided in an Excel file RSW_airfoil_coordinates_ricketts.xls . One sheet is with Non...

  12. Magnetic Coordinate Systems

    CERN Document Server

    Laundal, K M

    2016-01-01

    Geospace phenomena such as the aurora, plasma motion, ionospheric currents and associated magnetic field disturbances are highly organized by Earth's main magnetic field. This is due to the fact that the charged particles that comprise space plasma can move almost freely along magnetic field lines, but not across them. For this reason it is sensible to present such phenomena relative to Earth's magnetic field. A large variety of magnetic coordinate systems exist, designed for different purposes and regions, ranging from the magnetopause to the ionosphere. In this paper we review the most common magnetic coordinate systems and describe how they are defined, where they are used, and how to convert between them. The definitions are presented based on the spherical harmonic expansion coefficients of the International Geomagnetic Reference Field (IGRF) and, in some of the coordinate systems, the position of the Sun which we show how to calculate from the time and date. The most detailed coordinate systems take the...

  13. Dimensions of Organizational Coordination

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt; Aldewereld, Huib; Dignum, Virginia

    2013-01-01

    be supported to include organizational objectives and constraints into their reasoning processes by considering two alternatives: agent reasoning and middleware regulation. We show how agents can use an organizational specification to achieve organizational objectives by delegating and coordinating...

  14. Understanding social motor coordination.

    Science.gov (United States)

    Schmidt, R C; Fitzpatrick, Paula; Caron, Robert; Mergeche, Joanna

    2011-10-01

    Recently there has been much interest in social coordination of motor movements, or as it is referred to by some researchers, joint action. This paper reviews the cognitive perspective's common coding/mirror neuron theory of joint action, describes some of its limitations and then presents the behavioral dynamics perspective as an alternative way of understanding social motor coordination. In particular, behavioral dynamics' ability to explain the temporal coordination of interacting individuals is detailed. Two experiments are then described that demonstrate how dynamical processes of synchronization are apparent in the coordination underlying everyday joint actions such as martial art exercises, hand-clapping games, and conversations. The import of this evidence is that emergent dynamic patterns such as synchronization are the behavioral order that any neural substrate supporting joint action (e.g., mirror systems) would have to sustain.

  15. Analysis of intron sequence variability of the conservative HMG-box of Sox9 genes in allotetraploids and their original parents

    Institute of Scientific and Technical Information of China (English)

    Liu Jifang; Liu Shaojun; Tao Min; Li Wei; Liu Yun

    2007-01-01

    The Sox genes of allotetraploids and their original maternal red crucian carp ( Carassius caassius red var. ) and original paternal common carp ( Cyprinus carpio L. ) were detected by PCR with the designed primers based on the conserved HMG-box sequence in different species. Sequencing of Sox genes indicated that two Sox9 genes (Atsox9a and Atsox9b ) existed in allotetraploids, while only one Sox9 gene existed in red crucian carp ( Rcsox9a ) and common carp ( Ccsox9b ). All of the four Sox9 genes contained an intron in the HMG-box, with the sizes of 413 bp, 703 bp, 401 bp and 714 bp, respectively. Moreover, the introns obeyed the rule of "GT-AG". A high similarity was observed between introns of Atsox9a and Rcsox9a (94.4 % ), Atsox9b and Ccsox9b (97.8 % ). Interestingly, the deduced amino acid sequences of their corresponding exons all shared 100 % identity. Thus, introns of the HMG-domain of Sox9s in allotetraploids and their original parents have not only the length polymorphism but also intron variability. Our results provide significant molecular evidence for the origin and evolution of allotetraploids.

  16. Sox2 in the dermal papilla niche controls hair growth by fine-tuning BMP signaling in differentiating hair shaft progenitors.

    Science.gov (United States)

    Clavel, Carlos; Grisanti, Laura; Zemla, Roland; Rezza, Amelie; Barros, Rita; Sennett, Rachel; Mazloom, Amin Reza; Chung, Chi-Yeh; Cai, Xiaoqiang; Cai, Chen-Leng; Pevny, Larysa; Nicolis, Silvia; Ma'ayan, Avi; Rendl, Michael

    2012-11-13

    How dermal papilla (DP) niche cells regulate hair follicle progenitors to control hair growth remains unclear. Using Tbx18(Cre) to target embryonic DP precursors, we ablate the transcription factor Sox2 early and efficiently, resulting in diminished hair shaft outgrowth. We find that DP niche expression of Sox2 controls the migration speed of differentiating hair shaft progenitors. Transcriptional profiling of Sox2 null DPs reveals increased Bmp6 and decreased BMP inhibitor Sostdc1, a direct Sox2 transcriptional target. Subsequently, we identify upregulated BMP signaling in knockout hair shaft progenitors and demonstrate that Bmp6 inhibits cell migration, an effect that can be attenuated by Sostdc1. A shorter and Sox2-negative hair type lacks Sostdc1 in the DP and shows reduced migration and increased BMP activity of hair shaft progenitors. Collectively, our data identify Sox2 as a key regulator of hair growth that controls progenitor migration by fine-tuning BMP-mediated mesenchymal-epithelial crosstalk.

  17. Direct interaction of Sox10 with the promoter of murine Dopachrome Tautomerase (Dct) and synergistic activation of Dct expression with Mitf.

    Science.gov (United States)

    Jiao, Zhongxian; Mollaaghababa, Ramin; Pavan, William J; Antonellis, Anthony; Green, Eric D; Hornyak, Thomas J

    2004-08-01

    The murine dopachrome tautomerase (Dct) gene is expressed early in melanocyte development during embryogenesis, prior to other members of the tyrosinase gene family important for regulating pigmentation. We have used deletion mutants of the Dct promoter, transfections with developmentally relevant transcription factors, and gel shift assays to define transcriptional determinants of Dct expression. Deletion mutagenesis studies show that sequences within the proximal 459 nucleotides are critical for high level expression in melanocytic cells. This region of the promoter contains candidate binding sites for the transcription factors Sox10 and Mitf. Transfections into 293T and NIH3T3 cells show that Sox10 and Mitf independently activate Dct expression, and, when co-transfected, synergistically activate Dct expression. To support the notion that Sox10 acts directly upon the Dct promoter to activate gene expression, direct interaction of Sox10 was demonstrated using gel shifts of oligonucleotide probes derived from promoter sequences within the region required for Sox10-dependent induction. These results suggest that a combinatorial transcription factor interaction is important for expression of Dct in neural crest-derived melanocytes, and support a model for sequential gene activation in melanocyte development whereby Mitf, a Sox10-dependent transcription factor, is expressed initially before an early melanocyte differentiation gene, Dct, is expressed.

  18. Genome-wide Reconstruction of OxyR and SoxRS Transcriptional Regulatory Networks under Oxidative Stress in Escherichia coli K-12 MG1655

    Directory of Open Access Journals (Sweden)

    Sang Woo Seo

    2015-08-01

    Full Text Available Three transcription factors (TFs, OxyR, SoxR, and SoxS, play a critical role in transcriptional regulation of the defense system for oxidative stress in bacteria. However, their full genome-wide regulatory potential is unknown. Here, we perform a genome-scale reconstruction of the OxyR, SoxR, and SoxS regulons in Escherichia coli K-12 MG1655. Integrative data analysis reveals that a total of 68 genes in 51 transcription units (TUs belong to these regulons. Among them, 48 genes showed more than 2-fold changes in expression level under single-TF-knockout conditions. This reconstruction expands the genome-wide roles of these factors to include direct activation of genes related to amino acid biosynthesis (methionine and aromatic amino acids, cell wall synthesis (lipid A biosynthesis and peptidoglycan growth, and divalent metal ion transport (Mn2+, Zn2+, and Mg2+. Investigating the co-regulation of these genes with other stress-response TFs reveals that they are independently regulated by stress-specific TFs.

  19. Clinical and molecular characterization of a Brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutations

    Directory of Open Access Journals (Sweden)

    Eduardo P. Mattos

    2015-03-01

    Full Text Available Campomelic dysplasia (CD is an autosomal, dominantly inherited, skeletal abnormality belonging to the subgroup of bent bone dysplasias. In addition to bowed lower limbs, CD typically includes the following: disproportionate short stature, flat face, micrognathia, cleft palate, bell-shaped thorax, and club feet. Up to three quarters of 46, XY individuals may be sex-reversed. Radiological signs include scapular and pubic hypoplasia, narrow iliac wings, spaced ischia, and bowed femora and tibiae. Lethal CD is usually due to heterozygous mutations in SOX9, a major regulator of chondrocytic development. We present a detailed clinical and molecular characterization of nine Brazilian CD patients. Infants were either stillborn (n = 2 or died shortly after birth and presented similar phenotypes. Sex-reversal was observed in one of three chromosomally male patients. Sequencing of SOX9 revealed new heterozygous mutations in seven individuals. Six patients had mutations that resulted in premature transcriptional termination, while one infant had a single-nucleotide substitution at the conserved splice-site acceptor of intron 1. No clear genotype-phenotype correlations were observed. This study highlights the diversity of SOX9 mutations leading to lethal CD, and expands the group of known genetic alterations associated with this skeletal dysplasia.

  20. BMP-Smad4 signaling is required for precartilaginous mesenchymal condensation independent of Sox9 in the mouse.

    Science.gov (United States)

    Lim, Joohyun; Tu, Xiaolin; Choi, Kyunghee; Akiyama, Haruhiko; Mishina, Yuji; Long, Fanxin

    2015-04-01

    Bone morphogenetic proteins (BMPs) regulate multiple aspects of skeletal development in vertebrates. Although exogenously applied BMPs can induce chondrogenesis de novo, the role and mechanism of physiologic BMP signaling during precartilaginous mesenchymal condensation is not well understood. By deleting the type I BMP receptors or the transcription factor Smad4 in the limb bud mesenchyme, we find that loss of BMP-Smad signaling abolishes skeletal development due to a failure in mesenchymal condensation. In the absence of Smad4, expression of Sox9, an essential transcription factor for chondrogenesis, initiates normally in the proximal mesenchyme of the limb bud, but fails to maintain its level or expand to the more distal territory at the later stages. However, forced-expression of Sox9 does not restore cartilage formation in the Smad4-deficeint embryo. In vitro micromass cultures show that the Smad4-deficient cells fail to condense in a cell-autonomous manner, even though they express several cell adhesion molecules either normally or even at a higher level. Thus, BMP-Smad signaling critically controls mesenchymal condensation to initiate skeletal development likely through a Sox9-independent mechanism.

  1. Sox17 expression patterns during gastrulation and early neurulation in the rabbit suggest two sources of endoderm formation.

    Science.gov (United States)

    Hassoun, Romia; Püschel, Bernd; Viebahn, Christoph

    2010-01-01

    Most gastrointestinal tract and associated gland epithelia originate from the endoderm germ layer discovered by Pander in 1817. The recent surge in stem cell concepts revived interest in the findings of 30 years ago that the endoderm layer itself originates from the epiblast (which since Pander's time had been held to be the forerunner of the ectoderm and mesoderm germ layers only). However, the question as to which parts of the mammalian gastrulation-stage embryonic disc generate endoderm cells is still unresolved. Therefore, the expression of the gene coding for the transcription factor Sox17, a key transcription factor involved in endoderm formation in mouse, chick, frog, and zebrafish, was analyzed in the rabbit, a model organism for mammalian gastrulation morphology, using whole-mount in situ hybridization and high-resolution histological analysis of embryos at gastrulation and early neurulation stages. Sox17 mRNA in the mesoderm and lower layer (hypoblast) compartments within and adjacent to Hensen's node and the anterior segment of the primitive streak confirmed the validity of this approach, as this region had previously been shown to form endoderm in mouse and chick. However, Sox17 expression in central and posterior epiblast at pregastrulation stages together with a transient expression at the posterior extremity of the primitive streak suggest that endoderm (possibly hindgut) may be formed close to the emerging cloacal membrane, as well.

  2. microRNA-29b is a novel mediator of Sox2 function in the regulation of somatic cell reprogramming

    Institute of Scientific and Technical Information of China (English)

    Xudong Guo; Qidong Liu; Guiying Wang; Songcheng Zhu; Longfei Gao; Wujun Hong; Yafang Chen

    2013-01-01

    Fibroblasts can be reprogrammed into induced pluripotent stem cells (iPSCs) by the application of Yamanaka factors (OSKM),but the mechanisms underlying this reprogramming remain poorly understood.Here,we report that Sox2 directly regulates endogenous microRNA-29b (miR-29b) expression during iPSC generation and that miR-29b expression is required for OSKM-and OSK-mediated reprogramming.Mechanistic studies show that Dnmt3a and Dnmt3b are in vivo targets of miR-29b and that Dnmt3a and Dnmt3b expression is inversely correlated with miR-29b expression during reprogramming.Moreover,the effect of miR-29b on reprogramming can be blocked by Dnmt3a or Dnmt3b overexpression.Further experiments indicate that miR-29b-DNMT signaling is significantly involved in the regulation of DNA methylation-related reprogramming events,such as mesenchymal-to-epithelial transition (MET)and Dlk1-Dio3 region transcription.Thus,our studies not only reveal that miR-29b is a novel mediator of reprogramming factor Sox2 but also provide evidence for a muitistep mechanism in which Sox2 drives a miR-29b-DNMT signaling axis that regulates DNA methylation-related events during reprogramming.

  3. Continuous parallel coordinates.

    Science.gov (United States)

    Heinrich, Julian; Weiskopf, Daniel

    2009-01-01

    Typical scientific data is represented on a grid with appropriate interpolation or approximation schemes,defined on a continuous domain. The visualization of such data in parallel coordinates may reveal patterns latently contained in the data and thus can improve the understanding of multidimensional relations. In this paper, we adopt the concept of continuous scatterplots for the visualization of spatially continuous input data to derive a density model for parallel coordinates. Based on the point-line duality between scatterplots and parallel coordinates, we propose a mathematical model that maps density from a continuous scatterplot to parallel coordinates and present different algorithms for both numerical and analytical computation of the resulting density field. In addition, we show how the 2-D model can be used to successively construct continuous parallel coordinates with an arbitrary number of dimensions. Since continuous parallel coordinates interpolate data values within grid cells, a scalable and dense visualization is achieved, which will be demonstrated for typical multi-variate scientific data.

  4. Structure-function relationships of the Mycobacterium tuberculosis transcription factor WhiB1.

    Directory of Open Access Journals (Sweden)

    Laura J Smith

    Full Text Available BACKGROUND: Members of the WhiB-like (Wbl protein family possess iron-sulfur clusters and are implicated in the regulation of developmental processes in Actinomycetes. Mycobacterium tuberculosis possesses seven Wbl proteins. The [4Fe-4S] cluster of M. tuberculosis WhiB1 is relatively insensitive to O(2 but very sensitive to nitric oxide (NO. Nitric oxide nitrosylates the WhiB1 iron-sulfur cluster and promotes DNA-binding; the apo-forms of WhiB1 also bind DNA. However, the molecular requirements for iron-sulfur cluster acquisition and for DNA-binding by WhiB1 are poorly characterized. METHODS AND FINDINGS: WhiB1 variants were created by site-directed mutagenesis and the abilities of the corresponding proteins to acquire an iron-sulfur cluster and/or bind to whiB1 promoter DNA were assessed. All four Cys residues (Cys9, 37, 40, and 46 in the N-terminal region of WhiB1 were required for incorporation of a [4Fe-4S] cluster, whereas a possible alternative cluster ligand Asp13 (by analogy with M. smegmatis WhiB2 was not. The C-terminal region of WhiB1 is predicted to house the DNA-binding domain of the protein consisting of a predicted β-turn ((58GVWGG(62 followed by two amino acid motifs ((72KRRN(75 and (78TKAR(81 that are conserved in WhiB1 proteins. Gly residues (Gly58, 61 and 62 in the β-turn and positively-charged residues (Lys72, Arg73, Arg74, Lys79 and Arg81 in the downstream conserved regions were required for binding of WhiB1 DNA. CONCLUSIONS: Site-directed mutagenesis of M. tuberculosis whiB1 and characterization of the corresponding proteins has been used to explore structure-function relationships of the NO-responsive transcription factor WhiB1. This showed that all four conserved Cys residues in the N-terminal region are required for incorporation of iron-sulfur clusters but not for DNA-binding. Analysis of variants with amino acid substitutions in the C-terminal region revealed the crucial roles played by a predicted β-turn and two

  5. NR2F1 controls tumor cell dormancy via SOX9 and RARβ driven quiescence programs

    Science.gov (United States)

    Sosa, Maria Soledad; Parikh, Falguni; Maia, Alexandre Gaspar; Estrada, Yeriel; Bosch, Almudena; Bragado, Paloma; Ekpin, Esther; George, Ajish; Zheng, Yang; Lam, Hung-Ming; Morrissey, Colm; Chung, Chi-Yeh; Farias, Eduardo F.; Bernstein, Emily; Aguirre-Ghiso, Julio A.

    2014-01-01

    Metastases can originate from disseminated tumor cells (DTCs), which may be dormant for years before reactivation. Here we find that the orphan nuclear receptor NR2F1 is epigenetically upregulated in experimental HNSCC dormancy models and in DTCs from prostate cancer patients carrying dormant disease for 7–18 years. NR2F1-dependent dormancy is recapitulated by a co-treatment with the DNA demethylating agent 5-Aza-C and retinoic acid across various cancer types. NR2F1-induced quiescence is dependent on SOX9, RARβ and CDK inhibitors. Intriguingly, NR2F1 induces global chromatin repression and the pluripotency gene NANOG, which contributes to dormancy of DTCs in the bone marrow. When NR2F1 is blocked in vivo, growth arrest or survival of dormant DTCs is interrupted in different organs. We conclude that NR2F1 is a critical node in dormancy induction and maintenance by integrating epigenetic programs of quiescence and survival in DTCs. PMID:25636082

  6. Novel SOX10 mutation in a girl with type IV Waardenburg syndrome%Waardenburg综合征Ⅳ型患儿SOX10基因新突变研究

    Institute of Scientific and Technical Information of China (English)

    蔚开慧; 姜茜; 张震; 李颀; 肖萍; 苏琳; 邹继珍; 李龙; 潘尚领

    2016-01-01

    Objective To improve the disease causative gene mutation spectrum and provide new information for ge-netic counseling in Waardenburg syndrome type IV (WS4), we performed molecular genetic study in an isolated patient af-fected by WS4. Literature was reviewed for reported nonsense mutations in SOX10. Methods Detailed histories were col-lected through questionnaires and physical examination. Blood samples of the patient and her parents were collected after obtaining informed consents. Suspected mutations were amplified and verified by Sanger sequencing after the next genera-tion sequencing of 172 related genes. The raw data were analyzed using molecular biological websites and the GeneTool software. Results A new de novo heterozygous mutation (c.838G>T, p.E280X) in the fourth exon of SOX10 was found in the patient. Both parents were demonstrated to be wild-type and symptom free. Conclusions The novel mutation found in our study not only enriches the mutation spectrum but also is helpful for recurrent risk evaluation and genetic counseling for this family.%目的:通过分析研究一例Waardenburg综合征Ⅳ型(WS4)散发病例患儿的分子遗传学病因,丰富该致病基因突变谱,为WS4遗传咨询提供新的证据,并对该综合征相关的SOX10基因所有无义突变进行文献回顾和总结。方法收集一个WS4患儿的详细临床资料,签署知情同意书后获取血样,对包括SOX10、EDNRB、EDN3在内的172个先天性巨结肠及综合征相关基因进行二代测序,并用聚合酶链反应针对可疑致病突变进行扩增及Sanger测序验证,应用GeneTool软件及生物信息学网站的信息分析数据。结果发现患儿SOX10基因第4外显子存在一杂合无义突变(c.838G>T, p.E280X),父母均表现正常且未发现有该突变。结论发现一新的SOX10基因致病突变,丰富了致WS4的SOX10基因突变谱,并为父母提供再生育患儿的风险评估及必要的产前诊断咨询。

  7. Interaction of vitamin B1 with bovine serum albumin investigation using vitamin B1-selective electrode: potentiometric and molecular modeling study.

    Science.gov (United States)

    Hosseinzadeh, Reza; Khorsandi, Khatereh

    2016-09-01

    Vitamin B1 or thiamin is one of the B vitamins. All B vitamins help the body to convert food (carbohydrates) into fuel (glucose), which produces energy. The B vitamins are necessary for healthy skin, eyes, hair, and liver. It also could help the nervous system function properly, and is necessary for brain functions. Drug interactions with protein can affect the distribution of the drug and eliminate the drug in living systems. In this study, the binding of thiamine hydrochloride (vitamin B1) to bovine serum albumin (BSA) was evaluated using a new proposed vitamin B1 (thiamine)-selective membrane electrode under various experimental conditions, such as pH, ionic strength, and protein concentration; in addition molecular modeling was applied as well. The binding isotherms plotted based on potentiometric data and analyzed using the Wyman binding potential concept. The apparent binding constant was determined and used for the calculation of intrinsic Gibbs free energy of binding. According to the electrochemical and molecular docking results, it can be concluded that the hydrophobic interactions and hydrogen binding are major interactions between BSA and vitamin B1.

  8. Pathogenesis-Related Protein 1b1 (PR1b1) Is a Major Tomato Fruit Protein Responsive to Chilling Temperature and Upregulated in High Polyamine Transgenic Genotypes

    Science.gov (United States)

    Fatima, Tahira; Topuz, Muhamet; Bernadec, Anne; Sicher, Richard; Handa, Avtar K.; Mattoo, Autar K.

    2016-01-01

    Plants execute an array of mechanisms in response to stress which include upregulation of defense-related proteins and changes in specific metabolites. Polyamines – putrescine (Put), spermidine (Spd), and spermine (Spm) – are metabolites commonly found associated with abiotic stresses such as chilling stress. We have generated two transgenic tomato lines (556HO and 579HO) that express yeast S-adenosylmethionine decarboxylase and specifically accumulate Spd and Spm in fruits in comparison to fruits from control (556AZ) plants (Mehta et al., 2002). Tomato fruits undergo chilling injury at temperatures below 13°C. The high Spd and Spm tomato together with the control azygous line were utilized to address role(s) of polyamines in chilling-injury signaling. Exposure to chilling temperature (2°C) led to several-fold increase in the Put content in all the lines. Upon re-warming of the fruits at 20°C, the levels of Spd and Spm increased further in the fruit of the two transgenic lines, the higher levels remaining stable for 15 days after re-warming as compared to the fruit from the control line. Profiling their steady state proteins before and after re-warming highlighted a protein of ∼14 kD. Using proteomics approach, protein sequencing and immunoblotting, the ∼14-kD protein was identified as the pathogenesis related protein 1b1 (PR1b1). The PR1b1 protein accumulated transiently in the control fruit whose level was barely detectable at d 15 post-warming while in the fruit from both the 556HO and 579HO transgenic lines PR1b1 abundance increased and remained stable till d 15 post warming. PR1b1 gene transcripts were found low in the control fruit with a visible accumulation only on d 15 post warming; however, in both the transgenic lines it accumulated and increased soon after rewarming being several-fold higher on day 2 while in 556HO line this increase continued until d 6 than the control fruit. The chilling-induced increase in PR1b1 protein seems independent

  9. Determination of Aflatoxin B1 in Smokeless Tobacco Products by Use of UHPLC-MS/MS.

    Science.gov (United States)

    Zitomer, Nicholas; Rybak, Michael E; Li, Zhong; Walters, Matthew J; Holman, Matthew R

    2015-10-21

    This work developed a UHPLC-MS/MS method for the detection and quantitation of aflatoxins in smokeless tobacco products, which was then used to determine aflatoxin B1 concentrations in 32 smokeless tobacco products commercially available in the United States. Smokeless tobacco products were dried, milled, and amended with (13)C17-labeled internal standards, extracted in water/methanol solution in the presence of a surfactant, isolated through use of immunoaffinity column chromatography, and reconstituted in mobile phase prior to UHPLC-MS/MS analysis. The method was capable of baseline separation of aflatoxins B1, B2, G1, and G2 in a 2.5 min run by use of a fused core C18 column and a water/methanol gradient. MS/MS transition (m/z) 313.3 → 241.2 was used for aflatoxin B1 quantitation, with 313.3 → 285.1 used for confirmation. The limit of detection (LOD) for aflatoxin B1 was 0.007 parts per billion (ppb). Method imprecision for aflatoxin B1 (expressed as coefficient of variation) ranged from 5.5 to 9.4%. Spike recoveries were 105-111%. Aflatoxin B1 concentrations in the smokeless tobacco products analyzed ranged from snuffs and chews, whereas all moist snuff products tested were below LOD. The amounts of aflatoxin B1 detected were low relative to the 20 ppb regulatory limit established by the U.S. Food and Drug Administration for foods and feeds.

  10. Schisandrin A and B induce organic anion transporting polypeptide 1B1 transporter activity.

    Science.gov (United States)

    Guo, Cheng-Xian; Deng, Sheng; Yin, Ji-Ye; Liu, Zhao-Qian; Zhang, Wei; Zhou, Hong-Hao

    2015-01-01

    Organic anion transporting polypeptide 1B1 (OATP1B1) is the most important transporter in the organic anion transporting polypeptide family. OATP1B1 plays an important role in the hepatic uptake of many endogenous compounds and xenobiotics, including many clinical drugs. At present, the combinational usage of Chinese traditional herbal medicines and conventional chemical pharmaceuticals may affect the activity of enzymes and transporters activity and cause absorption of their substrates and metabolic changes. In this study, we aimed to investigate the effect of schisandrin A, schisandrin B and tanshinone IIA, which were extracted from medicinal plants, on OATP1B1 activity. HepG2 cells are used as in vitro models for OATP1B1 activity studies. A combination of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tertazolium bromide (MTT) assays, real-time RT-PCR, and transporter activity analysis were employed. We found that schisandrin A and B increased OATP1B1 mRNA levels by 1.81-fold (p Schisandrin A of 1 μM and 10 μM and schisandrin B of 10 μM significantly increased the uptake of [3H] estrone-3-sulfate (p schisandrin A and B induced OATP1B1 expression and increased its transporter activity in HepG2 cells.

  11. Spontaneous mutation 7B-1 in tomato impairs blue light-induced stomatal opening.

    Science.gov (United States)

    Hlavinka, Jan; Nauš, Jan; Fellner, Martin

    2013-08-01

    It was reported earlier that 7B-1 mutant in tomato (Solanum lycopersicum L.), an ABA overproducer, is defective in blue light (BL) signaling leading to BL-specific resistance to abiotic and biotic stresses. In this work, we examine responses of stomata to blue, red and white lights, fusicoccin, anion channel blockers (anthracene-9-carboxylic acid; 9-AC and niflumic acid; NIF) and ABA. Our results showed that the aperture of 7B-1 stomata does not increase in BL, suggesting that 7B-1 mutation impairs an element of BL signaling pathway involved in stomatal opening. Similar stomatal responses of 7B-1 and wild type (WT) to fusicoccin or 9-AC points out that activity of H(+)-ATPase and 9-AC-sensitive anion channels per se is not likely affected by the mutation. Since 9-AC restored stomatal opening of 7B-1 in BL, it seems that 9-AC and BL could block similar type of anion channels. The stomata of both genotypes did not respond to NIF neither in darkness nor in any light conditions tested. In light, 9-AC but not NIF restored stomatal opening inhibited by ABA in WT and 7B-1. We suggest that in comparison to WT, the activity of S-type anion channels in 7B-1 is more promoted by increased ABA content, and less reduced by BL, because of the mutant resistance to BL.

  12. Drug-drug interactions between rosuvastatin and oral antidiabetic drugs occurring at the level of oatp1b1s

    NARCIS (Netherlands)

    Steeg, E. van de; Greupink, R.; Schreurs, M.; Nooijen, I.H.G.; Verhoeck, K.C.M.; Hanemaaijer, R.; Ripken, D.; Monshouwer, M.; Vlaming, M.L.H.; DeGroot, J.; Verwei, M.; Russel, F.G.M.; Huisman, M.T.; Wortelboer, H.M.

    2013-01-01

    Organic anion-transporting polypeptide 1B1 (OATP1B1) is an important hepatic uptake transporter, of which the polymorphic variant OATP1B1*15 (Asn130Asp and Val174Ala) has been associated with decreased transport activity. Rosuvastatin is an OATP1B1 substrate and often concomitantly prescribed with o

  13. Spatiotemporal Expression Patterns and Antibody Reactivity of Taeniidae Endophilin B1.

    Science.gov (United States)

    Ahn, Chun-Seob; Bae, Young-An; Kim, Seon-Hee; Kim, Jeong-Geun; Yu, Jae-Ran; Yang, Hyun-Jong; Eom, Keeseon S; Wang, Hu; Kang, Insug; Yang, Yichao; Kong, Yoon

    2016-10-01

    Larval Taeniidae, such as metacestodes of Taenia solium, Echinococcus granulosus, and Echinococcus multilocularis, produce chronic and fatal helminthic diseases. Proper identification of these zoonotic cestodiases is often challenging and is hampered in some clinical settings. Endophilin B1 plays critical roles in the maintenance of membrane contours and endocytosis. We isolated proteins homologous to endophilin B1 from T. solium, Taenia saginata, and Taenia asiatica The three Taeniidae endophilin B1 proteins shared 92.9 to 96.6% sequence identity. They harbored a Bin1/amphiphysin/Rvs (BAR) domain and residues for a dimeric interface but lacked a SRC homology 3 (SH3) domain. Endophilin B1 showed a unique immunological profile and was abundantly expressed in the tegumental syncytium of Taeniidae metacestodes and adults. Bacterially expressed recombinant T. solium endophilin B1 (rTsMEndoB1) demonstrated a sensitivity of 79.7% (345/433 cases) for serodiagnosis of larval Taeniidae infections. The protein showed strong immune recognition patterns against sera from patients with chronic neurocysticercosis, cystic echinococcosis, or advanced-stage alveolar echinococcosis. Adult Taeniidae infections exhibited moderate degrees of positive antibody responses (65.7% [23/35 samples]). rTsMEndoB1 showed some cross-reactivity with sera from patients infected with Diphyllobothriidae (23.6% [25/106 samples]) but not with sera from patients with other parasitic diseases or normal controls. The specificity was 91.7% (256/301 samples). The positive and negative predictive values were 93.6% and 73.4%, respectively. Our results demonstrate that Taeniidae endophilin B1 may be involved in the control of membrane dynamics, thus contributing to shaping and maintaining the tegumental curvature. rTsMEndoB1 may be useful for large-scale screening, as well as for individual diagnosis and follow-up surveillance of Taeniidae infections.

  14. SF3B1 haploinsufficiency leads to formation of ring sideroblasts in myelodysplastic syndromes.

    Science.gov (United States)

    Visconte, Valeria; Rogers, Heesun J; Singh, Jarnail; Barnard, John; Bupathi, Manoj; Traina, Fabiola; McMahon, James; Makishima, Hideki; Szpurka, Hadrian; Jankowska, Anna; Jerez, Andres; Sekeres, Mikkael A; Saunthararajah, Yogen; Advani, Anjali S; Copelan, Edward; Koseki, Haruhiko; Isono, Kyoichi; Padgett, Richard A; Osman, Sami; Koide, Kazunori; O'Keefe, Christine; Maciejewski, Jaroslaw P; Tiu, Ramon V

    2012-10-18

    Whole exome/genome sequencing has been fundamental in the identification of somatic mutations in the spliceosome machinery in myelodysplastic syndromes (MDSs) and other hematologic disorders. SF3B1, splicing factor 3b subunit 1 is mutated in 60%-80% of refractory anemia with ring sideroblasts (RARS) and RARS associated with thrombocytosis (RARS-T), 2 distinct subtypes of MDS and MDS/myeloproliferative neoplasms (MDSs/MPNs). An idiosyncratic feature of RARS/RARS-T is the presence of abnormal sideroblasts characterized by iron overload in the mitochondria, called RS. Based on the high frequency of mutations of SF3B1 in RARS/RARS-T, we investigated the consequences of SF3B1 alterations. Ultrastructurally, SF3B1 mutants showed altered iron distribution characterized by coarse iron deposits compared with wild-type RARS patients by transmission electron microscopy. SF3B1 knockdown experiments in K562 cells resulted in down-regulation of U2-type intron-splicing by RT-PCR. RNA-sequencing analysis of SF3B1 mutants showed differentially used genes relevant in MDS pathogenesis, such as ASXL1, CBL, EZH, and RUNX families. A SF3B pharmacologic inhibitor, meayamycin, induced the formation of RS in healthy BM cells. Further, BM aspirates of Sf3b1 heterozygous knockout mice showed RS by Prussian blue. In conclusion, we report the first experimental evidence of the association between SF3B1 and RS phenotype. Our data suggest that SF3B1 haploinsufficiency leads to RS formation.

  15. SH2B1 regulation of energy balance, body weight, and glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    Liangyou; Rui

    2014-01-01

    The Src homology 2B(SH2B)family members(SH2B1,SH2B2 and SH2B3)are adaptor signaling proteins containing characteristic SH2 and PH domains.SH2B1(also called SH2-B and PSM)and SH2B2(also called APS)are able to form homo-or hetero-dimers via their N-terminal dimerization domains.Their C-terminal SH2 domains bind to tyrosyl phosphorylated proteins,including Janus kinase 2(JAK2),TrkA,insulin receptors,insulin-like growth factor-1 receptors,insulin receptor substrate-1(IRS1),and IRS2.SH2B1 enhances leptin signaling by both stimulating JAK2 activity and assembling a JAK2/IRS1/2 signaling complex.SH2B1 promotes insulin signaling by both enhancing insulin receptor catalytic activity and protecting against dephosphorylation of IRS proteins.Accordingly,genetic deletion of SH2B1 results in severe leptin resistance,insulin resistance,hyperphagia,obesity,and type 2 diabetes in mice.Neuronspecific overexpression of SH2B1βtransgenes protects against diet-induced obesity and insulin resistance.SH2B1 in pancreaticβcells promotesβcell expansion and insulin secretion to counteract insulin resistance in obesity.Moreover,numerous SH2B1 mutations are genetically linked to leptin resistance,insulin resistance,obesity,and type 2 diabetes in humans.Unlike SH2B1,SH2B2 and SH2B3 are not required for the maintenance of normal energy and glucose homeostasis.The metabolic function of the SH2B family is conserved from insects to humans.

  16. Genetic variation of Cytochrome P450 1B1 (CYP1B1) and risk of breast cancer among Polish women.

    Science.gov (United States)

    Gaudet, Mia M; Chanock, Stephen; Lissowska, Jolanta; Berndt, Sonja I; Yang, Xiaohong Rose; Peplonska, Beata; Brinton, Louise A; Welch, Robert; Yeager, Meredith; Bardin-Mikolajczak, Alicja; Sherman, Mark E; Sutter, Thomas R; Garcia-Closas, Montserrat

    2006-08-01

    Four single nucleotide polymorphisms (SNPs) in CYP1B1 (Ex2 + 143 C > G, Ex2 + 356 G > T, Ex3 + 251 G > C, Ex3 + 315 A > G) cause amino acid changes (R48G, A119S, L432V and N453S, respectively) and are associated with increased formation of catechol estrogens; however, epidemiologic evidence only weakly su